A Prospective Clinical Trial Evaluating Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy (SMART) for Pancreatic Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nThe use of ablative stereotactic body radiation therapy (SBRT) in pancreatic cancer is constrained by nearby radiation-sensitive organs. Magnetic resonance (MR)-guided adaptive radiation therapy (SMART) is an innovation that offers superior anatomical imaging during treatment allowing for daily plan adaptation based on the volumetric images prior to each treatment. We report results of a prospective phase 1 trial (NCT04115254) assessing feasibility of SMART and describe early outcomes of patients with pancreatic cancer. Secondary objectives included analysis of 90-day toxicity, local control, and patient-reported outcomes (PROMs) in patients undergoing SMART.\n\n\nMATERIALS/METHODS\nIn this prospective IRB approved study, patient eligibility criteria included: biopsy-proven diagnosis of pancreatic cancer, eligibility for SBRT, and ability to undergo and tolerate MRI imaging. Patients were ineligible if they had prior abdominal radiation, active ulcerative disease, or tumor invasion of the stomach, duodenum or bowel on endoscopy. Patients were monitored for acute and late grade ≥ 3 toxicity. PROMs included the FACT-HEP and PROMIS Physical and Mental Health batteries and were completed at baseline and during follow-up. Feasibility was defined as 1) enrolling patients and delivering SMART on the MR-Linac; 2) assessing tumor using MR guidance before, during and after MR-guided treatment and 3) generating adaptive plans.\n\n\nRESULTS\nAll 10 patients successfully completed SMART, receiving 40 Gy in 5 fractions with 48 of 50 fractions requiring adaptation to meet target or critical organ-at-risk metrics. The median follow up was 10.49 months (range 5.00 - 11.38). The median age was 72 (range 55 - 89), 60% were female, and 80% were white. Disease stages included 30% T1-T2, 10% T3, and 60% T4 disease, as well as 30% N0, 60% N1, 10% N2 disease, and 80% M0, 10% MX, and 10% M1. 90% of patients had other medical comorbidities. ECOG performance status was 0-1 in 90% of patients. There were no acute or late grade ≥ 3 treatment related toxicities. There were no local recurrences. The 6-month survival rate was 90% (95% CI 47.3-98.5) with two deaths due to progressive disease. The median change between baseline and follow-up within 6 months of treatment was -0.5 on FACT-HEP, -2.5 on PROMIS Physical, and -4.7 on PROMIS Mental Health (table 1).\n\n\nCONCLUSION\nWe successfully demonstrated the feasibility and safety of SMART with daily adaptation in patients with pancreatic cancer. PROMs highlight that patients tolerated treatment well with minimal toxicity. Further investigation in dose escalation in pancreatic cancer is warranted.