Dosimetric and Clinical Effects of Polyethylene Glycol Gel in Radical Concurrent Chemoradiation Therapy for Cervical Cancer: A Phase 3 Prospective Multicenter Randomized Controlled Trial

Purpose: This study evaluated the safety and efficacy of polyethylene glycol (PEG) hydrogels in reducing rectal radiation dose and complication during cervical cancer radical concurrent chemoradiation therapy. Methods and Materials: This phase 3, randomized, parallel-controlled trial (NCT 05690906) conducted across 9 centers in China (July 2022-January 2025). Participants were randomly assigned 1:1 to receive a 10 mL PEG hydrogel injection (experimental group) or no injection (control group) after 50.4 Gy/28 fractions (f) or 45 Gy/25 f external beam radiation therapy. Three-dimensional image guided brachytherapy plans were developed before each brachytherapy session using computed tomography or magnetic resonance imaging (MRI) imaging, delivered in a prescribed dose of 6 Gy × 5 f or 7 Gy × 4 f. Concurrent chemotherapy was administered during the radiation therapy course. Patients were followed up for 72 weeks. The primary endpoint was the cumulative rectal D2cc dose. Secondary endpoints included rectal D0.1cc and D5cc doses and D2cc of the sigmoid, bladder, and small intestine; changes in the perirectal space and hydrogel volume; quality of life (QOL) scores (QLQ-C30 and QLQ-CX24); and incidence of radiation-induced rectal complication. QOL was assessed before brachytherapy, immediately after completing brachytherapy, and at 4, 12, 24, 36, 48, and 72 weeks after brachytherapy. Radiation-induced rectal complication was assessed at each of the aforementioned follow-up timepoints and additionally evaluated on a weekly basis throughout the entire radiation therapy course. Results: Of 94 analyzed patients (45 experimental and 49 control), the experimental group showed significant reductions in rectal D2cc (64.23 ± 6.58 Gy vs 69.79 ± 6.10 Gy; P < .001), D0.1cc (74.67 ± 12.22 Gy vs 84.38 ± 9.91 Gy; P < .001), and D5cc (60.23 ± 4.96 Gy vs 63.18 ± 5.04 Gy; P = .003) doses, with no significant changes in doses to other organs The hydrogel increased the cervix-rectum distance during brachytherapy and remained stable until 24 weeks after treatment, with noticeable absorption occurring between weeks 24 and 36. No significant differences were observed between experimental group and control group in acute radiation-induced rectal injuries (55.6% vs 46.9%), chronic injuries (9.5% vs 16.7%), or QOL scores, except for higher constipation scores and symptom experience scores in the experimental group. One case (2.2%) of rectovaginal fistula occurred in the experimental group, with no other grade ≥3 adverse events observed. Conclusions: PEG hydrogel injection effectively reduced rectal radiation dose during cervical cancer radical concurrent chemoradiation therapy without increasing doses to other organs, preserving overall safety and QOL despite transient QOL variations and an isolated rectovaginal fistula.