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Influence of preoperative chemotherapy-induced leukopenia on survival in patients with esophageal squamous cell carcinoma: exploratory analysis of JCOG9907

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Abstract

Background

The relationship between chemotherapy-induced leukopenia (CIL) and survival has not been investigated in patients undergoing preoperative chemotherapy for esophageal squamous cell carcinoma (ESCC). We analyzed the association of CIL with survival outcomes using data from JCOG9907 on the efficacy of preoperative chemotherapy for stage II/III ESCC.

Methods

Preoperative chemotherapy consisted of two courses of 5-FU (800 mg/m2 days 1–5) and cisplatin (80 mg/m2 day 1) repeated every 3 weeks. Patients in the preoperative chemotherapy arm receiving at least one course of chemotherapy and undergoing subsequent surgery in JCOG9907 were divided into two subgroups: CIL ( +), those with grade 2–4 leukopenia at least once during preoperative chemotherapy; and CIL (−), those with grades 0–1. The association of CIL with overall survival (OS) and progression-free survival (PFS) was analyzed.

Results

Among 164 patients enrolled in JCOG9907, 152 patients were included in this analysis, 52 in CIL ( +) and 100 patients in CIL (−) subgroups. The 3-year OS for CIL ( +) was inferior to that for CIL (−) (48.1% vs. 73.9%); hazard ratio (HR) = 1.94 (95% CI 1.18–3.16, P < .01). For 3-year PFS, a similar tendency was observed (44.2% vs. 55.8%; HR = 1.38 (95% CI 0.88–2.17, P = .16). Multivariable analysis revealed that CIL was not an independent factor for OS (HR = 1.14, 95% CI 0.63–2.07, P = .67).

Conclusion

We showed that CIL during preoperative chemotherapy might not be a prognostic factor in patients with ESCC.

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References

  1. Fitzmaurice C, Dicker D, Pain A, et al. The Global Burden of Cancer 2013. JAMA Oncol. 2015;1(4):505–27.

    Article  PubMed  Google Scholar 

  2. Vital Statistics in Japan (Ministry of Health, Labour and Welfare) 2015.

  3. Tachimori Y, Ozawa S, Numasaki H, et al. Comprehensive registry of esophageal cancer in Japan, 2012. Esophagus. 2019;16(3):221–45.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012;19(1):68–74.

    PubMed  Google Scholar 

  5. Shitara K, Matsuo K, Takahari D, et al. Neutropaenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX. Eur J Cancer. 2009;45(10):1757–63.

    Article  CAS  PubMed  Google Scholar 

  6. Shitara K, Matsuo K, Takahari D, et al. Neutropenia as a prognostic factor in advanced gastric cancer patients undergoing second-line chemotherapy with weekly paclitaxel. Ann Oncol. 2010;21(12):2403–9.

    Article  CAS  PubMed  Google Scholar 

  7. Koutras AK, Fountzilas G, Dafni U, et al. Myelotoxicity as a prognostic factor in patients with advanced breast cancer treated with chemotherapy: a pooled analysis of two randomised trials conducted by the Hellenic cooperative oncology group. Anticancer Res. 2008;28(5b):2913–20.

    CAS  PubMed  Google Scholar 

  8. Miyoshi N, Yano M, Takachi K, et al. Myelotoxicity of preoperative chemoradiotherapy is a significant determinant of poor prognosis in patients with T4 esophageal cancer. J Surg Oncol. 2009;99(5):302–6.

    Article  CAS  PubMed  Google Scholar 

  9. Kim JJ, Park JY, Kim DY, et al. Is chemotherapy-induced neutropenia a prognostic factor in patients with ovarian cancer? Acta Obstet Gynecol Scand. 2010;89(5):623–8.

    Article  CAS  PubMed  Google Scholar 

  10. Ohira M, Kubo N, Yamashita Y, et al. Impact of chemoradiation-induced myelosuppression on prognosis of patients with locally advanced esophageal cancer after chemoradiotherapy followed by esophagectomy. Anticancer Res. 2015;35(9):4889–955.

    PubMed  Google Scholar 

  11. Trotti A, Byhardt R, Stetz J, et al. Common toxicity criteria: version 2.0. An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys. 2000;47(1):13–47.

    Article  CAS  PubMed  Google Scholar 

  12. Shitara K, Matsuo K, Oze I, et al. Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy. Cancer Chemother Pharmacol. 2011;68(2):301–7.

    Article  CAS  PubMed  Google Scholar 

  13. Bogani G, Sabatucci I, Maltese G, et al. Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in locally advanced cervical cancer. Eur J Obstet Gynecol Reprod Biol. 2017;208:41–5.

    Article  PubMed  Google Scholar 

  14. Yokota T, Ando N, Igaki H, et al. Prognostic factors in patients receiving neoadjuvant 5-fluorouracil plus cisplatin for advanced esophageal cancer (JCOG9907). Oncology. 2015;89(3):143–51.

    Article  CAS  PubMed  Google Scholar 

  15. Kurokawa Y, Shibata T, Ando N, Seki S, Mukaida H, Fukuda H. Which is the optimal response criteria for evaluating preoperative treatment in esophageal cancer: RECIST or histology? Ann Surg Oncol. 2013;20(9):3009–144.

    Article  PubMed  Google Scholar 

  16. Meredith KL, Weber JM, Turaga KK, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17(4):1159–67.

    Article  PubMed  Google Scholar 

  17. Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013;43(7):752–5.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to the members of the JCOG Data Center and JCOG Operations Office for their support in preparing data management (Ms. Aya Kimura and Ms. Naoko Murata), and oversight of the study management (Dr. Haruhiko Fukuda). JCOG9907 was supported in part by a Grant-in-Aid for Cancer Research (14S-3, 14S-4, 17S-3, 17S-5, 20S-3, 20S-6) from the Ministry of Health, Labor and Welfare of Japan and by a National Cancer Center Research and Development Fund (23-A-16, 23-A-19, 26-A-4, 29-A-3). We thank Libby Cone, MD, MA of DMC Corp. for editing drafts of this manuscript.

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Authors and Affiliations

  1. Department of Gastroenterology, Saitama Cancer Center, Komuro 780, Ina, Kitaadachi-gun, Saitama, 362-0806, Japan

    Hiroki Hara

  2. Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

    Junki Mizusawa & Kenichi Nakamura

  3. Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, Yufu, Oita, Japan

    Shuichi Hironaka

  4. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Ken Kato

  5. Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan

    Hiroyuki Daiko

  6. Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, Japan

    Tetsuya Abe

  7. International Goodwill Hospital, Yokohama, Japan

    Nobutoshi Ando

  8. Department of Surgery, Keio University School of Medicine, Tokyo, Japan

    Yuko Kitagawa

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  1. Hiroki Hara
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  7. Kenichi Nakamura
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  8. Nobutoshi Ando
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Correspondence to Hiroki Hara.

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All authors declare no conflicts of interest regarding this article.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 1964 Declaration of Helsinki and later versions.

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Hara, H., Mizusawa, J., Hironaka, S. et al. Influence of preoperative chemotherapy-induced leukopenia on survival in patients with esophageal squamous cell carcinoma: exploratory analysis of JCOG9907. Esophagus 18, 41–48 (2021). https://doi.org/10.1007/s10388-020-00752-7

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  • DOI: https://doi.org/10.1007/s10388-020-00752-7

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