Clark Chen

Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases

The treatment of metastatic brain lesions remains a central challenge in oncology. Because most chemotherapeutic agents do not effectively cross the blood–brain barrier, it is widely accepted that radiation remains the primary modality of treatment. The mode by which radiation should be delivered has, however, become a source of intense controversy in recent years. The controversy involves whether patients with a limited number of brain metastases should undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) delivered only to the radiographically visible tumours. Survival is comparable for patients treated with either modality. Instead, the controversy involves the neurocognitive function (NCF) of radiating cerebrum that appeared radiographically normal relative to effects of the growth from micro-metastatic foci. A fundamental question in this debate involves quantifying the effect of WBRT in patients with cerebral metastasis. To disentangle the effects of WBRT on neurocognition from the effects inherent to the underlying disease, we analysed the results from randomised controlled studies of prophylactic cranial irradiation in oncology patients as well as studies where patients with limited cerebral metastasis were randomised to SRS versus SRS+WBRT. In aggregate, these results suggest deleterious effects of WBRT in select neurocognitive domains. However, there are insufficient data to resolve the controversy of upfront WBRT versus SRS in the management of patients with limited cerebral metastases.

Clinical outcome after Hypofractionated Stereotactic Radiotherapy (HSRT) for benign skull base tumors

Objective: Surgical resection of skull base tumors can be associated with significant morbidity. In cases where the risks outweigh the benefits, radiation therapy can offer an alternative means to effectively control tumor growth. However, the optimal dose regime for radiation therapy remains controversial. The objective of this study was to assess the neurological outcome, local control rate and morbidity associated with a 5-fraction regime of hypofractionated stereotactic radiotherapy (HSRT) for benign skull base tumors. Methods: Twenty-six patients presenting with two of the most prevalent benign skull base tumors were included in the study. The tumors comprised 16 meningiomas and 10 acoustic neuromas. All patients exhibited preserved cranial nerve function prior to treatment, and a detailed audiological assessment was performed pre- and post-treatment for those patients with acoustic neuroma. Stereotactic radiosurgery was administered with the frameless CyberKnife Robotic Radiosurgery System. In each case, a 5-fraction HSRT regime was used: a dose of 5 Gy × 5 = 25 Gy to 6 Gy × 5 = 30 Gy was prescribed for skull base meningiomas, and 5 Gy × 5 = 25 Gy was prescribed for acoustic neuromas. Results: The clinical and radiographic median follow-up was 22 months (range: 6-54 months). Radiological assessment showed local control in all 26 tumors (100%), and in 5/26 patients (20%) the tumor showed a decrease in size. Cranial nerve function was preserved in all cases thus far studied; however, 28% of patients had transient Grade II side effects, including fatigue, headaches, unsteadiness and transient subjective worsening of hearing. In two of these patients, the period of transient worsening of hearing was associated with a temporary increase in the size of the tumor on control T2 MR images, consistent with radiation-induced edema. One patient had transient decrease in visual acuity from treatment-related edema. At the last follow-up, 3/16 patients with meningiomas (19%) and 2/10 with acoustic neuromas (20%) showed a decrease in tumor volume and improvement in hearing. Conclusion: A 5-fraction stereotactic radiotherapy regime, as used in this study, seems to be effective for local control of benign skull base tumors in this early follow-up evaluation. Neurological function preservation is excellent with this short regime in the early post-treatment period, but long-term follow-up is crucial for validation.

Localizing seizure-susceptible brain regions associated with low-grade gliomas using voxel-based lesion-symptom mapping

BACKGROUND Patients afflicted with low-grade glioma (LGG) frequently suffer from seizures. The mechanisms of seizure initiation in these patients remain poorly understood. Tumor location has been correlated with seizure initiation. However, these correlative studies relied on dichotomized data analysis based on arbitrary lobe assignments. As a result, the lesion-symptom correlation may be incorrectly interpreted. Here, we present the first study that used a voxel-wise quantitative lesion analysis to investigate the spatial correlation between tumor location and seizure susceptibility. METHODS We collected the medical records and magnetic resonance images of 410 LGG patients. The dataset was divided into a discovery set and a validation set. A voxel-based lesion-symptom correlative analysis was performed to determine whether tumor location was associated with seizure risk and could be related to the specific type of seizure. RESULTS For all seizure types, increased seizure risks were identified for LGGs that involved the left premotor area. The LGGs that involved the posterior portion of the left inferior and middle frontal gyrus were associated with increased risk of simple partial seizures. LGGs that involved the right temporal-insular region were associated with an increased risk of complex partial seizures. LGGs that involved the left premotor area were more likely to be associated with seizures that generalize. These correlations were consistently observed in both the discovery and the validation datasets. CONCLUSIONS Our quantitative neuroimaging analyses support the concept that the anatomic location of an LGG is a contributing factor in tumor-related seizure.

Ventriculoperitoneal shunting: Laparoscopically assisted versus conventional open surgical approaches.

Objectives: Ventriculoperitoneal shunting (VPS) is a mainstay of hydrocephalus therapy, but carries a significant risk of device malfunctioning. This study aims to compare the outcomes of laparoscopic ventriculoperitoneal shunting versus open ventriculoperitoneal shunting (OVPS) VPS-placement and reviews our findings in the pertinent context of the literature from 1993 to 2012. Materials and Methods: Between 2003 and 2012, a total of 232 patients underwent first time VPS placement at Beth Israel Deaconess Medical Center. Of those, 155 were laparoscopically guided and 77 were done conventionally. We analyzed independent variables (age, gender, medical history, clinical presentation, indication for surgery and surgical technique) and dependent variables (operative time, post-operative complications, length of stay in the hospital) and occurrence of shunt failure. Results: Mean operative time was 43.7 min (18.0-102.0) in the laparoscopic group versus 63.0 min (30.0-151.0) in the open group, (P < 0.05). Length of stay was similar, 5 days in the laparoscopic and in the open group, (P = 0.945). The incidence of shunt failure during the entire follow-up period was not statistically different between the two groups, occurring in 14.1% in the laparoscopic group and 16.9% in the open group, (P = 0.601). Kaplan-Meier analysis demonstrated no difference in shunt survival between the two groups (P = 0.868), with functionality in 85% at 6-months and 78.5% at 1-year. Conclusion: According to our study, LVPS-placement results compare similarly to OVPS placement in most aspects. Since laparoscopic placement is not routinely indicated, we suggest a prospective study to assess its value as an alternate technique especially suitable in obese patients and patients with previous abdominal operations.

‘Journal Bias’ in peer-reviewed literature: an analysis of the surgical high-grade glioma literature

The core premise of evidence-based medicine is that clinical decisions are informed by the peer-reviewed literature. To extract meaningful conclusions from this literature, one must first understand the various forms of biases inherent within the process of peer review. We performed an exhaustive search that identified articles exploring the question of whether survival benefit was associated with maximal high-grade glioma (HGG) resection and analysed this literature for patterns of publication. We found that the distribution of these 108 articles among the 26 journals to be non-random (p<0.01), with 75 of the 108 published articles (69%) appearing in 6 of the 26 journals (25%). Moreover, certain journals were likely to publish a large number of articles from the same medical academic genealogy (authors with shared training history and/or mentor). We term the tendency of certain types of articles to be published in select journals ‘journal bias’ and discuss the implication of this form of bias as it pertains to evidence-based medicine.

Molecular Etiology of Glioblastomas: Implication of Genomic Profiling From the Cancer Genome Atlas Project

Kimberly Ng.1, Santosh Kesari2, Bob Carter3,4 and Clark C. Chen1,5 1Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 2Department of Neurology, Moores UCSD Cancer Center, UCSD, 3Center for Theoretic and Applied Neuro-Oncology, University of California San Diego, San Diego, CA 4Department of Surgery, Division of Neurosurgery, University of California San Dieog, San Diego, CA 5Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA USA