Illustrative Case Series

Glioblastoma

By Samir Kanani, MD, Associate Clinical Professor of Radiation Oncology, George Washington University; Inova Fairfax Cancer Center. Dr. Kanani reports no relationships to this field of study.

A 78-year-old man was referred for evaluation and treatment of recently discovered glioblastoma. While dining with his children he collapsed from his chair and was observed to have a grand mal seizure. He had transiently lost consciousness and when he awoke he had weakness in both upper and lower extremities on the right side.

Past medical history is significant for long-term cigarette smoking, chronic obstructive pulmonary disease, hypertension, mild congestive heart failure, and type II diabetes mellitus.

He was taken to the emergency room where he was found to be slightly disoriented but awake. Blood pressure was 180/80, pulse 93/min, and respiratory rate 16/min. Oxygen saturation was 94% on room air. His chest was clear to auscultation and heart sounds were regular with an S4 gallop but no murmur. Neurologic exam revealed prominent right-sided weakness and slight facial asymmetry with weakness on the left. An MRI of the brain and spine revealed an enhancing solitary tumor mass of approximately 2 cm in diameter in the left prefrontal region with moderate surrounding edema. The patient was admitted and on the following day an open biopsy revealed a high-grade glioblastoma.

CASE DISCUSSION

In general, gliomas account for 60% of all central nervous system (CNS) malignancies and glioblastoma (GBM) is the most prevalent subtype of gliomas. Presenting symptoms of GBM are variable and depend on the location of the lesion. Seizures, headaches, nausea, vomiting, hemiparesis, personality change, and memory difficulties are the most common symptoms of CNS malignancies.

GBM can be classified into two general categories: primary and secondary. In this age group of patients older than 50, primary GBMs account for the vast majority of tumors. Although primary GBMs develop de novo over a few months, secondary brain tumors develop over years through malignant transformation of lower grade gliomas. Genetically, primary and secondary tumors develop from unique genetic pathways. Recent gene expression profiling has focused on identifying four subtypes of GBM: classical, mesenchymal, proneural, and neural.1 The use of genetic profiling in clinical practice currently remains experimental and is the subject of a number of current clinical trials.

No formal staging system exists to assist in managing patients with GBM; however, well-known prognostic factors can be applied to stratify patients for prognostic purposes and to assist in treatment decisions. Through recursive partition analysis (RPA), various prognostic groups can be identified. Two well-known and widely used RPAs are the RTOG2 and the EORTC.3 Age, performance status, neurologic status, and extent of surgery provide the backbone for defining RPA class. The RTOG RPA stratifies patients into prognostic groups based on studies where all patients were treated with radiation. The EORTC stratifies patients based on the landmark Stupp trial where patients received a combination of temozolomide and 6000cGy radiation followed by adjuvant temozolomide.4 The above patient with age > 50 years, ECOG 4 (bedridden), significant neurologic symptoms (hemiplegia), and post-biopsy alone, falls in RPA class V. According to both of the well-known RPAs, class V has the most dismal prognosis of 9-10 months with or without chemotherapy. I would not recommend chemotherapy in this patient based on the lack of any significant benefit in this RPA class. Radiation therapy alone or supportive care should be discussed with the patient. If the patient agrees to radiation therapy, serious consideration should be made for a short course or hypo-fractionated course of radiation therapy rather than the standard course of 6000cGy in 30 fractions. A randomized trial comparing the standard course of radiation to 4000cGy in 15 fractions in this patient population found no difference in median survival.5 The issues of transportation can be difficult in patients with significant neurologic complications; therefore, all patients should be given a realistic expectation of the results from radiation, and consultation with palliative care or hospice care should be initiated early in the process.

References

1. Parsons DW, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008;321:1807-1812.

2. Curran WJ Jr, et al. Rucursive Partitioning Analysis in three RTOG malignant glioma trials. J Natl Cancer Inst 1993;85:690-691.

3. Mirimanoff R, et al. Radiotherapy and temozalimide for newly diagnosed GBM: RPA of the EORTC 26981 Phase III randomized trial. J Clin Oncol 2006;24:2563-2569.

4. Stupp R, et al. Concomitant and adjuvant temozolomide for GBM. N Engl J Med 2005;352:987-996.

5. Roa W, et al. Abbreviated course of radiation therapy in older patients with GBM: A prospective randomized trial. J Clin Oncol 2004;22:1583-1588.