Meta-analysis of the incidence and patterns of second neoplasms after photon craniospinal irradiation in children with medulloblastoma.

BACKGROUND: Second neoplasms (SNs) are a well-established long-term adverse effect of radiation therapy (RT), but there are limited data regarding their incidence and location relative to the radiation field, specific to medulloblastoma (MB) survivors after craniospinal irradiation (CSI). METHODS: A systematic literature review, per Preferred Reporting Items for Systematic Reviews and Meta-Analyses, identified six studies reporting the incidence and locations of SNs for 1,114 patients with MB, after CSI, with a median follow-up of ∼9 years (7.6-15.4 years). The study-specific cumulative incidence (CI) of SNs, second benign neoplasms (SBNs), and second malignant neoplasms (SMNs) were standardized to a 10-year time frame. Meta-analysis was performed using random effects models, with pooled data from selected studies and an institutional cohort of 55 patients. RESULTS: The 10-year CI was 6.1% for all SNs (excluding skin cancer and leukemia), 3.1% for SBNs, and 3.7% for SMNs. Fifty-eight percent of SNs were malignant; high-grade glioma was the most common SMN (15/33; 45%) and meningioma, the most common SBN (16/24; 67%). Forty percent of SNs occurred outside the target central nervous system (CNS) field, with a majority in areas of exit RT dose. Seventy-four percent of extra-CNS tumors (17/23) were malignant, most commonly thyroid carcinoma (7/17; 41%) and bone and soft-tissue tumors (6/17, 35%). CONCLUSIONS: Survivors of MB are at risk of SNs both within and outside the CNS. A significant proportion of SNs occur in areas of exit RT dose. Studies are needed to determine whether the use of proton therapy, which has no exit RT dose, is associated with a lower incidence of SNs

Knowledge and Attitudes of Guam Residents Towards Cancer Clinical Trial Participation

Purpose/Background: Currently there are no cancer clinical trials conducted in Guam, but interest is growing. Limited information exists on the knowledge and attitudes of Guam’s population towards cancer clinical research, yet cancer is the second highest cause of death in Guam and among the CHamoru people, Guam’s indigenous population. CHamoru people suffer the highest rates of cancer mortality compared to other ethnic groups in Guam. The purpose of this study was to determine differences in knowledge and attitudes towards cancer clinical trials participation, and attitudes towards traditional medicine. Materials & Methods: A telephone survey instrument was designed, pilot-tested, IRB-approved, and implemented using a third-party marketing company. Questions were adapted from existing surveys and new questions were developed to address unique, Guam-specific interests. Recruited subjects were Guam residents adults 18 years of age and older with telephone service. Guam residents were called from October 6 to 10, 2018 to assess levels of knowledge and attitudes towards cancer clinical trials and the attitudes towards using traditional medicine to treat cancer. Descriptive statistics were computed for demographic variables by response category. Univariate logistic regression was conducted to investigate the bivariate association between a survey question and demographic variables. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated. Multivariable logistic regression model was developed for each question, adjusting for important covariates. Hosmer-Lemeshow tests and c-statistics were used to evaluate goodness of fit. Results: The survey respondents’ (n=152) demographic data closely reflected the US Census ethnicity data for Guam: CHamoru (47.0%), Filipino (26.5%), Caucasian (11.3%) and Other (15.2%). Fifty-three percent understood the term “clinical trial”; 73.7% would be willing to participate if they had cancer, and 59.9% believed they would receive good quality treatment from a clinical trial offered in Guam. Approximately 56.0% thought they would have to pay out-of-pocket expenses; and 67.0% disagreed or were not sure that clinical trial sponsors pay for the study drug while other costs are billed to the insurance company. Physician ethnicity was not important to 100% of Caucasians, but was important to at least 30.0% of non-Caucasians; family support was very important to 94.7% of respondents, while religious community support was important to 55.4%. Approximately 65.1% did not believe that people participating in clinical trials were treated like ‘guinea pigs’. Having college education (OR = 3.26; 95% CI: 1.53 – 6.98) and knowing English language well (OR=5.86; 95% CI: 1.21 – 28.38) were significantly associated with higher aggregated knowledge about clinical trials. Although the majority (67.2%) would seek traditional healing practices if diagnosed with cancer, most (84.9%) did not think a suruhano (CHamoru traditional healer) could treat cancer, and 94.7% did not believe cancer was caused by taotaomo’na (ancient spirits). Discussion/Conclusion: Knowledge and attitudes towards cancer clinical trials and the use of traditional medicine to treat cancer were significantly associated with key demographic variables including ethnicity, income, employment status, place of birth and insurance type. Knowledge about cancer clinical trials was as expected: more participants who are Caucasian, have a higher level of education, were born in U.S., are employed, have a higher income, private insurance, self-report that they speak English well, and do not follow religion, were more aware of what a clinical trial is than the other respondents. Though knowledge about cancer clinical trials is limited, attitudes towards participation in cancer clinical trials offered in Guam were largely positive

Selective Molecular Alterations in the Autophagy Pathway in Patients with Lewy Body Disease and in Models of α-Synucleinopathy

Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by α-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in α-synuclein clearance might play an important role. For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in α-synuclein transgenic mice.By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced. Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls. In DLB brains, mTor was more abundant in neurons displaying α-synuclein accumulation. These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes. Similar alterations were observed in the brains of α-synuclein transgenic mice. Intra-cerebral infusion of rapamycin, an inhibitor of mTor, or injection of a lentiviral vector expressing Atg7 resulted in reduced accumulation of α-synuclein in transgenic mice and amelioration of associated neurodegenerative alterations.This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and α-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects

How culturally unique are pandemic effects? Evaluating cultural similarities and differences in effects of age, biological sex, and political beliefs on COVID impacts

Despite being bio-epidemiological phenomena, the causes and effects of pandemics are culturally influenced in ways that go beyond national boundaries. However, they are often studied in isolated pockets, and this fact makes it difficult to parse the unique influence of specific cultural psychologies. To help fill in this gap, the present study applies existing cultural theories via linear mixed modeling to test the influence of unique cultural factors in a multi-national sample (that moves beyond Western nations) on the effects of age, biological sex, and political beliefs on pandemic outcomes that include adverse financial impacts, adverse resource impacts, adverse psychological impacts, and the health impacts of COVID. Our study spanned 19 nations (participant N = 14,133) and involved translations into 9 languages. Linear mixed models revealed similarities across cultures, with both young persons and women reporting worse outcomes from COVID across the multi-national sample. However, these effects were generally qualified by culture-specific variance, and overall more evidence emerged for effects unique to each culture than effects similar across cultures. Follow-up analyses suggested this cultural variability was consistent with models of pre-existing inequalities and socioecological stressors exacerbating the effects of the pandemic. Collectively, this evidence highlights the importance of developing culturally flexible models for understanding the cross-cultural nature of pandemic psychology beyond typical WEIRD approaches

Knowledge and Attitudes of Guam Residents towards Cancer Clinical Trial Participation

(1) Background: Currently there are no cancer clinical trials in Guam, where CHamoru people suffer the highest rates of cancer mortality, and interest to do so is growing. This study investigated the knowledge and attitudes of Guam residents towards cancer clinical trial participation prior to implementation. (2) Methods: A telephone survey was developed, tested, and conducted among Guam resident adults, 18 years of age and older. Survey questions were summarized by descriptive statistics. Logistic regression models were used to investigate the associations between Guam residents’ demographics and their clinical trial knowledge and attitudes. Adjusted odds ratios (aOR) and associated 95% confidence intervals (CI) were calculated. (3) Results: One hundred fifty-two people participated in the survey, most of whom were CHamoru (47.0%). Fifty-three percent had heard the term ‘clinical trial’; 73.7% would take part in a trial if they had cancer; and 59.9% believed they would receive good quality treatment from a trial offered in Guam. CHamoru were more likely than Whites to associate out-of-pocket expenses with clinical trial participation (aOR = 5.34, 95% CI = 1.68–17.00). Physician ethnicity was important to 30% of non-Whites and significantly associated with those who spoke a language other than English (aOR = 3.40, 95% CI = 1.29–8.95). Most people (65.0%) did not believe clinical trials participants were ‘guinea pigs’. (4) Conclusion: Though knowledge about cancer clinical trials is limited, attitudes were primarily positive towards participating in cancer clinical trials offered in Guam. Future delivery of cancer clinical trials will benefit from identifying potential barriers to recruitment and adopting an approach suited to Guam’s population