Cognitive Function After Radiation Therapy for Primary Brain Tumours

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: Recruiting
• Conditions: Cognitive Impairment; Radiation Toxicity; Primary Brain Tumour
• Intervention / Treatment: Other: Cognitive tests and Patient Reported Outcomes

Detailed Description

RT is fundamental in the treatment of primary brain tumours. RT contributes to improved local control and prolonged progression-free survival in patients with a broad range of tumour types. Irradiation to the normal brain may lead to cognitive impairments. Clarifying the nature and severity of impairment in adult RT-treated brain tumour patients, including region-specific effects, are important for optimal utilization of novel conformal RT technologies such as proton therapy.

The study is a prospective nationwide study including approximately 300 brain tumour patients from the Danish Center of Particle Therapy and the four Neuro Oncology Centers in Denmark.

The patients will be assessed with a comprehensive battery of standardized cognitive tests and complete a questionnaire (PRO's). They will do this prior to RT treatment and 1, 3, 5 and 10 years afterwards. The PRO's includes measures on quality of life, fatigue, sleep, depression, anxiety, and socio demographics. 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. 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 (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Morten Høyer, MD; Phone Number: +45 2328 2823; Email: morthoey@rm.dk
• Study Contact Backup: Name: Lene Haldbo-Classen, MD; Phone Number: +4523342761; Email: lenhaldb@rm.dk

Study Locations

• Denmark
  • Region Hovedstaden
    • Copenhagen, Region Hovedstaden, Denmark, 2100
      • Recruiting
      • Department of Oncology, Rigshospitalet
      • Contact: Aida Muhic; Phone Number: +45 35456942; Email: aida.muhic@regionh.dk
  • Region Midt
    • Aarhus, Region Midt, Denmark, 8200
      • Recruiting
      • Danish Center for Particel Therapy
      • Contact: Morten Høyer; Phone Number: +452328 2823; Email: morthoey@rm.dk
      • Contact: Lene Haldbo-Classen; Phone Number: +4523342761 +45 2334 2761; Email: lenhaldb@rm.dk
      • Principal Investigator: Petra Witt
    • Aarhus, Region Midt, Denmark, 8200
      • Recruiting
      • Department of Oncology, Aarhus University Hospital
      • Contact: Slavka Lucakova; Phone Number: +45 3027 2470; Email: slvkluka@rm.dk
      • Principal Investigator: Lene Haldbo-Classen
  • Region Nord
    • Aalborg, Region Nord, Denmark, 9000
      • Recruiting
      • Department of Oncology, Aalborg University Hospital
      • Contact: Charlotte Haslund; Phone Number: +45 97661414; Email: cah@rn.dk
  • Region Syd
    • Odense, Region Syd, Denmark, 5000
      • Recruiting
      • Department of Oncology, Odense University Hospital
      • Contact: Rikke Dahlrot; Phone Number: +45 26242142; Email: rikke.dahlrot@rsyd.dk

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.

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Glioblastoma
• Performance status 3-4 (Karnofsky Performances of 60 or less)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impairment of verbal learning and memory as assessed by the HVLT-r test	Examined by the Hopkins Verbal Learning Test revised. It will be correlated to the mean radiation dose to the hippocampus. Outcome is number of correct words (0-24)	10 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Processing speed I	Examined by the Trail making Test part A (TMT_A). Outcome for TMT_A is time in seconds (0-120 seconds).	10 years
Processing speed II	Examined by the Coding from Wechsler Adult Intelligence Scale (WAIS-IV). Outcome for Coding is number of correct (within 2 minutes) (0-100)	10 years
Attention and working memory	Examined by Wechsler Adult Intelligence Scale (WAIS_IV_digit_span). Outcome on WAIS digit span is number of correct (0-36)	10 years
Verbal learning and memory	Examine by the Hopkins Verbal Learning Test revised (HVLT-r) - total and delayed. Outcome is number of correct words (0-24)	10 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)	10 years
Executive function I	Examined by Trail making Test part B (TMT_B). Outcome for TMT_B is time in seconds (0-300).	10 years
Executive function II	Examined by the STROOP colour and word test (STROOP). Outcome for STROOP is number of corrects (0-120)	10 years
Global Health - Quality of life	Assessed by questionnaire; European organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) in order to examine the level of quality of life in brain tumour patients who has received radiation therapy. The total score is a number (0-100)	10 years
Side effects to radiation therapy	Assessed by EORTC Brain Neoplasm Questionnaire, BN20 (an addition to QLQ-C30 mentioned above) in order to measure side effects to radiation therapy for a brain tumour. the score is a number (0-100)	10 years
Quality of Sleep	Assessed by questionnaire: Pittsburgh Sleep Quality INDEX, (PSQI) in order to explore the level of quality of sleep in brain tumour patients who has received radiation therapy. Outcome is a number (0-33)	10 years
Fatigue	Assessed by questionnaire: Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue scale (version 4) in order to explore the level of fatigue in brain tumour patients who has received radiation therapy. Outcome is a number (0-52)	10 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. Outcome is a number (0-56)	10 years
Patient's Assessment of Own Functioning	Assessed by questionnaire; Patient's Assessment of Own Functioning Inventory (PAOFI), in order to assess patients own perception of cognitive function. Outcome is a number (35-210)	10 years

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Lene Haldbo-Classen, M.D, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Anticipated): March 31, 2034
• Study Completion (Anticipated): March 31, 2034

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Patient reported outcomes; Hippocampus; Cognitive function; Radiation therapy; Brain tumour
• 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: DNOG-2

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