Primary Tumor-Directed MRI-Guided Ablative Radiation Therapy for Patients with Metastatic Pancreatic Adenocarcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Survival remains poor for patients with metastatic pancreatic cancer and local progression is commonly associated with high rates of morbidity and mortality. MRI-guided adaptive radiation therapy (MRgART) with ablative dose may offer local disease control and improve clinical outcomes for selected metastatic patients with chemotherapy-responsive disease. <h3>Materials/Methods</h3> We performed a multi-institutional retrospective analysis of de novo metastatic pancreatic cancer patients who received high biological effective dose MRgART to their primary disease on a 0.35T MR-Linac in 5 fractions. Local and distant disease recurrence was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or by radiographic evidence of progression with initiation or change in systemic therapy. Toxicity was measured by Common Terminology Criteria for Adverse Events (v5) at routine follow up appointments. Primary clinical outcomes of interest were overall survival (OS) censored at last clinical follow up and freedom from local failure (FFLF) censored at last dedicated abdominal imaging. <h3>Results</h3> From December 2019 until April 2021 a total of 22 metastatic patients with a median age of 66 years and a slight male predominance (59%) were treated with induction FOLFIRINOX (64%, median 13 cycles, 224 days) or Gemcitabine/nab-Paclitaxel (36%, median 7 cycles, 220 days) followed by ablative dose MRgART to a median dose of 50 Gy (range 40-50). Median follow up from MRgART was 13.0 months. The median OS from diagnosis and from radiation were 23.9 months (95% CI 18.1-30.0) and 11.6 months (95% CI 9.6-13.6), respectively. The FFLF was 77% and 2 patients (9%) were documented with death due to local disease progression. At last follow up, 19 patients (86%) had experienced distant progression and 13 (69%) had died. A single patient underwent a margin negative distal pancreatectomy and metastasectomy of a treated retroperitoneal tumor implant and is without recurrence at 16 months post-diagnosis. Two patients experienced grade 3+ toxicity, one patient with duodenal involvement at diagnosis and on anti-coagulation during treatment experienced a gastrointestinal bleed at 69 days post-MRgART and portal vein pseudoaneurysm 168 days post-MRgART. The second patient developed gastric outlet obstruction 430 days post-MRgART. There was no grade 5 toxicity. <h3>Conclusion</h3> Some metastatic pancreatic cancer patients with stable or chemotherapy-responsive disease appear to benefit from aggressive local therapy which may mitigate morbidity of primary tumor progression. Further investigation into the optimal patient selection for this treatment is warranted.