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