PET-CT in Lung Cancer: Positron emission tomography – computed tomography to whom, when ?

PET-CT in Lung Cancer:Positron emission tomography computed tomography

to whom, when ?

Jann Mortensen, MD, DMSci

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet University Hospital of Copenhagen,Denmark

[email protected], 26 april 2008

Fused PET + CTCTPETAnato-metabolic imaging*PET - CT Investigates functional changes in the body tissues and anatomy simultaneusly

PET-CT is the fusion of functional and anatomic information acquired almost simultaneously

Principle of Positron Emission Tomography(109.77m)(stable)EC1,0.00.01+0+Frequent radioactive drug:

18Fluoro-Deoxy-Glucose

Positron Emission Tomografi (PET)preparation: avoid feeding for 6 h fast400 MBq 18-F FDG i.v., rest -1 hRegional or whole body scan:base of the skull to mid-thigh PET scan and CT scan < h

Normal cellGLUFDGGlut1 &3GLUGLU-6-PHOSFATECO2+H20FDGFDG-6-PHOSFATE

Cancer cells use much glucoseGLUFDGGlut 1 & 3GLUGLU-6-phoshateCO2+H20FDGFDG-6- phoshateMetabolic trapping(Warburg O. 1930, 129-169)*Also high amino acid and nucleic acid use hexokinaseglu-6-phosphatase

FDG signal in tumor is dependent on 1) delivery (blood flow),2) transport into the cells (glut), and 3) phosporylation (hexokinase)Physiology of FDG tumor uptakeFDG tumor uptake ~ number of viable cancer cellsR.Wahl. Priciples and practice of positron emission tomography, 2002

BrainSalivary glandsLarynxThyroidHeartGI tract incl liverGenito-urinary tractBone marrowLymphoid tissueBrown fatPhysiological uptake of FDG

Main indications for PET in lung cancerCharacterising pulmonary nodules which are borderline for malignancy on CT And cannot be easily biopsied

Staging in NSCLCPreoperative evaluation N and M (nodes and metastasis)55 studies with > 2000 patients with histologic or long-term follow-upFischer BM, Mortensen J, et al.Lancet Oncol 2001;2:659-66

Publications of PET & PET/CT in Lung cancer

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References

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Indeterminate single pulmonary nodule/mass on CTMalignant or benign ?

N=16 studiesSensitivity 0.96 (0,90-1,00)Specificity 0.78 (0,69-0.95)

Size: 1-4 cm1474 nodules (JAMA 2001; 285: 914-24)Only few nodules

FDG-PET can discriminate between malignant / benign 10 mm solid pulmonary nodules !!!

FDG-PET has a high negative predictive value, can correctly exclude malignancy in the vast majority of nodules seen in daily practice. ~ changes management in > 26 % of patients

A surgical procedure can be avoided, and a repeat CT after 3 (6, 12 and 24) months can be used to confirm the absence of growth.Lancet Oncol 2001; 2: 659-66 Lung Cancer 2004; 45: 29-30.FDG PET in >1 cm nodules

What is the diagnostic value in < 1 cm small nodules ?

9 mm nodule found on high-resolution CT18F-FDG PET 57 yr male with COPD

transaxial coronal saggitalattenuation corrected RH - PET / jm (ap)Diagnosis and staging(PET suggests T1 N0 M0) 57 yr male with COPD Fischer BM, Mortensen J, et. al. Nucl Med Commun 2004; 25: 3-9.

On going screening study in Copenhagen: Included 4000 Yearly CT vs. Control in 5 yrs now 3 year

Value of PET in characterising indeterminate SPN 6-15 mm detected with low-dose CT

- all SPNs followed-up with re-CT at 3 months to assess growthPET in The Danish randomisedlow-dose CT screening study of lung cancer

Initial 9x12x9 mm solid nodule in R3, PET positive + 2 N2

PETpos + CT growth -> Biopsi/Mediastinoscopy: T1N2M0 (->Chemotherapy)PET positive casePET in Danish randomised low dose CT screening

CT + PET axial10 mm solid nodule in L3 PET negative CT stationarya PET negative casePET in Danish randomised low dose CT screening

Jann Mortensen, klinisk fysiologi, nuklearmedicin og PET, Rigshospitalet*PET data from CT- screening in MilanoWith PET : complete diagnostic workup < 4 months at baseline and < 2 months at 2-5 yrs PET in 68 SPN >7 mm ~ 1,4% of 1.035 participantsDanish study:Accurracy.89%

Jann Mortensen, klinisk fysiologi, nuklearmedicin og PET, Rigshospitalet

Jann Mortensen, klinisk fysiologi, nuklearmedicin og PET, Rigshospitalet*I-ELCAP Spain. 911 participants

24 PET scans in non-calcif. nodules >10 mm or growing > 7 mm

PET pos in 11 (9 malignant),PET neg in 14 (4 malignant: 8-11 mm adenoc.(2 semi-solid, BAC))

Sens. 69%, Spec. 91%, PPV 90%, NPV 71%

Conclusion:PET pos nodules should be biopsiedPET neg nodules should be followed up with 3 months CT scan ~100% Sens. and NPV, if PET neg and no growth after 3 months.

Prevalens Histology / CT follow-upNegativPositivPET neg243PET pos18Sensitivitet0,73Specificitet0,96PosPred vrdi0,89NegPred vrdi0,89

Jann Mortensen, klinisk fysiologi, nuklearmedicin og PET, Rigshospitalet

Staging TN M status (in one exam)Conventional staging is inaccurate [Lancet 1996;347:649653]. Oturai, Mortensen, Eigtved et al. J Nucl Med 2004;45:1351-7Preoperative staging with FDG-PETPET for staging:Staging the MediastinumPET more accurate than CT for detection of locoregional metastases PET sensitivity >84%, specificity >89% (18 prospective studies)

Detecting distant metastases:PET sensitivity >90%, specificity >90%and better than CT (17 prospective studies)

Change in management >25% of patients (15 prospective studies)

Pieterman et al. N Engl J Med 2000;343:254-61102 patients with resectable NSCLC, 6 months follow-up,histopathological reference.(N) metastasisSensitivitySpecificity PET 91 %86 %CT 75 %66 %(M) metastasis: PET identified distant metastases not foundby standard methods in 11 of 102 patients: PET identified a different stage in 62 patients:stage was lowered in 20 and raised in 42Prospective study of Preoperative staging with PET vs. standard staging (CT, ultrasound, bone scanning/ biopsy)

Randomised study of PET staging

Effect parameter: no. unneccesary thoracotomys188 ptt. usual work-up +/- PET, 1 yr follow-up9 Deutch hospitals (1 dedicated PET center)

PET reduced the no. unneccesary thoracotomys:PET 32 (41%) , + PET 18 ptt (21%)

For each 5 PET scans one unneccesary thoracotomy was avoided reduced cost per patient with PET: > 1.000 EURO(PLUS study. Lancet 2002; 359: 1388-92)

Randomised PET studies of staging NSCLC

Mediastinoscopy, EUS, EBUS and PET/CT

Mediastinal staging with CT, PET, and endoscopic esophageal ultrasound (EUS)EUS+FNA better ? for locoregional staging (N) PET was superior (higher sensitivity and specificity), to CT but also to EUS.[Chest 2003;123(suppl 1):137S146S]. PET and EUS with fine-needle aspiration had similar sensitivities (79%) for advanced cancer, but EUS with FNA had a superior specificity (100% vs. 72%). [Am J Respir Crit Care Med 2003;168:12931297] EUS with fine-needle aspiration had higher sensitivity (87% vs. 61%), specificity (100% vs. 91) and accuracy (94% vs. 77%) than PET. [Clin Gastroenterol Hepatol 2006;4:846-51]. In 5 papers on > 300 patients with PET positive N (N1-3): EUS+FNA had high accuracy and in ~50% detected malignancy obviating the need for further surgical procedures [Chest 2005;128:3004-9 & 2005;127:130-7][Ann Thorac Surg 2005;80:1231-40][Thorax 2004;59:596-601][Lung Cancer 2004;44:59-60].

Mediastinal staging with CT, PET, and endobronchial ultrasound (EBUS) with TBNA 102 patients with potentially operable suspected lung cancer. Gold standard: histology-cytology [Chest 2006;130:710-718].EBUS with TBNA vs. PET vs. CT: Sensitivity (92% vs. 80% vs. 77%), Specificity (100% vs. 70% vs. 55%), Accuracy (98% vs. 73% vs. 61%).EBUS + TBNA better ? for locoregional staging (N)In the majority of 33 patients with PET positive N (N1-3): EBUS-TBNA could detect malignancy obviating the need for futher surgical procedures [Eur Respir J 2006;27:276-281].

Publications of PET & PET/CT in Lung cancer

Diagram1

40020

603

NSCLC

SCLC

References

PubMed April 2008

Ark1

PETPETCT

NSCLC40060460

SCLC20323

42063483

Ark1

0

0

PET PETCT

Ark2

00

00

NSCLC

SCLC

References

PubMed April 2008

Ark3

PET/CT improves staging in 20-40% of lung cancer patients compared to PET and CT (T and N status)Lardinois D et al. N Engl J Med 2003;348:2500-7PET/CT improves staging in lung cancer Compared to PET, PET/CT better predicts stage I and II, as well as T and N statusCerfolio RJ et al. Ann Thorac Surg 2004; 78: 101723PET/CT is significantly better than CT in NSCLC staging and provides enhanced accuracy and specificity in nodal staging (10 FN Nodes with CT and 5 with PET/CT) Shim SS et al. Radiology 2005; 236:1011-9PET-CT is more accurate, sensitive and specific compared to CT alone in nodal staging. Nael Al-Sarraf et al. Lung Cancer 2008;60:62-8PET/CT 10-15% more accurate than PET

PET/CT improves staging in 20-40% compared to PET and CT aloneLardinois D et al. N Engl J Med 2003;348:2500-7PET/CT improves staging in NSCLCIntroduced in 2001Lardinois, 2003: 49 patientsT PET/CT > PET+ CTN PET/CT = PET + CTM PET/CT PET +