Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology

NCT03462524 | Completed

• 1 other identifier: SJHDOS201701
• Study Type: observational
• Target: 384
• Locations: 1 country
• Sites: 2

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.

Conditions

Esophageal Cancer; Radiation Pneumonitis; Pulmonary Fibrosis; Respiratory Failure; Pneumonia; Surgery; Chemotherapy Effect; Radiation Fibrosis; Radiation Toxicity; Adenocarcinoma; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (5)

• Change in FEV1 following administration of neoadjuvant chemotherapy versus chemoradiation

  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.

  4-6 weeks post completion of neoadjuvant therapy

• Change in FVC following administration of neoadjuvant chemotherapy versus chemoradiation

  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.

  4-6 weeks post completion of neoadjuvant therapy

• Change in DLCO following administration of neoadjuvant chemotherapy versus chemoradiation

  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.

  4-6 weeks post completion of neoadjuvant therapy

• Incidence of postoperative pulmonary morbidity as per Esophagectomy Complications Consensus Group (ECCG) definitions

  Incidence of postoperative pulmonary morbidity, defined according to ECCG guidelines, will be compared after neoadjuvant chemotherapy versus chemoradiation.

  Up to 90 days postoperatively

• Global health-related quality of life (HR-QL) score as assessed by Eastern Co-operative Oncology Group QLQ-C30 questionnaire

  "Global health" HR-QL scores at one year postoperatively among disease-free patients will be compared between neoadjuvant chemotherapy and chemoradiation cohorts

  One year postoperatively

Secondary Outcomes (2)

• 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

• 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

Study Arms (2)

Neoadjuvant chemotherapy

Procedure: Esophagectomy

Neoadjuvant chemoradiation

Procedure: Esophagectomy

Interventions

Esophagectomy PROCEDURE

FEV1, FVC and DLCO will be assessed at baseline and one month post induction therapy. Radiation induced lung injury (RILI EORTC grade≥2), CCI, Clavien-Dindo, and pulmonary complications will be monitored. Changes in pulmonary function will be compared with cardiorespiratory symptoms and HR-QL among disease-free survivors.

Neoadjuvant chemoradiation; Neoadjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Records for all patients with LAEC treated with multimodal therapy with curative intent between 2010 and 2016 will be assessed for inclusion. Patients undergoing emergent or palliative surgery, or salvage esophagectomy will be excluded. All eligible patients for whom pulmonary function testing was undertaken at our Centre at a minimum of one preoperative timepoint will be included for analysis of operative and/or oncologic outcome. Then, HR-QL among disease-free patients at least one year postoperatively will be assessed using validated questionnaires (EORTC QLQC30, OG25 and OES18).

You may qualify if:

• 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

You may not qualify if:

• Salvage, palliative or emergency surgery

Sponsors & Collaborators

• St. James's Hospital, Ireland: lead

Study Sites (2)

Department of Surgery, St. James's Hospital

Dublin, D4, Ireland

Location

Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital

Dublin, D8, Ireland

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Radiation Pneumonitis; Pulmonary Fibrosis; Respiratory Insufficiency; Pneumonia; Radiation Fibrosis Syndrome; Radiation Injuries; Adenocarcinoma; Carcinoma, Squamous Cell

Interventions

Esophagectomy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Wounds and Injuries; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Infections; Infections; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgical Research Fellow

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 12, 2018
• Study Start: January 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2018
• Last Updated: March 12, 2018

Record last verified: 2018-03

Locations

IE (2)