TY - JOUR
T1 - 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
AU - Parikh, Parag Jitendra
AU - Lee, Percy
AU - Low, Daniel A
AU - Kim, Joshua
AU - Mittauer, Kathryn E
AU - Bassetti, Michael F
AU - Glide-Hurst, Carri K
AU - Raldow, Ann C
AU - Yang, Yingli
AU - Portelance, Lorraine
AU - Padgett, Kyle R
AU - Zaki, Bassem
AU - Zhang, Rongxiao
AU - Kim, Hyun
AU - Henke, Lauren E
AU - Price, Alex T
AU - Mancias, Joseph D
AU - Williams, Christopher L
AU - Ng, John
AU - Pennell, Ryan
AU - Pfeffer, M Raphael
AU - Levin, Daphne
AU - Mueller, Adam C
AU - Mooney, Karen E
AU - Kelly, Patrick
AU - Shah, Amish P
AU - Boldrini, Luca
AU - Placidi, Lorenzo
AU - Fuss, Martin
AU - Chuong, Michael D
N1 - Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023/10/15
Y1 - 2023/10/15
N2 - 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.
AB - 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.
KW - Humans
KW - Aged
KW - Pancreatic Neoplasms/diagnostic imaging
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Prospective Studies
KW - Radiotherapy Planning, Computer-Assisted
KW - Quality of Life
KW - Pancreas
KW - Magnetic Resonance Spectroscopy
KW - Radiosurgery/methods
U2 - 10.1016/j.ijrobp.2023.05.023
DO - 10.1016/j.ijrobp.2023.05.023
M3 - Article
C2 - 37210048
SN - 0360-3016
VL - 117
SP - 799
EP - 808
JO - International Journal of Radiation Oncology, Biology, Physics
JF - International Journal of Radiation Oncology, Biology, Physics
IS - 4
ER -