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The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood.

Methods

This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients.

Results

FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy.

Conclusions

This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.

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Abbreviations

PC:

Pancreatic cancer

FPC:

Familial pancreatic cancer

PDAC:

Pancreatic ductal adenocarcinoma

US:

Ultrasonography

CT:

Computed tomography

RPC:

Resectable pancreatic cancer

PV/SMV:

Portal vein and/or superior mesenteric vein

BRPC:

Borderline resectable pancreatic cancer

UICC:

Union for International Cancer Control

RFS:

Relapse-free survival

OS:

Overall survival

HR:

Hazard ratio

References

  1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941–53.

    Article  CAS  Google Scholar 

  2. Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol. 2019;10:10–27.

    Article  Google Scholar 

  3. Werner J, Combs SE, Springfeld C, et al. Advanced-stage pancreatic cancer: therapy options. Nat Rev Clin Oncol. 2013;10:323–33.

    Article  CAS  Google Scholar 

  4. Howlader N, Noone AM, Krapcho M, et al, editors. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute. Bethesda, MD based on November 2019 SEER data submission, posted to the SEER web site, Apr 2020. https://seer.cancer.gov/csr/1975_2017/. Accessed 25 Apr 2020.

  5. Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.

    Article  CAS  Google Scholar 

  6. Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.

    Article  CAS  Google Scholar 

  7. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395–406.

    Article  CAS  Google Scholar 

  8. Raufi AG, Manji GA, Chabot JA, et al. Neoadjuvant treatment for pancreatic cancer. Semin Oncol. 2019;46:19–27.

    Article  CAS  Google Scholar 

  9. Motoi F, Unno M. Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma. Jpn J Clin Oncol. 2020. https://doi.org/10.3390/ijms20030561.

    Article  PubMed  Google Scholar 

  10. Petersen GM. Familial pancreatic cancer. Semin Oncol. 2016;43:548–53.

    Article  Google Scholar 

  11. Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110:223–62.

    Article  Google Scholar 

  12. Wada K, Takaori K, Traverso LW, et al. Clinical importance of Familial Pancreatic Cancer Registry in Japan: a report from kick-off meeting at International Symposium on Pancreas Cancer 2012. J Hepatobiliary Pancreat Sci. 2013;20:557–66.

    Article  Google Scholar 

  13. Ohmoto A, Yachida S, Morizane C. Genomic features and clinical management of patients with hereditary pancreatic cancer syndromes and familial pancreatic cancer. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20030561.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mintziras I, Bartsch DK. Progress report: familial pancreatic cancer. Fam Cancer. 2019;18:359–62.

    Article  Google Scholar 

  15. Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64:2634–8.

    Article  CAS  Google Scholar 

  16. Goggins M, Overbeek KA, Brand R, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69:7–17.

    Article  CAS  Google Scholar 

  17. Humphris JL, Johns AL, Simpson SH, et al. Clinical and pathologic features of familial pancreatic cancer. Cancer. 2014;120:3669–75.

    Article  Google Scholar 

  18. Barton JG, Schnelldorfer T, Lohse CM, et al. Patterns of pancreatic resection differ between patients with familial and sporadic pancreatic cancer. J Gastrointest Surg. 2011;15:836–42.

    Article  Google Scholar 

  19. Norris AL, Roberts NJ, Jones S, et al. Familial and sporadic pancreatic cancer share the same molecular pathogenesis. Fam Cancer. 2015;14:95–103.

    Article  CAS  Google Scholar 

  20. Brierley JD, Gospondarowicz MK, Wittekind C. International Union Against Cancer. TNM classification of Malignant Tumours. 8th ed. Oxford: Wiley-Blackwell; 2017.

  21. Yamada M, Sugiura T, Okamura Y, et al. Microscopic venous invasion in pancreatic cancer. Ann Surg Oncol. 2018;25:1043–51.

    Article  Google Scholar 

  22. Sugiura T, Uesaka K, Mihara K, et al. Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery. 2013;154:1078–86.

    Article  Google Scholar 

  23. James TA, Sheldon DG, Rajput A, et al. Risk factors associated with earlier age of onset in familial pancreatic carcinoma. Cancer. 2004;101:2722–6.

    Article  Google Scholar 

  24. Bartsch DK, Kress R, Sina-Frey M, et al. Prevalence of familial pancreatic cancer in Germany. Int J Cancer. 2004;110:902–6.

    Article  CAS  Google Scholar 

  25. Takai E, Yachida S, Shimizu K, et al. Germline mutations in Japanese familial pancreatic cancer patients. Oncotarget. 2016;7:74227–35.

    Article  Google Scholar 

  26. Ji J, Forsti A, Sundquist J, et al. Survival in familial pancreatic cancer. Pancreatology. 2008;8:252–6.

    Article  Google Scholar 

  27. Yeo TP, Hruban RH, Brody J, et al. Assessment of “gene-environment” interaction in cases of familial and sporadic pancreatic cancer. J Gastrointest Surg. 2009;13:1487–94.

    Article  Google Scholar 

  28. Roberts NJ, Norris AL, Petersen GM, et al. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov. 2016;6:166–75.

    Article  CAS  Google Scholar 

  29. Wattenberg MM, Asch D, Yu S, et al. Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer. 2020;122:333–9.

    Article  CAS  Google Scholar 

  30. Blair AB, Groot VP, Gemenetzis G, et al. BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic ductal adenocarcinoma. J Am Coll Surg. 2018;226:630–7.

    Article  Google Scholar 

  31. Kondo T, Kanai M, Kou T, et al. Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer. Oncotarget. 2018;9:19817–25.

    Article  Google Scholar 

  32. Brandt A, Bermejo JL, Sundquist J, et al. Age of onset in familial cancer. Ann Oncol. 2008;19:2084–8.

    Article  CAS  Google Scholar 

  33. McFaul CD, Greenhalf W, Earl J, et al. Anticipation in familial pancreatic cancer. Gut. 2006;55:252–8.

    Article  CAS  Google Scholar 

  34. Singhi AD, Ishida H, Ali SZ, et al. A histomorphologic comparison of familial and sporadic pancreatic cancers. Pancreatology. 2015;15:387–91.

    Article  Google Scholar 

  35. Mavros MN, Xu L, Maqsood H, et al. Perioperative blood transfusion and the prognosis of pancreatic cancer surgery: systematic review and meta-analysis. Ann Surg Oncol. 2015;22:4382–91.

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank all the medical staff who were involved in this study.

Funding

There was no funding for this study.

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Authors

Contributions

KT and YO contributed to the study conception and design, and development of the methodology. All authors participated in acquisition, analysis and interpretation of the data. KT and YO were responsible for the first draft of the manuscript. All authors contributed to the review, and/or critical revision of the manuscript, and read and approved the final version.

Corresponding author

Correspondence to Yukiyasu Okamura.

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Tezuka, K., Okamura, Y., Sugiura, T. et al. The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy. J Gastroenterol 56, 101–113 (2021). https://doi.org/10.1007/s00535-020-01730-7

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  • DOI: https://doi.org/10.1007/s00535-020-01730-7

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