Altered-fractionation radiotherapy improves local control in early-stage glottic carcinoma: A systematic review and meta-analysis of 1762 patients

Objectives: To perform a systematic review of 1762 patients to comprehensively assess the benefit of altered-fractionation radiotherapy (ART) in early stage glottic carcinoma (ESGC). Materials and methods: Studies were identified in PubMed and EMBASE. Inclusion criteria were: (1) diagnosis of squamous cell ESGC (Tis, T1, T2); (2) ART versus conventionally-fractionationated radiotherapy (CRT); and (3) provision of number of local recurrence events and total numbers per fractionation arm. The random-effects model was fitted to estimate the pooled hazard ratio (HR). Subgroup sensitivity analyses were performed based on ART strategy (hypo- versus hyperfractionation), treatment-day reductions, machine type, tumor stage, and anterior commissure involvement. Results: Eleven studies met inclusion criteria: 4 randomized controlled trials (RCTs) and 7 two-arm retrospective studies. ART was associated with 38% fewer (HR 0.62; 95% CI: 0.46–0.82, p = 0.0009) and 60% fewer (HR 0.40; 95% CI: 0.24–0.66, p = 0.0003) local failure events in pooled analyses of the RCTs and retrospective studies, respectively. Both hyperfractionation (HR 0.65; 95% CI: 0.43–0.97, p = 0.03) and hypofractionation (HR 0.55; 95% CI: 0.33–0.91, p = 0.02) strategies were superior to CRT. The benefit persisted for all treatment- and tumor-related parameters, including anterior commissure involvement, with the exception of a pooled analysis of studies with predominantly T2 (<50% T1) cases (HR 0.60, 95% CI: 0.30–1.20, p = 0.15). Conclusion: Both hypofractionation and hyperfractionation improve local control in ESGC, including T1 tumors and for anterior commissure involvement. However, this benefit may not persist for T2 tumors, for which alternative strategies should be considered.