If left untreated, patients with oligodendroglioma may progress to develop seizures, focal neurological deficits, hydrocephalus, brain herniation, intracranial hemorrhage, and ultimately death.Common complications associated with oligodendroglioma include hydrocephalus, intracranial hemorrhage, coma, bone marrow metastasis, recurrence, venous thromboembolism, parkinsonism, and side effects of chemotherapy and radiotherapy. Oligodendroglioma is a slow growing tumor having a good prognosis overall with prolonged survival. But the prognosis of oligodendroglioma may vary depending upon various prognostic factors such as population based estimates, clinical factors, tumor grade (II versus III), mechanism of chemosensitivity, and molecular markers such as 1p/19q-codeletion, IDH1/2 mutation, and TERT promoter mutations. The median survival time for oligodendroglioma is 11.6 yearsfor grade II and 3.5 years for grade III.

• Oligodendrogliomas tend to be low grade and less aggressive than other types of gliomas.
• These tumors are slow growing.
• The tumors may be present for many years before they are diagnosed.^[1]
• Anaplastic oligodendroglioma usually grows quickly.
• These tumors may develop in one place or in many places throughout the brain.
• If left untreated, patients with oligodendroglioma may progress to develop seizures, focal neurological deficits, hydrocephalus, brain herniation, intracranial hemorrhage, and ultimately death.^[2]
• Recurrence is a very common feature of oligodendrogliomas.
• Recurrence can be either of the same grade or higher grade at the primary site.^[3]
• Transformation into glioblastoma (grade 4) may occur a few years later, which may be associated with gain of chromosome 7 and loss of chromosome 10.^[3]

Common complications associated with oligodendroglioma include:^{[4][5][6][7][8][9][10]}

• Hydrocephalus
• Intracranial hemorrhage
• Coma
• Bone marrow metastasis
• Recurrence
• Venous thromboembolism
• Parkinsonism
• Side effects of chemotherapy
• Side effects of radiotherapy

• Depending on the extent and grade of the tumor at the time of diagnosis, the prognosis of oligodendroglioma may vary.
• However, the prognosis is generally regarded as good overall.^[11][12]
• Oligodendrogliomas are slowly growing tumors with prolonged survival.
• In March 2001, 7 neuropathologists and 6 surgical pathologists experienced in brain tumor–diagnosis assessed 124 oligodendroglial tumors operated at the Mayo Clinic during the period of 1960 to 1990. In this study, the prognostic value of histological grading of oligodendroglial tumors in tumor grading was assessed, and following parameters of significant association with survival was found:^[13]

Following are the few prognostic factors associated with oligodendroglial tumors:

• According to the population based estimates, despite of the prolonged clinical course of oligodendroglial tumors, outcome is almost always fatal.
• Overall median survival for patients with low-grade oligodendroglioma is approximately 10 to 15 years.^[16][17]
• Median survival for patients with anaplastic oligodendroglioma is approximately 5 to 9 years.^[11]
• Median survival of patients with 1p/19q-codeleted oligodendrogliomas who are treated with radiation plus procarbazine, lomustine, and vincristine (PCV) may be closer to 20 years for grade II tumors and 15 years for grade III tumors.^[18][19][20]
• The presence of 1p/19q codeletion is associated with a better prognosis and greater chemosensitivity.^{[4][21][22][23]}
• Several other molecular markers have a potential clinical significance as IDH1 mutations, confirming the strong prognostic role for overall survival.^{[24][25][26][27][28][29]}
• The presence of EGFR gene mutation is associated with a worse prognosis.^[30]

Following is a list of more commonly identified clinical features that predict worse overall survival:

• Older age
• Poor functional status
• Baseline neurologic deficits
• Nonepilepsy presentation
• Tumor location other than frontal and parietal lobes
• Large tumor size (>4 to 5 cm)

Clinical features that are independently associated with improved overall survival in patients with anaplastic oligodendroglial tumors include:^[31][32]

• Younger age
• Confirmed absence of residual tumor by imaging after surgery
• Frontal tumor location
• Good performance status

• WHO grade III anaplastic oligodendrogliomas have worse prognosis comparative to low-grade tumors, with an average difference of approximately five years in overall survival(11.6 years for grade II and 3.5 years for grade III).^[29][33]
• The 5-year survival rates for oligodendroglioma and anaplastic oligodendroglioma varying with ages are tabulated below:^[34][13]

• 1p/19q-codeletion:
  • Presence of 1p/19q-codeletion is associated with improved survival in patients with IDH–mutant diffuse gliomas (with regard to both natural history of disease and better response to therapy).^{[35][36][37][38][39][40][24]}
  • Presence of polysomy of chromosomes 1 and 19 may be useful in identifying patients with poorer prognosis who have a subset of both anaplastic oligodendroglioma and a characteristic 1p/19q-codeletion.^[41][42]
  • Patients with 1p/19q loss and polysomy have a significantly shorter median progression-free survival compared with those without polysomy.^[41]
  • Capicua transcriptional repressor (CIC) inactivating mutations are associated with worse outcome in 1p/19q-codeleted oligodendrogliomas.^[43]
• IDH1/2 mutation:
  • IDH1 and IDH2 mutations are associated with improved survival in patients of glial tumors, irrespective of the treatment received.^[44][24]
  • Prognostic significance of IDH1/2 mutations is equally as strong as that of the 1p/19q-codeletion.^[24]
  • IDH mutations are found in diffuse gliomas with and without the 1p/19q-codeletion.
  • North American Radiation Therapy Oncology Group (RTOG) 9402 and 9802 studies suggested that IDH mutations are predictive for outcome to adjuvant chemotherapy, independent of other molecular factors.^{[18] [45]}
• TERT promoter mutations:
  • Prognostic significance is dependent on the genetic background of the tumor (as Telomerase reverse transcriptase (TERT) promoter mutations occur in virtually all 1p/19q-codeleted, IDH–mutant tumors and also in glioblastoma).
  • Negatively associated with alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutations (occur in most IDH–mutant astrocytomas).

• Studies have shown a high response rate with single-agent temozolomide.
• IDH mutations result in metabolic alterations, including:^[46]
  • Decreased alpha-ketoglutarate
  • Increased levels of 2-hydroxyglutarate (2HG)
  • Changes in nicotinamide adenine dinucleotide phosphate (NADP) levels
  • Decrease in alpha-ketoglutarate
  • Increase in 2HG
• This leads to epigenetic alterations and development of a CpG island hypermethylated phenotype (CIMP), which includes MGMT promoter methylation.^[47]
• MGMT is a nuclear enzyme responsible for deoxyribonucleic acid (DNA) repair following alkylating-agent chemotherapy and may mediate part of the cellular resistance to alkylating agents.
• MGMT expression can be silenced by methylation of its promoter.^[48]

Template:WikiDoc Sources