Primary central nervous system tumor treatment and survival in the United States, 2004-2015.

INTRODUCTION: Brain tumor treatment and survival information is generally limited in large-scale cancer datasets. We provide a clinical investigation of current patterns of care and survival estimates for central nervous system (CNS) tumors treated in the United States. METHODS: We analyzed the National Cancer Database from 2004-2015 for all patients with diagnosis of primary CNS tumors. We describe patient demographics, treatment modality, and analyzed survival estimates. RESULTS: 512,168 patient tumor records were examined. The most common histology was meningioma (43.6%), followed by glioblastoma (22.0%), and nerve sheath tumors (10.6%). Patients had a median age of 60 years, with a female (57.9%), white (85.0%), and non-Hispanic (87.8%) predominance. Tumors were reported as World Health Organization (WHO) grade I for 55.9% of the patients, grade II for 5.9%, grade III for 4.4%, grade IV for 24.3%, and grade unknown or not applicable for 9.4%. Overall, 56% underwent surgical procedures, 30.4% received radiation, and 20.6% received chemotherapy. Radiation plus chemotherapy and surgery was the most common treatment modality in high-grade tumors (40.5% in WHO grade III and 49.3% in WHO grade IV), while surgery only or watchful waiting was preferred in low-grade tumors. Older age, male gender, non-Hispanic origin, higher number of comorbidities, and lower socioeconomic status were identified as risk factors for mortality. CONCLUSIONS: Our analysis provides long-term survival estimates and initial treatment decisions for patients with CNS tumors in hospitals throughout the United States. Age, comorbidities, gender, ethnicity, and socioeconomic characteristics were determinants of survival.

Initial management of meningiomas: Analysis of the National Cancer Database.

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States. METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma. RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in community facilities, had higher Charlson-Deyo score, and a lower rate of private insurance. Watchful waiting was the most common treatment modality (46.7%), followed by surgery only (40%). Grade II and III patients were more likely to receive therapy. Watchful waiting increased from 35.2% in 2004 to 51.4% in 2014. Younger age, male gender, private insurance, and treatment in academic facilities were determinants for receipt of surgery and/or radiation. Median survival was 12.6 years, higher in histologically confirmed cases (13.1 years). Older patients, Blacks, males, those that received radiation plus surgery, and were treated in community facilities had an increased risk of mortality. CONCLUSIONS: Over half of patients were diagnosed by imaging, suggesting a higher role of clinical determinants over histological confirmation in treatment decisions. Watchful waiting as initial management is increasing. Our survival analysis favored histological confirmation. Patients receiving radiation and surgery had an increased risk of mortality.

A case-control study of trace-element status and lung cancer in Appalachian Kentucky.

Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies.

Dimensions of impulsive behavior: Predicting contingency management treatment outcomes for adolescent smokers.

BACKGROUND: Behavioral measures of impulsive behavior include the dimensions of behavioral disinhibition, decision-making, and lapses of attention. These behaviors are associated with a range of risky activities during adolescence, including cigarette smoking; however, few studies have evaluated their associations with tobacco treatment outcomes. The current study examined the relationship between impulsive behavior and contingency management treatment outcomes for adolescent smokers. METHODS: Data from two contingency management smoking cessation trials were combined (N = 189 adolescents). Participants provided breath carbon monoxide (CO) samples with incentives delivered contingent (i.e., active treatment [AT] condition) or non-contingent (i.e., control treatment [CT] condition) on CO level. Dimensions of impulsive behavior were assessed pre- and post-treatment using the Go/Stop Task, a measure of delay discounting, a continuous performance task, while self-reported impulsivity was assessed with the Barratt Impulsiveness Scale-Adolescent. Relationships between impulsive behavior and treatment outcomes (efficacy and adherence) were assessed using linear mixed effects models. RESULTS: Participants in the AT condition had significantly lower program CO levels at each treatment phase. Delay discounting in the AT condition predicted CO levels, with those discounting the most lowering their breath CO levels the least. Delay discounting also predicted program adherence across both conditions. CONCLUSIONS: Delay discounting may be the most relevant dimension of impulsive behavior to predict outcomes for adolescent smokers completing CM programs, both in terms of successful reductions in smoking and program adherence. Suggestions are made to reduce the effects of delay discounting for adolescent smokers using this treatment approach.

Comprehensive evaluation of treatment and outcomes of low-grade diffuse gliomas.

BACKGROUND: Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States. METHODS: We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma. RESULTS: We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most common primary site location was the cerebrum (79.9%). Overall, 72.2% received surgery, 36.0% radiation, and 27.3% chemotherapy. Treatment combinations included surgery only (41.5%), chemotherapy + surgery (6.6%), chemotherapy only (3.1%), radiation + chemotherapy + surgery (10.7%), radiation + surgery (11.5%), radiation only (6.1%), and radiotherapy + chemotherapy (6.7%). Radiation was more common in treatment of elderly patients, 1p/19q co-deletion (37.3% versus 24.3%, p<0.01), and tumors with midline location. Median survival was 11 years with younger age, 1p/19q co-deletion, and cerebrum location offered survival advantage. CONCLUSIONS: Tumor location, 1p/19q co-deletion, and age were the main determinants of treatment received and survival, likely reflecting tumor biology differences. Any form of treatment was preferred over watchful waiting in the majority of the patients (86.1% versus 8.1%). Survival of low-grade gliomas is higher than previously reported in the majority of clinical trials and population-based analyses. Our analysis provides a real world estimation of treatment decisions, use of molecular data, and outcomes.

Dose-dense temozolomide for recurrent high-grade gliomas: a single-center retrospective study.

There are limited treatment modalities after high-grade gliomas recurrence. MGMT depletion modulated by dose-dense temozolomide (ddTMZ) remains a debated therapy for initial TMZ responders. Patients were selected retrospectively from our practice with diagnosis of high-grade gliomas (WHO grade III or IV), and were followed since the start of ddTMZ until death or change of therapy. Twenty-one patients were reviewed, with a median age of 47 (25-61) years and a median of 5.8 (1.5-38.8) cycles of ddTMZ. The majority were males (71.4%). Sixty-six percent received 21 on/28 off ddTMZ schedule, 28.6% daily, and 1 patient received a 7 days on/7 days off schedule. IDH mutation status was available for 18 (85.7%) patients, with 7 (33.3%) IDH mutant and 11 (52.5%) IDH wild type. MGMT methylation was assessed in 6 (28.6%) of the patients, being MGMT methylated in 3 (14.3%) patients, and non-methylated in 3 (14.3%) patients. The majority of patients (57.1%) were receiving ddTMZ in addition to other forms of therapy, including either bevacizumab (38.1%) or tumor-treating fields (TTFields) (19.1%). Overall ddTMZ was well tolerated, with few adverse events reported. The estimated median overall survival after ddTMZ start was 11 months. Median progression-free survival (PFS) was 6 months. Outcomes did not vary between patients receiving ddTMZ alone or those using TTFields or bevacizumab as concomitant therapy, but there was a trend to longer survival with the use of concomitant TTFields. Our results demonstrate benefit of ddTMZ after previous treatment with standard TMZ dosing with no apparent increase in treatment-related toxicities. In summary, ddTMZ should be considered in TMZ responsive patients and warrants further investigation.

Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium.

Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan-Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage.Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08-1.72, P = 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84-1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190.Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors. Clin Cancer Res; 23(24); 7550-7. ©2017 AACR.

A feasibility study of home-based contingency management with adolescent smokers of rural Appalachia.

Cigarette smoking among adolescents remains a significant public health concern. This problem is compounded in regions such as rural Appalachia where rates of smoking are consistently higher than national averages and access to treatments is limited. The current research evaluated a home-based contingency management program completed over the Internet with adolescent smokers recruited from rural Appalachia. Participants (N = 62) submitted 3 video recordings per day showing their breath carbon monoxide (CO) levels using a handheld CO monitor. Participants were assigned to either an active treatment condition (AT; n = 31) in which reductions in breath CO were reinforced or a control treatment condition (CT; n = 31) in which providing timely video recordings were reinforced with no requirement to reduce breath CO. Results revealed that participants in the AT condition reduced their breath CO levels significantly more so during treatment than participants in the CT condition. Within-group comparisons revealed that participants in both conditions significantly reduced their breath CO, self-reported smoking, and nicotine dependence ratings during treatment. However, only participants in the AT condition significantly reduced urinary cotinine levels during treatment, and only participants in this condition maintained all reductions until 6-week post treatment. Participants in the CT condition only maintained self-reported smoking reductions until posttreatment assessments. These results support the feasibility and initial efficacy of this incentive-based approach to smoking cessation with adolescent smokers living in rural locations.

Delay discounting and self-reported impulsivity in adolescent smokers and nonsmokers living in rural Appalachia.

Background and Objectives This study evaluated whether impulsivity (delay discounting and BIS-11-A) is associated with adolescent smoking status in a region with strong environmental risk factors for smoking. Methods Forty-two adolescent smokers and nonsmokers from rural Appalachia completed discounting and self-reported impulsivity assessments. Results The BIS-11-A, but not the measure of discounting, was associated with smoking status; however, neither assessment predicted smoking status once parent/best-friend smoking variables were statistically accounted for. Discussion and Conclusions In regions with strong environmental risk factors for smoking, delay discounting may play a more limited role in risk of initiation. Scientific Significance Helps to better define impulsivity as risk factors for smoking in relation to familial and broader cultural variables.

Effectiveness of a primary care practice intervention for increasing colorectal cancer screening in Appalachian Kentucky.

OBJECTIVE: This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. METHODS: Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. RESULTS: A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double-contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). CONCLUSIONS: Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy.