2955 - Phase IA/IB Study of OAR-Based, Dose-Escalated SBRT with Real Time Adaptive MRI Guidance for Liver Metastases: Preliminary Safety and Efficacy Results

M. M. Basree¹, J. S. Witt², K. Ranta¹, S. A. Rosenberg³, C. Glide-Hurst¹, J. Crosby¹, D. A. Deming⁴, N. Anger⁵, K. Font⁵, D. Trask¹, M. Weiss¹, N. J. Hurst Jr^1,6, N. Uboha⁴, and M. F. Bassetti¹; ¹Department of Human Oncology, University of Wisconsin Hospitals and Clinics, Madison, WI, ²Cancer Care Specialists of Illinois/Cancer Care Center of OFallon, OFallon, IL, ³H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ⁴Department of Medical Oncology, University of Wisconsin Carbone Cancer Center, Madison, WI, ⁵University of Wisconsin School of Medicine and Public Health, Madison, WI, ⁶William S. Middleton Memorial Veterans Hospital, Madison, WI

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) for liver tumors is most often limited by adjacent bowel or uninvolved liver dose. Maximum safe constraints for these organs are incompletely defined. Utilizing MR-guidance in SBRT (MRgRT) allows for real-time monitoring and adjustment to minimize organ-at-risk (OAR) toxicity. The purpose of this study is to determine the maximum tolerated dose (MTD) based on increasing tolerance levels for bowel and liver doses in patients (pts) with liver metastases. Materials/

Methods: This is a single-institution phase IA/IB 4+4 OAR-based dose-escalation study of pts with liver metastases (NCT04020276). Treatment involved isotoxic dose escalation up to a MTD of 80 Gy using MRgRT in 5 fractions, with two arms defined by the most limiting OAR – bowel or liver. Starting dose constraints (bowel: V34 to 0.5cc; liver: uninvolved 700cc <17 Gy) were escalated in 2-Gy increments to V40 to 0.5cc and 700cc < 21 Gy, respectively. Patients were treated sequentially based on OAR tolerance until dose-limiting toxicity (DLT) occurred, which is defined as grade ³3 non-hematologic toxicity attributable to and occurring within 4 weeks of completion of SBRT. Liver function tests were allowed up to and including grade 3. Patients completed 1- and 2-month post-treatment study questionnaire ranking their pain, nausea, vomiting, diarrhea, and blood in stool symptoms. Secondary endpoints included survival outcomes, analyzed using statistical software for descriptive statistics, and Kaplan-Meier method to estimate local control (LC), out-of-field recurrence (OFR), and overall survival (OS) outcomes with log-rank test.

Results: Sixteen pts have thus far enrolled in the study, with 62.5% (n=10) being male and 81.3% (n=13) having colorectal primary cancer. The median age was 64 years (range, 45 – 74). Patients presented with a median of 2 liver lesions (range, 1 – 6), totaling 28 lesions, with a median lesion size of 4.1 cm (range, 1.6 – 13.2). Median SBRT dose was 80 Gy (range, 60 – 80. Seven pts had both bowel (V34 < 0.5cc [n=3] and V36 < 0.5cc [n=4]) and liver (700 cc < 17 Gy [n=3] and 700 cc < 19 Gy [n=4]) dose escalation performed simultaneously. No dose-limiting toxicities were observed. Fourteen out of 16 pts experienced definite or probable grade £2 treatment-related toxicity, most commonly fatigue (75%), skin reaction (60%), and gastrointestinal (47.6%). There were no grade ³3 treatment-related toxicities. The objective response rate at 3 months was 96.4%. Median follow-up was 16.4 months (range, 3.53 – 49.1), with a median OS of 26.1 months (range, 6.0 – 49.1). One-year KM estimates of LC, OFR, and OS were 100%, 78.1%, and 80.4%, respectively.

Conclusion: Preliminary results from this phase IA study demonstrate the feasibility and safety of OAR-based dose-escalated SBRT up to 80 Gy. A phase IB expansion cohort is currently underway, focusing on patients with limited metastatic colorectal cancer, to further evaluate toxicity and control using the constraints identified in this study.