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Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact

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Abstract

Purpose

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy.

Methods

Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses.

Results

Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis.

Conclusions

Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

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References

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma. Version 2. 2016 ed 2016. Available from http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed January 14, 2016.

  2. Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, Wang H, Abbruzzese J, Pisters PW, Vauthey JN, Charnsangavej C, Tamm E, Crane CH, Balachandran A (2012) Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 118:5749–5756. doi:10.1002/cncr.27636

    Article  PubMed  Google Scholar 

  3. Tzeng CW, Balachandran A, Ahmad M, Lee JE, Krishnan S, Wang H, Crane CH, Wolff RA, Varadhachary GR, Pisters PW, Aloia TA, Vauthey JN, Fleming JB, Katz MH (2014) Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford) 16:430–438. doi:10.1111/hpb.12154

    Article  Google Scholar 

  4. Boone BA, Steve J, Zenati MS, Hogg ME, Singhi AD, Bartlett DL, Zureikat AH, Bahary N, Zeh HJ 3rd (2014) Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol 21:4351–4358. doi:10.1245/s10434-014-3842-z

    Article  PubMed  Google Scholar 

  5. Sho M, Akahori T, Tanaka T, Kinoshita S, Nagai M, Tamamoto T, Ohbayashi C, Hasegawa M, Kichikawa K, Nakajima Y (2015) Importance of resectability status in neoadjuvant treatment for pancreatic cancer. J Hepatobiliary Pancreat Sci 22:563–570. doi:10.1002/jhbp.258

    Article  PubMed  Google Scholar 

  6. Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261:12–17. doi:10.1097/SLA.0000000000000867

    Article  PubMed  PubMed Central  Google Scholar 

  7. Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Ellison EC, Bloomston M, Bekaii-Saab T (2015) Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol 22:1153–1159. doi:10.1245/s10434-014-4225-1

    Article  PubMed  Google Scholar 

  8. Fujii T, Yamada S, Murotani K, Kanda M, Sugimoto H, Nakao A, Kodera Y (2015) Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment. Medicine (Baltimore) 94:e1647. doi:10.1097/MD.0000000000001647

    Article  CAS  Google Scholar 

  9. Williams JL, Kadera BE, Nguyen AH, Muthusamy VR, Wainberg ZA, Hines OJ, Reber HA, Donahue TR (2016) CA19-9 Normalization during pre-operative treatment predicts longer survival for patients with locally progressed pancreatic cancer. J Gastrointest Surg 20:1331–1342. doi:10.1007/s11605-016-3149-4

    Article  PubMed  Google Scholar 

  10. 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. doi:10.1007/s00534-013-0595-1

    Article  PubMed  Google Scholar 

  11. Murakami Y, Satoi S, Sho M, Motoi F, Matsumoto I, Kawai M, Honda G, Uemura K, Yanagimoto H, Shinzeki M, Kurata M, Kinoshita S, Yamaue H, Unno M (2015) National comprehensive cancer network resectability status for pancreatic carcinoma predicts overall survival. World J Surg 39:2306–2314. doi:10.1007/s00268-015-3096-3

    Article  PubMed  Google Scholar 

  12. Hirano S, Kondo S, Hara T, Ambo Y, Tanaka E, Shichinohe T, Suzuki O, Hazama K (2007) Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg 246:46–51. doi:10.1097/01.sla.0000258608.52615.5a

    Article  PubMed  PubMed Central  Google Scholar 

  13. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Nakagawa N, Sueda T (2013) Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma. J Surg Oncol 107:414–421. doi:10.1002/jso.23229

    Article  PubMed  Google Scholar 

  14. Murakami Y, Satoi S, Motoi F, Sho M, Kawai M, Matsumoto I, Honda G; Multicentre Study Group of Pancreatobiliary Surgery (MSG-PBS) (2015) Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma. Br J Surg 102:837–846. doi:10.1002/bjs.9799

    Article  CAS  PubMed  Google Scholar 

  15. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakagawa N, Ohge H, Sueda T (2008) Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 195:757–762. doi:10.1016/j.amjsurg.2007.04.018

    Article  CAS  PubMed  Google Scholar 

  16. Murakami Y, Uemura K, Hashimoto Y, Kondo N, Nakagawa N, Takahashi S, Shintakuya R, Sueda T (2016) Survival effects of adjuvant gemcitabine plus S-1 chemotherapy on pancreatic carcinoma stratified by preoperative resectablity status. J Surg Oncol 113:405–412. doi:10.1002/jso.24156

    Article  CAS  PubMed  Google Scholar 

  17. Kawa S, Oguchi H, Kobayashi T, Tokoo M, Furuta S, Kanai M, Homma T (1991) Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype. Br J Cancer 64:899–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2010) Internatinal Union Against Cancer (UICC): TNM Classification of Malignant Tumours, 7th edn. Wiley-Blackwell, New York

    Google Scholar 

  19. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  CAS  Google Scholar 

  20. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications. A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  21. Magnani JL, Steplewski Z, Koprowski H, Ginsburg V (1983) Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res 43:5489–5492

    CAS  PubMed  Google Scholar 

  22. Tempero MA, Uchida E, Takasaki H, Burnett DA, Steplewski Z, Pour PM (1987) Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer. Cancer Res 47:5501–5503

    CAS  PubMed  Google Scholar 

  23. Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, Konski A, Benson AB 3rd, MacDonald J, Willett CG (2008) Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 26:5918–5922. doi:10.1200/JCO.2008.18.6288

    Article  PubMed  PubMed Central  Google Scholar 

  24. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H (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  PubMed  Google Scholar 

  25. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW; European Study Group for Pancreatic Cancer (2010) European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine followed pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081. doi:10.1001/jama.2010.1275

    Article  CAS  PubMed  Google Scholar 

  26. 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) JASPAC 01 Study Group. 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. doi:10.1016/S0140-6736(16)30583-9

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Naru Kondo, Naoya Nakagawa, Kenjiro Okada, Shinya Takahashi & Taijiro Sueda

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  1. Yoshiaki Murakami
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  2. Kenichiro Uemura
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  3. Takeshi Sudo
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  4. Yasushi Hashimoto
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  5. Naru Kondo
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  6. Naoya Nakagawa
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  7. Kenjiro Okada
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  8. Shinya Takahashi
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  9. Taijiro Sueda
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Correspondence to Yoshiaki Murakami.

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There are no funding sources in this study.

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

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Murakami, Y., Uemura, K., Sudo, T. et al. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol 79, 801–811 (2017). https://doi.org/10.1007/s00280-017-3281-1

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  • DOI: https://doi.org/10.1007/s00280-017-3281-1

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