Trends in utilization of hypofractionated whole breast irradiation (HF-WBI) in triple negative breast cancer (TNBC): a national cancer database (NCDB) analysis.

PURPOSE: We sought to identify trends over time with respect to the use of hypofractionated whole breast irradiation (HF-WBI) in women with triple negative breast cancer (TNBC) in the national cancer database (NCDB). METHODS: Trends in utilization of HF-WBI in women diagnosed with T1-2N0 TNBC in the NCDB between 2008 and 2013 were analyzed. Case-matched luminal A women were used for comparison. Variables included age, race, year of diagnosis, insurance status, income quartile, receipt of neoadjuvant chemotherapy, and institution (academic vs. community). Chi square, logistic regression, and multivariate analysis was performed. RESULTS: Utilization of HF-WBI among the 53,269 TNBC women identified steadily increased from 4.7% in 2008 to 14.0% in 2013 for women with TNBC compared to luminal A cancer whose utilization increased from 7.3 to 23.3% over the same time frame (p < 0.001). On univariate analysis, HF-WBI was associated with increasing age (p < 0.001), Medicare insurance (p < 0.001), race (p = 0.041), diagnosis after 2011 (p < 0.001), higher income quartile (p < 0.001), and treatment at academic institutions (p < 0.001). On multivariate analysis, age (p < 0.001, OR 1.038 per year), income quartile (p = 0.002, OR 1.061 per increase in quartile), treatment at an academic institution (p < 0.001, OR 1.78) significantly increased use of HF-WBI. CONCLUSIONS: Treatment at an academic center and year of diagnosis were most correlated with increased HF-WBI in T1-2N0 TNBC women in the NCDB from 2008 to 2013, followed by increasing age and income. Only 14% of T1-2N0 TNBC women received HF-WBI in 2013. Focus on increased utilization is needed for non-academic centers, lower income, and younger women.

Utilization of hypofractionated whole-breast radiation therapy in patients receiving chemotherapy: a National Cancer Database analysis.

PURPOSE: Results from four major hypofractionated whole-breast radiotherapy (HF-WBRT) trials have demonstrated equivalence in select patients with early-stage breast cancer when compared with conventionally fractionated WBRT (CF-WBRT). Because relatively little data were available on patients receiving neoadjuvant or adjuvant chemotherapy, consensus guidelines published in 2011 did not endorse the use of HF-WBRT in this population. Our goal is to evaluate trends in utilization of HF-WBRT in patients receiving chemotherapy. METHODS AND MATERIALS: We retrospectively analyzed data from 2004 to 2013 in the National Cancer DataBase on breast cancer patients treated with HF-WBRT who met the clinical criteria proposed by consensus guidelines (i.e., age >0 years, T1-2N0, and breast-conserving surgery), regardless of receipt of chemotherapy. We employed logistic regression to delineate and compare clinical and demographic factors associated with utilization of HF-WBRT and CF-WBRT. RESULTS: A total of 56,836 women were treated with chemotherapy and WBRT (without regional nodal irradiation) from 2004 to 2013; 9.0% (n = 5093) were treated with HF-WBRT. Utilization of HF-WBRT increased from 4.6% in 2004 to 18.2% in 2013 (odds ratio [OR] 1.21/year; P < 0.001). Among patients receiving chemotherapy, factors most dramatically associated with increased odds of receiving HF-WBRT on multivariate analysis were academic facilities (OR 2.07; P < 0.001), age >80 (OR 2.58; P < 0.001), west region (OR 1.91; P < 0.001), and distance >50 miles from cancer reporting facility (OR 1.43; P < 0.001). Factors associated with decreased odds of receiving HF-WBRT included white race, income <$48,000, lack of private insurance, T2 versus T1, and higher grade (all P < 0.02). CONCLUSIONS: Despite the absence of consensus guideline recommendations, the use of HF-WBRT in patients receiving chemotherapy has increased fourfold (absolute = 13.6%) over the last decade. Increased utilization of HF-WBRT should result in institutional reports verifying its safety and efficacy.

Increasing utilization of regional nodal irradiation in elderly node-positive women and declining emphasis on demographic factors.

PURPOSE: To evaluate the practice patterns for the use of regional nodal irradiation (RNI) in treatment of elderly women with low volume node-positive breast cancer in the setting of breast conservation surgery (BCS). METHODS: Women aged 70-89 diagnosed with unilateral, pathologic T1-2N1M0 breast cancer from 2004 to 2013, who underwent BCS and received radiotherapy were identified from the National Cancer Database. In 2011, two major trials were presented that helped define indications for RNI. Patients were dichotomized into "early", i.e. diagnosed up to 2010, and "late" cohorts. Patient and treatment characteristics were compared between the cohorts and logistic regression used to determine independent factors associated with the receipt of RNI. RESULTS: 7228 women met inclusion criteria; 4330 (59.9%) in early and 2898 (40.1%) in late cohorts. Utilization of RNI increased from 33.9% in early to 42.5% in late cohorts (P ≤ 0.001) and was independent of a general increase in RNI utilization. RNI in the early and late cohorts was not different between the study population and younger women (P > 0.05). RNI utilization increased in both cohorts with increasing number of positive lymph nodes. In the early cohort, RNI was also associated with higher grade, white race and lower income. In the late cohort, RNI increased with the presence of multiple, predefined risk factors. CONCLUSIONS: There was an increase in utilization of RNI for elderly patients from 2004 to 2013. In more recent years, the primary factors associated with receipt of RNI were tumor related with declining importance of demographic factors.

Factors Influencing Management and Outcome in Patients with Occult Breast Cancer with Axillary Lymph Node Involvement: Analysis of the National Cancer Database.

BACKGROUND: Occult breast cancer (OBC) is rare and optimal local-regional (LR) management has not been defined. Using a patient registry database, we examine factors associated with treatment and outcomes in OBC. METHODS: Female patients with cT0 N1/2 M0 BC were selected from the National Cancer Database (2004-2013) and categorized into four treatment groups: MAST = mastectomy with axillary lymph node dissection (ALND) ± radiation (RT); RT + ALND = RT with ALND, no breast surgery; ALND = ALND alone; OBS = no breast surgery, RT, or ALND. Patient characteristics and overall survival (OS) were compared between groups, and multivariable analysis was used to identify factors associated with treatment and OS. RESULTS: Among 2.03 million BC cases, 1853 females (0.09%) with cT0 N1/2 M0 disease were identified and 1231 patients were categorized into a treatment group: MAST = 592, RT + ALND = 342, ALND = 106, OBS = 191. On logistic regression, care at an academic center was associated with a higher likelihood of RT + ALND compared with MAST (odds ratio 2.03, 95% confidence interval [CI] 1.50-2.74, p < 0.001). Patients treated with RT + ALND had significantly better OS on univariate survival analysis compared with patients treated with MAST (hazard ratio [HR] 0.475, 95% CI 0.306-0.736, p = 0.001). RT + ALND was independently associated with OS on multivariable survival analysis (HR 0.509, 95% CI 0.321-0.808, p = 0.004), after adjusting for covariates. CONCLUSIONS: Patients with OBC were more likely to undergo RT + ALND if they received care at an academic center. Patients treated with RT + ALND had significantly better OS compared with patients treated with MAST, after adjusting for covariates. This supports the use of RT + ALND as LR treatment for patients with OBC.

Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer.

Resistance to aromatase inhibitors (AIs) involves increased HER2. One mechanism by which HER2 may mediate resistance is through expansion of the tumor initiating cell (TIC) population. This study investigates whether combining all-trans retinoic acid (ATRA) and histone deacetylase inhibitor entinostat (ENT) can inhibit TICs and HER2 in AI-resistant cells and tumors. Modulation of cell viability and HER2 expression were assessed in AI-resistant cells treated with ATRA + ENT. Letrozole-resistant LTLT-Ca cells treated with ATRA + ENT were assayed for changes in TIC characteristics, such as TIC markers (BCRP, ALDH, and BMI-1), side population (SP), and mammosphere formation. Xenograft tumors of MCF-7Ca cells made resistant to letrozole were treated with ATRA, ATRA + letrozole, ATRA + ENT, or ATRA + ENT + letrozole. Resulting tumors were assayed for changes in TIC characteristics. Patient samples taken pre- and post-AI treatment were analyzed for changes in ERα and HER2 protein expression. Treatment with ATRA + ENT reduced HER2 expression and viability (P < 0.001) in AI-resistant cells, as well as decreased SP (P < 0.0001), mammosphere formation (P < 0.01), and expression of TIC molecular markers (P < 0.01) in LTLT-Ca. A reduction in tumor growth rate was observed in mice treated with ENT + ATRA + letrozole when compared to mice treated with single agents (P < 0.0001) or ENT + ATRA (P = 0.02). Decreased TIC characteristics, including mammosphere formation (P < 0.05), were observed in tumors from the triple combination. An increase in HER2 and downregulation in ERα protein expression was observed in patients upon resistance to AI (P < 0.005). These studies indicate that the combination of ATRA and ENT inhibits the TIC population of AI-resistant cells and may be effective in reducing tumor recurrence.

A Prospective Trial of Single-Fraction Radiation to the Tumor Bed with a Novel Breast-Specific Stereotactic Radiation Therapy Device: The GammaPod.

Purpose: Radiation therapy for early-stage breast cancer is typically delivered in a hypofractionated regimen to the whole breast followed by a tumor bed boost. This results in a treatment course of approximately 4 weeks. In this study, the tumor bed boost was delivered in a single fraction as part of a safety and feasibility study for FDA clearance of the device. Methods and Materials: Eligible women with early-stage breast cancer underwent lumpectomy followed by radiation therapy. Patients underwent breast immobilization using a system specific to the GammaPod followed by CT simulation, boost treatment planning, and boost treatment delivery all in a single treatment day. Patients then started whole-breast radiation therapy within 1 week of the boost treatment. Patients and treatments were assessed for safety and feasibility. Acute toxicities were recorded. Results: A single-fraction boost of 8 Gy was delivered to the tumor bed before a course of whole-breast radiation. The GammaPod treatment was successfully delivered to 14 of 17 enrolled patients. Acute toxicities from all radiation therapy, inclusive of the boost and whole-breast radiation, were limited to grade 1 events. Conclusions: The GammaPod device successfully delivered a single-fraction boost treatment to the tumor bed with no change in expected acute toxicities. The results of this study led to FDA clearance of the device through the Investigational Device Exemption process at the FDA. The GammaPod is in clinical use at 4e institutions nationally and internationally, with additional sites pending in 2023.

Dietary Composition, Meal Timing, and Cancer-Related Fatigue: Insights From the Women's Healthy Eating and Living Study.

BACKGROUND: Cancer-related fatigue is difficult to treat, and dietary interventions are promising yet underused. OBJECTIVE: We explored associations between dietary patterns and fatigue, and the effect of a dietary intervention versus control on fatigue using Women's Healthy Eating and Living study data, plus mediators and moderators of the intervention effect. METHODS: The Women's Healthy Eating and Living study was a randomized controlled trial among early-stage breast cancer survivors. The 4-year intervention encouraged fruits, vegetables, fiber, and 15% to 20% calories from fat. Fatigue outcomes included a 9-item energy scale and a single-item tiredness question. Dietary quality was estimated using a modified Healthy Eating Index (24-hour dietary recall) and serum carotenoid concentrations. Nutrient timing was obtained from 4-day food logs. RESULTS: Among 2914 total participants, lower body mass index was associated with less tiredness and more energy at baseline (P < .001 for both). Earlier start and end times for daily eating windows were associated with less tiredness (P = .014 and P = .027, respectively) and greater energy (P = .006 and P = .102, respectively). The intervention did not lead to improvements in fatigue on average (P > .125). However, the intervention was more effective for participants who were younger, had fewer comorbidities, and did not have radiation treatment. Mediators included increases in serum carotenoids, increases in the modified Healthy Eating Index, and weight loss/maintenance. CONCLUSION: Diet quality and earlier eating windows were associated with less fatigue. IMPLICATIONS FOR PRACTICE: Programs that encourage high diet quality and a morning meal and discourage nighttime eating should be tested for efficacy in reducing cancer-related fatigue in survivorship.

Advance Care Planning and Communication Skills Improve after an Interprofessional Team Simulation with Standardized Patients.

Background: Improving rates of advance care planning (ACP) and advance directive completion is a recognized goal of health care in the United States. No prior study has examined the efficacy of standardized patient (SP)-based student interprofessional ACP trainings. Objectives: The present study aims to evaluate an interprofessional approach to ACP education using SP encounters. Design: We designed a pre-post evaluation of an innovative interprofessional ACP training curriculum using multimodal adult learning techniques to test the effects of completing ACP discussions with SPs. Three surveys (pre-training T1, post-training T2, and post-clinical encounter T3) evaluated student knowledge, Communication Self-Efficacy (CSES), ACP self-efficacy, and interprofessional teamwork (using SPICE-R2). Setting/Subjects: Students from the schools of medicine, nursing, and social work attended three training modules and two SP encounters focused on ACP. Measurements/Results: During academic year 2018-2019, 36 students participated in the training at University of Maryland. Results demonstrated statistically significant improvements in ACP self-efficacy, M T1 = 2.9 (standard deviation [SD]T1 = 0.61) compared with M T3 = 3.9 (SDT3 = 0.51), p < 0.001, and CSES, M T1 = 4.6 (SDT1 = 1.35) versus M T3 = 7.3 (SDT3 = 0.51), p < 0.001, from T1 to T3. There was a medium-to-large improvement in knowledge from an average score of 4.3 (SD = 1.0) at T1 to an average score of 5.5 (SD = 1.4) at T2, p = 0.005, d = 0.67. Conclusions: Our interprofessional training module and SP encounter was successful in improving medical, social work, and nursing students' self-reported communication skills and knowledge regarding ACP.

Patterns of Failure in Triple Negative Breast Cancer Patients in an Urban, Predominately Black Population.

Triple negative breast cancers (TNBC) behave more aggressively than hormone-receptor positive breast cancers. They are also known preferentially to affect young black women, often leading to poorer outcomes compared with those for white women. We sought to evaluate the comprehensive patterns of failure associated with treatment for TNBC at an urban institution with a predominantly black population and to assess the impact of social determinants of health on treatment failure. A retrospective review of TNBC patients treated from 2005 to 2015 was conducted. Detailed patient, tumor, and treatment characteristics and information on patterns of failure were included. With a median follow-up of 46 months, 32 (16%) documented failures occurred. Locoregional failures comprised 84% of failure patterns whether isolated or in combination with distant failure. Treatment failure was associated with insurance type and smoking status, as well as several tumor characteristics. On multivariate analysis, pathologic nodal staging was the most significant predictor of treatment failure. In contrast to previous studies, we found that black women had higher overall survival than white women, but race was not associated with differences in recurrence patterns or with likelihood of treatment failure. Regardless of race, of the patients who recurred, 53% failed in distant and locoregional sites simultaneously, with an additional 34% failing locally only. These results highlight the need for aggressive local therapies in high-risk patients and suggest a need for improved follow-up focusing on detecting locoregional failures. Multidisciplinary care is essential in the management of these patients at time of failure.

Breast Health: Breast Cancer Survivorship.

Coordination of the care of breast cancer survivors between oncology subspecialists and family physicians is critical to achieving optimal health outcomes. Care of survivors includes surveillance for breast cancer recurrence, screening for second malignancies, assessment and management of adverse effects of treatment, and promotion of overall wellness. Adverse effects include hot flushes, depression and anxiety, lymphedema, cognitive impairment, neuropathy, decreased bone health, effects on sexual health, and cardiac dysfunction. Survivorship care plans can help guide care coordination among clinicians. Racial and ethnic disparities also affect outcomes for patients with breast cancer; optimization of survivorship interventions may help address these disparities.

Testing the Impact of a Cancer Survivorship Patient Engagement Toolkit on Selected Health Outcomes.

OBJECTIVES: To evaluate an interactive electronic Cancer Survivorship Patient Engagement Toolkit (CaS-PET) using a single-group pre-/post-test design. SAMPLE & SETTING: 30 cancer survivors with a mean age of 56.5 years (SD = 13.6) were recruited from the University of Maryland Medical Center in Baltimore. METHODS & VARIABLES: CaS-PET was designed to deliver survivorship care plans (SCPs) with multifactorial support and comprised of SCPs, biweekly follow-up using patient portal e-messages, and online resources. Outcomes included health-related quality of life, symptom burden, impact of cancer, fear of recurrence, physical activities, dietary behavior, patient-provider communication, adherence to treatment, and e-health literacy. RESULTS: At three months, there was a significant improvement in quality of life, physical symptom burden, and total symptom burden. IMPLICATIONS FOR NURSING: Findings suggest an excellent potential for using CaS-PET for survivors who are in transition from treatment to survivorship.

Working poor and working nonpoor cancer survivors: Work-related and employment disparities.

BACKGROUND: Many cancer survivors face challenges remaining at work during treatment or returning to work posttreatment. Workplace supports can ease the strain associated with managing the cancer-work interface. Limited research has examined the employment experiences of low-wage earning survivors, who are less likely to have access to workplace supports, overlooking a factor that may influence survivors' employment outcomes. AIMS: This study assessed differences in employment experiences between working poor (WP) and working nonpoor (WNP) cancer survivors in the United States. METHODS AND RESULTS: Data from the 2011 Medical Expenditure Panel Survey (MEPS) and the 2011 MEPS Experiences with Cancer Survivorship Supplement were analyzed to evaluate differences in workplace supports, cancer-related psychological job distress, productivity, and employment outcomes between WP and WNP cancer survivors. The sample included adults diagnosed with cancer within 5 years prior to survey completion and engaged in paid employment since diagnosis. Working poor respondents had income below 200% of the poverty level. Chi-square tests assessed differences between WP (n = 57) and WNP (n = 164) cancer survivors' demographic, cancer, and employment characteristics; cancer-related psychological job distress; employee productivity; and employment outcome measures. Multiple logistic regression analyses determined the independent association between WP status and these same variables controlling for sociodemographic confounders. Working poor survivors were more likely to take unpaid time off, change from full-time to part-time, to report cancer-related psychological job distress, negative influences on job productivity and employment outcomes, and less likely to have health insurance. In logistic regression analyses, those who took unpaid time off were more likely to be WP; being WP was also associated with poorer employment outcomes, after controlling for sociodemographics differences between WP and WNP. CONCLUSION: Working poor survivors had fewer workplace supports and poorer employment outcomes than WNP survivors, highlighting important occupational disparities for cancer survivors. Areas for future research are discussed.

Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors.

OBJECTIVES: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. METHODS: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. RESULTS: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). CONCLUSIONS: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

Effect of reduction mammoplasty on acute radiation side effects and use of lumpectomy cavity boosts.

PURPOSE: Reduction mammoplasty (RM) during breast-conserving surgery is popular among women with large-volume breasts because it reduces redundant breast folds and may decrease skin-related morbidity from radiation therapy. However, RM may obscure the lumpectomy cavity (LC) and pose challenges to administering an LC boost, potentially affecting local control. We investigated the impact of RM on acute side effects and use of LC boosts. METHODS AND MATERIALS: The records of 645 consecutive women treated with whole-breast irradiation at an urban university and 2 community practices between January 2012 and December 2014 were reviewed on an institutional review board-approved study. The primary endpoint was grade ≥3 radiation dermatitis; the secondary endpoint was use of LC boost. Student 2-sample t tests, Pearson χ2 tests, Fisher exact tests, and univariate and multivariable logistic regression analyses were performed. RESULTS: Forty-three (7%) RMs were performed in 650 treated breasts. No significant differences in grade 3 toxicities were identified among RM and non-RM patients. LC boost was delivered to 474 breasts. Fewer (16/43) RM patients received LC boosts compared with non-RM patients (458/607), P = .0001. RM patients were more likely to have neoadjuvant chemotherapy, stage III or multifocal disease, higher body mass index, larger planning treatment volumes, and conventional fractionation (P < .05). CONCLUSIONS: RM was associated with decreased use of LC boost without significant differences in acute toxicities. Further investigation to delineate LCs in patients undergoing RM or identify alternative strategies for delivering LC dose is needed.

Schistocytes, echinocytes, iron deficiency anemia, and thrombocytopenia - hematologic manifestations of splenic angiosarcoma.

Splenic angiosarcoma is a rare and aggressive malignancy with an incidence of less than one per million and a fatality rate over 90%.  Early diagnosis is of great importance for optimal management.  Here, we report the case of a patient with splenic angiosarcoma who presented with prominent schistocytes, echinocytes, thrombocytopenia, and iron deficiency anemia, which in combination with radiographic evidence of a splenic mass, raised the suspicion for angiosarcoma and resulted in a prompt surgical intervention with curative intent. Resolution of the hematologic findings following splenectomy suggests that patients with this malignancy should be monitored for recurrent hematologic abnormalities as they may herald recurrence of the disease. We present a literature review on the hematologic manifestations that is associated with this malignant disease.

CYFRA 21-1 as a prognostic and predictive marker in advanced non-small-cell lung cancer in a prospective trial: CALGB 150304.

BACKGROUND: Cytokeratin 19 and its soluble fragment CYFRA have been studied as markers that may be associated with response to therapy and survival in non-small-cell lung cancer (NSCLC). As a prospective correlative study of Cancer and Leukemia Group B 30203, a randomized phase II trial of carboplatin/gemcitabine with eicosanoid modulators (celecoxib, zileuton, or both) in advanced NSCLC, serum CYFRA levels were obtained before and during treatment. METHODS: Serum CYFRA levels were measured at baseline and after the first cycle of treatment using an electrochemoluminescent assay. Paired specimens were available from 88 patients. The logarithms of the initial concentration and of the difference in concentrations were analyzed for association with overall survival (OS) and failure-free survival (FFS). RESULTS: Lower baseline CYFRA levels were associated with both longer OS and FFS (p < 0.0001 and p = 0.0003). In addition, larger reductions in CYFRA levels correlated with longer OS and FFS (p = 0.0255 and p = 0.0068). CONCLUSION: CYFRA and change in CYFRA were found to be reliable markers for response to chemotherapy for NSCLC; however, a precise threshold to mark response has yet to be determined.