Advertisement

Outcomes in patients with pancreatic cancer as a secondary malignancy: a retrospective single-institution study

  • Sojun HoshimotoEmail author
  • Shoichi Hishinuma
  • Hirofumi Shirakawa
  • Moriaki Tomikawa
  • Iwao Ozawa
  • Yoshiro Ogata
Original Article
  • 8 Downloads

Abstract

Purpose

This study aimed to evaluate the clinicopathological features and oncological outcomes of pancreatic cancer (PC) patients with prior malignancies (2nd primary PC) compared with those of patients without any prior malignancies in their history (1st primary PC).

Methods

We retrospectively reviewed clinical data from 185 PC patients undergoing surgical resection. Patients were divided into the 1st and 2nd primary PC groups.

Results

Forty-three patients (23.2%) had a history of prior malignancy. The 2nd primary PC group was significantly older than the 1st primary PC group (mean, 72.1 vs. 65.9 years, respectively, P < 0.001) and was more frequently asymptomatic compared to the 1st primary PC group (67.4 vs. 31.0%, respectively, P < 0.001). The tumor size was larger, and extrapancreatic nerve plexus invasion, venous invasion, and lymph node metastasis were more frequently observed in the 1st primary PC group. The rate of adjuvant therapy administration was lower in 2nd primary PC patients (72.5 vs. 51.2%, P = 0.009). In the survival analysis, no significant difference in overall or disease-free survival was found between the two groups (16.8 vs. 16.4 months, P = 0.725, and 8.7 vs. 9.3 months, P = 0.284, respectively).

Conclusion

Despite significant surveillance bias, such as earlier detection in 2nd primary PC, the outcomes of patients with 2nd primary PC were comparable to those of patients with 1st primary PC. Further investigation with a larger sample size and matching for patient age and tumor stage in both groups is needed to elucidate the biological features of 2nd primary PC.

Keywords

Multiple primary malignancy Pancreatic cancer Second primary cancer Systemic inflammatory response 

Notes

Authors’ contributions

Hoshimoto S designed the report; Hishinuma S, Shirakawa H, Tomikawa M, Ozawa I, and Ogata Y were in charge of patient treatment and data acquisition; Hoshimoto S analyzed the data and drafted the manuscript; Hishinuma S and Ogata Y critically revised the manuscript. All authors approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

423_2019_1841_MOESM1_ESM.docx (20 kb)
ESM 1 (DOCX 19 kb)

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30.  https://doi.org/10.3322/caac.21387 CrossRefGoogle Scholar
  2. 2.
    Howell R (2012) Second primary cancers and cardiovascular disease after radiation therapy. NCRP report no. 170. Med Phys 39:7729–7731.  https://doi.org/10.1118/1.4765651 CrossRefPubMedGoogle Scholar
  3. 3.
    Murphy CC, Gerber DE, Pruitt SL (2018) Prevalence of prior cancer among persons newly diagnosed with cancer: an initial report from the surveillance, epidemiology, and end results program. JAMA Oncol 4:832–836.  https://doi.org/10.1001/jamaoncol.2017.3605 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Shen M, Boffetta P, Olsen JH, Andersen A, Hemminki K, Pukkala E, Tracey E, Brewster DH, McBride M, Pompe-Kirn V, Kliewer EV, Tonita JM, Chia KS, Martos C, Jonasson JG, Colin D, Scélo G, Brennan P (2006) A pooled analysis of second primary pancreatic cancer. Am J Epidemiol 163:502–511.  https://doi.org/10.1093/aje/kwj073 CrossRefPubMedGoogle Scholar
  5. 5.
    Travis LB, Rabkin CS, Brown LM, Allan JM, Alter BP, Ambrosone CB, Begg CB, Caporaso N, Chanock S, DeMichele A, Figg WD, Gospodarowicz MK, Hall EJ, Hisada M, Inskip P, Kleinerman R, Little JB, Malkin D, Ng AK, Offit K, Pui CH, Robison LL, Rothman N, Shields PG, Strong L, Taniguchi T, Tucker MA, Greene MH (2006) Cancer survivorship—genetic susceptibility and second primary cancers: research strategies and recommendations. J Natl Cancer Inst 98:15–25.  https://doi.org/10.1093/jnci/djj001 CrossRefPubMedGoogle Scholar
  6. 6.
    Kato H, Usui M, Isaji S, Nagakawa T, Wada K, Unno M, Nakao A, Miyakawa S, Ohta T (2013) Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese society of pancreatic surgery. J Hepatobiliary Pancreat Sci 20:601–610.  https://doi.org/10.1007/s00534-013-0595-1 CrossRefPubMedGoogle Scholar
  7. 7.
    Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW, European Study Group for Pancreatic Cancer (2017) Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet 389:1011–1024.  https://doi.org/10.1016/S0140-6736(16)32409-6 CrossRefGoogle Scholar
  8. 8.
    Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y, JASPAC 01 Study Group (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 388:248–257.  https://doi.org/10.1016/S0140-6736(16)30583-9 CrossRefGoogle Scholar
  9. 9.
    Ahmad J, Grimes N, Farid S, Morris-Stiff G (2014) Inflammatory response related scoring systems in assessing the prognosis of patients with pancreatic ductal adenocarcinoma: a systematic review. Hepatobiliary Pancreat Dis Int 13:474–481.  https://doi.org/10.1016/S1499-3872(14)60284-8 CrossRefPubMedGoogle Scholar
  10. 10.
    Aurello P, Tierno SM, Berardi G, Tomassini F, Magistri P, D’Angelo F, Ramacciato G (2014) Value of preoperative inflammation-based prognostic scores in predicting overall survival and disease-free survival in patients with gastric cancer. Ann Surg Oncol 21:1998–2004.  https://doi.org/10.1245/s10434-014-3533-9 CrossRefPubMedGoogle Scholar
  11. 11.
    Liu B, Huang Y, Sun Y, Zhang J, Yao Y, Shen Z, Xiang D, He A (2016) Prognostic value of inflammation-based scores in patients with osteosarcoma. Sci Rep 6:39862.  https://doi.org/10.1038/srep39862 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wei B, Yao M, Xing C, Wang W, Yao J, Hong Y, Liu Y, Fu P (2016) The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis. Onco Targets Ther 9:5567–5575.  https://doi.org/10.2147/OTT.S108419 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Aziz MH, Sideras K, Aziz NA et al (2018) The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on bilirubin levels: a retrospective multicenter cohort study. Ann Surg 270:139–146.  https://doi.org/10.1097/SLA.0000000000002660 CrossRefGoogle Scholar
  14. 14.
    Yamada S, Fujii T, Yabusaki N, Murotani K, Iwata N, Kanda M, Tanaka C, Nakayama G, Sugimoto H, Koike M, Fujiwara M, Kodera Y (2016) Clinical implication of inflammation-based prognostic score in pancreatic cancer: Glasgow prognostic score is the most reliable parameter. Medicine (Baltimore) 95:e3582.  https://doi.org/10.1097/MD.0000000000003582 CrossRefGoogle Scholar
  15. 15.
    Amin S, McBride RB, Kline JK, Mitchel EB, Lucas AL, Neugut AI, Frucht H (2012) Incidence of subsequent pancreatic adenocarcinoma in patients with a history of nonpancreatic primary cancers. Cancer 118:1244–1251.  https://doi.org/10.1002/cncr.26414 CrossRefPubMedGoogle Scholar
  16. 16.
    Hackert T, Tjaden C, Muller S, Hinz U, Hartwig W, Strobel O, Fritz S, Schmied B, Buchler MW, Werner J (2012) Extrapancreatic malignancies in patients with pancreatic cancer: epidemiology and clinical consequences. Pancreas 41:212–217.  https://doi.org/10.1097/MPA.0b013e3182240602 CrossRefPubMedGoogle Scholar
  17. 17.
    Jo JH, Cho IR, Jung JH, Lee HS, Chung MJ, Bang S, Park SW, Chung JB, Song SY, Park JY (2017) Clinical characteristics of second primary pancreatic cancer. PLoS One 12:e0179784.  https://doi.org/10.1371/journal.pone.0179784 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ (2003) Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer 89:1028–1030.  https://doi.org/10.1038/sj.bjc.6601242 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bosman FT, International Agency for Research on Cancer, World Health Organization (2010) WHO classification of tumours of the digestive system. International Agency for Research on Cancer. Lyon, FranceGoogle Scholar
  20. 20.
    Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250:187–196CrossRefGoogle Scholar
  21. 21.
    Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CR, Wolfgang CL, Yeo CJ, Salvia R, Buchler M, International Study Group on Pancreatic Surgery (ISGPS) (2017) The 2016 update of the international study group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 161:584–591CrossRefGoogle Scholar
  22. 22.
    Youlden DR, Baade PD (2011) The relative risk of second primary cancers in Queensland, Australia: a retrospective cohort study. BMC Cancer 11:83.  https://doi.org/10.1186/1471-2407-11-83 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Neugut AI, Ahsan H, Robinson E (1995) Pancreas cancer as a second primary malignancy: a population-based study. Cancer 76:589–592.  https://doi.org/10.1002/1097-0142(19950815)76:4<589::aid-cncr2820760408>3.0.co;2-9 CrossRefPubMedGoogle Scholar
  24. 24.
    Rahimi E, Batra S, Thosani N, Singh H, Guha S (2016) Increased incidence of second primary pancreatic cancer in patients with prior colorectal cancer: a population-based US study. Dig Dis Sci 61:1652–1660.  https://doi.org/10.1007/s10620-016-4170-x CrossRefPubMedGoogle Scholar
  25. 25.
    Cancer Statistics in Japan (2018) https://ganjoho.jp/reg_stat/statistics/brochure/backnumber/2017_jp.html. Accessed 30 Aug 2019
  26. 26.
    Matsubayashi H, Takaori K, Morizane C, Maguchi H, Mizuma M, Takahashi H, Wada K, Hosoi H, Yachida S, Suzuki M, Usui R, Furukawa T, Furuse J, Sato T, Ueno M, Kiyozumi Y, Hijioka S, Mizuno N, Terashima T, Mizumoto M, Kodama Y, Torishima M, Kawaguchi T, Ashida R, Kitano M, Hanada K, Furukawa M, Kawabe K, Majima Y, Shimosegawa T (2017) Familial pancreatic cancer: concept, management and issues. World J Gastroenterol 23:935–948CrossRefGoogle Scholar
  27. 27.
    Bannon SA, Montiel MF, Goldstein JB et al (2018) High prevalence of hereditary cancer syndromes and outcomes in adults with early-onset pancreatic cancer. Cancer Prev Res (Phila) 11:679–686CrossRefGoogle Scholar
  28. 28.
    Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103.  https://doi.org/10.1038/bjc.2011.189 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N (2013) Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer 108:914–923.  https://doi.org/10.1038/bjc.2013.32 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bang S, Kim HS, Choo YS, Park SW, Chung JB, Song SY (2006) Differences in immune cells engaged in cell-mediated immunity after chemotherapy for far advanced pancreatic cancer. Pancreas 32:29–36.  https://doi.org/10.1097/01.mpa.0000191651.32420.41 CrossRefPubMedGoogle Scholar
  31. 31.
    Liu C, Cheng H, Luo G, Lu Y, Jin K, Guo M, Ni Q, Yu X (2017) Circulating regulatory T cell subsets predict overall survival of patients with unresectable pancreatic cancer. Int J Oncol 51:686–694.  https://doi.org/10.3892/ijo.2017.4032 CrossRefPubMedGoogle Scholar
  32. 32.
    Serrano CV Jr, de Mattos FR, Pitta FG et al (2019) Association between neutrophil-lymphocyte and platelet-lymphocyte ratios and coronary artery calcification score among asymptomatic patients: data from a cross-sectional study. Mediat Inflamm 2019:6513847CrossRefGoogle Scholar
  33. 33.
    Davis JL, Moutinho V Jr, Panageas KS, Coit DG (2016) A peripheral blood biomarker estimates probability of survival: the neutrophil-lymphocyte ratio in noncancer patients. Biomark Med 10:953–957CrossRefGoogle Scholar
  34. 34.
    Fest J, Ruiter TR, Groot Koerkamp B, Rizopoulos D, Ikram MA, van Eijck CHJ, Stricker BH (2019) The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: the Rotterdam study. Eur J Epidemiol 34:463–470CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sojun Hoshimoto
    • 1
    Email author
  • Shoichi Hishinuma
    • 1
  • Hirofumi Shirakawa
    • 1
  • Moriaki Tomikawa
    • 1
  • Iwao Ozawa
    • 1
  • Yoshiro Ogata
    • 1
  1. 1.Department of Digestive SurgeryTochigi Cancer CenterUtsunomiyaJapan

Personalised recommendations