Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: A nationwide study

Eur J Cancer. 2018 Mar:91:76-85. doi: 10.1016/j.ejca.2017.12.009. Epub 2018 Jan 30.

Abstract

Introduction: The optimal time between end of neoadjuvant chemoradiotherapy (nCRT) and oesophagectomy is unknown. The aim of this study was to assess the association between this interval and pathologic complete response rate (pCR), morbidity and 30-day/in-hospital mortality.

Methods: Patients with oesophageal cancer treated with nCRT and surgery between 2011 and 2016 were selected from a national database: the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The interval between end of nCRT and surgery was divided into six periods: 0-5 weeks (n = 157;A), 6-7 weeks (n = 878;B), 8-9 weeks (n = 972;C), 10-12 weeks (n = 720;D), 13-14 weeks (n = 195;E) and 15 or more weeks (n = 180;F). The association between these interval groups and outcomes was investigated using univariable and multivariable analysis with group C (8-9 weeks) as reference.

Results: In total, 3102 patients were included. The pCR rate for the groups A to F was 31%, 28%, 26%, 31%, 40% and 37%, respectively. A longer interval was associated with a higher probability of pCR (≥10 weeks for adenocarcinoma: odds ratio [95% confidence interval]: 1.35 [1.00-1.83], 1.95 [1.24-3.07], 1.64 [0.99-2.71] and ≥13 weeks for squamous cell carcinoma: 2.86 [1.23-6.65], 2.67 [1.29-5.55]. Patients operated ≥10 weeks after nCRT had the same probability for intraoperative/postoperative complications. Patients from groups D and F had a higher 30-day/in-hospital mortality (1.80 [1.08-3.00], 3.19 [1.66-6.14]).

Conclusion: An interval of ≥10 weeks for adenocarcinoma and ≥13 weeks for squamous cell carcinoma between nCRT and oesophagectomy was associated with a higher probability of having a pCR. Longer intervals were not associated with intraoperative/postoperative complications. The 30-day/in-hospital mortality was higher in patients with extended intervals (10-12 and ≥15 weeks); however, this might have been due to residual confounding.

Keywords: Neoadjuvant chemoradiotherapy; Oesophageal carcinoma; Oesophageal surgery; Pathological complete response; Time-to-treatment; Treatment outcome.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Chemoradiotherapy, Adjuvant* / mortality
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Databases, Factual
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Esophageal Squamous Cell Carcinoma
  • Esophagectomy* / adverse effects
  • Esophagectomy* / mortality
  • Esophagogastric Junction* / drug effects
  • Esophagogastric Junction* / pathology
  • Esophagogastric Junction* / radiation effects
  • Esophagogastric Junction* / surgery
  • Female
  • Hospital Mortality
  • Humans
  • Infant
  • Infant, Newborn
  • Logistic Models
  • Male
  • Margins of Excision
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Neoplasm Staging
  • Netherlands
  • Odds Ratio
  • Postoperative Complications / mortality
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Time-to-Treatment*
  • Treatment Outcome
  • Young Adult

Supplementary concepts

  • Adenocarcinoma Of Esophagus