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March 11, 2021

Ablative Radiotherapy for Patients With Inoperable Pancreas Cancer—Ready for Prime Time?

Author Affiliations
  • 1Department of Radiation Oncology, Columbia University Irving Medical Center, New York, New York
  • 2Columbia University Herbert Irving Comprehensive Cancer Center, New York, New York
  • 3Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
JAMA Oncol. 2021;7(5):687-688. doi:10.1001/jamaoncol.2021.0028

The use of radiotherapy in treating inoperable pancreatic cancer is a controversial topic, with conventionally fractionated irradiation (1.8-2.0 Gy/fraction) combined with concurrent chemotherapy demonstrating equivocal survival results in 5 phase 3 randomized clinical trials.1-5 The contemporary LAP07 trial, in contrast to the older randomized trials, used smaller radiation fields that were limited to gross disease plus margin (54 Gy in 1.8 Gy fractions) in combination with capecitabine following 4 months of gemcitabine chemotherapy with or without erlotinib.3 While median overall survival was not improved by the addition of conventional chemoradiotherapy (16.5 vs 15.2 months; P = .08), the use of chemoradiotherapy was associated with significantly reduced rates of local disease progression (32% vs 46%; P = .03), longer time without receiving chemotherapy (6.1 vs 3.7 months; P = .02), and a trend toward improved progression-free survival (hazard ratio, 0.78; P = .06). This lack of overall survival benefit from long-course conventional radiation, coupled with technological improvements in the planning and delivery of radiation, has led to the use of stereotactic body radiotherapy (SBRT) in select patients with inoperable pancreas cancer.

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2 Comments for this article
Studies of Nonoperative treatment should exclude patients with resected tumors.
Christopher Crane, M. D. | Memorial Sloan Kettering Cancer Center
Consensus definitions that separate locally advanced radiographically unresectable (LAPC) from borderline pancreatic cancer were established in 2009 by the Americas Hepato-Pancreato-Biliary Association and Society of Surgical Oncology and subsequently adopted by the National Comprehensive Cancer Network.1 Since then, more active chemotherapeutic regimens have been introduced that have enabled the consideration of resection for increasing numbers of patients with initially staged locally LAPC.2 Limitations in the ability of radiographic staging to accurately segregate these populations in a consistent way and differences in and evolution of surgical practices such as the extent of vascular surgery performed have expanded the number of patients designated as LAPC that undergo resection. Since complete surgical resection confers a major survival benefit, the inclusion of these patients with patients who have not undergone resection confounds the interpretation of the survival outcomes of nonoperative treatments. For instance, a meta-analysis assessing the impact of FOLFIRINOX in patients with LAPC reported a median survival of 24mo, but 63.5% of patients also received conventional dose radiotherapy, and 34% underwent resection. The range of resection rates in studies that were included ranged from 0% to 43% which illustrates the heterogeneity of patient characteristics among these studies.3 As pointed out in the editorial that accompanied our study,4 a previous study from our institution in which patients received chemotherapy and conventional dose IMRT followed by resection in 19% reported a median survival duration of 23mo.5 The confounding effect of the inclusion of patients whose tumors were resected is illustrated by a subsequent analysis from our institution. The median OS was 15.7mo after IMRT (45-56Gy) or low dose SBRT (30-33Gy, bioequivalent dose 48-53Gy) when patients who underwent resection were excluded.6 In the current report we specifically avoided this confounding factor by including only patients with in situ primary tumors.
Our results suggest that there is now more hope on the horizon for patients who cannot undergo resection. Multidisciplinary feasibility of ablative radiation for LAPC is emerging using MRI adaptive technology. The most pressing information gap is the safety of surgery after these doses of radiation. Ideally, patients with initially unresectable locally advanced pancreatic cancer should have consideration of both ablative radiation and surgical resection as options for local tumor control. Since universal agreement of definitions of resectability is not realistic, the best way to compare results of nonoperative therapies is exclude patients that undergo resection.

Coauthor acknowledgments:

Marsha Reyngold MD, PhD1,†, Alice Wei, MD2, †, and Eileen M. O’Reilly, MD3, †

1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
2Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
3Department of Gastrointestinal Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York

†David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
Christopher Crane, M. D. | Memorial Sloan Kettering Cancer Center
1. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: Expert consensus statement. Annals of surgical oncology. 2009;16(7):1727-1733.
2. Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018;36(24):2545-2556.
3. Suker M, Beumer BR, Sadot E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801-810.
4. Horowitz DP, Goodman K, Kachnic LA. Ablative Radiotherapy for Patients With Inoperable Pancreas Cancer—Ready for
Prime Time? JAMA Oncology. 2021.
5. Huguet F, Hajj C, Winston CB, et al. Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection. Acta Oncol. 2017;56(3):384-390.
6. Park JJ, Hajj C, Reyngold M, et al. Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. Acta Oncol. 2017;56(12):1746-1753.