Neurocognitive Function After Proton Therapy in Children and Adolescents (ELBE-ProKids)

Neurocognitive Function /executive Functions After Proton Therapy in Children and Adolescents.

Brain tumors are the second most frequent malignant diseases in children and adolescents. In the study the short and medium term consequences of proton therapy on cognitive processes in particular on executive functions in pediatric patients shall be highlighted/analysed/evalutated. In a second step, these results are to be compared with

1. a group of children and adolescents who had only /exclusively had operative therapy and
2. with a healthy control group. Thus, the extent to which these treatment options differ in terms of their short and medium-term effect is assessed. Methods of neurocognitive/neurophysiology brain research approaches are applied that may potentially visualize even small / subtle changes in mental activities/neurocognitive function. Therefore the effects of treatment can be evaluated and the neuropsychological outcome of children and adolescents with brain tumors can be improved.

Study Overview

• Status: Recruiting
• Conditions: Primary Brain Tumor

Detailed Description

Radio(chemo)therapy with protons is conducted according to current treatment standards or, for patients participating in a clinical intervention study, according to the study protocols of the GPOH. Only patients with prescribed radiation doses > 40 Gy (RBE) will be included. Treatment planning, the target volume and radiotherapy will be performed according to the current treatment standards. For patients participating in a clinical intervention study, radiotherapy is corresponding to study protocol of the GPOH. Risk organs (e.g. brain stem, chiasma, optic nerves, gll. Lacrimals, lenses, inner ears and spine) are contoured and the radiation doses for these organs are limited according to institutional guidelines. Radiotherapy is performed according to guidelines, i.e. 5 days a week for 4-6 weeks, usually on an outpatient basis.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Mechthild Krause, Prof. Dr.; Phone Number: +49 351 458 2238; Email: mechthild.krause@uniklinikum-dresden.de

Study Locations

• Germany
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • University Hospital Carl GUstav Carus Dresden, Child and adolescent psychiatry and psychotherapy
      • Contact: Christian Beste, Prof. Dr.
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • University Hospital Carl GUstav Carus Dresden, Department of Neuropaediatrics
      • Contact: Maja von der Hagen, Prof. Dr.
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • University Hospital Carl GUstav Carus Dresden, Department of Radiation Therapy and Radiation Oncology
      • Contact: Mechthild Krause, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

30 patients with infra-tentorial or supra-tentorial tumors undergoing proton therapy, 30 patients undergoing surgical treatment and a control cohort of 30 adolescents. Therefore, a total of 90 persons will be evaluated.

Description

Indication: Patients with primary brain tumor

Inclusion Criteria:

• all groups: Patients in childhood and adolescence between 8-18 years of age
• all groups: no prior radiotherapy of the brain,
• all groups: The patient is able to perform repeated neuropsychological tests (approx. 1 hour per examination),
• all groups: corrected visual acuity not impaired below 80% or no subjective indication of visual acuity impairment,
• all groups: corrected hearing not impaired or no subjective evidence of hearing impairment,
• all groups: Patient is able to perform follow-up examinations,
• all groups: written consent of the patient/parent or guardian.
• Brain tumour groups with/without irradiation: Primary brain tumour
• brain tumor groups with/without radiation: curative or long-term palliative intention of therapy
• brain tumor groups with/without irradiation: life expectancy > 3 years
• Irradiation group only: planned proton therapy with a local radiation dose of at least 40 Gy(RBE)

Exclusion Criteria:

• Patients under 8 or over 18 years of age (We limit the study to children over 8 years of age due to the fact that executive functions mature very late.)
• Brain metastases from extracerebral tumors
• Patient receives intrathecal chemotherapy
• pure palliative treatment concept
• The patient is not able to perform repeated neuropsychological tests (approx. 1 hour per examination).
• Chronic diseases that may affect the results of neurological EEG and neuropsychological examinations.
• The patient is not in a position to perform follow-up examinations
• no written consent of the patient / parent or legal guardian
• Participation in an intervention study whose procedures contradict those of the present study

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Proton Therapy; Patients receive proton Radio(chemo)therapy according to clinical standard. Proton Treatment is indicated BEFORE inclusion into the trial ans is not part of the trial. Neurological status and neurocognitive testing on core executive functions (inhibition, working memory, cognitive flexibility) and Quality of life measurements are performed regularely during follow-up using standardized KINDL® questionnaires for general quality of life and specific for oncologic diseases. In addition to the treatment parameters of the radio(chemo)therapy protocol, further radiation doses to brain substructures and organs at risk are documented.
No Radiotherapy - Surgical only group; Patients are included AFTER surgery of their brain tumour and receive no radiotherapy due to their disease (i.e. according to clinical standard). This Treatment is not part of the trial, but stratifies the Patient in this second Group. Neurological status and neurocognitive testing on core executive functions (inhibition, working memory, cognitive flexibility) and Quality of life measurements are performed regularely during follow-up using standardized KINDL® questionnaires for general quality of life and specific for oncologic diseases.
Control Group; Healthy kids are recruited as Standard Group. Neurological status and neurocognitive testing on core executive functions (inhibition, working memory, cognitive flexibility) and Quality of life measurements are performed regularely using standardized KINDL® questionnaires for general quality of life and specific for oncologic diseases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurophysiological correlates of cognitive control (ERP amplitude measures, spectral power measures)	Neurophysiological processes are examined while subjects perform the cognitive tests.	2 years
Quality of Life Parameters (KINDL®)	QoL Parameters are measured and reported using KINDL® questionnaires for general quality of life and specific for oncologic diseases (also KINDL®). Scales for QoL items are 0-100 (with 100 being the Optimum, i.e. lower values indicating worse outcome). Evaluation is performed according to the standard published with the validated questionnaires (https://www.kindl.org/deutsch/fragebögen/)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dose-volume parameters to normal tissues, i.e. maximum irradiation doses, mean doses and doses to subvolumes	physical doses to substructures of the brain are collected and correlated with neurophysiological outcome measures	2 years

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: Gert und Susanna Mayer Stiftung
• Investigators: Study Chair: Mechthild Krause, Prof. Dr., University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Brain Tumor; EEG; Neuropsychological Tests; children and adolescents; Proton Therapy; neurocognitive function; neurocognitive or neuropsychological outcome; quality of life, LOQ; Neurosurgical Treatment
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: STR-ELBE-Pro-Kids-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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