Donita D. Lightner

Epidemiologic and Molecular Prognostic Review of Glioblastoma

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM, but the majority are sporadic, and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified, including younger age at diagnosis, cerebellar location, high performance status, and maximal tumor resection. GBMs comprise of primary and secondary subtypes, which evolve through different genetic pathways, affect patients at different ages, and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value. Cancer Epidemiol Biomarkers Prev; 23(10); 1985–96. ©2014 AACR.

Long-term treatment with temozolomide in malignant glioma.

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.

Surfer’s myelopathy without surfing: a report of two pediatric patients

Introduction:Surfer’s myelopathy (SM) is a rare disorder described in subjects presenting with acute paraparesis while learning how to surf. It is thought to be secondary to spinal ischemia triggered by hyperextension. Spinal magnetic resonance imaging (MRI) shows changes consistent with spinal cord ischemia on T2-weighted and diffusion-weighted imaging (DWI).Case Presentation:We report two patients who presented with acute onset paraplegia shortly after spinal hyperextension. They had no physical or radiological evidence of soft tissue injury. Their clinical and imaging findings closely resemble those described in SM.Discussion:We propose the use of the term ‘acute hyperextension myelopathy’ to categorize patients with spinal cord infarction secondary to hyperextension. DWI sequencing on MRI should be considered to evaluate for early signs of spinal cord ischemia in these patients. Use of a broader term for diagnostic classification can help include patients with spinal cord infarction due to a common mechanism.

Comprehensive evaluation of treatment and outcomes of low-grade diffuse gliomas

Background Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States. Methods We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma. Results We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most common primary site location was the cerebrum (79.9%). Overall, 72.2% received surgery, 36.0% radiation, and 27.3% chemotherapy. Treatment combinations included surgery only (41.5%), chemotherapy + surgery (6.6%), chemotherapy only (3.1%), radiation + chemotherapy + surgery (10.7%), radiation + surgery (11.5%), radiation only (6.1%), and radiotherapy + chemotherapy (6.7%). Radiation was more common in treatment of elderly patients, 1p/19q co-deletion (37.3% versus 24.3%, p<0.01), and tumors with midline location. Median survival was 11 years with younger age, 1p/19q co-deletion, and cerebrum location offered survival advantage. Conclusions Tumor location, 1p/19q co-deletion, and age were the main determinants of treatment received and survival, likely reflecting tumor biology differences. Any form of treatment was preferred over watchful waiting in the majority of the patients (86.1% versus 8.1%). Survival of low-grade gliomas is higher than previously reported in the majority of clinical trials and population-based analyses. Our analysis provides a real world estimation of treatment decisions, use of molecular data, and outcomes.

Brain tumors associated with psychogenic non-epileptic seizures: Case series

OBJECTIVE The association of psychogenic non-epileptic seizures (PNES) with primary or secondary brain tumors has not been well described in the literature. We aim to discuss their association, and their impact in brain tumor treatment. PATIENTS AND METHODS We identified four patients retrospectively from our practice. The diagnosis of PNES was based on clinical suspicion and standard EEG, supplemented with video-EEG recording in 2 patients. RESULTS The initial diagnosis of brain tumor was associated with a new onset seizure prior to diagnosis. The majority of the patients presented with ES followed by recurrent PNES during the course of their disease. Patients were treated with multiple anti-epileptic drugs, requiring frequent schedule adjustments. The preferred tumor treatment modality was chemotherapy, followed by surgical resection. The patients were offered psychological consultation achieving partial control of their events. These patients manifested recurrent disabling clinical events that required multiple medical consultations. None of these patients presented clinical evidence of tumor progression at the time of PNES presentation. CONCLUSION A high index of suspicion and early psychological consultation referral will likely mitigate the quality of life impact of PNES in these patients.