Is ¹⁸F-FDG-PET/CT a Valid Non-Invasive Predictor for Regression Grade after Neoadjuvant Treatment in Patients with NSCLC Stage III?

Abstract

Introduction: CT alone cannot provide sufficient information referring to response after neoadjuvant therapy in a timely manner. To evaluate the role of 18 F-FDG-PET after neoadjuvant chemoradiation as a valid, non-invasive predictor for early therapy response and its effect on survival as compared to histopathologic tumor response, data of 32 of 210 randomized patients with NSCLC stage IIIA/IIIB, who were treated in a prospective randomized controlled multicenter trial (LUCAS- MD), were re-evaluated. Material and Methods: For 32 patients with NSCLC stage IIIA (44%) IIIB (56%) neoadjuvant treatment consisted of two to three cycles of chemotherapy (225 mg/m 2 paclitaxel and carboplatin AUC 6 d1q22) and concomitant chemoradiation (50 mg/m 2 paclitaxel and carboplatin AUC 2 d1, d8, d15; 1.5 Gy b.i.d. up to 45 Gy). Documentation of involved lymph node stations as detected by 18 F-FDG-PET/CT and lymph node sampling during surgery according to the IASLC lymph node mapping (2009). Evaluation of histological regression grade (RG) according to Junker et al . (2001) and correlation with ¹⁸ F-FDG-PET/CT for primary tumor and each lymph node station. Calculation of disease free survival using Kaplan-Meier estimates and log rank tests. Results: Actuarial tumor specific survival for the 32 patients with concomitant chemoradiation plus chemotherapy: complete vs. incomplete metabolic remission prior to surgery after 60 months: 40% vs. 24% (p = 0.018). RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs. 15% (p = 0.006). 18/32 (56%) patients had RG III/IIb, 8/32 (25%) patients had regression grade III. 1/8 pts. with RG III were in the 18 F-FDG- PET/CT false positive, 10 pts. with RG IIb (i.e. all pts. with RG IIb) were in the 18 F-FDG-PET/CT false negative. One patient with RG IIa was in the 18 F-FDG-PET/CT false negative. Hence, the cut-off level in detecting vital tumor cells by 18 F-FDG-PET/CT after neoadjuvant chemoradiation for NSCLC is about 10%. Conclusion: Histological regression grading correlates well with metabolic remission as detected by 18 F-FDG-PET. Thus, 18 F-FDG-PET precedes CT in measuring the tumor response and may predict long-term therapeutic outcome in patients with stage III NSCLC. Invasive staging procedures may be avoided and patients who will not profit from resection due to insufficient downstaging after neoadjuvant treatment will be easily detected by using 18 F-FDG-PET as standard imaging in workup and evaluation of treatment response.