Long-time follow-up of radiotherapy boost in patients with lung cancer based on FMISO PET: Can we expect a better survival outcome? (RTEP5 3 years follow-up)

Background Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfying survival partially due to radiation resistance in hypoxic tissues, raising the question of targeted radiotherapy. Objective To evaluate the risk-benefit of radiotherapy boost on hypoxic tumors in NSCLC patients treated by curative-intent chemoradiotherapy in an open-label, nonrandomized, phase II clinical trial developed from 2012 to 2015 with a 3-year follow-up. Multicenter study performed in 15 French academic centers ( NCT01576796 ). Participants: eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. Seventy-nine patients underwent a run-in period, of which 54 were included. Twenty-four patients completed the study at 3 years. 18F-fluoromisonidazole (18F-MISO) positron emission tomography/computed tomography was performed to determine the hypoxic profile of patients (34 positive and 20 negative). Those with positive 18F-FMISO status and without organ-at-risk constraints (n = 24) received radiotherapy boost (70–84 Gy); the others received standard radiotherapy (66 Gy). Overall survival (OS), progression-free survival (PFS), and safety. Hypotheses tested were formulated before data collection. Results: fifty-four patients were evaluated, with a median age of 61 (41–76) years. OS and PFS rates at 1, 2, and 3 years were, respectively, 87%, 58.2%, and 48.5%, and 59.3%, 36.4%, and 28.8%. The median OS in the positive 18F-FMISO group was 25.8 months and was not reached at 3 years in the negative (P = 0.01). A difference was also observed for PFS (12 vs. 26.2 months, P = 0.048). By focusing on positive 18F-FMISO patients, no difference was observed in OS according to the dose, probably because of the small sample size (P = 0.30). However, the median OS seemed to be in favor of boosted patients (26.5 vs. 15.3 months, P = 0.71). In patients who underwent boost, no significant early or late toxicities were observed. Conclusions and relevance 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features. In the group of 18F-FMISO-positive patients, radiotherapy boost seems to improve the OS by 11.2 months. These results deserve further attention in a future clinical trial devoted to hypoxic patients to confirm boost efficacy.