1026 - Multi-Institutional Phase I Results from RT-PACE: Phase I/II Study of Adjuvant Whole Pelvic Hypofractionated Radiotherapy for Non-Metastatic Cervical and Endometrial Cancer
Presenter(s)
C. H. Son1, S. Y. Kim-Wang1, J. J. Sohn1, H. A. Al-Hallaq2, J. Cursio3, A. R. McCall1, R. Malik1, D. W. Golden1, K. Kurnit4, J. Chipman5, G. Suneja6, D. K. Gaffney6, and Y. Hasan1; 1Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL, 2Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, 3Department of Public Health Sciences, University of Chicago Medical Center, Chicago, IL, 4Department of Obstetrics and Gynecology, University of Chicago Medical Center, Chicago, IL, 5Department of Population Health Sciences, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, 6Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Purpose/Objective(s): Post-operative whole pelvic radiation therapy (WPRT) is recommended for patients with cervical and uterine cancer who are at high risk for local recurrence. Current standard of care using standard fractionation involves 25-28 daily treatments using 1.8-2 Gy/fraction. Hypofractionation has become widely used in other disease sites, but has not been well studied in gynecologic cancers. A multi-institutional Phase I/II study was designed to study this further. The primary objective of Phase I was to determine the maximum tolerated dose-per-fraction (MTD) regimen of WPRT, which would subsequently be used in Phase II.
Materials/Methods: Patients with non-metastatic uterine or cervical cancer who underwent hysterectomy without gross residual disease and were recommended WPRT were eligible. A keyboard design was used to determine the MTD, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3+ gastrointestinal (GI) or genitourinary (GU) toxicity rate =10% as reported on the last day of WPRT. The three escalating dose-per-fraction levels investigated were: (1) 44 Gy in 20 fractions, (2) 43.2 Gy in 18 fractions, and (3) 42.56 Gy in 16 fractions. Intensity-modulated radiation therapy and daily image guidance were required. Cylinder brachytherapy boost, sequential systemic therapy, and concurrent her2-targeted therapy were permitted. AEs were obtained on the last day of WPRT and 1, 3, 6, 9, 12, and 24 months after completion of WPRT. Two-year locoregional recurrence (LRR) and distant metastases (DM) were recorded.
Results: Three patients were sequentially recruited to each dose-per-fraction level (for a total of nine patients, ages 43-77). Most patients had FIGO stage IA-B disease (n=7; 1 with clear cell, 1 with dedifferentiated adenocarcinoma, and 1 with serous carcinoma), while 1 patient had stage II endometrioid adenocarcinoma and 1 patient had stage IIIC1 carcinosarcoma. Median follow-up time from end of WPRT was 24 months (range 6-25). There were no reports of grade 3+ acute toxicity; thus, dose level 3 was determined to be the MTD. On the last day of WPRT, there were three subjects (one in dose level 2, two in dose level 3) with grade 2 GI/GU toxicities. There were no grade 3+ late toxicities. Late grade 2 toxicities at any point from 1-24 months post-WPRT were diarrhea (n=1 in dose level 1), urinary frequency (n=1 in dose level 3), and urinary incontinence (n=1 in dose level 3); these AEs all later resolved to grade 0. Pattern of failure was n=1 with LRR (vaginal cuff) and n=2 with DM.
Conclusion: Phase I results demonstrate no acute or long-term grade 3+ GI/GU toxicities. Thus, a hypofractionated WPRT regimen of 42.56 Gy over 16 fractions was associated with a severe toxicity rate of =10% and is being used for further study in Phase II, which is currently ongoing.