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Effectiveness of Adjuvant Therapy in Patients with Pancreatic Cancer Who Underwent Neoadjuvant Therapy

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Neoadjuvant therapy (NAT) is used to treat not only advanced pancreatic cancer but also resectable lesions. The present study investigated the effectiveness of postoperative adjuvant chemotherapy for patients with pancreatic cancer who underwent surgical resection after NAT.

Methods

Patients who underwent macroscopically curative resection after NAT for pancreatic cancer were enrolled. Adjuvant chemotherapy was defined as at least 1 cycle of planned chemotherapy within 3 months after the date of surgery and included S-1, gemcitabine, or both. We retrospectively examined the effect of adjuvant chemotherapy on overall survival (OS) and recurrence-free survival (RFS) as a function of patients’ clinicopathological factors.

Results

Ninety-seven patients were included in the study, of which 68 (70.1%) underwent adjuvant chemotherapy. Administration of adjuvant chemotherapy was significantly associated with prolonged OS and RFS in patients whose elevated levels of carbohydrate antigen 19-9 or duke pancreatic monoclonal antigen type-2 did not normalize after NAT. In patients with pathological lymph node metastasis, the administration of adjuvant chemotherapy was significantly associated with longer OS but did not improve PFS.

Conclusions

Postoperative adjuvant chemotherapy was associated with prolonged postoperative survival in patients with pancreatic cancer who did not sufficiently respond to NAT as judged by tumor marker expression.

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References

  1. Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1–7.

    Article  CAS  Google Scholar 

  2. Ueno H, Kosuge T, Matsuyama Y, et al. 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. 2009;101:908–15.

    Article  CAS  Google Scholar 

  3. 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 

  4. 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 

  5. Neoptolemos JP, Palmer DH, Ghaneh P, et al. 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. 2017;389:1011–24.

    Article  CAS  Google Scholar 

  6. 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 

  7. Altman AM, Wirth K, Marmor S, et al. Completion of adjuvant chemotherapy after upfront surgical resection for pancreatic cancer is uncommon yet associated with improved survival. Ann Surg Oncol. 2019;26:4108–16.

    Article  Google Scholar 

  8. Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.

    Article  Google Scholar 

  9. Rose JB, Rocha FG, Alseidi A, et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol. 2014;21:1530–7.

    Article  Google Scholar 

  10. Kurahara H, Shinchi H, Ohtsuka T, et al. Significance of neoadjuvant therapy for borderline resectable pancreatic cancer: a multicenter retrospective study.Langenbecks Arch Surg. 2019;404:167–74.

    Article  Google Scholar 

  11. Nagakawa Y, Sahara Y, Hosokawa Y, et al. Clinical impact of neoadjuvant chemotherapy and chemoradiotherapy in borderline resectable pancreatic cancer: analysis of 884 patients at facilities specializing in pancreatic surgery.Ann Surg Oncol. 2019;26:1629–36.

    Article  Google Scholar 

  12. Eguchi H, Takeda Y, Takahashi H, et al. A Prospective, open-label, multicenter phase 2 trial of neoadjuvant therapy using full-dose gemcitabine and S-1 concurrent with radiation for resectable pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2019;26:4498–505.

    Article  Google Scholar 

  13. Motoi F, Kosuge T, Ueno H, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol. 2019;49:190–4.

    Article  Google Scholar 

  14. Barbour AP, Samra JS, Haghighi KS, et al. The AGITG GAP Study: A phase II study of perioperative gemcitabine and nab-paclitaxel for resectable pancreas cancer. Ann Surg Oncol. 2020;27:2506–15.

    Article  Google Scholar 

  15. Katz MH, Pisters PW, Lee JE, Fleming JB. Borderline resectable pancreatic cancer: what have we learned and where do we go from here? Ann Surg Oncol. 2011;18:608–10.

    Article  Google Scholar 

  16. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19–9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol. 2012;3:105–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Paniccia A, Hosokawa P, Henderson W, et al. Characteristics of 10-year survivors of pancreatic ductal adenocarcinoma. JAMA Surg. 2015;150:701–10.

    Article  Google Scholar 

  18. Qiu M, Qiu H, Jin Y, et al. Pathologic diagnosis of pancreatic adenocarcinoma in the United States: Its status and prognostic value. J Cancer. 2016;7:694–701.

    Article  CAS  Google Scholar 

  19. Kurahara H, Maemura K, Mataki Y, et al. A therapeutic strategy for resectable pancreatic cancer based on risk factors of early recurrence. Pancreas. 2018;47:753–8.

    Article  Google Scholar 

  20. Kurahara H, Maemura K, Mataki Y, et al. Clinical significance of serum carbohydrate antigen 19.9 and duke pancreatic monoclonal antigen type 2 for the prediction of hematogenous metastases in patients with pancreatic ducal adenocarcinoma. Pancreatology. 2016;16:1051–6.

    Article  CAS  Google Scholar 

  21. Sunagawa Y, Yamada S, Sato Y, et al. Novel prognostic implications of DUPAN-2 in the era of initial systemic therapy for pancreatic cancer. Ann Surg Oncol. 2020;27:2081–9.

    Article  Google Scholar 

  22. Aoki S, Motoi F, Murakami Y, et al. Decreased serum carbohydrate antigen 19–9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients. BMC Cancer. 2019;19:252.

    Article  Google Scholar 

  23. Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma version NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017;15:1028–61.

    Article  Google Scholar 

  24. Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC Cancer staging manual: pancreas and hepatobiliary cancers. Ann Surg Oncol. 2018;25:845–7.

    Article  Google Scholar 

  25. Shinchi H, Maemura K, Mataki Y, et al. A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer. J Hepatobiliary Pancreat Sci. 2012;19:152–8.

    Article  Google Scholar 

  26. Motoi F, Ishida K, Fujishima F, et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial. Ann Surg Oncol. 2013;20:3794–801.

    Article  Google Scholar 

  27. Park JK, Paik WH, Ryu JK, et al. Clinical significance and revisiting the meaning of CA 19–9 blood level before and after the treatment of pancreatic ductal adenocarcinoma: analysis of 1,446 patients from the pancreatic cancer cohort in a single institution. PLoS One. 2013;8:e78977.

    Article  CAS  Google Scholar 

  28. Kawa S, Tokoo M, Oguchi H, et al. Epitope analysis of SPan-1 and DUPAN-2 using synthesized glycoconjugates sialyllact-N-fucopentaose II and sialyllact-N-tetraose. Pancreas. 1994;9:692–7.

    Article  CAS  Google Scholar 

  29. van Roessel S, van Veldhuisen E, Klompmaker S, et al. Evaluation of adjuvant chemotherapy in patients with resected pancreatic cancer after neoadjuvant FOLFIRINOX treatment. JAMA Oncol. 2020. https://doi.org/10.1001/jamaoncol.2020.3537.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

This study was funded by a Grants-in-Aid for Scientific Research (18K08626) from the Japan Society for the Promotion of Science, which is under the direction of the Ministry of Health, Labor, and Welfare, Japan.

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Authors and Affiliations

  1. Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan

    Hiroshi Kurahara MD, PhD, Yuko Mataki MD, PhD, Tetsuya Idichi MD, PhD, Satoshi Iino MD, PhD, Yota Kawasaki MD, PhD, Takaaki Arigami MD, PhD, Shinichiro Mori MD, PhD, Ken Sasaki MD, PhD & Takao Ohtsuka MD, PhD

  2. Health Sciences, Kagoshima University, Kagoshima, Japan

    Hiroyuki Shinchi MD, PhD

Authors
  1. Hiroshi Kurahara MD, PhD
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  2. Yuko Mataki MD, PhD
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  3. Tetsuya Idichi MD, PhD
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  9. Hiroyuki Shinchi MD, PhD
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  10. Takao Ohtsuka MD, PhD
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Correspondence to Hiroshi Kurahara MD, PhD.

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Kurahara, H., Mataki, Y., Idichi, T. et al. Effectiveness of Adjuvant Therapy in Patients with Pancreatic Cancer Who Underwent Neoadjuvant Therapy. Ann Surg Oncol 28, 6238–6245 (2021). https://doi.org/10.1245/s10434-021-09712-6

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  • DOI: https://doi.org/10.1245/s10434-021-09712-6

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