Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology

Surgery Clinical Trial

Official title:

Neoadjuvant Therapy for Locally Advanced Esophageal Cancer: Impact on Cardiopulmonary Physiology, Short- and Long-term Morbidity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03462524
• Other study ID #: SJHDOS201701
• Status: Completed
• Phase: N/A
• First received: February 28, 2018
• Last updated: March 5, 2018
• Start date: January 1, 2010
• Est. completion date: January 1, 2018

Study information

• Verified date: March 2018
• Source: St. James's Hospital, Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 384
• Est. completion date: January 1, 2018
• Est. primary completion date: January 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Squamous Cell
• Chemotherapy Effect
• Esophageal Cancer
• Esophageal Neoplasms
• Fibrosis
• Pneumonia
• Pulmonary Fibrosis
• Radiation Fibrosis
• Radiation Pneumonitis
• Radiation Toxicity
• Respiratory Failure
• Respiratory Insufficiency
• Squamous Cell Carcinoma
• Surgery

Intervention

Procedure:
• Esophagectomy
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.

Locations

Country	Name	City	State
Ireland	Department of Surgery, St. James's Hospital	Dublin
Ireland	Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital	Dublin

Sponsors (1)

Lead Sponsor	Collaborator
St. James's Hospital, Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Disease-free survival	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.	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
Secondary	Overall survival	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.	To date of study completion or date of death, whichever occurs first, with a minimum of one year follow-up for all surviving patients