Know it, to control it

High-grade glioma – current challenges

High-grade gliomas (HGGs) are aggressive brain tumors, of these; glioblastoma (GBM) is the most malignant with a high rate of recurrence after initial resection. Malignant gliomas may develop at all ages, with the peak incidence being between 50-60 years of age. Exposure to ionizing irradiation has been associated with increased risk of development of glioma, while association with the use of cell phones has not been confirmed in epidemiological studies. Rare hereditary syndromes carry an increased risk for glioma: Cowden-, Turcot-, Lynch-, Li-Fraumeni syndrome and neurofibromatosis type 1. Lower tumour grade, radical tumour resection, younger age age age (> 50 years),  good performance status and an intact neurological function are favorable prognostic factors. Anaplastic astrocytoma and oligoastrocytoma have a better prognosis compared with GBM.

Earlier, standard treatment included surgery in the form of maximal safe resection and post-operative radio¬therapy (PORT). HGGs may be large at the time of diagnosis. This predisposes large volume of normal brain to high doses of radiation during postoperative radiation therapy. High precision techniques like Intensity Modulated Radiotherapy (IMRT) reduce high dose to normal brain thus reducing neuro-cognitive effects in long term survivors. Achieving long term survival in HGGs is usually not possible due to its aggressive nature, and despite advances in surgery, new chemotherapeutic agents, and techniques in radiotherapy the prognosis of HGGs is still poor.

Assessing HGGs is by magnetic resonance imaging (MRI) because of the focal brain lesion. Of note, in post-radiation MRI imaging, increased contrast enhancement and presumed tumour progression on imaging 4–12 weeks after the end of radiotherapy may be due to a reactive process following radiotherapy (pseudo-progression), with >60% pseudo-progression reported among patients with early radiological progression after radiochemotherapy. MRI also plays an important role post-surgery — the extent of tumour resection and determination of residual disease should be assessed within 24–48 h of surgery in order to distinguish post-surgical contrast enhancement from the residual tumor.

In newly diagnosed GBM, temozolomide used concomitantly with PORT, followed by adjuvant temozolomide significantly improved median survival from 12.1 months to 14.6 months. Since then, radio¬therapy plus concomitant and adjuvant temozolomide has become the standard of care in newly diagnosed GBM. The 2-year survival rate was found up to 26.5% for the combined treatment group. A study from India shows similar results. In addition, patients with glioblastoma containing a methylated MGMT promoter region showed an improved survival compared to those who did not have a methylated MGMT promoter region. Recurrence is common, and repeat surgery is indicated in HGGs exerting a mass effect.

In conclusion, HGG is the most common malignant tumor of the brain and remains a challenge for both the oncology and radiology communities. The bleak prognosis is due to innate cellular, genetic, and histological complexity. Radiother¬apy plus concomitant and adjuvant 6 cycles temozolomide yield encouraging outcomes in this population.The advances in molecular biology and newer therapeutic agents are expected to change this bleak outcome in future.