People diagnosed with brain cancer commonly present to the emergency department (ED). There is uncertainty about essential components and processes of optimal care from the perspective of consumers, and few guidelines exist to inform practice. This study examined the perceptions of outpatients and their support persons regarding what constitutes optimal care for people with brain cancer presenting to the ED.

A cross sectional descriptive survey study was undertaken. Participants included adults attending hospital outpatient clinics (n ​= ​181, 60% of eligible participants). Participants completed a survey assessing perceptions of optimal care for brain cancer patients presenting to emergency department and socio-demographic characteristics.

The survey items endorsed as 'essential' by participants included that the emergency department team help patients: 'understand signs and symptoms to watch out for' (51%); 'understand the next steps in care and why' (48%); 'understand if their medical condition suggests it is likely they will die in hospital' (47%); 'ask patients if they have a substitute decision maker and want that person told they are in the emergency department' (44%); 'understand the purpose of tests and procedures' (41%).

Symptom management, effective communication and supported decision-making should be prioritised by ED teams. Further research to establish the views of those affected by brain cancer about essential care delivered in the ED setting, and to compare these views with the quality of care that is actually delivered, is warranted.

Malignant brain tumors consist of primary malignant tumors and metastatic brain tumors. The global incidence and prevalence of CNS cancers are increasing, their mortality and morbidity are relatively higher than other cancers (e.g., bladder cancer), and the management of disease utilizes sophisticated and expensive diagnostic and therapeutic technology. Therefore, malignant brain tumors, both primary and metastatic, impose a significant economic burden on patients, their families, and healthcare systems all around the world. To the best of our knowledge, there is no comprehensive and global systematic review for examining the costs of brain tumors, though sporadic reports highlight the importance of the problem. Besides, each study takes place in a setting with different methods (e.g., different treatment methods) and costs to manage brain tumors; therefore, we are unable to compare the costs between countries. Nevertheless, the general patterns seem to suggest that, among all, gliomas and glioblastomas are the most financially burdensome types of malignant brain cancer. Finally, most of the available studies have examined the economic burden of all gliomas or only glioblastoma. Hence, we are left with a substantial gap in knowledge to understand the actual economic burden of metastatic brain tumors, and there is a need for further accurate and internationally comparable studies on the subject, particularly with a focus on indirect and intangible costs.

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.

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.

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.

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.

Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients' evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers.

We compared cost-effectiveness of cranial computed tomography (CT), fast sequence magnetic resonance imaging (fsMRI), and ultrasonography measurement of optic nerve sheath diameter (ONSD) for suspected acute shunt failure from the perspective of a health care organization.

We modeled 4 diagnostic imaging strategies: (1) CT scan, (2) fsMRI, (3) screening ONSD by using point of care ultrasound (POCUS) first, combined with CT, and (4) screening ONSD by using POCUS first, combined with fsMRI. All patients received an initial plain radiographic shunt series (SS). Short- and long-term costs of radiation-induced cancer were assessed with a Markov model. Effectiveness was measured as quality-adjusted life-years. Utilities and inputs for clinical variables were obtained from published literature. Sensitivity analyses were performed to evaluate the effects of parameter uncertainty.

At a previous probability of shunt failure of 30%, a screening POCUS in patients with a normal SS was the most cost-effective. For children with abnormal SS or ONSD measurement, fsMRI was the preferred option over CT. Performing fsMRI on all patients would cost $269 770 to gain 1 additional quality-adjusted life-year compared with POCUS. An imaging pathway that involves CT alone was dominated by ONSD and fsMRI because it was more expensive and less effective.

In children with low pretest probability of cranial shunt failure, an ultrasonographic measurement of ONSD is the preferred initial screening test. fsMRI is the more cost-effective, definitive imaging test when compared with cranial CT.

Several patients with new onset brain tumors present to the Emergency Department (ED) complaining for new symptoms. Although information exists on symptom prevalence in the entire population of patients with brain tumors, little is known about the clinical presentation in ED. This retrospective study was planned to investigate clinical presentation and epidemiology of brain tumors firstly diagnosed in a large urban ED throughout a 10-year period.

All medical records of patients aged ≥18 years, discharged from our ED with a diagnosis of brain tumor were retrieved from the electronic hospital database during a 10-year period (2006 to 2015). The records were reassessed for selecting only brain tumors firstly diagnosed in the ED. The symptoms at presentation were divided in six categories: (I) headache; (II) seizures; (III) focal signs; (IV) altered mental status; (V) nausea/vomiting/dizziness; (VI) trauma. For all cases, the hospital record was retrieved, to obtain histologic classification of tumors. Patients with inflammatory neoformations were excluded from the study.

Overall, 205 patients with firstly diagnosed brain tumor were identified among 870,135 ED visits (i.e., <1%). Glial tumors were the most frequent (50% of the entire sample). No significant differences were found between mean age of patients in the different histologically based groups (meningiomas 66±14; glioblastomas 65±16 years; metastases 66±13 years; other miscellaneous 66±19 years). Focal signs accounted for more than 50% of all presentation signs/symptoms.

First presentation of brain tumor in the ED is not a rare occurrence, so that the emergency physicians should be aware of this possibility.

Immunotherapy for brain cancer has evolved dramatically over the past decade, owed in part to our improved understanding of how the immune system interacts with tumors residing within the central nervous system (CNS). Glioblastoma (GBM), the most common primary malignant brain tumor in adults, carries a poor prognosis (<15 months) and only few advances have been made since the FDA's approval of temozolomide (TMZ) in 2005. Importantly, several immunotherapies have now entered patient trials based on promising preclinical data, and recent studies have shed light on how GBM employs a slew of immunosuppressive mechanisms that may be targeted for therapeutic gain. Altogether, accumulating evidence suggests immunotherapy may soon earn its keep as a mainstay of clinical management for GBM.

Here, we review cancer vaccines, checkpoint inhibitors, adoptive T-cell immunotherapy, and oncolytic virotherapy.

Checkpoint blockade induces antitumor activity by preventing negative regulation of T-cell activation. This platform, however, depends on an existing frequency of tumor-reactive T cells. GBM tumors are exceptionally equipped to prevent this, occupying low levels of antigen expression and elaborate mechanisms of immunosuppression. Therefore, checkpoint blockade may be most effective when used in combination with a DC vaccine or adoptively transferred tumor-specific T cells generated ex vivo. Both approaches have been shown to induce endogenous immune responses against tumor antigens, providing a rationale for use with checkpoint blockade where both primary and secondary responses may be potentiated.

The aim of this study was to compare the cost of comprehensive outpatient therapy (day rehabilitation) in individuals with malignant brain tumors to those with stroke and traumatic brain injury.

This was a prospective, nonrandomized, longitudinal study of 49 consecutive adults with malignant brain tumors enrolled in the 6 day rehabilitation sites of 1 institution over 35 months. The control group was composed of 50 patients with brain injury and 50 patients with stroke, who were also enrolled in the day rehabilitation program during the same period. A comparison was made of the total Medicare cost and the cost per day of day rehabilitation in patients with malignant brain tumors compared with the control group.

The patients with malignant brain tumors had lower total cost and cost per day than did the combined traumatic brain injury and stroke group during day rehabilitation (F2,143 = 3.056 [P = 0.05] and F2,142 = 5.046 [P = 0.008], respectively).

The cost of comprehensive outpatient rehabilitation in patients with malignant brain tumors is less expensive than that of patients with traumatic brain injury or stroke, which are neurological diagnoses commonly seen in day rehabilitation. This study shows that cost should not be a barrier to providing outpatient therapies to this patient population.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM. Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM. Expert opinion: Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.

Patients with high-grade gliomas and glioblastomas (GBMs) have poor survival despite optimal surgical and drug therapy. Minimally invasive diagnostic biomarkers would enable early diagnosis and tumor-specific treatments for 'personalized targeted' therapy, and would create the basis for response tracking in patients with GBM. Extracellular vesicles (EVs) isolated from cerebrospinal fluid and blood contain glioma-specific molecules, including tumor-derived EV RNAs that are detectable in small copy numbers in these biofluids. EV RNA mutations or expression changes are also detectable, the analysis of which gives rise to 'liquid biopsy' tumor profiling.

To improve the efficiency and appropriateness of computed tomography (CT) use in children with minor head trauma, clinical prediction rules were derived and validated by the Pediatric Emergency Care Applied Research Network (PECARN). The objective of this study was to conduct a cost-effectiveness analysis comparing the PECARN traumatic brain injury prediction rules to usual care for selective CT use.

We used decision analytic modeling to project the outcomes, costs, and cost-effectiveness of applying the PECARN rules compared with usual care in a hypothetical cohort of 1,000 children with minor blunt head trauma. Clinical management was directed by level of risk as specified by the presence or absence of variables in the PECARN traumatic brain injury prediction rules. Immediate costs of care (diagnostic testing, treatment [not including clinician time], and hospital stay) were derived on single-center data. Quality-adjusted life-year losses related to the sequelae of clinically important traumatic brain injuries and to radiation-induced cancers, number of CT scans, number of radiation-induced cancers, number of missed clinically important traumatic brain injury, and total costs were evaluated.

Compared with the usual care strategy, the PECARN strategy was projected to miss slightly more children with clinically important traumatic brain injuries (0.26 versus 0.02 per 1,000 children) but used fewer cranial CT scans (274 versus 353), resulted in fewer radiation-induced cancers (0.34 versus 0.45), cost less ($904,940 versus $954,420), and had lower net quality-adjusted life-year loss (-4.64 versus -5.79). Because the PECARN strategy was more effective (less quality-adjusted life-year loss) and less costly, it dominated the usual care strategy. Results were robust under sensitivity analyses.

Application of the PECARN traumatic brain injury prediction rules for children with minor head trauma would lead to beneficial outcomes and more cost-effective care.

Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society.

A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the study's publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another.

Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from $50,600 to $92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial.

With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively.

Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treatment includes surgical resection, irradiation with adjuvant temozolomide and, on recurrence, experimental chemotherapy. However, the survival of patients remains poor. There is a critical need for minimally invasive biomarkers for diagnosis and as measures of response to therapeutic interventions. Glioma shed extracellular vesicles (EVs), which invade the surrounding tissue and circulate within both the cerebrospinal fluid and the systemic circulation. These tumor-derived EVs and their content serve as an attractive source of biomarkers. In this review, we discuss the current state of the art of biomarkers for glioma with emphasis on their EV derivation.

The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

The ISPOR Oncology Special Interest Group formed a working group at the end of 2010 to develop standards for conducting oncology health services research using secondary data. The first mission of the group was to develop a checklist focused on issues specific to selection of a sample of oncology patients using a secondary data source.

A systematic review of the published literature from 2006 to 2010 was conducted to characterize the use of secondary data sources in oncology and inform the leadership of the working group prior to the construction of the checklist. A draft checklist was subsequently presented to the ISPOR membership in 2011 with subsequent feedback from the larger Oncology Special Interest Group also incorporated into the final checklist.

The checklist includes six elements: identification of the cancer to be studied, selection of an appropriate data source, evaluation of the applicability of published algorithms, development of custom algorithms (if needed), validation of the custom algorithm, and reporting and discussions of the ascertainment criteria. The checklist was intended to be applicable to various types of secondary data sources, including cancer registries, claims databases, electronic medical records, and others.

This checklist makes two important contributions to oncology health services research. First, it can assist decision makers and reviewers in evaluating the quality of studies using secondary data. Second, it highlights methodological issues to be considered when researchers are constructing a study cohort from a secondary data source.

Retrospective analysis of a population-based insurance claims data set.

To determine the risk of repeat fusion and total costs associated with bone morphogenetic protein (BMP) use in single-level lumbar fusion for degenerative spinal disease.

The use of BMP has been proposed to reduce overall costs of spinal fusion through prevention of repeat fusion procedures. Although radiographic fusion rates associated with BMP use have been examined in clinical trials, few data exist regarding outcomes associated with BMP use in the general population.

Using the MarketScan claims data set, 15,862 patients that underwent single-level lumbar fusion from 2003 to 2007 for degenerative disease were identified. Propensity scores were used to match 2372 patients who underwent fusion with BMP to patients who underwent fusion without BMP. Logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards models were used to examine risk of repeat fusion, length of stay, and 30-day readmission by BMP use. Cost comparisons were evaluated with linear regression models using logarithmic transformed data.

At 1 year from surgery, BMP was associated with a 1.1% absolute decrease in the risk of repeat fusion (2.3% with BMP vs. 3.4% without BMP, P = 0.03) and an odds ratio for repeat fusion of 0.66 (95% confidence interval [CI] = 0.47-0.94) after multivariate adjustment. BMP was also associated with a decreased hazard ratio for long-term repeat fusion (adjusted hazards ratio = 0.74, 95% CI = 0.58-0.93). Cost analysis indicated that BMP was associated with initial increased costs for the surgical procedure (13.9% adjusted increase, 95% CI = 9.9%-17.9%) as well as total 1-year costs (10.1% adjusted increase, 95% CI = 6.2%-14.0%).

At 1 year, BMP use was associated with a decreased risk of repeat fusion but also increased health care costs.

Using decision analysis, a cost-utility study evaluated the cost-effectiveness of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) in comparison to external beam radiation therapy in the treatment of metastatic spinal malignancies.

The published literature provided evidence on the effectiveness of the comparator interventions in the absence of primary outcomes data. Costs of care were derived from Centers for Medicare and Medicaid Services fee schedules. A Markov model was constructed from the payer perspective to simulate the outcomes of patients undergoing nonchemotherapeutic interventions for metastatic spinal tumors. Because cancer therapies bear significant health and economic consequences, the impact of treatment-related toxicities was integrated into the model. Given the terminal nature of these conditions and the limited life expectancy of the patient population, the time horizon for the analysis was limited to 12 months.

Patients treated with CyberKnife SRS gained an additional net health benefit of 0.08 quality-adjusted life year; the calculated cost of CyberKnife SRS was $1933 less than external beam radiation therapy for comparable effectiveness. The incremental cost per benefit for this strategy ($41 500 per quality-adjusted life year) met payers' willingness-to-pay criteria.

Cost-utility analysis demonstrated that CyberKnife SRS was a superior, cost-effective primary intervention for patients with metastatic spinal tumors compared with conventional external beam radiation therapy.

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent stem cell population based on their capacity of targeting brain tumors. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors is proposed to fill the gap in the current work flow of stem cell-based therapy. The organotypic slice platform has advantages of being mimic in vivo model, easier to manipulate to optimize parameters than in vivo models such as rodents and primates. This model serves as a framework to address the discrepancy between anticipated in vivo results and actual in vivo results, a critical barrier to timely progress in the field of the use of stem cells for the treatment of neurological disorders.

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent stem cell population based on their capacity of targeting brain tumors. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors is proposed to fill the gap in the current work flow of stem cell-based therapy. The organotypic slice platform has advantages of being mimic in vivo model, easier to manipulate to optimize parameters than in vivo models such as rodents and primates. This model serves as a framework to address the discrepancy between anticipated in vivo results and actual in vivo results, a critical barrier to timely progress in the field of the use of stem cells for the treatment of neurological disorders.