[Show abstract][Hide abstract] ABSTRACT: Purpose:
The decision to enroll in a clinical trial is complex given the uncertain risks and benefits of new approaches. Many patients also have financial concerns. We sought to characterize the association between financial concerns and the quality of decision making about clinical trials.
We conducted a secondary data analysis of a randomized trial of a Web-based educational tool (Preparatory Education About Clinical Trials) designed to improve the preparation of patients with cancer for making decisions about clinical trial enrollment. Patients completed a baseline questionnaire that included three questions related to financial concerns (five-point Likert scales): "How much of a burden on you is the cost of your medical care?," "I'm afraid that my health insurance won't pay for a clinical trial," and "I'm worried that I wouldn't be able to afford the costs of treatment on a clinical trial." Results were summed, with higher scores indicating greater concerns. We used multiple linear regressions to measure the association between concerns and self-reported measures of self-efficacy, preparation for decision making, distress, and decisional conflict in separate models, controlling for sociodemographic characteristics.
One thousand two hundred eleven patients completed at least one financial concern question. Of these, 27% were 65 years or older, 58% were female, and 24% had a high school education or less. Greater financial concern was associated with lower self-efficacy and preparation for decision making, as well as with greater decisional conflict and distress, even after adjustment for age, race, sex, education, employment, and hospital location (P < .001 for all models).
Financial concerns are associated with several psychological constructs that may negatively influence decision quality regarding clinical trials. Greater attention to patients' financial needs and concerns may reduce distress and improve patient decision making.
Preview · Article · Dec 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option.
Patients and methods:
A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials.
Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone.
These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving knowledge and reducing attitudinal barriers.
No preview · Article · Dec 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Importance:
Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association.
To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States.
Design, setting, and participants:
Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment.
Main outcomes and measures:
Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors.
The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P < .001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P < .001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P < .001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P < .001) and II (HR, 1.09; 95% CI, 1.05-1.13; P < .001) only, after adjusting for demographic, tumor, and treatment factors.
Conclusions and relevance:
Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.
[Show abstract][Hide abstract] ABSTRACT: Background: Conflicting data exist on the benefit of chemotherapy in the management of high-risk soft tissue sarcoma (STS). Use of chemotherapy may be dependent on patient, tumor, and facility characteristics. This study sought to identify these factors and compare survival between treatment groups. Patients and Methods: Patients with stage III STS were identified from the National Cancer Data Base (NCDB) from 1998 to 2012. Multiple logistic regression analysis was used to determine factors that influenced the probability of receiving chemotherapy. In a subset of patients, we determined the relationship between chemotherapy use and overall survival, using Kaplan-Meier curves and Cox regression analysis with propensity score adjustment. We also examined the effect of chemotherapy by histologic subgroup using interaction models. Results: A total of 16,370 patients were included (N = 5,377 for survival analysis). Patients who were younger than 40 years; male; yprivately insured; earned a higher income; had no comorbidities; had synovial sarcoma, angiosarcoma or "other" histology; and whose tumors were high-grade, greater than 10 cm, or from the lower extremity were significantly more likely to receive chemotherapy. Median unadjusted overall survival (OS) in the nonchemotherapy and chemotherapy groups was 51.3 and 82.7 months, respectively (P < .001). On adjusted analysis, the survival benefit remained significant (hazard ratio [HR], 0.85; P = .004). The benefit was particularly strong in the undifferentiated pleomorphic sarcoma (UPS) group on adjustment, with a median OS of 49.1 and 77.8 months for nonchemotherapy versus chemotherapy, respectively (HR, 0.77; P = .02). Conclusions: In addition to expected tumor and patient factors, histology, location of primary tumor, and socioeconomic status are associated with receipt/nonreceipt of chemotherapy in stage III STS. Chemotherapy use was associated with improved OS in the overall population, and specifically in the UPS subgroup. (J Natl Compr Canc Netw 2015;13:1366-1374)
No preview · Article · Nov 2015 · Journal of the National Comprehensive Cancer Network: JNCCN
[Show abstract][Hide abstract] ABSTRACT: Risk assessment for prostate cancer is challenging due to its genetic heterogeneity. In this study, our goal was to develop an operational framework to select and evaluate gene variants that may contribute to familial prostate cancer risk. Drawing on orthogonal sources, we developed a candidate list of genes relevant to prostate cancer, then analyzed germline exomes from 12 case-only prostate cancer patients from high-risk families to identify patterns of protein-damaging gene variants. We described an average of 5 potentially disruptive variants in each individual and annotated them in the context of public databases representing human variation. Novel damaging variants were found in several genes of relevance to prostate cancer. Almost all patients had variants associated with defects in DNA damage response. Many also had variants linked to androgen signaling. Treatment of primary T-lymphocytes from these prostate cancer patients versus controls with DNA damaging agents showed elevated levels of the DNA double strand break (DSB) marker γH2AX (p < 0.05), supporting the idea of an underlying defect in DNA repair. This work suggests the value of focusing on underlying defects in DNA damage in familial prostate cancer risk assessment and demonstrates an operational framework for exome sequencing in case-only prostate cancer genetic evaluation.
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.
OBJECTIVE:To identify mutation-specific cancer risks for carriers of BRCA1/2.
DESIGN, SETTING, AND PARTICIPANTS:Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.
EXPOSURES:Mutations of BRCA1 or BRCA2.
MAIN OUTCOMES AND MEASURES: Breast and ovarian cancer risks.
RESULTS:Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.
CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.
Full-text · Article · Apr 2015 · JAMA The Journal of the American Medical Association
[Show abstract][Hide abstract] ABSTRACT: Little is known about the impact of genetic and environmental risk assessment (GERA) feedback on colorectal cancer (CRC) screening. In a recently completed randomized trial, primary care patients received GERA feedback based on a blood test for genetic polymorphisms and serum folate level (GERA Group) versus usual care (Control Group). Subsequently, participants were offered CRC screening. Among participants who received GERA feedback, being at elevated risk was negatively associated with prospective CRC screening adherence. Secondary analyses of data from this study were performed to identify independent predictors of adherence among participants who received GERA feedback. We obtained baseline survey, follow-up survey, and endpoint medical records data on sociodemographic background, knowledge, psychosocial characteristics, risk status, and adherence for 285 GERA Group participants. Univariate and multivariable analyses were performed to identify predictors of CRC screening adherence. Following a 6-month outcomes observation period, we also conducted two focus groups with GERA Group participants to assess their perceptions of GERA risk feedback and screening. Content analyses of focus group data were evaluated to gain insights into participant response to risk feedback. Overall, half of GERA Group participants adhered to screening within 6 months after randomization. Multivariable analyses showed a statistically significant interaction between race and GERA feedback status relative to screening adherence (p = 0.043). Among participants who received average risk feedback, adherence was comparable among whites (49.7 %) and nonwhites (54.1 %); however, among those at elevated risk, adherence was substantially higher among whites (66.7 %) compared to nonwhites (33.3 %). Focus group findings suggest that whites were more likely than nonwhites to view elevated risk feedback as a prompt to screen. In response to receiving elevated risk feedback, nonwhites were more likely than whites to report feeling anxiety about the likelihood of being diagnosed with CRC. Further research is needed to explore race-related CRC screening differences in response to GERA feedback.
No preview · Article · Mar 2015 · Journal of Behavioral Medicine
[Show abstract][Hide abstract] ABSTRACT: Results: Overall screening rates for CRC did not statistically significantly differ between the usual care (35.7%) and GERA (33.1%) groups. After adjustment for baseline participant factors, the odds ratio for screening completion for GERA versus usual care was 0.88 (95% CI, 0.64 to 1.22). Within the GERA group, screening rates did not significantly differ between average-risk (38.1%) and elevated-risk (26.9%) participants. Odds ratios for elevated- versus average-risk participants remained nonsignificant after adjustment for covariates (odds ratio, 0.75 [CI, 0.39 to 1.42]). Limitation: Only 1 personalized genetic and environmental interaction and 1 health behavior (CRC screening) were assessed.
No preview · Article · Oct 2014 · Annals of internal medicine
[Show abstract][Hide abstract] ABSTRACT: Objective:
This article describes the rigorous development process and initial feedback of the PRE-ACT (Preparatory Education About Clinical Trials) web-based- intervention designed to improve preparation for decision making in cancer clinical trials.
The multi-step process included stakeholder input, formative research, user testing and feedback. Diverse teams (researchers, advocates and developers) participated including content refinement, identification of actors, and development of video scripts. Patient feedback was provided in the final production period and through a vanguard group (N=100) from the randomized trial.
Patients/advocates confirmed barriers to cancer clinical trial participation, including lack of awareness and knowledge, fear of side effects, logistical concerns, and mistrust. Patients indicated they liked the tool's user-friendly nature, the organized and comprehensive presentation of the subject matter, and the clarity of the videos.
The development process serves as an example of operationalizing best practice approaches and highlights the value of a multi-disciplinary team to develop a theory-based, sophisticated tool that patients found useful in their decision making process. Practice implications Best practice approaches can be addressed and are important to ensure evidence-based tools that are of value to patients and supports the usefulness of a process map in the development of e-health tools.