Induction chemoradiotherapy versus induction chemotherapy for potentially resectable stage IIIA (N2) non-small cell lung cancer: a systematic review and meta-analysis.

Background: Non-small cell lung cancer (NSCLC) accounts for 85% to 90% of lung cancer cases. At diagnosis, around 30% of NSCLC patients are already at stage IIIA (N2). One standard treatment for this stage is induction chemotherapy followed by surgery, whether induction chemoradiotherapy is superior to induction chemotherapy remains uncertain. We therefore performed a systematic review and meta-analysis of published randomized control trials to evaluate the therapeutic efficacy and toxicity of induction chemoradiotherapy versus induction chemotherapy for potentially resectable stage IIIA (N2) NSCLC.

Methods: We systematically searched for relevant studies in PubMed, Embase, Web of Science and Cochrane Library from the inception of each database to September 10, 2017. The primary endpoints were objective response rate (ORR), pathological complete response (pCR) rate of mediastinal lymph nodes, toxicity (grade 3-4 adverse events, i.e., nausea and vomiting, infections, leukopenia and anemia), overall survival (OS) and progression-free survival (PFS). Statistical analyses were performed using Review Manager v5.3.

Results: Four studies, containing 461 patients in total, were included for meta-analysis. Our analyses suggest that compared with induction chemotherapy, induction chemoradiotherapy improved ORR [odds ratio (OR) =1.97, 95% confidence interval (CI): 1.25-3.10, P<0.05] and pCR rate of mediastinal lymph nodes (OR =1.97, 95% CI: 1.00-3.86, P=0.05); but it did not significantly improve OS [hazard ratio (HR) =0.91, 95% CI: 0.73-1.14, P=0.42] or PFS (HR =1.01, 95% CI: 0.81-1.26, P=0.91); also it did not exacerbate the toxicity.

Conclusions: Induction chemoradiotherapy may have limited value concerning tumor response and pCR of mediastinal lymph nodes. However, current evidence does not support that addition of radiotherapy to induction chemotherapy followed by surgery can bring significant benefits to operable stage IIIA (N2) NSCLC patients. More studies are required to draw a better conclusion.