An independently validated nomogram for isocitrate dehydrogenase-wild-type glioblastoma patient survival.

BackgroundIn 2016, the World Health Organization reclassified the definition of glioblastoma (GBM), dividing these tumors into isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant GBM, where the vast majority of GBMs are IDH-wild-type. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a nomogram for IDH-wild-type patients with newly diagnosed GBM.MethodsData were obtained from newly diagnosed GBM patients from the Ohio Brain Tumor Study (OBTS) and the University of California San Francisco (UCSF) for diagnosis years 2007-2017 with the following variables: age at diagnosis, sex, extent of resection, concurrent radiation/temozolomide (TMZ) status, Karnofsky Performance Status (KPS), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and IDH mutation status. Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using the OBTS data and independently validated using the UCSF data. Models were internally validated using 10-fold cross-validation and externally validated by plotting calibration curves.ResultsA final nomogram was validated for IDH-wild-type newly diagnosed GBM. Factors that increased the probability of survival included younger age at diagnosis, female sex, having gross total resection, having concurrent radiation/TMZ, having a high KPS, and having MGMT methylation.ConclusionsA nomogram that calculates individualized survival probabilities for IDH-wild-type patients with newly diagnosed GBM could be useful to physicians for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free software for implementing this nomogram is provided: https://gcioffi.shinyapps.io/Nomogram_For_IDH_Wildtype_GBM_H_Gittleman/

The translocator protein (TSPO) genetic polymorphism A147T is associated with worse survival in male glioblastoma patients

Glioblastoma (GBM) is the most common primary brain tumor in adults, with few available therapies and a five-year survival rate of 7.2%. Hence, strategies for improving GBM prognosis are urgently needed. The translocator protein 18kDa (TSPO) plays crucial roles in essential mito-chondria-based physiological processes and is a validated biomarker of neuroinflammation, which is implicated in GBM progression. The TSPO gene has a germline single nucleotide polymorphism, rs6971, which is the most common SNP in the Caucasian population. High TSPO gene expression is associated with reduced survival in GBM patients; however, the relation between the most fre-quent TSPO genetic variant and GBM pathogenesis is not known. The present study retrospectively analyzed the correlation of the TSPO polymorphic variant rs6971 with overall and progression-free survival in GBM patients using three independent cohorts. TSPO rs6971 polymorphism was signif-icantly associated with shorter overall survival and progression-free survival in male GBM patients but not in females in one large cohort of 441 patients. We observed similar trends in two other independent cohorts. These observations suggest that the TSPO rs6971 polymorphism could be a significant predictor of poor prognosis in GBM, with a potential for use as a prognosis biomarker in GBM patients. These results reveal for the first time a biological sex-specific relation between rs6971 TSPO polymorphism and GBM

Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas

BACKGROUND: Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States. METHODS: Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC\u27s NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models were performed by age group, generating hazard ratios to assess male-to-female survival differences. RESULTS: Overall, glioma incidence was higher in males. Male-to-female incidence was lowest in ages 0-9 years (IRR: 1.04, 95% CI: 1.01-1.07, P = .003), increasing with age, peaking at 50-59 years (IRR: 1.56, 95% CI: 1.53-1.59, P \u3c .001). Females had worse survival for ages 0-9 (HR: 0.93, 95% CI: 0.87-0.99), though male survival was worse for all other age groups, with the difference highest in those 20-29 years (HR: 1.36, 95% CI: 1.28-1.44). Incidence and survival differences by age and sex also varied by histological subtype of glioma. CONCLUSIONS: To better understand the variation in glioma incidence and survival, investigating the intersection of age and sex is key. The current work shows that the combined impact of these variables is dependent on glioma subtype. These results contribute to the growing understanding of sex and age differences that impact cancer incidence and survival

Treatment Outcomes for Primary Hepatic Angiosarcoma: National Cancer Database Analysis 2004–2014

Background: To determine the risk of mortality and factors associated with survival amongst patients diagnosed with primary hepatic angiosarcoma (PHA). Methods: All patients diagnosed with hepatocellular carcinoma (HCC) or PHA from 2004 to 2014 were identified from the National Cancer Database (NCDB). Further analysis was performed within the cohort of patients with PHA to assess the impact of surgery, chemotherapy, radiation, and facility type on overall survival (OS). A multivariable analysis using the Cox proportional methods and a survival analysis using the Kaplan–Meier method were used. Results: A total of 117,633 patients with HCC were identified, out of whom 346 patients had PHA. Patients with PHA had a mean age of 62.9 years (SD 13.7), the majority were men (64.7%), white (85.8%), and had a Charlson comorbidity index (CCI) of zero (66.2%). A third of the patients with PHA (35.7%) received chemotherapy, and 14.6% underwent a surgical resection. The median survival was 1.9 months (1.8–2.4 months) compared to patients with HCC (10.4 months, 10.2–10.5) (aHR-2.41, 95% CI: 2.10–2.77, p < 0.0001). Surgical resection was associated with a higher median survival (7.7 versus 1.8 months, aHR-0.23, 95% CI: 0.15–0.37, p < 0.0001). A receipt of chemotherapy was associated with a higher median survival than no chemotherapy (5.1 versus 1.2 months, aHR-0.44, 95% CI: 0.32–0.60, p < 0.0001), although the survival benefit did not persist long term. Conclusion: PHA is associated with poor outcomes. A surgical resection and chemotherapy are associated with improved survival outcomes; however, the long-term benefits of chemotherapy are limited

Race is Related with Increased COVID-19 Infection and Outcomes in Oncology Patients

We seek to assess racial disparities in oncology patients with COVID19 compared to appropriately matched controls with and without COVID19. All patients treated at the Seidman Cancer Center with a diagnosis of COVID19 and cancer were identified from the electronic medical record using ICD9/ICD10 codes for cancer diagnoses and database of all patients diagnosed with COVID19. Two control groups, cancer patients without COVID19 and patients without cancer but with COVID19, were generated and matched 3:1 on age at date of data extraction, age at cancer diagnosis, and sex to COVID19 positive cancer cases. African Americans (AA) and Whites made up 8.6% vs. 76.9% of the baseline oncologic population without COVID19, respectively. AA representation (41.0%) was significantly increased in cancer patients positive for COVID19 compared to those negative for COVID19 (p<0.001). In the comparison of patients with COVID19 with or without cancer, the proportion of AA cases was greater in the non-oncologic population (41.0% vs. 47.6%, p=0.014). AA are disproportionately affected with COVID19 in oncologic and benign populations. Despite similar rates of adverse outcomes to COVID19 in cancer patients by race, we found a 32.4% increase in the AA proportion compared to those without COVID19. These findings suggest COVID19 prevention policies and future studies should account for racial differences in the oncology population

Aligning the Central Brain Tumor Registry of the United States (CBTRUS) histology groupings with current definitions.

BackgroundThe Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic markers more accurately stratify patients than histology alone and were incorporated into the 2016 update to the WHO Classification.MethodsCBTRUS and consulting neuropathologists reviewed and aligned histology groupings with the 2016 WHO update. "Obsolete" (terms not currently in use) histology nomenclature along with their International Classification of Disease, Oncology 3rd edition (ICD-O-3) codes were identified, some histologies were reclassified to 2016 WHO, and new codes found in 2016 WHO were incorporated. An evaluation of the frequency of histology codes affected in the realignment process, and incidence and survival pre- and post-realignment was conducted.ResultsAfter review, 67 codes were noted as obsolete, 51 codes were reclassified, and 12 new codes were incorporated. Histology groups most affected were mesenchymal tumors and neuronal/mixed neuronal-glial tumors. Reorganization resulted in 2588 (0.65%) cases with grouping reassignment or reporting change, indicating that the 2016 WHO Classification revision has impacted the collection and reporting of primary brain and other CNS tumors.ConclusionThis work demonstrates the need to be responsive to changes in classification and coding in order to ensure the most up-to-date and accurate statistics for brain and CNS tumors. This will require collaboration from all stakeholders within the brain tumor community, so to have the ability to reconcile clinical practices and surveillance requirements

Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States.

BACKGROUND: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. METHODS: Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCIs Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). RESULTS: BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas. CONCLUSIONS: Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis

A population study of clinical trial accrual for women and minorities in neuro-oncology following the NIH Revitalization Act.

BackgroundThe NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuroepithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks.MethodsRegistry study of published clinical trials for World Health Organization defined neuroepithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and χ 2 tests were used for data analysis.ResultsAmong 662 published clinical trials representing 49 907 participants, 62.5% of participants were men and 37.5% women (P < .0001) representing a mortality specific over-accrual for men (P = .001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with mortality, Blacks (47% of expected mortality, P = .008), Hispanics (17% of expected mortality, P < .001) and Asians (33% of expected mortality, P < .001) were underrepresented compared with Whites (114% of expected mortality, P < .001). Clinical trials meeting accrual benchmarks for race included minority authorship.ConclusionsFollowing the Revitalization Act, minorities and women remain underrepresented in therapeutic clinical trials for neuroepithelial tumors, relative to disease incidence and mortality. Study accrual has improved with time. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of underserved patients

The age of adult pilocytic astrocytoma cells

Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been unclear whether adult PAs arise early in life and remain asymptomatic until adulthood, or whether they develop during adulthood. We sought to determine the age and origin of adult human PAs using two types of 'marks' in the genomic DNA. First, we analyzed the DNA methylation patterns of adult and pediatric PAs to distinguish between PAs of different anatomic locations (n = 257 PA and control brain tissues). Second, we measured the concentration of nuclear bomb test-derive