Prediction Models for Complications After CRT in Esophageal Cancer (MODELS)

The aim of this project is to develop and validate NTCP-models for complications after nCRT (and surgical resection), that can be uses for model-based dose optimization for PhRT and PRT, and for model-based selection for PRT, in patients with esophageal cancer

Study Overview

• Status: Recruiting
• Conditions: The Aim of This Project is to Develop and Validate NTCP-models for Complications After nCRT (and Surgical Resection)
• Intervention / Treatment: Other: retrospective

Detailed Description

Plan of investigation

In the present project we aim to evaluate two potential strategies to predict and consider a broad spectrum of complications for radiotherapy plan optimization and patient selection:

A comprehensive set of separate NTCP-models for several cardiopulmonary and post-operative complications after nCRT, which results in an NTCP-profile.

A single multivariable NTCP-model for a so-called Complication Sum Score (CSS), which is a single composite complication endpoint including all complications after nCRT, weighted depending on severity and impact.

These prediction models can be used for RT plan optimization and patient selection.

In order to develop these prediction models the project consortium brings together existing prospective data registries for esophageal cancer, namely the Dutch Upper GI Cancer Audit (DUCA) and the Dutch Cancer Registry (NKR) (as well as the POCOP study).

The data of these registries will be linked to a retrospective radiotherapy database using the ProTRAIT infrastructure, resulting in a dataset of over 2000 patients.

In this retrospective cohort study, we will focus on esophageal cancer patients who were treated with nCRT, and for whom an esophagectomy was intended. We will include the patients who received nCRT and the esophagectomy in one of the participating centers. Patients who only received nCRT in one of the participating centers and for whom surgical resection was omitted will be included as well. Detailed eligibility criteria can be found in that section.

Eligible patients will be identified by the Dutch Cancer Registry. The surviving patients will be asked to provide informed consent for participation in this study, permission to combine the different data registries and for future use of their data. Patients who died will be included as well, unless they objected agains the use of there data in the participating centers.

Of the participating patients, the radiotherapy plan-CT and treatment plans (i.e. RTplan, RT struct, RT dose), will be pseudo-anonymized, uploaded and transferred to the UMCG data platform, by the participating radiotherapy centers.

A third trusted party, Zorg TTP, will be responsible for the pseudonymization of the three data sources; the Dutch upper GI cancer audit (DUCA), the Dutch Cancer Registry (NKR) and the RTregistry. After that the linkage will be performed at the UMCG.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Christina Muijs, Dr.; Phone Number: 0503616161; Email: c.t.muijs@umcg.nl

Study Locations

• Netherlands
  • Delft, Netherlands
    • Not yet recruiting
    • Holland PTC
    • Contact: Yvonne Klaver, MD, PHD
  • Groningen, Netherlands, 9715GZ
    • Recruiting
    • UMCG
    • Contact: Christina Muijs, MD, PHD; Phone Number: 0503616161; Email: c.t.muijs@umcg.nl
    • Principal Investigator: C. T. Muijs, MD, PHD
    • Sub-Investigator: J. A. Langendijk, Prof., MD, PHD
    • Sub-Investigator: B. van Etten, MD, PHD
    • Sub-Investigator: J. J. de Haan, MD, PHD
  • Heerlen, Netherlands
    • Recruiting
    • Zuyderland Hospital
    • Contact: Meindert Sosef, MD
  • Utrecht, Netherlands, 3584CX
    • Recruiting
    • UMCU
    • Contact: G Meijer, PHD
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525GA
      • Recruiting
      • Radboud UMC
      • Contact: H. Rutten, MD
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ET
      • Recruiting
      • Maastro Clinic
      • Contact: M. Berbee, MD, PHD
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Recruiting
      • Amsterdam UMC
      • Contact: P. van Rossum, MD, PHD
      • Principal Investigator: H.W.M. van Laarhoven, MD, PHD
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GE
      • Recruiting
      • Erasmus MC
      • Contact: J. Nuyttens, MD, PHD
      • Principal Investigator: B. Wijnhoven, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with esophageal cancer, treated with nCRT between 2015-2021 in the participating centers. See eligibility criteria above.

Description

Inclusion Criteria:

• Tumor in the esophagus, histologically proven or suspect for esophageal carcinoma
• WHO performance 0-2
• Age>18years
• No distant metastasis (M0)
• Treated with nCRT and planned for or followed by an esophagectomy between 2015 and 2021 in one of the participating centers.

Exclusion Criteria:

• Sarcoma, neuro-endocrine or small cell carcinoma of the esophagus
• Patients who underwent a surgical resection in a non-participating surgical center will be excluded

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multivariable NTCP models will be developed for the prediction of the following	Postoperative complications (graded by ECCG classification (3) ): Atrial fibrillation ≥grade 2 Pneumonia ≥grade 2 Respiratory failure requiring re-intubation Anastomotic leakage ≥ grade 2	Within 90 days after surgery
Cardiac events grade II or higher (CTCAE v 5.0), including:	Pericardial effusion Myocardial infarction and other acute coronary events Heart failure Pericardial effusion Myocardial infarction and other acute coronary events Heart failure Atrial fibrillation	1 and 2 year after nCRT
Mortality	Mortality	1 and 2 year after nCRT
Complication Sum Score, that will be determined in Delphi consensus	Complication Sum Score, that will be determined in Delphi consensus	1 year after nCRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-rated dysphagia	Patient-rated dysphagia	Up to 30 days after nCRT
Patient-rated nausea	Patient-rated nausea	Up to 30 day after nCRT
Patient-rated fatigue / daily functioning	Patient-rated fatigue / daily functioning	Up to 6 months after nCRT
Hospitalization after esophagectomy (days)	Hospitalization after esophagectomy (days)	Hospitalization after esophagectomy, average 12 days
Intensive care unit stay after esophagectomy (days)	Intensive care unit stay after esophagectomy (days)	Intensive care unit stay after esophagectomy, average 1.5 days

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Comprehensive Cancer Centre The Netherlands; Dutch Cancer Society; Dutch Institute for Clinical Auditing (DICA); ZorgTTP

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: April 14, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: prediction models; esophageal cancer (EC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: 11446

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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