The Role of F-18 FDG PET within Randomized Multicenter Phase III Trials for Multimodality Treatment of Non-Small Cell Lung Cancer Stage III

Abstract

Ziele: To evaluate the role of F-18 FDG PET) within clinical trials for staging, therapy management, molecular radiation treatment planning (MRTP) and early therapy response after neoadjuvant chemoradiation and its effect on survival as compared to histopathologic tumor response (regression grade), findings in 156 patients with non-small cell lung cancer (NSCLC) stage III are analyzed prospectively in a randomized, multicenter phase III trial. Methode: Neoadjuvant treatment: 2–3 cycles of paclitaxel/carboplatin and a block of chemoradiation. Staging: pretherapeutic PET scan in addition to spiral CT and/or MRI after randomisation, second PET after completion of neoadjuvant therapy prior to surgery. Lymph node sampling during surgery and documentation of lymph node involvement according to Naruke/ATS-LCSG classification. Correlation of regression grade with PET for each lymph node location. MRTP by using fused PET/CT data (HERMES Workstation). Ergebnis: Up-staging in 11/156 paients due to distant metastases, down-staging in 5/156 patients resulting in 10% stage migration within the clinical trial. Actuarial tumor specific survival: complete vs. incomplete metabolic remission after 48 months 60% vs. 34% (p=.0058), RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 48 months: 59% vs. 27% (p=.0006). If PET was used additionally for the 3D-planning procedure of radiation therapy, the planning target volume (PTV) was reduced substantially in 22% of the patients (mean 12%, maximum 25%, p < .05) leading to a reduction of dose to the organs at risk, e.g. Vlung(20Gy) could be reduced up to 17% (p=.02). Due to lymph node metastases the PTV based on PET was larger in 10% of the patients. Schlussfolgerung: Integration of PET in clinical trials enables a more accurate therapy management (10% stage migration). F-18 FDG PET precedes CT in measuring the tumor response after neoadjuvant treatment and may predict (long term) therapeutic outcome in stage III NSCLC. Histologic regression grade correlates well with metabolic (molecular) remission as detected by PET. The in-vivo detection limit of vital tumor cells by F-18 FDG PET in NSCLC after neoadjuvant treatment is found to be in the magnitude of 10% of vital malignant cells. This result will be of importance for target delineation in molecular radiation treatment planning. PET is a complementary tool to anatomic imaging modalities for an exact localization of nodal involvement and the extent of the primary tumor.