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Clark C. Chen, Paul Chapman, Joshua Petit and Jay Loeffler

Object

Photon energy deposition from gamma or photon sources follows the law of exponential decay. Consequently, energy is deposited over the entire path of the radiation beam, resulting in dose distribution before and after the target is reached. In contrast, the physical properties of protons are such that energy deposition occurs with no exit dose beyond the target volume. Therefore, relative to photons, proton beams represent a superior platform for the administration of radiosurgery.

Methods

In this review, the authors will discuss the fundamental principles underlying photon- and proton-based stereotactic radiosurgery (SRS). The clinical efficacy of proton-based SRS in the treatment of arteriovenous malformations, vestibular schwannomas, and pituitary adenomas is reviewed.

Results

Direct comparisons of clinical results attained using photon- and proton-based SRS are confounded by a bias toward reserving proton beams for the treatment of larger and more complex lesions. Despite this bias, the clinical outcomes for proton-based SRS have been excellent and have been at least comparable to those for photon-based treatments.

Conclusions

The physical properties of proton radiation offer superior conformality in dose distribution relative to photon irradiation. This advantage becomes more apparent as the lesion size increases and will probably be magnified with the development of intensity-modulated proton techniques.

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Gene H. Barnett, Clark C. Chen, Robert E. Gross and Andrew E. Sloan

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Leonardo Rangel-Castilla, Fangxiang Chen, Lawrence Choi, Justin C. Clark and Peter Nakaji

Object

An optimal entry point and trajectory for endoscopic colloid cyst (ECC) resection helps to protect important neurovascular structures. There is a large discrepancy in the entry point and trajectory in the neuroendoscopic literature.

Methods

Trajectory views from MRI or CT scans used for cranial image guidance in 39 patients who had undergone ECC resection between July 2004 and July 2010 were retrospectively evaluated. A target point of the colloid cyst was extended out to the scalp through a trajectory carefully observed in a 3D model to ensure that important anatomical structures were not violated. The relation of the entry point to the midline and coronal sutures was established. Entry point and trajectory were correlated with the ventricular size.

Results

The optimal entry point was situated 42.3 ± 11.7 mm away from the sagittal suture, ranging from 19.1 to 66.9 mm (median 41.4 mm) and 46.9 ± 5.7 mm anterior to the coronal suture, ranging from 36.4 to 60.5 mm (median 45.9 mm). The distance from the entry point to the target on the colloid cyst varied from 56.5 to 78.0 mm, with a mean value of 67.9 ± 4.8 mm (median 68.5 mm). Approximately 90% of the optimal entry points are located 40–60 mm in front of the coronal suture, whereas their perpendicular distance from the midline ranges from 19.1 to 66.9 mm. The location of the “ideal” entry points changes laterally from the midline as the ventricles change in size.

Conclusions

The results suggest that the optimal entry for ECC excision be located at 42.3 ± 11.7 mm perpendicular to the midline, and 46.9 ± 5.7 mm anterior to the coronal suture, but also that this point differs with the size of the ventricles. Intraoperative stereotactic navigation should be considered for all ECC procedures whenever it is available. The entry point should be estimated from the patient's own preoperative imaging studies if intraoperative neuronavigation is not available. An estimated entry point of 4 cm perpendicular to the midline and 4.5 cm anterior to the coronal suture is an acceptable alternative that can be used in patients with ventriculomegaly.

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Robert C. Rennert, Kate T. Carroll, Mir Amaan Ali, Thomas Hamelin, Leon Chang, Brian P. Lemkuil and Clark C. Chen

OBJECTIVE

Stereotactic laser ablation (SLA) is typically performed in the setting of intraoperative MRI or in a staged manner in which probe insertion is performed in the operating room and thermal ablation takes place in an MRI suite.

METHODS

The authors describe their experience, in which SLA for glioblastoma (GBM) treatment was performed entirely within a conventional MRI suite using the SmartFrame stereotactic device.

RESULTS

All 10 patients with GBM (2 with isocitrate dehydrogenase 1 mutation [mIDH1] and 8 with wild-type IDH1 [wtIDH1]) were followed for > 6 months. One of these patients underwent 2 independent SLAs approximately 12 months apart. Biopsies were performed prior to SLA for all patients. There were no perioperative morbidities, wound infections, or unplanned 30-day readmissions. The average time for a 3-trajectory SLA (n = 3) was 436 ± 102 minutes; for a 2-trajectory SLA (n = 4) was 321 ± 85 minutes; and for a single-trajectory SLA (n = 4) was 254 ± 28 minutes. No tumor recurrence occurred within the blue isotherm line ablation zone, although 2 patients experienced recurrence immediately adjacent to the blue isotherm ablation line. Overall survival for the patient cohort averaged 356 days, with the 2 patients who had mIDH1 GBMs exhibiting the longest survival (811 and 654 days).

CONCLUSIONS

Multitrajectory SLA for treatment of GBM can be safely performed using the SmartFrame stereotactic device in a conventional MRI suite.

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Robert C. Rennert, Reid R. Hoshide, Jason W. Signorelli, Deirdre Amaro, Jayson A. Sack, Cameron W. Brennan and Clark C. Chen

The authors report an unusual case of a widely metastatic glioblastoma. DNA copy number microarray profile of the resected specimen revealed complex rearrangements found throughout chromosome 6, a phenomenon known as chromothripsis. Such chromothripsis pattern was not observed in 50 nonmetastatic glioblastoma specimens analyzed. Analysis of the 1000+ gliomas profiled by The Cancer Genome Atlas (TCGA) data set revealed one case of chromosome 6 chromothripsis resembling the case described here. This TCGA patient died within 6 months of undergoing tumor resection. Implications of these findings are reviewed in the context of the current literature.

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Brandon A. McCutcheon, David C. Chang, Logan Marcus, David D. Gonda, Abraham Noorbakhsh, Clark C. Chen, Mark A. Talamini and Bob S. Carter

OBJECT

This study was designed to assess the relationship between insurance status and likelihood of receiving a neurosurgical procedure following admission for either extraaxial intracranial hemorrhage or spinal vertebral fracture.

METHODS

A retrospective analysis of the Nationwide Inpatient Sample (NIS; 1998–2009) was performed. Cases of traumatic extraaxial intracranial hematoma and spinal vertebral fracture were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Within this cohort, those patients receiving a craniotomy or spinal fusion and/or decompression in the context of an admission for traumatic brain or spine injury, respectively, were identified using the appropriate ICD-9 procedure codes.

RESULTS

A total of 190,412 patients with extraaxial intracranial hematoma were identified between 1998 and 2009. Within this cohort, 37,434 patients (19.7%) received a craniotomy. A total of 477,110 patients with spinal vertebral fracture were identified. Of these, 37,302 (7.8%) received a spinal decompression and/or fusion. On multivariate analysis controlling for patient demographics, severity of injuries, comorbidities, hospital volume, and hospital characteristics, uninsured patients had a reduced likelihood of receiving a craniotomy (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.71–0.82) and spinal fusion (OR 0.67, 95% CI 0.64–0.71) relative to insured patients. This statistically significant trend persisted when uninsured and insured patients were matched on the basis of mortality propensity score. Uninsured patients demonstrated an elevated risk-adjusted mortality rate relative to insured patients in cases of extraaxial intracranial hematoma. Among patients with spinal injury, mortality rates were similar between patients with and without insurance.

CONCLUSIONS

In this study, uninsured patients were consistently less likely to receive a craniotomy or spinal fusion for traumatic intracranial extraaxial hemorrhage and spinal vertebral fracture, respectively. This difference persisted after accounting for overall injury severity and patient access to high- or low-volume treatment centers, and potentially reflects a resource allocation bias against uninsured patients within the hospital setting. This information adds to the growing literature detailing the benefits of health reform initiatives seeking to expand access for the uninsured.

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David D. Gonda, Alexander A. Khalessi, Brandon A. McCutcheon, Logan P. Marcus, Abraham Noorbakhsh, Clark C. Chen, David C. Chang and Bob S. Carter

Object

Using a database that enabled longitudinal follow-up, the authors assessed the long-term outcomes of unruptured cerebral aneurysms repaired by clipping or coiling.

Methods

An observational analysis of the California Office of Statewide Health Planning and Development (OSHPD) database, which follows patients longitudinally in time and through multiple hospitalizations, was performed for all patients initially treated for an unruptured cerebral aneurysm in the period from 1998 to 2005 and with follow-up data through 2009.

Results

Nine hundred forty-four cases (36.5%) were treated with endovascular coiling, 1565 cases (60.5%) were surgically clipped, and 76 cases were treated with both coiling and clipping. There was no significant difference in any demographic variable between the two treatment groups except for age (median: 55 years for the clipped group, 58 years for the coiled group, p < 0.001). Perioperative (30-day) mortality was 1.1% in patients with coiled aneurysms compared with 2.3% in those with clipped aneurysms (p = 0.048). The median follow-up was 7 years (range 4–12 years). At the last follow-up, 153 patients (16.2%) in the coiled group had died compared with 244 (15.6%) in the clipped group (p = 0.693). The adjusted hazard ratio for death at the long-term follow-up was 1.14 (95% CI 0.9–1.4, p = 0.282) for patients with endovascularly treated aneurysms. The incidence of intracranial hemorrhage was similar in the two treatment groups (5.9% clipped vs 4.8% coiled, p = 0.276). One hundred ninety-three patients (20.4%) with coiled aneurysms underwent additional hospitalizations for aneurysm repair procedures compared with only 136 patients (8.7%) with clipped aneurysms (p < 0.001). Cumulative hospital costs per patient for admissions involving aneurysm repair procedures were greater in the clipped group (median cost $98,260 vs $81,620, p < 0.001) through the follow-up.

Conclusions

For unruptured cerebral aneurysms, an observed perioperative survival advantage for endovascular coiling relative to that for surgical clipping was lost on long-term follow-up, according to data from an administrative database of patients who were not randomly allocated to treatment type. A cost advantage of endovascular treatment was maintained even though endovascularly treated patients were more likely to undergo subsequent hospitalizations for additional aneurysm repair procedures. Rates of aneurysm rupture following treatment were similar in the two groups.

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David D. Gonda, Vincent J. Cheung, Karra A. Muller, Amit Goyal, Bob S. Carter and Clark C. Chen

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.

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Kristopher T. Kahle, David Kozono, Kimberly Ng, Grace Hsieh, Pascal O. Zinn, Masayuki Nitta and Clark C. Chen

Our understanding of glioblastoma multiforme (GBM), the most common form of primary brain cancer, has been significantly advanced by recent efforts to characterize the cancer genome using unbiased high-throughput sequencing analyses. While these studies have documented hundreds of mutations, gene copy alterations, and chromosomal abnormalities, only a subset of these alterations are likely to impact tumor initiation or maintenance. Furthermore, genes that are not altered at the genomic level may play essential roles in tumor initiation and maintenance. Identification of these genes is critical for therapeutic development and investigative methodologies that afford insight into biological function. This requirement has largely been fulfilled with the emergence of RNA interference (RNAi) and high-throughput screening technology. In this article, the authors discuss the application of genome-wide, high-throughput RNAi-based genetic screening as a powerful tool for the rapid and cost-effective identification of genes essential for cancer proliferation and survival. They describe how these technologies have been used to identify genes that are themselves selectively lethal to cancer cells, or synthetically lethal with other oncogenic mutations. The article is intended to provide a platform for how RNAi libraries might contribute to uncovering glioma cell vulnerabilities and provide information that is highly complementary to the structural characterization of the glioblastoma genome. The authors emphasize that unbiased, systems-level structural and functional genetic approaches are complementary efforts that should facilitate the identification of genes involved in the pathogenesis of GBM and permit the identification of novel drug targets.

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Logan P. Marcus, Brandon A. McCutcheon, Abraham Noorbakhsh, Ralitza P. Parina, David D. Gonda, Clark Chen, David C. Chang and Bob S. Carter

Object

Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection.

Methods

The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions.

Results

A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20–1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06–2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20–2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84–8.18).

Conclusions

Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.