The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study

Introduction The locoregional failure (LRF) rate in human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) remains disappointingly high and toxicity is substantial. Response prediction prior to or early during treatment would provide opportunities for personalised treatme...

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Main Authors: Aad van der Lugt, Dik C van Gent, Gerda M Verduijn, Marta E Capala, Nienke D Sijtsema, Iris Lauwers, Juan A Hernandez Tamames, Wilma D Heemsbergen, Aniel Sewnaik, Jose A Hardillo, Hetty Mast, Yvette van Norden, Maurice P H M Jansen, Mischa S Hoogeman, Bianca Mostert, Steven F Petit
Format: Article
Language:English
Published: BMJ Publishing Group 2022-05-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/12/5/e059345.full
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author Aad van der Lugt
Dik C van Gent
Gerda M Verduijn
Marta E Capala
Nienke D Sijtsema
Iris Lauwers
Juan A Hernandez Tamames
Wilma D Heemsbergen
Aniel Sewnaik
Jose A Hardillo
Hetty Mast
Yvette van Norden
Maurice P H M Jansen
Mischa S Hoogeman
Bianca Mostert
Steven F Petit
author_facet Aad van der Lugt
Dik C van Gent
Gerda M Verduijn
Marta E Capala
Nienke D Sijtsema
Iris Lauwers
Juan A Hernandez Tamames
Wilma D Heemsbergen
Aniel Sewnaik
Jose A Hardillo
Hetty Mast
Yvette van Norden
Maurice P H M Jansen
Mischa S Hoogeman
Bianca Mostert
Steven F Petit
author_sort Aad van der Lugt
collection DOAJ
description Introduction The locoregional failure (LRF) rate in human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) remains disappointingly high and toxicity is substantial. Response prediction prior to or early during treatment would provide opportunities for personalised treatment. Currently, there are no accurate predictive models available for correct OPSCC patient selection. Apparently, the pivotal driving forces that determine how a OPSCC responds to treatment, have yet to be elucidated. Therefore, the holistiC early respOnse assessMent for oroPharyngeaL cancer paTiEnts study focuses on a holistic approach to gain insight in novel potential prognostic biomarkers, acquired before and early during treatment, to predict response to treatment in HPV-negative patients with OPSCC.Methods and analysis This single-centre prospective observational study investigates 60 HPV-negative patients with OPSCC scheduled for primary radiotherapy (RT) with cisplatin or cetuximab, according to current clinical practice. A holistic approach will be used that aims to map the macroscopic (with Intra Voxel Incoherent Motion Diffusion Kurtosis Imaging (IVIM-DKI); before, during, and 3 months after RT), microscopic (with biopsies of the primary tumour acquired before treatment and irradiated ex vivo to assess radiosensitivity), and molecular landscape (with circulating tumour DNA (ctDNA) analysed before, during and 3 months after treatment). The main end point is locoregional control (LRC) 2 years after treatment. The primary objective is to determine whether a relative change in the mean of the diffusion coefficient D (an IVIM-DKI parameter) in the primary tumour early during treatment, improves the performance of a predictive model consisting of tumour volume only, for 2 years LRC after treatment. The secondary objectives investigate the potential of other IVIM-DKI parameters, ex vivo sensitivity characteristics, ctDNA, and combinations thereof as potential novel prognostic markers.Ethics and dissemination The study was approved by the Medical Ethical Committee of Erasmus Medical Center. The main results of the trial will be presented in international meetings and medical journals.Trial registration number NL8458.
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spelling doaj-art-19f15ce4516e4b28ada070fa85e6367a2025-08-20T02:16:56ZengBMJ Publishing GroupBMJ Open2044-60552022-05-0112510.1136/bmjopen-2021-059345The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational studyAad van der Lugt0Dik C van Gent1Gerda M Verduijn2Marta E Capala3Nienke D Sijtsema4Iris Lauwers5Juan A Hernandez Tamames6Wilma D Heemsbergen7Aniel Sewnaik8Jose A Hardillo9Hetty Mast10Yvette van Norden11Maurice P H M Jansen12Mischa S Hoogeman13Bianca Mostert14Steven F Petit15Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands6 Molecular Genetics, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands2 Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands3 Otorhinolaryngology and Head and Neck surgery, Erasmus Medical Center, Rotterdam, The Netherlands3 Otorhinolaryngology and Head and Neck surgery, Erasmus Medical Center, Rotterdam, The Netherlands4 Oral and Maxillofacial surgery, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands5 Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The Netherlands5 Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands1 Radiotherapy, Erasmus Medical Center, Rotterdam, The NetherlandsIntroduction The locoregional failure (LRF) rate in human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) remains disappointingly high and toxicity is substantial. Response prediction prior to or early during treatment would provide opportunities for personalised treatment. Currently, there are no accurate predictive models available for correct OPSCC patient selection. Apparently, the pivotal driving forces that determine how a OPSCC responds to treatment, have yet to be elucidated. Therefore, the holistiC early respOnse assessMent for oroPharyngeaL cancer paTiEnts study focuses on a holistic approach to gain insight in novel potential prognostic biomarkers, acquired before and early during treatment, to predict response to treatment in HPV-negative patients with OPSCC.Methods and analysis This single-centre prospective observational study investigates 60 HPV-negative patients with OPSCC scheduled for primary radiotherapy (RT) with cisplatin or cetuximab, according to current clinical practice. A holistic approach will be used that aims to map the macroscopic (with Intra Voxel Incoherent Motion Diffusion Kurtosis Imaging (IVIM-DKI); before, during, and 3 months after RT), microscopic (with biopsies of the primary tumour acquired before treatment and irradiated ex vivo to assess radiosensitivity), and molecular landscape (with circulating tumour DNA (ctDNA) analysed before, during and 3 months after treatment). The main end point is locoregional control (LRC) 2 years after treatment. The primary objective is to determine whether a relative change in the mean of the diffusion coefficient D (an IVIM-DKI parameter) in the primary tumour early during treatment, improves the performance of a predictive model consisting of tumour volume only, for 2 years LRC after treatment. The secondary objectives investigate the potential of other IVIM-DKI parameters, ex vivo sensitivity characteristics, ctDNA, and combinations thereof as potential novel prognostic markers.Ethics and dissemination The study was approved by the Medical Ethical Committee of Erasmus Medical Center. The main results of the trial will be presented in international meetings and medical journals.Trial registration number NL8458.https://bmjopen.bmj.com/content/12/5/e059345.full
spellingShingle Aad van der Lugt
Dik C van Gent
Gerda M Verduijn
Marta E Capala
Nienke D Sijtsema
Iris Lauwers
Juan A Hernandez Tamames
Wilma D Heemsbergen
Aniel Sewnaik
Jose A Hardillo
Hetty Mast
Yvette van Norden
Maurice P H M Jansen
Mischa S Hoogeman
Bianca Mostert
Steven F Petit
The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study
BMJ Open
title The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study
title_full The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study
title_fullStr The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study
title_full_unstemmed The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study
title_short The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study
title_sort complete trial holistic early response assessment for oropharyngeal cancer patients protocol for an observational study
url https://bmjopen.bmj.com/content/12/5/e059345.full
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