The role of F-18 FDG PET within randomized multicenter phase III trials for multi-modality treatment of non-small cell lung cancer stage III

Abstract

7213 Background: To evaluate the role of F-18 FDG PET within clinical trials for staging, therapy management, molecular radiation treatment planning (MRTP), early therapy response and its effect on survival as compared to histopathologic tumor response, findings in 156 patients with NSCLC are analyzed prospectively in a randomized, open, multicenter phase III trial (LUCAS-MD). Methods: Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. ECOG PS 0–1, adequate hematologic, renal, hepatic function. Primary end points: OS, DFS. Secondary end points: TTP, QoL, RR. Neoadjuvant treatment: 2–3 cycles of chemotherapy with paclitaxel/carboplatin and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant paclitaxel/carboplatin) followed by surgery. Randomization: early vs. late chemoradiation. Staging: PET in addition to CT and/or MRI after randomization. Second PET after completion of neoadjuvant therapy. Assessment of standardized uptake values (SUV) in primary tumor (PT) and all metastatic lymph nodes (LN). Documentation of involved LN as detected by PET and LN sampling during surgery according to Naruke/ATS-LCSG classification. Image fusion of PET with CT data followed by molecular radiation treatment planning. Evaluation of histological regression grade (RG) and correlation with PET for PT and each LN. Statistical analyses: Wilcoxon-, chi-square-, Mantel-Haenszel-test, Kaplan-Meier-method, multivariate Cox-regression. Results: Upstaging in 11 pts. due to distant metastases. Downstaging in 5 pts. Complete vs. incomplete metabolic remission after 48 months: 60% vs. 34% (p = 0.0058). RG III/IIb (no/less than 10% of vital tumor cells) vs. RGIIa/I (more than 10% vital tumor cells) after 48 months: 59% vs. 27% (p = 0.0006). Multivariate Cox-regression for SUV: p > 0.05. Statistical power of the tests: 75% so far. Due to PET findings, the planning target volume for MRTP was reduced substantially in 23%, increased in 10%. Conclusions: Integration of PET in clinical trials enables a more accurate MRTP and therapy management (10% stage migration). Histological regression grade correlates well with metabolic remission as detected by PET. F-18 FDG PET may predict (long term) therapeutic outcome in stage III NSCLC. No significant financial relationships to disclose.