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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
2
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
4
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
5
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
6
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
02.10.2013
7
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
8
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
9
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
10
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
11
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)
02.10.2013
12
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
13
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
14
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
2
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
01/10/2013
3
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
4
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
01/10/2013
5
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
01/10/2013
6
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
7
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
01/10/2013
8
� 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
01/10/2013
9
Métastase d’un
ostéosarcome
Granulome
Calcifications bénignes
Calcifications
rondes et centrales
Calcifications bénignes
Calcifications lamellaires
concentriques :
TUBERCULOME
Calcifications bénignes
Calcification en Pop-Corn
Hamartochondrome
01/10/2013
10
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
01/10/2013
11
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
12
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
1
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
2
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
3
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
24.09.2013
4
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
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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
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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
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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
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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
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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
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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
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3D
2D
Histogramme de densité
Valeur d’atténuation maximum
01.10.2013
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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
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01.10.2013
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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
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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
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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
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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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ved
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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ved
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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ved
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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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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%
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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 »
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
11
• 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
3
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
5
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
6
16 20.06.2013
Principe - Fusion
17 20.06.2013
Principe - Fusion
18 20.06.2013
Principe - Fusion
01.10.2013
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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
23 20.06.2013
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
10
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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31 20.06.2013
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.
01.10.2013
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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)
01.10.2013
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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
01.10.2013
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45 20.06.2013
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46 20.06.2013 46
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