Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology

Completed

• Conditions: Chemotherapy Effect; Radiation Toxicity; Esophageal Cancer; Pulmonary Fibrosis; Respiratory Failure; Surgery; Radiation Fibrosis; Adenocarcinoma; Squamous Cell Carcinoma; Radiation Pneumonitis
• Interventions: Procedure: Esophagectomy

• Registration Number: NCT03462524
• Lead Sponsor: St. James's Hospital, Ireland

Brief Summary

Although recent global trends indicate reduced postoperative mortality after esophagectomy, major morbidity, in particular pulmonary, remains high, with considerable health and economic costs. In a recent modern international collaborative series of 2704 patients from high-volume centers, with an approximate equal mix of open and minimally invasive approaches, respiratory complications were evident in 28% of patients, pneumonia in 15%, and respiratory failure in 7%.1 In other series, respiratory failure is reported in up to 15% of patients and is the most common cause of mortality. Prediction of risk and prevention of respiratory morbidity is therefore of considerable importance, and in this context baseline assessment of respiratory physiology compliments clinical assessment, history and enhanced recovery pathways representing key elements of current patient management.

In this study, which will include all prospective patients with locally advanced esophageal cancer treated at a National Center, pulmonary function will be systematically measured before and after neoadjuvant therapy. The investigators seek to evaluate the incidence of radiation induced lung injury (RILI), as well as subclinical changes in pulmonary physiology that may be linked to postoperative complications, and quality-of-life in survivorship, and to compare cohorts who received radiation therapy or chemotherapy alone, preoperatively.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-01
• Primary Completion: 2016-01-01
• Study Completion: 2018-01-01
• Study First Submitted: 2018-02-28
• Status Verified: 2018-03
• Study First Submitted QC: 2018-03-05
• Last Update Submitted: 2018-03-05
• Study First Posted: 2018-03-12
• Last Update Posted: 2018-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 384

Inclusion Criteria

• Locally advanced esophageal cancer undergoing multimodal therapy with curative intent at study centre during study period
• Pulmonary function assessed at a minimum of one preoperative timepoint

Exclusion Criteria

• Salvage, palliative or emergency surgery

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Neoadjuvant chemotherapy	Esophagectomy	-
Neoadjuvant chemoradiation	Esophagectomy	-

Primary Outcome Measures

Name	Time	Method
Change in FEV1 following administration of neoadjuvant chemotherapy versus chemoradiation	4-6 weeks post completion of neoadjuvant therapy	Changes in FEV1 (forced expiratory volume in one second, litres), both as a raw value, and as percentage of predicted values normalized for ethnicity, sex, age and height according to Global Lung Function Initiative algorithms will be determined.
Global health-related quality of life (HR-QL) score as assessed by Eastern Co-operative Oncology Group QLQ-C30 questionnaire	One year postoperatively	"Global health" HR-QL scores at one year postoperatively among disease-free patients will be compared between neoadjuvant chemotherapy and chemoradiation cohorts
Change in DLCO following administration of neoadjuvant chemotherapy versus chemoradiation	4-6 weeks post completion of neoadjuvant therapy	Changes in DLCO (pulmonary diffusion capacity for carbon monoxide, mmol·min.-1.kPa. -1), both as a raw value, and as percentage of predicted values normalized for ethnicity, sex, age and height according to Global Lung Function Initiative algorithms will be determined.
Incidence of postoperative pulmonary morbidity as per Esophagectomy Complications Consensus Group (ECCG) definitions	Up to 90 days postoperatively	Incidence of postoperative pulmonary morbidity, defined according to ECCG guidelines, will be compared after neoadjuvant chemotherapy versus chemoradiation.
Change in FVC following administration of neoadjuvant chemotherapy versus chemoradiation	4-6 weeks post completion of neoadjuvant therapy	Changes in FVC (forced vital capacity, litres), both as a raw value, and as percentage of predicted values normalized for ethnicity, sex, age and height according to Global Lung Function Initiative algorithms will be determined.

Secondary Outcome Measures

Name	Time	Method
Disease-free survival	To date of study completion or date of disease recurrence, whichever occurs first, with a minimum of one year follow-up for all surviving patients	Disease-free survival will be compared between neoadjuvant chemotherapy and chemoradiation groups using Kaplan-Meier methods, as well as multivariable Cox proportional hazards regression models adjusting for known prognostic factors.
Overall survival	To date of study completion or date of death, whichever occurs first, with a minimum of one year follow-up for all surviving patients	Disease-free survival will be compared between neoadjuvant chemotherapy and chemoradiation groups using Kaplan-Meier methods, as well as multivariable Cox proportional hazards regression models adjusting for known prognostic factors.

Trial Locations

Locations (2)

Department of Surgery, St. James's Hospital; 🇮🇪 Dublin, Ireland

Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital; 🇮🇪 Dublin, Ireland