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Neoadjuvant Chemoradiation Impacts the Prognostic Effect of Surgical Margin Status in Pancreatic Adenocarcinoma

Abstract

Background

Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown.

Objective

The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC.

Methods

All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS).

Results

Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (−SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with −SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04–4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00–1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72–1.65; p = 0.70).

Conclusion

Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.

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Acknowledgment

The authors would like to express their gratitude to the patients and caregivers who made this study possible.

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Correspondence to Joshua E. Meyer.

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Disclosures

The Fox Chase Cancer Center institution is supported by NCI grant number P30 CA006927. Elizabeth Handorf is supported by a Pfizer grant, unrelated to the current research, and Efrat Dotan has received research support, paid to the institution and unrelated to this published work, from Pfizer, Incyte, Lilly, Merck, Boston Biomedical, GSK, AstraZeneca, Immunomedics, Oncomed, Bayer. Eddie Zhang, Lora Wang, Talha Shaikh, J. Karen Wong, John P. Hoffman, Sanjay Reddy, Harry S. Cooper, Steven J. Cohen, and Joshua E. Meyer have no disclosures to declare.

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Zhang, E., Wang, L., Shaikh, T. et al. Neoadjuvant Chemoradiation Impacts the Prognostic Effect of Surgical Margin Status in Pancreatic Adenocarcinoma. Ann Surg Oncol (2021). https://doi.org/10.1245/s10434-021-10219-3

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