Prospective Assessment of Short-Term Response and Acute Toxicity With Accelerated Fractionation Radiotherapy Versus...

This study aims to compare treatment response, toxicity, and feasibility of accelerated fractionation radiotherapy (AFRT) versus concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer.

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.

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.

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.