First- vs second-line CDK 4/6 inhibitor use for patients with hormone receptor positive, human epidermal growth-factor receptor-2 negative, metastatic breast cancer in the real world setting.

PURPOSE: To compare CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) in the first- versus second-line setting for treatment of hormone receptor positive (HR+), HER2 negative, metastatic breast cancer (MBC) using real-world evidence. METHODS: Patients with HR+, HER2 negative MBC, diagnosed between 2/3/2015 and 11/2/2021 and having ≥ 3 months follow-up were identified from the nationwide electronic health record-derived Flatiron Health de-identified database. Treatment cohorts included: (1) first-line ET with a CDK 4/6i (1st-line CDK4/6i) versus (2) first-line ET alone followed by second-line ET with a CDK4/6i (2nd-line CDK4/6i). Differences in baseline characteristics were tested using chi-square tests and two-sample t-tests. Time to third-line therapy, time to start of chemotherapy, and overall survival were compared using Kaplan-Maier method. RESULTS: The analysis included 2771 patients (2170 1st-line CDK4/6i and 601 2nd-line CDK4/6i). Patients receiving 1st-line CDK4/6i were younger (75% vs 68% < 75 years old, p = 0.0001), less likely uninsured or not having insurance status documented (10% vs. 13%, p = 0.04), of better performance status (50% vs 43% with ECOG 0, p = 0.03), and more likely to have de novo MBC (36% vs. 24%, p < 0.001). Time to third-line therapy (49 vs 22 months, p < 0.001) and time to chemotherapy (68 vs 41 months, p < 0.001) were longer in those receiving first-line CDK4/6i. Overall survival (54 vs 49 months, p = 0.33) was similar between groups. CONCLUSION: Use of CDK4/6i with first-, vs second-, line ET was associated with longer time to receipt of 3rd-line therapy and longer time to receipt of chemotherapy.

Prevalence of Cognitive and Manual Dexterity Disorders Among Men Following Artificial Urinary Sphincter Placement.

PURPOSE: Cognitive ability and manual dexterity sufficient to operate an artificial urinary sphincter (AUS) are critical for device function and safety. We aimed to define the incidence of cognitive and/or dexterity disorders among men after AUS. We secondarily aimed to assess for association between these disorders and postimplant complications. MATERIALS AND METHODS: This is a retrospective cohort study using the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database (2000-2018). We included men ≥ 66 years diagnosed with prostate cancer between 2001 to 2015 who subsequently underwent AUS placement. We excluded patients with < 1-year continuous fee-for-service Medicare enrollment or cognitive and/or manual dexterity disorder diagnoses prior to AUS implant. Subsequent cognitive/dexterity disorders and implant-related complications were queried using appropriate ICD (International Classification of Diseases)-9/10 and/or CPT (Current Procedural Terminology) codes. Associations between cognitive/dexterity disorders and postimplant complications were assessed using extended Cox proportional hazards modeling. Secondary analysis focused on serious complications (device revision/removal, Fournier's gangrene, urethral erosion). RESULTS: We identified 1560 men who underwent AUS who met inclusion criteria. Median age was 73.0 (IQR 70-77) years. Cumulative incidence function analysis estimated 44% and 17% incidence of cognitive and manual dexterity disorder, respectively, at 15 years post-AUS. Presence of cognitive with/without manual dexterity disorder was associated with increased hazard of any, but not serious, complication during follow-up. CONCLUSIONS: A significant proportion of patients develop cognitive and/or manual dexterity disorders following AUS. These data support the need for close longitudinal monitoring after implant.

Investigating psychological mechanisms linking pain severity to depression symptoms in women cancer survivors at a cancer center with a rural catchment area.

PURPOSE: Women cancer survivors, especially those in rural areas, with high levels of depression may be acutely susceptible to pain due to the ways they think, feel, and behave. The current study seeks to elucidate the relationship between symptoms of depression and pain severity in women cancer survivors, by examining the putative mediators involved in this relationship, specifically their self-efficacy for managing their health, how overwhelmed they were from life's responsibilities, and relational burden. METHODS: Self-report data were collected from 183 cancer survivors of breast, cervical, ovarian, or endometrial/uterine cancer, who were between 6 months and 3 years post-active therapy. RESULTS: Women cancer survivors with higher (vs. lower) symptoms of depression had more severe pain. Individual mediation analyses revealed that survivors with higher levels of depression felt more overwhelmed by life's responsibilities and had lower self-efficacy about managing their health, which was associated with greater pain severity. When all mediators were simultaneously entered into the same model, feeling overwhelmed by life's responsibilities significantly mediated the link between survivors' symptoms of depression and their pain severity. CONCLUSIONS: The relationship between symptoms of depression and pain severity in women cancer survivors may be attributed in part to their self-efficacy and feeling overwhelmed by life's responsibilities. Early and frequent assessment of psychosocial factors involved in pain severity for women cancer survivors may be important for managing their pain throughout the phases of cancer survivorship.

Temporal summation in myopia and its implications for the investigation of glaucoma.

PURPOSE: We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non-pathological axial myopia compared to non-myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density. METHODS: Achromatic contrast thresholds were measured for a GIII-equivalent stimulus (0.43° diameter) of six different stimulus durations (1-24 frames, 1.1-187.8 ms) in 24 participants with axial myopia (mean spherical refractive error: -4.65D, range: -1.00D to -11.25D, mean age: 34.1, range: 21-57 years) and 21 age-similar non-myopic controls (mean spherical refractive error: +0.87D, range: -0.25D to +2.00D, mean age: 31.0, range: 18-55 years). Measurements were performed at 10° eccentricity along the 90°, 180°, 270° and 360° meridians on an achromatic 10 cd/m2 background. The upper limit of complete temporal summation (critical duration, CD) was estimated from the data with iterative two-phase regression analysis. RESULTS: There was no significant difference (p = 0.90, Mann-Whitney U-test) in median CD between myopes (median: 44.3 ms; IQR: 26.5, 51.2) and non-myopes (median: 41.6 ms; IQR: 27.3, 48.5). Despite RGC numbers underlying the stimulus being significantly lower in the myopic group (p < 0.001), no relationship was observed between the CD estimate and co-localised RGC number (Pearson's r = -0.13, p = 0.43) or ocular length (Pearson's r = -0.08, p = 0.61). CONCLUSIONS: Unlike spatial summation, temporal summation is unchanged in myopia. This contrasts with glaucoma where both temporal and spatial summation are altered. As such, perimetric methods optimised to test for anomalies of temporal summation may provide a means to differentiate between conditions causing only a reduced RGC density (e.g., myopia), and pathological processes causing both a reduced RGC density and RGC dysfunction (e.g., glaucoma).

Investigating the linkage between mesopic spatial summation and variations in retinal ganglion cell density across the central visual field.

PURPOSE: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established. METHODS: Achromatic luminance thresholds were measured for six incremental spot stimuli (0.009-2.07 deg2 ) and 190.4 ms duration, at four locations, each at 2.5°, 5° and 10° eccentricity in five healthy observers (mean age 61.4 years) under mesopic conditions (background 1.58 cd/m2 ). RA was estimated using two-phase regression analysis with the number of RGCs underlying RA being calculated using normative histological RGC counts. RESULTS: Ricco's area exhibited a small but statistically insignificant increase between 2.5° and 10° eccentricity. Compared with photopic conditions, RA was larger, with the difference between RA and the Goldmann III stimulus (0.43°) being minimised. RGC number underlying RA was also higher than reported for photopic conditions (median 70 cells, IQR 36-93), with no significant difference being observed across test locations. CONCLUSIONS: Ricco's area and the number of RGCs underlying RA do not vary significantly across the central visual field in mesopic conditions. However, RA is larger and more similar to the standard perimetric Goldmann III stimulus under mesopic compared with photopic adaptation conditions. Further work is required to determine if compensatory enlargements in RA occur in age-related macular degeneration, to establish the optimal stimulus parameters for AMD-specific microperimetry.

Evidence for ephemeral ring species formation during the diversification history of western fence lizards (Sceloporus occidentalis).

Divergence is often ephemeral, and populations that diverge in response to regional topographic and climatic factors may not remain reproductively isolated when they come into secondary contact. We investigated the geographical structure and evolutionary history of population divergence within Sceloporus occidentalis (western fence lizard), a habitat generalist with a broad distribution that spans the major biogeographical regions of Western North America. We used double digest RAD sequencing to infer population structure, phylogeny and demography. Population genetic structure is hierarchical and geographically structured with evidence for gene flow between biogeographical regions. Consistent with the isolation-expansion model of divergence during Quaternary glacial-interglacial cycles, gene flow and secondary contact are supported as important processes explaining the demographic histories of populations. Although populations may have diverged as they spread northward in a ring-like manner around the Sierra Nevada and southern Cascade Ranges, there is strong evidence for gene flow among populations at the northern terminus of the ring. We propose the concept of an "ephemeral ring species" and contrast S. occidentalis with the classic North American ring species, Ensatina eschscholtzii. Contrary to expectations of lower genetic diversity at northern latitudes following post-Quaternary-glaciation expansion, the ephemeral nature of divergence in S. occidentalis has produced centres of high genetic diversity for different reasons in the south (long-term stability) vs. the north (secondary contact).

Examining the concordance of retinal ganglion cell counts generated using measures of structure and function.

PURPOSE: There are several indirect methods used to estimate retinal ganglion cell (RGC) count in an individual eye, but there is limited information as to the agreement between these methods. In this work, RGC receptive field (RGC-RF) count underlying a spot stimulus (0.43°, Goldmann III) was calculated and compared using three different methods. METHODS: RGC-RF count was calculated at a retinal eccentricity of 2.32 mm for 44 healthy adult participants (aged 18-58 years, refractive error -9.75 DS to +1.75 DS) using: (i) functional measures of achromatic peripheral grating resolution acuity (PGRA), (ii) structural measures of RGC-layer thickness (OCT-model, based on the method outlined by Raza and Hood) and (iii) scaling published histology density data to simulate a global expansion in myopia (Histology-Balloon). RESULTS: Whilst average RGC-RF counts from the OCT-model (median 105.3, IQR 99.6-111.0) and the Histology-Balloon model (median 107.5, IQR 97.7-114.6) were similar, PGRA estimates were approximately 65% lower (median 37.7, IQR 33.8-46.0). However, there was poor agreement between all three methods (Bland-Altman 95% limits of agreement; PGRA/OCT: 55.4; PGRA/Histology-Balloon 59.3; OCT/Histology-Balloon: 52.4). High intersubject variability in RGC-RF count was evident using all three methods. CONCLUSIONS: The lower PGRA RGC-RF counts may be the result of targeting only a specific subset of functional RGCs, as opposed to the coarser approach of the OCT-model and Histology-Balloon, which include all RGCs, and also likely displaced amacrine cells. In the absence of a 'ground truth', direct measure of RGC-RF count, it is not possible to determine which method is most accurate, and each has limitations. However, what is clear is the poor agreement found between the methods prevents direct comparison of RGC-RF counts between studies utilising different methodologies and highlights the need to utilise the same method in longitudinal work.

The State of Breast Cancer Reconstruction in Virginia: An Evidence-Based Framework for Identifying Locoregional Health Disparities.

BACKGROUND: Age, race, socioeconomic status, and proximity to plastic surgeons have been shown to impact receipt of reconstruction after mastectomy in several national studies. Given that targeted outreach efforts and programs to address these discrepancies would occur locoregionally, investigation of these reconstructive trends on a state level is warranted. STUDY DESIGN: Patients diagnosed with breast cancer in Virginia between 2000 and 2018 were identified in the Virginia Department of Health Cancer Registry. Patients who underwent mastectomy breast conservation surgery, and/or breast reconstruction at the time of oncologic surgery were identified. Patient demographics were analyzed, and logistic regression analyses were used to determine the likelihood of receipt of mastectomy, receipt of mastectomy versus breast conservation surgery, receipt of mastectomy with reconstruction versus mastectomy alone, and receipt of mastectomy with reconstruction versus breast conservation surgery with respect to the demographic variables. Geographically weighted regression analyses were also performed to determine impact of geographic location on receipt of mastectomy and reconstruction after mastectomy. RESULTS: A total of 78,682 patients in Virginia underwent surgical treatment for breast cancer between 2000 and 2018. Living outside a metropolitan area, increased age, lower socioeconomic status, non-White race, and lower number of plastic surgeons within 50 miles were associated with decreased rates of postmastectomy reconstruction. Rural setting, lower socioeconomic status, and lower plastic surgeon supply were also associated with decreased rates of breast conservation surgery. Reconstruction after mastectomy was lowest in the northwest, central, and southwest regions of Virginia. CONCLUSIONS: Within the state of Virginia, programs to improve access to breast reconstruction for patients residing in rural regions, as well as non-White patients, older patients, and those in lower socioeconomic groups should be implemented. Future studies would implement and study the efficacy of such outreach programs, which could then be applied and tailored to other states or regions to address sociodemographic disparities in access to breast reconstruction.

Evaluating the feasibility of pharmacist-facilitated tobacco cessation interventions in independent community pharmacies in rural Appalachia.

BACKGROUND: Smoking rates in the United States are the highest in underserved rural regions. Thus, more points of contact are needed to link smokers to evidence-based cessation programs. OBJECTIVES: The purpose of this study was to conduct an evaluation to determine the feasibility, acceptability, and interest among rural pharmacists in implementing a pharmacist-facilitated smoking cessation program in independent community pharmacies in rural Appalachian communities in Virginia, North Carolina, Tennessee, and West Virginia. METHODS: This study utilized a complementary sequential mixed-methods approach to explore independent community pharmacists and technicians' experiences and beliefs about implementing a tobacco cessation program in their pharmacy. RESULTS: There were 49 pharmacists or technicians who completed the survey and 7 pharmacists who participated in the interviews. Four main findings emerged from the data: 1) pharmacies can help fill the gap in tobacco cessation services in rural communities, 2) under current practice, tobacco cessation resources when offered by independent community pharmacies are not always formalized, 3) there are known barriers, such as reimbursing for services, that need to be addressed to provide tobacco cessation in an independent pharmacy setting, and 4) the Ask-Advise-Connect model is a feasible tobacco cessation approach in a pharmacy. CONCLUSION: Although pharmacists may be ideally situated to build capacity for smoking cessation in rural areas, smoking cessation interventions need to use existing approaches that compensate pharmacists for their time spent counseling patients. Furthermore, simple documentation and billing systems are needed to maximize utilization of tobacco cessation products and services provided in the pharmacy.

Effects of Adjuvant Endocrine Therapy Adherence and Radiation on Recurrence and Survival Among Older Women with Early-Stage Breast Cancer.

BACKGROUND: The Cancer and Leukemia Group-B 9343 (CALGB 9343) trial demonstrated that women aged ≥ 70 years with early-stage breast cancer can safely omit radiation therapy (RT) and be treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET) alone. AET adherence is low, leaving an undertreated cohort who may be at increased risk of recurrence and death. We hypothesized that AET adherence and adjuvant treatment choice impact recurrence and survival among CALGB 9343 eligible women. PATIENTS AND METHODS: SEER-Medicare was used to identify CALGB 9343 eligible women who underwent BCS between 2007 and 2016. Medicare claims were used to identify AET use, and the proportion of days covered by AET was used to categorize adherent (PDC ≥ 0.80) versus nonadherent patients (PDC < 0.80). Recurrence-free, cancer-specific, and overall survival were assessed using Cox proportional hazards models. RESULTS: In total, 10,719 women were identified, of whom 780 (7.3%) underwent BCS alone, 1490 (13.9%) underwent BCS + RT, 1663 (15.5%) underwent BCS + AET, and 6786 (63.3%) had BCS + RT + AET. Among women treated with BCS + AET, adherent patients had lower recurrence than did nonadherent patients (HR = 0.65, 95% CI: 0.50-0.85). With respect to adjuvant treatment combinations, there was no recurrence difference between the BCS + RT + AET group and BCS + AET group (HR = 0.81, 95% CI: 0.54-1.21). There was equivalent cancer-specific but worse overall survival in the BCS + AET group versus the BCS + AET + RT group. CONCLUSIONS: While BCS + RT + AET may represent overtreatment for some, AET nonadherent women who omit RT are at risk for worse outcomes. Treatment decisions regarding RT omission should be tailored to the individual patient, taking into consideration the chances of AET nonadherence and the patients' own risk tolerance.

Patient Characteristics Associated With Patient-Reported Deterrents to Adjunct Breast Cancer Screening of Patients With Dense Breasts.

BACKGROUND. The success of adjunct breast cancer screening of women with dense breasts can be enhanced by identifying and addressing patient concerns regarding adjunct screening modalities. OBJECTIVE. The purpose of this study was to identify patient characteristics associated with patient-reported concerns about adjunct breast cancer screening to facilitate the development of a more effective screening model for women with dense breasts. METHODS. Patients with dense breasts completed surveys between March 2017 and February 2018 regarding factors that might deter them from adjunct screening and about which of three hypothetical screening examinations they might prefer. Additional patient data were extracted from medical records, and socioeconomic data were imputed from federal census data. Logistic regression analyses were conducted to identify associations between patient characteristics and patient attitudes toward adjunct screening. RESULTS. Surveys were completed by 508 women (median age, 59.0 years) with dense breasts. Lower confidence in the sensitivity of mammography of dense breasts was independently associated with lesser concern about adjunct screening examination time (1 divided by adjusted odds ratio [1/AOR], 0.55 [95% CI, 0.34-0.89]), additional imaging that could result (1/AOR, 0.51 [95% CI, 0.31-0.85]), and greater preference for a more sensitive hypothetical screening examination (1/AOR, 1.85 [95% CI, 1.20-2.86]). Concern about examination cost, the most commonly cited deterrent to adjunct screening (66.9%), was independently associated with younger age (1/AOR, 1.45 [95% CI, 1.01-2.08]) but not with imputed socioeconomic variables or other tested variables. Younger age was also associated with lesser concern about pain (1/AOR, 0.69 [95% CI, 0.48-0.99]), additional imaging that could result (1/AOR, 0.48 [95% CI, 0.31-0.76]), and IV contrast administration (1/AOR, 0.56 [95% CI, 0.37-0.83]). CONCLUSION. Younger age and lower confidence in the sensitivity of mammography among women with dense breasts are independently associated with lesser patient concern about common deterrents to adjunct breast cancer screening. Younger age is independently associated with greater concern about the cost of undergoing adjunct breast cancer screening. CLINICAL IMPACT. Concerns about adjunct screening may be reduced by educating patients about the lower sensitivity of mammography of dense breasts and by finding ways to address or mitigate the financial and daily-life impact of adjunct screening, especially for younger patients.

Resolution acuity and spatial summation of chromatic mechanisms in the peripheral retina.

Green stimuli are more difficult to detect than red stimuli in the retinal periphery, as reported previously. We examined the spatial characteristics of chromatic mechanisms using stimuli, modulated from an achromatic background to each pole of the "red-green" cardinal axis in DKL space at 20 deg eccentricity. The "blue-yellow" cardinal axis was also studied for comparison. By measuring both grating discrimination at the resolution limit (resolution acuity) and spatial summation, assessed by the Michaelis-Menten function, we demonstrated a marked "red-green" asymmetry. The resolution acuity was worse and spatial summation more extended for "green" compared to "red" stimuli, while showing significant individual variations. Ricco's area was also measured, but not determined for "green" spots because of the poor small stimuli detection. These results cannot be explained by differences in L- and M-cone numerosity and/or spatial arrangement, but rather have postreceptoral origin, probably at the cortical level.

Spatial analysis of colorectal cancer outcomes and socioeconomic factors in Virginia.

BACKGROUND: Colorectal cancer (CRC) disparities vary by country and population group, but often have spatial features. This study of the United States state of Virginia assessed CRC outcomes, and identified demographic, socioeconomic and healthcare access contributors to CRC disparities. METHODS: County- and city-level cross-sectional data for 2011-2015 CRC incidence, mortality, and mortality-incidence ratio (MIR) were analyzed for geographically determined clusters (hotspots and cold spots) and their correlates. Spatial regression examined predictors including proportion of African American (AA) residents, rural-urban status, socioeconomic (SES) index, CRC screening rate, and densities of primary care providers (PCP) and gastroenterologists. Stationarity, which assesses spatial equality, was examined with geographically weighted regression. RESULTS: For incidence, one CRC hotspot and two cold spots were identified, including one large hotspot for MIR in southwest Virginia. In the spatial distribution of mortality, no clusters were found. Rurality and AA population were most associated with incidence. SES index, rurality, and PCP density were associated with spatial distribution of mortality. SES index and rurality were associated with MIR. Local coefficients indicated stronger associations of predictor variables in the southwestern region. CONCLUSIONS: Rurality, low SES, and racial distribution were important predictors of CRC incidence, mortality, and MIR. Regions with concentrations of one or more factors of disparities face additional hurdles to improving CRC outcomes. A large cluster of high MIR in southwest Virginia region requires further investigation to improve early cancer detection and support survivorship. Spatial analysis can identify high-disparity populations and be used to inform targeted cancer control programming.

Financial hardship in Chinese cancer survivors.

BACKGROUND: The purpose of this study was to estimate the proportion of Chinese cancer survivors experiencing financial hardship and then examine the relationship between material and behavioral financial hardship. METHODS: This study surveyed 964 cancer survivors who were 30 to 64 years old and 644 survivors who were 65 years old or older during 2015-2016 (1608 survivors in all). Material financial hardship was measured by whether they had borrowed money because of cancer, its treatment, or the lasting effects of treatment, and behavioral financial hardship was measured by whether they had forgone some cancer-related medical care because of cost. Multivariable logistic regression models were used to examine factors associated with material financial hardship by age group. RESULTS: Approximately 44% of the cancer survivors who were 65 years old or older borrowed money or went into debt because of cancer, and 54% of younger patients (P < .01) reported cancer-related debts. Among these survivors with cancer care debt, survivors aged 65 years old or older had a lower proportion of borrowing more than 50,000 Chinese yuan (CNY; approximately US $7700) than survivors aged 30 to 64 years (14% vs 20%). In both age groups, approximately 10% of cancer survivors reported that they had experienced behavioral financial hardship. After adjustments for covariates, cancer survivors who reported material financial problems were more likely to report behavioral financial hardship (odds ratio [OR] for those aged 30-64 years, 3.72; 95% confidence interval [CI], 2.13-6.50; OR for those aged 65 years or older, 5.48; 95% CI, 2.69-11.15). CONCLUSIONS: Older cancer survivors in China experience significant material financial hardship, but it is not as noticeable as younger patients' hardship. The results highlight the importance of identifying cancer survivors who are more likely to experience financial hardship and improving the affordability of cancer care in China.

Predicting adjuvant endocrine therapy initiation and adherence among older women with early-stage breast cancer.

PURPOSE: The CALGB 9343 trial demonstrated that women age 70 or older with early-stage, estrogen receptor positive (ER +) breast cancer (BC) may safely forgo radiation therapy (RT) and be treated with breast conserving surgery followed by adjuvant endocrine therapy (AET) alone. However, most patients in this population still undergo RT in part because AET adherence is low. We sought to develop a predictive model for AET initiation and adherence in order to improve decision-making with respect to RT omission. METHODS: Women ages 70 and older with early-stage, ER + BC were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidities, socioeconomic measures, prescription medications, and demographics were collected as potential predictors. Bivariate analysis was performed to identify factors associated with AET initiation and adherence. Stepwise selection of significant predictors was used to develop logistic regression classifiers for initiation and adherence. Model performance was evaluated using the c-statistic and other measures. RESULTS: 11,037 patients met inclusion criteria. Within the cohort, 8703 (78.9%) patients initiated AET and 6685 (60.6%) were adherent to AET over 1 year. Bivariate predictors of AET initiation were similar to predictors of adherence. The best AET initiation and adherence classifiers were poorly predictive with c-statistics of 0.65 and 0.60, respectively. CONCLUSIONS: The best models in the present study were poorly predictive, demonstrating that the reasons for initiation and adherence to AET are complex and individual to the patient, and therefore difficult to predict. Initiation and adherence to AET are important factors in decision-making regarding whether or not to forgo adjuvant RT. In order to better formulate treatment plans for this population, future work should focus on improving individual prediction of AET initiation and adherence.

Evaluating the Long-Term Impact of a Cooperative Group Trial on Radiation Use and Adjuvant Endocrine Therapy Adherence Among Older Women.

BACKGROUND: Using long-term survival data from the C9343 trial as a temporal reference point, this study aimed to determine radiation therapy (RT) treatment trends for older patients with early-stage breast cancer. The study also examined rates of adherence to adjuvant endocrine therapy (AET). METHODS: The surveillance, epidemiology, and end results-medicare database was used to identify women with a diagnosis of breast cancer from 2007 through 2016. Bivariate associations were calculated to determine variable characteristics by time frame (group 1: 2007-2012 vs. group 2: 2013-2016). Multivariate logistic regression was used to estimate the effect of group on the RT use and AET adherence. The temporal rates for both RT and AET adherence over time were plotted. RESULTS: The final study cohort included 12,210 Medicare beneficiaries. Use of RT differed significantly between the groups, with a higher proportion omitting RT in the later period (25% of group 2 vs. 20% of group 1; p < 0.001). In both groups, after adjustment for covariates, the patients with RT omitted were statistically less likely to adhere to AET [group 1: odds ratio (OR), 0.74; p < 0.001 vs. group 2: OR, 0.66; p < 0.001]. CONCLUSION: This study, 15 years after publication of the of the C9343 trial results, showed minimal change in practice, with most older women receiving RT. Importantly, AET adherence was significantly lower in the non-RT group. For women who meet the criteria to have adjuvant RT omitted, nonadherence to AET could result in undertreatment of their breast cancer, and RT should not be considered overtreatment.

Long-term Impact of CALGB 9343 on Radiation Utilization.

BACKGROUND: The results of the Cancer and Leukemia Group B (CALGB) 9343 trial showed that radiation therapy (RT) did not improve survival for women older than 70 y with early-stage estrogen receptor + breast cancer treated with breast conserving surgery and adjuvant endocrine therapy. In 2005, guidelines were modified to allow for RT omission; however, minimal change in clinical practice has occurred. The aim of this study was to determine if CALGB long-term follow-up data have affected RT utilization, and to characterize the population still receiving RT after breast conserving surgery. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women diagnosed with early-stage breast cancer from 2004 to 2015 who matched the CALGB 9343 inclusion criteria. Multivariate logistic regression was carried out to identify the factors that affect the receipt of radiation therapy. We also plotted the overall use of RT over time juxtaposed with the temporal trends of CALGB 9343 clinical trial data, guideline recommendations, and publishing of long-term survival data. RESULTS: The study cohort included 25,723 Medicare beneficiaries, of whom 20,328 (79%) received RT and 5395 (21%) did not receive RT. In a multivariate model, the frequency of RT omission increased over time, with those diagnosed in year 2015 being 2.72 times more likely to omit RT compared with those diagnosed in 2004 (95% confidence interval 2.31-3.19). CONCLUSIONS: This study investigated the impact of long-term CALGB 9343 data on clinical practice. The results of this study support results from previous studies, extend the dates of analysis, and indicate that after long-term follow-up of CALGB 9343 data, RT was less used, but overall trends did not dramatically decrease.

Known-groups validity and responsiveness to change of the Patient Experience with Treatment and Self-management (PETS vs. 2.0): a patient-reported measure of treatment burden.

PURPOSE: The purpose of this study was to test the known-groups validity and responsiveness to change of the Patient Experience with Treatment and Self-management (PETS, vs. 2.0), a measure of treatment burden. METHODS: The PETS and other standard measures were mailed at baseline and 12-month follow-up to adults living with multiple chronic conditions in southeast Minnesota (USA). A sample of 365 people (mean age = 62.1 years) completed both surveys. Baseline, 12-month, and changes in PETS burden scores were examined. Clinical anchors used to test validity included number of diagnoses (2-4 vs. 5+), mental health diagnosis (yes/no), medication adherence and health literacy (suboptimal/optimal), and changes in self-efficacy, global physical, and global mental health (worsening/improving). Independent-samples t-tests were used to compare scores. RESULTS: PETS scales showed good internal consistency (αs ≥ 0.80). There were few differences across number of diagnoses, but having a mental health diagnosis was associated with higher baseline PETS burden scores (Ps < .05). Suboptimal medication adherence and health literacy over time were associated with worse 12-month PETS burden scores (Ps < .05). Compared with improvements, declines over time in self-efficacy, global physical health, and global mental health were each associated with worsening change scores on PETS impact summary, medical expenses, and bother due to medication reliance and medication side effects (Ps < .05). CONCLUSION: Among multi-morbid adults, the PETS demonstrated evidence of known-groups validity and responsiveness to change across both objective (e.g., mental health diagnoses) and subjective anchors (e.g., changes in self-efficacy, global physical, and global mental health).

Employment changes among Chinese family caregivers of long-term cancer survivors.

BACKGROUND: Family caregivers (FCGs) play a key role in the plan of care provision for long-term cancer survivors, yet few studies have been conducted on the impact of long-term caregiving on FCGs and their employment patterns. This study aims to further our understanding of the effect that caregiving role has on FCGs by identifying what cancer-related characteristics influence reduction of employment hours among FCGs in the post-treatment phase in China. METHODS: A total of 1155 cancer survivors participated in this study. Patients reported changes in the employment patterns of their FCGs. Descriptive analysis looked at demographic and cancer-related characteristics of cancer survivors and types of FCGs' employment changes in both primary- and post-treatment phases. Chi-square test was used to statistically test the association between survivors' characteristics and changes in FCGs' hours of labor force work in post-treatment phase. Separate multivariable logistic regression models were used to examine the relationship between cancer-related characteristics of participants and employment reduction patterns among FCGs in post-treatment phase while controlling for demographic factors. RESULTS: In the primary-treatment phase, 45.6% of all FCGs reduced their working hours and 17.4% stopped working altogether. In the post-treatment phase, 25.2% of FCGs worked fewer hours and 6.6% left the workforce completely. The results show that a higher probability of change in employment hours among FCGs is associated with the following patient characteristics: having comorbidities, receiving chemotherapy treatment, limited ability to perform physical tasks, limited ability to perform mental tasks, and diagnosis of stage II of cancer. CONCLUSIONS: Care for cancer patients in both primary- and post- treatment phases may have substantial impacts on hours of formal employment of Chinese FCGs. Interventions helping FCGs balance caregiving duties with labor force work are warranted.

Deriving and validating a brief measure of treatment burden to assess person-centered healthcare quality in primary care: a multi-method study.

BACKGROUND: In primary care there is a need for more quality measures of person-centered outcomes, especially ones applicable to patients with multiple chronic conditions (MCCs). The aim of this study was to derive and validate a short-form version of the Patient Experience with Treatment and Self-management (PETS), an established measure of treatment burden, to help fill the gap in quality measurement. METHODS: Patient interviews (30) and provider surveys (30) were used to winnow items from the PETS (60 items) to a subset targeting person-centered care quality. Results were reviewed by a panel of healthcare providers and health-services researchers who finalized a pilot version. The Brief PETS was tested in surveys of 200 clinic and 200 community-dwelling MCC patients. Surveys containing the Brief PETS and additional measures (e.g., health status, medication adherence, quality of care, demographics) were administered at baseline and follow-up. Correlations and t-tests were used to assess validity, including responsiveness to change of the Brief PETS. Effect sizes (ES) were calculated on mean differences. RESULTS: Winnowing and panel review resulted in a 34-item Brief PETS pilot measure that was tested in the combined sample of 400 (mean age = 57.9 years, 50% female, 48% white, median number of conditions = 5). Reliability of most scales was acceptable (alpha > 0.70). Brief PETS scores were associated with age, income, health status, and quality of chronic illness care at baseline (P < .05; rho magnitude range: 0.16-0.66). Furthermore, Brief PETS scores differentiated groups based on marital and education status, presence/absence of a self-management routine, and optimal/suboptimal medication adherence (P < .05; ES range: 0.25-1.00). Declines in patient-reported physical or mental health status over time were associated with worsening PETS burden scores, while improvements were associated with improving PETS burden scores (P < .05; ES range: 0.04-0.44). Among clinic patients, 91% were willing to complete the Brief PETS as part of their clinic visits. CONCLUSIONS: The Brief PETS (final version: 32 items) is a reliable and valid tool for assessing person-centered care quality related to treatment burden. It holds promise as a means of giving voice to patient concerns about the complexity of disease management.