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Prognostic Impact of Post-operative Infectious Complications in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: Post Hoc Analysis of a Randomized Controlled Trial, JCOG0501

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Abstract

Purpose

Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer.

Methods

The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses.

Results

There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655–2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226–1.456)).

Conclusion

This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected.

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Data Availability

The datasets generated during and analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. GLOBOCAN 2020: international agency for research on cancer. Available from: https://gco.iarc.fr/today/home. Accessed 20 Mar 2023.

  2. Tokunaga M, Kurokawa Y, Machida R, Sato Y, Takiguchi S, Doki Y, et al. Impact of postoperative complications on survival outcomes in patients with gastric cancer: exploratory analysis of a randomized controlled JCOG1001 trial. Gastric Cancer. 2021;24(1):214–23.

    Article  PubMed  Google Scholar 

  3. Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M. Poor survival rate in patients with postoperative intra-abdominal infectious complications following curative gastrectomy for gastric cancer. Ann Surg Oncol. 2013;20(5):1575–83.

    Article  PubMed  Google Scholar 

  4. Tsujimoto H, Ichikura T, Ono S, Sugasawa H, Hiraki S, Sakamoto N, et al. Impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Ann Surg Oncol. 2019;16(2):311–8.

    Article  Google Scholar 

  5. Tu RH, Lin JX, Li P, Xie JW, Wang JB, Lu J, et al. Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer. Cancer Med. 2017;6(12):2757–65.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kubota T, Hiki N, Sano T, Nomura S, Nunobe S, Kumagai K, et al. Prognostic significance of complications after curative surgery for gastric cancer. Ann Surg Oncol. 2014;21(3):891–8.

    Article  PubMed  Google Scholar 

  7. Pucher PH, Aggarwal R, Qurashi M, Darzi A. Meta-analysis of the effect of postoperative in-hospital morbidity on long-term patient survival. Br J Surg. 2014;101(12):1499–508.

    Article  CAS  PubMed  Google Scholar 

  8. Shimada H, Fukagawa T, Haga Y, Oba K. Does postoperative morbidity worsen the oncological outcome after radical surgery for gastrointestinal cancers? A systematic review of the literature. Ann Gastroenterol Surg. 2017;1(1):11–23.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sierzega M, Kolodziejczyk P, Kulig J, Polish Gastric Cancer Study G. Impact of anastomotic leakage on long-term survival after total gastrectomy for carcinoma of the stomach. Br J Surg. 2010;97(7):1035–42.

    Article  Google Scholar 

  10. Fujiya K, Tokunaga M, Mori K, Makuuchi R, Tanizawa Y, Bando E, et al. Long-term survival in patients with postoperative intra-abdominal infectious complications after curative gastrectomy for gastric cancer: a propensity score matching analysis. Ann Surg Oncol. 2016;23:S809–16.

    Article  Google Scholar 

  11. Andalib A, Ramana-Kumar AV, Bartlett G, Franco EL, Ferri LE. Influence of postoperative infectious complications on long-term survival of lung cancer patients: a population-based cohort study. J Thorac Oncol. 2018;8(5):554–61.

    Article  Google Scholar 

  12. Fernandez-Moreno MC, Dorcaratto D, Garces-Albir M, Munoz E, Arvizu R, Ortega J, et al. Impact of type and severity of postoperative complications on long-term outcomes after colorectal liver metastases resection. J Surg Oncol. 2020;122(2):212–25.

    Article  PubMed  Google Scholar 

  13. Bundred JR, Hollis AC, Evans R, Hodson J, Whiting JL, Griffiths EA. Impact of postoperative complications on survival after oesophagectomy for oesophageal cancer. BJS Open. 2020;4(3):405–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mrak K, Eberl T, Laske A, Jagoditsch M, Fritz J, Tschmelitsch J. Impact of postoperative complications on long-term survival after resection for rectal cancer. Dis Colon Rectum. 2013;56(1):20–8.

    Article  PubMed  Google Scholar 

  15. Jin LX, Sanford DE, Squires MH III, Moses LE, Yan Y, Poultsides GA, et al. Interaction of postoperative morbidity and receipt of adjuvant therapy on long-term survival after resection for gastric adenocarcinoma: results from the U.S. gastric cancer collaborative. Ann Surg Oncol. 2016;23(8):2398–408.

    Article  PubMed  Google Scholar 

  16. Cavassani KA, Carson WFt, Moreira AP, Wen H, Schaller MA, Ishii M, et al. The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. Blood. 2010;115(22):4403–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Eto K, Hiki N, Kumagai K, Shoji Y, Tsuda Y, Kano Y, et al. Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with postoperative complications. Gastric Cancer. 2018;21(4):703–9.

    Article  CAS  PubMed  Google Scholar 

  18. Hayashi M, Yoshikawa T, Yura M, Otsuki S, Yamagata Y, Morita S, et al. Does neoadjuvant chemotherapy cancel out the negative survival impact induced by surgical complications after gastrectomy? Gastric Cancer. 2019;22(6):1274–84.

    Article  PubMed  Google Scholar 

  19. Kano K, Aoyama T, Yoshikawa T, Maezawa Y, Nakajima T, Hayashi T, et al. The negative survival impact of infectious complications after surgery is canceled out by the response of neoadjuvant chemotherapy in patients with esophageal cancer. Ann Surg Oncol. 2018;25(7):2034–43.

    Article  PubMed  Google Scholar 

  20. Vicente D, Ikoma N, Chiang YJ, Fournier K, Tzeng CD, Song S, et al. (2018) Preoperative therapy for gastric adenocarcinoma is protective for poor oncologic outcomes in patients with complications after gastrectomy. Ann Surg Oncol. 2018;25(9):2720–30.

    Article  PubMed  Google Scholar 

  21. Iwasaki Y, Terashima M, Mizusawa J, Katayama H, Nakamura K, Katai H, et al. Gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer (JCOG0501): an open-label, phase 3, randomized controlled trial. Gastric Cancer. 2021;24(2):492–502.

    Article  CAS  PubMed  Google Scholar 

  22. Japanese Gastric Cancer A. Japanese classification of gastric carcinoma – 2nd English edition. Gastric Cancer. 1998;1(1):10–24.

    Article  Google Scholar 

  23. Common terminology criteria for adverse events v3.0 (CTCAE) [Internet]. National Cancer Institute. 2006. Available from: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_archive. Accessed 20 Mar 2023.

  24. Coccolini F, Nardi M, Montori G, Ceresoli M, Celotti A, Cascinu S, et al. Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. meta-analysis of randomized trials. Int J Surg. 2018;51:120–7.

    Article  PubMed  Google Scholar 

  25. Germano G, Allavena P, Mantovani A. Cytokines as a key component of cancer-related inflammation. Cytokine. 2008;43(3):374–9.

    Article  CAS  PubMed  Google Scholar 

  26. Goldfarb Y, Sorski L, Benish M, Levi B, Melamed R, Ben-Eliyahu S. Improving postoperative immune status and resistance to cancer metastasis: a combined perioperative approach of immunostimulation and prevention of excessive surgical stress responses. Ann Surg. 2011;253(4):798–810.

    Article  PubMed  Google Scholar 

  27. Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu Y, Zhang KC, Huang XH, Xi HQ, Gao YH, Liang WQ, et al. Timing of surgery after neoadjuvant chemotherapy for gastric cancer: impact on outcomes. World J Gastroenterol. 2018;24(2):257–65.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kang YK, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, et al. PRODIGY: a phase III study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer. J Clin Oncol. 2021;39:11.

    Article  Google Scholar 

  30. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):10.

    Article  Google Scholar 

  31. Martin AN, Das D, Turrentine FE, Bauer TW, Adams RB, Zaydfudim VM. Morbidity and mortality after gastrectomy: identification of modifiable risk factors. J Gastrointest Surg. 2016;20(9):1554–6.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The study was supported in part by the National Cancer Center Research and Development Funds (23-A-19, 26-A-4, 29-A-3, 2020-J-3, 2023-J-03) and a Grant-in-Aid for Clinical Cancer Research (H19-15, H22-23, H22-27) from the Ministry of Health, Labor, and Welfare of Japan.

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Authors and Affiliations

  1. Department of Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan

    Masato Hayashi

  2. Department of Gastric Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Takaki Yoshikawa

  3. JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

    Junki Mizusawa

  4. Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan

    Shinji Hato

  5. Department of Surgery, IMS Tokyo Katsushika General Hospital, Tokyo, Japan

    Yoshiaki Iwasaki

  6. Department of Surgery, Yodogawa Christian Hospital, Osaka, Japan

    Mitsuru Sasako

  7. Department of Surgery, Nagaoka Chuo General Hospital, Niigata, Japan

    Yasuyuki Kawachi

  8. Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan

    Hiroyasu Iishi

  9. Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan

    Yasuhiro Choda

  10. Department of Medical Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Narikazu Boku

  11. Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan

    Masanori Terashima

  12. Department of Gastroenterology, Itami City Hospital, Itami, Japan

    Hiroyasu Iishi

Authors
  1. Masato Hayashi
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Contributions

MH, TY, MS, NB, and MT contributed to conceptualization, methodology, writing—original draft, and writing—review and editing. JM contributed to formal analysis, investigation, resources, data curation, and writing—review and editing. SH, YK, YI, HI, and YC contributed to resources, data curation, and writing—review and editing.

Corresponding author

Correspondence to Takaki Yoshikawa.

Ethics declarations

Ethical Approval

The study protocol of JCOG0501 was approved by the JCOG Protocol Review Committee and the institutional review board of each participating hospital before the initiation of JCOG0501, and was performed in accordance with the international ethical recommendations stated in the Declaration of Helsinki and the Japanese Ethical Guidelines for Clinical Research. Informed consent including the secondary use of the collected data was obtained from the patients before enrollment. JCOG0501 was registered with UMIN-CTR, number C000000279.

Consent to Participate

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

Competing Interests

TY reports personal fees from MSD, BMS, Ono, Taiho, Eli Lilly, Chugai, Pfizer, Nihon Kayaku, TERUMO, Covidien, and Johnson & Johnson outside the submitted work. JM reports personal fees from Chugai Pharmaceutical and Taiho Pharmaceutical outside the submitted work, and his spouse is an employee of Pfizer. MS reports personal fees from Taiho Pharmaceutical during the study period. YC reports lecture fees from Ono Pharmaceutical and Bristol Myers Squibb Company. NB received a research grant from Ono and Takeda and honorarium from Taiho, Ono, Daiichi-Sankyo, and Bristol-Myers Squibb outside the submitted work. MT reports personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Yakult Honsha, Takeda Pharmaceutical, Eli Lilly Japan KK, Pfizer Pharmaceutical Japan, Daiichi Sankyo, Johnson and Johnson KK, Medtronic Japan, Intuitive Japan, and Olympus outside the submitted work. All other authors declare that there is no conflict of interest directly relevant to the content of this manuscript.

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Hayashi, M., Yoshikawa, T., Mizusawa, J. et al. Prognostic Impact of Post-operative Infectious Complications in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: Post Hoc Analysis of a Randomized Controlled Trial, JCOG0501. J Gastrointest Canc (2024). https://doi.org/10.1007/s12029-024-01061-3

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