Development and acceptability of PETS-Now, an electronic point-of-care tool to monitor treatment burden in patients with multiple chronic conditions: a multi-method study.

BACKGROUND: The aim of this study was to develop a web-based tool for patients with multiple chronic conditions (MCC) to communicate concerns about treatment burden to their healthcare providers. METHODS: Patients and providers from primary-care clinics participated. We conducted focus groups to identify content for a prototype clinical tool to screen for treatment burden by reviewing domains and items from a previously validated measure, the Patient Experience with Treatment and Self-management (PETS). Following review of the prototype, a quasi-experimental pilot study determined acceptability of using the tool in clinical practice. The study protocol was modified to accommodate limitations due to the Covid-19 pandemic. RESULTS: Fifteen patients with MCC and 18 providers participated in focus groups to review existing PETS content. The pilot tool (named PETS-Now) consisted of eight domains (Living Healthy, Health Costs, Monitoring Health, Medicine, Personal Relationships, Getting Healthcare, Health Information, and Medical Equipment) with each domain represented by a checklist of potential concerns. Administrative burden was minimized by limiting patients to selection of one domain. To test acceptability, 17 primary-care providers first saw 92 patients under standard care (control) conditions followed by another 90 patients using the PETS-Now tool (intervention). Each treatment burden domain was selected at least once by patients in the intervention. No significant differences were observed in overall care quality between patients in the control and intervention conditions with mean care quality rated high in both groups (9.3 and 9.2, respectively, out of 10). There were no differences in provider impressions of patient encounters under the two conditions with providers reporting that patient concerns were addressed in 95% of the visits in both conditions. Most intervention group patients (94%) found that the PETS-Now was easy to use and helped focus the conversation with the provider on their biggest concern (98%). Most providers (81%) felt they had learned something new about the patient from the PETS-Now. CONCLUSION: The PETS-Now holds promise for quickly screening and monitoring treatment burden in people with MCC and may provide information for care planning. While acceptable to patients and clinicians, integration of information into the electronic medical record should be prioritized.

The Breast-Imaging Operations, Practices and Systems Inventory: A framework to examine mammography facility effects on screening in rural communities.

PURPOSE: Develop and test a measurement framework of mammogram facility resources, policies, and practices in Appalachia. METHODS: Survey items describing 7 domains of imaging facility qualities were developed and tested in the Appalachian regions of Kentucky, Ohio, Pennsylvania, Virginia, and West Virginia. Medicare claims data (2016-2018) were obtained on catchment area mammogram services. Construct validity was examined from associations with facility affiliation, community characteristics, mammogram screening uptake, and market reach. Analyses were performed with t-tests and ANOVA. RESULTS: A total of 192 (of 377) sites completed the survey. Five factors were initially selected in exploratory factor analysis (FA) and refined in confirmatory FA: capacity, outreach & marketing, operational support, radiology review (NNFI = .94, GFI = 0.93), and diagnostic services (NNFI = 1.00, GFI = 0.99). Imaging capacity and diagnostic services were associated with screening uptake, with capacity strongly associated with catchment area demographic and economic characteristics. Imaging facilities in economically affluent versus poorer areas belong to larger health systems and have significantly more resources (P < .001). Facilities in economically distressed locations in Appalachia rely more heavily on outreach activities (P < .001). Higher facility capacity was significantly associated (P < .05) with larger catchment area size (median split: 48.5 vs 51.6), mammogram market share (47.4 vs 52.7), and screening uptake (47.6 vs 52.4). CONCLUSIONS: A set of 18 items assessing breast imaging services and facility characteristics was obtained, representing policies and practices related to a facility's catchment area size, market share, and mammogram screening uptake.

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.

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.

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.

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.

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.

Experiences with cancer survey in China.

BACKGROUND: China accounts for approximately 27% of global cancer deaths. However, to the authors' knowledge, the lasting effects of cancer and cancer treatments on patients have not been investigated in China. The authors developed a questionnaire, the China Survey of Experiences with Cancer, for Chinese cancer survivors. This article introduces the study design and domains covered in the questionnaire. METHODS: The Cancer Survivorship Supplement of the Medical Expenditure Panel Survey (MEPS) was used as a reference to develop the questionnaire. The final in-person surveys were conducted in 2015 and 2016. Samples were chosen through multistage sampling. The authors described the characteristics of the study participants and their cancer experiences. RESULTS: At the time of last follow-up, a total of 1166 patients had completed at least 1 component of the survey. Approximately 59% of the cancer survivors were aged ≥60 years. Greater than one-half of the participants had an elementary education level or less (51%) and a yearly family income of <$3174. Chinese cancer survivors were more likely to retire earlier than planned compared with American cancer survivors (37% vs 9%). The majority of Chinese cancer survivors (84%) reported that their work abilities were hindered by their cancer or cancer treatments. Approximately one-half of patients in China had to incur debt because of cancer, whereas <10% of patients in the United States reported having incurred debt. CONCLUSIONS: The survey provides information regarding the burden of cancer in China that to the authors' knowledge currently is unavailable from other sources, including medical care use, financial impacts, employment patterns, and life experience after a cancer diagnosis for survivors and their families.

Impact of patient race and geographical factors on initiation and adherence to adjuvant endocrine therapy in medicare breast cancer survivors.

To evaluate variations in the use of adjuvant endocrine therapy (AET) by race and geography, this research examined their influence on initiation and adherence to AET in female Medicare enrollees with breast cancer, diagnosed between 2007 and 2011.Using SEER (Surveillance, Epidemiology, and End Results Program)-Medicare data from 2007 to 2001, logistic regressions with random intercept for county of residence were used to predict AET initiation during 1st year and AET adherence assessed by the medication possession ratio (MPR) during year after initiation in a sample of fee-for-service medicare beneficiaries. Part D enrollment was required for the examination of adherence. Independent variables examined were race (black, white, or other) and geographical indicators (area deprivation, non-metropolitan status, and physician shortage).Overall, 23% of patients did not initiate AET within 1 year and 26% of the initiation sample was not adherent to AET, with average follow-up time among initiators of 141 days and an average MPR of 0.84. Significant heterogeneity (P < .01) was found between SEER sites, with initiation rates as low as 69% for Washington and as high as 81% for New Jersey; MPR adherence varied from 77% in New Jersey to 68% in Utah.Blacks had lower initiation, enrollees not in Medicaid had lower adherence, lower area deprivation counties had lower initiation, earlier SEER-Medicare years had both later initiation and nonadherence, and significant (P < .05) variations between SEER sites remained after accounting for area deprivation index, metropolitan status, and physician shortage. Subgroup analysis showed particular pockets of lower initiation for blacks with stage III tumors, on chemotherapy and lower adherence for blacks in youngest age group, with stage III tumors, tamoxifen use and blacks/others in oldest age group.Black women and women living in states with more rurality in the United States were less likely to receive guideline-recommended AET, which necessitates future efforts to alleviate these disparities to improve AET use and ultimately pursue more survival gains through optimizing adjuvant treatment use among cancer survivors.

Geographic disparities in adherence to adjuvant endocrine therapy in Appalachian women with breast cancer.

BACKGROUND: Appalachia is a largely rural, mountainous, poor and underserved region of the United States. Adherence to adjuvant endocrine therapy among Appalachian women with breast cancer is suboptimal. OBJECTIVES: To explore small-area geographic variations and clustering patterns of breast cancer patient adherence to adjuvant endocrine therapy and associated factors in Appalachia. METHODS: In this retrospective study, we analyzed Medicare claims data linked with cancer registries from four Appalachian states (PA, OH, KY, and NC) in 2006-2008. We included adult women who were diagnosed with stage I-III, hormone-receptor positive, primary breast cancer and who newly started adjuvant endocrine therapy after the primary treatment for breast cancer. Hot spot analysis was conducted to explore geographic variations in adjuvant endocrine therapy adherence. Geographically weighted logistic regression (GWLR) was used to examine whether the impacts of factors associated with adherence varied across the region. RESULTS: Breast cancer patients living in PA and OH showed higher adherence to adjuvant endocrine therapy than those living in KY and NC. We identified clusters of high adherence in most of PA but poor adherence in Erie County, PA and in Buncombe, Transylvania, Henderson, and Polk Counties, NC. Adherence to adjuvant endocrine therapy was significantly associated with the Health Professional Shortage Area designation, catastrophic coverage, dual-eligibility status of Medicaid and Medicare, adjuvant endocrine therapy drug class, and side effects. And among these factors, the impacts of dual-eligibility status and the use of pain medications to treat side effects on adherence were more pronounced in KY and NC than in PA. CONCLUSIONS: There were significant geographic disparities in adherence to adjuvant endocrine therapy in the Appalachian counties in PA, OH, KY, and NC. This study explored these geographic areas with poor adherence as well as geographically varying effects of predictors on adherence; our results may provide more localized information that may be used to improve adjuvant therapy use and breast cancer care in these high-risk and underserved areas.

What Predicts an Advanced-Stage Diagnosis of Breast Cancer? Sorting Out the Influence of Method of Detection, Access to Care, and Biologic Factors.

BACKGROUND: Multiple studies have yielded important findings regarding the determinants of an advanced-stage diagnosis of breast cancer. We seek to advance this line of inquiry through a broadened conceptual framework and accompanying statistical modeling strategy that recognize the dual importance of access-to-care and biologic factors on stage. METHODS: The Centers for Disease Control and Prevention-sponsored Breast and Prostate Cancer Data Quality and Patterns of Care Study yielded a seven-state, cancer registry-derived population-based sample of 9,142 women diagnosed with a first primary in situ or invasive breast cancer in 2004. The likelihood of advanced-stage cancer (American Joint Committee on Cancer IIIB, IIIC, or IV) was investigated through multivariable regression modeling, with base-case analyses using the method of instrumental variables (IV) to detect and correct for possible selection bias. The robustness of base-case findings was examined through extensive sensitivity analyses. RESULTS: Advanced-stage disease was negatively associated with detection by mammography (P < 0.001) and with age < 50 (P < 0.001), and positively related to black race (P = 0.07), not being privately insured [Medicaid (P = 0.01), Medicare (P = 0.04), uninsured (P = 0.07)], being single (P = 0.06), body mass index > 40 (P = 0.001), a HER2 type tumor (P < 0.001), and tumor grade not well differentiated (P < 0.001). This IV model detected and adjusted for significant selection effects associated with method of detection (P = 0.02). Sensitivity analyses generally supported these base-case results. CONCLUSIONS: Through our comprehensive modeling strategy and sensitivity analyses, we provide new estimates of the magnitude and robustness of the determinants of advanced-stage breast cancer. IMPACT: Statistical approaches frequently used to address observational data biases in treatment-outcome studies can be applied similarly in analyses of the determinants of stage at diagnosis. Cancer Epidemiol Biomarkers Prev; 25(4); 613-23. ©2016 AACR.

Effects of Hospital Type and Distance on Lymph Node Assessment for Colon Cancer Among Metropolitan and Nonmetropolitan Patients in Appalachia.

We studied differences in access to large or accredited cancer programs as a possible explanation for geographic disparities in adherence to the national guideline on lymph node assessment for Stages I to III colon cancer. State cancer registries were linked with Medicare claims of patients diagnosed from 2006 to 2008 from Appalachian counties of four states. Metropolitan and nonmetropolitan patients differed on adherence, proximity to high-volume or accredited hospitals, and hospital type. We modeled effects of hospital type on adherence with ordinary least squares and instrumental variables (instrumenting for hospital type with relative distance). The evidence was strongest for improved adherence in high-volume hospitals for nonmetropolitan patients. We estimate that roughly 100 deaths might be prevented over 5 years among each year's incident cases if the nonmetropolitan disparity in hospital volume were eliminated nationally. We conclude that regionalization or targeting smaller hospitals would improve adherence in nonmetropolitan areas, but also argue for improving adherence generally.

Clinical and Demographic Factors Associated With Receipt of Non Guideline-concordant Initial Therapy for Nonmetastatic Prostate Cancer.

OBJECTIVES: To determine the extent to which initial therapy for nonmetastatic prostate cancer was concordant with nationally recognized guidelines using supplemented cancer registry data and what factors were associated with receipt of nonguideline-concordant care. METHODS: Initial therapy for 8229 nonmetastatic prostate cancer cases diagnosed in 2004 from cancer registries in 7 states was abstracted as part of the Centers for Disease Control's Patterns of Care Breast and Prostate Cancer study conducted during 2007 to 2009. The National Comprehensive Cancer Network clinical practice guidelines version 1.2002 was used as the standard of care based on recurrence risk group and life expectancy (LE). A multivariable model was used to determine risk factors associated with receipt of nonguideline-concordant care. RESULTS: Nearly 80% with nonmetastatic prostate cancer received guideline-concordant care for initial therapy. Receipt of nonguideline-concordant care (including receiving either less aggressive therapy or more aggressive therapy than indicated) was related to older age, African American race/ethnicity, being unmarried, rural residence, and especially to being in the high recurrence risk group where receiving less aggressive therapy than indicated occurred more often than receiving more aggressive therapy (adjusted OR=4.2; 95% CL, 3.5-5.2 vs. low-risk group). Compared with life table estimates adjusted for comorbidity, physicians tended to underestimate LE. CONCLUSIONS: Receipt of less aggressive therapy than indicated among high-risk group men with >5-year LE based on life table estimates adjusted for comorbidity was a concern. Physicians may tend to underestimate 5-year survival among this group and should be alerted to the importance of recommending aggressive therapy when warranted. However, based on more recent guidelines, among those with low-risk disease, the proportion considered to be receiving less aggressive therapy than indicated may now be lower because active surveillance is now considered appropriate.

The Hand-Foot Skin Reaction and Quality of Life Questionnaire: An Assessment Tool for Oncology.

BACKGROUND: Skin toxicity (hand-foot syndrome/hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice, with potentially large impacts on health-related quality of life (HRQL). MATERIALS AND METHODS: A patient-reported questionnaire, the hand-foot skin reaction and quality of life (HF-QoL) questionnaire was developed to measure the HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL questionnaire was tested in a randomized trial of capecitabine with sorafenib/placebo in 223 patients with locally advanced/metastatic breast cancer. Other measures completed included patient ratings of condition severity, the Functional Assessment of Cancer Therapy-Breast cancer (FACT-B), and the clinician-rated National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0, hand-foot skin reaction grade. The psychometric properties of the HF-QoL tested included structural validity, internal consistency, construct validity, discriminant validity, and responsiveness. Finally, the minimal clinically important difference (MCID) was estimated. RESULTS: The HF-QoL instrument comprises a 20-item symptom scale and an 18-item daily activity scale. Each scale demonstrated excellent measurement properties and discriminated between NCI-CTCAE grade and patient-rated condition severity with large effect sizes. The daily activity scale had excellent internal consistency and correlated with the FACT-B and HF-QoL symptom scores. Both HF-QoL scale scores increased linearly with increasing patient-rated condition severity. The MCIDs were estimated as 5 units for daily activities and 8 units for symptoms mean scores. CONCLUSION: The HF-QoL was sensitive to symptoms and HRQL issues associated with HFS/R among participants treated with capecitabine with and without sorafenib. The HF-QoL appears suitable for assessing the HRQL impairment associated with HFS/R to cancer therapies. IMPLICATIONS FOR PRACTICE: Skin toxicity related to anticancer therapies is a significant issue in oncology practice. Several newer agents, as well as older therapies, are associated with the skin toxicity known as hand-foot skin reaction (HFSR) or hand-foot syndrome (HFS). This study describes the development and validation of a brief, patient-reported questionnaire (the hand-foot skin reaction and quality of life questionnaire) supporting its suitability for use in clinical research to aid in early recognition of symptoms, to evaluate the effectiveness of agents for HFS/R treatment within clinical trials, and to evaluate the impact of these treatments on HFS/R-associated patients' health-related quality of life.

Individual, Area, and Provider Characteristics Associated With Care Received for Stages I to III Breast Cancer in a Multistate Region of Appalachia.

PURPOSE: We describe individual, area, and provider characteristics associated with care patterns for early-stage breast cancer in Appalachian counties of Kentucky, North Carolina, Ohio, and Pennsylvania. METHODS: Cases of stages I to III breast cancer from 2006 to 2008 were linked to Medicare claims occurring within 1 year of diagnosis. Rates of guideline-concordant endocrine therapy (n = 1,429), chemotherapy (n = 1,480), and radiation therapy (RT) after breast-conserving surgery were studied; RT was studied in women age ≥ 70 years with stage I estrogen receptor (ER) -positive/progesterone receptor (PR) -positive cancer, for whom RT was optional (n = 1,108), and in all others, for whom RT was guideline concordant (n = 1,422). Univariable and multivariable analyses were performed. Independent variables included age, race, county-level economic status, state, surgeon graduation year and volume, comorbidity, diagnosis year, Medicaid/Medicare dual status, histology, tumor size, tumor sequence, positive lymph nodes, ER/PR status, stage, trastuzumab use, and surgery type. RESULTS: Population mean age was 74 years; 97% were white. For endocrine therapy, chemotherapy, and RT, guideline concordance was 76%, 48%, and 83%, respectively. Where it was optional, 77% received RT. Guideline-concordant endocrine therapy was lower in North Carolina versus Pennsylvania (odds ratio [OR], 0.60; 95% CI, 0.41 to 0.88) and higher if surgeon graduated between 1984 and 1988 versus ≥ 1989 (OR, 1.58; 95% CI, 1.06 to 2.34). Guideline-concordant chemotherapy varied significantly by state, county-level economic status, and surgeon volume. In guideline-concordant RT, lower surgeon volume (v highest) predicted RT use (OR, 1.63; 95% CI, 1.61 to 2.36). In optional RT, North Carolina residence (v Pennsylvania; OR, 0.29; 95% CI, 0.17 to 0.48) and counties with higher economic status (OR, 0.61; 95% CI, 0.40 to 0.94) predicated RT omission. CONCLUSION: Notable variation in care by geographic and surgical provider characteristics provides targets for further research in underserved areas.

Receipt of Regular Primary Care and Early Cancer Detection in Appalachia.

PURPOSE: The objective was to examine the impact of regular primary care encounters (PCE) on early breast cancer detection in an Appalachian sample of Medicare beneficiaries diagnosed 2006-2008. Determinants of PCE were investigated and a mediation analysis was conducted where PCE was a mediator to cancer stage. METHODS: A total of 3,589 cases were identified from Appalachian areas in Pennsylvania, Kentucky, Ohio, and North Carolina, and health care services were examined 2 months to 2 years prior to diagnosis. A regular care PCE variable was constructed with 4 ordinal levels: none, any, "annual," and "semi-annual." Association of PCE with stage, mortality and covariables was conducted using ordinal logistic regressions and Cox Proportional Hazards survival models. RESULTS: Sixty-eight percent of the cases had semi-annual PCE. Regular PCE was strongly associated with late-stage cancer rates (39%-13% by increasing PCE level, P < .0001) and 5-year all-cause mortality (42%-24%, P < .0001). Subgroup analysis revealed variations by hypertension and urban status, with nonhypertensives with no PCE being at particularly increased risk. Significant determinants of PCE included age, rural/urban status, comorbidity, dual Medicaid insurance, Appalachian region economic classification, state, select comorbidities, hypertension, and minimum distance to provider. Mediation analysis results were consistent with lower number of comorbidities leading to increased late cancer detection due to patients having a decreased PCE. CONCLUSION: PCE is an important determinant of cancer detection, with a dose-response relationship. Variations exist by geography and hypertension. Comorbidity may influence both PCE and late-stage rates with partial mediation through PCE.

Psychometric evaluation of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial.

PURPOSE: To describe the psychometric properties and identify the minimally important difference (MID) of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument. Chronic HCV infection and associated treatments negatively affect PROs of function and well-being. METHODS: In a phase 2 trial, HCV-infected patients received direct-acting antivirals (DAAs) for 12 weeks with peg-interferon/ribavirin (peg-IFN/RBV) for 48 weeks, or placebo plus peg-IFN/RBV. The HCV-PRO total score, SF-36 PCS and MCS scores, EQ-5D-3L, and EQ VAS were measured at baseline, week 8, end of DAA treatment (EODT), end of peg-IFN/RBV treatment (EOT), and posttreatment week 24 (SVR24). Convergent validity of the HCV-PRO was assessed by Pearson's correlation coefficients. Discriminant validity was assessed by analyzing mean HCV-PRO total scores by EQ-5D anxiety/depression and pain/discomfort domain scores (none vs. some) and presence/absence of depression or fatigue adverse events. MID was identified through effect size (ES) and receiver-operating characteristic (ROC) curve analyses (HCV-PRO response vs. SF-36 PCS/MCS and EQ VAS MID thresholds). RESULTS: In 74 patients (22 % female; 81 % White; 51 % ≥50 years), correlations (0.64-0.96) between HCV-PRO total scores, SF-36 PCS/MCS scores, and EQ VAS scores at all time points supported convergent validity. HCV-PRO total scores were reduced to 10-30 points in patients impaired by depression, pain, or fatigue symptoms. Impact of peg-IFN/RBV regimen on HCV-PRO ES increased over time (EODT -0.76; EOT -0.93). ES and ROC curve analyses indicated an MID of -10 points. CONCLUSION: The HCV-PRO was valid and responsive in the population studied. An MID of -10 points represented a threshold of clinical significance for the HCV-PRO.

Radiation therapy resources and guideline-concordant radiotherapy for early-stage breast cancer patients in an underserved region.

OBJECTIVE: To examine the relationship between radiation therapy resources and guideline-concordant radiotherapy after breast-conserving surgery (BCS) in Kentucky. DATA SOURCES: The SEER registry and Area Resource File provided county-level data describing cancer care resources and socioeconomic conditions of Kentucky residents. STUDY DESIGN: The outcome variable was rate of BCS without radiotherapy in each county for 2000-2007. Eight-year weighted average rates of radiation therapy providers and hospitals per 100,000 residents were explanatory variables of interest. Exploratory spatial data analyses and spatial econometric models were estimated. PRINCIPAL FINDINGS: Appalachian counties in Kentucky had significantly fewer radiation oncologists, hospitals with radiation therapy facilities, and surgeons per 100,000 residents than non-Appalachian counties. The likelihood of BCS without radiation was significantly higher among Appalachian compared to non-Appalachian women (42.5 percent vs. 29.0 percent, p < .001). Higher proportions of women not receiving recommended radiotherapy after BCS were clustered in Eastern Kentucky around Lexington. This geographic disparity was partially explained by significantly fewer radiation therapy facilities in Appalachian Kentucky in adjusted analyses. CONCLUSIONS: Scarce radiation therapy resources in Appalachian Kentucky are associated with disparities in receipt of guideline-concordant radiotherapy, suggesting that policy action is needed to improve the cancer treatment infrastructure in disadvantaged mountainous areas.

Clinical, safety, and economic evidence in radioactive iodine-refractory differentiated thyroid cancer: a systematic literature review.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy, with differentiated thyroid cancer (DTC) comprising ~93% of all thyroid cancers. While most cases of DTC are curable with the use of surgery and radioactive iodine (RAI) ablation of the remaining thyroid remnant, prognosis is dire and treatment options limited when DTC becomes RAI-refractory (RAI-R). Standard cytotoxic chemotherapy has limited efficacy, making enrollment in clinical trials of novel targeted therapies the preferred treatment approach. Thus, we conducted a comprehensive systematic review of the clinical trial scientific literature with a focus on efficacy, safety, and economics to identify all potential treatment options that have been or are currently being evaluated for the treatment of RAI-R DTC. METHODS: Embase.com (including Medline), Medline In-Process and other nonindexed citations, the Cochrane Libraries, ClinicalTrials.gov, and relevant recent conference proceedings were searched using predefined search criteria. Important inclusion criteria included English language, randomized controlled studies or interventional single-arm studies only, and studies of drug therapies only. Search results were screened utilizing the discretion of multiple researchers, and key data were abstracted. RESULTS: Forty-five unique trials (16 full-text, 4 conference abstracts, and 25 ClinicalTrials.gov entries) were included in the clinical review. No studies that met criteria for inclusion in the economic review were identified. Among 20 trials with results available, all were Phase II and only one was randomized. The most commonly studied drugs were tyrosine kinase inhibitors (TKIs); other drugs included celecoxib, doxorubicin with interferon alpha-2b, rosiglitazone, selumetinib (AZD6244), thalidomide, VEGF trap, and vorinostat. Overall, efficacy and safety profiles were specific to treatment regimen, with objective response rates (ORR) ranging from 0% on gefitinib, rosiglitazone, VEGF trap, and vorinostat to 50% on lenvatinib, a TKI. CONCLUSIONS: Limited clinical research and no economic research has been conducted in RAI-R DTC. Certain treatments, notably TKIs, have shown promise in Phase II trials, and two Phase III randomized placebo-controlled trials are ongoing. New research on the economic and humanistic burden of RAI-R DTC must be paired with the clinical evidence currently in development to examine the existing burden and future promise in treating patients with RAI-R DTC.