Introduction: Brainstem gliomas (BSGs) in adults are not well characterized due to their rarity, accounting for approximately 2% of all brain tumors in adults. These lesions tend to be clinically and radiographically heterogenous, with diffuse intrinsic low grade BSGs having a median survival of 7.3 years, compared to 11.2 to 17 months for malignant BSGs. As malignant BSGs account for a minority of BSGs in adults, their natural history, molecular characteristics, and prognostic factors are completely undefined.
Methods: We searched a comprehensive database containing all patient data from the Duke University Medical Center using the ICD-9 diagnosis code 191.7. Our cohort consisted of all histopathologically confirmed cases of adult malignant BSGs. Chart reviews were performed to collect a variety of patient and clinical factors.
Results: Examination of prognostic factors revealed age greater than 40 years (p=0.018), WHO grade IV (p=0.003), and time to progression less than 12 months (p=0.027) to significantly affect survival. However, WHO grade IV was the only variable approaching significance as an independent predictor of survival (HR: 7.1; 95%CI: 0.94-53.7; p=0.058). Immunohistochemical examination revealed positive EGFR, MGMT, and EGFRvIII staining in 93.3%, 64.7%, and 12.5% of examined cases, respectively. Also, fluorescence in situ hybridization analysis revealed EGFR and PTEN mutations in 92.9% and 61.5% of tested cases, respectively. Operative treatment most frequently consisted of stereotactic biopsy (58.6%), with resection occurring in the remaining cases. Though not significant, there was a trend for increased survival following resection (17.4 vs. 14.5 months, p=0.49). All patients underwent radiotherapy and received temozolomide, with other agents being added for cases with progression.
Conclusions: Malignant BSGs in adults are aggressive lesions with poor prognosis, with worse outcomes associated with older age and grade IV lesions. Additional studies are needed to evaluate the use of resection and anti-EGFR therapies for treatment of these tumors.
Patient Care: Brainstem gliomas in adults are an uncommon, clinically and radiographically heterogeneous group of tumors with widely varying survival times. While overall median survival time has been reported to be approximately 4.5 to 7 years, WHO grade significantly affects outcome, with low grade lesions having survival up to 168 months, compared to high grade lesions which have an approximate median survival from 11.2 to 17 months. In the few retrospective studies of adult brainstem gliomas, there has been little discussion of histologically proven high grade lesions due to the low number of cases. Thus far, the natural history, prognostic factors, molecular characteristics, and appropriate treatments are unknown. In this study, we present the largest institutional series of malignant brainstem gliomas in adults, and identify several poor prognostic factors, including age greater than 40 years, grade IV pathology, and time to progression less than 12 months. Additionally, for the first time, we reveal adult malignant brainstem gliomas to frequently harbor epidermal growth factor receptor (EGFR) mutations, with abnormalities occurring much more commonly than in their supratentorial counterparts, in which EGFR mutations are found in approximately 45% of tumors. As a result, anti-EGFR treatments should be investigated for the treatment of adult malignant brainstem gliomas. Also, the role of resection in the treatment of brainstem gliomas is controversial as resection in this highly eloquent region can involve significant morbidity and mortality. Though some studies in the pediatric literature have demonstrated improved survival for low grade brainstem gliomas, many authors have questioned the justification for resecting malignant lesions due to their infiltrative nature which results in a reduced extent of resection. We demonstrate a trend toward increased survival with resection of adult malignant brainstem gliomas and recommend resection for those which are focally enhancing. We hope that this study aids in the management of these uncommon tumors and stimulates further research into the treatment of these aggressive lesions.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of accurately diagnosing brainstem gliomas in adults, 2) Discuss, in small groups the prognostic factors and pathological characteristics of malignant brainstem gliomas in adults, 3) Identify an effective treatment for malignant brainstem gliomas in adults and identify other therapies which may increase survival in patients with these lesions.