Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis

Joseph A Miccio; Wesley J Talcott; Timil Patel; Henry S Park; Michael Cecchini; Ronald R Salem; Sajid A Khan; Stacey Stein; Jeremy S Kortmansky; Jill Lacy; Amol Narang; Joseph Herman; Salma K Jabbour; Christopher L Hallemeier; Kimberly Johung; Krishan R Jethwa

doi:10.1016/j.ctro.2020.12.003

Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis

Clin Transl Radiat Oncol. 2020 Dec 16:27:15-23. doi: 10.1016/j.ctro.2020.12.003. eCollection 2021 Mar.

Authors

Joseph A Miccio¹, Wesley J Talcott¹, Timil Patel², Henry S Park¹, Michael Cecchini², Ronald R Salem³, Sajid A Khan³, Stacey Stein², Jeremy S Kortmansky², Jill Lacy², Amol Narang⁴, Joseph Herman⁵, Salma K Jabbour⁶, Christopher L Hallemeier⁷, Kimberly Johung¹, Krishan R Jethwa¹

Affiliations

¹ Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.
² Department of Medical Oncology, Yale School of Medicine, New Haven, CT 06520, USA.
³ Department of Surgery, Yale School of Medicine, New Haven, CT 06520, USA.
⁴ Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
⁶ Department of Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
⁷ Department of Radiation Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.

Abstract

Purpose: Margin-negative (R0) resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Pre-operative multi-agent chemotherapy alone (MAC) or MAC followed by pre-operative radiotherapy (MAC + RT) may be used to improve resectability and potentially survival. However, the optimal pre-operative regimen is unknown.

Methods: Patients with non-metastatic PDAC from 2006 to 2016 who received pre-operative MAC or MAC + RT before oncologic resection were identified in the National Cancer Database. Univariable and multivariable (MVA) associates with R0 resection were identified with logistic regression, and survival was analyzed secondarily with the Kaplan Meier method and Cox regression analysis.

Results: 4,599 patients were identified (MAC: 3,109, MAC + RT: 1,490). Compared to those receiving MAC, patients receiving MAC + RT were more likely to have cT3-4 disease (76% vs 64%, p < 0.001) and cN + disease (33% vs 29%, p = 0.010), but were less likely to have ypT3-4 disease (59% vs 74%, p < 0.001) and ypN + disease (32% vs 55%, p < 0.001) and more likely to have a pathologic complete response (5% vs 2%, p < 0.001) and R0 resection (86% vs 80%, p < 0.001). On MVA, MAC + RT (OR 1.58, 95% CI 1.33-1.89, p < 0.001), evaluation at an academic center (OR 1.33, 95% CI 1.14-1.56, p < 0.001), and female sex (OR 1.43, 95% CI 1.23-1.67, p < 0.001) were associated with higher odds of R0 resection, while cT3-4 disease (OR 0.81, 95% CI 0.68-0.96, p = 0.013) was associated with lower odds of R0 resection.

Conclusion: For patients with localized PDAC who receive pre-operative MAC, the addition of pre-operative RT was associated with improved rates of R0 resection and pathologic response.

Keywords: AJCC, American Joint Committee on Cancer; Chemotherapy; IQR, interquartile range; LR, logistic regression; LVI, lymphovascular invasion; MAC, multiagent chemotherapy; MVA, multivariable analysis; NCDB, National Cancer Database; Neoadjuvant therapy; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; Pancreatic cancer; R0, margin negative; RT, radiotherapy; Radiotherapy; Surgery; UVA, univariable analysis; pCR, pathologic complete response.

Abstract

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