Patient characteristics and health system factors associated with adjuvant radiation therapy receipt in older women with early-stage endometrial cancer

Introduction: Among women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC. Materials & methods: Using data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004–2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors. Results: Adjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals. Discussion: Findings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT

Adjuvant radiation therapy and health-related quality of life among older women with early-stage endometrial cancer: an analysis using the SEER-MHOS linkage

Purpose: Radiation therapy (RT) has been associated with decreased health-related quality of life (HRQOL) in clinical trials of early-stage endometrial cancer (EC), but few studies have examined the association in real-world settings. We assessed HRQOL associated with adjuvant RT for older women with early-stage EC within a large U.S. population-based registry resource. Methods: The Surveillance Epidemiology and End Results and the Medicare Health Outcomes Survey linkage (1998–2017) was used to identify women with early-stage EC aged ≥ 65 years at survey who received surgery and were diagnosed ≥ 1-year prior (n = 1,140). HRQOL was evaluated with the 36-item Short-Form Health Survey (SF-36) until 2006 and the Veterans RAND 12-Item Health Survey (VR-12) post 2006. Ordinary least squares regression was used to estimate mean difference (MD) in T scores and 95% confidence intervals (CIs) comparing treatment groups (surgery alone, adjuvant external beam radiation therapy [EBRT], or adjuvant vaginal brachytherapy [VBT]) after accounting for confounders using propensity score weighting. Results: Overall, RT was not associated with physical health (MD = 0.97; 95% CI = − 1.13, 3.07) or mental health (MD = − 0.78; 95% CI = − 2.60, 1.05) relative to surgery alone. In analyses by RT type, adjuvant VBT was associated with better general health on the SF-36/VR-12 subscale (MD = 3.59; 95% CI = 0.56, 6.62) relative to surgery alone. No statistically significant associations were observed for adjuvant VBT and physical or mental health, or for adjuvant EBRT and any HRQOL domain. Conclusion: Older women with early-stage EC treated with adjuvant RT did not report worse physical and mental HRQOL scores compared to those treated with surgery alone, though relevant symptoms should be evaluated further to fully understand the disease and treatment specific aspects of the HRQOL

Real-world treatment patterns and outcomes for patients with advanced melanoma treated with immunotherapy or targeted therapy

Objective: To identify real-world patterns of first line treatment, treatment sequence and outcomes for older adults diagnosed with advanced melanoma who received immunotherapy or targeted therapy. Methods: The study population included older adults (ages 65+) diagnosed with unresectable or metastatic melanoma between 2012 and 2017 and who received first line immunotherapy or targeted therapy. Using the linked surveillance, epidemiology, and end results-medicare data, we described patterns of first line treatment and treatment sequence through 2018. We used descriptive statistics to report patient and provider characteristics by first line treatment receipt and changes in first line therapy use over calendar time. We also described overall survival (OS) and time to treatment failure (TTF) by first line treatment using the Kaplan–Meier method. For patterns of treatment sequence, we reported commonly observed treatment switch patterns by treatment sub-category and calendar year. Results: The analyses included 584 patients (mean age = 76.3 years). A majority (n = 502) received first line immunotherapy. There was a sustained increase in immunotherapy uptake, most notably from 2015 to 2016. The estimated median OS and TTF were longer with first line immunotherapy than with targeted therapy. Individuals treated with CTLA-4 + PD-1 inhibitors had the longest median OS (28.4 months). The most common treatment switch pattern was from a first line CTLA-4 inhibitor to a second line PD-1 inhibitor. Conclusions: Our findings inform understanding of treatment patterns of currently used immunotherapies and targeted therapies in older adults with advanced melanoma. Immunotherapy use has increased steadily with PD-1 inhibitors becoming a dominant treatment option since 2015

Limited Lifespan of Fragile Regions in Mammalian Evolution

An important question in genome evolution is whether there exist fragile regions (rearrangement hotspots) where chromosomal rearrangements are happening over and over again. Although nearly all recent studies supported the existence of fragile regions in mammalian genomes, the most comprehensive phylogenomic study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some doubts about their existence. We demonstrate that fragile regions are subject to a "birth and death" process, implying that fragility has limited evolutionary lifespan. This finding implies that fragile regions migrate to different locations in different mammals, explaining why there exist only a few chromosomal breakpoints shared between different lineages. The birth and death of fragile regions phenomenon reinforces the hypothesis that rearrangements are promoted by matching segmental duplications and suggests putative locations of the currently active fragile regions in the human genome

HI in the Outskirts of Nearby Galaxies

The HI in disk galaxies frequently extends beyond the optical image, and can trace the dark matter there. I briefly highlight the history of high spatial resolution HI imaging, the contribution it made to the dark matter problem, and the current tension between several dynamical methods to break the disk-halo degeneracy. I then turn to the flaring problem, which could in principle probe the shape of the dark halo. Instead, however, a lot of attention is now devoted to understanding the role of gas accretion via galactic fountains. The current $\rm \Lambda$ cold dark matter theory has problems on galactic scales, such as the core-cusp problem, which can be addressed with HI observations of dwarf galaxies. For a similar range in rotation velocities, galaxies of type Sd have thin disks, while those of type Im are much thicker. After a few comments on modified Newtonian dynamics and on irregular galaxies, I close with statistics on the HI extent of galaxies.Comment: 38 pages, 17 figures, invited review, book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres

Perceived Financial Barriers to Cervical Cancer Screening and Associated Cost Burden among Low-Income, Under-Screened Women

Background: Despite screening's effectiveness in reducing cervical cancer incidence and mortality, disparities in cervical cancer screening uptake remain, with lower rates documented among uninsured and low-income individuals. We examined perceived financial barriers to, and the perceived cost burden of, cervical cancer screening. Materials and Methods: We surveyed 702 low-income, uninsured or publicly insured women ages 25-64 years in North Carolina, U.S., who were not up to date on cervical cancer screening according to national guidelines. Participants were asked about perceived financial barriers to screening and how much they perceived screening would cost. We used multivariable logistic regression to assess the sociodemographic predictors of perceived financial barriers. Results: Seventy-two percent of participants perceived financial barriers to screening. Screening appointment costs (71%) and follow-up/future treatment costs (44%) were most commonly reported, followed by lost pay due to time missed from work (6%) and transportation costs (5%). In multivariable analysis, being uninsured (vs. publicly insured), younger (25-34 vs. 50-64 years), White (vs. Black), and not reporting income data were associated with perceiving screening costs and future treatment costs as barriers to screening. Participants reported wide-ranging estimates of the perceived out-of-pocket cost of screening ($0-$1300), with a median expected cost of $245. Conclusions: The majority of our sample of low-income women perceived substantial financial barriers to screening, particularly related to screening appointment costs and potential follow-up/future treatment costs. Providing greater cost transparency and access to financial assistance may reduce perceived financial barriers to screening, potentially increasing screening uptake among this underserved population. Clinicaltrials.gov registration number NCT02651883

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26–1.93; P = 4.79 × 10−5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10−8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size