Stereotactic MR-Guided On-Table Adaptive Radiation Therapy (SMART) for Patients with Borderline or Locally Advanced Pancreatic Cancer: Primary Endpoint Outcomes of a Prospective Phase II Multi-Center International Trial

Document Type

Conference Proceeding

Publication Date

12-1-2022

Publication Title

Int J Radiat Oncol Biol Phys

Keywords

CA 19-9 antigen, cobalt 60, endogenous compound, gemcitabine, unclassified drug, adaptive radiation, adenocarcinoma, advanced cancer, aged, cancer radiotherapy, cancer surgery, cancer survival, chemotherapy, cine magnetic resonance imaging, clinical trial, Common Terminology Criteria for Adverse Events, conference abstract, controlled study, distant metastasis, distant progression free survival, female, follow up, gastrointestinal toxicity, human, incidence, induction chemotherapy, major clinical study, male, MRI guided linear accelerator, multicenter study, outcome assessment, overall survival, pancreas cancer, phase 2 clinical trial, prospective study, quality of life, radiotherapy, retrospective study, signal transduction, soft tissue

Abstract

Purpose/Objective(s): Retrospective studies demonstrate that ablative stereotactic MR-guided on-table adaptive radiation therapy (SMART) achieves favorable local control (LC) and overall survival (OS) with limited grade 3+ toxicity compared to historical non-ablative outcomes for locally advanced and borderline resectable pancreatic cancer (LAPC/BRPC). We conducted an international multi-center single-arm phase 2 trial of ablative 5-fraction SMART for LAPC/BRPC. Materials/Methods: Subjectswere required to have biopsy-confirmed adenocarcinoma, receive ≥3 months of chemotherapy, have no distant metastasis and CA19-9 ≤500 U/mL. SMART was delivered on a 0.35T MR-60Co or MR-linac system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10]=100 Gy) using continuous intrafraction cine-MRI, soft tissue tracking, and automatic beam gating. The original plan was recomputed onto the daily anatomy and if that plan would not have met constraints, on-table adaptive replanning using an isotoxicity approach was performed. The primary objective was to demonstrate <15.8% acute grade 3+ gastrointestinal (GI) toxicity definitely related to SMART measured through 90 days and evaluated according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE). All patients have completed 90-day follow-up. Secondary objectives included OS, distant progression free survival (DPFS), and patient-reported quality of life. Results: 136 patients across 13 sites were enrolled between 2019-2021. Mean age was 65.7 years. Head of pancreas lesions were most common (66.9%; n=91). 43.4% (n=59) had BRPC, 56.6% (n=77) LAPC. Mean induction chemotherapy duration was 155.7 days, typically with FOLFIRINOX 65.4% (n=89) or gemcitabine doublet 16.9% (n=23). Mean CA19-9 after induction chemotherapy was 71.7 U/mL. On-table adaptive replanning was used for 93.1% of fractions. SMART was delivered in consecutive days (56.6%) or every other day (43.4%). Median follow-up was 16.4 months and 8.8 months from diagnosis and SMART, respectively. 31.6% (n=43) had surgery after SMART. The incidence of acute grade 3+ GI toxicity definitely and probably related to SMART were 0% and 2.2% (n=3), respectively. 1-year LC and DPFS from SMART were 82.9% and 50.6%, respectively. 1-year OS was 93.9% from diagnosis and 65.0% from SMART. Conclusion: This is the first prospective, multi-institutional study of ablative SMART with prescribed BED10 of 100 Gy delivered in 5 fractions for BRPC/LAPC. The primary objective was met, signaling that further prospective evaluation of ablative SMART for BRPC/LAPC is warranted with a focus on long-term LC and OS compared to chemotherapy alone.

Volume

114

Issue

5

First Page

1062

Last Page

1063

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