Sequential or concomitant chemotherapy with hypofractionated radiotherapy for locally advanced non-small cell lung cancer: a meta-analysis of randomized trials

BACKGROUND: For patients with locally advanced non-small cell lung cancer (NSCLC), the standard treatment is concurrent or sequential chemotherapy with radiotherapy. Most treatment schedules use radiotherapy with conventional fractionation; however, the application of hypofractionated radiotherapy (HYPO-RT) regimens is rising. A meta-analysis was performed to assess the efficacy and safety of chemotherapy combined with HYPO-RT and indirectly compare with the outcomes from previous studies employing concomitant conventional radiotherapy (CONV-RT). METHODS: Randomized controlled trials (RCTs) were identified on the electronic database sources through June 2020. Following the PRISMA guidelines, a meta-analysis was performed to assess if there were significant differences in the overall mortality (OM), local failure (LF), and disease progression (DP), comparing HYPO-RT-C vs. sequential chemotherapy followed HYPO-RT (HYPO-RT-S). To establish an indirect comparison with the current standard treatment, we calculate the risk ratio (RR) of the OM from RCTs using conventional chemoradiation, concurrent (CONV-RT-C), and sequential (CONV-RT-S), and compared with HYPO-RT. A P value <0.05 was considered significant. RESULTS: Two RCTs with a total of 288 patients were included. The RR for the OM, DP and LF at 3 year comparing HYPO-RT-C vs. HYPO-RT-S were 1.09 (95% CI: 0.96–1.28, P=0.17), 1.06 (95% CI: 0.82–1.23, P=0.610), and 1.06 (95% CI: 0.86–1.29, P=0.490), respectively. The late grade 3 pneumonitis and esophagitis had no significant difference between HYPO-RT groups. In the indirect comparison of RCTs using CONV-RT, the RR for the OM at 3 years was 1.03 (95% CI: 0.96–1.10, P=0.36) with no significant difference for the HYPO-RT arms 1.09 (95% CI: 0.96–1.28, P=0.17). DISCUSSION: HYPO-RT given with chemotherapy provides satisfactory OM, LF, and DP in locally advanced NSCLC with similar rates to the CONV-RT. These findings support HYPO-RT inclusion in future clinical trials as an experimental arm in addition to the incorporation of new strategies, such as immunotherapy.