Cognitive Function After Radiation Therapy for Brain Tumours (WP-12-pre)

This study will assess cognitive function in adult patients with a primary brain tumour treated with surgical resection with or without radiation therapy (RT). All types of brain tumours apart from glioblastoma will be included

Study Overview

• Status: Completed
• Conditions: Radiation Toxicity; Primary Brain Tumor
• Intervention / Treatment: Radiation: Cognitive testing

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 the investigators need to spare, to prevent cognitive dysfunction.

The study is a cross sectional study assessing cognitive function in patients with brain tumours previously treated with RT compared to a similar non irradiated group. 104 patients with specified brain tumours from Aarhus University Hospital treated in the period 2006-2016 will be included. 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.

• Study Type: Observational
• Enrollment (Actual): 104

Contacts and Locations

Study Locations

• Denmark
  • Region Midt
    • Aarhus, Region Midt, Denmark, 8000
      • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults with a primary brain tumour grade I-III

Description

Inclusion Criteria:

• The participant must be 18 years or older and Danish speaking.
• Performance status 0-2
• Capable of cooperating on testing

• Diagnosed with one of the following diagnoses according to WHO 2016 classification 16 and been treated between 2006 and 2016

  1. ZM93803 glioma (exclusive glioblastoma)
  2. ZM9401/3 anaplastic astrocytoma, IDH mutant
  3. ZM9400/3 diffuse astrocytoma, IDH-mutant
  4. ZM9411/3 gemistocytisk astrocytoma, IDH mutant
  5. ZM9400/3 diffuse astrocytoma, NOS
  6. ZM9451/3 anaplastic oligodendroglioma, IDH mutant and 1p/19q-co deleted
  7. ZM9450/3 oligodendroglioma, IDH mutant and 1p/19q-co deleted
  8. ZM9450/3 oligodendroglioma, NOS
  9. ZM9451/3 anaplastic oligodendroglioma, NOS
  10. ZM9530/0 meningioma
  11. ZM9470/3 medulloblastoma, NOS
  12. DD352A pituitary adenoma

  13. Other rare brain tumours including skull base sarcomas

      -

      Exclusion Criteria:

      Performance status 3-4 Progression after radiation therapy

      -

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Radiotherapy group; Patients receiving radiotherapy after surgery for brain tumor	Radiation: Cognitive testing; Patients will have their cognitive function tested by the use of standardized cognitive test and fill in questionnaires. Cognitive function will be assessed by standardized cognitive tests: Hopkins verbal learning test (HVLT), Trail Making Test part A and B (TMT A and TMT B), Pased Auditory Test (PASAT), Wechsler Adult Intelligence Scale coding and digit span (WAIS-IV), Controlled Oral Word Association Test (Cowat) and STROOP colour and word test (STROOP) Questionnaire include; Quality of life; EORTC QlQ-C30 (QlQ-C30), FACIT-Fatigue Scale (Version 4) (FACIT), Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Patient's Assessment of Own Functioning Inventory (PAOFI).
No radiotherapy group; Patients NOT receiving radiotherapy after surgery for brain tumor	Radiation: Cognitive testing; Patients will have their cognitive function tested by the use of standardized cognitive test and fill in questionnaires. Cognitive function will be assessed by standardized cognitive tests: Hopkins verbal learning test (HVLT), Trail Making Test part A and B (TMT A and TMT B), Pased Auditory Test (PASAT), Wechsler Adult Intelligence Scale coding and digit span (WAIS-IV), Controlled Oral Word Association Test (Cowat) and STROOP colour and word test (STROOP) Questionnaire include; Quality of life; EORTC QlQ-C30 (QlQ-C30), FACIT-Fatigue Scale (Version 4) (FACIT), Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Patient's Assessment of Own Functioning Inventory (PAOFI).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory impairment (as assessed by the HVLT-r)	To examine the correlation between memory impairment (assessed by HVLT-r) and mean dose to the hippocampus.	1-10 years after treatment
Neurocognitive function	Examine correlations cognitive decline and subvolumes of the brain. Cognitive function will be assessed by standardized cognitive tests: Hopkins verbal learning test (HVLT), Trail Making Test part A and B (TMT A and TMT B), Pased Auditory Test (PASAT), Wechsler Adult Intelligence Scale coding and digit span (WAIS-IV), Controlled Oral Word Association Test (Cowat) and STROOP colour and word test (STROOP). Measures on cognitive test is time in seconds or number of "corrects".	1-10 years after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1-10 years after treatment
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	1-10 years after treatment
Sleep quality	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	1-10 years after treatment
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	1-10 years after treatment
Patients assessment of own cognitive function	Assessed by questionnaire; Patient's Assessment of Own Functioning Inventory (PAOFI), in order to assess patients own perception of cognitive function	1-10 years after treatment

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Morten Høyer, M.D., Aarhus University Hospital

Publications and helpful links

General Publications

• Haldbo-Classen L, Amidi A, Lukacova S, Wu LM, Oettingen GV, Lassen-Ramshad Y, Zachariae R, Kallehauge JF, Hoyer M. Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours. Radiother Oncol. 2020 Jul;148:1-7. doi: 10.1016/j.radonc.2020.03.023. Epub 2020 Mar 28.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2017
• Primary Completion (Actual): February 2, 2018
• Study Completion (Actual): April 12, 2018

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: October 4, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 10, 2019
• Last Update Submitted That Met QC Criteria: October 7, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Cognitive function
• 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's precursor

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