Publications by authors named "Jacob S Young"

61 Publications

A single institution retrospective analysis on survival based on treatment paradigms for patients with anaplastic oligodendroglioma.

J Neurooncol 2021 Jul 14;153(3):447-454. Epub 2021 Jun 14.

Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, CA, USA.

Introduction: Anaplastic oligodendrogliomas are high-grade gliomas defined molecularly by 1p19q co-deletion. There is no curative therapy, and standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone has not been demonstrated in a randomized control trial. Given the potential long-term consequences of radiation therapy, such as cognitive impairment, arteriopathy, endocrinopathy, and hearing/visual impairment, there is an effort to balance longevity with radiation toxicity.

Methods: We performed a retrospective single institution analysis of survival of patients with anaplastic oligodendroglioma over 20 years.

Results: 159 patients were identified as diagnosed with an anaplastic oligodendroglioma between 1996 and 2016. Of those, 40 patients were found to have AO at original diagnosis and had documented 1p19q co-deletion with a median of 7.1 years of follow-up (range: 0.6-16.7 years). After surgery, 45 % of patients were treated with radiation and chemotherapy at diagnosis, and 50 % were treated with adjuvant chemotherapy alone. The group treated with chemotherapy alone had a trend of receiving more cycles of chemotherapy than patients treated with radiation and chemotherapy upfront (p = 0.051). Median overall survival has not yet been reached. The related risk of progression in the upfront, adjuvant chemotherapy only group was almost 5-fold higher than the patients who received radiation and chemotherapy (hazard ratio = 4.85 (1.74-13.49), p = 0.002). However, there was no significant difference in overall survival in patients treated with upfront chemotherapy compared to patients treated upfront with chemotherapy and radiation (p = 0.8). Univariate analysis of age, KPS, extent of resection, or upfront versus delayed radiation was not associated with improved survival.

Conclusions: Initial treatment with adjuvant chemotherapy alone, rather than radiation and chemotherapy, may be an option for some patients with anaplastic oligodendroglioma, as it is associated with similar overall survival despite shorter progression free survival.
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http://dx.doi.org/10.1007/s11060-021-03781-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279971PMC
July 2021

Oncology and Spinal Neurosurgeons Performing Resections of Intramedullary Ependymomas Compared with Single Neurosurgeons: A 13-Year Experience at a Single Institution.

World Neurosurg 2021 May 28. Epub 2021 May 28.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.

Objective: Resection of intramedullary spinal ependymomas carries great risk of postoperative neurological deficits. The objective of this study was to describe our experience using co-neurosurgeon teams to address intramedullary ependymomas to determine if the use of 2 experienced attending neurosurgeons with expertise in both neurosurgical oncology and spine pathology can improve outcomes for intramedullary ependymoma resections.

Methods: We retrospectively compared surgical and disease control outcomes in intramedullary ependymoma cases performed by co-neurosurgeon (one neurosurgical oncologist and one neurosurgeon trained in spinal surgery) and single-neurosurgeon teams over a 13-year period at a single institution.

Results: Co-neurosurgeons performed resections in 34 (47.9%) patients, and a single neurosurgeon performed resections in 37 (52.1%) patients. There were no significant differences in the frequency of gross total resection in the co-neurosurgeon versus single-neurosurgeon group (85.7% vs. 78.4%, P = 0.45). Posterior spinal fusion was more common in the co-neurosurgeon group (35.3%) compared with the single-neurosurgeon group (8.1%) (P = 0.01). Two (5.9%) patients in the co-neurosurgeon group and 5 (13.5%) patients in the single-neurosurgeon group had complications requiring surgical revision (P = 0.28). Recurrence rates were similar in both groups (5.9% vs. 10.8%, P = 0.50). At last follow-up, 76% of patients who presented with mild or no deficits remained functionally independent.

Conclusions: Resection of intramedullary ependymomas by co-neurosurgeon teams resulted in similar rates of gross total resection, postoperative complications, and recurrence compared with surgeries performed by a single neurosurgeon. Functional neurological outcomes were not impacted by co-neurosurgeons performing ependymoma resections.
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http://dx.doi.org/10.1016/j.wneu.2021.05.082DOI Listing
May 2021

Balancing task sensitivity with reliability for multimodal language assessments.

J Neurosurg 2021 May 28:1-8. Epub 2021 May 28.

1Department of Neurological Surgery, University of California, San Francisco, California; and.

Objective: Intraoperative tasks for awake language mapping are typically selected based on the language tracts that will likely be encountered during tumor resection. However, diminished attention and arousal secondary to perioperative sedatives may reduce a task's usefulness for identifying eloquent cortex. For instance, accuracy in performing select language tasks may be high preoperatively but decline in the operating room. In the present study, the authors sought to identify language tasks that can be performed with high accuracy in both situational contexts so the neurosurgical team can be confident that speech errors committed during awake language mapping result from direct cortical stimulation to eloquent cortex, rather than from poor performance in general.

Methods: We administered five language tasks to 44 patients: picture naming (PN), text reading (TR), auditory object naming (AN), repetition of 4-syllable words (4SYL), and production of syntactically intact sentences (SYNTAX). Performance was assessed using the 4-point scale of the quick aphasia battery 24 hours preoperatively and intraoperatively. We next determined whether or not accuracy on each task was higher preoperatively than intraoperatively. We also determined whether 1) intraoperative accuracy on a given task predicted intraoperative performance on the other tasks and 2) low preoperative accuracy on a task predicted a decrease in accuracy intraoperatively.

Results: Relative to preoperative accuracy, intraoperative accuracy declined on PN (3.90 vs 3.82, p = 0.0001), 4SYL (3.96 vs 3.91, p = 0.0006), and SYNTAX (3.85 vs 3.67, p = 0.0001) but not on TR (3.96 vs 3.94, p = 0.13) or AN (3.70 vs 3.58, p = 0.058). Intraoperative accuracy on PN and AN independently predicted intraoperative accuracy on the remaining language tasks (p < 0.001 and p < 0.01, respectively). Finally, low preoperative accuracy on SYNTAX predicted a decrease in accuracy on this task intraoperatively (R2 = 0.36, p = 0.00002).

Conclusions: While TR lacks sensitivity in identifying language deficits at baseline, accuracy on TR is stable across testing settings. Baseline accuracy on the other four of our five language tasks was not predictive of intraoperative performance, signifying the need to repeat language tests prior to stimulation mapping to confirm reliability.
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http://dx.doi.org/10.3171/2020.10.JNS202947DOI Listing
May 2021

Convergence of heteromodal lexical retrieval in the lateral prefrontal cortex.

Sci Rep 2021 Mar 18;11(1):6305. Epub 2021 Mar 18.

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.
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http://dx.doi.org/10.1038/s41598-021-85802-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973515PMC
March 2021

Preoperative Applications of Navigated Transcranial Magnetic Stimulation.

Front Neurol 2020 22;11:628903. Epub 2021 Jan 22.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.

Preoperative mapping of cortical structures prior to neurosurgical intervention can provide a roadmap of the brain with which neurosurgeons can navigate critical cortical structures. In patients undergoing surgery for brain tumors, preoperative mapping allows for improved operative planning, patient risk stratification, and personalized preoperative patient counseling. Navigated transcranial magnetic stimulation (nTMS) is one modality that allows for highly accurate, image-guided, non-invasive stimulation of the brain, thus allowing for differentiation between eloquent and non-eloquent cortical regions. Motor mapping is the best validated application of nTMS, yielding reliable maps with an accuracy similar to intraoperative cortical mapping. Language mapping is also commonly performed, although nTMS language maps are not as highly concordant with direct intraoperative cortical stimulation maps as nTMS motor maps. Additionally, nTMS has been used to localize cortical regions involved in other functions such as facial recognition, calculation, higher-order motor processing, and visuospatial orientation. In this review, we evaluate the growing literature on the applications of nTMS in the preoperative setting. First, we analyze the evidence in support of the most common clinical applications. Then we identify usages that show promise but require further validation. We also discuss developing nTMS techniques that are still in the experimental stage, such as the use of nTMS to enhance postoperative recovery. Finally, we highlight practical considerations when utilizing nTMS and, importantly, its safety profile in neurosurgical patients. In so doing, we aim to provide a comprehensive review of the role of nTMS in the neurosurgical management of a patient with a brain tumor.
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http://dx.doi.org/10.3389/fneur.2020.628903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862711PMC
January 2021

Using viral vectors to deliver local immunotherapy to glioblastoma.

Neurosurg Focus 2021 02;50(2):E4

The treatment for glioblastoma (GBM) has not seen significant improvement in over a decade. Immunotherapies target the immune system against tumor cells and have seen success in various cancer types. However, the efficacy of immunotherapies in GBM thus far has been limited. Systemic immunotherapies also carry with them concerns surrounding systemic toxicities as well as penetration of the blood-brain barrier. These concerns may potentially limit their efficacy in GBM and preclude the use of combinatorial immunotherapy, which may be needed to overcome the severe multidimensional immune suppression seen in GBM patients. The use of viral vectors to deliver immunotherapies directly to tumor cells has the potential to improve immunotherapy delivery to the CNS, reduce systemic toxicities, and increase treatment efficacy. Indeed, preclinical studies investigating the delivery of immunomodulators to GBM using viral vectors have demonstrated significant promise. In this review, the authors discuss previous studies investigating the delivery of local immunotherapy using viral vectors. They also discuss the future of these treatments, including the reasoning behind immunomodulator and vector selection, patient safety, personalized therapies, and the need for combinatorial treatment.
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http://dx.doi.org/10.3171/2020.11.FOCUS20859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011938PMC
February 2021

A Review of Cortical and Subcortical Stimulation Mapping for Language.

Neurosurgery 2021 Jan 14. Epub 2021 Jan 14.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Since the early descriptions of language function based on observations of patients with language deficits by Broca and Wernicke, neurosurgeons have been focused on characterizing the anatomic regions necessary for language perception and production, and preserving these structures during surgery to minimize patient deficits post operatively. In this supplementary issue on awake intraoperative mapping, we review language processing across multiple domains, highlighting key advances in direct electrical stimulation of different cortical and subcortical regions involved in naming, repetition, reading, writing, and syntax. We then discuss different intraoperative tasks for assessing the function of a given area and avoiding injury to critical, eloquent regions.
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http://dx.doi.org/10.1093/neuros/nyaa436DOI Listing
January 2021

Commentary: Planning Brain Tumor Resection Using a Probabilistic Atlas of Cortical and Subcortical Structures Critical for Functional Processing: A Proof of Concept.

Oper Neurosurg (Hagerstown) 2021 02;20(3):E184-E185

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

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http://dx.doi.org/10.1093/ons/opaa404DOI Listing
February 2021

Effects of ventricular entry on patient outcome during glioblastoma resection.

J Neurosurg 2021 Jan 8:1-9. Epub 2021 Jan 8.

1Department of Neurological Surgery.

Objective: Tumor proximity to the ventricle and ventricular entry (VE) during surgery have both been associated with worse prognoses; however, the interaction between these two factors is poorly understood. Given the benefit of maximal tumor resection, it is imperative for surgical planning and technique to know if VE has negative consequences for patient survival and tumor dissemination.

Methods: The University of California, San Francisco tumor registry was searched for patients with newly diagnosed and recurrent supratentorial glioblastoma (GBM) who underwent resection by the senior author between 2013 and 2018. Tumor location with respect to the subventricular zone (SVZ), size, and extent of resection were assessed using pre- and postoperative imaging. VE was determined by postoperative imaging and/or the operative report.

Results: In this 200-patient cohort of newly diagnosed and recurrent GBM, 26.5% of patients had VE during resection. Patients with VE were more likely to have preexisting subependymal disease (41.5% vs 15.0%, p < 0.001). Comparing patients with VE to those without VE, there was no difference in the rates of postoperative hydrocephalus (1.9% vs 4.8%, p = 0.36), ventriculoperitoneal shunting (0% vs 3.4%, p = 0.17), pseudomeningoceles (7.5% vs 5.4%, p = 0.58), or subdural hematomas (11.3% vs 3.4%, p = 0.07). Importantly, rates of subsequent leptomeningeal disease (7.5% vs 10.2%, p = 0.57) and distant parenchymal recurrence (17.0% vs 23.1%, p = 0.35) were not different between the groups. Newly diagnosed patients with tumors contacting the SVZ (type I or II) had worse survival than patients with tumors that did not contact the SVZ (type III or IV) (1.27 vs 1.84 years, p = 0.014, HR 1.8, 95% CI 1.08-3.03), but VE was not associated with worse survival in these patients with high-risk SVZ type I and II tumors (1.15 vs 1.68 years, p = 0.151, HR 0.59, 95% CI 0.26-1.34).

Conclusions: VE was well tolerated, with postoperative complications being rare events. There was no increase in leptomeningeal spread or distant parenchymal recurrence in patients with VE. Finally, although survival was worse for patients with preoperative subependymal disease, VE did not change survival for patients with tumors contacting the ventricle. Therefore, VE during GBM resection is not associated with adverse patient outcomes and should be used by surgeons to enhance extent of resection.■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective cohort; evidence: class II.
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http://dx.doi.org/10.3171/2020.7.JNS201362DOI Listing
January 2021

Immunologic aspects of viral therapy for glioblastoma and implications for interactions with immunotherapies.

J Neurooncol 2021 Mar 3;152(1):1-13. Epub 2021 Jan 3.

Department of Neurological Surgery, University of California, 505 Parnassus Ave, M-779, San Francisco, CA, 94143-0112, USA.

Introduction: The treatment for glioblastoma (GBM) has remained unchanged for the past decade, with only minimal improvements in patient survival. As a result, novel treatments are needed to combat this devastating disease. Immunotherapies are treatments that stimulate the immune system to attack tumor cells and can be either local or systemically delivered. Viral treatments can lead to direct tumor cell death through their natural lifecycle or through the delivery of a suicide gene, with the potential to generate an anti-tumor immune response, making them interesting candidates for combinatorial treatment with immunotherapy.

Methods: We review the current literature surrounding the interactions between oncolytic viruses and the immune system as well as the use of oncolytic viruses combined with immunotherapies for the treatment of GBM.

Results: Viral therapies have exhibited preclinical efficacy as single-agents and are being investigated in that manner in clinical trials. Oncolytic viruses have significant interactions with the immune system, although this can also vary depending on the strain of virus. Combinatorial treatments using both oncolytic viruses and immunotherapies have demonstrated promising preclinical findings.

Conclusions: Studies combining viral and immunotherapeutic treatment modalities have provided exciting results thus far and hold great promise for patients with GBM. Additional studies assessing the clinical efficacy of these treatments as well as improved preclinical modeling systems, safety mechanisms, and the balance between treatment efficacy and immune-mediated viral clearance should be considered.
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http://dx.doi.org/10.1007/s11060-020-03684-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011939PMC
March 2021

The Relationship Between Stimulation Current and Functional Site Localization During Brain Mapping.

Neurosurgery 2021 05;88(6):1043-1050

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Background: Gliomas are often in close proximity to functional regions of the brain; therefore, electrocortical stimulation (ECS) mapping is a common technique utilized during glioma resection to identify functional areas. Stimulation-induced seizure (SIS) remains the most common reason for aborted procedures. Few studies have focused on oncological factors impacting cortical stimulation thresholds.

Objective: To examine oncological factors thought to impact stimulation threshold in order to understand whether a linear relationship exists between stimulation current and number of functional cortical sites identified.

Methods: We retrospectively reviewed single-institution prospectively collected brain mapping data of patients with dominant hemisphere gliomas. Comparisons of stimulation threshold were made using t-tests and ANOVAs. Associations between oncologic factors and stimulation threshold were made using multivariate regressions. The association between stimulation current and number of positive sites was made using a Poisson model.

Results: Of the 586 patients included in the study, SIS occurred in 3.92% and the rate of SIS events differed by cortical location (frontal 8.5%, insular 1.6%, parietal 1.3%, and temporal 2.8%; P = .009). Stimulation current was lower when mapping frontal cortex (P = .002). Stimulation current was not associated with tumor plus peritumor edema volume, world health organization) (WHO grade, histology, or isocitrate dehydrogenase (IDH) mutation status but was associated with tumor volume within the frontal lobe (P = .018). Stimulation current was not associated with number of positive sites identified during ECS mapping (P = .118).

Conclusion: SISs are rare but serious events during ECS mapping. SISs are most common when mapping the frontal lobe. Greater stimulation current is not associated with the identification of more cortical functional sites during glioma surgery.
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http://dx.doi.org/10.1093/neuros/nyaa364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117445PMC
May 2021

Clinical Pearls and Methods for Intraoperative Awake Language Mapping.

Neurosurgery 2021 Jul;89(2):143-153

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.
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http://dx.doi.org/10.1093/neuros/nyaa440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279835PMC
July 2021

A Neurosurgeon's Guide to Cognitive Dysfunction in Adult Glioma.

Neurosurgery 2021 Jun;89(1):1-10

Department of Neurological Surgery, University of California San Francisco, San Francisco, California.

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.
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http://dx.doi.org/10.1093/neuros/nyaa400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203420PMC
June 2021

Functional Mapping for Glioma Surgery, Part 2: Intraoperative Mapping Tools.

Neurosurg Clin N Am 2021 Jan 5;32(1):75-81. Epub 2020 Nov 5.

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Intraoperative functional mapping of tumor and peri-tumor tissue is a well-established technique for avoiding permanent neurologic deficits and maximizing extent of resection. Motor, language, and other cognitive domains may be assessed with intraoperative tasks. This article describes techniques used for motor and language mapping including awake mapping considerations in addition to less traditional intraoperative testing paradigms for cognition. It also discusses complications associated with mapping and insights into complication avoidance.
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http://dx.doi.org/10.1016/j.nec.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687734PMC
January 2021

Surgical management of incidentally discovered low-grade gliomas.

J Neurosurg 2020 Oct 2:1-8. Epub 2020 Oct 2.

1Department of Neurological Surgery, University of California, San Francisco.

Objective: Although most patients with low-grade glioma (LGG) present after a seizure, a small proportion is diagnosed after neuroimaging is performed for a sign or symptom unrelated to the tumor. While these tumors invariably grow, some surgeons argue for a watchful waiting approach. Here, the authors report on their experience in the surgical treatment of patients with incidental LGG (iLGG) and describe the neurological outcomes, survival, and complications.

Methods: Relevant cases were identified from a prospective registry of patients undergoing glioma resection at the University of California, San Francisco, between 1997 and 2019. Cases were considered iLGG when the lesion was noted on imaging performed for a reason unrelated to the tumor. Demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. Tumor volumes, growth, and extent of resection were calculated from pre- and postoperative volumetric FLAIR sequences.

Results: One hundred thirteen of 657 (17.2%) first-time resections for LGG were for incidental lesions. The most common reasons for the discovery of an iLGG were headaches (without mass effect, 34.5%) or trauma (16.8%). Incidental tumors were no different from symptomatic lesions in terms of laterality or location, but they were significantly smaller (22.5 vs 57.5 cm3, p < 0.0001). There was no difference in diagnosis between patients with iLGG and those with symptomatic LGG (sLGG), incorporating both molecular and pathological data. The median preoperative observation time for iLGG was 3.1 months (range 1 month-12 years), and there was a median growth rate of 3.9 cm3/year. Complete resection of the FLAIR abnormality was achieved in 57% of patients with incidental lesions but only 23.8% of symptomatic lesions (p < 0.001), and the residual volumes were smaller for iLGGs (2.9 vs 13.5 cm3, p < 0.0001). Overall survival was significantly longer for patients with incidental tumors (median survival not reached for patients with iLGG vs 14.6 years for those with sLGG, p < 0.0001). There was a 4.4% rate of neurological deficits at 6 months.

Conclusions: The authors present the largest cohort of iLGGs. Patient age, tumor location, and molecular genetics were not different between iLGGs and sLGGs. Incidental tumors were smaller, a greater extent of resection could be achieved, and overall survival was improved compared to those for patients with sLGG. Operative morbidity and rates of neurological deficit were acceptably low; thus, the authors advocate upfront surgical intervention aimed at maximal safe resection for these incidentally discovered lesions.
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http://dx.doi.org/10.3171/2020.6.JNS201296DOI Listing
October 2020

WHO Grade I Meningioma Recurrence: Identifying High Risk Patients Using Histopathological Features and the MIB-1 Index.

Front Oncol 2020 28;10:1522. Epub 2020 Aug 28.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.

In this study, we identify clinical, radiographic, and histopathologic prognosticators of overall, early, and post-median recurrence in World Health Organization (WHO) grade I meningiomas. We also determine a clinically relevant cutoff for MIB-1 to identify patients at high risk for recurrence. A retrospective review of WHO grade I meningioma patients with available MIB-1 index data who underwent treatment at our institution from 2007 to 2017 was performed. Univariate and multivariate analyses, and recursive partitioning analysis (RPA), were used to identify risk factors for overall, early (within 24 months), and post-median (>24 months post-treatment) recurrence. A total of 239 patients were included. The mean age was 60.0 years, and 69.5% of patients were female. The average follow-up was 41.1 months. All patients received surgery and 2 patients each received either adjuvant radiotherapy (2/239) or gamma knife treatment (2/239). The incidence of recurrence was 10.9% (26/239 patients), with an average time to recurrence of 33.2 months (6-105 months). Posterior fossa tumor location ( = 0.004), MIB-1 staining ( = 0.008), nuclear atypia ( = 0.003), and STR ( < 0.001) were independently associated with an increased risk of recurrence on cox-regression analysis. RPA for overall recurrence highlighted extent of resection, and after gross total resection (GTR), a MIB-1 index cutoff of 4.5% as key prognostic factors for recurrence. Patients with a GTR and MIB-1 >4.5% had a similar incidence of recurrence as those with STR (18.8 vs. 18.6%). Variables independently associated with early recurrence on binary logistic regression modeling included STR ( = 0.002) and nuclear atypia ( = 0.019). RPA confirmed STR as associated with early recurrence. STR, posterior fossa location, nuclear atypia, and elevated MIB-1 index are prognostic factors for WHO grade I meningioma recurrence. Moreover, MIB-1 index >4.5% is prognostic for recurrence in patients with GTR. Verification of our findings in larger, multi-institutional studies could enable risk stratification and recommendations for adjuvant radiotherapy following resection of WHO grade I meningiomas.
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http://dx.doi.org/10.3389/fonc.2020.01522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483477PMC
August 2020

Achieving efficacious immunotherapy for patients with glioblastoma.

Authors:
Jacob S Young

Expert Rev Anticancer Ther 2020 11 10;20(11):909-911. Epub 2020 Oct 10.

Department of Neurological Surgery, University of California, San Francisco , San Francisco, California, USA.

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http://dx.doi.org/10.1080/14737140.2020.1814747DOI Listing
November 2020

Intraoperative Stereotactic Frame Registration Using a Three-Dimensional Imaging System with and without Preoperative Computed Tomography for Image Fusion.

Stereotact Funct Neurosurg 2020 20;98(5):313-318. Epub 2020 Aug 20.

Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA,

Background: The O-arm O2 imaging system (OAO2) is an intraoperative cone beam 3D tomogram imaging tool with a wide enough field of view to perform intraoperative fiducial registration with standard stereotactic frames. However, the OAO2 3D images (cone beam CT) provide limited tissue contrast, which may reduce the accuracy of fusion to a preoperative targeting MRI for planning awake deep brain stimulation (DBS) surgeries. Therefore, most users obtain a preoperative CT scan to use as the reference exam for computational fusion with the preoperative targeting MRI and the intraoperative OAO2 cone beam CT.

Objective: In this study, we retrospectively analyzed the discrepancy between stereotactic coordinates of deep brain targets on MRI derived from intraoperative OAO2 fiducial registration with and without the use of preoperative CT as the reference for image fusion.

Methods: Preoperative stereotactic CT/MRI and intraoperative OAO2 cone beam CT were retrospectively evaluated for 27 consecutive DBS patients, using two commercial surgical planning software packages (BrainLab Elements and Medtronic Stealth 8). The anterior commissure, posterior commissure, and left subthalamic nucleus were identified on preoperative MRI. Each patient had intraoperative fiducial registration using the OAO2 with a Leksell headframe. For each subject, the reference scan for image fusion was set as either the preoperative CT or the preoperative MRI (volumetric T1 with contrast). Computed stereotactic coordinates for each target were then compared.

Results: For 8 of 27 subjects, a discrepancy greater than 1.0 mm for at least one designated target was observed utilizing the Medtronic Stealth S8 planning station when a preoperative CT scan was not used. An additional 5 (5/27) had a discrepancy greater than 2 mm. The most common discrepancy was in the z axis. No coordinate discrepancies greater than 1 mm were observed utilizing BrainLab Elements.

Conclusions: Caution is advised in fusing intraoperative OAO2 images directly to preoperative MRI without a preoperative CT as the reference exam for image fusion, as the specific fusion algorithm employed may unpredictably affect targeting accuracy.
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http://dx.doi.org/10.1159/000509312DOI Listing
May 2021

Triple motor mapping: transcranial, bipolar, and monopolar mapping for supratentorial glioma resection adjacent to motor pathways.

J Neurosurg 2020 Jun 5:1-10. Epub 2020 Jun 5.

Departments of1Neurological Surgery and.

Objective: Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. The authors and other groups have described the use of bipolar or monopolar direct stimulation to identify functional tissue, as well as transcranial or transcortical motor evoked potentials (MEPs) to monitor motor pathways. Here, the authors describe their initial experience using all 3 modalities to identify, monitor, and preserve cortical and subcortical motor systems during glioma surgery.

Methods: Intraoperative mapping data were extracted from a prospective registry of glioma resections near motor pathways. Additional demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. All patients with new or worsened postoperative motor deficits were followed for at least 6 months.

Results: Between January 2018 and August 2019, 59 operations were performed in 58 patients. Overall, patients in 6 cases (10.2%) had new or worse immediate postoperative deficits. Patients with temporary deficits all had at least Medical Research Council grade 4/5 power. Only 2 patients (3.4%) had permanently worsened deficits after 6 months, both of which were associated with diffusion restriction consistent with ischemia within the corticospinal tract. One patient's deficit improved to 4/5 and the other to 4/5 proximally and 3/5 distally in the lower limb, allowing ambulation following rehabilitation. Subcortical motor pathways were identified in 51 cases (86.4%) with monopolar high-frequency stimulation, but only in 6 patients using bipolar stimulation. Transcranial or cortical MEPs were diminished in only 6 cases, 3 of which had new or worsened deficits, with 1 permanent deficit. Insula location (p = 0.001) and reduction in MEPs (p = 0.01) were the only univariate predictors of new or worsened postoperative deficits. Insula location was the only predictor of permanent deficits (p = 0.046). The median extent of resection was 98.0%.

Conclusions: Asleep triple motor mapping is safe and resulted in a low rate of deficits without compromising the extent of resection.
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http://dx.doi.org/10.3171/2020.3.JNS193434DOI Listing
June 2020

Clinical characteristics and outcomes of null-cell versus silent gonadotroph adenomas in a series of 1166 pituitary adenomas from a single institution.

Neurosurg Focus 2020 06;48(6):E13

3Department of Neurological Surgery, University of California, San Francisco, California.

Objective: Nonfunctioning pituitary adenomas present without biochemical or clinical signs of hormone excess and are the second most common type of pituitary adenomas. The 2017 WHO classification scheme of pituitary adenomas differentiates null-cell adenomas (NCAs) and silent gonadotroph adenomas (SGAs). The present study sought to highlight the differences in patient characteristics and clinical outcomes between NCAs and SGAs.

Methods: The records of 1166 patients who underwent transsphenoidal surgery for pituitary adenoma between 2012 and 2019 at a single institution were retrospectively reviewed. Patient demographics and clinical outcomes were collected.

Results: Of the overall pituitary adenoma cohort, 12.8% (n = 149) were SGAs and 9.2% (n = 107) NCAs. NCAs were significantly more common in female patients than SGAs (61.7% vs 26.8%, p < 0.001). There were no differences in patient demographics, initial tumor size, or perioperative and short-term clinical outcomes. There was no significant difference in the amount of follow-up between patients with NCAs and those with SGAs (33.8 months vs 29.1 months, p = 0.237). Patients with NCAs had significantly higher recurrence (p = 0.021), adjuvant radiation therapy usage (p = 0.002), and postoperative diabetes insipidus (p = 0.028). NCA pathology was independently associated with tumor recurrence (HR 3.64, 95% CI 1.07-12.30; p = 0.038), as were cavernous sinus invasion (HR 3.97, 95% CI 1.04-15.14; p = 0.043) and anteroposterior dimension of the tumor (HR 2.23, 95% CI 1.09-4.59; p = 0.030).

Conclusions: This study supports the definition of NCAs and SGAs as separate subgroups of nonfunctioning pituitary adenomas, and it highlights significant differences in long-term clinical outcomes, including tumor recurrence and the associated need for adjuvant radiation therapy, as well as postoperative diabetes insipidus. The authors also provide insight into independent risk factors for these outcomes in the adenoma population studied, providing clinicians with additional predictors of patient outcomes. Follow-up studies will hopefully uncover mechanisms of biological aggressiveness in NCAs and associated molecular targets.
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http://dx.doi.org/10.3171/2020.3.FOCUS20114DOI Listing
June 2020

Molecular characteristics of diffuse lower grade gliomas: what neurosurgeons need to know.

Acta Neurochir (Wien) 2020 08 30;162(8):1929-1939. Epub 2020 May 30.

Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA.

The importance of genomic information in intrinsic brain tumors is highlighted in the World Health Organization (WHO) 2016 classification of gliomas, which now incorporates both phenotype and genotype data to assign a diagnosis. By using genetic markers to both categorize tumors and advise patients on prognosis, this classification system has minimized the risk of tissue sampling error, improved diagnostic accuracy, and reduced inter-rater variability. In the neurosurgical community, it is critical to understand the role genetics plays in tumor biology, what certain mutations mean for the patient's prognosis and adjuvant treatment, and how to interpret the results of sequencing data that are generated following tumor resection. In this review, we examine the critical role of genetics for diagnosis and prognosis and highlight the importance of tumor genetics for neurosurgeons caring for patients with diffuse lower grade gliomas.
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http://dx.doi.org/10.1007/s00701-020-04426-2DOI Listing
August 2020

A Safe Transitions Pathway for post-craniotomy neurological surgery patients: high-value care that bypasses the intensive care unit.

J Neurosurg 2020 May 29;134(5):1386-1391. Epub 2020 May 29.

4University of California San Francisco Medical Center, San Francisco; and.

Objective: High-value medical care is described as care that leads to excellent patient outcomes, high patient satisfaction, and efficient costs. Neurosurgical care in particular can be expensive for the hospital, as substantial costs are accrued during the operation and throughout the postoperative stay. The authors developed a "Safe Transitions Pathway" (STP) model in which select patients went to the postanesthesia care unit (PACU) and then the neuro-transitional care unit (NTCU) rather than being directly admitted to the neurosciences intensive care unit (ICU) following a craniotomy. They sought to evaluate the clinical and financial outcomes as well as the impact on the patient experience for patients who participated in the STP and bypassed the ICU level of care.

Methods: Patients were enrolled during the 2018 fiscal year (FY18; July 1, 2017, through June 30, 2018). The electronic medical record was reviewed for clinical information and the hospital cost accounting record was reviewed for financial information. Nurses and patients were given a satisfaction survey to assess their respective impressions of the hospital stay and of the recovery pathway.

Results: No patients who proceeded to the NTCU postoperatively were upgraded to the ICU level of care postoperatively. There were no deaths in the STP group, and no patients required a return to the operating room during their hospitalization (95% CI 0%-3.9%). There was a trend toward fewer 30-day readmissions in the STP patients than in the standard pathway patients (1.2% [95% CI 0.0%-6.8%] vs 5.1% [95% CI 2.5%-9.1%], p = 0.058). The mean number of ICU days saved per case was 1.20. The average postprocedure length of stay was reduced by 0.25 days for STP patients. Actual FY18 direct cost savings from 94 patients who went through the STP was $422,128.

Conclusions: Length of stay, direct cost per case, and ICU days were significantly less after the adoption of the STP, and ICU bed utilization was freed for acute admissions and transfers. There were no substantial complications or adverse patient outcomes in the STP group.
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http://dx.doi.org/10.3171/2020.3.JNS192133DOI Listing
May 2020

The influence of race and socioeconomic status on therapeutic clinical trial screening and enrollment.

J Neurooncol 2020 May 29;148(1):131-139. Epub 2020 Apr 29.

Department of Neurological Surgery, University of California, 505 Parnassus Ave., Rm. M-779, San Francisco, CA, 94143-0112, USA.

Purpose: Under-enrollment in clinical trials significantly limits valid analyses of clinical interventions and generalizability of findings. Often it results in premature study termination, with estimates of 22% to 50% of clinical trials terminated due to poor accrual. Currently, there are limited reports addressing the influence of race/ethnicity and socioeconomic status on clinical trial enrollment in adult glioma patients. The goal of this study was to test the hypothesis that race and socioeconomic status negatively impact therapeutic clinical trial enrollment.

Methods: 988 adult patients were identified from the UCSF Tumor Board Registry and analyzed to determine the rate of therapeutic clinical trial screening and study enrollment.

Results: At initial diagnosis, 43.6% and 17.5% of glioma patients were screened and enrolled in a therapeutic clinical trial, respectively. At recurrence, 49.8% and 26.3% of patients were screened and enrolled in a clinical trial, respectively. Thirty-three percent of the study population belonged to a NIH-designated underrepresented minority group; Asian/Pacific-Islander comprised 19.6% of the overall cohort. On univariate analysis, only in-state location, distance to the hospital, and WHO grade were associated with enrollment at initial diagnosis and recurrence. Minority status, insurance type, median household income, and percent below poverty were not associated with clinical trial enrollment.

Conclusion: Minority and socioeconomic status did not impact adult glioma clinical trial enrollment. Proximity to the tertiary care cancer center may be an important consideration for minority patients. Patient screening should be carefully considered in order to avoid bias based on minority and socioeconomic status.
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http://dx.doi.org/10.1007/s11060-020-03503-xDOI Listing
May 2020

Awake glioma surgery: technical evolution and nuances.

J Neurooncol 2020 May 8;147(3):515-524. Epub 2020 Apr 8.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.

Introduction: Multiple studies have demonstrated that improved extent of resection is associated with longer overall survival for patients with both high and low grade glioma. Awake craniotomy was developed as a technique for maximizing resection whilst preserving neurological function.

Methods: We performed a comprehensive review of the literature describing the history, indications, techniques and outcomes of awake craniotomy for patients with glioma.

Results: The technique of awake craniotomy evolved to become an essential tool for resection of glioma. Many perceived contraindications can now be managed. We describe in detail our preferred technique, the testing paradigms utilized, and critically review the literature regarding functional and oncological outcome.

Conclusions: Awake craniotomy with mapping has become the gold standard for safely maximizing extent of resection for tumor in or near eloquent brain. Cortical and subcortical mapping methods have been refined and the technique is associated with an extremely low rate of complications.
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http://dx.doi.org/10.1007/s11060-020-03482-zDOI Listing
May 2020

The impact of high functional connectivity network hub resection on language task performance in adult low- and high-grade glioma.

J Neurosurg 2020 Apr 3;134(3):1102-1112. Epub 2020 Apr 3.

1Department of Neurological Surgery and.

Objective: Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)-negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance.

Methods: Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN).

Results: Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1-8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1-6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus.

Conclusions: Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.
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http://dx.doi.org/10.3171/2020.1.JNS192267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011942PMC
April 2020

Mesolimbic dopamine D2 receptors and neural representations of subjective value.

Sci Rep 2019 12 27;9(1):20229. Epub 2019 Dec 27.

Department of Psychology and Neuroscience, Duke University, Durham, United States.

The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct measures of dopamine receptors and neural representations of subjective value in humans. Here, we examined whether individual differences in D2R availability were related to neural subjective value signals during decision making. Human participants completed a monetary delay discounting task during an fMRI scan and on a separate visit completed a PET scan with the high affinity D2R tracer [18 F]fallypride. Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively correlated with subjective value-related activity in the ventromedial prefrontal cortex and midbrain but not with choice behavior. Whole-brain analyses revealed a positive correlation between ventral striatum D2R availability and subjective value-related activity in the left inferior frontal gyrus and superior insula. These findings identify a link between a direct measure of mesolimbic dopamine function and subjective value representation in humans and suggest a mechanism by which individuals vary in neural representation of discounted subjective value.
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http://dx.doi.org/10.1038/s41598-019-56858-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934551PMC
December 2019

Management of Noncatastrophic Internal Carotid Artery Injury in Endoscopic Skull Base Surgery.

Cureus 2019 Aug 30;11(8):e5537. Epub 2019 Aug 30.

Neurological Surgery, University of California, San Francisco, USA.

Arterial injuries are the most feared complication of endoscopic skull base surgery. During resection of the middle fossa component of a large ventral skull base chondrosarcoma, arterial bleeding was encountered near the right internal carotid artery (ICA). Durable hemostasis could not be achieved with packing and the patient was taken for an emergent angiogram that revealed a pseudoaneurysm of the proximal intradural ICA. Given the presence of good collateral flow through the anterior and posterior communicating arteries, the right ICA was sacrificed by coil embolization. The patient was taken back to the operating room for closure then transferred to the intensive care unit and maintained on vasopressors for five days to ensure adequate perfusion. The right ICA was coil embolized and the patient was taken back to the operating room for closure. The patient recovered without complication. Arterial injuries, although serious, are not always catastrophic. Critical steps are immediate recognition of bleeding, vascular imaging, and vessel sacrifice if necessary.
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http://dx.doi.org/10.7759/cureus.5537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819080PMC
August 2019

Disruption of Frontal Aslant Tract Is Not Associated with Long-Term Postoperative Language Deficits.

World Neurosurg 2020 Jan 28;133:192-195. Epub 2019 Sep 28.

Department of Neurosurgery, University of California, San Francisco, California, USA. Electronic address:

Background: The frontal aslant tract (FAT) is a white matter fiber pathway connecting the superior frontal gyrus to the Broca area. This tract in the dominant hemisphere has been shown to play a role in speech initiation and production, and direct subcortical stimulation can induce stuttering and speech arrest in a patient. However, controversy remains as to whether disruption of this pathway will lead to a permanent language deficit and if it is even necessary to map this tract during tumor resections of the dominant frontal lobe.

Case Description: Here, we report a case of a patient with a lower-grade diffuse glioma invading the dominant FAT that was removed with an asleep craniotomy. In the immediate postoperative state, the patient had a transcortical motor dysphasia and was unable to initiate speech. These immediate language deficits quickly recovered, and the patient was neurologically intact at the time of discharge a few days after surgery.

Conclusions: Given the high likelihood for a complete neurologic recovery including transient aphasia, we propose that awake mapping for the purpose of identifying the dominant FAT is unnecessary during tumor resection and that disruption of this tract is not associated with any long-term language deficits.
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http://dx.doi.org/10.1016/j.wneu.2019.09.128DOI Listing
January 2020

Insurance type impacts the economic burden and survival of patients with newly diagnosed glioblastoma.

J Neurosurg 2019 Jun 21:1-11. Epub 2019 Jun 21.

Objective: Glioblastoma (GBM) carries a high economic burden for patients and caregivers, much of which is associated with initial surgery. The authors investigated the impact of insurance status on the inpatient hospital costs of surgery for patients with GBM.

Methods: The authors conducted a retrospective review of patients with GBM (2010-2015) undergoing their first resection at the University of California, San Francisco, and corresponding inpatient hospital costs.

Results: Of 227 patients with GBM (median age 62 years, 37.9% females), 31 (13.7%) had Medicaid, 94 (41.4%) had Medicare, and 102 (44.9%) had private insurance. Medicaid patients had 30% higher overall hospital costs for surgery compared to non-Medicaid patients ($50,285 vs $38,779, p = 0.01). Medicaid patients had higher intensive care unit (ICU; p < 0.01), operating room (p < 0.03), imaging (p < 0.001), room and board (p < 0001), and pharmacy (p < 0.02) costs versus non-Medicaid patients. Medicaid patients had significantly longer overall and ICU lengths of stay (6.9 and 2.6 days) versus Medicare (4.0 and 1.5 days) and privately insured patients (3.9 and 1.8 days, p < 0.01). Medicaid patients had similar comorbidity rates to Medicare patients (67.8% vs 68.1%), and both groups had higher comorbidity rates than privately insured patients (37.3%, p < 0.0001). Only 67.7% of Medicaid patients had primary care providers (PCPs) versus 91.5% of Medicare and 86.3% of privately insured patients (p = 0.009) at the time of presentation. Tumor diameter at diagnosis was largest for Medicaid (4.7 cm) versus Medicare (4.1 cm) and privately insured patients (4.2 cm, p = 0.03). Preoperative (70 vs 90, p = 0.02) and postoperative (80 vs 90, p = 0.03) Karnofsky Performance Scale (KPS) scores were lowest for Medicaid versus non-Medicaid patients, while in subgroup analysis, postoperative KPS score was lowest for Medicaid patients (80, vs 90 for Medicare and 90 for private insurance; p = 0.03). Medicaid patients had significantly shorter median overall survival (10.7 months vs 12.8 months for Medicare and 15.8 months for private insurance; p = 0.02). Quality-adjusted life year (QALY) scores were 0.66 and 1.05 for Medicaid and non-Medicaid patients, respectively (p = 0.036). The incremental cost per QALY was $29,963 lower for the non-Medicaid cohort.

Conclusions: Patients with GBMs and Medicaid have higher surgical costs, longer lengths of stay, poorer survival, and lower QALY scores. This study indicates that these patients lack PCPs, have more comorbidities, and present later in the disease course with larger tumors; these factors may drive the poorer postoperative function and greater consumption of hospital resources that were identified. Given limited resources and rising healthcare costs, factors such as access to PCPs, equitable adjuvant therapy, and early screening/diagnosis of disease need to be improved in order to improve prognosis and reduce hospital costs for patients with GBM.
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http://dx.doi.org/10.3171/2019.3.JNS182629DOI Listing
June 2019
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