Cesium-131 brachytherapy for the treatment of brain metastases: Current status and future perspectives.

Adjuvant radiotherapy is often necessary following surgical resection of brain metastases to improve local tumor control and survival. Brachytherapy using cesium-131 offers a novel method for loco-regional radiotherapy. We reviewed the current literature reporting the use of cesium-131 brachytherapy for the treatment of brain metastases. Published studies and ongoing trials were reviewed to identify treatment protocols and clinical outcomes of cesium-131 brachytherapy for brain metastases. Cesium-131 brachytherapy was further compared to current outcomes for iodine-125 brachytherapy and stereotactic radiosurgery. Intraoperative brachytherapy allows patients to receive two treatment modalities in one setting while minimizing tumor cell repopulation. After initial interest, the use of iodine-125 brachytherapy has declined due to unfavorable rates of radiation necrosis without survival improvement. Recent data on intracavitary cesium-131 brachytherapy in brain metastases have demonstrated improved locoregional tumor control with low risks of radiation necrosis, with associated improvements in patients compliance and satisfaction. Cesium-131 isotope has a short half-life, delivers 90% of its dose within a month, shortens the time to initiation of systemic therapy compared to iodine-125 or external radiotherapy, and has an excellent radiation safety profile. Further analyses have demonstrated superior cost-effectiveness and quality-of-life improvement ratios of cesium-131 brachytherapy than adjuvant stereotactic radiosurgery. Cesium-131 brachytherapy is a safe and effective post-surgical treatment option for brain metastases with associated clinical and cost-effectiveness benefits in appropriately selected patients.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Brachytherapy for meningiomas.

Interstitial intracranial radiotherapy implants, or brachytherapy, is an adjuvant option for treatment of recurrent high-grade meningiomas after resection. The implants are placed in the resection cavity following tumor resection. The most commonly used isotope is Iodine-125 (I-125). While there are no controlled studies comparing treatment of meningiomas with or without brachytherapy, several case series report good long-term survival, suggesting that this may be a useful adjuvant for recurrent high-grade tumors. Complications can occur including radiation necrosis, impaired wound healing, hydrocephalus and infection. In the future, new isotopes are being explored that may have fewer complications and better safety profiles.

Spontaneous regression of a clival chordoma. Case report.

In this case report, we present a rare and previously unreported case of spontaneous regression of a histologically consistent clival chordoma. At the time of diagnosis, imaging demonstrated a T2 hyperintense and T1 isointense midline skull base mass, centered in the nasopharynx, with scalloping of the ventral clivus consistent with a chordoma measuring 3.1 × 1.9 × 3.0 cm (8.84 cm3). On pre-operative imaging 2 months later, with no intervening therapy, the mass had regressed by 61.7% to a size of 2.3 × 2.1 × 1.4 cm (3.38 cm3). The patient self-administered several herbal supplements and animal oils which may have contributed to tumor regression. The purpose of this report is to document this rare occurrence and provide a comprehensive description of the case details and list of the various medications, herbs, and supplements used prior to this rare event.

Intraoperative brachytherapy for resected brain metastases.

Brain metastases are the most common intracranial malignancies in adults. Surgical resection is the preferred treatment approach when a pathological diagnosis is required, for symptomatic patients who are refractory to steroids, and to decompress lesions causing mass effect. Radiotherapy is administered to improve local control rates after surgical resection. After a brief review of the literature describing the treatment of brain metastases using whole-brain radiotherapy, postoperative stereotactic radiosurgery, preoperative radiosurgery, and brachytherapy, we compare patient-related, technical, practical, and radiobiological considerations of each technique. Finally, we focus our discussion on intraoperative brachytherapy, with an emphasis on the technical aspects, benefits, efficacy, and outcomes of studies utilizing permanent Cs-131 implants.

Anterior communicating artery division in the endoscopic endonasal translamina terminalis approach to the third ventricle: an anatomical feasibility study.

BACKGROUND: Endonasal endoscopic approaches (EEA) to the third ventricle are well described but generally use an infrachiasmatic route since the suprachiasmatic translamina terminalis corridor is blocked by the anterior communicating artery (AComA). The bifrontal basal interhemispheric translamina terminalis approach has been facilitated with transection of the AComA. The aim of the study is to describe the anatomical feasibility and limitations of the EEA translamina terminalis approach to the third ventricle augmented with AComA surgical ligation. METHODS: Endoscopic dissections were performed on five cadaveric heads injected with colored latex using rod lens endoscopes attached to a high-definition camera and a digital video recorder system. A stepwise anatomical dissection of the endoscopic endonasal transtuberculum, transplanum, translamina terminalis approach to the third ventricle was performed. Measurements were performed before and after AComA elevation and transection using a millimeter flexible caliper. RESULTS: Multiple comparison statistical analysis revealed a statistically significant difference in vertical exposure between the control condition and after AComA elevation, between the control condition and after AComA division and between the AComA elevation and division (p < 0.05). The mean difference in exposed surgical area was statistically significant between the control and after AComA division and between elevation and AComA division (p < 0.01), whereas it was not statistically significant between the control condition and AComA elevation (NS). CONCLUSION: The anatomical feasibility of clipping and dividing the AComA through an EEA has been demonstrated in all the cadaveric specimens. The approach facilitates exposure of the suprachiasmatic optic recess within the third ventricle that may be a blind spot during an infrachiasmatic approach.

Minimally Invasive Robotic Laser Corpus Callosotomy: A Proof of Concept.

INTRODUCTION: We describe the feasibility of using minimally invasive robotic laser interstitial thermotherapy (LITT) for achieving an anterior two-thirds as well as a complete corpus callosotomy. METHODS: Ten probe trajectories were plotted on normal magentic resonance imaging (MRI) scans using the Brainlab Stereotactic Planning Software (Brainlab, Munich, Germany). The NeuroBlate® System (Monteris Medical, MN, USA) was used to conform the thermal burn to the corpus callosum along the trajectory of the probe. The distance of the ideal entry site from either the coronal suture and the torcula or nasion and the midline was calculated. The distance of the probe tip from the dorsal and ventral limits of the callosotomy in the sagittal plane were also calculated. RESULTS: Anterior two-thirds callosotomy was possible in all patients using a posterior parieto-occipital paramedian trajectory through the non-dominant lobe. The average entry point was 3.64 cm from the midline, 10.6 cm behind the coronal suture, and 9.2 cm above the torcula. The probe tip was an average of 1.4 cm from the anterior commissure. For a total callosotomy, an additional contralaterally placed frontal probe was used to target the posterior one-third of the corpus callosum. The average entry site was 3.3 cm from the midline and 9.1 cm above the nasion. The average distance of the probe tip from the base of the splenium was 0.94 cm. CONCLUSION: The directional thermoablation capability of the NeuroBlate® system allows for targeted lesioning of the corpus callosum, to achieve a two-thirds or complete corpus callosotomy. A laser distance of < 2 cm is sufficient to reach the entire corpus callosum through one trajectory for an anterior two-thirds callosotomy and two trajectories for a complete callosotomy.

Endonasal endoscopic reoperation for residual or recurrent craniopharyngiomas.

OBJECTIVE Craniopharyngiomas can be difficult to remove completely based on their intimate relationship with surrounding visual and endocrine structures. Reoperations are not uncommon but have been associated with higher rates of complications and lower extents of resection. So radiation is often offered as an alternative to reoperation. The endonasal endoscopic transsphenoidal approach has been used in recent years for craniopharyngiomas previously removed with craniotomy. The impact of this approach on reoperations has not been widely investigated. METHODS The authors reviewed a prospectively acquired database of endonasal endoscopic resections of craniopharyngiomas over 11 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, performed by the senior authors. Reoperations were separated from first operations. Pre- and postoperative visual and endocrine function, tumor size, body mass index (BMI), quality of life (QOL), extent of resection (EOR), impact of prior radiation, and complications were compared between groups. EOR was divided into gross-total resection (GTR, 100%), near-total resection (NTR, > 95%), and subtotal resection (STR, < 95%). Univariate and multivariate analyses were performed. RESULTS Of the total 57 endonasal surgical procedures, 22 (39%) were reoperations. First-time operations and reoperations did not differ in tumor volume, radiological configuration, or patients' BMI. Hypopituitarism and diabetes insipidus (DI) were more common before reoperations (82% and 55%, respectively) compared with first operations (60% and 8.6%, respectively; p < 0.001). For the 46 patients in whom GTR was intended, rates of GTR and GTR+NTR were not significantly different between first operations (90% and 97%, respectively) and reoperations (80% and 100%, respectively). For reoperations, prior radiation and larger tumor volume had lower rates of GTR. Vision improved equally in first operations (80%) compared with reoperations (73%). New anterior pituitary deficits were more common in first operations compared with reoperations (51% vs 23%, respectively; p = 0.08), while new DI was more common in reoperations compared with first-time operations (80% vs 47%, respectively; p = 0.08). Nonendocrine complications occurred in 2 (3.6%) first-time operations and no reoperations. Tumor regrowth occurred in 6 patients (11%) over a median follow-up of 46 months and was not different between first versus reoperations, but was associated with STR (33%) compared with GTR+NTR (4%; p = 0.02) and with not receiving radiation after STR (67% vs 22%; p = 0.08). The overall BMI increased significantly from 28.7 to 34.8 kg/m2 over 10 years. Six months after surgery, there was a significant improvement in QOL, which was similar between first-time operations and reoperations, and negatively correlated with STR. CONCLUSIONS Endonasal endoscopic transsphenoidal reoperation results in similar EOR, visual outcome, and improvement in QOL as first-time operations, with no significant increase in complications. EOR is more impacted by tumor volume and prior radiation. Reoperations should be offered to patients with recurrent craniopharyngiomas and may be preferable to radiation in patients in whom GTR or NTR can be achieved.

Neuro-oscillatory phase alignment drives speeded multisensory response times: an electro-corticographic investigation.

Even simple tasks rely on information exchange between functionally distinct and often relatively distant neuronal ensembles. Considerable work indicates oscillatory synchronization through phase alignment is a major agent of inter-regional communication. In the brain, different oscillatory phases correspond to low- and high-excitability states. Optimally aligned phases (or high-excitability states) promote inter-regional communication. Studies have also shown that sensory stimulation can modulate or reset the phase of ongoing cortical oscillations. For example, auditory stimuli can reset the phase of oscillations in visual cortex, influencing processing of a simultaneous visual stimulus. Such cross-regional phase reset represents a candidate mechanism for aligning oscillatory phase for inter-regional communication. Here, we explored the role of local and inter-regional phase alignment in driving a well established behavioral correlate of multisensory integration: the redundant target effect (RTE), which refers to the fact that responses to multisensory inputs are substantially faster than to unisensory stimuli. In a speeded detection task, human epileptic patients (N = 3) responded to unisensory (auditory or visual) and multisensory (audiovisual) stimuli with a button press, while electrocorticography was recorded over auditory and motor regions. Visual stimulation significantly modulated auditory activity via phase reset in the delta and theta bands. During the period between stimulation and subsequent motor response, transient synchronization between auditory and motor regions was observed. Phase synchrony to multisensory inputs was faster than to unisensory stimulation. This sensorimotor phase alignment correlated with behavior such that stronger synchrony was associated with faster responses, linking the commonly observed RTE with phase alignment across a sensorimotor network.

Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases.

OBJECT: Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS: After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS: The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS: The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Mapping phonemic processing zones along human perisylvian cortex: an electro-corticographic investigation.

The auditory system is organized such that progressively more complex features are represented across successive cortical hierarchical stages. Just when and where the processing of phonemes, fundamental elements of the speech signal, is achieved in this hierarchy remains a matter of vigorous debate. Non-invasive measures of phonemic representation have been somewhat equivocal. While some studies point to a primary role for middle/anterior regions of the superior temporal gyrus (STG), others implicate the posterior STG. Differences in stimulation, task and inter-individual anatomical/functional variability may account for these discrepant findings. Here, we sought to clarify this issue by mapping phonemic representation across left perisylvian cortex, taking advantage of the excellent sampling density afforded by intracranial recordings in humans. We asked whether one or both major divisions of the STG were sensitive to phonemic transitions. The high signal-to-noise characteristics of direct intracranial recordings allowed for analysis at the individual participant level, circumventing issues of inter-individual anatomic and functional variability that may have obscured previous findings at the group level of analysis. The mismatch negativity (MMN), an electrophysiological response elicited by changes in repetitive streams of stimulation, served as our primary dependent measure. Oddball configurations of pairs of phonemes, spectro-temporally matched non-phonemes, and simple tones were presented. The loci of the MMN clearly differed as a function of stimulus type. Phoneme representation was most robust over middle/anterior STG/STS, but was also observed over posterior STG/SMG. These data point to multiple phonemic processing zones along perisylvian cortex, both anterior and posterior to primary auditory cortex. This finding is considered within the context of a dual stream model of auditory processing in which functionally distinct ventral and dorsal auditory processing pathways may be engaged by speech stimuli.

Auditory-driven phase reset in visual cortex: human electrocorticography reveals mechanisms of early multisensory integration.

Findings in animal models demonstrate that activity within hierarchically early sensory cortical regions can be modulated by cross-sensory inputs through resetting of the phase of ongoing intrinsic neural oscillations. Here, subdural recordings evaluated whether phase resetting by auditory inputs would impact multisensory integration processes in human visual cortex. Results clearly showed auditory-driven phase reset in visual cortices and, in some cases, frank auditory event-related potentials (ERP) were also observed over these regions. Further, when audiovisual bisensory stimuli were presented, this led to robust multisensory integration effects which were observed in both the ERP and in measures of phase concentration. These results extend findings from animal models to human visual cortices, and highlight the impact of cross-sensory phase resetting by a non-primary stimulus on multisensory integration in ostensibly unisensory cortices.

Improvements in site-specific quality of life 6 months after endoscopic anterior skull base surgery: a prospective study.

OBJECT: Endoscopic skull base surgery (ESBS) is a minimal-access technique that provides an alternative to traditional approaches. Patient-reported outcomes are becoming increasingly important in measuring the success of surgical interventions. Endoscopic skull base surgery may lead to improvements in quality of life (QOL) since natural orifices are used to reach the pathology; however, sinonasal QOL may be negatively affected. The purpose of this study was to assess the impact of ESBS on both site-specific QOL, using the Anterior Skull Base Questionnaire (ASBQ), and sinonasal-related QOL, using the Sino-Nasal Outcome Test (SNOT-22). METHODS: Consecutive patients from a tertiary referral center who were undergoing ESBS were prospectively enrolled in this study. All patients completed the ASBQ and SNOT-22 preoperatively as well as at regular intervals after ESBS. RESULTS: Sixty-six patients were included in the study, and 57.6% of them had pituitary adenoma. There was no significant decline or improvement in the ASBQ-measured QOL at 3 and 6 weeks after ESBS, but there were significant improvements at 12 weeks and 6 months postoperatively (p < 0.05). Improvements were noted in all but one ASBQ subdomain at 12 weeks and 6 months postsurgery (p < 0.05). Preoperative QOL was significantly worse in patients who had undergone revision surgery and significantly improved postoperatively in patients who underwent gross-total resection (p < 0.05). Scores on the SNOT-22 worsened at 3 weeks postoperatively and returned to baseline thereafter. The presence of a nasoseptal flap or a graft-donor site did not contribute to a decreased QOL. CONCLUSIONS: Endoscopic skull base surgery is associated with an improvement in postoperative site-specific QOL as compared with the preoperative QOL. Short-term improvements are greater if gross-total resection is achieved. Sinonasal QOL transiently declines and then returns to preoperative baseline levels. Endoscopic skull base surgery is a valuable tool in the neurosurgical management of anterior skull base pathology, leading to improvements in site-specific QOL.

Oscillatory sensory selection mechanisms during intersensory attention to rhythmic auditory and visual inputs: a human electrocorticographic investigation.

Oscillatory entrainment mechanisms are invoked during attentional processing of rhythmically occurring stimuli, whereby their phase alignment regulates the excitability state of neurons coding for anticipated inputs. These mechanisms have been examined in the delta band (1-3 Hz), where entrainment frequency matches the stimulation rate. Here, we investigated entrainment for subdelta rhythmic stimulation, recording from intracranial electrodes over human auditory cortex during an intersensory audiovisual task. Audiovisual stimuli were presented at 0.67 Hz while participants detected targets within one sensory stream and ignored the other. It was found that entrainment operated at twice the stimulation rate (1.33 Hz), and this was reflected by higher amplitude values in the FFT spectrum, cyclic modulation of alpha-amplitude, and phase-amplitude coupling between delta phase and alpha power. In addition, we found that alpha-amplitude was relatively increased in auditory cortex coincident with to-be-ignored auditory stimuli during attention to vision. Thus, the data suggest that entrainment mechanisms operate within a delimited passband such that for subdelta task rhythms, oscillatory harmonics are invoked. The phase of these delta-entrained oscillations modulates alpha-band power. This may in turn increase or decrease responsiveness to relevant and irrelevant stimuli, respectively.

Staying within the lines: the formation of visuospatial boundaries influences multisensory feature integration.

The brain processes multisensory features of an object (e.g., its sound and shape) in separate cortical regions. A key question is how representations of these features bind together to form a coherent percept (the 'binding problem'). Here we tested the hypothesis that the determination of an object's visuospatial boundaries is paramount to the linking of its multisensory features (i.e., that the refinement of attended space through the formation of visual boundaries establishes the boundaries for multisensory feature integration). We recorded both scalp and intracranial electrophysiological data in response to Kanizsa-type illusory contour stimuli (in which pacman-like elements give the impression of a single object), their non-illusory counterparts, and auditory stimuli. Participants performed a visual task and ignored sounds. Enhanced processing of task-irrelevant sounds when paired with attended visual stimuli served as our metric for multisensory feature integration [e.g., Busse et al. (2005) Proc. Natl Acad. Sci. USA 102: 18751-18756]. According to our hypothesis, task-irrelevant sounds paired with Kanizsa-type illusory contour stimuli (which have well-defined boundaries) should receive enhanced processing relative to task-irrelevant sounds paired with non-illusory contour stimuli (which have ambiguous boundaries). The scalp data clearly support this prediction and, combined with the intracranial data, advocate for an important extension of models for multisensory feature integration. We propose a model in which (i) the visual boundaries of an object are established through processing in occipitotemporal cortex, and (ii) attention then spreads to cortical regions that process features that fall within the object's established visual boundaries, including its task-irrelevant multisensory features.

Audio-visual multisensory integration in superior parietal lobule revealed by human intracranial recordings.

Intracranial recordings from three human subjects provide the first direct electrophysiological evidence for audio-visual multisensory processing in the human superior parietal lobule (SPL). Auditory and visual sensory inputs project to the same highly localized region of the parietal cortex with auditory inputs arriving considerably earlier (30 ms) than visual inputs (75 ms). Multisensory integration processes in this region were assessed by comparing the response to simultaneous audio-visual stimulation with the algebraic sum of responses to the constituent auditory and visual unisensory stimulus conditions. Significant integration effects were seen with almost identical morphology across the three subjects, beginning between 120 and 160 ms. These results are discussed in the context of the role of SPL in supramodal spatial attention and sensory-motor transformations.