LE NODULE PULMONAIRESamedi 5 octobre 2013

Dr Catherine BEIGELMAN

LE NODULE PULMONAIRE 2013 – 8h15-16h15, Auditoire Jéquier Doge, PMU

CHUV, Lausanne

Dr Catherine BEIGELMAN-AUBRY

15, Auditoire Jéquier Doge, PMU

LE NODULE PULMONAIRE - Dr Catherine BEIGELMAN - AUBRY

Samedi 5 octobre 2013 – 8h15-16h15- Auditoire Jéquier Doge, PMU, CHUV, Lausanne

Programme 08h00 Café d’accueil Modérateurs : L. Nicod, T. Rochat

08h25 Introduction R. MEULI

08h30 Screening du cancer broncho-pulmonaire: où en est-on? R.LAZOR

09h00 Nodule pulmonaire solide: que faut-il savoir ? A.-L. HACHULLA JW. FITTING

09h30 Nodule pulmonaire en verre dépoli: que faut-il C. BEIGELMAN savoir ? P. DUMONT

10h00 Apport des systèmes CAD et limites C. BEIGELMAN

10h30 Pause Modérateurs : J-D. Aubert, S. Schmidt

11h00 Place de la TEP - Corrélations morphologiques, J. PRIOR métaboliques et histologiques C. BEIGELMAN I. LETOVANEC

11h30 Nodule pulmonaire: place de l’IRM A. KHALIL 12h00 Ponction percutanée: bonnes pratiques E. DE KERVILER 12h30 Aspects histo-pathologiques I. LETOVANEC 13h00 Pause déjeuner Modérateurs : M. Gonzalez, P. Bize

14h00 Moyens diagnostiques par endoscopie A. LOVIS

14h25 Nodule pulmonaire : indications chirurgicales HB. RIS

14h50 Destruction percutanée des tumeurs pulmonaires: où en est-on? P. BIZE

15h15 Nodule pulmonaire: indications de la radiothérapie stéréotaxique O. MATZINGER

15h45 Discussion - Table ronde 16h15 Fin de la journée Orateurs-Modérateurs Dr John-David Aubert Service de Pneumologie CHUV Lausanne Dr Catherine Beigelman-Aubry Service de Radiologie CHUV Lausanne Dr Pierre Bize Service de Radiologie CHUV Lausanne Pr Eric De Kerviler Service de Radiologie Hôpital Saint-Louis, Paris Dr Philippe Dumont Service de Pneumologie-Hôpital de Fribourg Pr Jean-William Fitting- Service de Pneumologie CHUV Lausanne Dr Anne-Lise Hachulla Service de Radiologie HUG Genève Dr Antoine Khalil Service de Radiologie Hôpital Tenon, Paris Dr Romain Lazor Service de Pneumologie CHUV Lausanne Dr Igor Letovanec Service d’Anatomo-pathologie CHUV Lausanne Dr Alban Lovis Service de Pneumologie CHUV Lausanne Dr Oscar Matzinger Service de Radiothérapie CHUV Lausanne Pr Reto Meuli Service de Radiologie CHUV Lausanne Dr Michel Gonzalez Service de Chirurgie Thoracique CHUV Lausanne Pr Laurent Nicod Service de Pneumologie CHUV Lausanne Pr John Prior Service de Médecine Nucléaire CHUV Lausanne Pr Hans-Beat Ris Service de Chirurgie Thoracique CHUV Lausanne Pr Thierry Rochat Service de Pneumologie HUG Genève Dr Sabine Schmidt Service de Radiologie CHUV Lausanne

02.10.2013

1

Dépistage du cancerbroncho-pulmonaire:où en est-on ?

Dr Romain LAZOR

Service de pneumologie

Centre hospitalier universitaire vaudois

Cancer du poumon: fréquence

femmes hommes

Office fédéral de la statistique 2011

Monde: 1.5 million décès / anSuisse: 3000 décès / an

Cancer du poumon: taux par âge

Office fédéral de la statistique 2011

(2003-2007)

dépistage

02.10.2013

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Distribution des stades et survie

Goldstraw J Thor Oncol 2007

But du dépistage

symptom-driven diag screening

localized

regional

distant

Transition de stade (« stage shift »)

Composants du dépistage

1 examen de dépistagedéterminer probabilité d’avoir une maladie chez des individus asymptomatiques

2examens complémentaires

poser le diagnostic

3interventions thérapeutiques

traiter en cas de diagnostic positif

Guessous Rev Med Suisse 2010

02.10.2013

3

Dépistage: enjeux éthiques

bienfaisance et non-

malfaisance

proposer des interventions à des patients qui ne les ont pas demandées → s'assurer que avantages > risques éventuels

autonomie du patient difficulté à communiquer les véritables risques et avantages aux patients

équité personnes vulnérables et démunies:• risque de maladie ↑• inclusion dans programmes de dépistage ↓

Dépistage: bénéfices et risques

population à risque

examen de dépistage

examen diagnostique

positif négatif

population à haut risque

maladie présente

maladie absente

population à bas risque

maladie présente

maladie absente

tabagisme

encouragé ?

dépistage

bénéfique dépistage

inefficace

inquiétude

inutile

inégalités

coûts

morbidité

mortalité

coûts

Temps de devancement et biais

détection par apparition

de symptômes

pas de dépistage

dépistage inefficace

dépistage efficace

détection précoce

par dépistage

temps de devancement

temps de devancement bénéfice

décès

cancer du poumon ≈≈≈≈ 4 ans

Biais de devancement = prolongement apparent de la survie,sans véritable réduction de mortalité

02.10.2013

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Biais de sélection pronostique (length time bias)

dépistage

début de la maladie

décès

maladie d’évolution lente

maladie d’évolution rapide

biais de sélection pronostique = sur-représentation de maladies indolentes lentement progressives

Biais de surdiagnostic

cancers détectés

population dépistée

détection efficace de cancers létaux

détection de cancers non-progressifs or non-létaux

Surdiagnostic:

� pas observable directement

� pas réduit par les études randomisées

� indésirable dans les programmes de dépistage

Surdiagnostic dans le cancer bronchique

� autopsies 1973-1982: cancer bronchique méconnu chez 1% hommes, dont 70% au stade I-II

� Études Mayo, John Hopkins et MSKCC, dépistage RX: 45 cancers stade T1-T2 non opérés:

� 20 irradiés

� 25 non traités → 5/45 (11%) en vie à 5 ans

� registre SEER → survie à 8 ans des stades IA :

� opérés: 60-75%

� non traités: 6-13%

� études Mayo + tchécoslovaque: 22-24% excès cancers dans bras dépistage

Henschke Lung Cancer 2003

02.10.2013

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Surdiagnostic dans le cancer bronchique

Veronesi Ann Intern Med 2012

Surdiagnostic dans le cancer bronchique

Veronesi Ann Intern Med 2012

Dépistage par radiographie (1)

� Prostate, Lung, Colorectal and Ovarian (PCLO) cancer screening trial

� randomisation:

� RX thorax initiale puis 1x/an pendant 3 ans → résultat au médecin traitant + patient → décision d’investigation

� Suivi ordinaire par médecin traitant

� suivi moyen 11 ans

� 154’901 participants

� 55 - 74 ans

� femmes 51 %

� fumeurs ou ex-fumeurs 52%

Oken JAMA 2011

02.10.2013

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Dépistage par radiographie (2)

� adhérence au dépistage 84%

� dépistage positif 9% à l’inclusion

� incidence de cancer/10’000 patients-années

� non fumeurs 3, ex-fumeurs 23, fumeurs 83

� incidence cumulée 20.1 vs 19.2 (p=NS)

� mortalité autres causes que cancer poumon 105 vs 107 /10’000 patients-années (p=NS)

Oken JAMA 2011

Dépistage par radiographie (3)

mortalité par cancer poumon 14.0 vs 14.2 /10’000 patients-années (p=NS)

Oken JAMA 2011

Dépistage par scanner (1)

� Scanner multi-détecteur hélicoïdal: résolution ↑, rapidité ↑, reconstruction

� Faible dose

� Études ouvertes dépistage par CT: survie ↑

Henschke NEJM 2006

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Detection and Screening of Early Cancer by Novel Imaging Technology and Molecular Essays - DANTE (1)

� N=2472 hommes

� fumeurs ou ex-fumeurs > 20 UPA

� âge 60-74

� espérance de vie >5 ans, pas de cancer <10 ans

� randomisation 1:1

� Scanner + visite clinique

� Visite clinique

� suivi ou bilan diagnostique selon taille du nodule dépisté

1x/an pendant 4 ans

Infante AJRCCM 2009

DANTE (2)

CT contrôles p

Anomalie au CT, % 27.5

Taux de détection de cancers, % 4.7 2.8 0.02

Stade I, % 2.6 1.0 0.004

Stade IIIB-IV, % 1.3 1.4 NS

Examens invasifs, % 7.5 3.0 <0.0001

Mortalité par cancer, % 1.6 1.7 0.84

Mortalité globale, % 3.6 3.8 0.83

Infante AJRCCM 2009

Après un suivi médian de 3 ans:

National Lung Screening Trial − NLST (1)

� 53’454 patients, 33 centres USA

� âge 55-74 ans

� tabagisme ≥ 30 UPA actif ou stoppé depuis < 15 ans

� exclus si: cancer pulmonaire, scanner thorax < 18 mois, ou perte pondérale inexpliquée

� randomisation en 2 groupes:

� scanner thoracique faible dose

� radiographie thoracique face profil

� si nodule non calcifié ≥ 4 mm au CT ou n’importe quelle taille à la RX → « suspicion de cancer » → bilan diagnostique et traitement

� variable principale: mortalité par cancer

Aberle NEJM 2011

1x/an pendant 3 ans

02.10.2013

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NLST (2)

� bilan diagnostique chez >90% des dépistés positifs

� fumeurs 48%, ex-fumeurs 52%

� adhérence au protocole ≥ 93%

� CT hors protocole dans groupe RX (contamination) 4.3%

� suivi médian 6.5 ans

Aberle NEJM 2011

NLST (3)

CT RX différence

≥≥≥≥ 1 dépistage positif 39% 16%

faux positifs 96.4% 94.5%

vrais positifs 3.6% 5.5%

incidence de cancer bronchique

/100’000 patients-années645 572 +13%

complications des investigations1.4%

(16 décès)1.6%

(10 décès)

mortalité par cancer bronchique

/100’000 patients-années247 309

-20%

p=0.004

mortalité globale

/100’000 patients-années1302 1395

-6.7%

p=0.02

Aberle NEJM 2011

Pour éviter 1 décès par cancer bronchique, il faut dépister 320 patients

NLST (4)

CT RX

Stade I 50.0% 31.1%

Stade II 7.1% 7.9%

Stade III 21.2% 24.8%

Stade IV 21.7% 36.1%

Aberle NEJM 2011

CT RX

Cancers détectés par dépistage 61.2% 29.6%

Cancers non détectés par dépistage 4.2% 14.6%

Cancers survenus hors dépistage 34.6% 55.8%

02.10.2013

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NLST (5)

Aberle NEJM 2011

surdiagnosticréduction de la mortalité par cancer

NLST(6)

Aberle J Natl Cancer Inst 2010

Population étudiée similaire à la population générale de fumeurs ?

NLST (7)

� conclusions:

� dépistage CT ↓ mortalité par cancer bronchique et mortalité globale p.r. à dépistage RX

� limitations:

� pas de comparaison directe scanner vs suivi ordinaire

� population dépistée différente de la population générale (possible effet volontaire sains)

� biais de surdiagnostic ?

� mortalité chirurgicale très faible (1% vs 4% attendu)

� dépistage stoppé après 3 cycles

� cancers radio-induits ?

Aberle NEJM 2011

02.10.2013

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Danish lung cancer screening trial – DLCST (1)

� N= 4104

� 50-70 ans

� Fumeurs actifs ≥ 20 UPA ou abstinence <10 ans

� VEMS >30% pred

� Exclu si : antécédent de cancer, espérance de vie < 10 ans, CT < 1 an

� Randomisation 1:1

� 5 CT annuels

� control group

Saghir Thorax 2012

DLCST (2)

� Nodules < 5 mm ou aspect bénin→ dépistage négatif

� nodules 5-15 mm → nouveau CT à 3 mois

� nodules > 15 mm ou croissance > 25% → dépistage positif → bilan diagnostique et traitement

� endpoint primaire : mortalité

� Faux positifs au CT initial 7.9%, puis <2%

� Taux de détection de cancers dans le groupe dépistage = 0.7%

Saghir Thorax 2012

DLCST (3)

� Davantage de cancers dans groupe dépistage (69 vs 24, p<0.001)

� 6 x plus de cancers au stade précoce dans groupe dépistage

� Nombre similaire de cancers au stade tardif (p=NS)

� Pas de « stage shift »

� suggère surdiagnostic de cancers au stade précoce

Saghir Thorax 2012

02.10.2013

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DLCST (4)

Saghir Thorax 2012

p=0.06

p=0.43

mortalité globale mortalité par cancer

Multicentric Italian Lung Detection – MILD (1)

� N=4099 âge >49 ans

� fumeurs ≥ 20 UPA, actifs ou arrêt <10 ans

� Pas de cancer < 5 ans

� Randomisation 1:1:1

� CT 1x/an

� CT 1x/2 ans

� Suivi ordinaire

� Nodules 5 - 8 mm → nouveau CT à 3 mois

� Nodules > 8 mm → PET-CT

Pastorino Eur J Cancer Prev 2012

MILD (2) : incidence cumulée de cancer du poumon

Pastorino Eur J Cancer Prev 2012

(yr)

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MILD (3) : mortalité cumulée par cancer du poumon

Pastorino Eur J Cancer Prev 2012

(yr)

Questions non résolues

Analyse du nodule: 2D vs 3D ?

Veronesi Lancet 2013

Augmentation de volume de 25% (significatif) mais diamètre augmenté de 8% (non significatif)

Augmentation de diamètre de 25% (significatif) → volume augmenté de 95% (très significatif)

Mesure du diamètre peu sensible

02.10.2013

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Analyse du nodule en 3D

� Étude NELSON (Hollande – Belgique) n=20’000

� randomisation:

� scanner à 0, 1 et 3 ans

� pas d’intervention

� Mesure semi-automatique du volume du nodule (non calcifié)

� Classification nodules selon volume:

� < 50 mm3 = négatif

� >500 mm3 = positif → évaluation multidisciplinaire

� 50-500 mm3 = indéterminé :

� nouveau scanner à 3 mois

� mesure de la croissance

Van Klaveren NEJM 2009

Analyse du nodule en 3D

� « croissance » si ↑ volume ≥ 25% (marge d’erreur = 20-25%)

� Si croissance→ temps de doublement :

� < 400 j → dépistage positif → évaluation multidisciplinaire

� > 400 j → dépistage négatif → nouveau scan à 1 an

� à 1 et 3 ans, nouveau dépistage avec même schéma

� Résultats:

� Dépistage initial positif: 2.6%

� vrais positifs (= cancer) 39.5%

� faux positifs (= maladie bénigne) 56.5%

� Étude en cours

Van Klaveren NEJM 2009

Coût-efficacité du dépistage

interventioncoût par année de vie

gagnée

dépistage du cancer colo-rectal 13’000 - 32’000 $

dépistage du cancer du sein 47’700 $

dépistage du cancer bronchique par scanner* 126’000 - 169’000 $

sevrage tabagique 17’000 $

dépistage cancer bronchique + sevrage tabagique* 130’500 - 159’700 $

McMahon J Thorac Oncol 2011*simulations

02.10.2013

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Perspective du patient

Woloshin NEJM 2012

Si dépistage individuel veut être proposé (hors étude)

British Thoracic Society:

� Déterminer le risque individuel de cancer

� scanner « faible dose »

� patient informé:

� des risques potentiels si découverte d’anomalies bénignes nécessitant des examens

� plus de chance de trouver une anomalie bénigne qu’un cancer

� expertise multidisciplinaire pour la prise en charge d’un nodule suspect

� intervalles de suivi clairement définis

� Si dépistage négatif, patient informé des symptômes de cancer

Kirkpatrick Thorax 2011

Conclusions

� Dépistage par radiographie n’améliore pas la survie

� Dépistage par scanner améliore la survie dans une grande étude, mais pas

dans 3 études plus petites.

� Autres études en cours (NELSON, …)

� Nombreuses questions encore non résolues

� Nécessité de programmes nationaux de démonstration

01/10/2013

1

Nodule pulmonaire solideQue faut-il savoir?

Dr Anne-Lise HachullaService de RadiologieHôpitaux Universitaires de Genève

Définitions - Fleischner Society

Hansell; Radiology 2008

� Micronodule� Opacité focale, arrondie, ± bien définie� Limite inférieure : 7mm / 5mm / 3mm

� Nodule < 3 cm

� Masse ≥ 3cm

� Distinction� Selon densité : Solide – Subsolide� Bénin – Malin – Indéterminé

Problématique

� Fréquence de découverte fortuite ++� 53 454 patients de 55-74 ans, > 30 PA à T0 :

• 9.2% à la radio de thorax• 27.3% au CT thoracique

� Prise en charge � Inquiétude chez le patient� Temps médical � Examens complémentaires

� Nécessité de standardisation des procédures

The National Lung Screening Trial Research Team. N Engl J Med 2011

01/10/2013

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Imagerie

� Radiographie de thorax� Taille - calcification� Limitée dans la caractérisation bénin / malin

� Scanner thoracique� Plus sensible mais moins bonne VPP � Paramètres de dose variés� Nouvelles technologies …

Itération - imagerie spectrale

Aberle. N Engl J Med 2013

1. Forme

2. Taille

3. Contours

4. Localisation

5. Contenu

Caractérisation du nodule

Morphologie : Forme

� Parfois assez caractéristique pour un diagnostic spécifique

Aspergillome

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Atélectasie par enroulement

� Masse ronde sous pleurale

� En regard d’un épaississement pleural

� Encorbellement des axes broncho-vasculaires

� Perte de volume du lobe atteint

Malformation Artério-Veineuse

Impaction mucoïde / bronchocèle

01/10/2013

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Opacité non nodulaire

� Forme et taille d’un lobule pulmonaire secondaire en axial

� Formation aplatie en reformation coronale et sagittale

Taille du Nodule

� Augmentation de la probabilité de cancer avec la taille du nodule

Mc Williams. N Engl J Med. 2013

� Prévalence du cancer pulmonaire � Nodule < 5mm : 0.1 – 1%

� Nodule de 5-10 mm : 1 - 30%

� Nodule >10 mm : 30 – 80%

12 mm

� Moyenne grand diamètre –petit diamètre

� Volumétrie

14 mm

12 mm

10 mm

Mesurer le nodule

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MIPMIP

MPR VRT

Nets et réguliersNon discriminant

(cancer et métastases possibles)

LobulésNon discriminant

(cancer et métastases possibles)

Spiculés ou irréguliersEn faveur de la malignité

(Interprétation difficile en cas d’emphysème)

Contours

Contours

Nets et Réguliers Lobulés Spiculés

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Interprétation parfois difficile en cas d’emphysème

Contrôle à 3 mois

Pneumonie organisée focale

Bords et contours

� Rétraction pleurale – scissurale

Harders SW; Acta Radiol. 2011

Augmentation

de 50% de

risque de cancer

01/10/2013

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Ganglion intra pulmonaire � Contours lisses, bien définis� Densité tissulaire homogène� De forme oblongue triangulaire� Localisation inférieure� < à 12 mm

Oshiro. J Comput Assist Tomogr; 2002

Localisation Sous pleurale – juxta scissurale

Mc Williams. N Engl J Med. 2013

PanCan Development Cohort :

2537 patients – 7008 nodules

0 cancer / 70 juxta scissural

BCCA Validation Cohort :

2537 patients - 5021 nodules

0 cancer / 501 juxta scissural

Localisation Sous pleurale – juxta scissurale

de Hoop. Radiology ; 2012

Localisation Sous pleurale – juxta scissurale

• Reconnaître les nodules juxta scissuraux atypiques :

• Nodule sphérique

• Bord concave

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� Vessel sign

Localisation: péri-vasculaire : dissémination hématogène ?

Harders SW; Acta Radiol. 2011

Augmentation

de la

probabilité de

cancer de 70%

Localisation

� Nodules malins:

� LSG - LSD +++

� LI – LM

Mc Williams. N Engl J Med. 2013

Contenu: calcifications

5. Excentrée5. Excentrée

6. Dispersée 6. Dispersée

1. Globale1. Globale 2. Centrale 2. Centrale

4. Lamellaire4. Lamellaire3. En pop3. En pop--corncorn

BénignesBénignes MalignesMalignes

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Métastase d’un

ostéosarcome

Granulome

Calcifications bénignes

Calcifications

rondes et centrales

Calcifications bénignes

Calcifications lamellaires

concentriques :

TUBERCULOME

Calcifications bénignes

Calcification en Pop-Corn

Hamartochondrome

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Calcifications

dispersées :

Tumeur carcinoïde

Calcifications malignes

Densité graisseuse

� Graisse: -40 à -120 UH• En faveur bénignité

• Attention si antécédents de liposarcome, cancer rénal

Hamartochondrome

- Forme sphérique

- Contours nets et réguliers

- Taille inférieure à 25mm

- Amas graisseux

- +/- Calcifications en pop corn

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Lipome

Contenu du nodule

Bronchogramme aérien - pseudocavitation� nodules malins (30%) vs nodules bénins (5%) � Adénocarcinome - lymphome

Excavation� Paroi épaisse ou irrégulière� Si épaisseur de la paroi > à 16mm =

plutôt malin� Si épaisseur de la paroi < à 4mm =

plutôt bénin

Seeman. Lung Cancer; 2004

Nombre de nodules

� Nb moyen nodules / personne :

� 5 (PanCan participants)

� 7 ( BCCA participants)

� Le nombre de nodules est < si un cancer est présent

Mc Williams. N Engl J Med. 2013

01/10/2013

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BéninBénin IndéterminéIndéterminé MalinMalin

Calcification globaleCalcification globaleHamartochondromeHamartochondromeLocalisation juxta Localisation juxta

scissuralescissuraleGanglion sousGanglion sous--

pleuralpleural

Taille > 20 mmTaille > 20 mmContours spiculésContours spiculésBronchogrammeBronchogramme

Calcifications Calcifications malignesmalignes

Nodule solide

STOPSTOPVérification Vérification histologiquehistologique

??

Exploration complémentaire possible

� Etude de l’activité biologique� PET – PET/CT au FDG

� Imagerie fonctionnelle� Swensen� Etude de perfusion

� IRM de diffusion

� Ponction/Biopsie sous CT � Biopsie chirurgicale

� Patient à risque d’une pathologie maligne

� Risque d’une biopsie – risque chirurgical

� Pertinence d’un traitement curatif

ACCP Guidelines. Chest 2013

ConclusionEvaluation du NPS au delà de l’imagerie

24.09.2013

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Prise en charge du nodule pulmonaire solide

Prof. Jean-William FittingService de pneumologie - CHUV

• Guidelines for management of small pulmonary nodules detected on CT scans: A statement from the FleischnerSociety.Radiology 2005; 237:395-400

• Diagnosis and management of lung cancer, 3rd ed: ACCP evidence-based clinical practice guidelines.Chest 2013; 143 (5 Suppl.)

ACCP Guidelines: champ d’application

• Nombre:– Nodule pulmonaire unique– Nodule pulmonaire dominant

+ 1 ou plusieurs plus petits (max. 10)

• Taille:– 1 - 8 mm

– 9 - 30 mm

• Contexte: – pas de différence entre screening et découvertes incidentes

(≠≠≠≠ Fleischner Society 2005)

Nodules: taille et risque de cancer

Mayo Clinic CT Screening Trial:

Taille du nodule: Risque de malignité:

< 3 mm 0.2 %4 – 7 mm 0.9 %8 – 20 mm 18.0 %> 20 mm 50.0 %

Midthun, Lung Cancer 2003; 41(suppl.2):S40

24.09.2013

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Nodules: taille et risque de cancer

Pan-Canadian Early Detection of Lung Cancer Study:

McWilliams, NEJM 2013; 369:910-9

Nodules de 1 à 8 mm

Recommandations pour les sujets asymptomatiques et sans tumeur extra-thoracique

• PET non recommandé

• Suivi recommandé par CT faible dose

• Facteurs de risque de cancer du poumon:(Fleischner Society 2005)

– Tabagisme– Cancer du poumon chez parent du 1er degré

– Exposition à l’amiante, uranium, radon

Gould, Chest 2013;143:93S-120S

24.09.2013

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Nodules de > 8 mm

Gould, Chest 2013;143:93S-120S

Estimation clinique de la probabilité de cancer

• Estimation par jugement clinique ou modèle quantitatif

• Modèle de prédiction Mayo Clinic:– Age OR = 1.04/an– Tabagisme OR = 2.2

– Cancer extra-thoracique (>5 ans) OR = 3.8– Taille du nodule OR = 1.14/mm

– Aspect spiculé OR = 2.8– Lobe supérieur OR = 2.2

Herder, Chest 2005; 128:2490-6

• Modèle de prédiction PanCanMcWilliams, NEJM 2013;369:910-9

Modèle de prédiction de malignité des nodules(40-75 ans, ≥ 30 UPA)

www.brocku.ca/cancerpredictionresearch

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Nodules de > 8 mm

Gould, Chest 2013;143:93S-120S

Choix de stratégie (1)

PET en principe pas obligatoire si:• Risque faible de cancer (< 5%) selon estimation clinique• Nodule périphérique cT1a (≤ 2 cm)

Diagnostic du nodule:• Biopsie à l’aiguille trans-thoracique:

– Nodule périphérique, pas d’emphysème, pas de scissure à traverser

• Bronchoscopie + EBUS radiaire ou/et électro-navigation:– Nodule proche d’une bronche, patient à risque élevé en cas de

pneumothorax

Choix de stratégie (2)

• Bilan d’extension médiastinal invasif indiqué si:– Adénopathies au CT, avec PET positif ou négatif– Ganglions normaux au CT, avec PET positif

• EBUS/EUS recommandé en 1ère intention

• En cas de prélèvement médiastinal négatif par EBUS/EUS, un bilan d’extension chirurgical est indiqué (médiastinoscopie ou thoracoscopie).

24.09.2013

5

Choix de stratégie (3)

En pratique, on considère simultanément:

• le diagnostic du nodule: – PET, bronchoscopie + EBUS radiaire ou/et électro-navigation

• le bilan d’extension médiastinal: – PET, bronchoscopie + EBUS (± EUS)

02.10.2013

1

NODULE PULMONAIRE EN VERRE DEPOLI

Que faut-il savoir?

Catherine BeigelmanCatherine Beigelman--AubryAubryCHUV CHUV

o Si dépistage effectifNational Lung Screening TrialRéduction mortalité de 20%Détection probablement augmentéeInvisibles en RX standard

o 69% des cancers pulmonaires méconnus

o Early Lung Cancer Action Project data44/233 résultats positifs: lésions avec GGO 19% 15/44 malignes 34%Composante solide 63% Verres dépolis purs 18%

National Lung Screening Trial Research Team, Aberle DR et al.Radiology 2011; 258:243Park CM RadioGraphics 2007; 27:3918Li F et al. Radiology 2002; 225:673–683Henschke CI et al. AJR Am J Roentgenol 2002;178:1053

ProbabilitéProbabilité de de malignitémalignité > nodules > nodules solidessolides

Ost DE, Gould MK. Am J Respir Crit Care Med 2012; Vol 185,363

02.10.2013

2

Période 60,000 CT entre 2000 – 2008

174 subsolid nodules n=171- GGO > 20% du nodule - < 2 cm

Taille initiale: 4 - 20 mm

Nodules: Non solid: 98 / Part solid: 76

Evolution: Suivi moyenne 29 mois (1-136)- Résolution n=18 - Stabilité: n=115- Croissance > 2 mm n=41

Histologie: HAA:3/ AIS: 36/ MIA: 11/ ADK inv: 6

Facteurs prédictifs de croissance:- Nodule >10 mm - ATCD de tumeur pulmonaire (non solid)

Facteur génétique ?

Matsugama H et al. Chest 2012

Méthodes de Kaplan-Meier

wth curves according to the type o 13 and 23% for nonsolid nodule,

respectively d 38 and 55% for part-solid nodule,

Time to 2-mm subsolid nodule growth curves apercentages of growing nodule were 13 and 23%

2- and 5-year cumulative % of growing nodule

Composante solide ? Composante solide ? Vaisseau?Vaisseau?

Les reconnaître …Les reconnaître …

10 12 09 03 10 11

1,25/0,6mm

5/5 mm

02.10.2013

3

� Non tumoral � Inflammation focale

� Fibrose interstitielle focale

� Hémorragie focale

� Oedème

� Tumorales

� HAA

� AIS

� AMI

� ADK invasifs

03 08 12 29 09 12

…….

Park CM et al. Eur Radiol 2007;17:2325

02.10.2013

4

Muzykewicz DA et al. J Comput Assist Tomogr 2012; 36(5):518Matsushita M et al. Jpn J Radiol 2012; 30:772Seo JB et al. Radiographics 2001; 21: 403Gaeta M et al.J Comput Assist Tomogr 1996; 20:300Okita R et al. The Annals of Thoracic Surgery 2005; 79(1)Kang J. et al. Clinical Imaging 2010; 34: 396

02.10.2013

5

Pneumonie focale organiséePneumonie focale organisée

02.10.2013

6

18 07 11 04 08 11

Nodule mixte

Nature inflammatoire ou infectieuse

Nodule mixte

Nature inflammatoire ou infectieuse

Absence de critère morphologique de Absence de critère morphologique de différenciation différenciation

Park CM et al. Eur Radiol 2007;17:2325Kim HY et aé. Radiology 2007: Vol 245;1

Forme polygonale, contours lobulés, spiculés

02.10.2013

7

28/10/05 21/09/12

> 0,5mm

Collapsus alvéolaire focalProlifération fibroblastique active

Progressive Multifocale

de Hoop B. et al. Radiology 2010: Vol 255: 1

Détection d’une composante solide au sein GGNDétection d’une composante solide au sein GGNAgrément intra et Agrément intra et interobservateurinterobservateur modérémodéré

Mesure masse GGN (Mesure masse GGN (volumevolume x x valeur HUvaleur HU): ): Variabilité < volume GGNVariabilité < volume GGN

Suivi nodules malinsSuivi nodules malinsAugmentation % masse > volume ou diamètreAugmentation % masse > volume ou diamètreDétection croissance plus rapideDétection croissance plus rapide

Kakinuma R et al. J Comput Assist Tomogr 2004; 28:17J.H. Min et al. / Lung Cancer 69 (2010) 123–126

Progression tumorale

02.10.2013

8

� 54 nodules subsolides Patients n= 52

- ADK T1N0M0 n= 47 - HAA n= 4- Lymphoprolifération n= 1

� AAH −682 ± 64 HU

Type A −544 ± 179 HUType B −496 ± 147 HU

Invasives −371 ± 142 HU

� 7 GGO: lésions pré-invasives- Diamètre maximum ≤1 cm - m-CT value ≤ −600 HU

�16/22 (73 %): lésions invasives- Diamètre maximum >1 cm - m-CT value > −600 HU

� > 1 cm ou −600 HU : Résection > Surveillance

-620 UH !Composante invasive

possible

-301 HU Résection

Suivi

15 mm

Kitami A. Gen Thorac Cardiovasc Surg. 2012 July; 60(7): 425Ikeda K et al. Chest. 2007;132:984

Nomori H et al. Ann Thorac Surg. 2003;76:867Yanagawa M et al. Br J Radiol. 2009;82:532

8 mm

29/11/10 07/07/11

Park CM et al. Eur Radiol 2007;17:2325

02.10.2013

9

Aoki et al. Radiology 2001; 220: 803

N = 127 adénocarcinomes < 3 cm

Gg métastatiquesInvasion vasculaire

Plus raresMeilleur pronostic

Pas de gg métastatique ni invasion vasculaire

Takashima S et al.AJR Am J Roentgenol 2003;180:817Kuriyama K et al. AJR Am J Roentgenol 1999;173:465

02.10.2013

10

105 adénocarcinomes pulmonaires ≤ 20 mm < 50% GGO

Signes: - Encoches- Bronchogramme aérien- Rétraction pleurale- Spiculation- Envahissement veineux- GGO

Corrélation histo-pathologique

Présence de notches: 50% des cas-Taux de récidive >>- Incidence > avec croissance tumorale- Fréquent dans ADK peu différenciés

Ikeharaa M et al. European Journal of Radiology 81 (2012) 189– 194

Takahashi S. Jpn J Radiol 2012; 30:206

GGO n=150Patients n=111Imagerie initiale, 2 ans, final

n = 131stables 87,3 %

n= 19 ↑ 12,7 %- Après suivi 66 ± 25 mois

- 6 /19 stables à 2 ans 31,6%- TD moyen:1248 j 360-2439 j

Taille > 10 mmAspect « Bubble like »

Contours lobulésInvasion stromale fibroblastique

02.10.2013

11

Bubble like: pseudo-cavitation

Bronchogramme aérien

Spiculation> 2mm

Pleural indentation

Saito H et al.J Comput Assist Tomogr.2009;33:42Kuriyama K et al. AJR Am J Roentgenol. 1991;156:921

Notches

HAA

AIS Non mucineux

Uniques ou multiples

AIS Mucineux

ADK invasifs ADK invasifs mucineux

Travis WD et al., Journal of Thoracic Oncology 2011; Vol 6, 2, 244

AMI Non mucineux AMI Mucineux

Synthèse

Questions et remarques

Plusieurs GGO de causes diverses

� HAA: 4 foyers

� Léiomyomatose focalisée : 3

� Foyers de bronchiolite respiratoire

� Adénocarcinomes: 2

AIS- Adénocarcinome acinaire

02.10.2013

12

OverdiagnosisOverdiagnosis? ?

Suivi Suivi

-- GGO < 5 mm ?GGO < 5 mm ?-- GGO > 5 mmGGO > 5 mm

< 10 mm sans < 10 mm sans bubblebubble likelike ni ni lobulationlobulation1/an > 2ans …..1/an > 2ans …..

-- GGO > 10 mmGGO > 10 mm1/6 mois à 1 an1/6 mois à 1 an

Nuances selon densité du verre dépoliNuances selon densité du verre dépoli

Chevauchements morphologiquesChevauchements morphologiques

Impact sur le TImpact sur le T

01.10.2013

1

Kim JS et al. Radiology 2005; 236: 295-299

Rubin GD et al. Radiology 2005; 234:274-283

Nodules ? Vaisseaux ? Nodules ? Vaisseaux ?

Deux domaines

Volumétrie

Suivi temporel

Caractérisation lésionnelle

Réduction de la charge du radiologue

↑ de la sensibilité détection et confianceDiederich et al. Cancer Imaging 2006

Chen H et al. Acad Radiol. 2010 17(5) 595

Différenciation malin-bénin

01.10.2013

2

Bae et al. Radiology 2005; 236: 286 Kim et al. Radiology 2005; 236:295

Brown et al. Radiology 2003; 226:256 Wormanns et al. Eur Radiol 2002; 12: 1052

Marten et al. Eur Radiol 2005;15: 203

Das et al. Radiology 2006; 241: 564 Matsumoto et al. Eur J of Radiol 82 2013; 1332

Marten et al. Clinical Radiology 2005; 60: 196 Naidich et al. J Thorac Imaging 1993; 8: 291

Modification approche thérapeutique

Potentiel de Compensation déficiences humaines dans

détection de petites lésions

Diminution de la variabilité inter-observateurs

Accélération du workflow

Sensibilité moyenne

Brochu et al. J Radiol. 2007 Apr;88(4):573 Bae et al. Radiology 2005; 236: 286

Rubin et al. Radiology 2005; 234: 274

Radiologues seuls 50% (41-60%)

Double lecture 63% (56-67%)

Radiologue + CAD 76% (73-78%)

195 nodules non calcifiés

Bénéfice du CAD utilisé comme 2° lecteur +++

Même comparé à la double lecture

01.10.2013

3

Goo et al. Korean J Radiol 12(2), Mar/Apr 2011

CAD: Nodules isolés et de petite taille

Radiologues: Nodules attachés ou de plus grande taille

Indications:

o Suspicion d’EP n= 33o Dépistage du cancer broncho-pulmonaire n = 28o Suivi de néoplasie n = 39

Résultats du CAD R2Patients: n = 33Lésions Significatives n = 53

12.1%

21.4%

23.11%

Peldschus K et al. Chest 2005; 128: 1517

Réduction de diagnostics méconnus

Erreurs de perception

70% des poursuites en imagerie médicale

Significativité

Haute et/ou intermédiaire

100 scanners thoraciques interprétés normaux

5% > 1cm

méconnues

01.10.2013

4

Schramm et al. Interactive CardioVascular and Thoracic Surgery 12 (2011) 20

CT Préopératoire Sep-Dec 09 n=18

CAD n= 64 (3,6; 1-7)

Intervention n= 91 (5; 1-11)

Nodules additionnels: 27

Histologie- Nodules additionnels: n= 27 Bénins

- Métastases n= 30 CAD +

Thoracotomie avec palpation versus VATS

Proposition de marques selon un agencement spécifique

Validation par le radiologue

Sagittal 0,7 mm

Coronal MIP 4,9 mmMIP 4,8 mm

GEGEGEGE

Nodules solidesNodules solides

01.10.2013

5

3D

2D

Histogramme de densité

Valeur d’atténuation maximum

01.10.2013

6

Mesures 2D en suivi TDM:

Gestion des nodules pulmonaires non calcifiés

de cause indéterminée

Yankelevitz et al. Radiology 2000;217:251

Croissance d’un nodule: 3D

Possible croissance asymétrique

Doublement du volume d’un nodule :

↑ de 26% du diamètre

Revel et al. Radiology, 2004; 231:453

Revel et al. Radiology 2004; 231:459

Mauvais agrément intra- et inter-observateur

Volumétrie automatique 3D plus fiable /

Estimations volume > mesures 2D

Reproductibilité ++

Sources de variabilité

01.10.2013

7

01.10.2013

8

Erasmus et al. Radiographics 2000;20:59

Revel MP et al. AJR 2006; 187:135

Quantification de la réponse tumorale

Progression en cas de nodules malins

Calcul du temps de doublement

Nodules malins : 30 - 400 jours

Moyenne: 100 jours

Nodules solidesNodules solides

Caractérisation

Marten et al. Eur Radiol 2006

Revel MP et al. AJR 2006; 187:135

4.918 cm3

4.517 cm3

10%

SOFT

LUNG

Augmentation Volume > 25%

Inspiration - Expiration

526 mm3

724 mm3

27%

01.10.2013

9

Couplage des nodules complexe

Position des nodules variable entre deux examens

Augmentation significative de volume

85 jours

RECIST stable …

Initial

PET scan négatif….

Contrôle 2 ans

Après antibiothérapie

01.10.2013

10

Synchronisation rétrospective Inclusion des vaisseaux

Non détectée par Lung VCAR 3 ans 265 jours

Intégration des structures vasculaires

Examen Initial Scanner de contrôle

Temps de doublement concordant avec une lésion maligne

252 jours

01.10.2013

11

Gain significatif en sensibilité sans coût de temps

Performance en terme de détection, capacité de pairing

et temps de lecture

Système R2

Beigelman-Aubry, AJR 2007: 189; 948

Temps moyen par marque de CAD: 5-8 secondes

Temps moyen pour toutes marques: 39 secondes

Temps de doublement > 1000 jours pour les nodules malins

Nodules malins en verre dépoli stables dans 33 / 34 cas

Hasegawa. Br J Radiol 2000; 73: 1252

Nakata et al. Chest 2002; 121: 1464

Douleur thoracique

Stable sur 4 ans

Densité: -301 HU

…..

Nodules non solidesNodules non solides

Qualité d’extraction

pour volumétrie parfaite et….

01.10.2013

12

Histogramme de densité

Oda S et al. Acad Radiol 2011; 18:63–69

Courbe de profil densitométrique

ADK pulmonaire périphérique:

Corrélations avec le type de Noguchi

Li et al. AJR 2004; 183: 1209

Shah et al. Acad Radiol 2005; 12: 1310

Murata et al. Radiation Medicine 2004; 22: 20-24

Kido et al. J Comput Assisted Tomogr 2003; 27: 56

Suzuki et al. IEEE Trans Med Imaging 2005; 24: 1138

Way et al. Med Phys 2006; 33: 2323

Analyse Fractale de texture

interne et périphérique

Réseau neuronaux artificiels

avec entraînement massif

Analyse de signes morphologiques et densitométriques

�Nodules pulmonaires méconnus en revue clinique +++

�CAD en 2° lecture permet d’augmenter

�Le débit du radiologue

Temps d’interprétation ↑

Disponibilité pour la prise en charge des nodules

�La confiance du radiologue

Réel confort dans l’interprétation

�Plusieurs seuils de détection disponibles

�Analyse volumétrique et densitométrique

01.10.2013

13

Sensibilité de détection des nodules solides > 4 mm ↑ ++ avec le CAD

Temps de lecture pour comparaison temporelleNon affecté par le CAD

Suivi des nodules indéterminésScreening - Contexte oncologique

Planification chirurgicale

03.10.13

1

Dr C. Beigelman, Service de radiodiagnostic Pr J. Prior, Service de médecine nucléaire Dr I. Letovanec, Service de pathologie

Nodule pulmonaire: Place de la TEP Corrélations morphologiques, métaboliques et histologiques

Le nodule pulmonaire – 5 octobre 2013 Dr Catherine Beigelman Aubry

Place de la TEP/TDM

Radiotraceur 18F-FDG : métabolisme glucose et tumeur

Tumeur : •  ↑GLUT1,3 •  ↑Hexokinase

(isoforme II) •  ↑métabolisme

(favorise voie anaérobe, moins efficace)

03.10.13

2

Valeur TEP / diagnostic NPU : haute sensibilité (>8-10mm)

0%

20%

40%

60%

80%

100%

Fischer 2002

Gould 2001

Hellwig 2001

Wahidi 2007

Ung 2007

Moyenne

Sensibilité Spécificité

Hellwig et al. Nuklearmedizin 2009

92%

77%

Méta-analyses

TEP/TDM ne remplace pas l’histologie

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

SUV 0–2.5 SUV 2.6–4.0 SUV >4.0

Bénin Malin

Sim et al. Lung 2013 N=641 NPU

62%

62%

73%

94%

TEP : 2 critères de positivité & FP

greater than 2.5, which were the same false-positive lesions

on semiquantitative assessment using SUVmax on PET

scans.Five cases of false-negative nodules based on visual

analysis were moderate- to well- differentiated carcinomas

and a metastasis from granulosa cell tumour, as detailed inTable 6. All five lesions with ‘‘likely benign’’ morpho-

logical features demonstrate low FDG uptake (\2.5).The results of SUVmax based on pathology are shown

in Table 7.

Although the range of SUVmax overlapped between thecategories of malignant and benign nodules, patients with

malignant nodules had higher median SUVmax.

Of 186 SPNs, there were 149 nodules (80 %) in ourseries with SUVmax greater than the cutoff value of 2.5.

With increasing SUVmax, the likelihood of malignancy is

greater. The number of malignant versus benign nodules inrelation to SUVmax values is depicted in Table 8. If the

SUVmax is between 2.6 and 4.0, there is a 73 % chance the

nodule is malignant. If the SUVmax of a pulmonary noduleis greater than 4.1, there is a 94 % chance it is malignant.

However, when the SUVmax is \2.5, there is still a 62 %

chance the nodule is malignant.Of the 186 cases included in our series, 33 patients had

history of malignancy within 3 years before PET–CT scan

for investigation of SPN. The sites of original primarytumour and pathology of SPNs in these patients are sum-

marized in Table 9. In these 33 patients with history of

malignancy, 15 nodules (46 %) were metastatic fromknown primary tumour; 13 nodules (39 %) were confirmed

as a second primary malignant lesion, and 5 nodules(15 %) were benign.

Discussion

Increasing number of patients is referred for PET–CT scansto further evaluate SPN, which most often are detected

incidentally on CT scans performed for a myriad of clinical

reasons. The Fleischner Society guidelines for managementof small pulmonary nodules are widely adopted, outlining

appropriate imaging follow-up according to patient risk

stratification and nodule size [18]. For pulmonary noduleslarger than 8 mm, in addition to follow-up CT at approx-

imately 3, 9, and 24 months, options such as dynamic

contrast-enhanced CT, PET, and/or biopsy can be

Table 3 Causes of false positive PET–CT scans for SPN character-ization (n = 14) using cutoff SUVmax of 2.5

Cause Numberofpatients

Median valueof SUVmax(range)

Chronic inflammation/granuloma 4 2.8 (2.6–5.5)

Aspergillus infection 2 4.1 (2.8–5.3)

Abscess/infection (no specifiedorganism)

2 5.1 (4.7–5.4)

Classical carcinoid tumoursa 2 3.7 (3.6–3.8)

Granulomatous process(TB or sarcoidosis)

1 10.2 (10.2)

Tuberculosis 1 4.4 (4.4)

Mixed dust pneumoconiosis 1 6 (6)

Fibrosis 1 3.1 (3.1)

a These two carcinoid tumours were classified as benign by twopathologists independently reviewing the histology

Table 4 Causes of false-negative PET–CT scans(n = 21) using cutoff SUVmaxof 2.5

Cause Number ofpatients

Median size(range) (mm)

MedianSUVmax(range)

Degree of differentiation

Adenocarcinoma 12 15 (10–30) 1.8 (0.9–2.3) Well- (3), moderately differentiated(9)

Squamous cellcarcinoma

5 12 (9–15) 1.7 (0.7–2.2) Moderately differentiated

Metastasis 3 11 (10–19) 1.2 (1.2–2.1) Colorectal cancer (1), renal cellcancer (1), granulosa cell (1)

Bronchioloalveolarcarcinoma

1 25 (25) 1.4 (1.4) Not available

Table 5 False-positive nodules based on visual analysis of nodulemorphology (n = 21)

Causes Number of patients

Chronic inflammation/granuloma 7

Infection/abscess 6

Classical carcinoid tumour 2

Chondroid hamartoma 1

Fibrosis 1

Granulomatous process (TB or sarcoidosis) 1

Mixed dust pneumoconiosis 1

Benign rheumatoid nodule 1

Solitary fibrous tumour 1

Lung

123

greater than 2.5, which were the same false-positive lesions

on semiquantitative assessment using SUVmax on PET

scans.Five cases of false-negative nodules based on visual

analysis were moderate- to well- differentiated carcinomas

and a metastasis from granulosa cell tumour, as detailed inTable 6. All five lesions with ‘‘likely benign’’ morpho-

logical features demonstrate low FDG uptake (\2.5).The results of SUVmax based on pathology are shown

in Table 7.

Although the range of SUVmax overlapped between thecategories of malignant and benign nodules, patients with

malignant nodules had higher median SUVmax.

Of 186 SPNs, there were 149 nodules (80 %) in ourseries with SUVmax greater than the cutoff value of 2.5.

With increasing SUVmax, the likelihood of malignancy is

greater. The number of malignant versus benign nodules inrelation to SUVmax values is depicted in Table 8. If the

SUVmax is between 2.6 and 4.0, there is a 73 % chance the

nodule is malignant. If the SUVmax of a pulmonary noduleis greater than 4.1, there is a 94 % chance it is malignant.

However, when the SUVmax is \2.5, there is still a 62 %

chance the nodule is malignant.Of the 186 cases included in our series, 33 patients had

history of malignancy within 3 years before PET–CT scan

for investigation of SPN. The sites of original primarytumour and pathology of SPNs in these patients are sum-

marized in Table 9. In these 33 patients with history of

malignancy, 15 nodules (46 %) were metastatic fromknown primary tumour; 13 nodules (39 %) were confirmed

as a second primary malignant lesion, and 5 nodules(15 %) were benign.

Discussion

Increasing number of patients is referred for PET–CT scansto further evaluate SPN, which most often are detected

incidentally on CT scans performed for a myriad of clinical

reasons. The Fleischner Society guidelines for managementof small pulmonary nodules are widely adopted, outlining

appropriate imaging follow-up according to patient risk

stratification and nodule size [18]. For pulmonary noduleslarger than 8 mm, in addition to follow-up CT at approx-

imately 3, 9, and 24 months, options such as dynamic

contrast-enhanced CT, PET, and/or biopsy can be

Table 3 Causes of false positive PET–CT scans for SPN character-ization (n = 14) using cutoff SUVmax of 2.5

Cause Numberofpatients

Median valueof SUVmax(range)

Chronic inflammation/granuloma 4 2.8 (2.6–5.5)

Aspergillus infection 2 4.1 (2.8–5.3)

Abscess/infection (no specifiedorganism)

2 5.1 (4.7–5.4)

Classical carcinoid tumoursa 2 3.7 (3.6–3.8)

Granulomatous process(TB or sarcoidosis)

1 10.2 (10.2)

Tuberculosis 1 4.4 (4.4)

Mixed dust pneumoconiosis 1 6 (6)

Fibrosis 1 3.1 (3.1)

a These two carcinoid tumours were classified as benign by twopathologists independently reviewing the histology

Table 4 Causes of false-negative PET–CT scans(n = 21) using cutoff SUVmaxof 2.5

Cause Number ofpatients

Median size(range) (mm)

MedianSUVmax(range)

Degree of differentiation

Adenocarcinoma 12 15 (10–30) 1.8 (0.9–2.3) Well- (3), moderately differentiated(9)

Squamous cellcarcinoma

5 12 (9–15) 1.7 (0.7–2.2) Moderately differentiated

Metastasis 3 11 (10–19) 1.2 (1.2–2.1) Colorectal cancer (1), renal cellcancer (1), granulosa cell (1)

Bronchioloalveolarcarcinoma

1 25 (25) 1.4 (1.4) Not available

Table 5 False-positive nodules based on visual analysis of nodulemorphology (n = 21)

Causes Number of patients

Chronic inflammation/granuloma 7

Infection/abscess 6

Classical carcinoid tumour 2

Chondroid hamartoma 1

Fibrosis 1

Granulomatous process (TB or sarcoidosis) 1

Mixed dust pneumoconiosis 1

Benign rheumatoid nodule 1

Solitary fibrous tumour 1

Lung

123

Sim et al. Lung 2013

Se 81% Sp 50% PPV 91% NPV 40%

Ex 81%

Se 91% Sp 25% PPV 88% NPV 58%

Ex 94%

Critère PET+ : SUV > 2.5 Critère PET+ : captation visible

Faux-positifs Faux-positifs

03.10.13

3

SUV : pas discriminant pour origine

5.9 8.4

6.5 4.7

1.8

0

5

10

15

20

25

30

adénoCA épidermoïde autreCA infectieux autre bénin Sim et al. Lung 2013

N=641 NPU

62%

SUV moyen±[min;max] (g/mL) Median size 18 mm [8–30]

TEP/TDM : FP & FN existent Faux-positifs

•  Infections (bactéries, myco-bactéries, aspergillose)

•  Inflammation: sarcoïdose, nodule rhumatoïde, granu-lomatose de Wegener, his-toplasmose, collagénoses

•  Artefact d’atténuation •  Embolies pulmonaires,

emboles iatrogéniques •  Amyloïdose

Faux-négatifs

•  Faible métabolisme : ca in situ, carcinoïde

•  Résolution spatiale de la TEP : 4–8 mm

•  Mauvais alignement entre la TEP et la TDM

•  Hyperglycémie •  Captation de base FDG

dans les cellules normales

TEP/TDM : nodule pulmonaire <10 mm ?

•  Utilité démontrée si <10 mm [4–8 mm] –  Parfois nodule pulmonaire indéterminé ou mal interprété sur CT

(impaction mucoïde) –  Captation TEP fortement dépendante de la taille et de la biologie

tumorale –  Visualisation nécessaire des images TEP non corrigées

Calcagni et al World J Surg Oncology 2012

malignant can be compromised by ‘metabolic’ causes and‘technical’ aspects, which lead to false-negative results.The metabolic causes which can reduce sensitivity are:

(1) a high blood glucose level, because of competitive reac-tion [11]; (2) 18 F-FDG avidity related to the histologicalpattern: low in some tumor types and in slow-growingtumors (bronchiolo-alveolar carcinoma, carcinoid, metasta-sis of clear-cell renal-cell carcinoma, etc.) [12]; (3) the18 F-FDG uptake related to the degree of cell differentiation:lower in well-differentiated cells than in moderately differ-entiated ones [13]; (4) the number of viable malignant cells.Fischer et al. [14] demonstrated ‘in vitro’ that the theoret-ical detection limit of 18 F-FDG is in the magnitude of 105

to 106 malignant cells, depending on the glucose turnoverof the specific cancer. Recently, Wahl et al. [15] reported‘in vivo’ that the limit of 18 F-FDG PET for detecting can-cers is generally in the magnitude of 108-109 cells, whichtranslates into a tumor size between 0.4 and 1 cm indiameter.The technical aspects that can determine an underesti-

mation of the true 18 F-FDG activity, especially innodules smaller than 1 cm, are: the respiratory motionbecause of the displacement caused by shallow breathing,particularly in nodules located in the periphery and inthe base of the lungs; the partial volume effect becausenodules smaller than the resolution of the PET scanners

Figure 4 The undetermined nodule. 18 F-FDG PET-CT: CT (a), PET (b), and fused (c) axial images. A focus of intense 18 F-FDG uptake was evidentin the lower right lobe corresponding to the nodule located in the context of an atelectatic band (black arrow).

Figure 3 The not recognized nodule. (a) 18 F-FDG PET-CT fused axial image: intense 18 F-FDG uptake in the mass of the upper right lobe.Another focus of intense 18 F-FDG uptake was evident medially in the upper right lobe. (b, c) A retrospective analysis of contrast-enhanced CTrevealed a small nodule located near vessels corresponding to the site of 18 F-FDG uptake (white arrow).

Calcagni et al. World Journal of Surgical Oncology 2012, 10:71 Page 5 of 8http://www.wjso.com/content/10/1/71

(ranging from 6 to 10 mm in clinical applications) are not,or only faintly visualized [8,16,17]. Likewise, 18 F-FDG PETspecificity for characterizing pulmonary nodules as prob-ably malignant can be compromised by ‘metabolic’ causesand ‘technical’ aspects, which lead to false-positive results.The metabolic causes are: benign neoplasms (sclerosis

hemangioma, leiomyoma, and so on), infection (tubercu-losis, sarcoidosis, and so on) or inflammation (acute inflam-mation associated with bronchiectasis or thromboembolicdisease, and so on) [12,18-20]. To our knowledge, a pul-monary micro-embolism provoked during 18 F-FDG injec-tion can be considered the only reason ‘technically’responsible for a false-positive result. The vascular endo-thelium can be damaged by several factors, such as a para-venous or ‘in bolo’ injection, producing micro-emboli. Thecellular activation process at the site of pulmonary micro-emboli requires energy with a consequent increased glu-cose uptake [21,22]. From a ‘scintigraphic’ point of view,this is evident as a focal 18 F-FDG lung uptake but, thanksto CT integrated with the PET scanner, its artifactualnature should be suspected in the absence of correspond-ing abnormalities at the co-registered CT [23].Our first case showed focal 18 F-FDG activity in the lung

parenchyma in the absence of any detectable abnormality,even at co-registered unenhanced CT. We could excludean artifact caused by the micro-embolism provoked duringinjection because: we routinely inject the radiotracersthrough a venous cannula avoiding a para-venous injectionand repeated blood aspirations; no bolus injection was per-formed and no vascular activity due to a para-venous in-jection in the arm was evident in the images. The focus of18 F-FDG activity projecting onto the subpleural paren-chyma was considered as non-specific, also because atcontrast-enhanced CT performed only ten days before, noother morphological abnormalities were detectable except

the known mass. It is very interesting to note that the 18 F-FDG activity was already evident 7 months before the CTappearance of a 1 cm nodule, therefore indicating its ma-lignant nature. The absence of a detectable nodule at thefirst CT examination suggests that the area of focal 18 F-FDG uptake contained a very small number of tumor cells,not enough for anatomical detection, and therefore, itwould be reasonably to say around the lowest 18 F-FDGdetection limit, as reported [15]. This supports the well-known concept that the metabolic/functional alterationsmay precede the morphologic ones, and PET can some-times detect early changes not, or only minimally revealedby morphological imaging [24].Also in case 2 we could exclude an artifact due to a

micro-embolism by applying the same considerationspreviously described. Differently from case 1, taking intoaccount the very high oncologic risk of this patient, thePET finding was considered highly suspicious for malig-nancy, even in the absence of any clear morphologicabnormalities at co-registered unenhanced CT. No clearevidence of a nodule at co-registered unenhanced CTcould be explained by some technical acquisition rea-sons: slice thickness (5 mm), free breathing and ‘lowdose’ setting (tube current of about 40 mA/s). These ac-quisition parameters could limit the detection of smallpulmonary nodules at co-registered unenhanced PET-CT, especially in a juxtavascular location. A volumetrichigh-resolution CT was suggested to overcome theselimits; with this technique, slice thickness is 1 mm or less,in a single, breath-held inspiration, with a full radiationdose, allowing the identification of small pulmonarynodules. However, a delay of 3 months was suggested toidentify dimensional growth, as this is the only reliable cri-terion in favor of malignancy; the other criteria commonlyused to define malignancy of a nodule (dimensions, site,

Figure 5 The smallest nodule. 18 F-FDG PET-CT: CT (a), PET (b), and fused (c) axial images. A focal 18 F-FDG uptake was evident in a very smallnodule (black arrow) located in the upper left lobe.

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4

pattern, which was diffuse hypermetabolic activity along themain bronchus. On the contrary, 8 patients (50%) in the NIPAgroup demonstrated the isometabolic halo pattern, 6 patients(38%) demonstrated the isometabolic nodule pattern, and no patientsdemonstrated the hypermetabolic nodule pattern. The remaining

2 patients (12%) with NIPA were classified as ‘‘other’’ becausethere was no visible metabolic activity in 1 patient and focal

FIGURE 1. PET/CT images showing visual uptake patterns of pulmonary aspergillosis. Isometabolic halo pattern (A), isometabolic nodulepattern (B), and hypermetabolic nodule pattern (higher activity than in the mediastinum) (C).

TABLE 1. Demographic and Clinical Features of the PatientsWith Pulmonary Aspergillosis

IPA (n = 8) NIPA (n = 16) P

Age, mean T SD, y 48 T 17 62 T 12 0.035*Male, n (%) 6 (75) 10 (63) NS†Immunocompromisedstatus, n (%)

7 (88)‡ 1 (6)§ G0.001†

*Determined using the Student t test.†Determined using the W2 test.‡Due to acute myelogenous leukemia (n = 2), liver transplantation

(n = 2), ongoing chemotherapy for lung cancer (n = 1), ongoing targetedtherapy for malignant rectal gastrointestinal stromal tumor (n = 1), orautologous peripheral blood stem cell transplantation for Ewing sarcoma(n = 1).

§Due to ongoing chemotherapy for advanced ovary cancer (n = 1).NS indicates not significant.

TABLE 2. Visual Analysis of 18F-FDG PET/CT Images ObtainedFrom the IPA and NIPA Groups

Uptake Pattern IPA* (n = 8) NIPA† (n = 16)

Isometabolic halo‡ 0 (0%) 8 (50%)Isometabolic nodule§ 1 (13%) 6 (38%)Hypermetabolic nodule|| 6 (75%) 0 (0%)Other¶ 1 (13%)# 2 (12%)**

*†P = 0.006 determined using linear-by-linear association.‡Central cold soft tissue area with surrounding areas of increased

metabolism.§Mild hypermetabolic (similar to or less than the mediastinum)

nodule or consolidative lesion.||Hypermetabolic (higher than the mediastinum) nodule or consolidative

lesion.¶Not specified.#Diffuse hypermetabolic activity along the bronchus (n = 1).**No visible activity (n = 1) and focal hypermetabolic activity in a

mild hypermetabolic mass-like consolidation (n = 1).

Kim et al J Comput Assist Tomogr & Volume 37, Number 4, July/August 2013

598 www.jcat.org * 2013 Lippincott Williams & Wilkins

Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

pattern, which was diffuse hypermetabolic activity along themain bronchus. On the contrary, 8 patients (50%) in the NIPAgroup demonstrated the isometabolic halo pattern, 6 patients(38%) demonstrated the isometabolic nodule pattern, and no patientsdemonstrated the hypermetabolic nodule pattern. The remaining

2 patients (12%) with NIPA were classified as ‘‘other’’ becausethere was no visible metabolic activity in 1 patient and focal

FIGURE 1. PET/CT images showing visual uptake patterns of pulmonary aspergillosis. Isometabolic halo pattern (A), isometabolic nodulepattern (B), and hypermetabolic nodule pattern (higher activity than in the mediastinum) (C).

TABLE 1. Demographic and Clinical Features of the PatientsWith Pulmonary Aspergillosis

IPA (n = 8) NIPA (n = 16) P

Age, mean T SD, y 48 T 17 62 T 12 0.035*Male, n (%) 6 (75) 10 (63) NS†Immunocompromisedstatus, n (%)

7 (88)‡ 1 (6)§ G0.001†

*Determined using the Student t test.†Determined using the W2 test.‡Due to acute myelogenous leukemia (n = 2), liver transplantation

(n = 2), ongoing chemotherapy for lung cancer (n = 1), ongoing targetedtherapy for malignant rectal gastrointestinal stromal tumor (n = 1), orautologous peripheral blood stem cell transplantation for Ewing sarcoma(n = 1).

§Due to ongoing chemotherapy for advanced ovary cancer (n = 1).NS indicates not significant.

TABLE 2. Visual Analysis of 18F-FDG PET/CT Images ObtainedFrom the IPA and NIPA Groups

Uptake Pattern IPA* (n = 8) NIPA† (n = 16)

Isometabolic halo‡ 0 (0%) 8 (50%)Isometabolic nodule§ 1 (13%) 6 (38%)Hypermetabolic nodule|| 6 (75%) 0 (0%)Other¶ 1 (13%)# 2 (12%)**

*†P = 0.006 determined using linear-by-linear association.‡Central cold soft tissue area with surrounding areas of increased

metabolism.§Mild hypermetabolic (similar to or less than the mediastinum)

nodule or consolidative lesion.||Hypermetabolic (higher than the mediastinum) nodule or consolidative

lesion.¶Not specified.#Diffuse hypermetabolic activity along the bronchus (n = 1).**No visible activity (n = 1) and focal hypermetabolic activity in a

mild hypermetabolic mass-like consolidation (n = 1).

Kim et al J Comput Assist Tomogr & Volume 37, Number 4, July/August 2013

598 www.jcat.org * 2013 Lippincott Williams & Wilkins

Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Aspergillose (invasive vs. noninvasive)

•  N=24 pat. immunocom-promis avec aspergillose

•  Forme invasive différen-ciable forme noninvasive

Kim et al. J Comput Assist Tomogr 2013

isometabolic nodule pattern

isometabolic halo pattern

hypermetabolic nodule pattern

invasive

non-invasive

SUV

invasive

noninvasive

TEP/TDM et lésions en verre dépoli •  Faible sensibilité TEP/TDM (10–20%) : utilité reste à

démontrer (recommandable si composante mixte existe) •  Chiu et al. (Clin Imaging 2012) : différenciation

impossible lésions bénignes vs. malignes en verre dépoli par TEP/TDM en 2 temps (n=19)

3.79±4.46 (range, 0.70–19.37), respectively; P=.001]. In thesolid SPN group, mean percentage change in maximum SUV(retention index) was also higher in the malignant subgroupthan in the benign subgroup; however, this did not achieve alevel of statistical significance [17.51±18.08 (range, !25.03to 69.64) vs. 11.45±19.48 (range, !23.81 to 64.26),respectively; P=.181].

On the other hand, in the patient group with GGNs,mean early maximum SUV was lower in the malignantsubgroup than in the benign subgroup [1.89±0.85 (range,0.76–3.46) vs. 2.86±2.36 (range, 1.35–6.35), respective-ly], even though this was not statistically significant(P=.549). In the GGN group, mean delayed maximum

SUV was also lower in the malignant subgroup than inthe benign subgroup [2.20±1.10 (range, 0.93–4.49) vs.3.45±2.80 (range, 1.73–7.62), respectively], although thisagain was not statistically significant (P=.424). In thispatient group, mean percentage change in maximumSUV was also lower in the malignant subgroup than inthe benign subgroup [15.65±12.72 (range, !3.12 to44.67) vs. 21.98±6.23 (range, 14.22 to 28.24), respec-tively], but this still did not achieve statistical signifi-cance (P=.230).

ROC analysis for the patient subgroup with solidpulmonary nodules revealed an area under the curve(AUC) of 0.733, 0.747, and 0.599 for early, delayed, and

Table 1Statistical data of FDG uptake measures by patient subgroup

Pathologic status

Solid SPNs Ground-glass SPNs

Benign Malignant P value Benign Malignant P value

Number of patients 22 53 4 15Early maximum SUV .002⁎ .549Mean 3.41 5.78 2.86 1.89Minimum 0.60 0.85 1.35 0.76Maximum 18.32 16.57 6.35 3.46Standard deviation 4.13 3.66 2.36 0.85Delayed maximum SUV .001⁎ .424Mean 3.79 6.75 3.45 2.20Minimum 0.70 0.64 1.73 0.93Maximum 19.37 18.72 7.62 4.49Standard deviation 4.46 4.27 2.80 1.10% Change in max SUV .181 .230Mean 11.45 17.51 21.98 15.65Minimum !23.81 !25.03 14.22 !3.12Maximum 64.26 69.64 28.24 44.67Standard deviation 19.48 18.08 6.23 12.72

*P values are statistically significant.

Fig. 3. Distribution of FDG uptake measures by patient subgroup.

512 C.-F. Chiu et al. / Clinical Imaging 36 (2012) 509–514

p=0.5 p=0.4

p=0.2

verre dépoli

verre dépoli verre

dépoli

SUV1 SUV2 ∆SUV%

Place de la TEP/TDM

D. Groheux et coll.

1052

Rev Mal Respir 2009 ; 26 : 1041-55

[8] considèrent trois groupes depatients : probabilité très faible(< 5 %), probabilité faible àmodérée (5 à 60 %), probabilitéélevée (> 60 %).

De manière générale, laTEP n’a pas de place dans la stra-tégie d’exploration des NPS detaille inférieure à 8 mm. Quatreraisons à cela : le pourcentageélevé de ces nodules dans la popu-lation générale ; la probabilité fai-ble de malignité (d’autant plusfaible que le nodule est pluspetit) ; les mauvaises performan-ces de la TEP et son coût ;l’absence de preuve, qu’en cas demalignité établie suite à la sur-veillance par TDM, le retard autraitement ait un impact sur lasurvie à ce stade. Nous nous limi-terons donc au NPS de taillecomprise entre 8 et 30 mm.

Si la probabilité prétest demalignité est très faible, unedémarche de surveillance parTDM est suffisante. En l’absenced’augmentation de taille sur unepériode de deux années, le NPSpeut être classé comme bénin.

Chez les patients présentant une probabilité prétest fai-ble à modérée (5 à 60 %), un examen TEP-TDM

18

F-FDGest recommandé. Soulignons néanmoins, que l’absenced’hypermétabolisme ne permet pas d’exclure formellement lamalignité, d’où la nécessité d’une surveillance TDM ulté-rieure.

Si la probabilité prétest de malignité est élevée, Gould etcoll. [8] suggèrent que la réalisation d’une TEP devient inu-tile car, même devant un examen négatif, la sanction chirur-gicale ne pourra être évitée. Nous n’adhérons pas à ce pointde vue. Un risque élevé de malignité rend souhaitable unbilan d’extension pour rechercher une atteinte ganglionnaire,des métastases, voire un cancer primitif inattendu.

Un arbre décisionnel reprenant la place de l’imagerieTEP-TDM

18

F-FDG dans la démarche diagnostique glo-bale devant un NPS est représenté en

figure 6

.

Conclusion

La TEP-TDM est un examen performant pourl’exploration d’un NPS supra-centimétrique. Les per-formances de la technique restent néanmoins faibles si lenodule est de petite taille, surtout lorsqu’il est localisé au

niveau des bases pulmonaires où les mouvements respiratoi-res sont importants. En raison du risque de faux négatif, laTEP n’est pas indiquée dans la caractérisation des nodules demoins de 8 mm. Mais pour les nodules de moins de 8 mm,un examen positif doit bien entendu être considéré commecontributif. Les tumeurs carcinoïdes typiques et les carcino-mes bronchiolo-alvéolaires purs sont connus pour être sour-ces de faux négatifs. Les données de la littérature suggèrentqu’une captation faible du FDG pourrait refléter une plusfaible évolutivité et un meilleur pronostic. Ainsi, malgré unesensibilité imparfaite, en pratique clinique, devant une lésionnon kystique ne fixant pas le

18

F-FDG, l’abstention chirur-gicale peut être proposée au profit d’une surveillance cliniqueet radiologique pour s’assurer de l’absence d’évolutivité [8,69].

A contrario

, les nodules d’origine infectieuse et/ouinflammatoire peuvent présenter une hyperactivité. L’opti-misation des acquisitions TDM de l’examen TEP-TDMdevrait permettre d’améliorer l’analyse morphologique dunodule et donc de diminuer les faux négatifs et les faux posi-tifs. De plus, la synchronisation de l’enregistrement des don-nées TEP sur le cycle respiratoire pourrait améliorer lasensibilité de la technique. La TEP-TDM

18

F-FDG est unoutil devant s’intégrer dans les arbres décisionnels, prenanten compte notamment les données scannographiques, clini-

Fig. 6.Arbre de décision sur la place de la TEP-TDM 18F-FDG dans la stratégie globaled’exploration du NPS.

Chirurgie et/ou biopsie

NPS

diamètre < 8mm Taille entre 8 et 30 mm

Surveillance par scanner Évaluation de la probabilité pré test de malignité

< 5 % 5 à 60 % > 60 %

TEP-TDM dans le cadre

du bilan d’extension pré-opératoire

TEP-TDM (-)Surveillance par scanner

TEP -TDM (+)

Nodule pulmonaire (solide)

Groheux et al. Rev Mal Respir 2009

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5

Dépistage NPU : effet de la prévalence du cancer / VPN

injected dose and the weight or body surface area of thepatient [37]. Due to high reproducibility of SUV and possi-ble correlation with prognosis [38–40], SUV is oftenreported in clinical studies and is considered mandatorywhen using PET for therapy evaluation [41•]. A recentretrospective study on 363 patients in stage I–II, performingpreoperative FDG-PET/CT, found that SUV was a predictorof overall survival, but that this correlation was not inde-pendent of stage [42]. SUV has also been suggested as auseful tool for separating malignant and benign SPN [43, 44].The use of SUV is intriguing—captivating the nature of thetumor (malignant or benign) as well as the prognosis of thepatient in a single number. However, SUV is highly dependenton a number of factors related to the patient (eg, length of fast,period between injection of FDG and scan time), the type ofscanner, and reconstruction algorithm, making it unsuitablefor uncritical comparison between different scanners, centers,and time periods. Further, most studies exploring the prog-nostic value of SUV try to establish an optimal SUV cutoff,based on ROC analysis of own data without performing avalidation study in another dataset. This has made comparisonbetween studies difficult and numerous different cutoff valueshave been suggested [42]. Thus outside clinical trials, SUVshould be used with caution, if at all [45].

Staging non–small cell lung cancer

Non–small cell lung cancer is staged according to the TNMsystem as initially suggested by Mountain [46], and recentlyrevised by the International Association of Lung Cancer [47,48]. Only patients with localized disease (TNM stage I–IIB,possibly IIIA) will be candidates for primary curative sur-gery [49]. For most patients with advanced disease (stageIV) palliative treatment with chemotherapy will be the onlyoption. Thus, in order to allocate the patient to the correcttreatment, accurate description of possible 1) distant metas-tases and 2) mediastinal spread (N) is mandatory, whereas

the T stage at this point will substantially influence thetreatment choice only in the case of tumor invasion makingresection impossible (Fig. 4).

Primary tumor (T stage)

Single-modality PET is insufficient for an accurate descriptionof T stage, whereas combined PET/CT is significantly moreaccurate than both PET [50–52] and standard CT (diagnosticquality with intravenous contrast) [53, 54]. A recent studycompared the measurement of primary T1 and T2 NSCLC atPET/CT to determine the correlation with histological find-ings: A high concordance was found between both PET andCT measurements and histological measurements, but PETwas better for delineating the tumor in the presence of sur-rounding atelectasis or consolidation [55].

Mediastinal lymph nodes (N stage)

Mediastinal staging is, in patients without distant metasta-ses, the most significant factor for treatment planning asmediastinal spread (N2–N3 disease) excludes the patientfrom primary surgery. Initial studies on PET reported veryhigh accuracy with regard to N-staging, significantly higherthan the accuracy of CT [56]. In more recent studies thisdifference seems to narrow down, probably due to theimproved quality of CT, but still a staging strategy includingPET/CT appears more sensitive with regard to mediastinaldisease [54, 57]. The European Society of Thoracic Surgery(ESTS) as well as the American College of Chest Physicians(ACCP) has published guidelines for proper preoperativemediastinal staging [58, 59], both including a PET/CT ex-amination. However, it remains more uncertain what con-sequences should be drawn from the PET/CT result. Forexample, it has been suggested that mediastinoscopy orother invasive staging can be omitted in cases where themediastinum is PET-negative [58, 59]. But by doing this,16% of the patients will have occult N2 disease [57, 60]. In

Table 2 Positive and negativepredictive value (PPV and NPV)of PET/CT and CT with regardto solitary pulmonary nodules

Prevalence oflung cancer

PET/CT CT

PPV NPV PPV NPV(95% CI) (95% CI) (95% CI) (95% CI)

Kagna et al.[26], 2009

0.38 0.66 0.95 0.53 0.97

(0.52–0.78) (0.85–0.99) (0.41–0.65) (0.83–0.99)

Jeong et al.[27], 2008

0.40 0.71 0.90 0.62 0.83

(0.79–0.96) (0.70–0.91) (0.48–0.74) (0.58–0.82)

Kim et al.[28], 2007

0.69 0.93 0.92 0.75 0.67

(0.79–0.98) (0.65–0.99) (0.59–0.86) (0.30–0.90)

Yi et al.[25], 2006

0.66 0.94 0.92 0.96 0.71

(0.86–0.97) (0.79–0.97) (0.88–0.98) (0.58–0.82)

34 Curr Respir Care Rep (2012) 1:30–39

Fischer & Mortensen, Cur Resp Care Rep 2012 CT PET/CT

Utilité TEP/TDM dans le dépistage •  Dépistage cancer

pulmonaire •  Re-scan à 3 mois •  CT : temps de

doublement (VDT) •  PET : SUV>médiastin •  54 nodules réséqués •  Prévalence cancer

37% Ashraf H et al. Thorax 2011

Dépistage : ex. 2 adénocarcinomes

a positive combined PET and VDT test indicating malignancywas when one or both of the tests were positive. The positivelikelihood ratio (+LR) was 5.1 (95% CI 4.1 to 6.3) and thenegative likelihood ratio (!LR) was 0.12 (95% CI 0.0 to 0.5).

If, instead, the criterion for malignancy is that both PET andVDT should be positive (group C, table 3), the sensitivity was50% (95% CI 27% to 73%) and the specificity was 100% (95% CI90% to 100%) but the LRs were not applicable because thespecificity is 100%.

DISCUSSIONWhen screening for lung cancer, unnecessary invasive surgicalprocedures for benign lung nodules should be kept toa minimum. The substantial risk incurred by surgical resectionof a nodule suspected of being malignant should not be under-estimated. Even though minimal invasive techniques are avail-able, not all hospitals offer these treatments. In many cases theresection is only possible with an open thoracotomy procedure.This increases the risk of complications and mortality, whichultimately can damage the potential beneficial effect of lungcancer screening. On the other hand, correct diagnosis ofa malignant nodule is essential for the survival of patients withlung cancer. The use of diagnostic tools that can distinguishbenign from malignant nodules is therefore crucial beforedeciding whether or not a nodule should be examined by aninvasive procedure.

In this study both PET (OR 3.7, p"0.003) and VDT (OR 3.3,p"0.006) were associated with lung cancer in the multivariatelogistical model (table 2). PET and VDT may therefore predictlung cancer independently of each other. The fact that both PETand VDTwere significant in the multivariate analysis indicates

that a combination of the two was better at predicting lungcancer than either procedure alone.In the ROC analysis, cut-off values for malignancy using

VDT (<365 days) and PET (>II, ie, probably or likely malignant)are consistent with earlier clinical trials.9 10 This resulted in thehighest sensitivity (71%) and specificity (91%) for both PETandVDT. Combining PETand VDTusing the cut-off value from theROC analysis resulted in the highest sensitivity (90%) andspecificity (82%), which again underlines the additive effect ofPET and VDT (table 3). The cut-off value was malignancyindicated by either PET or VDT, in which case the likelihood ofmalignancy increased approximately fivefold (+LR"5.1) As anexample, if the pre-test probability of malignancy is 50%, thepost-test probability will be >80%. If both PET and VDT arenegative the eLR of 0.12 indicates that, for a pre-test probabilityof 50% for malignancy, the post-test probability is <10%.Our study suggests that, when PETand VDTare in accordance,

there is only a small probability of false diagnosis (5%) comparedwith when PET and VDT differ (43%, p<0.01; figures 2 and 3).We therefore recommend nodules to be considered benign/indolent when both PET and VDT are negative. These nodulesshould be scheduled for rescanning after a year as part of theregular screening regime. If both PET and VDT indicate malig-nancy (ie, a positive PET result and a VDT of <1 year), werecommend referral for invasive diagnostic investigation becauseof a high probability of cancer. In fact, in our study all cases withpositive PET and VDT were malignant. Ideally, this should bedone with the use of video-assisted thoracoscopic surgery(VATS), with which the DLCST has had good experience.6 VATSis minimally invasive and therefore the complication rate is keptlow, which is preferable, especially in screening settings.

Figure 2 Positron emission tomography (PET) and volume doubling time (VDT) differ. Volumetric measurement of a nodule at (A) baseline and (B)3 months later at rescan. VDT was calculated as 186 days. The PET scan (C1) was negative (area with nodule highlighted by red circle). A transverseCT scan (lung window) (C2) showing a nodule at baseline in the right lung. The nodule was removed and was diagnosed as lung cancer(adenocarcinoma).

Figure 3 Positron emission tomography (PET) and volume doubling time (VDT) differ. Volumetric measurement of a nodule (D) at baseline and (E)3 months later at rescan. VDT was calculated as !1949 days. The PET scan (F1) was positive (area with nodule highlighted by red circle). Atransverse CT scan (lung window) (F2) showing a nodule at baseline in the right lung. The nodule was removed and was diagnosed as lung cancer(adenocarcinoma).

318 Thorax 2011;66:315e319. doi:10.1136/thx.2010.136747

Lung cancer

group.bmj.com on May 26, 2012 - Published by thorax.bmj.comDownloaded from

a positive combined PET and VDT test indicating malignancywas when one or both of the tests were positive. The positivelikelihood ratio (+LR) was 5.1 (95% CI 4.1 to 6.3) and thenegative likelihood ratio (!LR) was 0.12 (95% CI 0.0 to 0.5).

If, instead, the criterion for malignancy is that both PET andVDT should be positive (group C, table 3), the sensitivity was50% (95% CI 27% to 73%) and the specificity was 100% (95% CI90% to 100%) but the LRs were not applicable because thespecificity is 100%.

DISCUSSIONWhen screening for lung cancer, unnecessary invasive surgicalprocedures for benign lung nodules should be kept toa minimum. The substantial risk incurred by surgical resectionof a nodule suspected of being malignant should not be under-estimated. Even though minimal invasive techniques are avail-able, not all hospitals offer these treatments. In many cases theresection is only possible with an open thoracotomy procedure.This increases the risk of complications and mortality, whichultimately can damage the potential beneficial effect of lungcancer screening. On the other hand, correct diagnosis ofa malignant nodule is essential for the survival of patients withlung cancer. The use of diagnostic tools that can distinguishbenign from malignant nodules is therefore crucial beforedeciding whether or not a nodule should be examined by aninvasive procedure.

In this study both PET (OR 3.7, p"0.003) and VDT (OR 3.3,p"0.006) were associated with lung cancer in the multivariatelogistical model (table 2). PET and VDT may therefore predictlung cancer independently of each other. The fact that both PETand VDTwere significant in the multivariate analysis indicates

that a combination of the two was better at predicting lungcancer than either procedure alone.In the ROC analysis, cut-off values for malignancy using

VDT (<365 days) and PET (>II, ie, probably or likely malignant)are consistent with earlier clinical trials.9 10 This resulted in thehighest sensitivity (71%) and specificity (91%) for both PETandVDT. Combining PETand VDTusing the cut-off value from theROC analysis resulted in the highest sensitivity (90%) andspecificity (82%), which again underlines the additive effect ofPET and VDT (table 3). The cut-off value was malignancyindicated by either PET or VDT, in which case the likelihood ofmalignancy increased approximately fivefold (+LR"5.1) As anexample, if the pre-test probability of malignancy is 50%, thepost-test probability will be >80%. If both PET and VDT arenegative the eLR of 0.12 indicates that, for a pre-test probabilityof 50% for malignancy, the post-test probability is <10%.Our study suggests that, when PETand VDTare in accordance,

there is only a small probability of false diagnosis (5%) comparedwith when PET and VDT differ (43%, p<0.01; figures 2 and 3).We therefore recommend nodules to be considered benign/indolent when both PET and VDT are negative. These nodulesshould be scheduled for rescanning after a year as part of theregular screening regime. If both PET and VDT indicate malig-nancy (ie, a positive PET result and a VDT of <1 year), werecommend referral for invasive diagnostic investigation becauseof a high probability of cancer. In fact, in our study all cases withpositive PET and VDT were malignant. Ideally, this should bedone with the use of video-assisted thoracoscopic surgery(VATS), with which the DLCST has had good experience.6 VATSis minimally invasive and therefore the complication rate is keptlow, which is preferable, especially in screening settings.

Figure 2 Positron emission tomography (PET) and volume doubling time (VDT) differ. Volumetric measurement of a nodule at (A) baseline and (B)3 months later at rescan. VDT was calculated as 186 days. The PET scan (C1) was negative (area with nodule highlighted by red circle). A transverseCT scan (lung window) (C2) showing a nodule at baseline in the right lung. The nodule was removed and was diagnosed as lung cancer(adenocarcinoma).

Figure 3 Positron emission tomography (PET) and volume doubling time (VDT) differ. Volumetric measurement of a nodule (D) at baseline and (E)3 months later at rescan. VDT was calculated as !1949 days. The PET scan (F1) was positive (area with nodule highlighted by red circle). Atransverse CT scan (lung window) (F2) showing a nodule at baseline in the right lung. The nodule was removed and was diagnosed as lung cancer(adenocarcinoma).

318 Thorax 2011;66:315e319. doi:10.1136/thx.2010.136747

Lung cancer

group.bmj.com on May 26, 2012 - Published by thorax.bmj.comDownloaded from

VDT+ (186d)

VDT– (1949d)

PET–

PET+

Chirurgie à adénocarcinome

Chirurgie à adénocarcinome

Ashraf H et al. Thorax 2011

Cas 1

Cas 2

03.10.13

6

Dépistage : Combinaison PET et VDT

7%

57%

100%

0%

20%

40%

60%

80%

100%

PET et VDT– PET ou VDT+ PET et VDT+

Probabilité de cancer

Ashraf H et al. Thorax 2011

VDT et PET : à Se 90%, Sp 82% à recommandée dans dépistage cancer pulmonaire avec CT basse dose

Economicité PET pour NPU ? •  Lejeune et al (Eur J Health Econ 2005) :

–  bonne qualité méthodologique – CT vs. CT+PET vs. wait & watch – Coût/année gagnée CT€4’790, CT+PET €3’022 – CT+PET = plus coût-efficace si probabilité cancer

entre 6–87% (si 0.3%–5% à W&W meilleur) •  Confirmé dans d’autres études américaines,

australiennes (mais pas japonaise ou allemande), essentiellement par évitement chirurgies futiles si découverte M+

Recommandations utilisation TEP

•  Patients avec probabilité basse–modérée (5–60%) de CA et nodule >8–10mm (niveau I) : àoffre la possibilité d’éviter les complications de la chirurgie chez personnes à risque élevé

•  Patients avec PET– doivent être suivis •  Patients avec différenciation tumeur

endocrine devraient avoir une imagerie aux analogues de la somatostatin (TEP 68Ga-DOTA-peptides, 18F-DOPA ou octréoscan®)

03.10.13

7

Futur ? •  TEP/TDM en deux-temps (1h et 2–4h) : résultats

encore incertains – Utilité si SUV <2.5 et forte prévalence granu-

lomatoses (plus spécifique) – Seuil ∆SUV% >+10% ? Aussi possible /infections – Pas de différence si 2e acquisition à 2h ou 3h

(max. SUV atteint @5h) •  Nouveau traceurs ?

–  18F-FLT : résultats prometteurs –  18F-FAMT18F-α-méthyl-tyrosine : associé avec un

mauvais pronostic dans le NSCLC

PET/CT 4-D : Synchronisation respiratoire

Mac Manus (Sem Nucl Med 2012) Améliorations techniques en cours (à suivre)

Résumé : TEP/TDM et nodule pulmonaire

•  PET/CT fait partie de la prise en charge du nodule pulmonaire >8–10mm (contributif si <8–10mm et TEP+)

•  Faux positifs et faux négatifs existent •  Bénéfice supérieur au CT (aussi pour le

médiastin et les métastases à distance) •  Utilité comme 2e étape dans diagnostic et

suivi nodule pulmonaire et possiblement dans dépistage

03.10.2013

1

4 UH 4 UH ±± 00

03.10.2013

2

7 UH 7 UH ±± 11

24/07/13

04/09/13

03.10.2013

3

03.10.2013

4

DiagnosticDiagnostic

• Granulome nécrosant gigantocellulaire

• Carcinome neuroendocrine de haut grade

Composante tissulaire excentréeRétraction scissurale

03.10.2013

5

03.10.2013

6

03.10.2013

7

03.10.2013

8

DiagnosticDiagnostic

• Adénocarcinome à prédominance lépidique

• Adénocarcinome microinvasif àAdénocarcinome microinvasif à prédominance mucineuse

• Hyperplasies adénomateuses atypiques

• Tumorlets

15/12/1115/12/11 04/05/12

03.10.2013

9

03.10.2013

10

DiagnosticDiagnostic

• Adénocarcinome invasif, à prédominance acinaire

• Bronchopneumonie aspergillaire

03.10.2013

11

12/09/13

03.10.2013

12

12/09/13

29/07/13

12/09/13

03.10.2013

13

12/09/13

17/09/13

03.10.2013

14

03/08/05 09/08/05

20/10/0509/08/05

07/09/06

03.10.2013

15

13/11/06

03.10.2013

16

03.10.2013

17

DiagnosticDiagnostic

• Wedge nodules :

Inflammation granulomateuse sur infection à 

mycobactéries atypiques (m Xénopi)y yp q ( p )

• Wedge de pneumothorax : Inflammation granulomateuse sur infection à 

myocobactéries atypiques (M Xénopi)

Adénocarcinome solide, peu différencié sous pleural de 0,7cm de grand axe

01/10/13  

1  

Antoine KHALIL

Introduction

•  Détection: – TDM-volumique millimétrique: examen de référence – Place de l’IRM

•  Caractérisation: – TDM – TEP-CT –  IRM (Y-a-t-il une place?)

T1/T2 EG Steady state EG GEMS: FIESTA Philips: bFFE Siemens: True FISP Toshiba: True SSFP

T1-EG Résolution spatiale maximale GEMS: APGR Philips: FFE Siemens: Flash 3D Toshiba: DRKS

Séquences Standard du rachis SE T1 / TSE T2 / STIR

T1-EG Echo-sharing GEMS: TRICKS Philips: TRAK Siemens: TWIST Toshiba: DRKS

T2 FSE Asservissement respiratoire GEMS: FSE Philips: TSE Siemens: TSE-rt Toshiba: FSE

DWI Asservissement respiratoire (+/-) GEMS: DWI Philips: DWIBS Siemens: REVEAL Toshiba: Body vision

T2 FSE Codage de phase rotationnel GEMS: PROPELLER Philips: MultiVue Siemens: BLADE Toshiba: JET

T2 FS/STIR Asservissement respiratoire (+/-) GEMS: FSE fs/STIR Philips: TSE fs/STIR Siemens: TSE fs/STIR Toshiba: FSE fs/STIR

T1-EG Volumique GEMS: LAVA Philips: THRIVE Siemens: VIBE Toshiba: Quick3D

T2 FSE Acquisition de la moitié du PF GEMS: 1/2Nex FSE Philips: Halfscan FSE Siemens: HASTE Toshiba: AF1 RO

Ciné IRM Cycle cardiaque GEMS: Philips: Siemens: Toshiba:

Ciné IRM Mouvements respiratoires GEMS: FIESTA Philips: bFFE Siemens: True FISP Toshiba: True SSFP

01/10/13  

2  

Détection Auteurs (année)

IRM Gold standard

Séquences Taille Sensibilité

Koyama et al (2008)

Philips 1,5T

4-MDCT T1WI (respiratoire et cardiaque) T2WI (respiratoire et cardiaque) STIR (respiratoire)

1-30 1-30 1-30

96,1 96,1 96,1

Schroeder et al (2005)

Siemens 1,5T

4-MDCT HASTE HASTE HASTE HASTE

<3 3-5 6-10 >10

73,6 84,3 95,7 100

Bruegel et al (2007)

Siemens 1,5T

64-MDCT T2WI HASTE (apnée) T2W IR HASTE (apnée) T2WI TSE (apnée) STIR (apnée) 3D VIBE (avant Gado) 3D VIBE (après Gado) STIR (respiratoire et battement)

1-31 1-31 1-31 1-31 1-31 1-31 1-31

47,1-48,4 44,0-47,1 68,0-69,8 60,0-66,2 52,0-55,6 48,9-52,4 70,2-73,3

Freicks et al (2008)

Siemens 1,5T

16-MDCT STIR (plusieurs apnées) T2 TSE (respiratoire) 3D VIBE (après Gado)

1-61 1-61 1-61

92,5 90,8 87,3

Yi et al (2007)

Philips 3T

4-MDCT 3D TSE T1WI BBTSE T2WI inversion triple

13-80 13-80

57 56

!Koyama H et al. MR imaging for lung cancer. J Thorac Imaging 2013;28:138-150

T1/T2 EG Steady state EG GEMS: FIESTA Philips: bFFE Siemens: True FISP Toshiba: True SSFP

T1-EG Résolution spatiale maximale GEMS: APGR Philips: FFE Siemens: Flash 3D Toshiba: DRKS

Séquences Standard du rachis SE T1 / TSE T2 / STIR

T1-EG Echo-sharing GEMS: TRICKS Philips: TRAK Siemens: TWIST Toshiba: DRKS

T2 FSE Asservissement respiratoire GEMS: FSE Philips: TSE Siemens: TSE-rt Toshiba: FSE

DWI Asservissement respiratoire (+/-) GEMS: DWI Philips: DWIBS Siemens: REVEAL Toshiba: Body vision

T2 FSE Codage de phase rotationnel GEMS: PROPELLER Philips: MultiVue Siemens: BLADE Toshiba: JET

T2 FS/STIR Asservissement respiratoire (+/-) GEMS: FSE fs/STIR Philips: TSE fs/STIR Siemens: TSE fs/STIR Toshiba: FSE fs/STIR

T1-EG Volumique GEMS: LAVA Philips: THRIVE Siemens: VIBE Toshiba: Quick3D

T2 FSE Acquisition de la moitié du PF GEMS: 1/2Nex FSE Philips: Halfscan FSE Siemens: HASTE Toshiba: AF1 RO

Ciné IRM Cycle cardiaque GEMS: Philips: Siemens: Toshiba:

Ciné IRM Mouvements respiratoires GEMS: FIESTA Philips: bFFE Siemens: True FISP Toshiba: True SSFP

01/10/13  

3  

Détection des nodules pulmonaires Koyama et al è161 patients et 200 nodules

Intera T-1.5; Philips medical System

Séquences: (5mm jointives) T1 ES (respiratoire et cardiaque): Durée moyenne 7 min (4 à 15 min) TE TSE (respiratoire et cardiaque): Durée moyenne 7 min (4 à 15 min) T2 STIR (respiratoire): durée moyenne 9 min (4 à 15 min)

Taille des nodules: diamètre moyen 15,6 (1 à 30 mm)

Concordance inter observateur: TDM: 0,77 T1-ES: 0,87 T2-TSE: 0,91 T2-STIR: 0,95

Eur Radiol (2008) 18: 2120–2131DOI 10.1007/s00330-008-1001-2 CHEST

Hisanobu KoyamaYoshiharu OhnoAtsushi KonoDaisuke TakenakaYoshimasa ManiwaYoshihiro NishimuraChiho OhbayashiKazuro Sugimura

Received: 28 December 2007Revised: 22 March 2008Accepted: 27 March 2008Published online: 6 May 2008# European Society of Radiology 2008

Quantitative and qualitative assessmentof non-contrast-enhanced pulmonary MRimaging for management of pulmonary nodulesin 161 subjects

Abstract This study aimed atprospectively compared efficacy ofnon-contrast-enhanced (non-CE) MRIand MDCT for management ofpulmonary nodules. A total of 161patients with 200 nodules underwentMDCT and non-CE MRI (T1WI,T2WI, and STIR) in conjunction withpathological and/or more than 2 yearsof follow-up examinations. Tocompare qualitative detection ratesbetween both modalities, all nodules

were visually assessed. To comparequantitative and qualitative diagnosticcapabilities of MRI, calculation ofcontrast ratio and visual assessment ofprobability for malignancy in eachnodule were performed. Then, detec-tion rate and diagnostic capabilitywere statistically compared. Althoughthe overall detection rate of each MRsequence (82.5%) was significantlylower than that of MDCT (97.0%,p<0.05), that of malignant nodulesshowed no significant difference(p>0.05). The diagnostic capability ofSTIR was significantly higher thanthose of other MR sequences(p<0.05). Non-CE MR imaging wasfound to be as useful as MDCT formanagement of pulmonary nodules.

Keywords Lung . MR . CT .Primary neoplasm . Screening

Introduction

The challenge of detection, diagnosis and management ofpulmonary nodules is one of the most common and mostimportant areas of pulmonary medicine because pulmonarynodules are caused by a variety of conditions, ranging frombenign granulomas to operable primary malignant lungnodules [1–3]. Ideally, the goal of screening and manage-ment of pulmonary nodules is to promptly detect and bring tosurgery all patients with operable malignant nodules whileavoiding unnecessary thoracotomy for patients with benignlesions. It is therefore important to detect small pulmonarynodules and differentiate malignant from benign nodules in

the least invasivemanner andwith the least ionizing radiationexposurewhile making the diagnosis as specific and accurateas possible [2–13]. Many reports on CT findings for thispurpose have been published in this connection, although ithas been sometimes difficult to distinguish malignant frombenign nodules by using only radiological findings. In anattempt to find a solution for this problem, severalinvestigators have assessed the utility of dynamic CT,dynamic magnetic resonance (MR) imaging and positron-emission tomography (PET) or integrated and/or co-registered PET/CT for this purpose [6–13].

In the last decade, continuing technological progress inMR systems and sequencing and reconstruction methods,

This work was supported by Philips MedicalSystems and the Knowledge Cluster Initiativeof the Ministry of Education, Culture, Sports,Science and Technology of Japan.

H. Koyama (*) . Y. Ohno . A. Kono .D. Takenaka . K. SugimuraDepartment of Radiology, KobeUniversity Graduate School ofMedicine,7–5–2 Kusunoki-cho,Chuo-ku, Kobe, 650–0017 Kobe, Japane-mail: hkoyama@med.kobe-u.ac.jpTel.: +81-78-3826104Fax: +81-78-3826129

Y. ManiwaDivision of Cardiovascular, Thoracicand Pediatric Surgery, Kobe UniversityGraduate School of Medicine,Kobe, Japan

Y. NishimuraDivision of Cardiovascular andRespiratory Medicine, Department ofInternal Medicine, Kobe UniversityGraduate School of Medicine,Kobe, Japan

C. OhbayashiDivision of Pathology, Hyogo CancerCenter,Tokyo, Japan

Détection des nodules pulmonaires Koyama et al è161 patients et 200 nodules

Détection globale des nodules

MDCT >> IRM (n’importe quelle séquence; p<0,05)

Nodules non vus par IRM: n = 35 Bronchiolo-alvéolaire n=4 Hyperplasie adénomatoïde atypique n=3 Nodules bénins (suivi) n=28

Nodules MDCT IRM Malin 103/103 (100%) 99/103 (96,1%) P>0,05 Bénin 91/97 (93,8%) 66/97 (68,1%) P<0,05

Eur Radiol (2008) 18: 2120–2131DOI 10.1007/s00330-008-1001-2 CHEST

Hisanobu KoyamaYoshiharu OhnoAtsushi KonoDaisuke TakenakaYoshimasa ManiwaYoshihiro NishimuraChiho OhbayashiKazuro Sugimura

Received: 28 December 2007Revised: 22 March 2008Accepted: 27 March 2008Published online: 6 May 2008# European Society of Radiology 2008

Quantitative and qualitative assessmentof non-contrast-enhanced pulmonary MRimaging for management of pulmonary nodulesin 161 subjects

Abstract This study aimed atprospectively compared efficacy ofnon-contrast-enhanced (non-CE) MRIand MDCT for management ofpulmonary nodules. A total of 161patients with 200 nodules underwentMDCT and non-CE MRI (T1WI,T2WI, and STIR) in conjunction withpathological and/or more than 2 yearsof follow-up examinations. Tocompare qualitative detection ratesbetween both modalities, all nodules

were visually assessed. To comparequantitative and qualitative diagnosticcapabilities of MRI, calculation ofcontrast ratio and visual assessment ofprobability for malignancy in eachnodule were performed. Then, detec-tion rate and diagnostic capabilitywere statistically compared. Althoughthe overall detection rate of each MRsequence (82.5%) was significantlylower than that of MDCT (97.0%,p<0.05), that of malignant nodulesshowed no significant difference(p>0.05). The diagnostic capability ofSTIR was significantly higher thanthose of other MR sequences(p<0.05). Non-CE MR imaging wasfound to be as useful as MDCT formanagement of pulmonary nodules.

Keywords Lung . MR . CT .Primary neoplasm . Screening

Introduction

The challenge of detection, diagnosis and management ofpulmonary nodules is one of the most common and mostimportant areas of pulmonary medicine because pulmonarynodules are caused by a variety of conditions, ranging frombenign granulomas to operable primary malignant lungnodules [1–3]. Ideally, the goal of screening and manage-ment of pulmonary nodules is to promptly detect and bring tosurgery all patients with operable malignant nodules whileavoiding unnecessary thoracotomy for patients with benignlesions. It is therefore important to detect small pulmonarynodules and differentiate malignant from benign nodules in

the least invasivemanner andwith the least ionizing radiationexposurewhile making the diagnosis as specific and accurateas possible [2–13]. Many reports on CT findings for thispurpose have been published in this connection, although ithas been sometimes difficult to distinguish malignant frombenign nodules by using only radiological findings. In anattempt to find a solution for this problem, severalinvestigators have assessed the utility of dynamic CT,dynamic magnetic resonance (MR) imaging and positron-emission tomography (PET) or integrated and/or co-registered PET/CT for this purpose [6–13].

In the last decade, continuing technological progress inMR systems and sequencing and reconstruction methods,

This work was supported by Philips MedicalSystems and the Knowledge Cluster Initiativeof the Ministry of Education, Culture, Sports,Science and Technology of Japan.

H. Koyama (*) . Y. Ohno . A. Kono .D. Takenaka . K. SugimuraDepartment of Radiology, KobeUniversity Graduate School ofMedicine,7–5–2 Kusunoki-cho,Chuo-ku, Kobe, 650–0017 Kobe, Japane-mail: hkoyama@med.kobe-u.ac.jpTel.: +81-78-3826104Fax: +81-78-3826129

Y. ManiwaDivision of Cardiovascular, Thoracicand Pediatric Surgery, Kobe UniversityGraduate School of Medicine,Kobe, Japan

Y. NishimuraDivision of Cardiovascular andRespiratory Medicine, Department ofInternal Medicine, Kobe UniversityGraduate School of Medicine,Kobe, Japan

C. OhbayashiDivision of Pathology, Hyogo CancerCenter,Tokyo, Japan

T1SE T2-TSE STIR

Eur

Radiol

(2008)18:

2120–2131DOI10.1007/s00330-008-1001-2

CHEST

Hisanobu

Koyam

aYoshiharu

Ohno

Atsushi

Kono

Daisuke

Takenaka

Yoshim

asaManiw

aYoshihiro

Nishim

uraChiho

Ohbayashi

Kazuro

Sugimura

Received:

28Decem

ber2007

Revised:

22March

2008Accepted:

27March

2008Published

online:6May

2008#

European

Societyof

Radiology

2008

Quantitativeand

qualitativeassessm

entofnon-contrast-enhanced

pulmonary

MR

imaging

formanagem

entofpulmonary

nodulesin

161subjects

Abstract

This

studyaim

edat

prospectivelycom

paredefficacy

ofnon-contrast-enhanced

(non-CE)MRI

andMDCTfor

managem

entof

pulmonary

nodules.Atotal

of161

patientswith

200nodules

underwent

MDCTand

non-CEMRI(T1W

I,T2W

I,andST

IR)in

conjunctionwith

pathologicaland/ormore

than2years

offollow

-upexam

inations.Tocom

parequalitative

detectionrates

between

bothmodalities,allnodules

were

visuallyassessed.To

compare

quantitativeand

qualitativediagnostic

capabilitiesof

MRI,calculation

ofcontrastratio

andvisualassessm

entofprobability

formalignancy

ineach

nodulewere

performed.T

hen,detec-tion

rateand

diagnosticcapability

were

statisticallycom

pared.Although

theoverall

detectionrate

ofeach

MR

sequence(82.5%

)was

significantlylow

erthan

thatofMDCT(97.0%

,p<0.05),thatof

malignant

nodulesshow

edno

significantdifference

(p>0.05).T

hediagnostic

capabilityof

STIR

was

significantlyhigher

thanthose

ofother

MRsequences

(p<0.05).N

on-CEMRim

agingwas

foundto

beas

usefulasMDCTfor

managem

entofpulm

onarynodules.

Keyw

ordsLung

.MR

.CT.

Primary

neoplasm.Screening

Introduction

The

challengeof

detection,diagnosis

andmanagem

entof

pulmonary

nodulesis

oneof

themost

common

andmost

importantareas

ofpulm

onarymedicine

becausepulm

onarynodules

arecaused

byavariety

ofconditions,ranging

frombenign

granulomas

tooperable

primary

malignant

lungnodules

[1–3].Ideally,

thegoal

ofscreening

andmanage-

mentofpulm

onarynodulesisto

promptly

detectandbring

tosurgery

allpatients

with

operablemalignant

noduleswhile

avoidingunnecessary

thoracotomyfor

patientswith

benignlesions.It

istherefore

important

todetectsm

allpulm

onarynodules

anddifferentiate

malignantfrom

benignnodules

in

theleastinvasive

mannerand

with

theleastionizing

radiationexposure

while

making

thediagnosisasspecific

andaccurate

aspossible

[2–13].Many

reportson

CTfindings

forthis

purposehave

beenpublished

inthis

connection,althoughit

hasbeen

sometim

esdifficultto

distinguishmalignant

frombenign

nodulesby

usingonly

radiologicalfindings.

Inan

attempt

tofind

asolution

forthis

problem,several

investigatorshave

assessedthe

utilityof

dynamic

CT,

dynamic

magnetic

resonance(M

R)im

agingand

positron-em

issiontom

ography(PE

T)

orintegrated

and/orco-

registeredPE

T/CTfor

thispurpose

[6–13].In

thelast

decade,continuingtechnological

progressin

MR

systemsand

sequencingand

reconstructionmethods,

This

work

was

supportedby

PhilipsMedical

Systemsand

theKnow

ledgeClusterInitiative

ofthe

Ministry

ofEducation,C

ulture,Sports,Science

andTechnology

ofJapan.

H.K

oyama(*

).Y

.Ohno

.A.K

ono.

D.Takenaka

.K.Sugim

uraDepartm

entof

Radiology,

Kobe

University

Graduate

Schoolof

Medicine,

7–5–2Kusunoki-cho,

Chuo-ku,K

obe,650–0017Kobe,Japan

e-mail:

hkoyama@

med.kobe-u.ac.jp

Tel.:+81-78-3826104

Fax:+81-78-3826129

Y.Maniw

aDivision

ofCardiovascular,

Thoracic

andPediatric

Surgery,Kobe

University

Graduate

Schoolof

Medicine,

Kobe,

Japan

Y.Nishim

uraDivision

ofCardiovascular

andRespiratory

Medicine,

Departm

entof

InternalMedicine,

Kobe

University

Graduate

Schoolof

Medicine,

Kobe,

Japan

C.Ohbayashi

Division

ofPathology,

Hyogo

Cancer

Center,

Tokyo,Japan

Cancer bronchique

du LIG

Nodule bénin sur le

suivi

01/10/13  

4  

Détection des nodules pulmonaires Schroeder et al è36 patients et 1102 nodules

Magnetom Sonata, Siemens MS

Séquences: (5mm jointives; 2,4x1,3mm2) HASTE (apnée et asservissement cardiaque): 17 à 19 sec

Plan: axial et coronal

AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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Taille des nodules

Nombre HASTE Sensibilité

< 3 383 336 73% 3-5 300 281 86% 6-10 232 225 95,7% >10 187 189 100%

Détection des nodules pulmonaires

AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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AJR:185, October 2005 979

AJR 2005;185:979–984

0361–803X/05/1854–979

© American Roentgen Ray Society

Schroeder et al.HASTE MRI Versus MDCT of Pulmonary Nodules

C h e s t I m ag i n g • O r i g i n a l R e s e a rc h

Detection of Pulmonary Nodules Using a 2D HASTE MR Sequence: Comparison with MDCT

Tobias Schroeder1

Stefan G. RuehmJörg F. DebatinMark E. LaddJörg BarkhausenSusanne C. Goehde

Schroeder T, Ruehm SG, Debatin JF, Ladd ME, Barkhausen J, Goehde SC

DOI:10.2214/AJR.04.0814

Received May 23, 2004; accepted after revision November 10, 2004.

1All authors: Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, Essen 45122, Germany. Address correspondence to T. Schroeder (tobias.schroeder@uni-essen.de).

OBJECTIVE. The objective of our study was to determine the diagnostic performanceof MRI based on a HASTE sequence for the detection of pulmonary nodules in comparisonwith MDCT.

MATERIALS AND METHODS. Thirty patients with known pulmonary nodules under-went both MRI and CT. CT of the lung served as the standard of reference and was performedon a 4-MDCT scanner using a routine protocol. MRI was performed with axial and coronalHASTE sequences using a high-performance 1.5-T MR scanner. Image data were analyzed inthree steps after completion of all data acquisition. Step 1 was the analysis of all the CT imagedata. Step 2 was the analysis of all the MR image data while blinded to the results of the CT find-ings. Step 3 closed with a simultaneous review of all corresponding CT and MRI data, includinga one-to-one correlation of the size and location of all the nodules that were detected.

RESULTS. Compared with the sensitivity of CT, the sensitivity values for the HASTE MRsequence were as follows: 73% for lesions less than 3 mm, 86.3% for lesions between 3 and5 mm, 95.7% for lesions between 6 and 10 mm, and 100% for lesions larger than 10 mm. Theoverall sensitivity of the HASTE sequence for the detection of all pulmonary lesions was 85.4%.

CONCLUSION. An MRI examination that consists of a HASTE sequence allows one todetect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesionssmaller than 5 mm still need to be validated using CT.

ts unsurpassed potential forsoft-tissue discrimination, multi-planar imaging, and inherent ca-pabilities for dynamic and func-

tional analyses has advanced MRI to be thetechnique of choice for the assessment ofmany organ systems. MRI of the lungs, on theother hand, has not yet reached any clinicalrelevance. The reasons include limited spatialresolution [1, 2], high susceptibility differ-ences between air spaces and pulmonary in-terstitium, and the presence of respiratory andcardiac motion artifacts [3].

At the same time, the lungs have provedideal for exploiting the advantages inherent toCT [4, 5]: The vast density differences be-tween the air-filled alveoli and the pulmonaryinterstitium allow easy discrimination of thelatter and quick identification of dense pulmo-nary masses even without the administration ofIV contrast material. Based on the ability of CTto detect even small amounts of calcium, be-nign lesions can be readily characterized assuch. Hence, there is general agreement thatCT represents the standard of reference regard-

ing the detection and characterization of pul-monary lesions.

On the downside, CT is inherently asso-ciated with sometimes considerable levelsof exposure to ionizing radiation and the po-tential of nephrotoxicity when contrastagents are applied. Although these issuesare largely ignored in the setting of knowndisease, exposure to ionizing radiation com-plicates the attempt to exploit the potentialbenefits associated with CT-based pulmo-nary screening [5–7]. Thus, the potential toreduce the high incidence of primary andsecondary pulmonary malignancies byscreening large populations at risk has mo-tivated investigators to search for alterna-tive imaging techniques with lower expo-sure to radiation [8].

The availability of high-performance gradi-ent systems, in conjunction with phased-arrayreceiver coils and optimized imaging se-quences, has introduced new, potentially inter-esting approaches to MR-based pulmonary im-aging [9–12]. These have ranged frompulmonary MR angiography [13] to ventila-

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om IP

add

ress

164

.2.2

55.2

44. C

opyr

ight

AR

RS.

For

per

sona

l use

onl

y; a

ll rig

hts r

eser

ved

Faux négatif

Mme C. âgée de 76 ans ATCD de cancer du sein et de l’endomètre

6x10mm  

5x7mm  

01/10/13  

1  

4x3mm  

4,5mm  

15x16mm  

6x7mm  

La séquence utilisée est T2-TSE Propeller (correction des mouvements) Asservissement respiratoire Epaisseur de la coupe: 5 mm Espacement: 0 mm TR: en fonction de la FR TE: 111 ms Suppression de la graisse

Le dépistage et l’IRM Rêve ou réalité?

01/10/13  

2  

RESEARCH ARTICLE Open Access

Magnetic resonance imaging for lung cancerdetection: Experience in a population of morethan 10,000 healthy individualsNai-Yuan Wu1,2,3, Hui-Cheng Cheng1,4, James S Ko1,4, Yu-Chen Cheng1,4, Po-Wei Lin1,4, Wei-Chan Lin1,4,Cheng-Yen Chang4*† and Der-Ming Liou2*†

Abstract

Background: Recent refinements of lung MRI techniques have reduced the examination time and improveddiagnostic sensitivity and specificity. We conducted a study to assess the feasibility of MRI for the detection ofprimary lung cancer in asymptomatic individuals.

Methods: A retrospective chart review was performed on images of lung parenchyma, which were extracted fromwhole-body MRI examinations between October 2000 and December 2007. 11,766 consecutive healthy individuals(mean age, 50.4 years; 56.8% male) were scanned using one of two 1.5-T scanners (Sonata and Sonata Maestro,Siemens Medical Solutions, Erlangen, Germany). The standard protocol included a quick whole-lung survey with T2-weighted 2-dimensional half Fourier acquisition single shot turbo spin echo (HASTE) and 3-dimensional volumetricinterpolated breath-hold examination (VIBE). Total examination time was less than 10 minutes, and scanning timewas only 5 minutes. Prompt referrals and follow-ups were arranged in cases of suspicious lung nodules.

Results: A total of 559 individuals (4.8%) had suspicious lung nodules. A total of 49 primary lung cancers werediagnosed in 46 individuals: 41 prevalence cancers and 8 incidence cancers. The overall detection rate of primarylung cancers was 0.4%. For smokers aged 51 to 70 years, the detection rate was 1.4%. TNM stage I diseaseaccounted for 37 (75.5%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm).The most histological types were adenocarcinoma in 38 (77.6%).

Conclusion: Rapid zero-dose MRI can be used for lung cancer detection in a healthy population.

BackgroundLung cancer is the leading cause of cancer death world-wide [1-3]. The overall 5-year survival rate is approxi-mately 15% in the United States and less than 10% inEurope [4-6]. Because most lung cancers generate nosymptoms at early stages, they are usually diagnosed at anadvanced stage and have a poor prognosis. However,many lung cancer deaths could be avoided if tumors weredetected at an early stage when they were still resectable.For stage Ia non-small cell lung cancer, the 5-year survivalrate is higher than 80%. Prognosis and treatment

outcomes have been found to be related to the diseasestage at the time of diagnosis [7-9]. Various modalitieshave been investigated for detecting early lung cancer andconsequently reducing lung cancer mortality. In the 1970s,several randomized controlled trials of chest radiography,alone or combined with sputum cytology, were performed.However, because of the poor sensitivity of these methods,the reported data indicated no evidence of benefit in termsof reduction in lung cancer mortality [10-12]. In the 1990s,many observational clinical trials were begun of low-dosespiral computed tomography (LDCT). Those studiesshowed that although LDCT can detect more early lungcancers than chest radiography, it does not result in adecrease in lung cancer deaths [13-19].Until recently, magnetic resonance imaging (MRI) was

regarded as an inappropriate tool for lung cancer

* Correspondence: cmychang@vghtpe.gov.tw; dmliou@ym.edu.tw† Contributed equally2Institute of BioMedical Informatics, National Yang-Ming University, Taipei,Taiwan4Department of Radiology, Taipei Veterans General Hospital, Taipei, TaiwanFull list of author information is available at the end of the article

Wu et al. BMC Cancer 2011, 11:242http://www.biomedcentral.com/1471-2407/11/242

© 2011 Wu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

Protocole: (1,5 T Sonata et Sonata Maestro; Siemens MS)

2D T2 HASTE (Half Fourrier Acquisition Single shot Turbo spin Echo)

VIBE (3D Volumetric Interpolated Breath-hold Examination) Durée total des acquisitions: 5-6 minutes Durée total de l’examen: 10 minutes

Nodule de 1,1 cm Carcinome épidermoïde stade Ia

01/10/13  

3  

Les limitations

•  Etude rétrospective: Perdu de vue •  TDM: seulement en cas d’anomalie observée

en IRM •  L’injection du Gadolinium: – Avec Gadolinium 9003 (64%) – Sans Gadolinium 5037 ( 36%)

•  Gadolinium: Augmente le nombre des nodules détectés, bénins ou malin (p<0,001)

Conclusion 1 Détection

•  Points positifs: – Faisabilité – Taille: >5mm proche de 100% de sensibilité – Séquences: Apnée et en asservissement respiratoire – T2 avec suppression de la graisse

•  Durée de l’examen: 10 à 20 mn

•  Coût et disponibilité des machines

Caractérisation

•  Signal en T1/T2

•  Comportement en diffusion

•  Type de la prise de contraste

01/10/13  

4  

•  Homme de 75 ans •  Tabac= 0 •  Mineur •  Caractérisation de

nodule

SUV: 10

Nodule pulmonaire: place de l’IRM Caractérisation

Fiesta FS STIR DWI B 600

Coro  STIR   Coro  DWI  Reichert M, et al. PET Imaging in Patients with Coal Workers Pneumoconiosis and Suspected Malignancy. Journal of Thoracic Oncology 2009;4:649-651

01/10/13  

1  

Un autre mineur

TSE-T2 Propeler

TSE-T2 IDEAL

01/10/13  

2  

Imagerie Water/Eau

Imagerie Fat/Graisse

Imagerie In phase/En phase

Imagerie Out-phase/ Opposition de phase

01/10/13  

3  

T2  Propeller  

T2  IDEAL  

SET1  DB  

01/10/13  

4  

Caractérisation

•  Signal en T1/T2: – Nodule silicotique – Nodule à contenu hématique – Nodule graisseux – Atélectasie ronde

•  Comportement en diffusion

•  Type de la prise de contraste

Nodule silicotique Hématocèle

Pnp lipidique Atélectasie ronde

Koh DM, et al. AJR 2007;188:1622-1635

S/S0 = e-b.ADC

01/10/13  

1  

Caractérisation tissulaire: Carte ADC Plusieurs valeurs de b (0, … 1000) b>800 sec/mm2

b = 50 sec/mm2

b = 200 sec/mm2

b = 600 sec/mm2

b = 1000 sec/mm2

Carte ADC

Imagerie de diffusion et nodule pulmonaire

b = 0 sec/mm2 b = 200 sec/mm2 b = 600 sec/mm2

b = 1000 sec/mm2

ADC map

ADC-avg: 1.4 10-3mm2/sec ADC-min: 0.6 10-3mm2/sec ADC-max: 2.12 10-3mm2/sec

Histology: adenocarcinoma

b = 1000 sec/mm2 STIR

Imagerie de diffusion et nodule pulmonaire

01/10/13  

2  

Imagerie de diffusion et nodule pulmonaire

Adenopathy: ADC-avg: 2.4 10-3mm2/sec Tumor ADC-avg: 0.9 10-3mm2/sec

Imagerie de diffusion et nodule pulmonaire

Auteurs (année)

IRM Etude N° des

patients

Nodule Malin / Bénin

b

s/mm2

seuil

Sensibilité (95% CI)

Spécificité (95% CI)

Valeur Dg

(95% CI)

Mori et al

(2008)

Achieva Prospective 114 106/34 0 / 1000 1.1 0.7 (0.6-0.79)

0.97 (0.84-1.00)

0.76 (0.69-0.84)

Satoh et al

(2008)

Intera Retrospective Consecutive

51 36/18 0 / 1000 ND 0.89 (0.74-0.97)

0.61 (0.36-0.83)

0.80 (0.69-0.90)

Ohba et al

(2008)

Achieva Retrospective Consecutive

110 96/28 0 / 1000 1.2 0.84 (0.74-0.91)

0.93 (0.68-1.00)

0.78 (0.71-0.85)

Uto et al (2009)

Signa Prospective 28 18/10 0 / 1000 0.834 0.72 (0.47-0.90)

0.10 (0.00-0.45)

0.5 (0.42-0.68)

Liu et al (2010)

Twin-Speed

Infinity

Retrospective Consecutive

62 54/12 0 / 500 1.4 0.83 (0.69-0.92)

0.74 (0.45-0.92)

0.7 (0.59-0.81)

Ohba et a1

(2011)

Achieva (1.5T)

Prospective 58 58/18 0 / 1000 1 0.91 (0.84-0.99)

0.94 (0.83-1.00)

0.92 (0.86-0.98)

Ohba et al

(2011)

Achieva (3T)

Prospective 58 58/18 0 / 1000 1.85 0.90 (0.82-0.98)

0.94 (0.83-1.00)

0.91 (0.85-0.97)

Tondo et al

(2011)

Achieva Retrospective 34 30/4 0 / 500 / 1000

1.25 0.90 (0.73-0.98)

1.00 (0.40-1.00)

0.91 (0.82-1.00)

Sommer et al

(2012)

Avanto Prospective 31 28 / 3 0 / 800 ND 0.93 (0.84-1.00)

0.5 (0-0-1.00)

0.89 (0.77-1.00)

!!!Khalil  A,  et  al.  Contribu7on  of  MRI  in  lung  cancer  staging.  JBR-­‐BTR  2013;96:132-­‐141    

01/10/13  

3  

6/9/2012   8/11/2012  

T2  Propeler  avec  FS   T1  EG  FS   T1  EG  FS  +  Gado  

b  =  0  mm/sec  

b  =  1000  mm/sec  

b  =  0  mm/sec  

b  =  1000  mm/sec  

01/10/13  

4  

Imagerie de diffusion et nodule pulmonaire

Contribution of MRI in Lung Cancer Detection / Caractérisation

Database: Medline, EMBASE, Cancerlit and Cochrane Library Period: January 2001 to August 2011 N° of studies: 10 N° of patients 545 Pooled sensitivity / specificity: 0.84 (95% CI, 0.76–0.90) 0.84 (95% CI, 0.64–0.94). Conclusion: Diffusion weighted magnetic resonance imaging can be used to differentiate malignant from benign pulmonary lesions. High-quality prospective studies regarding DWI in the evaluation of pulmonary nodules are still needed to be conducted.

Conclusion

•  Caractérisation du nodule: –  IRM •  Plus spécifique que la TEP-CT •  Moins sensible que la TEP-CT

– Taille du nodule: > 10 mm – Limites de la séquence de diffusion: •  Taille du nodule •  Localisation (apex?) •  Adénocarcinome

– N’oubliez pas les séquences standards!!!!!

02/10/13

1

Ponction des nodules pulmonaires : Bonnes pratiques

E. de Kerviler, Cédric de Bazelaire, Service de Radiologie, Hôpital Saint-Louis, APHP 

1

Bonnes pratiques : les grandes questions

2

}  Comment optimiser ses prélèvements ? }  Biopsier en fonction des caractéristiques des nodules ?

}  Taille }  Aspect

}  Rôle de la TEP ? }  Quelles sont les complications ?

Comment ? Problèmes complexes, hypothèses multiples

Prélèvements multiples à l’aide d’un système coaxial, conditionnement irréprochable

3

Aiguille à biopsie

Stylet déployé

Introducteur

Aiguille de 18G

02/10/13

2

Conditionnement des prélèvements

4

Fixation }  Morphologie

}  Imunohistochimie

Congélation }  Biologie moléculaire

}  Imunohistochimie

Molecular markers: Beyond morphology

Morphology Molecular studies

5

NSCLC }  Adenocarcinoma }  Squamous }  Large cell

}  SCLC

}  EGFR mutations }  EML4-ALK translocation }  KRAS mutations }  HER2 mutations }  BRAF mutations }  P13K mutations

Linderman NI et al. Arch Pathol Lab Med 2013;137:828-60

6

02/10/13

3

Optimiser son prélèvement

7

}  Contrôler la position de la fenêtre de prélèvement }  Les poumons bougent

(bases > sommets) }  Les nodules fuient }  Certaines lésions sont

proches des structures vitales

Vérifier la position de la fenêtre de prélèvement

Masse du lobe Inférieur droit. Suspicion de cancer.

8

Dg = Mucormycose

02/10/13

4

Vérifier la position de la fenêtre de prélèvement

Nodule du lobe supérieur gauche. Suspicion de cancer.

10

11

n engl j med 366;10 nejm.org march 8, 2012 883

The new england journal of medicineestablished in 1812 march 8, 2012 vol. 366 no. 10

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Marco Gerlinger, M.D., Andrew J. Rowan, B.Sc., Stuart Horswell, M.Math., James Larkin, M.D., Ph.D., David Endesfelder, Dip.Math., Eva Gronroos, Ph.D., Pierre Martinez, Ph.D., Nicholas Matthews, B.Sc.,

Aengus Stewart, M.Sc., Patrick Tarpey, Ph.D., Ignacio Varela, Ph.D., Benjamin Phillimore, B.Sc., Sharmin Begum, M.Sc., Neil Q. McDonald, Ph.D., Adam Butler, B.Sc., David Jones, M.Sc., Keiran Raine, M.Sc., Calli Latimer, B.Sc., Claudio R. Santos, Ph.D., Mahrokh Nohadani, H.N.C., Aron C. Eklund, Ph.D., Bradley Spencer-Dene, Ph.D.,

Graham Clark, B.Sc., Lisa Pickering, M.D., Ph.D., Gordon Stamp, M.D., Martin Gore, M.D., Ph.D., Zoltan Szallasi, M.D., Julian Downward, Ph.D., P. Andrew Futreal, Ph.D., and Charles Swanton, M.D., Ph.D.

A bs tr ac t

From the Cancer Research UK London Research Institute (M. Gerlinger, A.J.R., S.H., D.E., E.G., P.M., N.M., A.S., B.P., S.B., N.Q.M., C.R.S., B.S.-D., G.C., G.S., J.D., C.S.), Royal Marsden Hospital De-partment of Medicine (J.L., M.N., L.P., G.S., M. Gore), Wellcome Trust Sanger Institute (P.T., I.V., A.B., D.J., K.R., C.L., P.A.F.), Barts Cancer Institute at the Barts and the London School of Medicine and Dentistry (M. Gerlinger), and the Uni-versity College London Cancer Institute (C.S.) — all in London; the Technical Uni-versity of Denmark, Lyngby (A.C.E., Z.S.); and Harvard Medical School, Boston (Z.S.). Address reprint requests to Dr. Swanton at the Cancer Research UK London Research Institute, Translational Cancer Therapeu-tics Laboratory, 44 Lincoln’s Inn Fields, London WC2A 3LY, United Kingdom, or at charles.swanton@cancer.org.uk.

Drs. Gerlinger, Larkin, Gronroos, Martinez, and Swanton and Mr. Rowan, Mr. Hors-well, Mr. Endesfelder, Mr. Matthews, and Mr. Stewart contributed equally to this article.

N Engl J Med 2012;366:883-92.Copyright © 2012 Massachusetts Medical Society.

BackgroundIntratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.

MethodsTo examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples ob-tained from primary renal carcinomas and associated metastatic sites. We character-ized the consequences of intratumor heterogeneity using immunohistochemical analy-sis, mutation functional analysis, and profiling of messenger RNA expression.

ResultsPhylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple dis-tinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prog-nosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tu-mor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors.

ConclusionsIntratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, asso-ciated with heterogeneous protein function, may foster tumor adaptation and thera-peutic failure through Darwinian selection. (Funded by the Medical Research Council and others.)

The New England Journal of Medicine Downloaded from nejm.org at ASSISTANCE PUBLIQUE HOPITAUX PARIS on June 19, 2012. For personal use only. No other uses without permission.

Copyright © 2012 Massachusetts Medical Society. All rights reserved.

Intr atumor Heterogeneity Revealed by multiregion Sequencing

n engl j med 366;10 nejm.org march 8, 2012 887

tion through loss of SETD2 methyltransferase func-tion driven by three distinct, regionally separated mutations on a background of ubiquitous loss of the other SETD2 allele on chromosome 3p.

Convergent evolution was observed for the X-chromosome–encoded histone H3K4 demeth-ylase KDM5C, harboring disruptive mutations in R1 through R3, R5, and R8 through R9 (missense

and frameshift deletion) and a splice-site mutation in the metastases (Fig. 2B and 2C).

mTOR Functional Intratumor HeterogeneityThe mammalian target of rapamycin (mTOR) ki-nase carried a kinase-domain missense mutation (L2431P) in all primary tumor regions except R4. All tumor regions harboring mTOR (L2431P) had

B Regional Distribution of Mutations

C Phylogenetic Relationships of Tumor Regions D Ploidy Profiling

A Biopsy Sites

R2 R4

DI=1.43

DI=1.81

M2bR9

Tetraploid

R4b

R9 R8R5

R4a

R1R3R2

M1M2b

M2a

VHL

KDM5C (missense and frameshift)mTOR (missense)

SETD2 (missense)KDM5C (splice site)

SETD2 (splice site)

?

SETD2 (frameshift)

PreP

PreM

Normal tissue

PrePPreMR1R2R3R5R8R9R4M1M2aM2b

C2o

rf85

WD

R7SU

PT6H

CD

H19

LAM

A3

DIX

DC

1H

PS5

NRA

PKI

AA

1524

SETD

2PL

CL1

BCL1

1AIF

NA

R1$

DA

MTS

10

C3

KIA

A12

67.

RT4

CD

44A

NKR

D26

TM7S

F4SL

C2A

1D

AC

H2

MM

AB

ZN

F521

HM

G20

AD

NM

T3A

RLF

MA

MLD

1M

AP3

K6H

DA

C6

PHF2

1BFA

M12

9BRP

S8C

IB2

RAB2

7ASL

C2A

12D

USP

12A

DA

MTS

L4N

AP1

L3U

SP51

KDM

5CSB

F1TO

M1

MYH

8W

DR2

4IT

IH5

AKA

P9FB

XO1

LIA

STN

IKSE

TD2

C3o

rf20

MR1

PIA

S3D

IO1

ERC

C5

KLALK

BH8

DA

PK1

DD

X58

SPA

TA21

ZN

F493

NG

EFD

IRA

S3LA

TS2

ITG

B3FL

NA

SATL

1KD

M5C

KDM

5CRB

FOX2

NPH

S1SO

X9C

ENPN

PSM

D7

RIM

BP2

GA

LNT1

1A

BHD

11U

GT2

A1

MTO

RPP

P6R2

ZN

F780

AW

SCD

2C

DKN

1BPP

FIA

1THSS

NA

1C

ASP

2PL

RG1

SETD

2C

CBL

2SE

SN2

MA

GEB

16N

LRP7

IGLO

N5

KLK4

WD

R62

KIA

A03

55C

YP4F

3A

KAP8

ZN

F519

DD

X52

ZC

3H18

TCF1

2N

USA

P172

X4KD

M2B

MRP

L51

C11

orf6

8A

NO

5EI

F4G

2M

SRB2

RALG

DS

EXT1

ZC

3HC

1PT

PRZ

1IN

TS1

CC

R6D

OPE

Y1A

TXN

1W

HSC

1C

LCN

2SS

R3KL

HL1

8SG

OL1

VHL

C2o

rf21

ALS

2CR1

2PL

B1FC

AM

RIF

I16

BCA

S2IL

12RB

2

PrivateUbiquitous Shared primary Shared metastasis

Private

Ubiquitous

Lungmetastases

Chest-wallmetastasis

Perinephricmetastasis

M110 cm

R7 (G4)

R5 (G4)

R9

R3 (G4)

R1 (G3) R2 (G3)

R4 (G1)

R6 (G1)

Hilu

m

R8 (G4)

Primarytumor

Shared primaryShared metastasis

M2b

M2a

Propidium Iodide Staining

No.

of C

ells

The New England Journal of Medicine Downloaded from nejm.org at ASSISTANCE PUBLIQUE HOPITAUX PARIS on June 19, 2012. For personal use only. No other uses without permission.

Copyright © 2012 Massachusetts Medical Society. All rights reserved.

Intr atumor Heterogeneity Revealed by multiregion Sequencing

n engl j med 366;10 nejm.org march 8, 2012 889

balances on chromosomes 3p and 10q were the only ubiquitous aberrations (Fig. 11 in the Supple-mentary Appendix).

Trimethylated H3K36 staining was absent from tumor cells in regions with SETD2 frame-shift or missense mutations (Fig. 12 in the Sup-plementary Appendix), indicating that both muta-tions together with a 3p deletion confer convergent loss of function. Regions with either a splice-site mutation or a missense mutation in PTEN, a negative regulator of the PI3 kinase–Akt pathway located on chromosome 10, showed increased phospho-Akt staining, as compared with PTEN

wild-type regions (Fig. 13 in the Supplementary Appendix), consistent with loss of PTEN function and convergent phenotypic evolution.

Regional allelic-imbalance profiling of prima-ry tumors from Patients 3 and 4 provided further evidence of genetic intratumor heterogeneity (Fig. 11 in the Supplementary Appendix). Only 4 of 30 samples from four patients had identical allelic-imbalance profiles (tumor from Patient 3 in R1, R3, R4, and R9). Chromosome 3p aberrations oc-curred ubiquitously in all regions from all tumors, and allelic imbalances of 10q (in tumor from Pa-tient 2) and in 5q and 6q (in tumor from Patient 4)

C Prognostic Signature Genes

B Immunoblotting of Caki1 CellsA mTOR Staining

Moc

k

Wild

type

L243

1P

Moc

k

Wild

type

L243

1P

Phospho-S6

S6

GFP-mTOR

Serum Starvation10% Serum

Actin

Phospho-S6

Phospho-4EBP

R4

R4

R5

R5

mTOR (wild type)

mTOR (wild type)

mTOR (L2431P)

mTOR (L2431P)

M2aM2b

R4R8R5R1R3R2

Genes Up-regulated in ccB Genes Up-regulated in ccA

!2 0 1 2!1z Score

Figure 3. Correlations between Genotype and Phenotype in Patient 1.

Panel A shows phospho-S6 (Ser235/236) and phospho-4EBP (Thr37/46) staining. All tumor regions harboring mTOR (L2431P) had increased staining of the downstream mTOR-pathway targets phospho-S6 and phospho-4EBP. Regions harboring wild-type mTOR had absent phospho-S6 and phospho-4EBP staining in tumor cells. Panel B shows immu-noblotting of Caki1 cells (derived from a human renal-cell carcinoma) that were transiently transfected with green flu-orescent protein (GFP) vector alone (mock), GFP-mTOR (wild type), or GFP-mTOR (L2431P) with and without serum starvation. Panel C shows hierarchical clustering of samples on the basis of prognostic signature genes of two molec-ular subgroups: clear-cell A (ccA), which indicates a good prognosis, and clear-cell B (ccB), which indicates a poor prognosis. The metastatic sites (M2a and M2b) and the primary-tumor site R4 segregated together, enriched for genes in the clear-cell A subgroup, in contrast to the remaining tumor regions that were enriched for the clear-cell B subgroup, showing that gene-expression signatures may not correctly predict outcomes if samples are obtained from a single biopsy. The brackets on the right side of the heat map (dendrogram) indicate the hierarchical clustering of the samples according to the expression of the analyzed genes. The z scores indicate the difference in standard devia-tions between the mRNA expression of a gene in a sample and its mean mRNA expression across all samples.

The New England Journal of Medicine Downloaded from nejm.org at ASSISTANCE PUBLIQUE HOPITAUX PARIS on June 19, 2012. For personal use only. No other uses without permission.

Copyright © 2012 Massachusetts Medical Society. All rights reserved.

Vérifier la position de la fenêtre de prélèvement

Nodule du lobe inférieur gauche. Biopsie en sextant.

12

02/10/13

5

Caractéristiques des nodules

Verre dépoli, taille …

13

Image-guided biopsy of GGO

14

}  FN rate 20-30% }  Concordance with

resection in only 70%

Author N Diagnostic yield Shimizu K. Lung Cancer 2006;51:173-9

96 Overall 64% <10mm 48.5% 11-15mm 62.5% 16-20mm 83.9%

Kim TJ. AJR 2008;190:234-9

50 91%

Hur J. AJR 2009;192:629-34

28 80-88%*

* Depending en percentage of GGO

Performance des biopsies pulmonaires

Sensitivity (%) Acuracy (%) No of Procedures Ref.

Overall 82%

87%

91%

88%

77%

94%

61

162

846

Wallace MJ, Radiology 2002

Ohno Y, AJR 2003

Geraghty PR, Radiology 2003

Malignancy

-­‐  <10mm

-­‐  <10mm

-­‐  <15mm

-­‐  >15mm

-­‐  >20mm

89%

88%

67%

72%

94%

75%

91%

92%

80%

74%

96%

88%

604

47

10

70

27

8

Montaudon M, Eur Radiol 2004

Wallace MJ, Radiology 2002

Hur J, AJR 2009

Li H, AJR 1996

Li H, AJR 1996

Hur J, AJR 2009

Infection

-­‐  Fungal

70.6%

76.4%

17

Nosari A, Haematologica 2003

02/10/13

6

Les petits nodules (<10 mm)

Aiguillé « décalée » par rapport au nodule

16

Utilisation de pistolets automatiques

17

}  Avantages }  Tir très rapide

}  Inconvénients }  Plus lourds }  Saignement un peu plus

fréquent

ATCD de lymphome de MALT traité. Réapparition de nodules pulmonaires

Dg = Métastase de mélanome

02/10/13

7

Biopsie au pistolet automatique

ATCD de K urothélial

19

Rôle de la TEP

20

La TEP, grande pourvoyeuse de biopsies …

TEP réalisée dans le bilan d’une fièvre inexpliquée. Tabagisme.

21

Contrôle à 2 mois

02/10/13

8

22

23

Adénocarcinome

Les complications

24

02/10/13

9

Complications

Risk No of Procedures Needle Ref.

Pneumothorax (total/

chest tube)

23% / 5%

62% / 31%

28% / 2.5%

26% / 8%

21% / 2%

17% / 2%

17% / 0.5%

660

61

162

846

97

135

605

19G CNB

18G PNAB

22G PNAB

19G PNAB

19G PNAB

17G CNB

19G CNB

Yeoh KM, Chest 2004

Wallace MJ, Radiology 2002

Ohno Y, AJR 2003

Geraghty PR, Radiology 2003

Li H, AJR 1996

Khan MF, Eur Radiol 2008

Montaudon M, Eur Radiol 2004

Bleeding (total/

hemoptysis)

30% / 4%

-/ 2%

27% / 6%

20% / 3.8%

660

846

135

604

19G CNB

19G PNAB

17G CNB

19G CNB

Yeoh KM, Chest 2004

Geraghty PR, Radiology 2003

Khan MF, Eur Radiol 2008

Montaudon M, Eur Radiol 2004

Vasovagal response 0.3% 846 19G PNAB Geraghty PR, Radiology 2003

5-30%

2-60%

27

02/10/13

10

Recommandations

*Guidelines for radiologically guided lung biopsy. Thorax 2003; 58:920-936

Index Recommandations

Plaquettes > 100 000

INR < 1.5

TP > 60%

Complications Hémoptysie 5%

Pneumothorax grave Total

Nécessitant drainage

20% 3%

Une complication peut en cacher une autre

Masse pulmonaire sous pleurale du lobe supérieur gauche chez un patient emphysémateux et coronarien. Hémostase normale. Toutes les conditions sont réunies pour obtenir un pneumothorax. Le drain est prêt...

29

Hémoptysie Hémorragie alvéolaire

Le patient avoue finalement être sous Plavix® pour un stent coronarien …

Comment éviter/gérer les complications ?

}  Bonne coopération du patient }  Bilan d’hémostase }  EFR en fonction ATCD }  Avoir un chariot d’urgence }  Prévoir des marges de sécurité }  Avoir un scanner réactif }  Anticiper les problèmes

02/10/13

11

Attention aux lésions sous pleurales !

31

Introducteur en place

…Pneumothorax Post exsufflation

Introducteur ouvert…

Ne pas viser les organes nobles

Espace de sécurité derrière une lésion.

32

Patiente étrangère, ne parlant pas le français, très peu coopérante

Tamponnade : drainage péricardique en urgence

02/10/13

12

Eviter les scissures et la plèvre

34

Eviter le parenchyme sain

Masse pulmonaire, suspicion de cancer.

35

Plèvre, parenchyme aéré

Eviter de traverser le parenchyme aéré

“Pleural tail”

Aiguille à biopsie

02/10/13

13

BPCO, masse du hile pulmonaire droit, fibroscopie négative

Eviter les vaisseaux

39

02/10/13

14

Savoir injecter … parfois

ATCD de Leucémie Lymphoïde Chronique. Apparition d’une masse spiculée du lobe supérieur droit : Cancer ? Lymphome ? Infection ?

40

Hémoptysie MIP

Conclusion

Technique incontournable Limites

}  Rendement }  Tolérance

}  Taille des nodules à 10 mm }  Densité des nodules : +/- }  Localisation des nodules : +/- }  Emphysème à oui }  Hémostase à +/-

Kim TJ et al. AJR 2008; 190:234-239

Dr Igor LETOVANEC

Médecin associé

Service d’Anatomo-Pathologie, CHUV Lausanne

Le terme « nodule pulmonaire » (qu’il soit unique ou pas) ne

reflète (mal)heureusement pas la très grande diversité des

lésions, images histologiques ou pathologies pouvant

l’expliquer, allant de la tumeur maligne primitive ou

métastatique à la simple lésion inflammatoire ou infectieuse

(cf tableau 1 et 2)(1). Bien entendu l’attitude

(thérapeutique/clinique) dépendra du diagnostic (chirurgie,

chimiothérapie, antibiotiques, surveillance ou simple mépris…)

qui relève en partie du pathologiste.

Concernant les carcinomes pulmonaires, de grands efforts ont

été fait pour standardiser la nomenclature, notamment sur les

biopsies et des guidelines ont été éditées pour améliorer la

communication et la compréhension entre les radiologues,

pneumologues, chirurgiens et oncologues d’un côté et les

pathologistes de l’autre, notamment dans la dernière

classification de IASLC/ATS/ERS qui est multidisciplinaire

(3). Le tableau 3 résume ces recommandations qui reflètent

essentiellement le fait qu’une biopsie n’échantillonne qu’une

partie de la lésion qui est bien souvent hétérogène. Ces

données sont essentielles en cas d’adénocarcinome

d’architecture lépidique prédominante (adénocarcinome in situ,

adénocarcinome micro-invasif ou à prédominance lépidique).

Pour les adénocarcinomes essentiellement, il existe donc une

classification séparée pour les biopsies et les résections.

La question de l’échantillonnage et de l’hétérogénéité des

lésions en cas de biopsie instrumentale est valable pour les

autres images histologiques également, une réaction

inflammatoire, pneumonie en organisation ou remaniement

fibreux pouvant accompagner ou constituer une partie

importante d’une lésion tumorale.

Le message essentiel à retenir est l’importance de la

confrontation des résultats de biopsie à l’imagerie et à la

clinique, dont le poid est inversément proportionnel à la

taille de l’échantillon diagnostic soumis au pathologiste.

Bibliographie :

1: Patel VK, Naik SK, Naidich DP, Travis WD, Weingarten JA,

Lazzaro R, Gutterman DD, Wentowski C, Grosu HB, Raoof S. A

practical algorithmic approach to the diagnosis and management

of solitary pulmonary nodules: part 2: pretest

probability and algorithm. Chest. 2013 Mar;143(3):840-6.

2: Patel VK, Naik SK, Naidich DP, Travis WD, Weingarten JA,

Lazzaro R, Gutterman DD, Wentowski C, Grosu HB, Raoof S. A

practical algorithmic approach to the diagnosis and management

of solitary pulmonary nodules: part 1: radiologic

characteristics and imaging modalities. Chest. 2013

Mar;143(3):825-39.

Dr Igor LETOVANEC

Médecin associé

Service d’Anatomo-Pathologie, CHUV Lausanne

3 : Travis WD, Brambilla E, Noguchi M, Nicholson AG, & al.

International association for the study of lung

cancer/american thoracic society/european respiratory society

international multidisciplinary classification of lung

adenocarcinoma. J Thorac Oncol. 2011 Feb;6(2):244-85.

Tableau 1 : métastases pulmonaires unique (1)

Dr Igor LETOVANEC

Médecin associé

Service d’Anatomo-Pathologie, CHUV Lausanne

Tableau 2 : diversité des lésions pulmonaires (1)

Dr Igor LETOVANEC

Médecin associé

Service d’Anatomo-Pathologie, CHUV Lausanne

Tableau 3 : Classification des carcinomes sur petites biopsies

(3)

03.10.2013

1

Nodule pulmonaire, 05 oct. 2013

Moyens diagnostiques par endoscopie

Dr Alban Lovis

Plan de la présentation :

1. -le problème du screening et du taux élevé de faux positif

2. -bilan endoscopique ou percutané?

3. -bilan par bronchoscopie,

nécessité d’une méthode de guidage et d’une méthode de visualisation de la cible

la radioscopie

l’EBUS radiaire

la navigation électromagnétique

le bronchoscope ultrafin

approche combinée, méthode de guidage+visualisation de la cible

EBUS+ navigation électro magnétique

EBUS+bronchoscopie virtuelle

4. -conclusion

La lésion pulmonaire périphérique :p p p qEndoscopiquement «invisible»

03.10.2013

2

Screening du cancer pulmonaire :

Toutes les recommandations américaines préconisent un screeningNCCN, A. Lung association, ACCP, ATS, A. Society of clinical oncology, ACS..

Prévalence du nodule pulmonaire solitaire(SPN) ds les études de screening du ca pulmonaire par CT scan : 8-51%

NLST : au premier screen, 24% investigations diagnostiques supplémentaires12% de ces 24% bronchoscopie, TTNA, surgery

Besoin d’une stratégie diagnostique performante

Probabilité à priori de tumeur

Anamnèse et caractéristiques morphologiques de la lésion, clichés comparatifs

Lésion bénigne STOP

~5%

Haute prob. etPatient opérable

chirurgie

~20-30%

Probabilité intermédiaireOu non opérable

-Besoin de tissu

~75%

CT-G-Biopsy.

bronchoscopie

-Pneumothorax-Pas d’information endoluminale

A Practical Algorithmic Approach to theDiagnosis and Management of SolitaryPulmonary Nodules; ACCP CHEST 2013

-Suivi Rx

03.10.2013

3

CT-guided needle biopsy Bronchoscopie

Avantage Bonne performance diagnostiqueDisponible Délai courtCoût peu élevéIndépendant de l’axe bronchique

Bonne performance diagnostiqueStatus endobronchiqueDisponible Délai courtCoût peu élevé

Désavantage Complications respiratoiresIrradiation patientIrradiation personnel«Minimalement invasif»

Dépendant de l’axe bronchique«minimalement invasif»

« L’évaluation des voies aériennes supérieures et inférieure a été positive pour des lésions endoscopiquement visibles ds 12.6% des cas «

Status endoscopique :

Tout patient bilanté pour une tumeur pulmonaire devrait avoir un bilan endobronchique

Complications :

D.P. Steinfort, J. Vincent

03.10.2013

4

CT-guided needle biopsy Bronchoscopie

Sous pleural, absence de signe bronchique

Lésion centrale, signe bronchique,Status emphysèmateux

Bronchoscopie :

Lésions pulmonaires périphériques,

endoscopiquement «invisibles»

???

???

Méthode de guidage

Visualisation de la cible

03.10.2013

5

Méthode de guidage

Lésion pulmonaire périphérique, approche par bronchoscopie

Navigation virtuelle

navigationÉlectro-magnétique

Aveugle

Bronchoscopievirtuelle

Navigation réelle

Visualisation de la cible

fluoroscopie

En temps réel, direct

Radial probeultrasound

Ultrathin bronchoscopy

CHUV trial 2012

Technique de guidage par radioscopie :

Sensibilité de la fluoroscopie :

Schreiber, Chest 2003; 115: 128

69% 46% 67%

03.10.2013

6

TBNA, transBronchial Needle Aspiration

Wang KP, Haponik EF, Britt EJ, Khouri N, Erozan Y. Chest 1984; 86: 819-823

Fluoroscopie, sensibilité dpt de la taille

<2cm = 33% >2cm = 62%

Fluoroscopie, sensibilité dpt du signe bronchique

Signe bronchique négatif: signe bronchique positif :

Se (32%) Se (55%)

Naidich D.P. et Al: Chest 1988; 93: 595-598

03.10.2013

7

Le rendement diagnostique est significativement influencé par

-le diamètre, > vs < 2cm, (63 vs 34%)

La radioscopie dans lalésion pulmonaire périphérique :

-la présence vs absence de signe bronchique au CT (60 vs 25%)

-le nombre de prélévement (70% si 6 vs 45% si 1)

-l’expérience de l’opérateur

-l’usage de l’aiguille(TBNA) en plus que de la pince

-l’usage de technique de guidage, d’imagerie

EBUS : EndoBronchial UltraSound

EBUS radiaire pour les lésions périphérique

Mini sonde radiaire de 20-MHz introduit dans le canal de travail Lésion échogène

EBUS

Guide Sheath, guide

N. Kurimoto, CHEST 2004

03.10.2013

8

Rendement diagnostic de l’EBUS dans les lésions pulm. périphériques :

D.Y. de 60-80%

1)Guidance methods

Etude CHUV 2012

2)Target visualization

3)Sampling under fluoroscopic control

Identification of the bronchus proximal to the lesion

UM-S20-17S , ultra-thin, 1.4mm radial ultrasonic probe, operating frequency of 20 MHz

Feasibility :

outpatient care.

Moderate sedation and local anesthesia for all patients

Short duration of the exam, 5-10 min local anesthesia, 5-15 min inspection+

Search of the target, 5-20min for sampling

All case(51/51) have had the assesment with fluoroscopy + EBUS radial probe,

followed by sampling (brush, +/-LBA, +/-TBB if EBUS visible, +/-TBNA if target adjacent)

03.10.2013

9

Side Effects :

Minor hemorrhage following - EBUS, ~25%,

- sampling, frequent, >90%

Major hemorrhage requiring interruption of the procedure, 1/51

Pneumothorax 0/51

Respiratory failure requiring noninvasive or invasive ventilation 0/51

Mean Age 66.4 +/-9 years old

Mean size of the PPL= 25.725.7 +/-15.0mm

Mean distance to the pleura :                                12.012.0 +/‐12.4 mm

Results :

p /

Mean distance to the hile                                        38.538.5 +/‐ 20.7 mm

Bronchus sign 28/51

Visible with radial probe EBUS :                              42/51 ( 82.3%)

Diagnostic yield :

51 patients with PPL investigated by EBUS radial probe +scopy in 2012

37 diagnostics : 31 NSCLC1 MALT lymphoma1 melanome metastasis3 COP

Diagnostic yield

37/51= 72.5%14 without diagnostic :

1 TBC

3 suspected TBC, with regression under TBC TTT

1 NSCLC and 1 intestinal metastasis proved by surgery

2 suspected NSCLC ttt by radiotherapy(1 with TTNAneg)

1 suspected lymphoma with regression under chimioth.

1 sampling interrupt because hemorrhage, D by 2ième Broncho

2 patients lost

2 indeterminated but stable at the CT follow up at 1 year

1 spontaneous normalization

9 false negative

3 True negative

27 NSCLC confirmed by surgery1 lymphoma, resolution under chimio1 COP, good evolution under steroids1 Tbc, good evolution under TTT

3 with irradiation1 without treatment refused by the patient3 patients lost

Follow up :

No evidence of false positive

03.10.2013

10

Factors influencing the Diagnostic Yield :

Size of PPL Diagnostic/total nb

D.Y.

<1 2/4 50%

1-2cm 15/21 71.4%

2-3 cm 8/11 72.7%

>3cm 7/9 77.7%

With Bronchussign

23/28 82.1%

without 12/19 63.15%

Factors influencing the Diagnostic Yield :

Learning curve ? Diagnostic Yield :

First 10 70%

11-20 50%

21-30 80%

31-40 80%

41-51 82%

Pneumologue Diag./Total nb. Diagnostic Yield

A 3/6 50%

B 34/45 75.5%

Factors influencing the Diagnostic Yield :

Type of sampling

Diag/Total nb. Diagnostic Yield

BAL 8/26 32%

Bronchial aspiration 19/41 37.25%

brush 19/42 45%

Transbronchial lungbiopsy(TBLB)

21/42 50%

Transbronchial needle 12/19 63%Transbronchial needleaspiration(TBNA)

12/19 63%

Type of Lesion : 

Pure Ground Glass 1/616.66%

mixte 3/475%

solide 33/4180.48%

EBUS visible

invisible 5/9 55.5%

visible 32/42 76.2%

Intra lesion 20/25 80%

03.10.2013

11

Conclusion

association of a guidance method and a target confirmation is key

EBUS radial probe + fluoroscopic guidance is an easy to perform, not expensive,accurate, performant combination for the diagnostic of peripheral pulmonary lesion

A guide sheath can improve the diagnostic yield in case of difficult, curved access

A good Ctscan analysis +/- 3D airway reconstruction(guidance method) is key

The TBNA is probably the best diagnostic tool, especially for extra-bronchus lesion

1er étape : (10min)Création broncho virtuelleMarquage des 7 points Marquage de la lésion

La navigation électromagnétique(NEM)

2ième étape : (1h)Bronchoscopie normaleBronchoscopie virtuelle prélévements

1) Logiciel de reconstruction 3D depuis des images de CT thoracique

2)Sonde souple à extrémités orientable 8 directions

3)Cathéter prolongateur du canal de travail

4)Champ électromagnétique

03.10.2013

12

Rendement diagnostic de la NEMdans les lésions pulm. périphériques :

D.Y. de 60-80%

G. Gex et al Rev Med Suisse 2010

Diagnostic yield : 17/30= 56%

Vrai + Faux - Vrai -?

D. yield pr <2cm :9/19 = 47%

D. Yield pr <1cm1/7 = 14%

La NEM des lésions pulmonaires périphériques :

Avantage :

Rendement diagnostique de 59-74%

Le rendement ne semble pas diminuer pas pour des lésions <2 cm

La navigation n’est pas précise pour des lésions < 8mm

Le rendement est moins bon dans les lobes inférieurs

Limites :

Nécessité d’une sédation profonde/A.G.

La durée de la bronchoscopie augmente significativement

Les coûts sont élevés

La cible est virtuelle, pas d’imagerie en temps réel…

La survenue de pneumothorax est de ~5%

03.10.2013

13

Bronchoscope ultra-fin

Bronchoscope 2.8 aveccanal de travail 1.2mm

Au CHUV le plus petit bronchoscope est De diamètre 2.0mm sans canal de travail

Rendement diagnostic du bronchoscope ultra-fin Dans les lésions pulmonaires périphériques

D.Y. de 60-80%

Approche endoscopique de la lésion pulmonaire périphérique

J. S. Wang Memoli, Chest 2012

« The overall adverse event rate is 1.5%,with the majority reporting pneumothorax »

03.10.2013

14

Am J Resp Crit Care Med 2007

Approche combinée, méthode de guidage+visualisation de la cible

EBUS=69% ENB=59% EBUS+ENB=88%

T. Ishida

Approche combinée, méthode de guidage+visualisation de la cible

N=200, prospective multicentrique randomisée EBUS +/- navigation virtuelle

Approche combinée, méthode de guidage+visualisation de la cible

EBUS+VN=80%

03.10.2013

15

ROSE : Rapid On Site Examination

Améliore le rendement diagnostiquePermet de diminuer la durée de l’examenDiminue les complications Diminue le nombre de prélèvement

Conclusion :

Le rendement diagnostic des méthodes de bronchoscopie « guidée » est bon

Ce rendement est nettement amélioré en combinant une méthode de guidage et une visualisation de la cible

Le faible risque de complications est un avantage par rapport aux ponctions percutanées

Les techniques endoscopiques sont complémentaires à celles percutanées

03.10.2013

1

Nodule pulmonaire: indications chirurgicales

Dr Michel Gonzalez

Service de Chirurgie Thoracique

Le Nodule Pulmonaire 5 octobre 2013

CT-Scan thoracique hélicoïdalScreening trials dans les populations à risque

Prise en charge des petits nodules, notamment en verre dépoli (ground-glass opacity).

Le Nodule Pulmonaire 5 octobre 2013

Définition du nodule pulmonaireDéfinition du nodule pulmonaire

Lésion unique, bien circonscrite, de < 3cm entourée de parenchyme pulmonaire aéré.(pas d’atélectasie, pas d’épanchement, pas d’adénopathie associés)

- micronodule: < 10mm- macronodule: 10-30mm- masse: > 30mm

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

2

DistinctionDistinction� Taille: - < 8mm

- > 8mm

� Aspect: - solide- verre dépoli

� Critères de bénignité:- calcification en pop-corn- centre graisseux

� Evolution avec le temps

Le Nodule Pulmonaire 5 octobre 2013

Prise en chargePrise en charge

« Before embarking on a potentially inconvenient, risky, and expensive evaluation, it is important to establish the individual’s suitability and desire for

curative treatment. »

Le Nodule Pulmonaire 5 octobre 2013

ACCP Evidence-Based Guidelines 3rd ed.Chest 2013

Résection en cas d’absence de contre-indication 1A

Lobectomie plutôt que segmentectomie / wedge

en cas de réserves cardio-pulmonaires suffisantes 1A

Segmentectomie pour patients avec stade I NSCLC

qui peuvent tolérer une intervention chirurgicale mais

pas une lobectomie (fonctions pulmonaires / comorbidités) 1A

ACCP Evidence-Based Guidelines 3rd ed.Chest 2013

Le Nodule Pulmonaire 5 octobre 2013

Recommandations actuellesRecommandations actuelles

NSCLC Stade I/IINSCLC Stade I/II

03.10.2013

3

VATS- lobectomie pour stade I est préférée par rapport 2C

à la thoracotomie

Curage ganglionnaire médiastinal au lieu du sampling1 1B

1Dans 3 RCT, le curage ganglionnaire augmente la survie (p<0.005) etdiminue la récidive locale (p<0.01) par rapport au sampling

Recommandations actuellesRecommandations actuelles

NSCLC Stade I/IINSCLC Stade I/II

ACCP Evidence-Based Guidelines 3rd ed.Chest 2013

Le Nodule Pulmonaire 5 octobre 2013

VATS VATS lobectomielobectomie

Le Nodule Pulmonaire 5 octobre 2013

VATS VATS lobectomielobectomieAvantagesAvantages

- Diminution de la morbidité:

- douleurs

- fuites aériennes- pneumonie- FA

- Durée d’hospitalisation

- Reprise du travail

- Meilleure compliance au ttt adjuvantDowney J, et al. Innovations, 2010

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

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VATS VATS lobectomielobectomie pour NSCLC pour NSCLC précoceprécoce

RécidiveRécidive

Systematic Review and Meta-Analysis of Randomized and Nonrandomized Trials on Safety and Efficacy of Video-Assisted Thoracic Surgery Lobectomy for Early-Stage Non-Small-Cell Lung Cancer. Yan T, et al. J Clin Oncol (2009) 27:2553-2562

Le Nodule Pulmonaire 5 octobre 2013

VATS VATS lobectomielobectomie pour NSCLC pour NSCLC précoceprécoce

SurvieSurvie

Systematic Review and Meta-Analysis of Randomized and Nonrandomized Trials on Safety and Efficacy of Video-Assisted Thoracic Surgery Lobectomy for Early-Stage Non-Small-Cell Lung Cancer. Yan T, et al. J Clin Oncol (2009) 27:2553-2562

Le Nodule Pulmonaire 5 octobre 2013

Lésion solide < 8mmLésion solide < 8mm

Prise en chargePrise en charge

ACCP Evidence-Based Guidelines 3rd ed.Chest 2013

Pas de place pour la chirurgie

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

5

Probabilité de malignité:

- Facteurs cliniques- Métabolisme au PET-CT

- Résultats de la biopsie non chirurgicale- Surveillance au CT-Scan

Lésion solide >8mmLésion solide >8mm

Le Nodule Pulmonaire 5 octobre 2013

Lésion solide >8mmLésion solide >8mmFacteurs cliniquesFacteurs cliniques

– Âge– Tabac– Cancer extrathoracique (>5 ans)– Taille du nodule– Aspect spiculé– Localisation lobe supérieur

Le Nodule Pulmonaire 5 octobre 2013

Swensen. Arch Intern Med 1997Herder. Chest 2005

Risque: - bas (<5%)- intermédiaire (5-65%)- haut (>65%)

Lésion solide >8mmLésion solide >8mmPETPET--CTCT

• Sensibilité: 72-94%• Cost-effective en cas de discordance pré-

test clinique et CT-Scan

ACCP Evidence-Based Guidelines 3rd ed.Chest 2013

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

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Lésion solide >8mmLésion solide >8mmProbabilité de malignitéProbabilité de malignité

Faible < 5% Modéré (5-65%) Haut (>65%)

Facteurs cliniques

Jeune, pas de tabac, pas de cancer, petite taille, margerégulière, pas lobe supérieur

Mixte Agé, fumeur, ATCD cancer, taille, spiculé, bord irrégulier, lobe supérieur

FDG PET-CT Pas d’activité Métabolisme modéré

Hypermétabolique

Biopsie non-chirurgicale

Bénin Non diagnostic Suspect

CT-Scan surveillance

Résolution ou diminution de taille

NA Croissance

Le Nodule Pulmonaire 5 octobre 2013

Lésion solide >8mmLésion solide >8mmPossibilité de prise en chargePossibilité de prise en charge

Procédure Bénéfices InconvénientsBiopsie chirurgicale (wedge)

Diagnostic définitif (100%)Eviter les complications d’une biopsie non chirurgicaleRassurer si bénignitéCompléter la lobectomie en cas de tumeurAnalyse moléculaire

-Air leak (3-5%)-Pneumonie (1-8%)-Décès (0.5%)

Chirurgie inutile si lésion bénigne

Biopsie par bronchoscopie

Diagnostic 60-90% - Hémorragie (2-5%)- Pneumothorax (2-4%)Nécessite quand même une chirurgie si non contributif ou cancerFaux-négatif 30-70%

Biopsie parCT-Scan

Diagnostic<15mm (70-80%)>15mm (90%)

Pneumothorax (15%) Nécessite quand même une chirurgie si non contributif ou cancer

Surveillance Pas de complications RadiationIncertitudeTraitement différé du cancer

Lésion solide >8mmLésion solide >8mmACCP Guidelines 2013ACCP Guidelines 2013

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

7

Lésion solide >8mmLésion solide >8mmACCP Guidelines 2013ACCP Guidelines 2013

Le Nodule Pulmonaire 5 octobre 2013

Lésion en verre dépoliLésion en verre dépoliACCP Guidelines 2013ACCP Guidelines 2013

Pure verre dépoli de <5mm- Pas d’évaluation

Pure verre dépoli de >5mm- CT-Scan annuel

Verre dépoli de < 8mm en partie solide- CT-Scan à 3, 12, 24 mois et annuel jusqu’à 3 ans

Verre dépoli de > 8mm en partie solide- CT- Scan à 3 mois, PET, biopsie non et/ou chirurgicale

Le Nodule Pulmonaire 5 octobre 2013

Nouvelle classification de Nouvelle classification de l’adénocarcinomel’adénocarcinome

Travis. J Thorac Oncol 2011

Distinction:- lésion pré-invasive- adénocarcinome minimal invasif

- adénocarcinome invasif

Nouvelles sous-catégories:adénocarcinome in situadénocarcinome minimal invasif

“Carcinome bronchiolo-alvéolaire”

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

8

Nouvelle classification de l’adénocarcinomeNouvelle classification de l’adénocarcinome

Traitement selon GuidelinesTraitement selon Guidelines

Adénocarcinome in situ (AIS)Lésion de < 3cm

Croissance lépidique pure sans invasion

Adénocarcinome minimal invasif (MIA) Lésion de < 3cmCroissance lépidique pure avec invasion de ≤0.5 cm

Adénocarcinome invasif>5mm invasion

100% survie à 5 ans

100% survie à 5 ans

Travis. J Thorac Oncol 2011Yoshizawa Mod Pathol 2011

50-90% survie à 5 ans

Technique chirurgicaleTechnique chirurgicale

• Découverte d’un nodule spiculé du LSG chez tabagique de 68 ans

• VEMS et DLCO > 80%

• Pas de lésion à distance

• Mise en place d’un fil d’Ariane

Le Nodule Pulmonaire 5 octobre 2013

Technique Technique chirugicalechirugicale

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

9

Technique Technique chirugicalechirugicale

Le Nodule Pulmonaire 5 octobre 2013

Carcinome épidermoïde de 1cm

pT1a pN0 (0/15) R0

Suites simples

Retour à domicile à J+4

Pneumonectomie

Lobectomie

Résection sub-lobaireSegmentectomieWedge

Taux de survie et récidive

?

Mortalité: 3.0 to 25%

Mortalité: <2%

Le Nodule Pulmonaire 5 octobre 2013

Résection sub-lobaireRésection sub-lobaire

Morbidité/Mortalité- équivalente à la lobectomie

Diminution durée hospitalisation

Epargne parenchyme pulmonaire- tumeur synchrone/métachrone

Keenan et al. Ann Thorac Surg 2004

Okami et al. Ann Thor Surg 2010

Chamogeorgakis T. Interact Cardiovasc Thorac Surg. 2009

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

10

246 patients

Résection sub-lobaire augmente- Récidive locale 300%- Récidive locale + à distance 75%- Mortalité tumorale 50% (p=0.09)

Problèmes- Mélange wedge/segmentectomie- Perte du suivi- Augmentation du taux de récidive locale mais pas de la survie globale

Le Nodule Pulmonaire 5 octobre 2013

Auteurs

Okada(2005)

El-Sherif(2006)

Schuchert(2012)

Okumura(2007)

Nombre de patients

L: 919S: 258W:64

L:577S:85W:122

L: 432S:325

L: 1241S:144

Survie à 5 ans

L: 92% L: 81%S: 96% S: 62%W:85% W: 0%

L:71% L: 58%S+W:70% S+W 50%

L: 79%S: 77%

L: 81% L: 78%S:83% S: 58%

< 2cm > 3cm

< 2cm> 2cm

Résection sub-lobaire

Résultats oncologiques NSCLCRésection sub-lobaire

Résultats oncologiques NSCLC

< 2cm> 2cm

Le Nodule Pulmonaire 5 octobre 2013

Résection sub-lobaire

Résultats oncologiques GGO (< 2cm)Résection sub-lobaire

Résultats oncologiques GGO (< 2cm)

Auteurs Nombre Intervention Survie à 5ans

Nakamura 27 Wedge/ 100%(2004) Segmentectomie

Nakata 28 Wedge 100%(2003)

Yoshida 40 Lobectomie/ 100%(2005) Segmentectomie/

Wedge

Le Nodule Pulmonaire 5 octobre 2013

03.10.2013

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• Nombreuses publications (non-randomisées/rétrospectives) suggèrent que la résection sub-lobaire peut être un traitement adéquat.

• Pas de différences dans la survie et la récidive loco-régionale (tumeur <2cm).

Résection sub-lobaireRésection sub-lobaire

Le Nodule Pulmonaire 5 octobre 2013

Résection sub-lobaire

PerspectivesRésection sub-lobaire

Perspectives

2 études prospectives randomisées actuellement en cours comparant la lobectomie vs segmentectomie pour les tumeurs de < 2cm

CALBG 140503 (USA)JCOG 0802 (Japon)

Le Nodule Pulmonaire 5 octobre 2013

Résection sub-lobaire

VATSRésection sub-lobaire

VATS

- Techniquement plus difficile et peu répandue

- Résultats équivalents en terme de morbidité, mortalité et résultats oncologique entre VATS lobectomie et segmentectomie (T1-T2 N0).

Série Seg/Lob VATS Survie à 5ans

Zhong et al 39/81 80%/81%2012

Shapiro et al 31/101 80%/78%2009

Le Nodule Pulmonaire 5 octobre 2013

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Technique chirurgicaleTechnique chirurgicale

Le Nodule Pulmonaire 5 octobre 2013

Résection complète

Marge de résectionRésection complète

Marge de résectionSchuchert et al. Anatomic segmentectomy in the treatment of stage I non-small cell lung cancer Ann Thorac Surg 2007

Récidive loco-régionale: 27/184 (17.3%)85% des récidives en cas de ratio marge chirurgicale/taille tumorale < 1

Le Nodule Pulmonaire 5 octobre 2013

ConclusionConclusion

Le Nodule Pulmonaire 5 octobre 2013

• La prise en charge d’un nodule pulmonaire dépend de sa taille, de l’aspect radiologique et de la probabilité de malignité.

• La prise en charge peut aller de la surveillance à la biopsie chirurgicale.

03.10.2013

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ConclusionConclusion

Le Nodule Pulmonaire 5 octobre 2013

• L’approche chirurgicale permet également de traiter un éventuel cancer dans le même temps.

• La résection sub-lobaire est en cours d’investigation pour les tumeurs de < 2cm.

Le Nodule Pulmonaire 5 octobre 2013

Merci de votre attention

30.09.2013

1

Percutaneousablation of lungmetastasis

Dr Pierre BizeRadiologie CHUV

Introduction:

20-44%Renal cell carcinoma

31-49.5%Breast carcinoma

21-48%Colon carcinoma

40.9-47%Head & neck carinoma

18-28%Soft tissue sarcoma

20-50%Osteogenic sarcoma

5 year survival after surgical resection of isolated pulmonary metastasis according to type of cancer

vanSonnenberg E, McMullen, Solbiati L. Tumor Ablation. Springer 2005.

de Gregorio MA, Rivas de Andrés JJ. Radiofrequency ablation of primary and secondary lung tumors: Is the promise of this scalpel free technique now a reality? Acta Bronconeumol, 2008;44(2):55-7

Overall 5 years survival after surgical resection of lung metastases: 32.4%

Metastasis

Surgery is an accepted treatment for limited secondary cancers when the primary tumor is cured or controlled

Most cancer eventually metastasize to the lung

What if if the patient cannot be operated?

Stereotactic radiation therapy?

Percutaneous ablation (RFA, MWA, CRA)?

Newer techniquesSmall and heterogeneous seriesBUTEncouraging results

30.09.2013

2

What is RFA?RFA = Radio Frequency Ablation. • Alternative current 450-500KHZ emitted by an electrode converts ion

agitation in heat.• Cellular lesions appears above 46°C.

– Immediate coagulation of cell protein at 50°C– Loss of intracellular fluids so called dessication– Loss of electrical conduction capacity

RFA can be successfully used to treat tumors in the lung, liver, kidney, and bone.

45 C death45 C deathin 10mnin 10mn

Time

5050°°C deathC deathIn few secIn few sec

DeshydratationDeshydratationProteic destructionProteic destruction

8080°° dessicationdessicationAround the needleAround the needle

Efficacy zone

Temperature

RFA basic principles

Factors affecting energy deposit:Impedance

Definition: total opposition to the electrical flow in an AC circuit (Ohms)

Combined of

Resistance :static value

Reactance: capacity to store and release energy

The lung represents the ideal situation:

Insulation by air (oven effect)

High impedance

High energy deposition

30.09.2013

3

The feasibility of lung RFA has been demonstrated in animals.

First report of thermal ablation of lung tumor in human in 2000.

Surgical resection performed immediately after RFA: -80% necrosis in 87.5% of tumors >2cm, -100% necrosis in tumors < 2 cm.

RFA of tumors has gained interest and acceptance due to its potential to produce a large volume tissue ablation in a controlled fashion.

Lung RFA Background

Miao Y, Ni Y, Bosmans H, et al. Radiofrequency ablation for eradication of pulmonary tumor in rabbits. J Surg Res 2001; 99:265-271.

Dupuy DE, Zagoria RJ, Akerley W, Mayo-Smith WW, Kavanagh PV, Safran H. Percutaneous radiofrequency ablation of malignancies in the lung. AJR Am J Roentgenol 2000; 174:57-59.

Nguyen CL, Scott WJ, Young NA, Rader T, Giles LR, Goldberg M. Radiofrequency ablation of primary lung cancer: results from an ablate and resect pilot study. Chest 2005; 128:3507-3511.

Typical patient:

- Tumors 3cm or smaller

- 5 lesions or less

- Patient with early stage disease who cannot undergo surgery (poor lung function, other coexisting diseases, poor general performance status)

- Patients with lung tumors that either do not respond to maximum conventional therapy or recur after treatment.

- Patients who cannot afford to lose any more lung tissue.

- Few studies report that RFA can be safely performed in tumors close to vital organs such as the aorta or the heart, BUT tumors that are close to the hilum are not amenable to RFA

Who is suitable for RFA?

Nomori H, Imazu Y, Watanabe K, et al. Radiofrequency ablation of pulmonary tumors and normal lung tissue in swine and rabbits. Chest 2005; 127:973-977.Steinke K, Haghighi KS, Wulf S, Morris DL. Effect of vessel diameter on the creation of ovine lung radiofrequency lesions in vivo: preliminary results. J Surg Res 2005; 124:85-91.

How do I perform RFA?

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4

•General anesthesia or sedation•CT guidance•IV antibiotics•Energy deposition (10-30min)•Post procedure CT•24 hour hospital stay

Following RFA, the tumor is monitored with serial CT (or better, PET CT).

Immediately after RFA: ground glass opacity surrounding the tumor on CT. The ablation zone should be larger than the original tumor.

Within one week: ground glass changes to consolidation.

An increase in the size of the ablated lesion can occur within the first three months after RFA. Beyond that time, growth of the ablation zone should be viewed as incomplete tumor destruction and recurrent tumor.

It may be difficult to determine if the tumor was fully ablated in the first few months after RFA.

Cavities may develop within the ablation zone without related symptoms. The cavities usually spontaneously contract with time.

What happens to the tumor following RFA?

30.09.2013

5

before RFA

RFA RFA

1 month after RFA 4 months after RFA

67 years old man with metastasis from CRC

PET 1 month after RFAPET 6 months after RFA

56 years old women with metastases from melanoma

The complication are similar to CT-guided lung biopsy procedures

• 10-15% pneumothorax • 5% bleeding • 2-5% infection • Skin burn.• Pleural effusion• Sensitive pleurae limiting exercise • Horner’s Syndrome• Phrenic nerve injury• Postop Neuralgia and parasthesias• Damage to heart if pacemaker present• Subcutaneous emphysema• Possible conversion to open thoracotomy• Possible recurrence of symptoms• Possible necessity for re-do operations• Rare: Death

Heart attackStroke

• Damage to adjacent organs or tissues

What are the potential complications of RFA procedure?

Simon CJ, Dupuy DE, DiPetrillo TA, et al. Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients. Radiology 2007; 243:268-275.de Baere T, Palussiere J, Auperin A, et al. Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: prospective evaluation. Radiology 2006; 240:587-596Hiraki T, Tajiri N, Mimura H, et al. Pneumothorax, pleural effusion, and chest tube placement after radiofrequency ablation of lung tumors: incidence and risk factors. Radiology 2006; 241:275-283.

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Before RFA

RFA

Immediately after RFA48 hours atfer RFA

3 month after RFA

63 years old woman with controlateral metastase of a locally contralled NSCLC

Simon et al: overal survival of patients with lung mets treated by RFA - 1 year survival 70 % - 2 years survival 54% - 5 year survival 44%

Simon et al: patients with lung mets from CRC treated by RFA - 1 year survival 87 % - 2 years survival 78% - 5 year survival 57%

Yan et al: 55 patients with lung metastases treated by RFA - median overall survival 33 months- 1 year survival 85 % - 2 years survival 64% - 3 year survival 46%

Yan et al: - larger size, location in the lung and repeat RFA are associated with significantly lower overall survival

Results in lung metastases

Simon CJ, Dupuy DE, DiPetrillo TA, et al. Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients. Radiology 2007; 243:268-275.

Yan TD, King J, Sjarif A, et al. Treatment failure after percutaneous radiofrequency ablation for nonsurgical candidates with pulmonary metastases from colorectal carcinoma. Ann Surg Oncol 2007; 14:1718-1726.

Yan TD, King J, Sjarif A, Glenn D, Steinke K, Morris DL. Percutaneous radiofrequency ablation of pulmonary metastases from colorectal carcinoma: prognostic determinants for survival. Ann Surg Oncol 2006; 13:1529-1537.

de Gregorio MA, Rivas de Andrés JJ. Radiofrequency ablation of primary and secondary lung tumors: Is the promise of this scalpel free technique now a reality? Acta Bronconeumol, 2008;44(2):55-7

Overall survival at 5 years: 45%

Surgical removal of metastatic lung tumors is an accepted curative therapy provided the primary tumor is cured or controlled. Overall 5 years survival is 32.4%

Results in lung metastases

Pastorino U, Buyse M, Friedel G, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. The International Registry of Lung Metastases. J Thorac Cardiovasc Surg 1997; 113:37-49.

BUT

RFA could be an interesting less invasive alternative in selected patients.

However

RFA is a newer technique

Lack of randomized studies

Historical comparisons of limited value

RFA seems to offer similar if not better survival rate than surgery at 5 years

30.09.2013

7

The feasibility and safety profile of lung tumor RFA in humans are well established

RFA is a promising local therapy for the treatment of primary and secondary cancers in the lung.

RFA has a complications rate similar to those of CT-guided lung biopsies.

RFA can be safely offered to patients who cannot undergo surgical resection.

Conclusion:

RFA is a highly promising modality that may be used to our patients' advantage either as a solitary treatment or in combination with conventional therapy.

However

Long term results beyond 5 years are not yet available.

The role of RFA in patients who are candidates for surgical resection is unproven

There is no evidence on whether RFA is more or less effective than sterotactic radiation therapy

Thank you for your attention

01.10.2013

1

1 20.06.2013

Nodule pulmonaire : indications de la radiothérapie stéréotaxique

Centre de cancérologie des Hôpitaux de la Riviera et du Chablais

Oscar Matzinger Chef de service, service de radio-oncologie, Vevey Médecin Adjoint, service de radio-oncologie, CHUV

Privat Docent & MER, Faculté de biologie et de médecine

2 20.06.2013

Plan de l’exposé

1. Radiothérapie, mais qu’est-ce que c’est?

2. Développement techniques récents

3. Exemples cliniques

3 20.06.2013

Historique

1895: Röntgen: découverte

1896: réactions de peau thérapie ?

1896: Freund: naevus pilus (1ère application)

Despeignes: cancer de l'estomac ?

1897: Schmitt & Kümmel: lupus vulgaris

Gocht: 1ère RT antalgique

1898: Ziemmsen: psoriasis

Jutassy: naevus

Hahn: eczéma chronique

Schmitt: lupus érythémateux

1899: Sjögren & Steinbeck: carcinome de peau

1903: Senn: 1ère irradiation profonde (CLL)

01.10.2013

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4 20.06.2013

Radiothérapie?

5 20.06.2013

1920: lampe de Finsen

6 20.06.2013

01.10.2013

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7 20.06.2013

Radiations ionisantes Unité (Joules/kg): Gray (Gy)

1 Gy 1’000 cassures simple brains

&

40 double brains

Cible principale: ADN

8 20.06.2013

Normal tumor growth Apoptosis vs. Clonogenic tumor death

Non irradiated, REC:myc cells

Apoptosis:

RT: 4 Gy

Clonogenic

tumor death:

RT: 4 Gy

9

Intervalle thérapeutique:

Facteur limitant:

Toxicité aux tissus

sains

Importance de

l’optimisation de

l’intervalle

thérapeutique

01.10.2013

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10 20.06.2013

Amélioration intervalle thérapeutique:

1. IMRT ( gradient de dose)

2. Traitement rotationnel (Vmat) ( vitesse de traitement) 3. Contrôle quotidien de positionnement (IGRT) (diminution des marges)

4. Imagerie fonctionnelle (Pet-CT; IRM…)

5. Traitement adaptatifs (évolution anatomique)

6. 4-D ( mouvements respiratoires)

7. Radio-chirurgie (SBRT) (dose unique)

11 20.06.2013

100 0

33 33

33

33 33

33 100

100

100

Il y a 5 ans Il y a 10 ans

Champs d’irradiation

12 20.06.2013

Accelerator collimateur multi-lame

01.10.2013

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13 20.06.2013

IMRT

14 20.06.2013

Dynamic arc IMRT (Vmat)

15 20.06.2013

IGRT Principe - Fusion

MV CT

kV CT

01.10.2013

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16 20.06.2013

Principe - Fusion

17 20.06.2013

Principe - Fusion

18 20.06.2013

Principe - Fusion

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19 20.06.2013

Principe - Fusion

20

RTH adaptative

21 20.06.2013

Imagerie fonctionnelle (Pet CT)

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22 20.06.2013

Plannification PET

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Mouvements respiratoires (4D)

Moyennes:

lobe sup. 0 - 0.5cm

lobe inf 1.5 - 4.0cm

lobe moyen 0.5 - 2.5cm

hile 1.0 - 1.5cm

24

Internal target volume (ITV)

Based on 4-D CT:

4D: Mouvements respiratoires

01.10.2013

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25

Contrôle quotidien de position en 4D

26

4D: Mouvements respiratoires Système «active breath control» (ABC)

27

Radio-chirurgie (SBRT) Dose unique

0 2 4 6 8 10 12 14 16 18 20 22 24

10-9

10-8

10-7

10-6

10-5

10-4

10-3

10-2

10-1

100

Su

rviv

ing

fra

cti

on

Dose/Gy

1 x 20 Gy

Fractionation and the Linear-Quadratic model

01.10.2013

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28

Diminution des effets secondaires tardifs:

fractionnement

0 10 20 30 40 50 60 7010

-11

10-10

10-9

10-8

10-7

10-6

10-5

10-4

10-3

10-2

10-1

100

Dose

Su

rviv

ing

fra

cti

on

Modeling fractionation

n fractions each of dose d

E

overall

effect

D

total

dose

T overall treatment time

29

0 2 4 6 8 10 12 14 16 18 20 22 24

10-9

10-8

10-7

10-6

10-5

10-4

10-3

10-2

10-1

100

10 x 2 Gy

5 x 4 Gy4 x 5 Gy

2 x 10 Gy

Su

rviv

ing

fra

cti

on

Dose/Gy

1 x 20 Gy

Fractionation and the Linear-Quadratic modelRadiochirurgie (SBRT)

30 20.06.2013

Phase I (Indiana University) 1. Stage I medically inoperable NSCLC

2. Primary endpoint: Maximum tolerated dose (MTD)

3. Forty-seven patients; T1N0 & T2N0; NSCLC

4. SABR escalating from

– 24 Gy over 3 fractions (8 Gy per fraction) up to

– 72 Gy in 3 fractions (24 Gy per fraction)

5. MTD: 66 Gy in 3 fr. for T2 tumors larger than 5 cm

6. not reached for T1 tumors at 60 Gy in 3 fractions

7. T2 tumors less than 5 cm at 66 Gy in 3 fractions

McGarry RC, et al. Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: phase I study. Int J Radiat Oncol Biol Phys. 2005

Timmerman al. Extracranial stereotactic radioablation: results of a phase I study in medically inoperable stage I non-small cell lung cancer. Chest. 2003

01.10.2013

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1. Phase II: efficacy and safety of SABR

2. Doses established in the phase I trial

3. 70 patients with stage I NSCLC

1. Median follow up of 50 months: 3-year local control of 88% and survival rates of 42%

2. 6 treatment-related deaths

3. Severe toxicity (grades 3-5) in ‘‘central’’ tumors.

Phase II (Indiana University)

Timmerman R, McGarry R, Yiannoutsos C, et al. Excessive toxicity when treating central tumors in a phase II study of

stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol. 2006

Fakiris AJ, McGarry RC, Yiannoutsos CT, et al. Stereotactic body ra- diation therapy for early-stage non-small-cell lung

carcinoma: four-year results of a prospective phase II study. Int J Radiat Oncol Biol Phys. 2009

32

Stereotactic Body RT (SBRT): Initial reports

33 20.06.2013

RTOG 02–36; multicentric phase II 59 inoperable patients (median follow-up: 34.4 months)

SBRT: 3 * 20 Gy

Robert Timmerman, M., et al., Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung

Cancer. JAMA, 2010. 303(11): p. 1070 - 1076.

Results @ 3 years:

- Primary tumor control rate: 97.6%

- Primary tumor and involved lobe

control rate: 90.6%.

- Local-regional control rate: 87.2%.

- Disease- free survival: 48.3%

- Overall survival: 55.8%.

Adverse events:

- Grade 3 : 12.7%

- Grade 4: 3.6%.

- No grade 5.

01.10.2013

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34 20.06.2013

Exclusion of central zone (within 2 cm of the ‘‘proximal bronchial tree’’ )

Robert Timmerman, M., et al., Stereotactic Body Radiation Therapy for Inoperable Early

Stage Lung Cancer. JAMA, 2010. 303(11): p. 1070 - 1076.

35 20.06.2013

Prospective database (VU University Medical Center)

1. April 2003 - december 2010

2. 706 patients

3. Stage IA-IB NSCLC

4. Prospective institutional database.

Lagerwaard, F.J., et al., Outcomes of Stereotactic Ablative Radiotherapy in Patients with Potentially Operable Stage I Non-

Small-Cell Lung Cancer. Int J Radiat Oncol Biol Phys, 2011.

36 20.06.2013

Prospective database (VU University Medical Center)

• Local control rate: 93% at 3 years

• comparable to surgical series

• No 30-day mortality following

SABR

≠

• Predicted 30-day surgical

mortality of 2.6% determined by

using the Thoraco- score.

Lagerwaard, F.J., et al., Outcomes of Stereotactic Ablative Radiotherapy in Patients with Potentially

Operable Stage I Non-Small-Cell Lung Cancer. Int J Radiat Oncol Biol Phys, 2011.

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37 20.06.2013

SBRT vs Surgery?

Onishi, H., et al., Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung

cancer: can SBRT be comparable to surgery? Int J Radiat Oncol Biol Phys, 2011. 81(5): p. 1352-8.

38 20.06.2013

39

Radiochirurgie (indications)

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40

Radiochirurgie extra-cranienne

41 20.06.2013

Série SBRT CHUV (en voie de publication)

23.3.2011 4.7.2012

17 patients

Aucune tox grade III

Suivi median: 12 mois

Contrôle local: 88% (2 progressions)

42 20.06.2013

M. S. 1953

1. Status post-carcinome épidermoïde peu différencié du lobe

2. inférieur gauche de stade pT2 pN0 M0, avec status postlobectomie

3. inférieure gauche et curage ganglionnaire en août 2009

4. Carcinome pulmonaire non à petites cellules au niveau lobaire inférieur

droit (apical) et lobaire moyen droit.

– Status post-radiothérapie hypofractionnée

– au niveau des deux lésions lobaire moyenne droite et lobaire inférieure droite

– 60 Gy en 5 fractions de 12

– effectuée les 13, 15, 19, 22 et 26 juillet 2011

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