Comparing Acute Toxicity of Proton and Photon Radiation Therapy in Newly Diagnosed Gynecologic Primaries

Although gynecologic malignancies are common and have high rates of radiation therapy utilization, no current randomized trial compares proton to photon therapy in this indication, and retrospective data are limited. The objective of this retrospective study is to compare acute toxicities in patients treated with intensity modulated proton therapy (IMPT) to those treated with photon therapy using volumetric modulated arc therapy (VMAT).

We analyzed patients who received conventional radiation therapy as part of curative treatment for their cervical, endometrial, or vaginal cancer from 2016 to 2023. Acute toxicity was compared between treatment modalities and racial groups using χ² and Mann-Whitney U tests as appropriate. Binary logistic regression was used to determine factors predictive for various toxicities.

One hundred fifty-five patients were eligible for analysis, with 49 IMPT and 106 VMAT cases. On multivariate analysis, nonhematologic acute grade 2+ toxicities were fewer with IMPT (13 patients, 27%) than with VMAT (46, 43%) (odds ratio, 0.36; 95% CI, 0.15-0.86; P = .02), as were acute grade 2 gastrointestinal toxicities, 5 (10%) versus 26 (25%) (odds ratio, 0.26; 95% CI, 0.08-0.85; P = .026). Toxicity-related treatment breaks or prematurely discontinued treatment courses were more frequent in the VMAT cohort 14 (13%) versus 2 (4%) (P = .08).

This study shows significantly lower acute grade 2+ gastrointestinal toxicity with IMPT and overall nonhematologic acute grade 2+ toxicity. Patients receiving IMPT had fewer toxicity-related treatment breaks/early treatment terminations. Given the detriment of prolonged or abbreviated treatments, these data warrant further exploration with a randomized study.