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

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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] Antalya, 26 april 2008. - PowerPoint PPT Presentation

Text of 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

    PubMed April 2008

    Ark1

    PETPETCT

    NSCLC40060460

    SCLC20323

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    PET PETCT

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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

  • FDG PET in small nodules (
  • 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 +

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