Publications by authors named "Michael C Jin"

36 Publications

Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015.

J Neurosurg Pediatr 2021 Jun 18:1-9. Epub 2021 Jun 18.

Objective: Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG.

Methods: A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients.

Results: In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010).

Conclusions: Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.1.PEDS20859DOI Listing
June 2021

Defining and Describing Treatment Heterogeneity in New-Onset Idiopathic Lower Back and Extremity Pain Through Reconstruction of Longitudinal Care Sequences.

Spine J 2021 May 22. Epub 2021 May 22.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA. Electronic address:

Background Context: Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices.

Purpose: To describe treatment heterogeneity in surgically-managed LBP and LEP.

Study Design/setting: Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016).

Patient Sample: A population-based sample of opioid-naïve adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up.

Exposure: Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion).

Outcome Measures: Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage.

Methods: Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance.

Results: A total of 2,496,908 opioid-naïve adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs 63.8%, p<0.001). Non-outlier sequences were more frequently characterized by early conservative interventions (31.9% vs 7.4%, p<0.001).

Conclusions: Surgically-managed LBP and LEP care sequences demonstrate high heterogeneity despite established practice guidelines. Outlier sequences associated with high opioid usage and costs can be identified and are characterized by increased early imaging and decreased early conservative management. Elements that may portend suboptimal longitudinal management could provide opportunities for standardization of patient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2021.05.019DOI Listing
May 2021

Status epilepticus after intracranial neurosurgery: incidence and risk stratification by perioperative clinical features.

J Neurosurg 2021 May 14:1-13. Epub 2021 May 14.

Departments of1Neurosurgery and.

Objective: Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE).

Methods: Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates.

Results: A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183-1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388-5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016-2.061) and CSF diversion (aHR 1.307, 95% CI 1.076-1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99-104.80).

Conclusions: Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.10.JNS202895DOI Listing
May 2021

Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma.

J Clin Oncol 2021 Apr 28:JCO2002573. Epub 2021 Apr 28.

Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA.

Purpose: Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias.

Patients And Methods: We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome.

Results: Short DTI was associated with advanced-stage disease ( .001) and higher IPI ( .001). We also found an inverse correlation between DTI and TMTV (0.37; .001). Similarly, pretreatment ctDNA levels were significantly associated with stage, IPI, and TMTV (all .001), demonstrating that both DTI and ctDNA reflect disease burden. Notably, patients with shorter DTI had higher pretreatment ctDNA levels ( .001). Pretreatment ctDNA levels predicted short DTI independent of the IPI ( .001). Although each risk factor was significantly associated with event-free survival in univariable analysis, ctDNA level was prognostic of event-free survival independent of DTI and IPI in multivariable Cox regression (ctDNA: hazard ratio, 1.5; 95% CI [1.2 to 2.0]; IPI: 1.1 [0.9 to 1.3]; -DTI: 1.1 [1.0 to 1.2]).

Conclusion: Short DTI largely reflects baseline tumor burden, which can be objectively measured using pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02573DOI Listing
April 2021

Intraoperative Neuromonitoring for Cerebral Arteriovenous Malformation Embolization: A Propensity-Score Matched Retrospective Database Study.

Cureus 2021 Jan 27;13(1):e12946. Epub 2021 Jan 27.

Radiology, Stanford University School of Medicine, Stanford, USA.

Introduction The treatment of cerebral arteriovenous malformations (AVMs) may result in neurologic morbidity, particularly when an AVM is located in or adjacent to eloquent brain regions. Intraoperative neurophysiologic monitoring (IONM) may be utilized to reduce the risk of iatrogenic injury during endovascular AVM embolization; however, IONM for endovascular AVM embolization is not ubiquitously the standard of care. Methods Admissions for AVM embolization were assessed from the IBM MarketScan® Commercial and Medicare Supplemental databases (IBM Watson Health, Somers, NY). Inclusion criterion for patients was continuous enrollment six months before and after the index encounter. The use of IONM and presence of intracranial hemorrhage (ICH) were noted. Propensity-score matched cohorts with and without IONM were generated to minimize bias between treatment groups (adjusting for age, sex, and comorbidities). Results From 2007 to 2016, there were 16,279 patients diagnosed with cerebral AVM in the MarketScan database. Embolized patients were stratified into IONM and non-IONM cohorts; there were 357 patients in the IONM cohort and 1775 patients in the non-IONM cohort. Provider types were significantly different between cohorts (p<0.005). Unruptured AVMs were significantly more likely to be embolized with adjunctive IONM (17.7%) compared to ruptured AVMs (7.9%) (p<0.005). After balancing for baseline comorbidities, there were 266 patients in the IONM cohort, and 1347 patients in the non-IONM cohort. Among unruptured AVM patients, IONM was linked to a significantly shorter length of stay (2.72 versus 4.92 days; p<0.005), significantly lower rates of complications within 30 days of discharge (0.00% versus 1.88%; p=0.038), and significantly lower total payment ($40,179 versus $50,844; p<0.0001). Conclusion Endovascular embolization for unruptured AVMs performed with adjunctive IONM was associated with shorter length of stay, lower complication rates, and hospitalization costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.12946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910512PMC
January 2021

National Trends in Opioid Prescriptions Following Outpatient Otologic Surgery, 2005-2017.

Otolaryngol Head Neck Surg 2021 04 23;164(4):841-849. Epub 2021 Feb 23.

Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, USA.

Objective: To describe opioid stewardship in ambulatory otologic surgery from 2005 to 2017.

Study Design: Descriptive study of US private insurance claims.

Setting: Nationwide deidentified private insurance claims database (Clinformatics DataMart; Optum).

Methods: A total of 17,431 adult opioid-naïve outpatients were included in the study. Patients were identified from codes () as having undergone middle ear or mastoid surgery. Multiple regression was used to determine sociodemographic and geographic predictors of postoperative morphine milligram equivalents (MMEs) prescribed, including procedure type, year of procedure, age, sex, education, income level, and geographic region of the United States.

Results: The mean prescribed perioperative dose over the examined period was 203.03 MMEs (95% CI, 200.27-205.79; 5-mg hydrocodone pill equivalents, 40.61). In multivariate analysis, patients undergoing mastoid surgery were prescribed more opioids than those undergoing middle ear surgery (mean difference, 39.89 MME [95% CI, 34.37-45.41], < .01; 5-mg hydrocodone pill equivalents, 8.0). Men were prescribed higher doses than women (mean difference, 15.39 [95% CI, 9.87-20.90], < .01; 5-mg hydrocodone pill equivalents, 3.1). Overall MMEs prescribed by year demonstrates a sharp drop in MMEs from 2015 to 2017.

Conclusion: While the amount of opioids prescribed perioperatively has declined in recent years, otologists should continue to be cognizant of potential overprescribing in light of previous studies of patients' relatively low opioid intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599821994755DOI Listing
April 2021

Management of brain tumors presenting in pregnancy: a case series and systematic review.

Am J Obstet Gynecol MFM 2021 01 17;3(1):100256. Epub 2020 Oct 17.

Departments of Neurosurgery, Stanford University School of Medicine, Stanford, CA. Electronic address:

Patients who present with brain tumors during pregnancy require unique imaging and neurosurgical, obstetrical, and anesthetic considerations. Here, we review the literature and discuss the management of patients who present with brain tumors during pregnancy. Between 2009 and 2019, 9 patients were diagnosed at our institution with brain tumors during pregnancy. Clinical information was extracted from the electronic medical records. The median age at presentation was 29 years (range, 25-38 years). The most common symptoms at presentation included headache (n=5), visual changes (n=4), hemiparesis (n=3), and seizures (n=3). The median gestational age at presentation was 20.5 weeks (range, 11-37 weeks). Of note, 8 patients (89%) delivered healthy newborns, and 1 patient terminated her pregnancy. In addition, 5 patients (56%) required neurosurgical procedures during pregnancy (gestational ages, 14-37 weeks) because of disease progression (n=2) or neurologic instability (n=3). There was 1 episode of postneurosurgery morbidity (pulmonary embolism [PE]) and no surgical maternal mortality. The median length of follow-up was 15 months (range, 6-45 months). In cases demonstrating unstable or progressive neurosurgical status past the point of fetal viability, neurosurgical intervention should be considered. The physiological and pharmacodynamic changes of pregnancy substantially affect anesthetic management. Pregnancy termination should be discussed and offered to the patient when aggressive disease necessitates immediate treatment and the fetal gestational age remains previable, although neurologically stable patients may be able to continue the pregnancy to term. Ultimately, pregnant patients with brain tumors require an individualized approach to their care under the guidance of a multidisciplinary team.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajogmf.2020.100256DOI Listing
January 2021

An Analysis of Public Interest in Elective Neurosurgical Procedures During the COVID-19 Pandemic Through Online Search Engine Trends.

World Neurosurg 2021 04 4;148:e282-e293. Epub 2021 Jan 4.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA. Electronic address:

Objective: In the wake of the COVID-19 pandemic, the Centers for Medicare & Medicaid Services (CMS) has recommended the temporary cessation of all elective surgeries. The effects on patients' interest of elective neurosurgical procedures are currently unexplored.

Methods: Using Google Trends, search terms of 7 different neurosurgical procedure categories (trauma, spine, tumor, movement disorder, epilepsy, endovascular, and miscellaneous) were assessed in terms of relative search volume (RSV) between January 2015 and September 2020. Analyses of search terms were performed for over the short term (February 18, 2020, to April 18, 2020), intermediate term (January 1, 2020, to May 31, 2020), and long term (January 2015 to September 2020). State-level interest during phase I reopening (April 28, 2020, to May 31, 2020) was also evaluated.

Results: In the short term, RSVs of 4 categories (epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the intermediate term, RSVs of 5 categories (miscellaneous, epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the long term, RSVs of nearly all categories (endovascular, epilepsy, miscellaneous, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. Only the movement disorder procedure category had significantly higher RSV in states that reopened early.

Conclusions: With the recommendation for cessation of elective surgeries, patient interests in overall elective neurosurgical procedures have dropped significantly. With gradual reopening, there has been a resurgence in some procedure types. Google Trends has proven to be a useful tracker of patient interest and may be used by neurosurgical departments to facilitate outreach strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.12.143DOI Listing
April 2021

Impact of proton radiotherapy on treatment timing in pediatric and adult patients with CNS tumors.

Neurooncol Pract 2020 Dec 18;7(6):626-635. Epub 2020 Jun 18.

Palo Alto Veterans Affairs Health Care System, Palo Alto, California.

Background: Despite putative benefits associated with proton radiotherapy in the setting of CNS tumors, numerous barriers limit treatment accessibility. Given these challenges, we explored the association of proton use with variations in treatment timing.

Methods: Pediatric and adult patients with histologically confirmed CNS tumors were identified from the National Cancer Database (2004-2015). Univariable and multivariable regression models were constructed to assess factors impacting radiation timing. Multivariable Cox regression was used to evaluate the effect of treatment delay on survival.

Results: A total of 76 157 patients received photon or proton radiotherapy. Compared to photons, time to proton administration was longer in multiple pediatric (embryonal, ependymal, nonependymal glial, and other) and adult (ependymal, nonependymal glial, meningeal, other) tumor histologies. On adjusted analysis, proton radiotherapy was associated with longer delays in radiotherapy administration in pediatric embryonal tumors (+3.00 weeks, = .024) and in all adult tumors (embryonal [+1.36 weeks, = .018], ependymal [+3.15 weeks, < .001], germ cell [+2.65 weeks, = .024], glial [+2.15 weeks, < .001], meningeal [+5.05 weeks, < .001], and other [+3.06 weeks, < .001]). In patients with high-risk tumors receiving protons, delays in adjuvant radiotherapy were independently associated with poorer survival (continuous [weeks], adjusted hazard ratio = 1.09, 95% CI = 1.02-1.16).

Conclusions: Proton radiotherapy is associated with later radiation initiation in pediatric and adult patients with CNS tumors. In patients with high-risk CNS malignancies receiving protons, delayed adjuvant radiotherapy is associated with poorer survival. Further studies are needed to understand this discrepancy to maximize the potential of proton radiotherapy for CNS malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nop/npaa034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716142PMC
December 2020

Trends in Use and Timing of Intratympanic Corticosteroid Injections for Sudden Sensorineural Hearing Loss.

Otolaryngol Head Neck Surg 2020 Dec 8:194599820976177. Epub 2020 Dec 8.

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Stanford, California, USA.

Objective: Oral corticosteroids are treatment mainstays for idiopathic sudden sensorineural hearing loss (SSNHL). Recent studies suggest that intratympanic (IT) steroid injections may be effective as an alternate or adjunctive therapy. We sought to investigate nationwide trends in treatment patterns for SSNHL.

Study Design: Retrospective cross-sectional study.

Setting: A large nationwide health care claims database spanning 2007 to 2016.

Methods: Patients with SSNHL were identified from the IBM Watson Health MarketScan Database. Multivariable logistic, linear, and Cox regression were used for demographic- and comorbidity-adjusted analyses.

Results: Overall, 19,670 patients were included. Between 2007 and 2016, use of oral corticosteroids alone decreased (83.6% to 64.6%, < .001), while use of IT corticosteroids alone and combination IT-oral corticosteroids increased (IT only, 7.9% to 15.1%, = .002; IT-oral, 8.5% to 20.4%, < .001). During the study period, time to treatment initiation decreased for both administration modalities, though more dramatically for IT corticosteroids (IT, 124.0 to 10.6 days, < .001; oral, 42.6 to 12.7 days, < .001). In patients receiving both IT and oral corticosteroids, concurrent first-line use increased (25.2% to 52.8%, < .001). Repeat injections have also become more common but may raise risk of persistent tympanic membrane perforations (vs no injection; hazard ratio [first injection] = 7.95, 95% CI = 5.54-11.42; hazard ratio [fifth or higher injection] = 17.47, 95% CI = 6.93-44.05).

Conclusion: SSNHL management increasingly involves early IT steroids as an alternative or adjunctive option to oral steroids. Use of repeat IT corticosteroid injections has also increased but may raise risk of persistent tympanic membrane perforations and subsequent tympanoplasty. Future decision analysis and cost-effectiveness studies are necessary to identify an optimal care pattern for SSNHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599820976177DOI Listing
December 2020

Resection of Olfactory Groove Meningiomas Through Unilateral vs. Bilateral Approaches: A Systematic Review and Meta-Analysis.

Front Oncol 2020 22;10:560706. Epub 2020 Oct 22.

Department of Neurosurgery, Kaiser Permanente, Redwood City, CA, United States.

Consensus is limited regarding optimal transcranial approaches (TCAs) for the surgical resection of olfactory groove meningiomas (OGMs). This systematic review and meta-analysis aims to examine operative and peri-operative outcomes of unilateral compared to bilateral TCAs for OGMs. Electronic databases were searched from inception until December 2019 for studies delineating TCAs for OGM patients. Patient demographics, pre-operative symptoms, surgical outcomes, and complications were evaluated and analyzed with a meta-analysis of proportions. A total of 27 observational case series comparing 554 unilateral vs. 451 bilateral TCA patients were eligible for review. The weighted pooled incidence of gross total resection is 94.6% (95% CI, 90.7-97.5%; = 59.0%; = 0.001) for unilateral and 90.9% (95% CI, 85.6-95.4%; = 58.1%; = 0.003) for bilateral cohorts. Similarly, the incidence of OGM recurrence is 2.6% (95% CI, 0.4-6.0%; = 53.1%; = 0.012) and 4.7% (95% CI, 1.4-9.2%; = 55.3%; = 0.006), respectively. Differences in oncologic outcomes were not found to be statistically significant ( = 0.21 and 0.35, respectively). Statistically significant differences in complication rates in bilateral vs. unilateral TCA cohorts include meningitis (1.0 vs. 0.0%; = 0.022) and mortality (3.2 vs. 0.2%; = 0.007). While both cohorts have similar oncologic outcomes, bilateral TCA patients exhibit higher post-operative complication rates. This may be explained by underlying tumor characteristics necessitating more radical resection but may also indicate increased morbidity with bilateral approaches. However, evidence from more controlled, comparative studies is warranted to further support these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.560706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642686PMC
October 2020

Facial Nerve Paralysis Following Endovascular Embolization: A Case Report and Review of the Literature.

Ann Otol Rhinol Laryngol 2021 Jul 2;130(7):848-855. Epub 2020 Nov 2.

Department of Otolaryngology, Stanford Hospital, Stanford University School of Medicine, Stanford, CA, USA.

Objective: We report a case of facial nerve paralysis post-endovascular embolization of a sigmoid sinus dural arterio-venous fistula from initial presentation to current management and discuss the merits of observation versus decompression through a systematic review of relevant literature.

Patient: 61 F with right facial palsy.

Intervention: Following a single intravenous dexamethasone injection with oral steroids over 2 months, patient was observed with no additional treatment other than Botox chemodenervation and facial rehabilitation.

Outcome And Results: The patient initially presented with complete right facial palsy (HB 6/6). Post-op CT imaging indicated Onyx (ev3, Irvine, California, USA) particles present at the geniculate segment of the facial nerve. Observation was chosen over surgical intervention. At the most current follow up of 8 months, facial function has improved substantially (HB 2/6).

Conclusion: Facial palsy is a serious, though rare, complication of transarterial endovascular embolization. With our case report and literature review, we highlight not only how conservative observation is the recommended treatment, but also that facial nerve recovery should be expected to reach near complete recovery, but not sooner than in 3 months.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003489420966611DOI Listing
July 2021

Medical malpractice in spine surgery: a review.

Neurosurg Focus 2020 11;49(5):E16

Medical malpractice is an important but often underappreciated topic within neurosurgery, particularly for surgeons in the early phases of practice. The practice of spinal neurosurgery involves substantial risk for litigation, as both the natural history of the conditions being treated and the operations being performed almost always carry the risk of permanent damage to the spinal cord or nerve roots, a cardiopulmonary event, death, or other dire outcomes. In this review, the authors discuss important topics related to medical malpractice in spine surgery, including tort reform, trends and frequency of litigation claims in spine surgery, wrong-level and wrong-site surgery, catastrophic outcomes including spinal cord injury and death, and ethical considerations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.8.FOCUS20602DOI Listing
November 2020

Adverse Events and Bundled Costs after Cranial Neurosurgical Procedures: Validation of the LACE Index Across 40,431 Admissions and Development of the LACE-Cranial Index.

World Neurosurg 2021 02 28;146:e431-e451. Epub 2020 Oct 28.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA. Electronic address:

Objective: Anticipating postdischarge complications after neurosurgery remains difficult. The LACE index, based on 4 hospitalization descriptors, stratifies patients by risk of 30-day postdischarge adverse events but has not been validated in a procedure-specific manner in neurosurgery. Our study sought to explore the usefulness of the LACE index in a population undergoing cranial neurosurgery and to develop an enhanced model, LACE-Cranial.

Methods: The OptumClinformatics Database was used to identify cranial neurosurgery admissions (2004-2017). Procedures were grouped as trauma/hematoma/intracranial pressure, open vascular, functional/pain, skull base, tumor, or endovascular. Adverse events were defined as postdischarge death/readmission. LACE-Cranial was developed using a logistic regression framework incorporating an expanded feature set in addition to the original LACE components.

Results: A total of 40,431 admissions were included. Predictions of 30-day readmissions was best for skull base (area under the curve [AUC], 0.636) and tumor (AUC, 0.63) admissions but was generally poor. Predictive ability of 30-day mortality was best for functional/pain admissions (AUC, 0.957) and poorest for trauma/hematoma/intracranial pressure admissions (AUC, 0.613). Across procedure types except for functional/pain, a high-risk LACE score was associated with higher postdischarge bundled payment costs. Incorporating features identified to contribute independent predictive value, the LACE-Cranial model achieved procedure-specific 30-day mortality AUCs ranging from 0.904 to 0.98. Prediction of 30-day and 90-day readmissions was also improved, with tumor and skull base cases achieving 90-day readmission AUCs of 0.718 and 0.717, respectively.

Conclusions: Although the unmodified LACE index shows inconsistent classification performance, the enhanced LACE-Cranial model offers excellent prediction of short-term postdischarge mortality across procedure groups and significantly improved anticipation of short-term postdischarge readmissions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.10.103DOI Listing
February 2021

Predictive modeling of long-term opioid and benzodiazepine use after intradural tumor resection.

Spine J 2020 Oct 13. Epub 2020 Oct 13.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States. Electronic address:

Background Context: Despite increased awareness of the ongoing opioid epidemic, opioid and benzodiazepine use remain high after spine surgery. In particular, long-term co-prescription of opioids and benzodiazepines have been linked to high risk of overdose-associated death. Tumor patients represent a unique subset of spine surgery patients and few studies have attempted to develop predictive models to anticipate long-term opioid and benzodiazepine use after spinal tumor resection.

Methods: The IBM Watson Health MarketScan Database and Medicare Supplement were assessed to identify admissions for intradural tumor resection between 2007 and 2015. Adult patients were required to have at least 6 months of continuous preadmission baseline data and 12 months of continuous postdischarge follow-up. Primary outcomes were long-term opioid and benzodiazepine use, defined as at least 6 prescriptions within 12 months. Secondary outcomes were durations of opioid and benzodiazepine prescribing. Logistic regression models, with and without regularization, were trained on an 80% training sample and validated on the withheld 20%.

Results: A total of 1,942 patients were identified. The majority of tumors were extramedullary (74.8%) and benign (62.5%). A minority of patients received arthrodesis (9.2%) and most patients were discharged to home (79.1%). Factors associated with postdischarge opioid use duration include tumor malignancy (vs benign, B=19.8 prescribed-days/year, 95% confidence interval [CI] 1.1-38.5) and intramedullary compartment (vs extramedullary, B=18.1 prescribed-days/year, 95% CI 3.3-32.9). Pre- and perioperative use of prescribed nonsteroidal anti-inflammatory drugs and gabapentin/pregabalin were associated with shorter and longer duration opioid use, respectively. History of opioid and history of benzodiazepine use were both associated with increased postdischarge opioid and benzodiazepine use. Intramedullary location was associated with longer duration postdischarge benzodiazepine use (B=10.3 prescribed-days/year, 95% CI 1.5-19.1). Among assessed models, elastic net regularization demonstrated best predictive performance in the withheld validation cohort when assessing both long-term opioid use (area under curve [AUC]=0.748) and long-term benzodiazepine use (AUC=0.704). Applying our model to the validation set, patients scored as low-risk demonstrated a 4.8% and 2.4% risk of long-term opioid and benzodiazepine use, respectively, compared to 35.2% and 11.1% of high-risk patients.

Conclusions: We developed and validated a parsimonious, predictive model to anticipate long-term opioid and benzodiazepine use early after intradural tumor resection, providing physicians opportunities to consider alternative pain management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2020.10.010DOI Listing
October 2020

Opioid Prescribing Patterns Following Pediatric Tonsillectomy in the United States, 2009-2017.

Laryngoscope 2021 05 7;131(5):E1722-E1729. Epub 2020 Oct 7.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, U.S.A.

Objectives: Assess national trends in opioid prescription following pediatric tonsillectomy: 1) overall percentage receiving opioids and mean quantity, 2) changes during 2009-2017, and 3) determinants of prescription patterns.

Methods: Cross-sectional analysis using 2009-2017 Optum claims data to identify opioid-naïve children aged 1-18 with claims codes for tonsillectomy (n = 82,842). Quantities of opioids filled in outpatient pharmacies during the perioperative period were extracted and converted into milligram morphine equivalents (MMEs) for statistical comparison. Demographic, clinical, and socioeconomic predictors of opioid fill rate and quantity were determined using regression analyses.

Results: In 2009, 83.3% of children received opioids, decreasing to 58.3% by 2017. Rates of all-cause readmissions and post-tonsillectomy hemorrhages were similar over time. Mean quantity received was 153.47MME (95% confidence intervals [95%CI]: 151.19, 155.76) and did not significantly change during 2009-2017. Opioids were more likely in older children and those with higher household income, but less likely in children with obstructive sleep apnea, other comorbidities, and Hispanic race. Higher quantities of opioids were more likely in older children, while lower quantities were associated with female sex, Hispanic race, and higher household income. Outpatient steroids were prescribed to 8.04% of patients, who were less likely to receive opioids.

Conclusion: While the percentage of children receiving post-tonsillectomy opioids decreased during 2009-2017, prescribed quantities remain high and have not decreased over time. Prescription practices were also influenced by clinical and sociodemographic factors. These results highlight the need for guidance, particularly with regard to opioid quantity, in children after tonsillectomy.

Level Of Evidence: N/A Laryngoscope, 131:E1722-E1729, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.29159DOI Listing
May 2021

Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition.

Cell 2020 10 1;183(2):363-376.e13. Epub 2020 Oct 1.

Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell School of Medicine, New York, NY, USA; Parker Institute for Cancer Immunotherapy at MSK, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572899PMC
October 2020

Long-term follow-up of neurosurgical outcomes for adult patients in Uganda with traumatic brain injury.

J Neurosurg 2020 Jul 3:1-11. Epub 2020 Jul 3.

2Department of Neurosurgery, Stanford University, Palo Alto, California.

Objective: Traumatic brain injury (TBI) is a major cause of mortality and morbidity in Uganda and other low- and middle-income countries (LMICs). Due to the difficulty of long-term in-person follow-up, there is a paucity of literature on longitudinal outcomes of TBI in LMICs. Using a scalable phone-centered survey, this study attempted to investigate factors associated with both mortality and quality of life in Ugandan patients with TBI.

Methods: A prospective registry of adult patients with TBI admitted to the neurosurgical ward at Mulago National Referral Hospital was assembled. Long-term follow-up was conducted between 10.4 and 30.5 months after discharge (median 18.6 months). Statistical analyses included univariable and multivariable logistic regression and Cox proportional hazards regression to elucidate factors associated with mortality and long-term recovery.

Results: A total of 1274 adult patients with TBI were included, of whom 302 (23.7%) died as inpatients. Patients who died as inpatients received surgery less frequently (p < 0.001), had more severe TBI at presentation (p < 0.001), were older (p < 0.001), and were more likely to be female (p < 0.0001). Patients presenting with TBI resulting from assault were at reduced risk of inpatient death compared with those presenting with TBI caused by road traffic accidents (OR 0.362, 95% CI 0.128-0.933). Inpatient mortality and postdischarge mortality prior to follow-up were 23.7% and 9%, respectively. Of those discharged, 60.8% were reached through phone interviews. Higher Glasgow Coma Scale score at discharge (continuous HR 0.71, 95% CI 0.53-0.94) was associated with improved long-term survival. Tracheostomy (HR 4.38, 95% CI 1.05-16.7) and older age (continuous HR 1.03, 95% CI 1.009-1.05) were associated with poor long-term outcomes. More than 15% of patients continued to suffer from TBI sequelae years after the initial injury, including seizures (6.1%) and depression (10.0%). Despite more than 60% of patients seeking follow-up healthcare visits, mortality was still 9% among discharged patients, suggesting a need for improved longitudinal care to monitor recovery progress.

Conclusions: Inpatient and postdischarge mortality remain high following admission to Uganda's main tertiary hospital with the diagnosis of TBI. Furthermore, posttraumatic sequelae, including seizures and depression, continue to burden patients years after discharge. Effective scalable solutions, including phone interviews, are needed to elucidate and address factors limiting in-hospital capacity and access to follow-up healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.4.JNS193092DOI Listing
July 2020

Recurrence of cavernous malformations after surgery in childhood.

J Neurosurg Pediatr 2020 May 1:1-10. Epub 2020 May 1.

Departments of1Neurosurgery and.

Objective: Cavernous malformations (CMs) are commonly treated cerebrovascular anomalies in the pediatric population; however, the data on radiographic recurrence of pediatric CMs after surgery are limited. The authors aimed to study the clinical presentation, outcomes, and recurrence rate following surgery for a large cohort of CMs in children.

Methods: Pediatric patients (≤ 18 years old) who had a CM resected at a single institution were identified and retrospectively reviewed. Fisher's exact test of independence was used to assess differences in categorical variables. Survival curves were evaluated using the Mantel-Cox method.

Results: Fifty-three patients aged 3 months to 18 years underwent resection of 74 symptomatic CMs between 1996 and 2018 at a single institution. The median length of follow-up was 5.65 years. Patients most commonly presented with seizures (45.3%, n = 24) and the majority of CMs were cortical (58.0%, n = 43). Acute radiographic hemorrhage was common at presentation (64.2%, n = 34). Forty-two percent (n = 22) of patients presented with multiple CMs, and they were more likely to develop de novo lesions (71%) compared to patients presenting with a single CM (3.4%). Both radiographic hemorrhage and multiple CMs were independently prognostic for a higher risk of the patient requiring subsequent surgery. Fifty percent (n = 6) of the 12 patients with both risk factors required additional surgery within 2.5 years of initial surgery compared to none of the patients with neither risk factor (n = 9).

Conclusions: Patients with either acute radiographic hemorrhage or multiple CMs are at higher risk for subsequent surgery and require long-term MRI surveillance. In contrast, patients with a single CM are unlikely to require additional surgery and may require less frequent routine imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.2.PEDS19543DOI Listing
May 2020

Neurological adverse effects due to programmed death 1 (PD-1) inhibitors.

J Neurooncol 2020 Jun 29;148(2):291-297. Epub 2020 Apr 29.

Neurosurgery Service, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, 02215, USA.

Purpose: PD-1 Immunotherapy is integral in treating multiple cancers, but has been associated with neurological adverse events (nAEs). Our study was aimed at identifying the clinical spectrum of nAEs associated with pembrolizumab and nivolumab.

Methods: We performed an IRB approved single-center retrospective cohort study on patients receiving either pembrolizumab or nivolumab. Patients that developed nAEs within 12 months of treatment were identified. Descriptive statistics were conducted, and differences between groups were analyzed by the Chi-square or t test method.

Results: In total, 649 patients were identified. Seventeen patients (2.6%) developed nAEs. Eight of those were on pembrolizumab and nine were on nivolumab. Average age was 62.1 years. Ten were males and 7 were females. Most patients had melanoma (6, 35.3%). Patients who developed nAEs more frequently had intracranial lesions at initiation of anti PD-1 therapy compared to those who did not develop nAEs (76.5% vs 27.8%; p-value < 0.001). Fifteen patients (88.2%) permanently stopped PD-1 therapy. In 8 patients, treatment termination resolved symptoms attributed to immune checkpoint blockade. The majority of patients developed grade 3 or 4 nAEs (10 patients, 58.8%), and required hospitalization (11 patients, 64.7%). Eight patients died for nAEs referable causes.

Conclusion: Pembrolizumab and nivolumab are associated with the development of nAEs associated with increased risk of permanent discontinuation of treatment, hospitalization, and death. Melanoma patients might be at a particularly high risk of such side effects. Future studies are still required to better assess which patients benefit most from such therapies, while minimizing the risk of complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03514-8DOI Listing
June 2020

Integrating genomic features for non-invasive early lung cancer detection.

Nature 2020 04 25;580(7802):245-251. Epub 2020 Mar 25.

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality; however, a small minority of eligible individuals undergo such screening in the United States. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq), a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2140-0DOI Listing
April 2020

Boda Bodas and Road Traffic Injuries in Uganda: An Overview of Traffic Safety Trends from 2009 to 2017.

Int J Environ Res Public Health 2020 03 22;17(6). Epub 2020 Mar 22.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.

Introduction: Road traffic injuries (RTIs) are an important contributor to the morbidity and mortality of developing countries. In Uganda, motorcycle taxis, known as boda bodas, are responsible for a growing proportion of RTIs. This study seeks to evaluate and comment on traffic safety trends from the past decade.

Methods: Traffic reports from the Ugandan police force (2009 to 2017) were analyzed for RTI characteristics. Furthermore, one month of casualty ward data in 2015 and 2018 was collected from the Mulago National Referral Hospital and reviewed for casualty demographics and trauma type.

Results: RTI motorcycle contribution rose steadily from 2009 to 2017 (24.5% to 33.9%). While the total number of crashes dropped from 22,461 to 13,244 between 2010 and 2017, the proportion of fatal RTIs increased from 14.7% to 22.2%. In the casualty ward, RTIs accounted for a greater proportion of patients and traumas in 2018 compared to 2015 (10%/41% and 36%/64%, respectively).

Conclusions: Although RTIs have seen a gross reduction in Uganda, they have become more deadly, with greater motorcycle involvement. Hospital data demonstrate a rising need for trauma and neurosurgical care to manage greater RTI patient burden. Combining RTI prevention and care pathway improvements may mitigate current RTI trends.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17062110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143574PMC
March 2020

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma.

Front Oncol 2020 11;10:337. Epub 2020 Mar 11.

Department of Neurosurgery, Stanford University Medical Center, Stanford, CA, United States.

Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], = 0.0252). Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078164PMC
March 2020

Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma.

Neurosurgery 2020 05;86(5):E426-E435

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California.

Background: Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.

Objective: To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.

Methods: A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.

Results: Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).

Conclusion: Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyaa023DOI Listing
May 2020

Evaluating Shunt Survival Following Ventriculoperitoneal Shunting with and without Stereotactic Navigation in Previously Shunt-Naïve Patients.

World Neurosurg 2020 Apr 26;136:e671-e682. Epub 2020 Jan 26.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California. Electronic address:

Background: Ventriculoperitoneal shunts are used to alleviate elevated intracranial pressure due to either hydrocephalus or idiopathic intracranial hypertension; however, shunt failure is a significant neurosurgical problem. Despite increases in intraoperative stereotactic navigation usage over the past decade, its effect on shunt survival remains unclear.

Methods: Shunt-naïve pediatric and adult patients receiving ventriculoperitoneal shunting between 2007 and 2015 were identified in a national administrative database. Multivariable logistic and Cox regressions were used to evaluate factors affecting stereotaxy usage and shunt survival. Matched cohorts were generated by propensity score balancing.

Results: Of 9677 patients identified, 932 received image-guided shunt placement. Total shunt failure rate was not associated with stereotaxy use (20.3% with stereotaxy vs. 19.4% without, P = 0.4602). In the matched setting, shunt survival was not extended by use of image guidance during placement (hazard ratio = 1.134, 95% confidence interval 0.923-1.393). Late shunt failures (defined as failures occurring at least 30 days after shunt placement) caused by infection occurred more frequently in the stereotaxy cohort (hazard ratio = 2.207, 95% confidence interval 1.115-4.366), whereas late shunt failures attributable to mechanical shunt failure were more common in the nonstereotaxy cohort (hazard ratio = 1.406, 95% confidence interval 1.002-1.973).

Conclusions: Our findings suggest stereotaxy use during ventriculoperitoneal shunt placement does not affect shunt survival. Late shunt failures caused by infection occurred more frequently in the stereotaxy cohort, whereas late failures caused by mechanical shunt malfunction were more commonly encountered in the nonstereotaxy cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.01.138DOI Listing
April 2020

Liquid biopsy for pediatric diffuse midline glioma: a review of circulating tumor DNA and cerebrospinal fluid tumor DNA.

Neurosurg Focus 2020 01;48(1):E9

1Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland; and.

Diffuse midline glioma (DMG) is a highly malignant childhood tumor with an exceedingly poor prognosis and limited treatment options. The majority of these tumors harbor somatic mutations in genes encoding histone variants. These recurrent mutations correlate with treatment response and are forming the basis for molecularly guided clinical trials. The ability to detect these mutations, either in circulating tumor DNA (ctDNA) or cerebrospinal fluid tumor DNA (CSF-tDNA), may enable noninvasive molecular profiling and earlier prediction of treatment response. Here, the authors review ctDNA and CSF-tDNA detection methods, detail recent studies that have explored detection of ctDNA and CSF-tDNA in patients with DMG, and discuss the implications of liquid biopsies for patients with DMG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.9.FOCUS19699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340556PMC
January 2020

Proton radiotherapy and treatment delay in head and neck squamous cell carcinoma.

Laryngoscope 2020 11 14;130(11):E598-E604. Epub 2019 Dec 14.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford.

Objective: For patients with head and neck squamous cell carcinoma (HNSCC), delays in the initiation of radiotherapy (RT) have been closely associated with worse outcomes. We sought to investigate whether RT modality (proton vs. photon) is associated with differences in the time to initiation of RT.

Methods: The National Cancer Database was queried for patients diagnosed with nonmetastatic HNSCC between 2004 and 2015 who received either proton or photon RT as part of their initial treatment. Wilcoxon rank-sum and chi-square tests were used to compare continuous and categorical variables, respectively. Multivariable logistic regression was used to determine the association between use of proton RT and delayed RT initiation.

Results: A total of 175,088 patients with HNSCC receiving either photon or proton RT were identified. Patients receiving proton RT were more likely to be white, reside in higher income areas, and have private insurance. Proton RT was associated with delayed RT initiation compared to photon RT (median 59 days vs. 45, P < 0.001). Receipt of proton therapy was independently associated with RT initiation beyond 6 weeks after diagnosis (adjusted OR [aOR, definitive RT] = 1.69; 95% confidence interval [CI] 1.26-2.30) or surgery (aOR [adjuvant RT] = 4.08; 95% CI 2.64-6.62). In the context of adjuvant proton RT, increases in treatment delay were associated with worse overall survival (weeks, adjusted hazard ratio = 1.099, 95% CI 1.011-1.194).

Conclusion: Use of proton therapy is associated with delayed RT in both the definitive and adjuvant settings for patients with HNSCC and could be associated with poorer outcomes.

Level Of Evidence: 2b Laryngoscope, 122:0000-0000, 2019 Laryngoscope, 130:E598-E604, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.28458DOI Listing
November 2020

Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of Over 500 Cavities.

Int J Radiat Oncol Biol Phys 2020 03 27;106(4):764-771. Epub 2019 Nov 27.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. Electronic address:

Purpose: Postoperative stereotactic radiosurgery (SRS) has less detrimental effect on cognition and quality of life compared with whole brain radiation therapy (WBRT) and is increasingly used for resected brain metastases (BMs). Postoperative SRS techniques are not standardized, and there is a concern for a different pattern of failure after postoperative SRS compared with WBRT. We aim to study the efficacy, toxicity, and failure pattern of postoperative SRS.

Methods And Materials: We retrospectively reviewed outcomes of patients with resected BMs treated with postoperative SRS between 2007 and 2018. Overall survival and cumulative incidences of local failure, overall distant intracranial failure (distant parenchymal failure, nodular leptomeningeal disease [nLMD], classical leptomeningeal disease [cLMD]), and adverse radiation effect were reported. Neurologic death was determined for patients with leptomeningeal disease (LMD).

Results: A total of 442 patients with 501 resected BMs were treated over 475 total SRS courses. Median clinical follow-up and overall survival after SRS were 10.1 months (interquartile range, 3.6-20.7 months) and 13.9 months (95% confidence interval [CI], 11.8-15.2 months), respectively. At 12 months, event rates were 7% (95% CI, 5%-10%) for local failure, 9% (95% CI, 7%-12%) for adverse radiation effect, 44% (95% CI, 40%-49%) for overall distant intracranial failure, 37% (95% CI, 33%-42%) for distant parenchymal failure, and 13% (95% CI, 10%-17%) for LMD. The overall incidence of LMD was 15.8% (53% cLMD, 46% nLMD). cLMD was associated with shorter survival than nLMD (2.0 vs 11.2 months, P < .01) and a higher proportion of neurologic death (67% vs 41%, P = .02). A total of 15% of patients ultimately received WBRT.

Conclusions: We report the largest clinical experience of postoperative SRS for resected BMs, showing excellent local control and low toxicity. Intracranial failure was predominantly distant, with a rising incidence of LMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2019.11.022DOI Listing
March 2020

Stereotactic Radiosurgery for Pediatric and Adult Intracranial and Spinal Ependymomas.

Stereotact Funct Neurosurg 2019 7;97(3):189-194. Epub 2019 Oct 7.

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.

Objective/background: We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma.

Methods: We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method.

Results: Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects.

Conclusions: SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000502653DOI Listing
February 2020

Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction.

Cell 2019 07 4;178(3):699-713.e19. Epub 2019 Jul 4.

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA; Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA. Electronic address:

Accurate prediction of long-term outcomes remains a challenge in the care of cancer patients. Due to the difficulty of serial tumor sampling, previous prediction tools have focused on pretreatment factors. However, emerging non-invasive diagnostics have increased opportunities for serial tumor assessments. We describe the Continuous Individualized Risk Index (CIRI), a method to dynamically determine outcome probabilities for individual patients utilizing risk predictors acquired over time. Similar to "win probability" models in other fields, CIRI provides a real-time probability by integrating risk assessments throughout a patient's course. Applying CIRI to patients with diffuse large B cell lymphoma, we demonstrate improved outcome prediction compared to conventional risk models. We demonstrate CIRI's broader utility in analogous models of chronic lymphocytic leukemia and breast adenocarcinoma and perform a proof-of-concept analysis demonstrating how CIRI could be used to develop predictive biomarkers for therapy selection. We envision that dynamic risk assessment will facilitate personalized medicine and enable innovative therapeutic paradigms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2019.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380118PMC
July 2019