301 - Five-Year Outcomes of a Phase II Study of Post-Operative Proton Beam Radiation for Gynecologic Cancers

A. L. Russo¹, N. Horick², N. Depauw³, J. A. Nyamwanda¹, F. Giap⁴, M. Del Carmen³, R. Penson³, A. Goodman³, J. Y. Wo⁴, T. F. DeLaney⁴, and A. H. Russell⁵; ¹Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, ²Biostatistics Center, Massachusetts General Hospital, Boston, MA, ³Massachusetts General Hospital, Boston, MA, ⁴Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁵Massachusetts General Hospital, Department of Radiation Oncology, Boston, MA

Purpose/Objective(s): Patients with node-positive (LN+) uterine or cervical cancer often require post-operative radiation (RT) to the pelvis and para-aortics. Proton therapy allows for more conformal delivery of RT. A prospective phase II study was conducted to evaluate the safety and efficacy of proton beam RT for patients with LN+ uterine or cervical cancer, including dosimetric comparison and quality of life. Materials/

Methods: Patients with IIIC uterine and cervical cancer status post hysterectomy and lymphadenectomy were eligible. Patients received 45 Gy (RBE) in 25 fractions with proton pencil beam scanning (PBS-PT), followed by vaginal brachytherapy (VB) boost. Patients were followed per protocol for 5 years. Primary endpoint was comparison of dose volume histogram (DVH) of PBS-PT vs IMRT and 3DCRT. Secondary endpoints include progression free survival (PFS), overall survival (OS), toxicity (CTCAE v4.02), patterns of recurrence, and quality of life (QOL using FACT-En/Cx V4). QOL was assessed at baseline and post-treatment at 6 months, and annually until 5 years post-treatment. FACT-Cx scores were scaled to have the same range (0-172) as the FACT-En scores. A linear mixed effects model was used to assess QOL change over time using the combined FACT-En/FACT-Cx scores with adjustment for disease site.
Results: 21 patients completed RT between 10/2013 and 10/2018. Median follow-up was 60.6 months (range, 11.2 – 68.8). Median age was 59.7 years (range, 31.5-79.2). 15 patients had IIIC uterine cancer and 6 patients had cervical cancer. 52% received sequential and 29% received concurrent chemotherapy. 4 received pelvic and 17 extended-field-RT. DVH comparisons showed significantly less volume and % organ treated with PBS compared to both 3D-CRT and IMRT for bowel, bone marrow, and kidney (all p<0.05). Acute and late grade 3 GI toxicity were 14% and 5%, respectively. Acute grade 3 GU toxicity was 0% with no late toxicities. Acute and late grade 3 hematologic toxicity was 24% and 9.5% (lymphopenia), respectively. The 2- and 5- year PFS was 81% (95% CI, 56%-92%) and 76% (95% CI, 51%-89%). Of the 5 patients that recurred, 4 were peritoneal and 1 was abdominal wall and lung; with no in-field recurrences. The 2- and 5-year OS was 86% (95% CI, 62%-95%) and 80% (95% CI, 55%-92%). The QOL mean score was 129 at baseline, 134 at 6 months, 132 at 1 year, 134 at 2 years, and 149 at 5 years. The QOL increased significantly over time with an average increase of 10.7 points from baseline to 5 years (95% CI: 0.9 to 20.4, p=0.032).
Conclusion: Adjuvant PBS-PT treats quantitatively less normal tissue volume and appears effective in preventing local-regional recurrence in LN+ uterine and cervical cancer. Acute and late toxicity are low and severe late effects have not been observed. Quality of life significantly improved from baseline to 5 years.