3009 - MRI-Guided Adaptive Radiation Therapy for Organ Preservation in Rectal Cancer (MRI-ENHANCE): A Phase I Dose-Escalation Trial for Locally Advanced Rectal Cancer

E. Kolyvas¹, A. Banerjee², K. Ludwig³, T. Ridolfi³, P. Tolat⁴, E. S. Paulson⁴, B. A. Erickson⁴, C. Peterson³, and W. A. Hall⁴; ¹Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI, ²Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, ³Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, ⁴Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI

Purpose/Objective(s): Colorectal cancer is the fourth most diagnosed cancer and has a rising incidence in patients under the age of 65. The new standard of care for locally advanced rectal cancer is total neoadjuvant therapy (TNT) with radiation doses of 4500 to 5040 cGy given over 25-28 fractions. In general, this dose is not considered tumoricidal. Despite this, non-operative strategies for organ preservation have been reported with this radiation dose in TNT strategies. Intensification of radiation therapy (RT) may provide a higher rate of organ preservation in this setting. No studies to date have utilized real-time MRI guidance of dose-escalated RT. We hypothesize that higher doses of adaptive MRI-guided RT can be determined in a phase I setting with acceptable toxicity. Materials/

Methods: This study is a prospective, open-label, phase I single-arm clinical trial of dose escalation with adaptive MR-guided external beam RT for organ preservation in adult patients with locally advanced rectal adenocarcinoma who are fit to undergo all treatments. Radiation dosing is applied as a 45-60Gy dose to nodes in 25 fractions + variable boost (B) to tumor and nodes in the following 3 arms: i) 64 Gy over 32-34 total fractions, ii) 68 Gy total over 34-36 total fractions and iii) 72 Gy total over 36-38 total fractions. A two-stage adaptive time-to-event continual reassessment method (TITE-CRM) is used for enrolling patients. Primary objective is to determine the maximum tolerated dose of radiation with both early (3 months) and late (12 months) toxicities monitored. Most common anticipated toxicities include diarrhea, bleeding, and proctitis. Secondary endpoints include quality of life reports including bowel function, surgical complication rates, and radiographic predictors of local disease progression or recurrence. Patients are evaluated with imaging and endoscopic exams prior to and following radiation to assess efficacy of treatment.

Results: TBD

Conclusion: The study is open and recruiting at the Medical College of Wisconsin, NCT04808323.