Clinical Outcomes of Patients Treated With Intensity Modulated Proton Therapy (IMPT) Re-Irradiation for Gynecologic Malignancies

Abstract

Pelvic re-irradiation for patients with gynecologic cancers remains a challenge due to toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients treated with re-irradiation to the pelvis/abdomen with IMPT for gynecologic cancers.A single-institution retrospective IRB-approved analysis was conducted of all gynecologic cancer patients treated between 2015-2020 with IMPT re-irradiation with at least partial overlap with the treated volume of the prior treatment. Toxicities were graded according to CTCAE v5.0. The Kaplan-Meier (KM) method was used to estimate local control (LC), freedom from progression (FFP), overall survival (OS), and late toxicity with their 95% confidence interval (CI).A total of 29 patients received re-irradiation to the pelvis and/or abdomen with IMPT. One patient received a 2nd course of re-irradiation. Primary sites included endometrial (n = 15), cervical (n = 7), vaginal (n = 3), vulvar (n = 2) and ovarian cancer (n = 2). Twenty-five patients were treated for a recurrence of their gynecological cancer while 4 patients had re-irradiation for a new gynecological primary. Three patients were treated in the adjuvant setting, 6 patients received brachytherapy boost, and 3 patients received concurrent hyperthermia. Fifteen patients received systemic therapy associated with their course of re-irradiation, 11 of which was concurrent. The majority of patients received radiation (RT) to their pelvis only (n = 22), while 5 patients received RT to their pelvis + abdomen and 4 patients received RT to para-aortic field only. Median age at time of re-irradiation was 65 years (range 34-95). Median dose of prior RT was 45 Gy (range 30-59.4 Gy). Median time between initial RT and re-irradiation was 2 years (range 7 months - 39 years). Median re-irradiation dose was 49.2 Gy (range 30-61.6 Gy). Fractionation included conventional (n = 21), hyperfractionation (n = 7), and IMPT-SBRT (n = 2). Median follow-up was estimated at 17 months (range 1-34 months) using the inverse-Kaplan-Meier method; 11 patients had either local, regional, or distant progression. 12-month LC was 90% (95% CI 78%-100%), 12 month-OS was 62% (95% CI 42%-100%), and 12-month FFP was 57% (95% CI 35%-79%). Two patients developed acute grade 3+ toxicity (grade 3 diarrhea, grade 3 anemia). Two patients developed late grade 3+ toxicity (grade 3 sacral ulcer; 1 patient with grade 3 vulvar radiation necrosis and grade 3 radiation proctitis). 12-month freedom from toxicity was 96% (95% CI 88%-100%), and 24 month freedom from toxicity was 86% (95% CI 65%-100%).This is the first series to report on clinical outcomes for re-irradiation with IMPT for gynecological malignancies. While extended long term follow-up is needed, our study demonstrates excellent local control with acceptable acute and late toxicity.A.E. Pollock: None. H. Risher: None. S.M. Bentzen: Travel Expenses; University of Copenhagen. D.M. Roque: None. G. Rao: None. E.M. Nichols: Arrange consortium meetings, help lead multi-institutional trials; GammaPod Research Consortium. Medical Director of University of Maryland Medical Center practice; University of Maryland School of Medicine. Oversee clinical operations of all UMSOM Radiation Oncology practices; University of Maryland School of Medicine. P. Mohindra: The Executive Committee shall recommend to the Board of Directors overall Alliance policy and direction, as well as Alliance priorities and activities. It shall approve, by majority vote, appointments of chairs for scientific and administrative committee; Alliance for Clinical Trials in Oncology. Participate in various activities of the f.