Prospective Assessment of Short-Term Response and Acute Toxicity With Accelerated Fractionation Radiotherapy Versus Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer

Objectives: This study aims to compare treatment response, toxicity, and feasibility of accelerated fractionation radiotherapy (AFRT) versus concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer. Materials and methods: In this prospective, non-randomized study, 92 patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IIIB cervical cancer (May 2018-July 2019) were allocated to AFRT (n=44; external beam radiotherapy (EBRT) 50 Gy/25 fractions, six fractions/week, no chemotherapy) or CCRT (n=48; EBRT 50 Gy/25 fractions, five fractions/week, weekly cisplatin 40 mg/m²) based on fitness for concurrent chemotherapy. All received high-dose-rate intracavitary brachytherapy (7 Gy × 3). The primary endpoint was local response; the secondary endpoints were acute and late toxicities. Given the non-randomized allocation, age-adjusted (Firth's penalized where indicated) logistic regression was performed for key endpoints. Results: The AFRT arm was older (median age: 62.5 versus 51 years), reflecting the selection criteria. The overall treatment time (OTT) was significantly shorter with AFRT (51 versus 56 days; p=0.0043). Complete response at three months was comparable (93.2% versus 95.8%; p=0.57; age-adjusted odds ratio (OR): 1.98, 95% confidence interval (CI): 0.28-14.1, p=0.50). CCRT showed a significantly higher incidence of grade 2 leucopenia (4.5% versus 23%; p=0.01; age-adjusted OR: 9.95, 95% CI: 1.97-50.3, p=0.005), a numerically higher rate of grade 3 leucopenia (0% versus 8%), and higher grade 2 skin toxicity (4.5% versus 18.75%; p=0.03). Acute kidney injury (AKI) occurred exclusively with CCRT (22.9%; p=0.0007; age-adjusted OR: 28.5, 95% CI: 1.60-507, p=0.023), including grade 1 AKI in 14.6% (p=0.008). Gastrointestinal toxicities were comparable (p>0.05). Late toxicities, assessed in a subset of patients (24 AFRT and 22 CCRT) due to short follow-up, showed no significant differences, although wide, overlapping 95% confidence intervals indicate limited power to detect true differences. Conclusion: In this short-term analysis (median follow-up: 5 months), AFRT achieved response rates comparable to CCRT while significantly shortening treatment time and reducing hematological and renal toxicity, and these associations persisted after age adjustment. Given the non-randomized design, baseline age difference, and short follow-up, findings are hypothesis-generating and pertain to short-term response and acute toxicity rather than long-term outcomes. AFRT may be a feasible option for patients unsuitable for concurrent chemotherapy, meriting further evaluation in larger randomized studies with longer follow-up.