A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer

Int J Radiat Oncol Biol Phys. 2023 Nov 15;117(4):799-808. doi: 10.1016/j.ijrobp.2023.05.023. Epub 2023 May 19.

Abstract

Purpose: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).

Methods and materials: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART.

Results: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%.

Conclusions: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Trial registration: ClinicalTrials.gov NCT03621644.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Magnetic Resonance Spectroscopy
  • Pancreas
  • Pancreatic Neoplasms* / diagnostic imaging
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / radiotherapy
  • Prospective Studies
  • Quality of Life
  • Radiosurgery* / methods
  • Radiotherapy Planning, Computer-Assisted

Associated data

  • ClinicalTrials.gov/NCT03621644