Pharmaceutical equivalent 5-aminolevulinic acid fluorescence guided resection of central nervous system tumors: feasibility, safeness and cost-benefit considerations.

PURPOSE: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness. METHODS: From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported. RESULTS: there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration. CONCLUSION: FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable.

Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Economic burden of central nervous system metastases in human epidermal growth factor receptor 2-positive breast cancer.

Aim: Compare healthcare resource utilization and costs among patients with HER2+ metastatic breast cancer (MBC) with and without central nervous system (CNS) metastases. Methods: Retrospective matched cohort study using IQVIA's PharMetrics® Plus claims database. Results: Patients with CNS metastases (n = 753) experienced more outpatient, emergency room and inpatient visits versus controls (n = 753; all p < 0.05). In the post-index year, median total all-cause healthcare costs were significantly higher among patients with CNS metastases versus controls ($112,402 vs $50,835; p < 0.0001); outpatient costs primarily drove the cost differential. Conclusion: More effective therapies are needed that improve clinical outcomes and reduce economic burden associated with CNS metastases in patients with HER2+ MBC.

Geographical variation in malignant and benign/borderline brain and CNS tumor incidence: a comparison between a high-income and a middle-income country.

PURPOSE: There is large variability in reported incidence rates of primary brain/CNS tumors across the world, with mostly higher rates in higher-income countries. The aim was to compare malignant and benign brain/CNS tumor incidence between Zurich (Switzerland), a high-income country, and Georgia, a lower middle-income country. METHODS: For the period March 2009 to February 2012, we extracted the following tumors based on topography according to ICD-O3: C70.0-C72.9, and C75.1 (pituitary gland). Data were categorized into histology groups based on the WHO 2007 histological classification. Age-standardized rates per 100,000 person-years were calculated by subgroups. RESULTS: We included 1104 and 1476 cases of primary brain/CNS tumors for Zurich and Georgia, respectively. Mean age of patients was significantly lower in Georgia compared to Zurich (50.0 versus 58.3 years). Overall age-standardized incidence rates for malignant and benign brain/CNS tumors were 10.5 (95% CI 9.9-11.0) for Georgia and 23.3 (95% CI 21.9-24.7) for Zurich with a ratio of benign to malignant tumors of 1.656 for Georgia and 1.946 for Zurich. The most frequent histology types were meningiomas in both regions, followed by glioblastomas in Zurich, but pituitary tumors in Georgia. CONCLUSION: Age-adjusted incidence rates of brain/CNS tumors were considerably higher in Zurich compared to Georgia, both for benign and malignant tumors, which is in line with other studies reporting higher rates in high-income than in low- and middle-income countries. The frequency distribution may be related to differences in diagnosing techniques and the population age structure.

Socioeconomic differences in the risk of childhood central nervous system tumors in Denmark: a nationwide register-based case-control study.

PURPOSE: Differences in the risk of childhood central nervous system (CNS) tumors by socioeconomic status (SES) may enhance etiologic insights. We conducted a nationwide register-based case-control study to evaluate socioeconomic differences in the risk of childhood CNS tumors in Denmark and examined whether associations varied by different SES measures, time points of assessment, specific tumor types, and age at diagnosis. METHODS: We identified all children born between 1981 and 2013 and diagnosed with a CNS tumor at ages 0-19 years (n = 1,273) from the Danish Cancer Registry and sampled four individually matched controls per case (n = 5,086). We used conditional logistic regression models to estimate associations with individual-level and neighborhood-level socioeconomic measures. RESULTS: We observed elevated risks of ependymoma and embryonal CNS tumors in association with higher parental education (odds ratios (ORs) of 1.6-2.1 for maternal or paternal high education and ependymoma) and higher risk of all tumor types in association with higher maternal income, e.g., OR 1.93; 95% CI 1.05-3.52 for high versus low income for astrocytoma and other gliomas. Associations were often stronger in children diagnosed at ages 5-19 years. We found little evidence for an association with neighborhood SES. CONCLUSION: This large nationwide register study with minimal risk of bias showed that having parents with higher educational level and a mother with higher income was associated with a higher risk of childhood CNS tumors. Bias or under-ascertainment of cases among families with low income or basic education is unlikely to explain our findings.

Genomic Biomarker Assessment in Gliomas: Impacts of Molecular Testing on Clinical Practice and Trial Design.

Recent discoveries elucidating the genetic underpinnings of glial neoplasms have revealed myriad recurrent alterations that have clinical value by improving accuracy of diagnosis and prognosis. Furthermore, this wealth of genomic information provides the basis for targeted therapies and the subsequent design of biomarker-based clinical trials. This review summarizes the current landscape of clinically relevant molecular alterations in gliomas and describes the role of routine molecular testing in context of treatment planning for standards of care and clinical trials.

Racial/ethnic and socioeconomic survival disparities for children and adolescents with central nervous system tumours in the United States, 2000-2015.

BACKGROUND AND OBJECTIVES: Central nervous system (CNS) malignancy is the commonest cause of cancer death in children and adolescents (0-19 years) in high-income settings. There is limited data on survival inequalities by race/ethnicity and socioeconomic position (SEP), for young patients, we aim to analyse their influence on survival from childhood CNS tumour. METHODS: 9577 children and adolescents diagnosed with primary malignant CNS tumours during 2000-2015, followed up until Dec 31 st, 2015, and reported to cancer registries (Surveillance, Epidemiology and End Results programme) were included in the analysis. Cox regression models estimated the hazard ratios for race/ethnicity, SEP, and individual insurance status, adjusting for sex, age, diagnostic period, and tumour type. Individual-level insurance status data were available from 2007. RESULTS: 62.5 % children and adolescents were non-Hispanic White, 10.6 % were non-Hispanic Black and 26.9 % were Hispanic. Race/ethnicity was strongly associated with survival (p < 0.001), even after adjusting for SEP, with Black (HR = 1.39 [95 %CI 1.23-1.58]) and Hispanic children (HR = 1.40 [95 %CI 1.28-1.54]) having higher hazards of death than White children. This association remained after adjusting for insurance status. There was an apparent positive association between SEP and survival that was largely attenuated after adjustment for insurance status (p = 0.20). Survival was comparable between those privately and Medicaid-insured. CONCLUSIONS: Non-Hispanic Black and Hispanic children had lower survival than their White counterparts. This association, not fully explained by differences in SEP, tumour subtype or health insurance, could be related to racially/ethnically-driven barriers to optimal healthcare, warranting further investigation.

The magnitude and predictors of therapy abandonment in pediatric central nervous system tumors in low- and middle-income countries: Systematic review and meta-analysis.

BACKGROUND: Outcomes of pediatric central nervous system (CNS) tumors in low- to middle-income countries (LMIC) are poorer than their high-income counterparts. Abandonment of therapy is increasingly recognized as a key contributor to this disparity, but has been poorly quantified. We performed a meta-analysis to determine the magnitude of abandonment in pediatric CNS tumors in LMIC, and risk factors and interventions aimed at reducing this. PATIENTS AND METHODS: We searched seven databases for pediatric CNS tumor cohorts followed up from diagnosis and treated in LMIC. All languages were included. Two reviewers independently selected articles and extracted data on abandonment rates (ARs) and predictors. The authors were contacted for additional information. RESULTS: Of 50 660 publications, 643 in five languages met criteria for full review; 131 met analysis inclusion criteria. ARs were not reported in the majority, and a small number were available from the authors. Available ARs ranged from 0% to 59%, from 38 studies (2497 children in 14 countries), and these were quantitatively analyzed. Lower-middle-income countries had higher ARs than upper-middle-income countries (27%, 95% confidence interval [CI] 20%-36% vs 9%, 95% CI 6%-14%, P < 0.0001), with significant heterogeneity within each (LMIC I2  = 78%, P < 0.00001, UMIC I2  = 85%, P < 0.00001). Common predictors for abandonment included distance to treatment centers, financial hardship, and prognostic misconceptions. CONCLUSION: In LMICs, ARs are highest in lower-MICs. However, the paucity of published data limits further evaluation. Given the increasing burden of pediatric CNS tumors in LMIC, addressing deficits in abandonment reporting is critical. Consistent reporting is needed for developing interventions to improve outcomes.

Feasibility of high-dose chemotherapy protocols to treat infants with malignant central nervous system tumors: Experience from a middle-income country.

BACKGROUND: Results of high-dose chemotherapy (HDCT) protocols for the management of malignant central nervous system (CNS) tumors in infants are mostly reported in high-income countries. We evaluated the feasibility and results of such protocols in a middle-income country (Jordan). METHODS: A retrospective study of infants' charts with CNS tumors between 2006 and 2015 who were treated according to HeadStart (HS) protocols. Data included patients' demographics, chemotherapy complications, and cost. RESULTS: We identified 18 patients with median age 29 months (range, 9-62 months) at diagnosis (12 HS-I and six HS-II). Distribution according to pathology was: atypical teratoid rhabdoid tumors (ATRT) (nine), primitive neuoroectodermal tumors (PNET)/pineoblastoma (five), and medulloblastoma (four). Six patients (33%) had metastatic disease, and 14 (78%) had an incomplete resection. Eleven patients achieved partial or complete remission, two stabilized, and five progressed. Ten patients did not proceed to HDCT due to progression (five), financial reasons (two), failure to collect stem cells (one), and undocumented reasons (two). Seventy-eight chemotherapy cycles were administered (median interval 26 days). Main complications during induction and consolidation were febrile neutropenia (73% and 100%), documented infections (8% and 13%), and mucositis (12% and 88%), respectively. Three patients developed moderate hearing loss. No protocol-related mortality was reported. At the last follow-up, five patients were alive: three with medulloblastoma (19, 29, and 89 months) and two with ATRT (18 and 42 months). Three survivors received focal/craniospinal radiation. The median cost of a complete HS protocol, excluding surgery/radiotherapy, was $103 500 per patient; 39% of the median cost was related to pharmacy expenses. CONCLUSIONS: These protocols were manageable in our context of limited health care resources. However, considering the significant costs and the modest survival rate, better selection criteria need to be used to identify patients likely to benefit from this approach.

Long-term effects of cancer on earnings of childhood, adolescent and young adult cancer survivors - a population-based study from British Columbia, Canada.

BACKGROUND: The patterns and determinants of long-term income among young people surviving cancer, and differences compared to peers, have not yet been fully explored. The objectives of this paper are to describe long-term income among young survivors of cancer, the impact of socio-demographic, disease, and treatment factors on long-term income, and income relative to the general population. METHODS: Retrospective cohort study with comparison group from the general population, using linked population-based registries, clinical data, and tax-records. Multivariate random effects regression models were used to determine survivor income, compare long-term income between survivors and comparators, and assess income determinants. Subjects included all residents of British Columbia (BC), Canada, diagnosed with cancer before 25 years of age and surviving 5 years or more. Comparators were selected from the BC general population matched by gender and birth year. RESULTS: Young cancer survivors earned significantly less than the general population. In addition, survivors of central nervous system tumors have significantly lower incomes than lymphoma survivors. Survivors who received radiation therapy have significantly lower income. Results should be interpreted with caution as the comparator group was matched by gender and date of birth. CONCLUSIONS: Depending on original diagnosis, treatment, and other characteristics, survivors face significantly lower income than peers and may require supports to gain and retain paid employment. Lower income will affect their opportunity for independent living, and will reduce productivity in the labour force.

Funding source, conflict of interest and positive conclusions in neuro-oncology clinical trials.

We aimed to test any association between authors' conclusions and self-reported COI or funding sources in central nervous system (CNS) studies. A review was performed for CNS malignancy clinical trials published in the last 5 years. Two investigators independently classified study conclusions according to authors' endorsement of the experimental therapy. Statistical models were used to test for associations between positive conclusions and trials characteristics. From February 2010 to February 2015, 1256 articles were retrieved; 319 were considered eligible trials. Positive conclusions were reported in 56.8% of trials with industry-only, 55.6% with academia-only, 44.1% with academia and industry, 77.8% with none, and 76.4% with not described funding source (p = 0.011). Positive conclusions were reported in 60.4% of trials with unrelated COI, 60% with related COI, and 60% with no COI reported (p = 0.997). Factors that were significantly associated with the presence of positive conclusion included trials design (phase 1) [OR 11.64 (95 CI 4.66-29.09), p < 0.001], geographic location (outside North America or Europe) [OR 1.96 (95 CI 1.05-3.79), P = 0.025], primary outcomes (non-overall or progression free survival) [OR 3.74 (95 CI 2.27-6.18), p < 0.001], and failure to disclose funding source [OR 2.45 (95 CI 1.22-5.22), p = 0.011]. In a multivariable regression model, all these factors remained significantly associated with trial's positive conclusion. Funding source and self-reported COI did not appear to influence the CNS trials conclusion. Funding source information and COI disclosure were under-reported in 14.1 and 17.2% of the CNS trials. Continued efforts are needed to increase rates of both COI and funding source reporting.

Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO classification of tumors of the central nervous system recommendations.

BACKGROUND: Due to the decreasing prevalence of IDH1 mutations in older patients, the 2016 World Health Organization (WHO) classification of brain tumors proposed not to perform sequencing for isocitrate dehydrogenase (IDH) in glioblastoma patients ≥55 years old. We present a cost-effectiveness analysis to estimate the financial impact of these guidelines. METHODS: From 2010 to 2015 we performed 1023 IDH tests in gliomas, amounting to ~$1.09 million in direct laboratory test costs. Samples were tested using R132H-specific immunohistochemistry, DNA sequencing validated for detection of noncanonical IDH1/2 mutations, or both methods. RESULTS: In cases tested by DNA sequencing, the fraction of non-R132H mutations was 5.4%, which included only 2 high-grade gliomas in patients ≥55 years (0.9%). When remodeling the optimal age cutoff in our patient population using 5-year age-binning, we found a 10-times higher pretest probability for the presence of a noncanonical IDH1 mutation in the setting of a negative IDH1-R132H immunohistochemistry result in patients <55 years. Applying the independently confirmed age cutoff of 55 years to glioblastoma patients (64%) would result in $403200 saved (43%). By not performing sequencing in patients ≥55 years, the turn-around time to final integrated neuropathological diagnosis is reduced by 53%, allowing these patients to gain earlier benefits from personalized genomic medicine. CONCLUSION: The negligible prevalence of noncanonical IDH mutations in glioblastoma patients ≥55 years argues against universal IDH sequencing in this population. We predict that adoption of this age-based sequencing cutoff recommendation from the 2016 WHO guidelines will result in significant cost and time savings throughout the global health care system.

Costs for Childhood and Adolescent Cancer, 90 Days Prediagnosis and 1 Year Postdiagnosis: A Population-Based Study in Ontario, Canada.

BACKGROUND: Childhood and adolescent cancers are uncommon, but they have important economic and health impacts on patients, families, and health care systems. Few studies have measured the economic burden of care for childhood and adolescent cancers. OBJECTIVES: To estimate costs of cancer care in population-based cohorts of children and adolescents from the public payer perspective. METHODS: We identified patients with cancer, aged 91 days to 19 years, diagnosed from 1995 to 2009 using cancer registry data, and matched each to three noncancer controls. Using linked administrative health care records, we estimated total and net resource-specific costs (in 2012 Canadian dollars) during 90 days prediagnosis and 1 year postdiagnosis. RESULTS: Children (≤14 years old) numbered 4,396: 36% had leukemia, 21% central nervous system tumors, 10% lymphoma, and 33% other cancers. Adolescents (15-19 years old) numbered 2,329: 28.9% had lymphoma. Bone and soft tissue sarcoma, germ cell tumor, and thyroid carcinoma each comprised 12% to 13%. Mean net prediagnosis costs were $5,810 and $1,127 and mean net postdiagnosis costs were $136,413 and $62,326 for children and adolescents, respectively; the highest were for leukemia ($157,764 for children and $172,034 for adolescents). In both cohorts, costs were much higher for patients who died within 1 year of diagnosis. Inpatient hospitalization represented 69% to 74% of postdiagnosis costs. CONCLUSIONS: Treating children with cancer is costly, more costly than treating adolescents or adults. Substantial survival gains in children mean that treatment may still be very cost-effective. Comprehensive age-specific population-based cost estimates are essential to reliably assess the cost-effectiveness of cancer care for children and adolescents, and measure health system performance.

Health disparities and impact on outcomes in children with primary central nervous system solid tumors.

OBJECTIVE Health disparities in access to care, early detection, and survival exist among adult patients with cancer. However, there have been few reports assessing how health disparities impact pediatric patients with malignancies. The objective in this study was to examine the impact of racial/ethnic and social factors on disease presentation and outcome for children with primary CNS solid tumors. METHODS The authors examined all children (age ≤ 18 years) in whom CNS solid tumors were diagnosed and who were enrolled in the Texas Cancer Registry between 1995 and 2009 (n = 2421). Geocoded information was used to calculate the driving distance between a patient's home and the nearest pediatric cancer treatment center. Socioeconomic status (SES) was determined using the Agency for Healthcare Research and Quality formula and 2007-2011 US Census block group data. Logistic regression was used to determine factors associated with advanced-stage disease. Survival probability and hazard ratios were calculated using life table methods and Cox regression. RESULTS Children with advanced-stage CNS solid tumors were more likely to be < 1 year old, Hispanic, and in the lowest SES quartile (all p < 0.05). The adjusted odds ratios of presenting with advanced-stage disease were higher in children < 1 year old compared with children > 10 years old (OR 1.71, 95% CI 1.06-2.75), and in Hispanic patients compared with non-Hispanic white patients (OR 1.56, 95% CI 1.19-2.04). Distance to treatment and SES did not impact disease stage at presentation in the adjusted analysis. Furthermore, 1- and 5-year survival probability were worst in children 1-10 years old, Hispanic patients, non-Hispanic black patients, and those in the lowest SES quartile (p < 0.05). In the adjusted survival model, only advanced disease and malignant behavior were predictive of mortality. CONCLUSIONS Racial/ethnic disparities are associated with advanced-stage disease presentation for children with CNS solid tumors. Disease stage at presentation and tumor behavior are the most important predictors of survival.

Symptoms and socio-economic impact of ependymoma on adult patients: results of the Adult Ependymoma Outcomes Project 2.

Ependymoma is a rare central nervous system tumor of adults. Reports of patient symptoms, interference patterns and costs encountered by patients and families are limited. Adult ependymoma patients completed the online Ependymoma Outcomes Questionnaire II. The survey assesses disease and functional status as well as socio-economic factors. Descriptive statistics were used to report disease characteristics as well as economic and social impact. Independent samples t test was used to test if differences exist between high- and low-income groups in terms of symptom severity. Correlations were calculated between symptoms and cost estimates. 86 international patients participated (male = 50 %). The economic analysis focused on 78 respondents from the US. 48 % were employed and 55 % earned ≥$60,000. Tumors were located in the brain (44 %), spine (44 %) or both (12 %). Spine patients compared to brain patients reported significantly worse pain (4.4 versus 2.2, p < .003), numbness (5.3 versus 2.2, p < .001), fatigue (5.1 versus 3.6, p < .03), changes in bowel patterns (3.8 versus 1.4, p < .003) and weakness (4.2 versus 2.1, p < .006). Brain patients compared with spine patients had increased lack of appetite (.4 versus 2, p < .014). Patients with lower income (≤$59,999) had more problems concentrating (p < .024) and worse cognitive module severity scores (p < .024). Estimated average monthly out-of-pocket spending was $168 for medical co-pays and $59 for prescription medication. Patients with ependymoma are highly affected by their symptoms. Spinal patients report higher severity of symptoms. Patients in the lower income group report significantly higher severity of cognitive symptoms independent of disease site.

Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: a cost-effectiveness analysis.

BACKGROUND: In immunocompetent patients with primary central nervous system lymphoma (PCNSL), combined modality therapy (CMT) using high-dose methotrexate and radiotherapy (WBRT) has improved response rates compared with chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity (NT). METHODS: A cost-effectiveness analysis using a Markov model compared CMT with chemotherapy alone in age-stratified patients with PCNSL. Baseline probabilities were derived from a systematic literature review. Direct and lost productivity costs were collected from a Canadian perspective and presented in Can$ in 2011. Outcomes were life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. RESULTS: The quality-adjusted life expectancy was 1.55 QALYs for CMT and 1.53 QALYs for chemotherapy alone. In younger patients (aged <60 years), CMT yielded 2.44 QALYs, compared with 1.89 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0.55 QALYs or 6.6 quality-adjusted months. The CMT strategy dominated in younger patients, as it was Can$11 951 less expensive than chemotherapy alone. The chemotherapy-alone strategy dominated in older patients, as it was Can$11 244 less expensive than CMT, and there was no difference in QALYs between the strategies. The model was robust in sensitivity analyses of key variables tested through the plausible ranges obtained from costing sources and published literature. CONCLUSION: The preferred induction strategy for younger patients with PCNSL appears to be CMT, which minimized cost while maximizing life expectancy and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone.

Treatment patterns, clinical outcomes and health care costs associated with HER2-positive breast cancer with central nervous system metastases: a French multicentre observational study.

BACKGROUND: The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. METHODS: This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. RESULTS: 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. CONCLUSION: A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies.

Area-based socioeconomic position and adult glioma: a hierarchical analysis of surveillance epidemiology and end results data.

BACKGROUND: Glioma rates vary by demographic factors and geo-political boundaries and this variation suggests higher glioma rates in groups of higher socioeconomic position. The primary goal of this analysis is to investigate the relationship between glioma and county socioeconomic position using U.S. Surveillance Epidemiology and End Results (SEER) data. METHODS: Cases were individuals 25+ years diagnosed with glioma between 2000 and 2006 and residing within the SEER-17 catchment area. County-, sex-, race-, age-specific rates were created in order to investigate individual-level associations (population data from U.S. Census 2000). A Bayesian hierarchical Poisson spatial conditionally autoregressive (CAR) model was utilized to simultaneously estimate individual- and county-level associations while controlling for county spatial dependence. RESULTS: Those residing in counties of the second, third, and fourth highest quartiles of socioeconomic position have glioma incidence rates that are 1.10 (95% CI: 1.02,1.19), 1.11 (95% CI: 1.02,1.20), 1.14 (95% CI: 1.05,1.23) times that of the first quartile, respectively. A CAR model properly controlled for error spatial dependence. Investigated lag times suggest year 2000 census data yields superior model fit. CONCLUSION: Demographically adjusted rates of glioma are elevated in counties of higher socioeconomic position. More well-grounded theory concerning the glioma-socioeconomic position association along with socioeconomic data collected at multiple levels is recommended for future studies investigating this relationship.

Proton beam therapy and accountable care: the challenges ahead.

PURPOSE: Proton beam therapy (PBT) centers have drawn increasing public scrutiny for their high cost. The behavior of such facilities is likely to change under the Affordable Care Act. We modeled how accountable care reform may affect the financial standing of PBT centers and their incentives to treat complex patient cases. METHODS AND MATERIALS: We used operational data and publicly listed Medicare rates to model the relationship between financial metrics for PBT center performance and case mix (defined as the percentage of complex cases, such as pediatric central nervous system tumors). Financial metrics included total daily revenues and debt coverage (daily revenues - daily debt payments). Fee-for-service (FFS) and accountable care (ACO) reimbursement scenarios were modeled. Sensitivity analyses were performed around the room time required to treat noncomplex cases: simple (30 minutes), prostate (24 minutes), and short prostate (15 minutes). Sensitivity analyses were also performed for total machine operating time (14, 16, and 18 h/d). RESULTS: Reimbursement under ACOs could reduce daily revenues in PBT centers by up to 32%. The incremental revenue gained by replacing 1 complex case with noncomplex cases was lowest for simple cases and highest for short prostate cases. ACO rates reduced this incremental incentive by 53.2% for simple cases and 41.7% for short prostate cases. To cover daily debt payments after ACO rates were imposed, 26% fewer complex patients were allowable at varying capital costs and interest rates. Only facilities with total machine operating times of 18 hours per day would cover debt payments in all scenarios. CONCLUSIONS: Debt-financed PBT centers will face steep challenges to remain financially viable after ACO implementation. Paradoxically, reduced reimbursement for noncomplex cases will require PBT centers to treat more such cases over cases for which PBT has demonstrated superior outcomes. Relative losses will be highest for those facilities focused primarily on treating noncomplex cases.

Central nervous system lesions in Malawian children: identifying the treatable.

In Malawi, children with central nervous system (CNS) tumours are seldom able to be treated with curative intent. A study was undertaken of 29 children who underwent CNS MRI during a two year period. A combination of neoplastic and non-neoplastic diagnoses were noted, seven of which were revised on review. As a result an effective system has been set up for remote urgent review to guide prognosis and treatment. The opinion of a paediatric neuro-radiologist greatly assists in differentiating infectious and non infectious causes of CNS lesions and can enable the local team to effectively triage patients.