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The role of optical spectroscopy in epilepsy surgery in children

Sanjiv Bhatia, John Ragheb, Mahlon Johnson, Sanghoon Oh, David I. Sandberg, and Wei-Chiang Lin


Surgery is an important therapeutic modality for pediatric patients with intractable epilepsy. However, existing imaging and diagnostic technologies such as MR imaging and electrocochleography (ECoG) do not always effectively delineate the true resection margin of an epileptic cortical lesion because of limitations in their sensitivity. Optical spectroscopic techniques such as fluorescence and diffuse reflectance spectroscopy provide a nondestructive means of gauging the physiological features of the brain in vivo, including hemodynamics and metabolism. In this study, the authors investigate the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to assist epilepsy surgery in children.


In vivo static fluorescence and diffuse reflectance spectra were acquired from the brain in children undergoing epilepsy surgery. Spectral measurements were obtained using a portable spectroscopic system in conjunction with a fiber optic probe. The optical investigations were conducted at the normal and abnormal cortex as defined by intraoperative ECoG and preoperative imaging studies. Biopsy samples were taken from the investigated sites located within the zone of resection. The optical spectra were classified into multiple subsets in accordance with the ECoG and histological study results. The authors used statistical comparisons between 2 given data subsets to identify unique spectral features. Empirical discrimination algorithms were developed using the identified spectral features to determine if the objective of the study was achieved.


Fifteen pediatric patients were enrolled in this pilot study. Elevated diffuse reflectance signals between 500 and 600 nm and/or between 650 and 850 nm were observed commonly in the investigated sites with abnormal ECoG and/or histological features in 10 patients. The appearance of a fluorescent peak at 400 nm was observed in both normal and abnormal cortex of 5 patients. These spectral alterations were attributed to changes in morphological and/or biochemical characteristics of the epileptic cortex. The sensitivities and specificities of the empirical discrimination algorithms, which were constructed using the identified spectral features, were all > 90%.


The results of this study demonstrate the feasibility of using static fluorescence and diffuse reflectance spectroscopy to differentiate normal from abnormal cortex on the basis of intraoperative assessment of ECoG and histological features. It is therefore possible to use fluorescence and diffuse reflectance spectroscopy as an aid in epilepsy surgery.

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Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non–small cell lung cancer and brain metastases

Cheng-Chia Lee, Sanford P. C. Hsu, Chung-Jung Lin, Hsiu-Mei Wu, Yu-Wei Chen, Yung-Hung Luo, Chi-Lu Chiang, Yong-Sin Hu, Wen-Yuh Chung, Cheng-Ying Shiau, Wan-Yuo Guo, David Hung-Chi Pan, and Huai-Che Yang


The presence of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).


This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.


The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).


The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

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Combined stereotactic radiosurgery and tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone for the treatment of non–small cell lung cancer patients with brain metastases

Guan-Ying Chiou, Chi-Lu Chiang, Huai-Che Yang, Chia-I Shen, Hsiu-Mei Wu, Yu-Wei Chen, Ching-Jen Chen, Yung-Hung Luo, Yong-Sin Hu, Chung-Jung Lin, Wen-Yuh Chung, Cheng-Ying Shiau, Wan-Yuo Guo, David Hung-Chi Pan, and Cheng-Chia Lee


Whether combined radiation and tyrosine kinase inhibitor (TKI) therapy in non–small cell lung cancer (NSCLC) patients with brain metastases (BMs) and epidermal growth factor receptor (EGFR) mutations confers additional benefits over TKI therapy alone remains a matter of debate. The goal of this study was to compare outcomes between combined TKI therapy with stereotactic radiosurgery (SRS) versus TKI therapy alone in NSCLC patients with BMs and EGFR mutations.


Consecutive cases of NSCLC patients with EGFR mutations and BMs treated with TKIs were selected for inclusion in this study. Patients were categorized into two groups based on SRS: TKI therapy alone (group I) and combined SRS and TKI therapy (group II). Patients who had SRS or TKI as salvage therapy and those with prior radiation treatment for BMs were excluded. Tumor control (< 10% increase in tumor volume) and overall survival (OS) rates were compared using Kaplan-Meier analyses. Independent predictors of tumor control and OS were identified using multivariable Cox regression analyses.


The study cohort comprised 280 patients (n = 90 in group I and n = 190 in group II). Cumulative tumor control rates were higher in group II than in group I (79.8% vs 31.2% at 36 months, p < 0.0001). Cumulative OS rates were comparable between groups I and II (43.8% vs 59.4% at 36 months, p = 0.3203). Independent predictors of tumor control were older age (p < 0.01, HR 1.03), fewer BMs (p < 0.01, HR 1.09), lack of extracranial metastasis (p < 0.02, HR 0.70), and combined SRS and TKI therapy (p < 0.01, HR 0.25). Independent predictors of OS were fewer BMs (p < 0.01, HR 1.04) and a higher Karnofsky Performance Status score (p < 0.01, HR 0.97).


Although the OS rate did not differ between TKI therapy with and without SRS, the addition of SRS to TKI therapy resulted in improvement of intracranial tumor control. The lack of effect on survival rate with the addition of SRS may be attributable to extracranial disease progression. The addition of SRS to TKI therapy is recommended for intracranial disease control in NSCLC patients with BMs and EGFR mutations. Potential benefits may include prevention of neurological deficits and seizures. Future prospective studies may help clarify the clinical outcome benefits of SRS in these patients.

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2017 AANS Annual Scientific Meeting Los Angeles, CA • April 22–26, 2017

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Oral Presentations 2015 AANS Annual Scientific Meeting Washington, DC • May 2–6, 2015

Published online August 1, 2015; DOI: 10.3171/2015.8.JNS.AANS2015abstracts