Cerebral Morbidity After Radiation Therapy for Brain Tumors (WP-12)

This study will assess cognitive function in patients with a primary brain tumour treated with radiation therapy (RT) to generate radio-sensitivity and volume effect parameters for the development of cognitive dysfunction. All types of brain tumours apart from glioblastoma will be included.

Study Overview

• Status: Active, not recruiting
• Conditions: Cognitive Impairment; Brain Tumor; Radiation Toxicity
• Intervention / Treatment: Other: Cognitive tests and Patient Reported Outcome

Detailed Description

RT to brain tumours causes cognitive dysfunction. The extent of RT induced changes in cognitive function and radio-sensitivity of the brain is unknown. RT with protons instead of photons spares the healthy brain tissue more and is believed to reduce the risk of cognitive dysfunction. There is modest knowledge on which parts of the brain we need to spare, to prevent cognitive dysfunction.

The study is a prospective nationwide study including approximately 60 brain tumour patients from the four neuro oncology centres in Denmark. The patients will do patient reported outcome (PRO) and undergo neuropsychological assessment with standardized tests: They will do this prior to RT treatment and ½, 1, 3 and 5 years afterwards. The PRO's included measures on quality of life, fatigue, sleep, depression, anxiety, and socio demografica. The standardized tests are: Trail making Test (TMT); Hopkins Verbal Learning Test (HVLT); Controlled Oral Word Association Test (COWAT) - Animals and S; Coding and Digit Span from WAIS-IV; Paced Auditory Serial Addition Test (PASAT). The correlation between cognitive scores and RT dose-volume parameters to specific areas in the brain will be tested.

This study will elucidate the dose-response relationship in radiation-induced damage to substructures of the brain such as hippocampus, thalamus, temporal and frontal lobes that will allow the clinician to prioritize these structures in planning of proton radiotherapy.

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• Denmark
  • Region H
    • Copenhagen, Region H, Denmark, 2100
      • Rigshospital
  • Region Midt
    • Aarhus, Region Midt, Denmark, 8000
      • Department of Oncology
  • Region Nord
    • Aalborg, Region Nord, Denmark, 9000
      • Aalborg University Hospital
  • Region Syd
    • Odense, Region Syd, Denmark, 5000
      • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The patients will be diagnosed with a primary brain tumour and referred to radiation therapy. They will be recruited from the four neuro oncology centers in Denmark

Description

Inclusion Criteria:

• 18 years or older and Danish speaking.
• Performance status WHO 0-2
• Capable of cooperating on testing
• Tumor histology (WHO 2016 classification) of the following types: anaplastic astrocytoma (IDH mutant), diffuse astrocytoma (IDH-mutant), gemistocytic astrocytoma (IDH mutant), diffuse astrocytoma (NOS), oligidendroglioma, meningioma, medulloblastoma (NOS), pituitary adenoma, other brain tumours including skull base sarcomas

Exclusion Criteria:

• Glioblastoma
• Performance status 3-4

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impairment of memory as assessed by the HVLT-r test	Examined by the Hopkins Verbal Learning Test. It will be correlated to the mean radiation dose to the hippocampus. Outcome is number of correct words (0-24)	5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Processing speed	Examined by the Trail making Test part A (TMT_A) and the Coding from WAIS-IV. Outcome for TMT_A is time in seconds (0-120 seconds). Outcome for Coding is number of correct (within 2 minutes) (0-100)	5 Years
Attention and working memory	Examined by WAIS_IV_digit_span and PASAT (Pased Auditory Seriel Addition Test). Outcome on WAIS digit span is number of correct (0-36) and outcome for PASAT is number of incorrects (0-60)	5 Years
Verbal learning and memory	Examine by the Hopkins Verbal Learning Test (HVLT) - total and delayed. Outcome is number of correct words (0-24)	5 Years
Verbal fluency	Examined by the Controlled Oral Word Association Test (COWAT) - Animals and letter_S. Outcome is number of words produced in 1 minute (0-100)	5 Years
Executive function	Examined by Trail making Test part B (TMT-B) and the STROOP colour and word test (STROOP). Outcome for TMT_B is time in seconds (0-300). Outcome for STROOP is number of corrects (0-120)	5 Years
Global Health - Quality of life	Assessed by questionnaire; EORTC QlQ-C30 in order to examine the level of quality of life in brain tumour patients who has received radiation therapy. Quality of life will be assessed by EORTC QIQ-C-30	5 Years
Fatigue	Assessed by questionnaire: FACIT-Fatigue scale (version 4) in order to explore the level of fatigue in brain tumour patients who has received radiation therapy.	5 years
Qulity of Sleep	Assessed by questionnaire:Pittsburg Sleep Quality INDEX, PSQI in order to explore the level of quality of sleep in brain tumour patients who has received radiation therapy	5 years
Depression/Anxiety	Assessed by questionnaire: Hospital anxiety and depression Scale (HADS) in order to explore level of depression and anxiety in patients treated with radiation therapy for their brain tumour	5 years
Patient's Assessment of Own Functioning Inventory	Assessed by questionnaire; Patient's Assessment of Own Functioning Inventory (PAOFI), in order to assess patients own perception of cognitive function	5 years

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Morten Høyer, M.D, Danish Center for Particel Therapy, Aarhus University Hospital, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Brain tumor; Hippocampus; Cognitive function; Radiation Therapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: WP-12

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