1024 - Phase I Study of Hypofractionated Whole Pelvis Radiation in Endometrial Cancer Using a Novel Patient-Reported Outcomes Continual Reassessment Method (PRO-CRM)
Presenter(s)
S. Feldkamp1, B. Nelson2, N. A. Wages3, J. R. Kharofa1, S. M. C. Sittenfeld1, C. Billingsley4, T. J. Herzog4, A. Jackson4, L. Pinder4, and T. Meier1; 1Department of Radiation Oncology, University of Cincinnati Cancer Center, Cincinnati, OH, 2Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, 3Virginia Commonwealth University, Richmond, VA, 4University of Cincinnati Division of Gynecologic Oncology and Advanced Pelvic Surgery, Cincinnati, OH
Purpose/Objective(s):
Treatment of stage III endometrial cancer after surgery includes adjuvant chemotherapy ± Whole Pelvis Radiation (WPRT). WPRT has historically been delivered to 45-50.4 Gy at 1.8 Gy per fraction. Hypofractionation can offer greater convenience to patients with condensed treatment package time, however the tolerance of hypofractionated WPRT regimens for gynecologic cancers is not well described. Clinician reported toxicity often underestimates patient reported toxicity during pelvic RT. This phase I study aimed to identify the maximum tolerated dose per fraction for hypofractionated WPRT using a novel patient-reported outcomes-CRM design incorporating both acute clinician and patient reported Dose-Limiting-Toxicity (DLT) criteria.Materials/Methods:
Tumor and normal tissue BED & EQD2 calculations were utilized to select 2 hypofractionated regimens most equivalent to standard WPRT- Arm 1: 41.25 Gy in 15 fractions and Arm 2: 38 Gy in 10 fractions. Eligibility included histologically confirmed endometrial cancer (Stage I-III) requiring WPRT, age =18 years, & ECOG =2. Patients with gross residual disease, para-aortic nodal involvement, or RT contraindications were excluded. The maximum target accrual was 15 patients. GI & GU toxicity was assessed at baseline, weekly during RT, 2 weeks post RT, & 3 months post RT using CTCAE 5.0 and PRO-CTCAE. Clinician dose-limiting toxicity (CDLT) was defined as Grade 3 or higher GI or GU toxicity with an unacceptable rate of >20%. Patient dose-limiting toxicity (PDLT) was defined by a score of =4 on the PRO-CTCAE with an unacceptable rate of >55% selected based on prior published data from RTOG 1203. Quality of life was assessed with the Functional Assessment of Cancer Therapy (FACT-En).Results:
Seven patients completed treatment from 2021-2023 on Arm 1 (41.25 Gy/15 fx). Four of the 7 patients received chemotherapy + WPRT and 3 WPRT alone. No CDLTs were identified. PDLTs were identified in 5 (71%) patients, commonly occurring in week 3 of RT and 2 weeks post RT. The most common PDLTs were urinary urgency and diarrhea in 4 (57%) patients. At 3-month follow-up all PDLT adverse effects had resolved. Per the CRM, the rate of PDLTs was too high to begin accrual for Arm 2. No stopping rules for Arm 1 were met. At 3 months post RT, FACT-En scores were improved or stable compared to baseline. Enrollment was closed early due to a change in standard of care with the incorporation of immunotherapy.Conclusion:
These results demonstrate expected toxicities of WPRT during and shortly after hypofractionated RT with rapid symptom resolution within three months of treatment. The high rates of toxicity during and shortly after WPRT emphasize the importance of the timing of patient reported toxicity data collection for future hypofractionated WPRT trials.