Long Term Implications of Rare Brain Tumours'

May 10, 2023 updated by: Galina Velikova

Understanding the Long-term Implications of Treatment of Rare Brain Tumours on Health-related Quality of Life: A European Cross-sectional Study

Patients diagnosed with oligodendroglioma with a specific molecular profile represent rare tumour groups (about 10% of adult gliomas) with relatively favourable prognosis (median survival between 8 and 12 years). These patients are often treated with surgery, chemotherapy and/or radiotherapy. However, as patients live for a long period of time, they may also experience long-term toxic side-effects of treatment. The long-term consequences of treatment- and disease-related factors on quality of life and cognitive functioning of these patients are largely unknown. This study aims to investigate quality of life and cognitive functioning in long-term survivors of oligodendroglioma (with IDH mutation and 1p/19q codeletion). This knowledge can support health care professionals prepare patients for any long-term consequences of treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The WHO classification of primary brain tumours has recently been updated and now also takes molecular parameters into account to provide clinicians with more accurate information on the expected disease course and to guide treatment decisions.1 Patients with oligodendrogliomas of WHO grades II or grade III (OII and OIII) defined by IDH mutation and 1p/19q co-deletion represent rare tumour groups (~10% of adult gliomas) with relatively favourable prognosis (median survival 11.9 years for OII and 8.5 years for OIII).2 However, this disease remains life-threatening as over time, all tumours are likely to progress with a more malignant phenotype.

Recent changes in the management of these patients followed after the publication of long-term follow-up data from two landmark studies on OIII carried out by EORTC and RTOG in the 1990s,3, 4 and a RTOG study on low-grade glioma including OII.5 These data suggest that standard treatment should comprise surgical resection of the tumour as feasible followed by radiotherapy and chemotherapy. These studies used radiotherapy doses of 54-60 Gy and PCV (procarbazine, CCNU, vincristine) polychemotherapy. Among high-risk WHO grade II glioma patients, including OII, postoperative temozolomide chemotherapy was not superior in terms of progression-free survival or health-related quality of life (HRQOL) compared to postoperative radiotherapy.6,7 The discussion on whether temozolomide or PCV would be the better chemotherapy in these two patient groups is still ongoing. With patients surviving longer whilst receiving more treatments that may have long-term toxic side-effects, additional questions are raised regarding the effects on HRQOL and cognitive functioning of patients. Indeed, investigating the long-term effects of treatment is listed as a top priority in neuro-oncology research. 8

Preliminary research

The investigational team has almost three decades of research experience in the area of HRQOL and cognitive deficits after glioma treatment. Previous research has found that patients with both low- and high-grade gliomas can experience compromised HRQOL and cognitive functioning, which was generally more pronounced in the high-grade glioma group. However in those with stable, low-grade glioma, HRQOL and cognitive deficits were highly correlated, supporting the notion that even subtle cognitive deficits can affect autonomy in long-term glioma survivors.

While short-term negative effects of chemotherapy on HRQOL are well-documented, longer-term effects of antineoplastic drugs (e.g., bevacizumab) are unknown. Moreover, even low fraction doses of radiotherapy have been shown to have negative consequences for patients' cognitive functioning. WHO grade I and II glioma survivors were assessed on average 12 years after diagnosis and while cognitive functioning had remained stable in patients who had not been treated with radiotherapy, even those who received presumed safe doses (</= 2 Gy) showed a progressive decline in cognitive functioning.9 Moreover, a considerable number of patients showed detectable decline on one or more aspects of HRQOL despite long-term stable disease.6 More recently there have also been investigation into long-term functioning of patients with anaplastic oligo- and oligoastrocytoma. In progression-free patients, HRQOL remained relatively stable whereas cognitive functioning was highly variable across patients, regardless of PCV treatment.7

Despite the recent changes in diagnostics and treatment outlined above, there are no prospective datasets derived from OII/OIII patients treated with the current standards of care. As patients with OII and OIII often receive a range of different treatments for often many years on end, investigating their cognitive functioning and HRQOL becomes ever more important. The long-term consequences of treatment- and disease-related factors on HRQOL and cognitive functioning of patients with OII/OIII 1p/19q codeleted tumours is at present, unknown.

Given the rare occurrence and favourable prognosis of OII/OIII IDH-mutant, 1p/19q codeleted tumours, a cross-European approach is warranted. A collaboration between the EORTC QLG and EORTC BTG provides a unique opportunity to collect pertinent data on how these patients fare after primary treatment. This project aligns with the increased recognition of the issues that cancer survivors face in the long term, both in terms of long-term care needs and in integration in society.

The overall aim of this study is to investigate HRQOL and cognitive functioning of long-term survivors of OII and OIII (with IDH mutation and 1p/19q codeletion). This knowledge can support health care professionals prepare patients for any long-term consequences of treatment, and may even aid in determining to what extent patients might benefit from supportive interventions.

This is a cross-sectional multicentre study, taking place across several European countries. The research co-ordinator and principle investigator are based in Leeds, UK. The co-principle investigator is based in Amsterdam, the Netherlands. Prior to the start of local patient recruitment, each centre will have obtained all relevant ethical and governance approvals.

Patients with OII and OIII with IDH mutation and 1p/19q codeletion diagnosed at least 5 years ago will be recruited, and data on diagnosis and treatment (from medical records), quality of life, mood, fatigue and self-reported cognitive functioning (patient-reported outcomes) and objectively measured cognitive functioning (neuropsychological tests) will be collected.

Study Type

Observational

Enrollment (Actual)

267

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • North Hollan
      • Amsterdam, North Hollan, Netherlands, 1105 AZ
        • Amsterdam UMC
  • United Kingdom
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS9 7FT
        • Leeds institute of Medical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population consists of patients with a primary brain tumour (histologically confirmed oligodendroglioma) who are patients at participating centres in the United Kingdom, the Netherlands, Germany, France, and other European countries (discussions with countries/centres are ongoing).

Description

Inclusion Criteria:

  • Histologically confirmed oligodendroglioma WHO grade II or III with IDH mutation and 1p/19q co-deletion
  • Diagnosis must have been ≥5 years ago
  • Patient is ≥18 years of age
  • Willing and able to provide written informed consent

Exclusion Criteria:

  • They are expected to be unable to complete consent procedures and/or study outcomes due to legal incompetence or insufficient mastery of the language of the country in which they live as determined by their treating physician.
  • They do not provide written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Oligodendroglioma (Grade II and III) Patients
Patients diagnosed with a WHO Grade II or III Oligodendroglioma
Other: Health-related Quality of Life
Health-related quality of life (HRQOL) is an individual's or a group's perceived physical and mental health over time.
Other: Psychological Distress
Measured of the distress experienced by patients
Other: Fatigue
Measure of the extreme tiredness resulting from mental or physical exertion or illness
Other: Cognitive Functioning
Cognitive functioning refers to multiple mental abilities, including learning, thinking, reasoning, remembering, problem solving, decision making, and attention. This will be measured through self-report and cognitive testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health Related Quality of Life - EORTC QLQ-C30
Time Frame: through study completion, an average of 1 year
To assess the effects of an Oligodendroglioma diagnosis on health related quality of life, The EORTC QLQ-C30 assesses functioning domains (e.g. physical, emotional, role) and common cancer symptoms (e.g. fatigue, pain, nausea/vomiting, appetite loss - the higher the score of each item, the greater the intensity/frequency of the experience e.g., 'Have you had pain?' (1 = not at all, 2 = a little , 3 = quite a bit, 4 = very much)
through study completion, an average of 1 year
Disease Specific Quality of Life - EORTC QLQ-BN20
Time Frame: through study completion, an average of 1 year
To assess the disease specific quality of life of brain tumour patients. The EORTC QLQ-BN20 consists of 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. The higher the score of each item, the greater the intensity/frequency of the experience e.g., 'Did you have difficulty speaking?' (1 = not at all, 2 = a little , 3 = quite a bit, 4 = very much)
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Psychological Distress - Hospital Anxiety and Distress Scale (HADS)
Time Frame: through study completion, an average of 1 year
To measure the psychological distress felt by patients, the HADS is is a 14-item measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score - e.g.- 'I feel tense or 'wound up' (Most of the time, A lot of the time, Time to time, Not at all).
through study completion, an average of 1 year
Fatigue - Multidimensional Fatigue Inventory (MFI)
Time Frame: through study completion, an average of 1 year
To assess the level of fatigue experienced by patients, the Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. - E.G. 'I feel fit' (Yes that is true - No, that is not true (scale going from 1-5, 1 being true, 5 being not true.)
through study completion, an average of 1 year
Hopkins Verbal Learning Test - Recall
Time Frame: through study completion, an average of 1 year
The HVLT-R is a learning test, which consists of 12 words within three semantic groups. The test consists of three acquisition trials in which the administrator reads the words aloud and then asks the participant to repeat as many as they can remember. A delayed recall trial is introduced after 20 min, in which the participant is asked to simply retrieve as many of the words listed in the acquisition trial as he/she can remember. Lower raw scores indicate difficulties with word learning and recall, thus suggesting cognitive impairment.
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Galina Velikova

Collaborators

The Leeds Teaching Hospitals NHS Trust
European Organisation for Research and Treatment of Cancer - EORTC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2020

Primary Completion (Actual)

February 28, 2023

Study Completion (Actual)

February 28, 2023

Study Registration Dates

First Submitted

January 7, 2021

First Submitted That Met QC Criteria

January 11, 2021

First Posted (Actual)

January 14, 2021

Study Record Updates

Last Update Posted (Actual)

May 15, 2023

Last Update Submitted That Met QC Criteria

May 10, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 279885

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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