Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) ...Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival.
Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (KPS) of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 μg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) before every subcutaneous (s.c.) administration.
Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (OS) is 27%.
AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted.
NCT, NCT03400917 , Registered 10 January 2018.
We studied 571 patients with intracranial meningioma for clinical characteristics and tumor location associated with high grade meningioma (WHO II/III).
Patients were participants in a multicentre ...epidemiologic study of risk factors for primary brain tumors including meningioma recruited from September 2005 to November 2019. We included patients 18 or older with a recent diagnosis of a primary intracranial meningioma of any subtype (ICD9/10: 9530-0, 9531-0, 9532-0, 9537-0, 9533-0, 9534-0, 9530-0, 9538-1, 9538-3) who were enrolled at neuro-oncology and neuro-surgery clinics in the southeastern U.S.
The median patient age was 58 years (IQR: 48-68) and the majority of patients were female (n = 415; 72.7%) and Caucasian (n = 516; 90.4%). Most patients were symptomatic (n = 460; 80.6%) and their tumours more commonly occurred in a non-skull base location (n = 298; 52.2%). A total of 86 patients (15.0%) had a WHO grade II/III meningioma. Compared to patients with WHO grade I tumours, patients with WHO II/III meningiomas were over 3-times more likely to be male (odds ratio (OR): 3.25; 95% confidence interval (CI): 1.98, 5.35) adjusting for age, race, symptomatic presentation, and skull-based location. Moreover, a WHO grade II/III meningioma was substantially less likely to be observed in asymptomatic patients (OR: 0.15, 95% CI: 0.04, 0.42), and in patients with a skull-based tumour (OR: 0.40, 95% CI: 0.24, 0.66), adjusting for other factors. Male gender, symptomatic tumour, and a non-skull base location were independently associated with WHO grade II/III meningioma.
These findings may shed additional light on the underlying pathogenesis of meningioma.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on ...its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 μg/g and 0.069 μg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 μg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.
Lung cancer remains a devastating disease associated with substantial morbidity and mortality. Recent research has suggested
that lung cancer screening with spiral computed tomography scans might ...reduce lung cancer mortality. Studies of lung cancer
screening have also suggested that significant numbers of participants quit smoking after screening. However, most have relied
solely on self-reported smoking behavior, which may be less accurate among participants in lung cancer screening. To assess
the validity of self-reported smoking status among participants in a lung cancer screening trial, this study compared self-reported
smoking status against urinary cotinine levels. The sample included 55 consecutive participants enrolled in a randomized clinical
trial comparing annual spiral computed tomography and chest X-ray for lung cancer screening. Participants were a mean of 59
years of age and predominantly Caucasian (96%) and male (55%). Self-reported smoking status was assessed before and after
participants learned of the purpose of the biochemical verification study. Using urinary cotinine as the “gold standard,”
the sensitivity and specificity of self-reported smoking status were 91% and 95%, respectively ( κ = 0.85, P < 0.001, 95% confidence interval = 0.71-0.99). Total misclassification rate was 7%. However, three of the four misclassified
participants reported concurrent use of nicotine replacement strategies. Eliminating these cases from the analysis revealed
sensitivity of 100% and specificity of 95% ( κ = 0.96, P < 0.001, 95% confidence interval = 0.88-1.00). In conclusion, self-reported smoking status among participants in a lung cancer
screening trial was highly consistent with urinary cotinine test results. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1825–8)
Gender-specific incidence patterns and the presence of hormonal receptors on tumor cells suggest that sex hormones may play a role in the onset of primary brain tumors. However, epidemiological ...studies on the relation of hormonal risk factors to the risk of brain tumors have been inconsistent. We examined the role of reproductive factors in the onset of glioma and meningioma in a case–control study conducted in the Southeastern US that included 507 glioma cases, 247 meningioma cases, and 695 community-based and friend controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CI) adjusting for age, race, US state of residence, and education. An older age at menarche was associated with an increased risk of glioma (≥15 vs. ≤12 years: OR 1.65; 95 % CI 1.11–2.45), with a stronger association observed in pre-menopausal (OR 2.22; 95 % CI 1.12–4.39) than post-menopausal (OR 1.55; 95 % CI 0.93–2.58) women. When compared to controls, meningioma cases were more likely to have undergone natural menopause (OR 1.52; 95 % CI 1.04–2.21) whereas glioma cases were less likely to be long term users of oral contraceptives (OR 0.47; 95 % CI 0.33–0.68). Increasing parity was not related to the risk of either tumor. Current findings are consistent with a limited role for hormones in the onset of brain tumors in women. Results contribute to a growing body of evidence that a later age at menarche increases the risk of glioma in women.
Malignant gliomas are the most common and deadly brain tumors. Although their etiology remains elusive, recent studies have narrowed the search for genetic loci that influence risk. We examined ...variants implicated in recent cancer genome-wide association studies (GWAS) for associations with glioma risk in a US case–control study. Cases were identified from neurosurgical and neuro-oncology clinics at major academic centers in the Southeastern US. Controls were identified from the community or were friends or other associates of cases. We examined a total of 191 susceptibility variants in genes identified in published cancer GWAS including glioma. A total of 639 glioma cases and 649 controls, all Caucasian, were included in analysis. Cases were enrolled a median of 1 month following diagnosis. Among glioma GWAS-identified variants, we detected associations in
CDKN2B
,
RTEL1
,
TERT
and
PHLDB1
, whereas we did not find overall associations for
CCDC26
. Results showed clear heterogeneity according to histologic subtypes of glioma, with
TERT
and
RTEL
variants a feature of astrocytic tumors and glioblastoma (GBM),
CCDC26
and
PHLDB1
variants a feature of astrocytic and oligodendroglial tumors, and
CDKN2B
variants most prominent in GBM. No examined variant in other cancer GWAS was found to be related to risk after adjustment for multiple comparisons. These results suggest that GWAS-identified SNPs in glioma mark different molecular etiologies in glioma. Stratification by broad histological subgroups may shed light on molecular mechanisms and assist in the discovery of novel loci in future studies of genetic susceptibility variants in glioma.
Introduction: Increased height and greater adiposity have been linked to an increased risk of many cancer types, though few large studies have examined these associations in glioma. We examined body ...weight and height as potential risk factors for glioma in a large US-based case–control study. Methods: The analysis included 1,111 glioma cases and 1,096 community controls. In a structured interview, participants reported their height and weight at 21 years of age, lowest and highest weight in adulthood, and weight 1–5 years in the past. Results: Being underweight at age 21 (BMI < 18.5 kg/m²) was inversely associated with the risk of glioma development. This protective association was observed in both men and women, but reached statistical significance in women only (multivariate OR 0.68; 95 % CI 0.48, 0.96). When BMI at age 21 was assessed as a continuous variate, a small but significant increase in risk was observed per unit increase in kg/m² (OR 1.04; 95 % CI 1.02, 1.07). Adult height, recent body weight, and weight change in adulthood were not associated with glioma risk. All results were similar among never smokers and were consistent after stratifying by glioma subtype. Conclusion: The present data suggest that a low body weight in early adulthood is associated with a reduced risk of glioma later in life. Results are consistent with previous studies in showing no material association of glioma risk with usual adult body weight. The present study does not support any association of adult stature with glioma risk.
•Selenium in toenails was not associated with the risk of developing glioma.•Nail selenium had no association with survival in patients with high grade glioma.•No evidence was found implicating ...germline variation in selenoproteins with the risk of glioma.
Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse.
In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study.
None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70).
The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.
Handedness and the risk of glioma Miller, Briana; Peeri, Noah C.; Nabors, Louis Burt ...
Journal of neuro-oncology,
05/2018, Letnik:
137, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological ...conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case–control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case–control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51–0.83 after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52–0.91), and non-GBM (OR = 0.59, 95% CI 0.42–0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67–1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.
Purpose
To examine the association of age when adult height was attained with glioma risk.
Methods
We analyzed data from a US-based case–control study of glioma risk factors. Logistic regression was ...used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated between age at attainment of adult height and glioma risk. Multivariate models were adjusted for age, race, sex, education, and state of residence. We examined associations overall, and according to glioma grade, sex, and final adult height.
Results
The study set included
n
= 951 controls and
n
= 776 cases, with a median age of 56 (18–92); the majority was male (53.8%) and identified as Caucasian. Older age at height completion was associated with an increased risk of glioma. A significant positive trend was observed both for glioblastoma (OR 1.10; 95% CI 1.04–1.17 per 1-year increase in age) and lower grade non-glioblastoma subtypes combined (OR 1.18; 95% CI 1.10–1.28 per year increase in age). The association was observed in men and women, and in all categories of final adult height.
Conclusions
We observed for the first time a positive association between glioma risk and a prolonged adolescent growth phase. Our results suggest a role for factors governing the timing and intensity of growth in adolescence as risk-determining exposures in adult glioma.
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