Metachronic Brain Metastases After Esophagectomy for Esophageal Cancer (METABREC) (METABREC)

Risk Factors and Treatment Options for Metachronic Brain Metastases After Esophagectomy for Esophageal Cancer: a Multicentric Retrospective Cohort Study (METABREC)

Esophagectomy is the cornerstone of the curative treatment of esophageal carcinoma. Despite this treatment, patients can suffer from locoregional or distant metastatic disease and only a very selected group of patients can be cured: mostly those with recurrence in one single organ.

Brain metastases are rare after esophagectomy for cancer, but they have a serious impact on survival. Agressive treatment is often moren difficult for brain metastases compared to other metastases and some risk factors have been identified earlier.

There is an impression that the incidence of brain metastases in esophageal cancer patients has increased since the introduction of neoadjuvant treatment schemes. However, this is not clear yet. A potential explanation could be that chemotherapy disturbs the blood-brain-barrier, hereby facilitating the migration of tumor cells to the brain.

The purpose of this study is to retrospectively analyze the incidence and potential risk factors of brain metastases in patients who underwent esophagectomy for esophageal cancer. Patients treated between 2000 and 2019 will be included and outcome parameters are Odds Ratio for brain metastases (comparison between primary surgery and neoadjuvant treatment followed by surgery), time to recurrence and risk factors, number and characteristics of the brain metastases.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Neoplasms; Brain Metastases; Esophagectomy
• Intervention / Treatment: Procedure: Esophagectomy for esophageal cancer

• Study Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

• Study Contact: Name: Lieven P Depypere, PhD; Phone Number: +32 16 346820; Email: lieven.depypere@uzleuven.be
• Study Contact Backup: Name: Johnny Moons, Msc; Phone Number: +32 16 346820; Email: johnny.moons@uzleuven.be

Study Locations

• Belgium
  • Gent, Belgium
    • Not yet recruiting
    • Universitair Ziekenhuis Gent
    • Contact: Inge Vandenbroucke
    • Principal Investigator: Elke Van Daele
• France
  • Lille, France
    • Not yet recruiting
    • Centre Hospitalier Régional Universitaire de Lille
    • Contact: Sébastien Degisors
    • Principal Investigator: Guillaume Piessen, PhD
• Ireland
  • Dublin, Ireland
    • Not yet recruiting
    • Saint James Hospital
    • Contact: Noel E Donlon
    • Principal Investigator: John Reynolds
• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC
    • Contact: Daan Voeten
    • Principal Investigator: Mark Van Berge Henegouwen, PhD
  • Heerlen, Netherlands
    • Not yet recruiting
    • Zuyderland MC
    • Contact: Julie Van Den Bosch, MD
    • Principal Investigator: Meindert Sosef, PhD
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Erasmus MC
    • Contact: x gao
    • Principal Investigator: Bas Wijnhoven, PhD
• Sweden
  • Stockholm, Sweden
    • Recruiting
    • Karolinska Institutet
    • Contact: Biying Huang
    • Principal Investigator: Magnus Nilsson, PhD
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • MD Anderson Cancer Center
      • Contact: Patricia Abraham
      • Principal Investigator: Wayne Hofstetter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients receiving surgical treatment for esophageal cancer between 1 januari 2000 and 31 december 2019

Description

Inclusion Criteria:

• Patients receiving surgical treatment for esophageal cancer between 1 januari 2000 and 31 december 2019
• All types of neoadjuvant treatment followed by surgery, primary surgery or salvage surgery.
• Adenocarcinoma or squamous cell carcinoma histology

Exclusion Criteria:

• other histology type than adenocarcinoma or squamous cell carcinoma
• Hypopharyngeal carcinoma extending to the esophagus (requiring total laryngo-pharyngo-esophagectomy)
• Early esophageal carcinoma (cT IS-1a N0 M0)
• palliative esophagectomy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odds ratio (OR) for brain metastasis	Odds ratio (OR) for brain metastasis compared between primary surgery and neoadjuvant treatment plus surgery, OR for different neoadjuvant treatment regimes, corrected for gender and tumor factors (histology, stage, tumor differentiation,…) .	1 January 2000 - 1 March 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival after diagnosis of brain metastases stratified for treatment regimens applied.	1 January 2000 - 1 March 2020
Time to recurrence	Time to recurrence, between incidence date of esophageal cancer and diagnosis of brainM+	1 January 2000 - 1 March 2020
Risk factors for single site brain metastasis	such as different neoadjuvant treatment regimes, age, gender,and tumor factors (histology, stage, tumor differentiation,…)	1 January 2000 - 1 March 2020
Number of brain metastases	Number of brain metastases	1 January 2000 - 1 March 2020
Characteristics of brain metastases	solitary/multiple; location /side in the brain; treatment) and the effects on 'OS after recurrence' (e.g. is there a significant survival benefit in patients with brainM+ if they are treated with brain-surgery and/or stereotactic radiotherapy compared to non-treated BrainM+ or palliative treatments of brainM+	1 January 2000 - 1 March 2020

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Lieven P Depypere, PhD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Esophageal Diseases; Neoplasm Metastasis; Brain Neoplasms; Esophageal Neoplasms
• Other Study ID Numbers: S64060

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No