Patient activation reduces effects of implicit bias on doctor-patient interactions.

Disparities between Black and White Americans persist in medical treatment and health outcomes. One reason is that physicians sometimes hold implicit racial biases that favor White (over Black) patients. Thus, disrupting the effects of physicians' implicit bias is one route to promoting equitable health outcomes. In the present research, we tested a potential mechanism to short-circuit the effects of doctors' implicit bias: patient activation, i.e., having patients ask questions and advocate for themselves. Specifically, we trained Black and White standardized patients (SPs) to be "activated" or "typical" during appointments with unsuspecting oncologists and primary care physicians in which SPs claimed to have stage IV lung cancer. Supporting the idea that patient activation can promote equitable doctor-patient interactions, results showed that physicians' implicit racial bias (as measured by an implicit association test) predicted racially biased interpersonal treatment among typical SPs (but not among activated SPs) across SP ratings of interaction quality and ratings from independent coders who read the interaction transcripts. This research supports prior work showing that implicit attitudes can undermine interpersonal treatment in medical settings and provides a strategy for ensuring equitable doctor-patient interactions.

Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019.

BACKGROUND: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). FINDINGS: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration. CONCLUSIONS: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

Patient characteristics associated with delayed time to adjuvant chemotherapy among women treated for stage I-IIIA breast cancer.

For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression.

Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system.

PURPOSE: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. METHODS: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. RESULTS: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. CONCLUSION: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.

The landscape of use of NCCN-guideline chemotherapy regimens in stage I-IIIA breast cancer in an integrated healthcare delivery system.

PURPOSE: The National Comprehensive Cancer Network (NCCN) guidelines recommend a variety of drug combinations with specific administration schedules for the treatment of early-stage breast cancer, allowing physicians to deliver treatments recognizing individual patient complexities, including comorbidities, and patient-physician preference. While use of guideline regimens has shifted over time, there is little data to describe changes in how treatment for early-stage breast cancer has evolved over time. METHODS: In a cohort of 34,109 women treated for stage I-IIIA breast cancer between 2006-2019 at Kaiser Permanente Northern California and Kaiser Permanente Washington, we present the changes in chemotherapy regimens over time, and explore use of NCCN-guideline regimens (GR), guideline regimens used when said regimens were not included in guidelines, referred to as time-discordant regimens (TDR), and non-guideline regimens (NGR). Results are presented by drug combination and over time. RESULTS: Among 12,506 women receiving chemotherapy, 77.4% (n = 9681) received GRs, 9.1% (n = 1140) received TDRs, and 13.5% (n = 1685) received NGRs. In 2006, AC-T (cyclophosphamide-doxorubicin, paclitaxel) was the most common regimen, with TC (cyclophosphamide-docetaxel) becoming the most prevalent by 2019. NGRs were more common in cyclophosphamide-methotrexate-5-fluorouracil (CMF); cyclophosphamide-doxorubicin-paclitaxel-trastuzumab (ACTH); and paclitaxel-trastuzumab (TH). The use of GR has increased over time (p-trend < 0.001), while use of NGR (both in terms of administration schedule and drug combination) and TDR have decreased, although patterns vary by drug combination. CONCLUSION: Chemotherapy delivery has changed markedly over time, with a move toward more use of GR. These data are important for understanding the landscape of chemotherapy delivery in community healthcare settings.

Impact of barriers and motivators on intention and confidence to undergo hereditary cancer genetic testing.

Genetic testing for hereditary cancer syndromes can provide lifesaving information allowing for individualized cancer screening, prevention, and treatment. However, the determinants, both barriers and motivators, of genetic testing intention are not well described. A survey of barriers and motivators to genetic testing was emailed to adult patients eligible for genetic testing based on cancer diagnosis who previously have not had genetic testing (n = 201). Associations between barriers/motivators with testing intention and confidence were examined first by correlation followed by multivariable linear regression model holding constant potential covariates. Seven barrier items from two domains (logistics and genetic testing knowledge) were found to significantly negatively correlate with genetic testing intention. Unexpectedly, three barrier items had significant positive correlation with genetic testing intention; these were related to family worry (passing a condition on to future generations) and testing knowledge (needing more information on the genetic testing process and what it has to offer). Ten barrier items had significant negative correlation with confidence to get a genetic test and encompassed four domains: stigma, insurance/genetic discrimination, knowledge, and cost. All motivator items were associated with intention to get a genetic test, while none were associated with confidence. Multivariable analysis yielded six total barriers (five from the knowledge domain, one from cost domain) and two motivators (relieved to know and treatment impact) that were significantly associated with genetic testing intention or confidence when controlling for demographic characteristics. These findings indicate the need for tailored interventions to amplify motivating factors and counter-message barriers to enhance patient motivation and confidence to undergo testing.

Methodologic Approaches for Using Electronic Medical Records to Identify Experiences of Violence in Transgender and Cisgender People: Closing the Gap Between Diagnostic Coding and Lived Experiences.

BACKGROUND: Transgender people experience extreme rates of violence and the electronic medical record (EMR) remains a mostly untapped resource to study the medical sequelae of such experiences. OBJECTIVES: To develop and test a method for identifying experiences of violence using EMR data. RESEARCH DESIGN: Cross-sectional study utilizing EMR data. PEOPLE: Transgender and cisgender people seen at a regional referral center in Upstate New York. MEASURES: We tested the utility of keyword searches and structured data queries to identify specific types of violence at various ages and in various contexts among cohorts of transgender and cisgender people. We compared the effectiveness of keyword searches to diagnosis codes and a screening question, "Are you safe at home?" using McNemar's test. We compared the prevalence of various types of violence between transgender and cisgender cohorts using the χ 2 test of independence. RESULTS: Of the transgender cohort, 47% had experienced some type of violence versus 14% of the cisgender cohort (χ 2P value <0.001). Keywords were significantly more effective than structured data at identifying violence among both cohorts (McNemar P values all <0.05). CONCLUSIONS: Transgender people experience extreme amounts of violence throughout their lives, which is better identified and studied using keyword searches than structured EMR data. Policies are urgently needed to stop violence against transgender people. Interventions are also needed to ensure safe documentation of violence in EMRs to improve care across settings and aid research to develop and implement effective interventions.

Experiences of Transgender People Reviewing Their Electronic Health Records, a Qualitative Study.

BACKGROUND: The 21st Century Cures Act and the OpenNotes movement have brought patients immediate access to their electronic health records (EHRs). The experiences of marginalized people, including transgender people, accessing and reviewing their EHRs could inform documentation guidelines to improve patient-clinician rapport and reduce harm. OBJECTIVE: To investigate the experiences of transgender people reviewing EHRs. DESIGN: Qualitative study using community-engaged research and an interpretive description methodology. Participants were recruited via social media, snowball sampling was employed, and purposive sampling was used to ensure diversity in terms of age, race/ethnicity, and other factors. In focus groups, participants were asked to discuss their experiences reviewing their EHRs and, for those participants who were clinicians, their experiences reviewing other clinicians' documentation. PARTICIPANTS: Thirty transgender adults aged 20 to 67 years, including 10 clinicians. APPROACH: Digital audio-recordings of focus groups were transcribed verbatim. Content was analyzed to identify emerging essential elements and analysis was continued until no new themes emerged (i.e., saturation). KEY RESULTS: Four themes were noted. (1) Using the wrong name, pronoun, or gender marker for patients is common in the EHR, erodes trust, and causes trauma. (2) Various aspects of clinicians' notes contradict, blame, or stigmatize patients, across multiple axes of oppression. (3) Limitations of EHR capabilities create barriers to quality care. (4) Certain medical customs set the stage for marginalizing, objectifying, and pathologizing transgender people. CONCLUSIONS: Transgender people experience harm via various aspects of EHR documentation, suggesting that changes must be made to improve patient-clinician relationships and reduce ill-effects for patients.

Transgender People's Experiences Sharing Information With Clinicians: A Focus Group-Based Qualitative Study.

PURPOSE: Investigating transgender people's experiences sharing health information in clinical encounters may yield insights for family medicine clinicians. METHODS: This was a qualitative study using a community-based participatory research approach and interpretive description methodology. Seven qualitative focus groups were conducted with 30 transgender adults living in North America. We used purposive sampling to ensure diversity. The focus groups were transcribed verbatim, and 2 investigators independently reviewed and coded each transcript, then they mutually reviewed the transcripts, reconciled their coding, and summarized the codes into themes. Themes were reviewed with community members, participants, and uninvolved clinically oriented investigators for member checking and peer debriefing. RESULTS: Four themes were noted: (1) transgender people often perceive clinicians' questions as voyeuristic, stigmatizing, or self-protective; (2) patients describe being pathologized, denied or given substandard care, or harmed when clinicians learned they are transgender; (3) transgender people frequently choose between risking stigma when sharing information and risking ineffective clinical problem solving if clinicians do not have all the information about their medical histories; (4) improving the safety of transgender people is difficult in the context of contemporary medical systems. CONCLUSIONS: Transgender people often must choose between stigma and potentially suboptimal care. Improvements in medical culture, policies, procedures, and data collection tools are necessary to improve the quality and safety of clinical care for transgender people. Institutional and systems changes may be required to safely and effectively implement sexual orientation and gender identity (SOGI) data collection in clinical settings.

Examining the effects of physician burnout on pain management for patients with advanced lung cancer.

PURPOSE: Physician burnout is generally associated with worse clinical outcomes. The purpose of this study is to examine the effects of physician burnout on the quality of physicians' pain assessment and opioid prescribing for patients with advanced lung cancer. Moreover, we test whether these relationships are moderated by patient-level factors, such as patient race and activation level, that have a demonstrated impact on clinical encounters. METHODS: We conducted a secondary analysis of data from a multisite randomized field experiment. From 2012 to 2016, 96 primary care physicians and oncologists who treated solid tumors were recruited from hospitals and medical sites in three small metropolitan and rural areas in the USA. Physicians saw two unannounced standardized patients who presented with advanced lung cancer. Standardized patients varied across race (Black or White) and activation level (activated, typical). Visits were audio recorded and transcribed. Pain management was evaluated by the quality of pain assessment and opioid prescribing during these visits. RESULTS: Mixed-effects linear regression and generalized mixed-effects modeling showed that higher levels of burnout were associated with a greater likelihood of prescribing an opioid and prescribing stronger opioid doses for patients. These effects were not moderated by patient race or activation level. CONCLUSION: Findings from this work inform our understanding of physician-level factors that impact clinical decision-making in the context of cancer pain management. Specifically, this study identifies the role of physician burnout on the quality of prescribing for patients with advanced lung cancer.

Muscle mass affects paclitaxel systemic exposure and may inform personalized paclitaxel dosing.

AIMS: Patients with low muscle mass have increased risk of paclitaxel-induced peripheral neuropathy, which is dependent on systemic paclitaxel exposure. Dose optimization may be feasible through the secondary use of radiologic data for body composition. The objective of this study was to interrogate morphomic parameters as predictors of paclitaxel pharmacokinetics to identify alternative dosing strategies that may improve treatment outcomes. METHODS: This was a secondary analysis of female patients with breast cancer scheduled to receive 80 mg/m2 weekly paclitaxel infusions. Paclitaxel was measured at the end of initial infusion to estimate maximum concentration (Cmax ). Computed tomography (CT) scans were used to measure 29 body composition features for inclusion in pharmacokinetic modelling. Monte Carlo simulations were performed to identify infusion durations that limit the probability of exceeding Cmax > 2885 ng/mL, which was selected based on prior work linking this to an unacceptable risk of peripheral neuropathy. RESULTS: Thirty-nine patients were included in the analysis. The optimal model was a two-compartment pharmacokinetic model with T11 skeletal muscle area as a covariate of paclitaxel volume of distribution (Vd). Simulations suggest that extending infusion of the standard paclitaxel dose from 1 hour to 2 and 3 hours in patients who have skeletal muscle area 4907-7080 mm2 and <4907 mm2 , respectively, would limit risk of Cmax > 2885 ng/mL to <50%, consequently reducing neuropathy, while marginally increasing overall systemic paclitaxel exposure. CONCLUSION: Extending paclitaxel infusion duration in ~25% of patients who have low skeletal muscle area is predicted to reduce peripheral neuropathy while maintaining systemic exposure, suggesting that personalizing paclitaxel dosing based on body composition may improve treatment outcomes.

Motivational interviewing for genetic counseling: A unified framework for persuasive and equipoise conversations.

Genetic counselors (GCs) have traditionally been trained to adopt a position of equipoise or clinical neutrality. They provide information, answer questions, address barriers, and engage in shared decision-making, but generally, they do not prescribe a genetic test. Historically, GCs have generally been trained not to persuade the ambivalent or resistant patient. More recently, however, there has been discussion regarding when a greater degree of persuasion or directionality may be appropriate within genetic counseling (GC) and what role MI may play in this process. The role for "persuasive GC" is based on the premise that some genetic tests provide actionable information that would clearly benefit patients and families by impacting treatment or surveillance. For other tests, the benefits are less clear as they do not directly impact patient care or the benefits may be more subjective in nature, driven by patient values or psychological needs. For the former, we propose that GCs may adopt a more persuasive clinical approach while for the latter, a more traditional equipoise stance may be more appropriate. We suggest that motivational interviewing (MI) could serve as a unifying counseling model that allows GCs to handle both persuasive and equipoise encounters. For clearly beneficial tests, while directional, the MI encounter can still be non-directive, autonomy-supportive, and patient-centered. MI can also be adapted for equipoise situations, for example, placing less emphasis on eliciting and strengthening change talk as that is more a behavior change strategy than a shared decision-making strategy. The core principles and strategies of MI, such as autonomy support, evocation, open questions, reflective listening, and affirmation would apply to both persuasive and equipoise encounters. Key issues that merit discussion include how best to train GCs both during their initial and post-graduate education.

Improving the delivery of team-based survivorship care after primary breast cancer treatment through a multi-level intervention: a pilot randomized controlled trial.

PURPOSE: We developed and tested a multi-level intervention, ConnectedCancerCare (CCC), which includes a tailored website and appointment reminder system for women with early-stage breast cancer and a provider summary letter sent to their medical oncologist and primary care provider to improve the delivery of team-based survivorship care. METHODS: We conducted a pilot randomized controlled trial to establish the feasibility and acceptability of CCC. Women diagnosed with stages 0-II breast cancer within one year of completing primary treatment were randomized to CCC (intervention) or a static online survivorship care plan (control). Participants completed baseline and 3-month follow-up surveys online. Post-trial interviews with 5 PCPs, 6 oncology providers, and 8 intervention patients were conducted. RESULTS: Of the 160 eligible women invited to participate, 66 completed the baseline survey and were randomized (41%) and 54 completed a follow-up survey (83%). Participants in the intervention arm found the CCC content to be acceptable, with 82% reporting it was easy to use and 86% reporting they would recommend it to other patients. Women randomized to CCC (vs. control) more often reported scheduling a PCP follow-up visit (64% vs. 42%), communicating with their PCP about provider roles (67% vs. 18%), and higher mean team-based cancer care knowledge scores (3.7 vs. 3.4). CONCLUSION: Deploying CCC in medical oncology practices was feasible, and the intervention content was acceptable. CCC shows promise for improving patient knowledge and patient-provider communication about provider roles in team-based cancer care and encouraging patients to engage with their PCP early in the survivorship period.

Improving the predictive value of bioaccessibility assays and their use to provide mechanistic insights into bioavailability for toxic metals/metalloids - A research prospectus.

Widespread contamination of soil, dust, and food with toxic metal(loid)s pose a significant public health concern. Only a portion of orally ingested metal(loid) contaminants are bioavailable, which is defined as the fraction of ingested metal(loid)s absorbed across the gastrointestinal barrier and into systemic circulation. Bioaccessibility tools are a class of in vitro assays used as a surrogate to estimate risk of oral exposure and bioavailability. Although development and use of bioaccessibility tools have contributed to our understanding of the factors influencing oral bioavailability of metal(loid)s, some of these assays may lack data that support their use in decisions concerning adverse health risks and soil remediation. This review discusses the factors known to influence bioaccessibility of metal(loid) contaminants and evaluates experimental approaches and key findings of SW-846 Test Method 1340, Unified BARGE Method, Simulated Human Intestinal Microbial Ecosystem, Solubility Bioaccessibility Research Consortium assay, In Vitro Gastrointestinal model, TNO-Gastrointestinal Model, and Dutch National Institute for Public Health and the Environment bioaccessibility models which are used to assess oral absolute bioavailability and relative bioavailability in solid matrices. The aim of this review was to identify emerging knowledge gaps and research needs with an emphasis on research required to evaluate these models on (1) standardization of assay techniques and methodology, and (2) use of common criteria for assessing the performance of bioaccessibility models.

Clinical and sociodemographic factors associated with anticoagulant use for cancer associated venous thromboembolism.

Cancer associated thrombosis (CAT) is a leading cause of death among patients with cancer. It is not clear if non-clinical factors are associated with anticoagulation receipt. We conducted a retrospective cohort study of Optum's de-identified Clinformatics® Database of adults with cancer diagnosed between 2009 and 2016 who developed CAT, treated with an outpatient anticoagulant (warfarin, low molecular weight heparin (LMWH), or a direct oral anticoagulant (DOAC)). Of 12,622 patients, three months after an episode of CAT, 1,485 (12%) were on LMWH, 1,546 (12%) on DOACs, and 9,591 (76%) were on warfarin. When controlling for other factors, anticoagulant use was significantly associated with socioeconomic factors, region, co-morbidities, type of thrombosis, and cancer subtype. Patients with a bachelor's degree or greater level of education were less likely to receive warfarin (OR: 0.77; 95% CI: [0.59, 0.99]; p < 0.046) or DOACs (OR: 0.67; 95% CI: [0.55, 0.82]; p < 0.001) compared to LMWH. Patients with higher income levels were more likely to receive LMWH or DOACs compared to warfarin, while patients across all income levels were equally likely to receive LMWH or DOACs. Non-clinical factors including income, education, and region, are associated with anticoagulation receipt three months after an episode of CAT. Sociodemographic factors may result in some patients receiving suboptimal care and contribute to non-guideline concordant care for CAT.

Factors Associated With Job Satisfaction in Medical Oncology Practices: Results From a Multisite Survey.

OBJECTIVE: The aim of this study was to examine the factors influencing job satisfaction of nurses, physicians, and advanced practice providers in ambulatory oncology settings. BACKGROUND: Job satisfaction is essential to clinician well-being and quality of care. METHODS: In 2017, clinicians from 29 ambulatory medical oncology practices completed anonymous paper questionnaires that examined job satisfaction, clinician-to-clinician communication, and perceptions of patient safety. Linear regression, adjusted for clustered observations, examined the relationship between job satisfaction, clinician communication, and patient safety perceptions. RESULTS: Of 280 respondents (response rate of 68%), 85% reported that they were satisfied or very satisfied with their current position. Patient safety and accuracy of clinician communication were positively and significantly associated with job satisfaction. CONCLUSIONS: Although most surveyed clinicians were satisfied, 15% were dissatisfied and reported communication and safety concerns. Leadership efforts to strengthen clinician communication actions and develop positive safety cultures are promising strategies to promote clinician well-being and high-quality cancer care.

Vitamin D deficiency increases severity of paclitaxel-induced peripheral neuropathy.

PURPOSE: Approximately 25% of patients receiving weekly paclitaxel for breast cancer require treatment disruptions to avoid severe, irreversible peripheral neuropathy (PN). Vitamin insufficiencies are PN risk factors in many diseases, but their relevance to chemotherapy-induced PN is unknown. METHODS: We investigated whether baseline insufficiency of vitamin D, vitamin B12, folate, or homocysteine increased PN in patients with breast cancer receiving weekly paclitaxel in a retrospective analysis of a prospective observational study. Patient-reported PN was collected at baseline and during treatment on the Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (CIPN20). The primary analysis tested associations between vitamin deficiency and the maximum increase from baseline in the CIPN20 sensory subscale (ΔCIPN8). Secondary analyses tested for association with PN-induced treatment disruptions and adjusted associations for treatment and clinical variables. RESULTS: 25-hydroxy-vitamin D was the only nutrient with sufficient deficiency (< 20 ng/mL) for analysis (15/37 = 41%). Vitamin D-deficient patients had a greater mean PN increase than non-deficient patients (ΔCIPN8 ± SD, 36 ± 23 vs. 16 ± 16, p = 0.003) and a non-significant, approximately threefold increase in risk of treatment disruption (OR 2.98, 95% CI [0.72, 12.34], p = 0.16). In multivariable models adjusted for clinical and treatment variables, baseline vitamin D level was inversely associated with PN (ß = - 0.04, p = 0.02). CONCLUSION: Pre-treatment vitamin D deficiency was associated with PN in women receiving weekly paclitaxel for breast cancer. Vitamin D deficiency may be an easily detected PN risk factor that could be resolved prior to treatment to prevent PN, avoid treatment disruptions, and improve treatment outcomes.

Genetic variation in EPHA contributes to sensitivity to paclitaxel-induced peripheral neuropathy.

AIMS: Chemotherapy-induced peripheral neuropathy (PN) is a treatment limiting toxicity of paclitaxel. We evaluated if EPHA genetic variation (EPHA4, EPHA5, EPHA6, and EPHA8) is associated with PN sensitivity by accounting for variability in systemic paclitaxel exposure (time above threshold). METHODS: Germline DNA from 60 patients with breast cancer was sequenced. PN was measured using the 8-item sensory subscale (CIPN8) of the patient-reported CIPN20. Associations for 3 genetic models were tested by incorporating genetics into previously published PN prediction models integrating measured paclitaxel exposure and cumulative treatment. Significant associations were then tested for association with PN-related treatment disruption. RESULTS: EPHA5 rs7349683 (minor allele frequency = 0.32) was associated with increased PN sensitivity (ß-coefficient = 0.39, 95% confidence interval 0.11-0.67, p = 0.007). Setting a maximum tolerable threshold of CIPN8 = 30, optimal paclitaxel exposure target is shorter for rs7349683 homozygous (11.6 h) than heterozygous (12.6 h) or wild-type (13.6 h) patients. Total number of missense variants (median = 0, range 0-2) was associated with decreased PN sensitivity (ß-coefficient: -0.42, 95% confidence interval -0.72 to -0.12, P = .006). No association with treatment disruption was detected for the total number of missense variants or rs7349683. CONCLUSION: Isolating toxicity sensitivity by accounting for exposure is a novel approach, and rs7349683 represents a promising marker for PN sensitivity that may be used to individualize paclitaxel treatment.

Partnered status and receipt of guideline-concordant adjuvant chemotherapy among patients with colon cancer.

BACKGROUND: Partnered status is an independent predictor of clinical outcomes, including overall survival, among patients with cancer. However, the mechanisms by which partnered status impacts survival are not fully understood and to the authors' knowledge the associations between partnered status and the specific attributes of chemotherapy have not been studied to date. METHODS: The current study was an observational study of patients with resected American Joint Committee on Cancer (AJCC) stage III colon cancer diagnosed from 2008 through 2015 and recruited from an academic cancer center and 2 large community oncology practices. Outcome measures were specific attributes of adjuvant chemotherapy. Partnered status (partnered vs unpartnered) was the primary independent variable. Bivariate comparisons between independent variables and the primary outcomes were performed. Associations between partnered status and the outcomes also were analyzed using multivariable generalized estimating equations using a logit link. RESULTS: Data were collected from 436 patients. Of these patients, approximately 65% were from community oncology practices. Approximately 62% were partnered (married or living with a partner), and approximately 86% received adjuvant chemotherapy. Among these individuals, 87% received multiagent chemotherapy and 65% completed 6 months of therapy. Partnered patients were found to have a higher odds of completing chemotherapy (odds ratio, 1.98; 95% CI, 1.04-3.77). CONCLUSIONS: In this innovative investigation of the associations between partnered status and specific attributes of curative-intent chemotherapy, approximately 35% of patients terminated chemotherapy early. Having a partner increased the odds of completing therapy, which may be one mechanism through which having a partner improves disease-specific outcomes among patients with colon cancer. Identifying those aspects of partner support that can be reproduced with community or clinical personnel may help unpartnered patients to complete the recommended course of curative-intent chemotherapy.

Factors influencing the use of extended adjuvant endocrine therapy.

PURPOSE: Extending adjuvant endocrine therapy (ET) beyond 5 years has been shown to improve outcomes in breast cancer; however, limited data are available about if and why women pursue extended ET. The primary objective was to estimate the proportion of women who were willing to receive extended ET if recommended by their physician and secondarily, to determine what factors were associated with this decision. METHODS: This descriptive cross-sectional study surveyed 131 women with AJCC 7th Edition stages I-III breast cancer who had been taking adjuvant ET for 3-5 years. The survey inquired about the willingness to continue ET, quality of life (FACT-ES), and beliefs about medications (BMQ). Logistic regression was used to test for associations between clinical and disease factors, FACT-ES, BMQ, and the primary outcome. RESULTS: One hundred and twelve (85%) patients reported "moderate" (n = 30, 23%), "quite a bit" (n = 41, 31%), or "extreme" (n = 41, 31%) willingness to pursue extended ET; 19 (14%) patients were "not at all" or were "unlikely" to be willing to take extended ET. On univariate analysis, lower total and social well-being FACT-ES scores, and lower perceived necessity and higher concerns on BMQ were associated with lower willingness to pursue extended ET. On multivariable analysis, greater patient perception of necessity of ET was the only factor associated with willingness to pursue extended ET (OR 1.34, 95% CI 1.15-1.57, p = 0.0005). CONCLUSIONS: Most women who have taken ET for multiple years report being willing to pursue extended ET if recommended. When discussing extended ET, the data from this study support exploring patients' belief of medication necessity.