Clinical trial NCT04708548: Long Term Implications of Rare Brain Tumours'
Official title: Understanding the Long-term Implications of Treatment of Rare Brain Tumours on Health-related Quality of Life: A European Cross-sectional Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Quality of Life
Cognitive Impairment
WHO Grade II Oligodendroglial Tumor
WHO Grade III Oligodendroglial Tumor
Long-term Effects of Cancer Treatment
Health-related Quality of Life
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: The Leeds Teaching Hospitals NHS Trust
First posted: 2021-01-14
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
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).

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Health Related Quality of Life - EORTC QLQ-C30
timeFrame: through study completion, an average of 1 year
measure: Disease Specific Quality of Life - EORTC QLQ-BN20
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Psychological Distress - Hospital Anxiety and Distress Scale (HADS)
timeFrame: through study completion, an average of 1 year
measure: Fatigue - Multidimensional Fatigue Inventory (MFI)
timeFrame: through study completion, an average of 1 year
measure: Hopkins Verbal Learning Test - Recall
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: North Hollan
city: Leeds
country: United Kingdom
facility: Leeds Institute of Medical Research
state: West Yorkshire
Study officials:
References: