Radiosensitising strategies in locally advanced head and neck cancer: a systematic review and network meta-analysis of randomised controlled trials (RADIANCE-NMA)

Summary: Background: Radiosensitiser enhance radiotherapy efficacy in locally advanced head and neck squamous cell carcinoma (HNSCC). Although cisplatin-based chemoradiotherapy is the standard-of-care, over two dozen radiosensitising strategies have been evaluated in randomised trials with no network meta-analysis comparing all drug classes.

Methods

PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to 26 June 2026 for Phase IIb–III randomised controlled trials evaluating concurrent radiosensitiser therapy in adults with locally advanced head and neck squamous cell carcinoma (nasopharyngeal carcinoma excluded). Studies lacking overall survival data and induction-only comparisons were excluded. The primary outcome was overall survival (OS). All treatment-effect estimates are reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Data were independently extracted by two reviewers. Risk of bias in individual trials was assessed with the Cochrane Risk of Bias (RoB 2) tool and confidence in the network estimates using the Confidence in Network Meta-Analysis (CINeMA) framework. Random-effects network meta-analysis was done with frequentist (netmeta) and Bayesian (gemtc) frameworks. Between-study heterogeneity was quantified using the I 2 statistic and τ 2 ; publication bias and small-study effects were assessed using comparison-adjusted funnel plots and Egger's regression test. This study is registered with the Open Science Framework ( https://osf.io/cygsh ).