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Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma

  • Vincent P. Groot
  • Georgios Gemenetzis
  • Alex B. Blair
  • Ding Ding
  • Ammar A. Javed
  • Richard A. Burkhart
  • Jun Yu
  • Inne H. Borel Rinkes
  • I. Quintus Molenaar
  • John L. Cameron
  • Elliot K. Fishman
  • Ralph H. Hruban
  • Matthew J. Weiss
  • Christopher L. Wolfgang
  • Jin He
Pancreatic Tumors

Abstract

Background

After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC.

Objective

The aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC.

Methods

This single-center cohort study included patients undergoing pancreatectomy at the Johns Hopkins Hospital between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. Sites of first recurrence were stratified into five groups and survival outcomes were estimated using Kaplan–Meier curves. The association of specific recurrence locations with overall survival (OS) was analyzed using Cox proportional-hazards models with and without landmark analysis.

Results

Accurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (n = 227, 4.7 months) or liver-only recurrence (n = 166, 7.2 months) had significantly worse median survival after recurrence when compared with lung- (n = 93) or local-only (n = 158) recurrence (15.4 and 9.7 months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24 months, confirmed these findings.

Conclusions

This study demonstrates that specific patterns of PDAC recurrence result in different survival outcomes. Furthermore, distinct first recurrence locations have unique independent predictive values for OS, which could help with prognostic stratification and decisions regarding treatment after the diagnosis of recurrence.

Notes

Acknowledgement

The authors would like to thank the Foundation “De Drie Lichten”, Prins Bernhard Cultuurfonds, VSBfonds, Prof. Michaël-van Vloten Fonds, Nijbakker-Morra Foundation, and the Living With Hope Foundation (all from The Netherlands) for funding this study in the form of grants for a research fellowship by VPG.

Disclosures

Vincent P. Groot, Georgios Gemenetzis, Alex B. Blair, Ding Ding, Ammar A. Javed, Richard A. Burkhart, Jun Yu, Inne H. Borel Rinkes, I. Quintus Molenaar, John L. Cameron, Elliot K. Fishman, Ralph H. Hruban, Matthew J. Weiss, Christopher L. Wolfgang, and Jin He have no financial disclosures or conflicts of interest to declare.

Supplementary material

10434_2018_6558_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 18 kb)
10434_2018_6558_MOESM2_ESM.docx (13 kb)
Supplementary material 2 (DOCX 13 kb)

References

  1. 1.
    Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.CrossRefPubMedGoogle Scholar
  2. 2.
    Riall TS, Cameron JL, Lillemoe KD, Winter JM, Campbell KA, Hruban RH, et al. Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery. 2006;140:764–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244:10–15.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cameron JL, He J. Two thousand consecutive pancreaticoduodenectomies. J Am Coll Surg. 2015;220:530–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200.CrossRefPubMedGoogle Scholar
  6. 6.
    Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35:600–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Hernandez JM, Morton CA, Al-Saadi S, Villadolid D, Cooper J, Bowers C, et al. The natural history of resected pancreatic cancer without adjuvant chemotherapy. Am Surg. 2010;76:480–5.PubMedGoogle Scholar
  8. 8.
    Suenaga M, Fujii T, Kanda M, Takami H, Okumura N, Inokawa Y, et al. Pattern of first recurrent lesions in pancreatic cancer: hepatic relapse is associated with dismal prognosis and portal vein invasion. Hepatogastroenterology. 2014;61:1756–61.PubMedGoogle Scholar
  9. 9.
    Groot VP, Daamen LA, Hagendoorn J, Borel Rinkes IHM, van Santvoort HC, Molenaar IQ. Use of imaging during symptomatic follow-up after resection of pancreatic ductal adenocarcinoma. J Surg Res. 2018;221:152–60.CrossRefPubMedGoogle Scholar
  10. 10.
    Groot VP, Rezaee N, Wu W, Cameron JL, Fishman EK, Hruban RH, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267:936–45.PubMedGoogle Scholar
  11. 11.
    Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.CrossRefPubMedGoogle Scholar
  12. 12.
    Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1:710–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Weeden S, Grimer RJ, Cannon SR, Taminiau AH, Uscinska BM. The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer. 2001;37:39–46.CrossRefPubMedGoogle Scholar
  14. 14.
    Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011;4:363–71.CrossRefPubMedGoogle Scholar
  15. 15.
    Hallet J, Sa Cunha A, Adam R, Goéré D, Bachellier P, Azoulay D, et al. Factors influencing recurrence following initial hepatectomy for colorectal liver metastases. Br J Surg. 2016;103:1366–76.CrossRefPubMedGoogle Scholar
  16. 16.
    Groot VP, Gemenetzis G, Blair AB, Rivero-Soto RJ, Yu J, Javed AA, et al. Defining and predicting early recurrence in 957 Patients with resected pancreatic ductal adenocarcinoma. Ann Surg. Epub 23 Mar 2018.  https://doi.org/10.1097/sla.0000000000002734.
  17. 17.
    Tani M, Kawai M, Miyazawa M, Hirono S, Ina S, Nishioka R, et al. Liver metastasis as an initial recurrence has no impact on the survival of patients with resectable pancreatic adenocarcinoma. Langenbecks Arch Surg. 2009;394:249–53.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang Y, Frampton AE, Kyriakides C, Bong, J.J., Habib, N., Ahmad, R, et al. Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy. J Cancer Res Clin Oncol. 2012;138:1063–71.CrossRefPubMedGoogle Scholar
  19. 19.
    Groot VP, van Santvoort HC, Rombouts SJE, Hagendoorn J, Borel Rinkes IH, van Vulpen M, et al. Systematic review on the treatment of isolated local recurrence of pancreatic cancer after surgery; re-resection, chemoradiotherapy and SBRT. HPB (Oxford). 2017;19:83–92.CrossRefPubMedGoogle Scholar
  20. 20.
    Ryan JF, Groot VP, Rosati LM, Hacker-Prietz A, Narang AK, McNutt TR, et al. Stereotactic body radiation therapy for isolated local recurrence after surgical resection of pancreatic ductal adenocarcinoma appears to be safe and effective. Ann Surg Oncol. 2018;25:280–89.CrossRefPubMedGoogle Scholar
  21. 21.
    Arnaoutakis GJ, Rangachari D, Laheru DA, Iacobuzio-Donahue CA, Hruban RH, Herman JM, et al. Pulmonary resection for isolated pancreatic adenocarcinoma metastasis: an analysis of outcomes and survival. J Gastrointest Surg. 2011;15:1611–7.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Downs-Canner S, Zenati M, Boone BA, Varley PR, Steve J, Hogg ME, et al. The indolent nature of pulmonary metastases from ductal adenocarcinoma of the pancreas. J Surg Oncol. 2015;112:80–85.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wangjam T, Zhang Z, Zhou XC, Lyer L, Faisal F, Soares KC, et al. Resected pancreatic ductal adenocarcinomas with recurrence limited in lung have a significantly better prognosis than those with other recurrence patterns. Oncotarget. 2015;6:36903–10.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Lu F, Poruk KE, Weiss MJ. Surgery for oligometastasis of pancreatic cancer. Chin J Cancer Res. 2015;27:358–67.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Yamashita K, Miyamoto A, Hama N, Asaoka T, Maeda S, Omiya H, et al. Survival impact of pulmonary metastasis as recurrence of pancreatic ductal adenocarcinoma. Dig Surg. 2015;32:464–71.CrossRefPubMedGoogle Scholar
  26. 26.
    Zheng B, Ohuchida K, Yan Z, Okumura T, Ohtsuka T, Nakamura M. Primary recurrence in the lung is related to favorable prognosis in patients with pancreatic cancer and postoperative recurrence. World J Surg. 2017;41: 2858–66.CrossRefPubMedGoogle Scholar
  27. 27.
    Poruk KE, Kim Y, Cameron JL, He J, Eckhauser FE, Rezaee N, et al. What is the significance of indeterminate pulmonary nodules in patients undergoing resection for pancreatic adenocarcinoma? J Gastrointest Surg. 2015;19:841–47.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Vincent P. Groot
    • 1
    • 2
  • Georgios Gemenetzis
    • 1
  • Alex B. Blair
    • 1
  • Ding Ding
    • 1
  • Ammar A. Javed
    • 1
  • Richard A. Burkhart
    • 1
  • Jun Yu
    • 1
  • Inne H. Borel Rinkes
    • 2
  • I. Quintus Molenaar
    • 2
  • John L. Cameron
    • 1
  • Elliot K. Fishman
    • 3
  • Ralph H. Hruban
    • 4
  • Matthew J. Weiss
    • 1
  • Christopher L. Wolfgang
    • 1
  • Jin He
    • 1
  1. 1.Department of Surgery, The Sol Goldman Pancreatic Cancer Research CenterThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of SurgeryUMC Utrecht Cancer Center, University Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Department of Radiology, The Sol Goldman Pancreatic Cancer Research CenterThe Johns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of Pathology, The Sol Goldman Pancreatic Cancer Research CenterThe Johns Hopkins University School of MedicineBaltimoreUSA

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