1. A prospective study of PET/CT in initial staging of small-cell lung cancer : comparison with CT, bone scintigraphy and bone marrow analysis B. M. Fischer1, J. Mortensen1, S. W. Langer2, A. Loft1, A. K. Berthelsen1, B. L. Petersen3, G. Daugaard2, U. Lassen2 & H. H. Hansen Annals of Oncology 18: 338–345, 2007

2. BACKGROUND Small-cell lung cancer (SCLC) : 15%~20% Small-cell lung cancer (SCLC) : 15%~20% Limited disease (LD) : confined to one hemithorax Limited disease (LD) : confined to one hemithorax → chemotherapy combined with radiotherapy Extensive disease (ED) : outside one hemithorax Extensive disease (ED) : outside one hemithorax → chemotherapy alone is standard treatment Initial response rate to CTx : high (70%–80%) Initial response rate to CTx : high (70%–80%) but relapse shortly after treatment : current therapy is not effective enough : current staging procedure & therapy evaluation is not sufficiently sensitive

3. BACKGROUND FDG-PET : high diagnostic yield in solitary pulmonary nodules and in staging NSCLC FDG-PET might improve and simplify the current staging of SCLC Brink I, Schumacher T,. Impact of FDG-PET on the primary staging of SCLC. Eur J Nucl Med Mol Imaging 2004; 31 (12): 1614–1620 Until now, no studies have assessed the value of PET/CT in staging SCLC Role of combined PET/CT and PET compared with CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy in staging of SCLC

4. METHODS

5.  February 2003 to December 2004  4 pts : failed to receive initial PET/CT  1 pt : lost to followup  LD : 28% (8/29)  Diagnostic accuracy for standard staging, PET and PET/CT : Sensitivity Specificity Positive & negative predictive values Likelihood ratio (LR)

6. RESULTS Patient demographics Patient demographics Intra-thoracic findings Intra-thoracic findings Extra-thoracic findings Extra-thoracic findings Metastases to bone & BM Metastases to bone & BM Discordant stage by standard staging, PET and PET/CT Discordant stage by standard staging, PET and PET/CT Diagnostic accuracy in ED Diagnostic accuracy in ED

7. Patient Demographics (n = 34)

8. Table 1. Intra-thoracic Findings 8 pts 1 pt 6 pts 4 pts 9 pts 3 pts 6 pts 4 pts 5 pts 3 pts

9. Table 2. Extra-thoracic Findings 5 / 3 / 4 6 / 5 / 6

10. Metastases to bone or bone marrow : 38% (13 of 34) Sensitivity of CT : 30% Sensitivity of PET and PET/CT: 80% bone scintigraphy sensitivity : 75% specificity : 58% The sensitivity of conventional bone marrow analysis : 58% immunocytochemical analysis : 82% Table 3. Metastases to bone & BM

11. Standard staging methods (LD) : 33% PET/CT and at final staging (LD) : 28% PET/CT suggested a different stage in 5 of 29 patients (17%), PET in 9 patients (31%) Stage suggested by PET and PET/CT : most likely correct in 3 patients and equivocal in 1 In one patient, PET and PET/CT overlooked a liver metastasis (follow-up confirmed the finding by CT) PET 3 pts : pleural effusion, 1 pt : chronic infection interpreted as a contralateral metastasis (all four correctly diagnosed by PET/CT) Table 4. Discordant stage by standard staging, PET and PET/CT

12. Table 5. Diagnostic accuracy in ED

13. DISCUSSION This prospective study investigated the value of PET/CT in staging of 29 SCLC patients PET/CT : correctly changed the stage in 3 pts out of 29 (10%) PET alone : change of stage in nine patients, but erroneously down-staged three patients, and up-staged one patient with a chronic infection Brink et al. : FDG-PET alone was significantly better than standard staging in detecting extra-thoracic lymph node involvement and distant metastases. PET is inferior to CT in detecting pleural effusion; however, PET might be useful in discriminating between malignant and benign pleural effusion

14. DISCUSSION The role of pleural effusion in management of SCLC is ambiguous. isolated pleural effusion pts : survive as long as other patients with LD other series indicate that survival with an isolated pleural effusion is comparable to a single metastatic site Including all patients with pleural effusion sensitivity of standard staging, PET and PET/CT : 86%, 81%, 95% specificity : 100%, 83% 100%

15. DISCUSSION A common problem in SCLC : detection of metastases to the bones and bone marrow (up to 40%) → bone scintigraphy and bone marrow biopsy (analysed by conventional histology and immunocytochemistry) PET and PET/CT : just as sensitive as bone scintigraphy and bone marrow biopsy (similar to previous studies on NSCLC) Medical costs comparison associated with staging and primary therapy PET/CT strategy will diagnose more patients with ED shorten the length of hospital admission no significant difference in the costs of each strategy

16. DISCUSSION lack of consequent histological verification of discordant findings SCLC pts : relatively poor performance status immediate initiation of therapy is mandatory Thus, it is difficult and ethically questionable to obtain biopsies from all affected sites No patients presented with brain metastases impossible to estimate the value of PET/CT in this setting previous studies : PET alone is not suited for the diagnosis of brain metastasis

17. CONCLUSION Is there a role for PET/CT in the staging of SCLC? The answer is : most likely By including whole-body PET/CT in staging patients with SCLC, conventional Thorax, Abd CT, bone scintigraphy and bone marrow biopsy can be omitted saving precious time and making rapid initiation of therapy PET/CT can significantly improve the accuracy of SCLC staging and positively influence patient management ? unsettled Larger clinical trial, preferably with histological confirmation, is warranted