Introduction: Brainstem gliomas (BSGs) are primarily found in the pediatric population, accounting for 10% of all brain tumors in these patients [1]. These lesions peak in incidence around the first decade of life and have varying prognosis that is dependent on location, morphology, and histological grade [2]. Pediatric malignant BSGs typically present as diffuse pontine lesions and have a median survival less than 1 year [3]. As BSGs in children are primarily diagnosed by appearance on magnetic resonance imaging, current studies have had few cases of pathologically confirmed malignant BSGs.

Methods: The Surveillance Epidemiology and End-Results (SEER) database was utilized to identify pediatric patients diagnosed with malignant brainstem gliomas (anaplastic astrocytoma and glioblastoma) between 1973 and 2008 (n = 189). We assessed the impact of various patient, tumor, and treatment factors on survival.

Results: The overall median survival was 9 months, with patients with grade III and IV tumors demonstrating significantly different survival (10 vs. 8 months, p=0.0053). Multivariate stepwise regression analysis revealed female gender (HR:1.4; 95%CI:1.04-1.91; p=0.027) and grade IV pathology (HR:1.5; 95%CI:1.12-2.05; p=0.0071) to be independent poor prognostic factors, with resection (HR:0.46; 95%CI:0.27-0.77; p=0.003) and age (HR:0.96; 95%CI:0.93-0.99; p=0.025) as favorable prognostic factors. The timing of radiation with respect to surgery, use of external beam radiation, and race did not affect survival. Subgroup analysis revealed age (HR:1.03; 95%CI:1.01-1.04; p<0.0001) to be a poor prognostic factor in those with grade III tumors, with resection (HR:0.47; 95%CI:0.29-0.75; p=0.0017) and use of external beam radiation (HR:0.51; 95%CI:0.33-0.78; p=0.0021) being associated with improved survival. For those with grade IV lesions, only resection (HR:0.56; 95%CI:0.37-0.86; p=0.0085) was a significant predictor of survival.

Conclusions: Pediatric malignant brainstem gliomas are aggressive lesions with an overall poor prognosis, with female gender and grade IV pathology predicting worse survival. Resection in select cases may improve survival in patients with these lesions.

Patient Care: Pediatric malignant brainstem gliomas are aggressive, universally fatal lesions which typically present as diffuse lesions. Magnetic resonance imaging (MRI) typically reveals an expansile pontine lesion with indistinct margins, reflecting their high grade nature. However, high grade brainstem gliomas may also present as focal or exophytic masses, complicating diagnosis. Currently, the majority of pediatric brainstem gliomas are diagnosed by appearance on MRI, resulting in few small studies with pathological confirmed cases of pediatric malignant brainstem gliomas. In this study, we examine a nationally selected cohort of patients and identify several prognostic factors. Female gender and grade IV pathology were revealed as poor prognostic factors, while resection and increasing age significantly improved survival. Interestingly, the use of external beam radiation did not significantly influence survival in the total cohort though it is accepted that radiotherapy is the only life-prolonging therapy for pediatric brainstem gliomas. However, subgroup analysis revealed radiotherapy to significantly increase survival in those with grade III, not grade IV lesions. For those with grade IV lesions, the only prognostic factor identified was the use of resection. Surgical treatment of pediatric brainstem gliomas is highly controversial, with many authors discouraging resection due to potentially significant morbidity and mortality. However, many studies have demonstrated increases in survival with the resection of focally enhancing brainstem lesions with acceptable postoperative morbidity. As these studies mainly demonstrated improvements in survival for those with focal low grade lesions, many still question the utility of resection for malignant brainstem gliomas. Here we demonstrate that the use of resection for select malignant brainstem lesions may increase survival, and therefore warrants consideration. We hope this study stimulates further research to identify effective therapies for the treatment of these deadly tumors.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of accurate diagnosis and aggressive treatment of pediatric malignant brainstem gliomas, 2) Discuss, in small groups the natural history, prognostic factors, and treatment of pediatric malignant brainstem gliomas, 3) Identify an effective treatment for pediatric brainstem gliomas which may involve resection for select lesions.

References: 1. Farwell JR, Dohrmann GJ, Flannery JT. Central nervous system tumors in children. Cancer. Dec 1977;40(6):3123-3132. 2. Tokuriki Y, Handa H, Yamashita J, Okumura T, Paine JT. Brainstem glioma: an analysis of 85 cases. Acta neurochirurgica. 1986;79(2-4):67-73. 3. Farmer JP, Montes JL, Freeman CR, Meagher-Villemure K, Bond MC, O'Gorman AM. Brainstem Gliomas. A 10-year institutional review. Pediatric neurosurgery. Apr 2001;34(4):206-214.