Gliomas are the most common type of primary malignant brain tumor in adults, representing one third of all primary and central nervous system (CNS) tumors and 80% of malignant tumors diagnosed in the ...Western world. Epidemiological data indicate that the overall incidence and mortality of cancer is higher in males, while females have a better prognosis. The goal of this study is to determine whether there are sex differences in the time to treat and clinical outcomes in patients with glioma.
Glioblastoma (GB) and Lower Grade Glioma (LGG) patients were defined per the Central Brain Tumor Registry of the United States (CBTRUS) from the National Cancer Database (NCDB) for diagnosis years 2004 to 2016. Associations between sex and time to treatment variables as well as associations between sex and multiple clinical outcomes were assessed using univariable and multivariable models.
A total of 176,100 patients were used for analysis (124,502 GBM and 51,598 LGG). Males had a statistically significant association with >7 days to surgery (OR = 1.09, CI 1.05-1.13, p < 0.001) but this association was not observed in the multivariable model (OR = 1.05, CI 0.96-1.16, p = 0.25). After adjustment for key variables including time to treat variables, males with GB and LGG had a higher risk of death (HR = 1.11, CI 1.09-1.13, p < 0.001, HR = 1.09, CI 1.03-1.15, p < 0.001; respectfully). Sex differences in 90-day mortality for GBM were not found after adjustment (OR for males = 0.99, CI 0.91-1.08, p = 0.93). For LGG, both the univariable and multivariable logistic regression models showed no sex differences in 90-day mortality (OR for males = 1.03, CI 0.94-1.12, p = 0.45; multivariable OR for males = 0.81, CI 0.62-1.06, p = 0.13).
Based on NCDB data, there were no statistically significant differences in time to treatment between males and females, however males had a higher proportion of GB and LGG as well as a higher risk of death compared to females.
Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis ...of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10
, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10
, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10
, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10
, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10
, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10
, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10
, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10
, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10
, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10
, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10
, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10
, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10
, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
Background
The Appalachian region is a large geographic and economic area, representing 7.69% of the United States (US). This region is more rural, whiter, older, and has a higher level of poverty as ...compared to the rest of the US. Limited research has been done on primary brain and other central nervous system tumors (PBT) epidemiology in this region. In this analysis we characterize incidence, mortality, and survival patterns.
Methods
Data from 2006 to 2015 were obtained from the central brain tumor registry of the US (provided by CDC and NCI). Appalachian counties were categorized using the Appalachia Regional Council scheme. Overall and histology-specific age-adjusted incidence and mortality rates per 100,000 population were generated. 1-, 5-, and 10-year relative survival (RS) was estimated using CDC national program of cancer registry data from 2001 to 2014.
Results
Overall PBT incidence within Appalachia was 22.62 per 100,000, which is not significantly different from the non-Appalachian US (22.77/100,000, p = 0.1189). Malignant incidence was 5% higher in Appalachia (7.55/100,000 vs. 7.23/100,000, p < 0.0001), while non-malignant incidence was 3% lower (15.07/100,000 vs. 15.54/100,000, p < 0.0001). 5-year RS for malignant PBT was lower (31.4% vs. 36.0%), and mortality due to malignant PBT was higher in Appalachia (4.86/100,000 vs. 4.34/100,000, p < 0.0001).
Conclusion
Appalachia has increased malignant and decreased non-malignant PBT incidence, and poorer survival outcomes for malignant PBT compared to the non-Appalachian US.
Purpose
Primary central nervous system lymphoma (PCNSL) in patients living with HIV (PLWH) is a distinct entity; however, the management is adopted from patients without HIV. The study aims to ...examine the differences in presentation, treatment, and outcomes of PCNSL patients with or without HIV.
Methods
We retrospectively compared the characteristics of 144 patients with PCNSL with and without HIV, and analyzed factors associated with overall and progression-free survival. Results were compared to the Central Brain Tumor Registry of the United States (CBTRUS) and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) system.
Results
Among all patients with PCNSL, 19% had HIV. PLWH were younger (38 vs. 63 years;
p
< 0.01) and more likely to be African American (59% vs. 7%;
p
< 0.01) and male (74% vs. 49%;
p
= 0.02) than patients without HIV. PLWH were more likely to have multiple lesions (67% vs. 43%;
p
= 0.02), hemorrhage (59 vs. 37%;
p
= 0.03), and peripheral rim enhancement (57% vs. 7%;
p
< 0.01) on imaging; to receive palliative care (15% vs. 2%) or whole brain radiation (63% vs. 3%); and less likely to receive chemotherapy (22% vs. 95%) (
p
< 0.01). Twenty-four patients, none PLWH, underwent stem cell transplant. Not receiving transplant was an independent factor in mortality and disease progression. Our cohort of patients, compared to the national database, were younger (60 vs. 65 years), 58% were white vs. 75%, and had longer median overall survival 43 vs. 25 months.
Conclusion
Epidemiology, imaging, and treatment options for patients with PCNSL with and without HIV differ, but HIV was not an independent factor of mortality or disease progression. More efforts are needed to improve access to research and treatment options for PLWH with PCNSL.
The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. ...Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival.
Glioblastoma (GBM) is the most common primary malignant brain tumor. Nomograms are often used for individualized estimation of prognosis. This study aimed to build and independently validate a ...nomogram to estimate individualized survival probabilities for patients with newly diagnosed GBM, using data from 2 independent NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials.
This analysis included information on 799 (RTOG 0525) and 555 (RTOG 0825) eligible and randomized patients with newly diagnosed GBM and contained the following variables: age at diagnosis, race, gender, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and survival (in months). 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 0525 data and were independently validated using the 0825 data. Models were internally validated using 10-fold cross-validation, and individually predicted 6-, 12-, and 24-month survival probabilities were generated to measure the predictive accuracy and calibration against the actual survival status.
A final nomogram was built using the Cox proportional hazards model. Factors that increased the probability of shorter survival included greater age at diagnosis, male gender, lower KPS, not having total resection, and unmethylated MGMT status.
A nomogram that assesses individualized survival probabilities (6-, 12-, and 24-mo) for patients with newly diagnosed GBM could be useful to health care providers for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free software for implementing this nomogram is provided: http://cancer4.case.edu/rCalculator/rCalculator.html.
There are currently no molecular targeted approaches to treat small-cell lung cancer (SCLC) similar to those used successfully against non-small-cell lung cancer. This failure is attributable to our ...inability to identify clinically-relevant subtypes of this disease. Thus, a more systematic approach to drug discovery for SCLC is needed. In this regard, two comprehensive studies recently published in Nature, the Cancer Cell Line Encyclopedia and the Cancer Genome Project, provide a wealth of data regarding the drug sensitivity and genomic profiles of many different types of cancer cells. In the present study we have mined these two studies for new therapeutic agents for SCLC and identified heat shock proteins, cyclin-dependent kinases and polo-like kinases (PLK) as attractive molecular targets with little current clinical trial activity in SCLC. Remarkably, our analyses demonstrated that most SCLC cell lines clustered into a single, predominant subgroup by either gene expression or CNV analyses, leading us to take a pharmacogenomic approach to identify subgroups of drug-sensitive SCLC cells. Using PLK inhibitors as an example, we identified and validated a gene signature for drug sensitivity in SCLC cell lines. This gene signature could distinguish subpopulations among human SCLC tumors, suggesting its potential clinical utility. Finally, circos plots were constructed to yield a comprehensive view of how transcriptional, copy number and mutational elements affect PLK sensitivity in SCLC cell lines. Taken together, this study outlines an approach to predict drug sensitivity in SCLC to novel targeted therapeutics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atypical teratoid/rhabdoid tumor is a rare malignant CNS tumor that most often affects children ≤ 3 years old. The Central Brain Tumor Registry of the United States contains the largest aggregation ...of population-based incidence data for primary CNS tumors in the US. Its data were used to describe the incidence, associated trends, and relative survival after diagnosis of atypical teratoid/rhabdoid tumor.
Using data from 50 cancer registries between 2001 and 2010, age-adjusted incidence rates per 100 000 and 95% CIs were calculated by sex, race, Hispanic ethnicity, age at diagnosis, and location of tumor in the CNS for children aged 0 to 19 years. Relative survival rates and 95% CIs were also calculated.
The average annual age-adjusted incidence rate was 0.07 (95% CI: 0.07, 0.08). Incidence rates did not significantly vary by sex, race, or ethnicity. Age had a strong effect on incidence rate, with highest incidence among children <1 year, and decreasing incidence with increasing age. The 6-month, 1-year, and 5-year relative survival rates for all ages were 65.0%, 46.8%, and 28.3%, respectively. Atypical teratoid/rhabdoid tumor can occur anywhere in the CNS, but supratentorial tumors were more common with increasing age.
We confirm differences in survival by age at diagnosis, treatment pattern, and location of tumor in the brain. This contributes to our understanding of these tumors and may stimulate research leading to improved treatment of this devastating childhood disease.
The integrated histopathologic and molecular diagnoses of the 2016 WHO classification of central nervous system tumors have revolutionized patient care by improving diagnostic accuracy and ...reproducibility; however, the frequency and consequences of misclassification of histologically diagnosed diffuse gliomas are unknown.
Patients with newly diagnosed ICD-O-3 (International Classification of Diseases) histologically encoded diffuse gliomas from 2010-2015 were identified from the National Cancer Database, the misclassification rates and overall survival (OS) of which were assessed by WHO grade and 1p/19q status. In addition, misclassification rates by isocitrate dehydrogenase (IDH), ATRX, and p53 statuses were examined in an analogous multi-institutional cohort of registry-encoded diffuse gliomas.
Of 74,718 patients with diffuse glioma, only 74.4% and 78.8% of molecularly characterized WHO grade II and III oligodendrogliomas were in fact 1p/19q-codeleted. In addition, 28.9% and 36.8% of histologically encoded grade II and III "oligoastrocytomas", and 6.3% and 8.8% of grade II and III astrocytomas had 1p/19q-codeletion, thus molecularly representing oligodendrogliomas if also IDH mutant. OS significantly depended on accurate WHO grading and 1p/19q status.
On the basis of 1p/19q, IDH, ATRX, and p53, the misclassification rates of histologically encoded oligodendrogliomas, astrocytomas, and glioblastomas are approximately 21%-35%, 6%-9%, and 9%, respectively; with significant clinical implications. Our findings suggest that when compared with historical histology-only classified data, in national registry, as well as, institutional databases, there is the potential for false-positive results in contemporary trials of molecularly classified diffuse gliomas, which could contribute to a seemingly positive phase II trial (based on historical comparison) failing at the phase III stage. Critically, findings from diffuse glioma clinical trials and historical cohorts using prior histology-only WHO schemes must be cautiously reinterpreted.
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