2995 - MRI-Defined Moderate Radiation Dose-Escalation for Locally Advanced Pancreas Cancer: A Phase II Study

J. Hirshberg¹, W. A. Hall¹, A. Li¹, E. S. Paulson¹, A. Tai¹, P. Prior², X. Chen¹, M. Aldakkak³, D. B. Evans³, K. Christians³, S. Tsai³, B. George⁴, M. Kamgar⁴, J. Thomas², C. Clarke³, A. Shreenivas², M. Hohenwalter⁵, P. Knechtges⁶, M. J. Zhang², S. Jasti⁷, A. Banerjee⁸, and B. A. Erickson¹; ¹Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, ²Medical College of Wisconsin, Milwaukee, WI, ³Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, ⁴Department of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, ⁵Froedtert Memorial Lutheran Hospital, Milwaukee, WI, ⁶Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, ⁷The Medical College of Wisconsin, Milwaukee, WI, ⁸Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI

Purpose/Objective(s): Technological advancements for locally advanced pancreatic cancer (LAPC) have enabled higher radiation doses to tumor and lower doses to nearby Organs at Risk (OAR). We present a single-institutional prospective phase-II study investigating the efficacy of MRI-defined moderate dose-escalated radiation (RT) in patients with LAPC after induction chemotherapy (IC). Materials/

Methods: Patients with LAPC after > 4 months of IC were eligible. All underwent CT and MRI simulation for accurate GTV definition. Doses of 50.4 Gy-51.15 Gy in 28-31 fractions (fx) were prescribed to an elective CTV, and a SIB was delivered at 2.25Gy/fx from 63 - 69.75Gy to the GTV, prescribing to the highest dose level (within protocol ranges) while prioritizing OAR constraints. Those enrolled after 2020 were treated on a 1.5T MR-LINAC. The coprimary endpoints were 2yr overall survival (OS) and median survival (MS). Secondary endpoints included Local Control (LC), Distant Metastasis-Free Survival (DMFS), 1yr OS, and toxicity. This study was designed with 80% power to detect a 15mo increased MS compared to historical controls with alpha=0.05, requiring 23 patients. Descriptive statistics, Kaplan Meier and log-rank test were performed.
Results: This study enrolled 23 patients from 2016-2021. Five patients were treated to 63gy/28fx (22%), 8 to 65.25gy/29fx (34%), 5 to 67.5gy/30fx (22%), and 5 to 69.75gy/31fx (22%). Six patients (26%) were treated on an MR-LINAC, 5 of which were treated to the highest dose level and used an adapt-to-position workflow. All had cT4 disease, and 61% were cN0. Most lesions were in the head / body of the pancreas (88%). FOLFIRINOX (70%) or Gemcitabine/nab-paclitaxel (30%) represented an average of 7.9 (5-13) cycles of IC. All received concurrent gemcitabine (95%) or capecitabine (5%) with RT. All patients completed treatment per protocol. Median follow-up was 28.1 months. Acute grade 2 toxicity was seen in 35% of patients. There were no acute grade > 3 GI events. Late grade > 2 GI toxicity was seen in 35%, and 17% had grade 3 events. There were no late grade >4 GI events. Table 1 shows the study endpoints.
Conclusion: This study demonstrated favorable MS and OS for patients with inoperable LAPC after IC treated with moderate dose-escalated RT to an MRI-defined GTV, representing a statistically significant improvement from historical controls measuring from diagnosis. Treatment was well tolerated. Further studies may determine the optimal dose escalation strategy to further improve outcomes.

Abstract 2995 – Table 1

Measurement:	1yr LC	1yr DMFS	1yr OS	2yr OS	MS
From Dx:	91.3%	82.6%	100%	56.5%*	28.1mo*
From RT:	52.2%	60.9%	61%	39.1% (NSS)	20.2mo (NSS)
Historical:				33% (p=0.029)*	15mo (p<0.01)*