The financial burden and distress of patients with cancer: Understanding and stepping-up action on the financial toxicity of cancer treatment.

"Financial toxicity" has now become a familiar term used in the discussion of cancer drugs, and it is gaining traction in the literature given the high price of newer classes of therapies. However, as a phenomenon in the contemporary treatment and care of people with cancer, financial toxicity is not fully understood, with the discussion on mitigation mainly geared toward interventions at the health system level. Although important, health policy prescriptions take time before their intended results manifest, if they are implemented at all. They require corresponding strategies at the individual patient level. In this review, the authors discuss the nature of financial toxicity, defined as the objective financial burden and subjective financial distress of patients with cancer, as a result of treatments using innovative drugs and concomitant health services. They discuss coping with financial toxicity by patients and how maladaptive coping leads to poor health and nonhealth outcomes. They cover management strategies for oncologists, including having the difficult and urgent conversation about the cost and value of cancer treatment, availability of and access to resources, and assessment of financial toxicity as part of supportive care in the provision of comprehensive cancer care. CA Cancer J Clin 2018;68:153-165. © 2018 American Cancer Society.

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.

Impact of reactive changes on multigene testing: histopathologic analysis of low-grade breast cancers with high-risk 21-gene recurrence scores.

PURPOSE: The 21-gene recurrence score (RS) assay predicts the recurrence risk and magnitude of chemotherapy benefit in patients with invasive breast cancer (BC). This study examined low-grade tumors yielding a high-risk RS and their outcomes.Kindly check the edit made in the article titleOk  METHODS: We compared patients with grade 1 BC and a high-risk RS to those with low-risk RS. Histologic sections were reviewed and features reported to elevate the RS were noted, mainly biopsy cavity and reactive stromal changes (BXC). RESULTS: A total of 54 patients had high-risk RS (median RS of 28, range 26-36). On review, BXC were seen in all cases. Thirty BCs in this group also had low to negative PR. Treatment regimens included: chemoendocrine therapy (63%), endocrine therapy alone (31%) and no adjuvant therapy (6%). There were no additional breast cancer events over a median follow-up of 54.0 months (range 6.2 to 145.3). A total of 108 patients had low-risk RS (median RS of 7, range 0-9). BXC were seen in 47% of cases and none were PR negative. One patient had a recurrence at 64.8 months while the rest had no additional events over a median of 68.1 months (2.4 to 100). CONCLUSION: We provide further evidence that reactive stromal changes and/or low-PR scores enhance the elevation of the RS. A high-RS result in low grade, PR-positive BC may not reflect actual risk and any suspected discrepancies should be discussed with the management teams. Multigene testing results should be interpreted after correlation with pathologic findings to optimize patient care.

Optimization of alert notifications in electronic patient-reported outcome (ePRO) remote symptom monitoring systems (AFT-39).

PURPOSE: Clinical benefits result from electronic patient-reported outcome (ePRO) systems that enable remote symptom monitoring. Although clinically useful, real-time alert notifications for severe or worsening symptoms can overburden nurses. Thus, we aimed to algorithmically identify likely non-urgent alerts that could be suppressed. METHODS: We evaluated alerts from the PRO-TECT trial (Alliance AFT-39) in which oncology practices implemented remote symptom monitoring. Patients completed weekly at-home ePRO symptom surveys, and nurses received real-time alert notifications for severe or worsening symptoms. During parts of the trial, patients and nurses each indicated whether alerts were urgent or could wait until the next visit. We developed an algorithm for suppressing alerts based on patient assessment of urgency and model-based predictions of nurse assessment of urgency. RESULTS: 593 patients participated (median age = 64 years, 61% female, 80% white, 10% reported never using computers/tablets/smartphones). Patients completed 91% of expected weekly surveys. 34% of surveys generated an alert, and 59% of alerts prompted immediate nurse actions. Patients considered 10% of alerts urgent. Of the remaining cases, nurses considered alerts urgent more often when patients reported any worsening symptom compared to the prior week (33% of alerts with versus 26% without any worsening symptom, p = 0.009). The algorithm identified 38% of alerts as likely non-urgent that could be suppressed with acceptable discrimination (sensitivity = 80%, 95% CI [76%, 84%]; specificity = 52%, 95% CI [49%, 55%]). CONCLUSION: An algorithm can identify remote symptom monitoring alerts likely to be considered non-urgent by nurses, and may assist in fostering nurse acceptance and implementation feasibility of ePRO systems.

Timing of exercise therapy when initiating adjuvant chemotherapy for breast cancer: a randomized trial.

AIMS: The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer. METHODS AND RESULTS: Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens-concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20-50 min at 55%-100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, -0.88 mL O2·kg-1·min-1; 95% confidence interval (CI): -3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg-1·min-1, P < 0.001). CONCLUSION: There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.

Risk factors for financial toxicity in patients with gynecologic cancer.

BACKGROUND: The cost of cancer care is high and rising. Evidence of increased patient cost burden is prevalent in the medical literature and has been defined as "financial toxicity," the financial hardship and financial concerns experienced by patients because of a disease and its related treatments. With targeted therapies and growing out-of-pocket costs, patient financial toxicity is a growing concern among patients with gynecologic cancer. OBJECTIVE: This study aimed to determine the prevalence of financial toxicity and identify its risk factors in patients with gynecologic cancer treated at a large cancer center using objective data. STUDY DESIGN: Using institutional databases, we identified patients with gynecologic cancer treated from January 2016 to December 2018. Patients with a preinvasive disease were excluded. Financial toxicity was defined according to institutionally derived metrics as the presence of ≥1 of the following: ≥2 bills sent to collections, application or granting of a payment plan, settlement, bankruptcy, financial assistance program enrollment, or a finance-related social work visit. Clinical characteristics were gathered using a 2-year look-back from the time of the first financial toxicity event or a randomly selected treatment date for those not experiencing toxicity. Risk factors were assessed using chi-squared tests. All significant variables on univariate analysis were included in the logistic regression model. RESULTS: Of the 4655 patients included in the analysis, 1155 (25%) experienced financial toxicity. In the univariate analysis, cervical cancer (35%), stage 3 or 4 disease (24% and 30%, respectively), younger age (35% for age <30 years), nonpartnered marital status (31%), Black (45%) or Hispanic (37%) race and ethnicity, self-pay (48%) or commercial insurance (30%), clinical trial participation (31%), more imaging studies (39% for ≥9), ≥1 emergency department visit (36%), longer inpatient stays (36% for ≥20 days), and more outpatient clinician visits (41% for ≥20 visits) were significantly associated with financial toxicity (P<.01). In multivariate analysis, younger age, nonpartnered marital status, Black and Hispanic race and ethnicity, commercial insurance, more imaging studies, and more outpatient physician visits were significantly associated with financial toxicity. CONCLUSION: Financial toxicity is an increasing problem for patients with gynecologic cancer. Our analysis, using objective measures of financial toxicity, has suggested that demographic factors and healthcare utilization metrics may be used to proactively identify at-risk patients for financial toxicity.

Oral Chemotherapy Metric Performance in Quality Oncology Practice Initiative Practices: Updated Trends and Analysis.

BACKGROUND: Oral chemotherapy performance measures were first introduced into ASCO's Quality Oncology Practice Initiative (QOPI) in 2013. This study examined performance on these measures among QOPI-participating practices and evaluated whether it differed among practices based on meeting QOPI Certification Program standards. METHODS: A total of 192 QOPI-participating practices (certified, n=50 [26%]; not certified, n=142 [74%]) reported performance on oral chemotherapy measures in 2017 and 2018. Inclusion was limited to practices reporting on ≥3 charts for ≥1 oral chemotherapy measure. Performance was defined as the percentage of charts examined that adhered to the measure. Descriptive analyses were used to characterize performance within and across practices, and mixed-effects logistic regression models were conducted to compare performance based on certification status. RESULTS: Median performance across practices for the 9 oral chemotherapy measures examined ranged from 44% (education before the start of treatment addressing missed doses, toxicities, and clinical contact instructions [composite measure]) to 100% (documented dose, documented plan, and education about toxicities). Certified practices were more likely to provide education about clinic contact instructions than noncertified practices (odds ratio, 4.87; 95% CI, 1.00-24.0). Performance on all other measures was not significantly associated with certification status. CONCLUSIONS: There is wide variability in quality related to performance on oral chemotherapy measures across all QOPI-participating practices, and several areas were identified in which administration of oral chemotherapy could be improved. Our findings highlight the need for the development and implementation of appropriate standards that apply to oral chemotherapy and address the complexities that set it apart from parenteral treatment.

Effects of patient-reported outcome assessment order.

BACKGROUND: In clinical trials and clinical practice, patient-reported outcomes are almost always assessed using multiple patient-reported outcome measures at the same time. This raises concerns about whether patient responses are affected by the order in which the patient-reported outcome measures are administered. METHODS: This questionnaire-based study of order effects included adult cancer patients from five cancer centers. Patients were randomly assigned to complete questionnaires via paper booklets, interactive voice response system, or tablet web survey. Linear Analogue Self-Assessment, Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, and Patient-Reported Outcomes Measurement Information System assessment tools were each used to measure general health, physical function, social function, emotional distress/anxiety, emotional distress/depression, fatigue, sleep, and pain. The order in which the three tools, and domains within tools, were presented to patients was randomized. Rates of missing data, scale scores, and Cronbach's alpha coefficients were compared by the order in which they were assessed. Analyses included Cochran-Armitage trend tests and mixed models adjusted for performance score, age, sex, cancer type, and curative intent. RESULTS: A total of 1830 patients provided baseline patient-reported outcome assessments. There were no significant trends in rates of missing values by whether a scale was assessed earlier or later. The largest order effect for scale scores was due to a large mean score at one assessment time point. The largest difference in Cronbach's alpha between the versions for the Patient-Reported Outcomes Measurement Information System scales was 0.106. CONCLUSION: The well-being of a cancer patient has many different aspects such as pain, fatigue, depression, and anxiety. These are assessed using a variety of surveys often collected at the same time. This study shows that the order in which the different aspects are collected from the patient is not important.

Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial.

Importance: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene. Objective: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes. Design, Setting, and Participants: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021. Interventions: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care. Main Outcomes and Measures: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available. Results: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P = .02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P = .002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P = .002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P = .009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P = .003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P = .006). Conclusions and Relevance: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03249090.

Work Status Reduction and Cost-Related Nonadherence during Cancer Treatment.

Many cancer patients experience a reduction in work status during cancer treatment. Authors analyzed cross-sectional survey data from U.S. cancer patients and survivors to examine the relationship between reduced work status and cost-related nonadherence, defined as skipping or forgoing medical treatments or medications due to cost. Of 381 respondents who were working at the time of diagnosis, 143 reported a reduction in work status during treatment. Age, racial identity, level of education, and treatment type were associated with reductions in work status. Respondents who reduced work status had higher odds of engaging in cost-related nonadherence than those with stable employment. Authors conclude that reduced work status is associated with nonadherence that can undermine treatment benefit and lead to disease progression. This association is troubling given that African American respondents were more likely to report reduced work status during treatment, potentially exacerbating existing cancer health disparities. To reduce treatment nonadherence, social workers should assess for potential employment problems and be prepared to intervene through counseling, community resource referrals, and direct financial assistance. Social workers should be aware of how structural racism is reproduced through inequitable labor policies and practices that have direct implications for health and access to care.

Neoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic.

PURPOSE: Physician treatment preferences for early stage, estrogen positive breast cancer (ER + BC) patients were evaluated during the initial surge of the COVID-19 pandemic in the US when neoadjuvant endocrine therapy (NET) was recommended to allow safe deferral of surgery. METHODS: A validated electronic survey was administered May-June, 2020 to US medical oncologists (MO), radiation oncologists (RO), and surgeons (SO) involved in clinical trials organizations. Questions on NET use included practice patterns for locoregional management following NET. RESULTS: 114 Physicians from 29 states completed the survey-42 (37%) MO, 14 (12%) RO, and 58 (51%) SO. Before COVID-19, most used NET 'rarely' (49/107, 46%) or 'sometimes' (36, 33%) for ER + BC. 46% would delay surgery 2 months without NET. The preferred NET regimen was tamoxifen for premenopausal and aromatase inhibitor for postmenopausal women. 53% planned short term NET until surgery could proceed. Most recommended omitting axillary lymph node dissection (ALND) for one micrometastatic node after 1, 2, or 3 months of NET (1 month, N = 56/93, 60%; 2 months, N = 54/92, 59%; 3 months, N = 48/90, 53%). With longer duration of NET, omission of ALND decreased, regardless of years in practice, percent of practice in BC, practice type, participation in multidisciplinary tumor board, or number of regional COVID-19 cases. CONCLUSION: More physicians preferred NET for ER + BC during the pandemic, compared with pre-pandemic times. As the duration of NET extended, more providers favored ALND in low volume metastatic axillary disease. The Covid-19 pandemic affected practice of ER + BC; it remains to be seen how this may impact outcomes.

Food Insecurity among Cancer Patients Enrolled in the Supplemental Nutrition Assistance Program (SNAP).

Purpose: Food insecurity, which leads to adverse health outcomes, has even more severe implications for cancer patients. Yet medically underserved cancer patients are more likely to be food insecure than the general population.Methods: This study is a cross-sectional analysis of intake data from patients who participated in the Integrated Cancer Care Access Network (ICCAN). ICCAN is a specialized program that addresses socioeconomic barriers to cancer care among underserved cancer patients in NYC. This study utilized ICCAN data from 2011 to 2017. The USDA food insecurity score, self-reported SNAP receipt, and SNAP eligibility based on household income were compared between SNAP and non-SNAP recipients.Results: 681 patients were assessed for food insecurity. Sixty-nine percent of participants lived in food insecure households. Despite SNAP assistance, most SNAP recipients (68%) were food insecure; 69% of respondents who did not receive SNAP were also food insecure.Conclusions: Underserved cancer patients who receive SNAP are still food insecure, hence at more significant risk for its associated negative outcomes. Supplemental programs for patients with chronic diseases are needed in clinics with large low income populations. SNAP benefits should account for the additional financial burden posed by treatment costs and exceptional circumstances faced by cancer patients.

Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer.

This report describes the rationale, purpose and design of A011801 (CompassHER2 RD), an ongoing prospective, multicenter, Phase III randomized trial. Eligible patients in the United States (US) and Canada with high-risk (defined as ER-negative and/or node-positive) HER2-positive (HER2+) residual disease (RD) after a predefined course of neoadjuvant chemotherapy and HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 and placebo, versus T-DM1 and tucatinib. Patients have also received adjuvant radiotherapy and/or endocrine therapy, if indicated per standard of care guidelines. The primary objective of the trial is to determine if the invasive disease-free survival (iDFS) with T-DM1 plus tucatinib is superior to iDFS with T-DM1 plus placebo; other outcomes of interest include overall survival (OS), breast cancer-free survival (BCFS), distant recurrence-free survival (DRFS), brain metastases-free survival (BMFS) and disease-free survival (DFS). Correlative biomarker, quality of life (QoL) and pharmacokinetic (PK) end points are also evaluated.

Lay abstract In this research study (A011801; CompassHER2 RD), patients with early stage HER2-positive breast cancer who already received treatment with chemotherapy and anti-HER2 targeted therapies followed by surgery are mainly enrolled. If cancer is still present in the breast and/or lymph nodes at the time of surgery, there is a higher risk of a recurrence in the future, and enrollment on A011801 is an option. Usually, if there is tumor remaining after chemotherapy and anti-HER2 targeted therapies, the main treatment is the use of an FDA-approved intravenous drug called T-DM1. Additional treatment may also include radiotherapy and/or medications to block the activity of estrogen. The usual treatment approach reduces the likelihood of breast cancer recurring in the future. This study has been performed to answer the following question: Is the combination of T-DM1 and a newer drug tucatinib better than usual treatment with T-DM1 alone at preventing cancer from returning? Study participants will receive treatment with T-DM1 and placebo (a pill that looks like the study drug but contains no medication) or T-DM1 and tucatinib, for up to 14 cycles, unless their breast cancer returns or the side effects become too severe. Research bloods are taken on study along with standard blood work, and we also request a stored tumor sample from the original biopsy and from the breast cancer surgery for research purposes. Optional Quality of Life Questionnaires are also included in the trial. After the study, participants finish T-DM1 and placebo, or T-DM1 and tucatinib, and their doctor will continue to follow their condition with clinic visits every 6 months for 10 years and watch for side effects and for signs of breast cancer recurring. Clinical Trial Registration: NCT04457596 (ClinicalTrials.gov).

The association between housing and food insecurity among medically underserved cancer patients.

PURPOSE: To assess the prevalence of socioeconomic needs and associations between housing characteristics and food insecurity among low-income cancer patients, among whom housing and food insecurity are particularly prevalent. METHODS: Low-income cancer patients in active treatment (N = 1618) were enrolled in a comprehensive patient navigation program. Food insecurity was assessed using the 18-item US Department of Agriculture US Household Food Security Survey Module. Participants self-reported their need for assistance with housing issues/type of assistance needed, perception of overcrowding, satisfaction with living situation, and household density via a cross-sectional survey. Descriptive analyses, cross-tabulations and tests of proportions, and binary logistic regression were used in data analyses. RESULTS: Seventy percent of patients were food insecure. Housing characteristics associated with food insecurity were homelessness or living in sheltered/supportive housing (83.3% food insecure), renting (71.9%), and homeownership (58.1%; p < .001); living situation satisfaction (not satisfied, 79.4%; somewhat satisfied, 25.6%; very satisfied, 66%; p < .001); need of housing assistance (79.2%; p < .001), and feeling crowded in their living unit (77.6%; p < .05). Associations of living unit type with food insecurity were significant in the binary logistic regression model (renters 1.68 OR, homeless/sheltered housing 2.80 OR vs homeowners). CONCLUSION: The vulnerability to food insecurity of patients in this low-income sample was underlined by the high rates found, and clear associations with housing characteristics of homelessness, housing assistance needs, and feeling overcrowded were identified. These results could help shape priorities around screening patients for nutrition and housing needs and developing interventions to address them.

Dermatologic adverse events related to the PI3Kα inhibitor alpelisib (BYL719) in patients with breast cancer.

PURPOSE: Rash develops in approximately 50% of patients receiving alpelisib for breast cancer, often requiring dose modifications. Here, we describe the clinicopathologic, laboratory, and management characteristics of alpelisib-related dermatologic adverse events (dAEs). METHODS: A single center-retrospective analysis was conducted. Data were abstracted from electronic medical records. RESULTS: A total of 102 patients (mean age 56 years, range 27-83) receiving alpelisib most frequently in combination with endocrine therapy (79, 77.5%) were included. We identified 41 (40.2%) patients with all-grade rash distributed primarily along the trunk (78%) and extremities (70%) that developed approximately within two weeks of treatment initiation (mean 12.8 ± 1.5 days) and lasted one-week (mean duration 7.1 ± 0.8 days). Of 29 patients with documented morphology of alpelisib-related dAEs, 26 (89.7%) had maculopapular rash. Histology showed perivascular and interface lymphocytic dermatitis. All-grade rash correlated with an increase in serum eosinophils from 2.7 to 4.4%, p < 0.05, and prophylaxis with non-sedating antihistamines (n = 43) was correlated with a reduction of grade 1/2 rash (OR 0.39, p = 0.09). Sixteen (84.2%) of 19 patients with grade 3 dAEs resulted in interruption of alpelisib, which were managed with antihistamines, topical and systemic corticosteroids. We did not observe rash recurrence in 12 (75%) patients who were re-challenged. CONCLUSIONS: A maculopapular rash associated with increased blood eosinophils occurs frequently with alpelisib. While grade 3 rash leads to alpelisib therapy interruption, dermatologic improvement is evident with systemic corticosteroids; and most patients can continue oncologic treatment at a maintained or reduced dose upon re-challenge with alpelisib.

Racial disparities in chemotherapy administration for early-stage breast cancer: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to measure the extent to which race is associated with delayed initiation or receipt of inadequate chemotherapy among women with early-stage breast cancer. METHODS: We performed a systematic search of all articles published from January 1987 until June 2017 within four databases: PubMed/Medline, EMBASE, CINAHL, and Cochrane CENTRAL. Eligible studies were US-based and examined the influence of race on chemotherapy delays, cessation, or dose reductions among women with stage I, II, or III breast cancer. Data were pooled using a random effects model. RESULTS: A total of twelve studies were included in the quantitative analysis. Blacks were significantly more likely than whites to have delays to initiation of adjuvant therapy of 90 days or more (OR 1.41, 95% CI 1.06-1.87; X² = 31.05, p < 0.00001; I² = 90%). There was no significant association between race and chemotherapy dosing. Due to overlap between studies assessing the relationship between race and completion of chemotherapy, we conducted two separate analyses. Black patients were significantly more likely to discontinue chemotherapy, however, this was no longer statistically significant when larger numbers of patients with more advanced (stage III) breast cancer were included. CONCLUSIONS: These results suggest that black breast cancer patients experience clinically relevant delays in the initiation of adjuvant chemotherapy more often than white patients, which may in part explain the increased mortality observed among black patients.

Living with chronic pain: perceptions of breast cancer survivors.

PURPOSE: Breast cancer treatments may lead to chronic pain. For some breast cancer survivors (BCS), this experience can develop into the perception of living with chronic pain. The majority of BCS are postmenopausal and have hormone receptor-positive (HR+) breast cancer requiring aromatase inhibitors (AIs). Neither the prevalence nor risk factors associated with the perception of living with chronic pain among this population are well defined. METHODS: We conducted a cross-sectional survey among postmenopausal, HR+ BCS who previously took or were currently taking AIs. The primary outcome was patients' perception of living with chronic pain over the past 6 months. We measured pain and demographic and clinical variables. Multivariable logistic regression analysis was performed to evaluate risk factors associated with the perception of chronic pain. RESULTS: Among 1280 participants, 167 (13%) reported having the perception of living with chronic pain before their breast cancer diagnosis; 426 (34%) reported this perception after completion of non-hormonal cancer treatment. Seventy-eight percent of BCSs reported experiencing at least one type of treatment-related pain within the past 7 days, with 23% experiencing at least three types. The most common types of pain were AI-induced musculoskeletal pain (49%) and pain at the surgery or radiation site (31%). Younger age (< 56), BMI > 25, and the perception of living with chronic pain before diagnosis were risk factors associated with the perception of living with chronic pain. CONCLUSIONS: One in three postmenopausal, HR+ BCS considered themselves to be living with chronic pain. Effective interventions to reduce chronic pain are needed.

A pilot randomized controlled trial of cognitive bias modification to reduce fear of breast cancer recurrence.

BACKGROUND: The most common, persistent concern among survivors of breast cancer is the fear that their disease will return, yet to the authors' knowledge, few interventions targeting fear of cancer recurrence (FCR) have been developed to date. The current pilot study examined the feasibility, acceptability, and preliminary efficacy of a home-delivered cognitive bias modification intervention to reduce FCR. The intervention, called Attention and Interpretation Modification for Fear of Breast Cancer Recurrence (AIM-FBCR), targeted 2 types of cognitive biases (ie, attention and interpretation biases). METHODS: A total of 110 survivors of breast cancer were randomized to receive 8 sessions of 1 of 2 versions of AIM-FBCR or a control condition program. Computer-based assessments of cognitive biases and a self-report measure of FCR were administered before the intervention, after the intervention, and 3 months after the intervention. RESULTS: Improvements in health worries (P = .019) and interpretation biases (rates of threat endorsement [P<.001] and reaction times for threat rejection [P = .007]) were found in those survivors who received AIM-FBCR compared with the control arm. Although only 26% of participants who screened into the study agreed to participate, the trial otherwise appeared feasible and acceptable, with 83% of those who initiated the intervention completing at least 5 of 8 sessions, and 90% reporting satisfaction with the computer-based program used. CONCLUSIONS: The results of the current pilot study suggest the promise of AIM-FBCR in reducing FCR in survivors of breast cancer. Future research should attempt to replicate these findings in a larger-scale trial using a more sophisticated, user-friendly program and additional measures of improvement in more diverse samples. Cancer 2017;123:1424-1433. © 2016 American Cancer Society.

Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST).

BACKGROUND: Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. METHODS: Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. RESULTS: A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test-retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = -0.26; P<.001), and HRQOL, as measured by the FACT-G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49). CONCLUSIONS: The COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient-centered outcome. Cancer 2017;123:476-484. © 2016 American Cancer Society.

Provider Differences in Use of Implanted Ports in Older Adults With Cancer.

BACKGROUND: Identifying unwarranted variation in health care can highlight opportunities to reduce harm. One often discretionary process in oncology is use of implanted ports to administer intravenous chemotherapy. While there are benefits, ports carry risks. This study's objective was to assess provider-driven variation in port use among cancer patients receiving chemotherapy. RESEARCH DESIGN: Retrospective assessment using population-based SEER-Medicare data to assess differences in port use across health care providers of older adults with cancer. Participants included over 18,000 patients ages 66 and older diagnosed with breast, colorectal, lung, or pancreatic cancer in 2005-2007, treated by approximately 2900 providers. We identified port use for patients receiving treatment from hospital outpatient facilities versus physicians' offices. Our main analysis assessed the likelihood of a patient receiving a port given port use by the provider's last patient. For a subset of high-use providers, we examined individual provider-level variation by estimating the risk-adjusted likelihood of insertion. RESULTS: Patients receiving chemotherapy in hospital outpatient facilities were significantly less likely to receive a port than those treated in physicians' offices, with adjusted odds ratios (AOR) varying from 0.50 to 0.75 across cancer sites. Implanting a port was associated with increased likelihood of port insertion in the provider's next patient (AOR varied from 1.71 to 2.25). Significant between-provider variation was found among providers with at least 10 patients. CONCLUSIONS: Our findings support the idea that there is provider-driven variation in the use of ports for chemotherapy administration. This variation highlights an opportunity to standardize practice and reduce unnecessary use.