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The effectiveness of adjuvant chemotherapy for Stage I pancreatic cancer based on the UICC 8th edition

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Abstract

Background

Adjuvant chemotherapy is recommended for patients with pancreatic cancer after curative resection. However, there is limited evidence regarding the efficacy and prognostic factors for adjuvant chemotherapy in patients with stage I pancreatic cancer. This study aimed to identify patients in whom chemotherapy was effective and to detect prognostic factors for stage I pancreatic cancer based on guidelines of the 8th edition of the Union for International Cancer Control (UICC).

Methods

Between 2009 and 2017, 108 patients diagnosed with stage I pancreatic cancer were enrolled in this study. They were distributed into invasion (n = 68) and non-invasion (n = 40) groups. The relationship between clinicopathological variables, including various prognostic factors, disease-free survival (DFS), and overall survival (OS), were investigated by univariate and multivariate analyses.

Results

Five-year survival in all patients with stage I pancreatic cancer was 38.9%. Adjuvant chemotherapy failed to improve DFS or OS in patients with stage I cancer (DFS, p = 0.26; OS, p = 0.30). In subgroup analysis, adjuvant chemotherapy significantly improved DFS (multivariate-adjusted hazard ratio (HR), 0.40; 95% confidence interval [CI], 0.21–0.78; p = 0.007) and OS (multivariate-adjusted HR, 0.32; 95% CI, 0.15–0.68; p = 0.003) in the invasion group than in non-invasion group. In contrast, in the non-invasion group, adjuvant chemotherapy failed to improve DFS and OS in univariate analysis (DFS, p = 0.992; OS, p = 0.808).

Conclusion

For stage I pancreatic cancer, based on guidelines of the UICC 8th edition, adjuvant chemotherapy may benefit patients with extrapancreatic invasion.

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References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29

    Article  Google Scholar 

  2. Hidalgo M (2010) Pancreatic cancer. N Engl J Med 362:1605–1617

    Article  CAS  Google Scholar 

  3. Yeo CJ, Cameron JL, Lillemoe KD et al (2002) Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 236:355–366

    Article  Google Scholar 

  4. Birkmeyer JD, Stukel TA, Siewers AE et al (2003) Surgeon volume and operative mortality in the United States. N Engl J Med 349:2117–2127

    Article  CAS  Google Scholar 

  5. Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277

    Article  CAS  Google Scholar 

  6. Oettle H, Neuhaus P, Hochhaus A et al (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310:1473–1481

    Article  CAS  Google Scholar 

  7. Ueno H, Kosuge T, Matsuyama Y et al (2009) A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer 101:908–915

    Article  CAS  Google Scholar 

  8. Ueno H, Ioka T, Ikeda M et al (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clinical Oncol : official J American Soc Clin Oncol 31:1640–1648

    Article  CAS  Google Scholar 

  9. Neoptolemos JP, Stocken DD, Bassi C et al (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081

    Article  CAS  Google Scholar 

  10. Uesaka K, Boku N, Fukutomi A et al (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). The Lancet 388:248–257

    Article  CAS  Google Scholar 

  11. Winter JM, Cameron JL, Campbell KA et al (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 10:1199–1210

    Article  Google Scholar 

  12. van Roest MH, Gouw AS, Peeters PM et al (2008) Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization. Ann Surg 248:97–103

    Article  Google Scholar 

  13. Jamieson NB, Denley SM, Logue J et al (2011) A prospective comparison of the prognostic value of tumor- and patient-related factors in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma. Ann Surg Oncol 18:2318–2328

    Article  Google Scholar 

  14. Brierley JD, Gospodarowicz MK, Wittekind C (2017) TNM classification of malignant tumours. Eighth ed, John Wiley & Sons, Inc. Oxford, UK, Hoboken, NJ

  15. Uwagawa T, Li Z, Chang Z et al (2007) Mechanisms of synthetic serine protease inhibitor (FUT-175)-mediated cell death. Cancer 109:2142–2153

    Article  CAS  Google Scholar 

  16. Uwagawa T, Chiao PJ, Gocho T et al (2009) Combination chemotherapy of nafamostat mesilate with gemcitabine for pancreatic cancer targeting NF-kappaB activation. Anticancer Res 29:3173–3178

    CAS  Google Scholar 

  17. Uwagawa T, Misawa T, Sakamoto T et al (2009) A phase I study of full-dose gemcitabine and regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer. Ann Oncol 20:239–243

    Article  CAS  Google Scholar 

  18. Uwagawa T, Misawa T, Tsutsui N et al (2013) Phase II study of gemcitabine in combination with regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer. Am J Clin Oncol 36:44–48

    Article  CAS  Google Scholar 

  19. Uwagawa T, Sakamoto T, Yasuda J et al (2021) Phase II study of adjuvant chemotherapy with gemcitabine and nafamostat mesilate for pancreatic cancer. Pancreas 50:313–316

    Article  CAS  Google Scholar 

  20. Saka B, Balci S, Basturk O et al (2016) Pancreatic ductal adenocarcinoma is spread to the peripancreatic soft tissue in the majority of resected cases, rendering the AJCC T-tage protocol (7th Edition) Edition inapplicable and insignificant a size based staging system (pT1: </=2, pT2: >2-</=4, pT3: >4 cm) 4 cm is more valid and clinically relevant. Ann Surg Oncol 23:2010–2018

    Article  Google Scholar 

  21. Allen PJ, Kuk D, Castillo CF et al (2017) Multinstitutional validation study of the American Joint Commission on Cancer (8th Edition) changes for T and N staging in patients with pancreatic adenocarcinoma. Annal Surg 265:185–91

    Article  Google Scholar 

  22. Japanese Gastric Cancer Society (2018) Japanese Gastric Cancer Society, 5th edition. Guidelines for the Treatment of Gastric Cancer

  23. Watanabe T, Muro K, Ajioka Y et al (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23:1–34

    Article  Google Scholar 

  24. Hartwig W, Strobel O, Hinz U et al (2013) CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol 20:2188–2196

    Article  Google Scholar 

  25. Sohn HJ, Kim H, Kim SJ et al (2022) Oncologic outcomes according to the location and status of resection margin in pancreas head cancer: role of radiation therapy in R1 resection. Ann Surg Treat Res 102:10–19

    Article  CAS  Google Scholar 

  26. Haruki K, Shiba H, Shirai Y et al (2016) The C-reactive protein to albumin ratio predicts long-term outcomes in patients with pancreatic cancer after pancreatic resection. World J Surg 40:2254–2260

    Article  Google Scholar 

  27. La Torre M, Nigri G, Cavallini M et al (2012) The Glasgow prognostic score as a predictor of survival in patients with potentially resectable pancreatic adenocarcinoma. Ann Surg Oncol 19:2917–2923

    Article  Google Scholar 

  28. Heikkila K, Ebrahim S, Lawlor DA (2007) A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epid Commu Health 61:824–833

    Article  Google Scholar 

  29. Mantovani A, Allavena P, Sica A et al (2008) Cancer-related inflammation. Nature 454:436–444

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by JSPS KAKENHI Grant Number JP21K08805 and by a research grant from the Uehara Memorial Foundation.

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Authors and Affiliations

  1. Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Ryoga Hamura, Koichiro Haruki, Yuki Fujiwara, Masashi Tsunematsu, Yoshihiro Shirai, Kenei Furukawa, Shinji Onda, Takeshi Gocho, Hiroaki Shiba, Tadashi Uwagawa & Toru Ikegami

  2. Department of Surgery, The Jikei University Katsushika Medical Center, Tokyo, Japan

    Teruyuki Usuba

  3. Department of Surgery, The Jikei University Kashiwa Hospital, Chiba, Japan

    Shuichi Fujioka

  4. Department of Surgery, The Jikei University Daisan Hospital, Tokyo, Japan

    Tomoyoshi Okamoto

Authors
  1. Ryoga Hamura
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Contributions

Each of the author have participated sufficiently in the work to take public responsibility for appropriate portions of the content. Study concept and design: Ryoga Hamura, Yuki Fujiwara, Koichiro Haruki. Acquisition of data: Ryoga Hamura, Yoshihiro Shirai, Tadashi Uwagawa, Teruyuki Usuba, Shuichi Fujioka, Tomoyoshi Okamoto. Analysis and interpretation of data: Ryoga Hamura, Yuki Fujiwara. Drafting of manuscript: Ryoga Hamura. Critical revision: Yuki Fujiwara, Koichiro Haruki, Hiroaki Shiba, Toru Ikegami.

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Correspondence to Koichiro Haruki.

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Hamura, R., Haruki, K., Fujiwara, Y. et al. The effectiveness of adjuvant chemotherapy for Stage I pancreatic cancer based on the UICC 8th edition. Langenbecks Arch Surg 407, 3437–3446 (2022). https://doi.org/10.1007/s00423-022-02686-3

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