Abstract
Background
Definitive chemoradiotherapy (CRT), used for treatment of patients with an initial diagnosis of unresectable locally advanced esophageal cancer, has led to unsatisfactory long-term prognosis. Moreover, CRT can lead to esophageal fistula, perforation, and strictures. Therefore, strong induction chemotherapeutic treatments are necessary to reduce the tumor volume for subsequent radical esophagectomy. This study aimed to determine the oncological utility of docetaxel plus cisplatin and 5-fluorouracil (DCF) and the technical feasibility of subsequent esophagectomy for locally advanced esophageal cancer.
Methods
Eighty-seven patients with clinical borderline unresectable T3 and T4 esophageal squamous cell carcinoma without distant metastases were included in this study. There were 44 patients in primary DCF group and 43 patients in definitive CRT group, and perioperative and long-term oncological outcomes were compared between the two groups.
Results
Twenty-two patients (50%) achieved R0 resection in the DCF group. Albeit not significant, the rate of curative treatment was higher in the DCF group than the definitive CRT group (p = 0.099). The overall survival (OS) and progression-free survival (PFS) were better with DCF than with definitive CRT (median OS, 29 vs. 17 months, p = 0.206; median PFS, 10 vs. 6 months, p = 0.020). Specifically, the OS of patients with a Charlson score of less than 3 among the DCF-treated patients tended to be better than those among the definitive CRT-treated patients.
Conclusion
DCF and subsequent esophagectomy achieved R0 resection in 50% of the patients and was associated with better long-term oncological outcomes in patients with initially unresectable esophageal cancer if their systemic status is acceptable.
Similar content being viewed by others
References
Rustgi AK, El-Serag HB (2014) Esophageal carcinoma. N Engl J Med 371:2499–2509
Gamliel Z, Krasna MJ (2005) Multimodality treatment of esophageal cancer. Surg Clin North Am 85:621–630
Ohtsu A, Boku N, Muro K et al (1999) Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 17:2915–2921
Matsubara T, Ueda M, Kokudo N et al (2001) Role of esophagectomy in treatment of esophageal carcinoma with clinical evidence of adjacent organ invasion. World J Surg 25:279–284. https://doi.org/10.1007/s002680020060
Markar SR, Karthikesalingam A, Penna M et al (2013) Assessment of short-term clinical outcomes following salvage esophagectomy for the treatment of esophageal malignancy: systematic review and pooled analysis. Ann Surg Oncol 21:922–931
Tachimori Y, Kanamori N, Uemura N et al (2009) Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 137:49–54
Tsushima T, Mizusawa J, Sudo K et al (2016) Risk factors for esophageal fistula associated with chemoradiotherapy for locally advanced unresectable esophageal cancer. Medicine 95:e3699
Okuno T, Wakabayashi M, Kato K et al (2017) Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303). Int J Clin Oncol 22:1042–1049
Ishikura S, Nihei K, Ohtsu A et al (2003) Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol 21:2697–2702
Shimoji H, Karimata H, Nagahama M et al (2013) Induction chemotherapy or chemoradiotherapy followed by radical esophagectomy for T4 esophageal cancer: results of a prospective cohort study. World J Surg 37:2180–2188. https://doi.org/10.1007/s00268-013-2074-x
Miyata H, Yamasaki M, Kurokawa Y et al (2012) Clinical relevance of induction triplet chemotherapy for esophageal cancer invading adjacent organs. J Surg Oncol 106:441–447
Yokota T, Kato K, Hamamoto Y et al (2016) Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer. Br J Cancer 115:1328–1334
Japanese Classification of Esophageal Cancer (2016) 11th Edition: part I. Esophagus 14:1–36
Quan H, Li B, Couris CM et al (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173:676–682
Sobin L, Gospodarowicz MWC (eds) (2009) TNM classification of malignant tumours, 7th edn. Wiley-Liss, New York
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247
Thompson WM, Halvorsen RA, Foster WL Jr et al (1983) Computed tomography for staging esophageal and gastroesophageal cancer: reevaluation. AJR Am J Roentgenol 141:951–958
Picus D, Balfe DM, Koehler RE et al (1983) Computed tomography in the staging of esophageal carcinoma. Radiology 146:433–438
Yokota T, Hatooka S, Ura T et al (2011) Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer. Anticancer Res 31:3535–3541
Kaburagi T, Takeuchi H, Kawakubo H et al (2013) Clinical utility of a novel hybrid position combining the left lateral decubitus and prone positions during thoracoscopic esophagectomy. World J Surg 38:410–418. https://doi.org/10.1007/s00268-013-2258-4
Matsuda S, Takeuchi H, Kawakubo H et al (2016) Clinical outcome of transthoracic esophagectomy with thoracic duct resection. Medicine 95:e3839
Dindo D, Demartines N, Clavien P-A (2004) Classification of surgical complications. Ann Surg 240:205–213
Takeuchi H, Saikawa Y, Oyama T et al (2009) Factors influencing the long-term survival in patients with esophageal cancer who underwent esophagectomy after chemoradiotherapy. World J Surg 34:277–284. https://doi.org/10.1007/s00268-009-0331-9
Poon LC, Wright D, Rolnik DL et al (2017) Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history. Am J Obstet Gynecol 217:585e1–585e5
Satake H, Tahara M, Mochizuki S et al (2016) A prospective, multicenter phase I/II study of induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by chemoradiotherapy in patients with unresectable locally advanced esophageal carcinoma. Cancer Chemother Pharmacol 78:91–99
Hara H, Tahara M, Daiko H et al (2013) Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma. Cancer Science 104:1455–1460
Makino T, Yamasaki M, Miyazaki Y et al (2017) Utility of initial induction chemotherapy with 5-fluorouracil, cisplatin, and docetaxel (DCF) for T4 esophageal cancer: a propensity score-matched analysis. Dis Esophagus 31:dox130
Takeuchi H, Miyata H, Gotoh M et al (2014) A risk model for esophagectomy using data of 5354 patients included in a Japanese nationwide web-based database. Ann Surg 260:259–266
Takeuchi M, Takeuchi H, Kawakubo H et al (2018) Perioperative risk calculator predicts long-term oncologic outcome for patients with esophageal carcinoma. Ann Surg Oncol 25:837–843
Takeuchi M, Kawakubo H, Mayanagi S et al (2018) Postoperative pneumonia is associated with long-term oncologic outcomes of definitive chemoradiotherapy followed by salvage esophagectomy for esophageal cancer. J Gastrointest Surg 22:1881–1889
Kataoka K, Takeuchi H, Mizusawa J et al (2017) Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer. Ann Surg 265:1152–1157
Yokota T, Yasuda T, Kato H et al (2018) Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer. Int J Clin Oncol 23:73–80
Hamamoto Y, Nojima M, Aoki Y et al (2017) Inter-evaluator heterogeneity of clinical diagnosis for locally advanced esophageal squamous cell carcinoma. Esophagus 14:324–332
Acknowledgements
The authors thank Kumiko Motooka in the Department of Surgery at Keio University School of Medicine for her help in the preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Yuko Kitagawa have personal fees from sanofi K.K, personal fees from ETHICON PART OF JOHNSON AND JOHNSON FAMILY OF COMPANIES, personal fees from Medtronic Japan Co., Ltd., grants from KYOWA HAKKO KIRIN CO., LTD, outside the submitted work.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplemental Figure 1
(a) Kaplan–Meier curves for overall survival in patients who underwent R1/R2 resection. (b) Kaplan–Meier curves for progression-free survival in patients who underwent R1/R2 resection. (c) Kaplan–Meier curves for overall survival in patients who underwent palliative treatment. (d) Kaplan–Meier curves for progressive-free survival in patients who underwent palliative treatment. Red and blue lines indicate the DCF and definitive CRT groups, respectively. (EPS 377 kb)
Rights and permissions
About this article
Cite this article
Takeuchi, M., Kawakubo, H., Mayanagi, S. et al. The Benefits of Docetaxel Plus Cisplatin and 5-Fluorouracil Induction Therapy in Conversion to Curative Treatment for Locally Advanced Esophageal Squamous Cell Carcinoma. World J Surg 43, 2006–2015 (2019). https://doi.org/10.1007/s00268-019-05000-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-019-05000-3