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.

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 (\

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

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).