Brain Irradiation for Childhood Cancer - Endocrine Monitoring During the First Years (BIChE-1)

Endocrine Follow-up After Cerebral Radiotherapy Performed Before Age 16 (Direct Cerebral Field or Following Facial, Cervical or High Ear, Nose, and Throat Radiotherapy)

BICHE- 1: Brain Irradiation for Childhood cancer - Endocrine monitoring during the first five years is a study of endocrine monitoring after cerebral radiotherapy.

The study concerns patients in remission at the end of oncological treatment aged between 4 and 18 years at the time of inclusion and who have had radiotherapy before the age of 16, irradiating all or part of the brain, with a delay between the end of radiotherapy and inclusion of less than 5 years. Patients will be included during a routine visit to the paediatric endocrinologist.

The protocol for the Biche 1 study has been designed and discussed in a multidisciplinary and multicentre manner, based on data from the literature and the French reference document (September 2021) "National protocol for diagnosis and care - congenital pituitary deficiency".

In this population, the investigators will conduct a descriptive and exploratory study to establish recommendations for medium-term follow-up; to improve screening for endocrine deficiencies affecting the hypothalamic-pituitary axis in order to improve patients' quality of life and state of health; and to better define dose-volume constraints on the axis.

The study will also focus on better detection and characterisation of chronic fatigue as a potential sequela of pituitary deficiencies, in particular by means of a questionnaire assessing fatigue (PedsQL Multidimensional Fatigue scale) which will also be systematically administered and completed annually.The expected sample size is 100-150 patients treated for a brain tumour and 60-80 patients treated for another tumour but with an irradiation field covering all or part of the brain.

Study Overview

• Status: Recruiting
• Conditions: Radiotherapy Side Effect; Endocrine; Deficiency; Hypothalamo-Pituitary Disorder
• Intervention / Treatment: Radiation: Blood sample, urine sample, osteodensitometry

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charlotte Demoor-Goldschmidt, Dr; Phone Number: +33 0241353565; Email: Charlotte.DemoorGoldschmidt@chu-angers.fr

Study Locations

• France
  • Angers, France, 49033
    • Recruiting
    • CHU Angers
    • Contact: Natacha Bouhours-Nouet; Phone Number: 0241353863; Email: nabouhours-nouet@chu-angers.fr
  • Bron, France, 69500
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Mélanie DAVAL-COTE; Phone Number: 0472118890; Email: melanie.daval-cote@chu-lyon.fr
  • Rennes, France, 35023
    • Recruiting
    • CHU Rennes
    • Contact: Tommaso DE GIORGIS; Phone Number: 0299267114; Email: Tommaso.De.Giorgis@chu-rennes.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient aged 4 years or more (≥4) and less than 18 years (<18) at inclusion
• Treated with radiotherapy to part or all of the brain for cancer or hematological malignancy before age 16 (≤15)
• Post-radiotherapy time less than or equal to 5 years (≤5)
• In remission of this pathology at the end of oncological treatments, or, with stable residual disease without treatment for 2 years or more (≥2)
• Signature of informed consent from parents or legal guardian
• Patient affiliated to the social security system or beneficiary of such a system

Exclusion Criteria:

• Patients who have relapsed or developed a second cancer with a post-treatment delay of < 1 year
• Patient in palliative situation
• Brain irradiation with dosimetric data showing sparing of the hypothalamic-pituitary axis (Dmax hypothalamic-pituitary axis < 15 Gy)
• Patient with a known hypothalamic-pituitary axis endocrine deficit prior to radiotherapy
• Refusal of child or parents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study Arm; Specific interventions: For all patients, an insulin level is added every 2 years. For patients under 8 years of age, additional elements such as testosterone (in male patients), Luteinizing hormone , Follicle-stimulating hormone, estradiol (in female patients), inhibin B +/- Anti-Müllerian hormone are measured during the usual blood test. A urinary check-up is systematically added for all patients, whereas it is usually only prescribed after certain chemotherapies (platinum salts, ifosfamide), nephrectomy, radiotherapy to the flanks as part of routine care. This check-up will be carried out at 2 and 4 years post-radiotherapy. For patients aged 12 and over, a second bone densitometry is performed at the end of follow-up, even if the first is normal. In routine care, international guidelines recommend this first bone densitometry, and the second is usually performed only if the first was abnormal.

Radiation: Blood sample, urine sample, osteodensitometry; Blood sample, urine sample, osteodensitometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endocrine toxicities assessment after radiotherapy involving all or part of the brain in children, adolescents and young adults treated for cancer before the age of 16 (≤15 years)	Measurement of hormon level for : growth hormone deficiency; gonadal insufficiency; hypothyroidism; adrenal insufficiency	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define risk factors for anterior pituitary insufficiency in patients who received brain radiotherapy, taking into account treatment characteristics and clinical data.	Dose absorbed (Gy) by sensitive organs: This parameter corresponds to the total amount of radiation absorbed by the hypothalamus and pituitary gland, two key structures of the endocrine axis. A cumulative dose above certain thresholds is associated with a higher risk of long-term endocrine dysfunction - possibly after adjustment for the biological equivalent dose (which also takes fractionation into account).	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
To define risk factors for anterior pituitary insufficiency in patients who received brain radiotherapy, taking into account treatment characteristics and clinical data.	Maximum dose (Dmax): The maximum dose received by a small portion of tissue in these critical organs.	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
To define risk factors for anterior pituitary insufficiency in patients who received brain radiotherapy, taking into account treatment characteristics and clinical data.	Volume irradiated (%): This parameter measures the proportion of the organ exposed to radiotherapy.	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
To define risk factors for anterior pituitary insufficiency in patients who received brain radiotherapy, taking into account treatment characteristics and clinical data.	Average dose (Dmean) and D50%: The average and median dose received by the whole organ.	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
To define risk factors for anterior pituitary insufficiency in patients who received brain radiotherapy, taking into account treatment characteristics and clinical data.	Minimum dose (Dmin): minimum dose received by the organ.	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
To define risk factors for anterior pituitary insufficiency in patients who received brain radiotherapy, taking into account treatment characteristics and clinical data.	Dose-volume histogram (DVH): The DVH analysis enables you to visualize the dose distribution over the entire organ, and to identify any thresholds other than those listed above.	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
Hormone deficiencies on fatigue in adult patients	Measurement by a questionnaire assessing fatigue (PedsQL Multidimensional Fatigue scale) composed of 18 items comprising 3 dimensions. 5-point Likert scale from: 0 (Never) to 4 (Almost always) 3-point Likert scale from: 0 (Not at all), 2 (Sometimes) and 4 (A lot) for the Child Report for Young Children (ages 5-7) then Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
Hormone deficiencies on cognitive disorders in adult patients	Measurement by a questionnaire assessing fatigue (PedsQL Multidimensional Fatigue scale) composed of 18 items comprising 3 dimensions. 5-point Likert scale from: 0 (Never) to 4 (Almost always) 3-point Likert scale from: 0 (Not at all), 2 (Sometimes) and 4 (A lot) for the Child Report for Young Children (ages 5-7) then Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy
Fatigue measurement in patients after the introduction of hormone replacement therapy	Measurement by a questionnaire assessing fatigue (PedsQL Multidimensional Fatigue scale) composed of 18 items comprising 3 dimensions. 5-point Likert scale from: 0 (Never) to 4 (Almost always) 3-point Likert scale from: 0 (Not at all), 2 (Sometimes) and 4 (A lot) for the Child Report for Young Children (ages 5-7) then Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0	Follow-up of 4 years, within a maximum of 5 years post-radiotherapy

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: September 27, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: brain tumours; Hypothalamic-pituitary axis deficiency; cerebral radiotherapy; endocrine monitoring; follow-up protocol
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Radiation Injuries; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 49RC24_0193

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No