Clinical trial NCT04746729: Health Effects of CArdiac FluoRoscopy and MOderN RadIotherapy in PediatriCs - Radiotherapy
Official title: Health Effects of CArdiac FluoRoscopy and MOderN RadIotherapy in PediatriCs - Radiotherapy (HARMONIC-RT)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neoplasms
Keywords: Radiotherapy
Oncology
Paediatrics
Late toxicities
Radiation-induced neoplasms
Radiation-induced vascular damages
Radiation-induced cardiac damages
Radiation-induced endocrine damages
Quality of life
Social outcomes
External beam radiotherapy
Photon therapy
Proton therapy
Cohort
Registry
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: Barcelona Institute for Global Health
name: The West German Proton Therapy Centre, Essen
name: Gustave Roussy, Cancer Campus, Grand Paris
name: Centre Francois Baclesse
name: KU Leuven
name: University of Aarhus
name: Princess Maxima Center for Pediatric Oncology
name: University Medical Center Groningen
name: Stockholm University
name: National Research Council, Institute of Clinical Physiology, Italy
name: University of Zurich
name: Commissariat A L'energie Atomique
name: Luxembourg Institute of Science and Technology
name: University Hospital, Essen
name: Aarhus University Hospital
First posted: 2021-02-10
Enrollment: 2670
Sex: ALL
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children, adolescents and young adults treated with external beam radiation therapy for a first primary neoplasm

Brief summary: The goal of the HARMONIC-RT study is to evaluate late health and social outcomes of contemporary techniques of external beam radiotherapy in paediatric patients, based on the setting-up of a European, long-term registry complemented by a biobank.

Detailed description: Specific objectives:

* To develop the infrastructure and instruments for setting-up a European, long-term registry of paediatric patients treated with contemporary techniques of modern external radiotherapy;
* To assess the incidence and severity of late health outcomes, primarily endocrine dysfunctions, cardiovascular toxicities, neurovascular damages, and subsequent primary neoplasms, in relation to the dose-volume distribution to non-targeted organs and tissues, radiation delivery technique and beam quality factors, and potential modifying factors (i.e. age at exposure, genetic predispositions, comorbidities, and systemic treatments including chemotherapy, targeted therapy, immunotherapy and hormonal drugs) that may underlie differences in individual susceptibility for these outcomes ;
* To assess societal aspects of advances in radiotherapy, primarily health-related quality of life and academic achievement, in paediatric patients treated with modern external radiotherapy techniques.

Secondary scientific objectives:

* To assess multidimensional fatigue in paediatric patients treated with modern external radiotherapy techniques, and identify clinical and therapeutic determinants of fatigue;
* To improve estimation of patient-specific doses to the whole body and non-targeted organs and substructures from different radiotherapy delivery techniques;
* To investigate radiation-induced cellular responses and biological mechanisms related to the occurrence of vascular diseases and subsequent primary neoplasms in samples of blood and saliva ; to identify biomarkers of susceptibility and health effects ; to evaluate differences in disease biomarkers in relation to the radiation delivery technique and beam quality factors ; to explore the relevance of the use of saliva as a biosampling method for paediatric cohorts regarding feasibility and the quality and reproducibility for different measured biomarkers.

Secondary strategic objectives:

* To promote sustained collaborative research activities for improvement of patient care, and inform health care providers and policy makers on the clinical and social impact of advances in radiotherapy in paediatric settings;
* To serve as a pilot for a future long-term pan-European registry of children and adolescents treated with particle and photon beam therapy, including a biobank of saliva and blood samples collected before and after treatment;
* To contribute in future collaborative projects with existing cohorts or registries in Europe
* To contribute in future international research studies on late outcomes of modern radiotherapy techniques for management of paediatric cancers

Funding: The HARMONIC project has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 847707.

Eligibility criteria: Retrospective inclusion of study participants

Inclusion Criteria:

* First external beam radiation therapy (EBRT) started in 2000 or after for management of a first primary neoplasm
* Age under 22 years at the time of first EBRT initiation
* Radiation treatment plan (first EBRT) stored in DICOM format
* Usual residency in the country of EBRT to enable a long-term follow-up

Exclusion Criteria:

* Patients with poor prognosis (e.g. diffuse pontine glioma or high grade glioma) at first EBRT initiation
* Prior external or internal radiation therapy
* Patients who refused to participate in the study

Prospective inclusion of study participants

Inclusion Criteria:

* Scheduled first EBRT for management of a first primary neoplasm
* Age under 22 years at the time of scheduled first EBRT
* Radiation treatment plan stored in DICOM format
* Affiliate or beneficiary of health insurance (or any required equivalent as defined in applicable national law)
* Usual residency in the country of EBRT to enable a long-term follow-up
* Signed informed consent/assent

Exclusion Criteria:

* Patients with poor prognosis (e.g. diffuse pontine glioma or high grade glioma)
* Prior external or internal radiation therapy;
* Protected adults (persons under curatorship, tutorship / individuals under guardianship by court order, persons deprived of their liberty)
* Adult/parent(s)/legal representative(s) who cannot read or understand the informed consent in the applicable language(s) in the country of EBRT

Primary outcomes:
measure: Endocrinopathies
timeFrame: up to 20 years after RT
measure: Cardiovascular diseases
timeFrame: up to 20 years after RT
measure: Neurovascular diseases
timeFrame: up to 20 years after RT
measure: Second and subsequent primary neaoplasms
timeFrame: up to 20 years after RT
measure: Health-related quality of life (physical, emotional, social, and school functioning) assessed by the PedsQL™ core scale (validated questionnaire)
timeFrame: up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
measure: Academic achievement
timeFrame: up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
Secondary outcomes:
measure: Dysfunctions in endocrine hormone levels
timeFrame: up to 10 years after radiation therapy
measure: Changes in blood markers of cardiovascular diseases
timeFrame: up to 10 years after radiation therapy
measure: Changes in imaging markers of cardiovascular diseases
timeFrame: up to 10 years after radiation therapy
measure: Changes in imaging markers of neurovascular damages
timeFrame: up to 5 years after radiation therapy
measure: Changes in blood/saliva markers of protein activation relating to vascular damages
timeFrame: up to 1 year after radiation therapy
measure: Changes in blood/saliva markers of oxidative stress response
timeFrame: up to 1 year after radiation therapy
measure: Changes in blood/saliva markers of inflammatory response
timeFrame: up to 1 year after radiation therapy
measure: Changes in blood/saliva markers of carcinogenesis
timeFrame: up to 1 year after radiation therapy
measure: Multidimensional fatigue (general, sleep/rest, and cognitive fatigue)
timeFrame: up to 10 years after radiation therapy or attained age 25 years, whichever occurs first
measure: Clinical events other than those mentioned as primary outcomes
timeFrame: up to 20 years after radiation therapy
measure: All-cause and cause-specific mortality
timeFrame: up to 20 years after radiation therapy
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: KU Leuven
city: Aarhus
country: Denmark
facility: Aarhus University hospital
city: Caen
country: France
facility: Centre Régional François Baclesse
city: Villejuif
country: France
facility: Gustave Roussy
city: Essen
country: Germany
facility: University Hospital Essen, The West German Proton Therapy Centre Essen
Study officials:
affiliation: UK Essen
name: Beate Timmermann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Neige Journy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Stéphanie Bolle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barcelona Institute for Global Health
name: Isabelle Thierry-chef, PhD
role: STUDY_CHAIR
References:
citation: Journy N, Bolle S, Brualla L, Dumas A, Fresneau B, Haddy N, Haghdoost S, Haustermans K, Jackson A, Karabegovic S, Lassen-Ramshad Y, Thariat J, Wette MR, Botzenhardt S, De Wit I, Demoor-Goldschmidt C, Christiaens M, Hoyer M, Isebaert S, Jacobs S, Henriksen LT, Maduro JH, Ronckers C, Steinmeier T, Uyttebroeck A, Van Beek K, Walsh L, Thierry-Chef I, Timmermann B. Assessing late outcomes of advances in radiotherapy for paediatric cancers: Study protocol of the "HARMONIC-RT" European registry (NCT 04746729). Radiother Oncol. 2024 Jan;190:109972. doi: 10.1016/j.radonc.2023.109972. Epub 2023 Nov 2. No abstract available.