Patient Selection is Critical When Evaluating Candidates for 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy (SMART) for Locally Advanced Pancreatic Cancer

Abstract

Stereotactic magnetic resonance image-guided adaptive radiotherapy (SMART) allows for the safe delivery of biologically effective doses (BED10 ∼ 100 Gy) to patients with pancreatic cancer who otherwise have limited therapeutic avenues. In this study, we analyze long-term outcomes in the largest cohort of patients with borderline-resectable (BR), locally advanced (LA), or medically inoperable (MI) pancreatic cancer treated with a 5-fraction SMART technique. A single institution analysis of patients with BR, LA, or MI pancreatic cancer treated with SMART between 2015 and 2021 was performed. Patients with locally recurrent disease, non-adenocarcinoma histology, de-novo metastatic disease, or who did not receive induction chemotherapy were excluded. Baseline and treatment characteristics were collected. Local control (LC), progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and factors associated with outcomes were evaluated using Cox regression analyses. Oncologic outcomes measured from time of initial diagnosis; local control defined as freedom from local progression. A total of 129 patients were reviewed. Median age at diagnosis was 67 years. The majority were male (60%) and White (84%). 23% of patients had an ECOG 2. Most patients had LA disease (66%), followed by BR (20%) and MI (14%). Median follow up was 17.0 months (6-61 months). Median LC was not reached, and LC was 81%, 54%, and 48% at 1, 2, and 3-years, respectively. Median PFS was 12.9 months [95% confidence interval 11.8-14.71] with 1, 2, and 3-year PFS of 60%, 20%, and 7%, respectively. Median OS was 17.7 months [15.7-19.7] with 1, 2, and 3-year OS of 78%, 28%, 11%, respectively. On univariate analysis, increased duration of induction chemotherapy had a statistically significant impact on PFS and OS. Those receiving equal to or greater than 4 months of induction chemotherapy had a median OS of 19.2 months [17.2-21.2] as compared to 13.6 [11.9-15.3] for those with less than 4 months. In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.