Because of their prolonged survival, patients with 1p/19q-codeleted low-grade oligodendrogliomas treated with RT + PCV are at risk of neurocognitive deterioration. We make the hypothesis that withholding radiotherapy until tumor progression could reduce the risk of neurocognitive deterioration without impairing overall survival.

Inclusion Criteria:

• Tumor is co-deleted for 1p and 19q based and IDH-mutant (IDH1 or IDH2) according to local diagnosis

• Histological confirmation of low-grade oligodendroglioma by central pathological review according to WHO 2016 classification

• Age ≥ 18 years

• Patients with one or several prior surgical procedure for a low-grade oligodendroglioma and who undergo a resurgery are eligible if they have not received prior radiotheray or chemotherapy and if the last histological diagnosis is a low-grade oligodendroglioma prior use of specific HDI prohibitions is permitted

• Patients who undergo an initial follow-up after surgery or re-surgery are eligible if there is no evidence of anaplastic transformation on MRI (no new contrast enhancement, no obvious modification of the growth rate)

• Patients requiring an oncological treatment other than surgery because of one or more of the following characteristics:

  • Progressive disease defined as documented growth prior to inclusion
  • Symptomatic disease defined as the presence of neurological or cognitive symptoms or refractory seizures defined as having both persistent seizures interfering with everyday life activities other than driving a car and three lines of anti-epileptic drug regimen had not worked, including at least one combination regimen.
  • Age ≥ 40 and any surgical therapy
  • Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)

• Willing and able to complete neurocognitive examination and the QOL

• Karnofsky performance status ≥ 60

• Laboratory values obtained between 21 days before inclusion andrandomization, respecting the following criteria:

• Absolute neutrophil count (ANC) ≥1500 /mm3

• Platelet count ≥100,000 / mm3

• Hemoglobin > 9.0 g/dL

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

• SGOT (AST) ≤ 3 x ULN

• Negative serum or urine pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.

• Provide informed written consent

Exclusion Criteria:

• Pregnant and nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception for up to 6 months following the completion of PCV.
• Received any prior radiation therapy or chemotherapy for any CNS neoplasm.
• Co-morbid systemic illnesses or other severe concurrent disease which would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Concomitant serious immunocompromised status (other than that related to concomitant steroids).
• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm (except specific inhibitors of IDH)
• Other active malignancy within 5 years of registration. Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• Contra-indication to CCNU: hypersensitivity to CCNU, wheat allergy, association to yellow fever vaccin
• Contra-indication to Procarbazine: severe renal failure, severe hepatic failure, hypersensitivity to procarbazine, association to yellow fever vaccin
• Contra-indication to Vincristine: hypersensitivity to vincristine, neuromuscular disorder (for example demyelinating Charcot-Mary Tooth neuropathy), severe renal failure, severe hepatic failure.
• Not depending from the french system of health assurance