Long-Term Results of a Phase 2 Study of Adjuvant Proton Radiation Therapy for Node-Positive Cancer of the Uterus and Cervix.

PURPOSE: Patients with node-positive (LN+) uterine or cervical cancer often require postoperative radiation therapy (RT) to the pelvis and para-aortic nodes. A prospective phase 2 study was conducted to evaluate the efficacy of proton beam RT for LN+ uterine or cervical cancer.

METHODS AND MATERIALS: Patients with IIIC uterine and cervical cancer post hysterectomy and lymphadenectomy were eligible. Patients received 45 Gy(relative biological effectiveness) in 25 fractions with pencil beam scanning proton therapy (PBS-PT). Primary endpoints included comparing dose-volume histogram and toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events v4.02) between PBS-PT and intensity modulated RT or 3-dimensional conformal RT. Secondary endpoints included progression-free survival, overall survival, patterns of recurrence, and quality of life (QOL using Functional Assessment of Cancer Therapy-Endometrial/Cervix Version 4, FACT-En/Cx V4).

RESULTS: Twenty-one patients completed RT between October 2013 and October 2018. Median follow-up was 60.6 months (range, 11.2-68.8). There were 15 uterine and 6 cervical cancer patients. Four received pelvic and 17 received extended-field RT. Dose-volume histogram comparisons showed significantly less volume treated with PBS-PT compared to 3-dimensional conformal RT and intensity modulated RT for bowel, bone marrow, and kidney (all P < .05) at all dose levels except V45 bladder and bowel. Acute and late grade 3 gastrointestinal toxicity were 14% and 4.7%, respectively. There were no acute or late grade 3 genitourinary toxicities. Acute and late grade 3 hematologic toxicities were 24% and 4.7%, respectively. There was 1 late grade 3 lymphedema. The 2- and 5-year progression-free survival were 81% (95% CI, 56%-92%) and 76% (95% CI, 51%-89%). There were no in-field recurrences. The 2- and 5-year overall survival were 86% (95% CI, 62%-95%) and 80% (95% CI, 55%-92%). QOL increased significantly over time with an average increase of 10.7 points from baseline to 5 years (95% CI, 0.9-20.4, P = .032).

CONCLUSIONS: Compared to photon RT, PBS-PT treats significantly less normal tissue volume. PBS-PT appears effective in preventing local-regional recurrence in LN+ patients with minimal acute and late toxicity. QOL significantly improved from baseline to 5 years.