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Predictors, Patterns, and Timing of Recurrence Provide Insight into the Disease Biology of Invasive Carcinomas Arising in Association with Intraductal Papillary Mucinous Neoplasms

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Journal of Gastrointestinal Surgery

Abstract

Objectives

To identify predictors, patterns, and timing of recurrence after resection of invasive carcinomas arising in association with an IPMN.

Background

Postoperative management of an invasive carcinoma arising in association with an intraductal papillary mucinous neoplasm (IPMN), a biologically distinct entity from PanIN-derived pancreatic ductal adenocarcinoma (PDAC), remains largely based on guidelines for PanIN-derived PDAC. To minimize treatment failure and inform disease-specific management, cancer recurrence must be better characterized.

Methods

Patients were identified from a prospectively maintained registry between 1996 and 2018. Predictors of recurrence were evaluated by employing Cox regression models to determine risk-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). The patterns and timing of recurrence were recognized and compared utilizing a log-rank test, respectively.

Results

Of the 213 patients included, 92 (43.2%) recurred with a median RFS of 23.7 months (16.7–30.7). The predominant pattern of recurrence included any systemic (65.2%). The median time to local recurrence was longer than systemic (21.6 versus 11.4 months, p = 0.05). Poor differentiation [HR: 3.01, 95%CI (1.06–8.61)] and nodal disease [N1, HR: 2.23, 95%CI (1.12–4.60); and N2, HR: 5.67 95%CI (2.93–10.99)] emerged as independent predictors of systemic recurrence. For local-specific recurrences, poor differentiation [HR: 3.73, 95%CI (1.04–13.45)] and an R1 margin [high-grade dysplasia or invasive carcinoma; HR: 2.66, 95%CI (1.14–6.21)] emerged as independent predictors.

Conclusions

The predominant pattern of recurrence after resection of invasive carcinomas arising in association with IPMNs is systemic, and occurs earlier than local recurrence. Poor differentiation and nodal disease are associated with systemic recurrence while poor differentiation and an R1 margin are associated with local recurrence. Future studies should investigate the role of systemic (chemotherapy) versus local (radiation) therapies and surveillance strategies in a personalized manner.

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Funding

This work was supported by the Nikki Mitchell Foundation, the Ben and Rose Cole Charitable Pria Foundation, and the Faith Hope Love Gala. BK is supported by the German Research Foundation (KI 2437/2–1).

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Authors and Affiliations

  1. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Joseph R. Habib, Benedict Kinny-Köster, Neda Amini, Sami Shoucair, John L. Cameron & Jin He

  2. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elizabeth D. Thompson & Ralph H. Hruban

  3. Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elliot K. Fishman

  4. Division of Hepatobiliary and Pancreatic Surgery, NYU Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA

    Ammar A. Javed & Christopher L. Wolfgang

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Contributions

Conception and study design: JRH, BK, NA, and CLW; acquisition of data: SS and AAJ; analysis and interpretation of data: JRH, JLC, EDT, EKF, RHH, JH, and CLW; review of imaging and pathologic slides: EKF, EDT, and RHH; manuscript drafting: JRH, BK, NA, SS, and AAJ; critically revised the manuscript: JLC, EDT, EKF, RHH, JH, and CLW; final approval of the manuscript version to be published: all authors.

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Correspondence to Christopher L. Wolfgang.

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Habib, J.R., Kinny-Köster, B., Amini, N. et al. Predictors, Patterns, and Timing of Recurrence Provide Insight into the Disease Biology of Invasive Carcinomas Arising in Association with Intraductal Papillary Mucinous Neoplasms. J Gastrointest Surg 26, 2311–2320 (2022). https://doi.org/10.1007/s11605-022-05428-4

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