EXERT-BC: A pilot study of an exercise regimen designed to improve functional mobility, body composition, and strength after the treatment for breast cancer.

PURPOSE: Resistance training may offer several unique advantages within breast cancer (BC) survivorship care; however, safety concerns have limited the application of high-intensity compound movements necessary to elicit optimal changes in body composition, strength, and quality of life in this population. The EXERT-BC trial assesses the safety and feasibility of an evidence-based, dose-escalated resistance training regimen among BC survivors, with the goal of improving physical and metabolic function, mobility, muscle mass, and body composition. METHODS: Participants included women with breast cancer underwent a 3-month thrice weekly exercise regimen involving dose escalation of high-intensity compound exercises. Coprimary outcomes included safety and adherence. Pre- and post-regimen assessment included body composition testing, functional mobility and balance, total load (weight × repetitions × sets) across compound exercises, and patient reported quality of life. Pairwise comparison was performed via the paired t test. RESULTS: Fourty participants completed a 3-month exercise regimen, with a median age of 57 years (range, 27-74 years) and 73% having stage 0-2 BC. BC therapies concurrent with exercise included anti-estrogen therapy (80%), radiotherapy (30%), and non-hormonal systemic therapy (15%). No adverse events were observed aside from a single case of self-limited knee pain. Session attendance exceeded a prespecified threshold of 75%, and 98% patients reported ongoing compliance to an exercise regimen following regimen completion. Significant reductions in percent body fat (p < 0.001) and increases in percent muscle mass (p = 0.011) were observed. Significant increases in resting metabolic rate (p = 0.023), bilateral grip strength (p < 0.001), functional movement screen (p < 0.001), bilateral Y-Balance testing (p < 0.001), and Godin questionnaire scores (p < 0.001) were observed. CONCLUSION: A 3-month dose-escalated resistance training regimen comprising high-intensity compound movements appears safe with a high degree of adherence among breast cancer survivors, resulting in demonstrable improvements in body composition, metabolic parameters, strength increases, and patient-reported quality of life.

Long-Term Follow-Up of the Anthracyclines in Early Breast Cancer Trials (USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 [NRG Oncology]).

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary joint efficacy analysis of the Anthracyclines in Early Breast Cancer (ABC) trials reported in 2017 failed to demonstrate nonanthracycline adjuvant therapy was noninferior to anthracycline-based regimens in high-risk, early breast cancer. Full analyses of the studies had proceeded when the prespecified futility boundary was crossed at a planned futility analysis for the ability to demonstrate noninferiority of a nonanthracycline regimen with continued follow-up. These results were presented with 3.3 years of median follow-up. This manuscript reports results of the final analyses of the study efficacy end points conducted with 6.9 years of median follow-up. Long-term analysis of invasive disease-free survival (IDFS), the primary end point of the ABC trials, remains consistent with the original results, as noninferiority of the nonanthracycline regimens could not be declared on the basis of the original criteria. The secondary end point of recurrence-free interval, which excluded deaths not due to breast cancer as events, favored anthracycline-based regimens, and tests for heterogeneity were significant for hormone receptor status (P = .02) favoring anthracycline regimens for the hormone receptor-negative cohorts. There was no difference in overall survival, and review of the type of IDFS events in the groups suggested reductions in cancer recurrences achieved with anthracycline regimens were offset by late leukemias and deaths unrelated to breast cancer.

EXERT-BC: Prospective Study of an Exercise Regimen After Treatment for Breast Cancer.

Purpose EXERT-BC is a dose-escalated resistance training regimen created to improve body composition, strength, and balance in women treated for breast cancer (BC). Herein, we report the interim analysis. Women treated for BC underwent this 3-month exercise regimen in an exercise oncology facility with continual monitoring of load and strength. Twenty women completed the IRB-approved protocol, with a mean age of 57 years (range 41-74). Concurrent therapies included anti-estrogen therapy (73%), chemotherapy (14%), and radiotherapy (23%). 27% of women endorsed prior exercise. Subjects missed an average of 1.75 classes (range 0-7), with all meeting adherence over 75%. No injuries or adverse events were reported aside from muscle soreness and 2 days of knee pain. Significant differences in body composition at completion included reduced body fat (38.2% vs. 36.7%, p=0.003), and increased muscle mass (33.1% vs. 37.1%, p<0.001), functional mobility screening (9.82 vs. 11.73, p=0.018), and Y-balance (left: 72.4 vs. 85.3, p=0.001; right: 70.3 vs. 85.2. p<0.001). Significant increases in load were demonstrated: split squat (p<0.001), trap bar deadlift (p=0.035), inclined dumbbell press (p<0.001), and bird dog rows (p<0.001). Dose-escalated resistance training in women with BC is safe and feasible, endorsing significant improvements across body composition, balance, and strength.

Feasibility of Symptom Monitoring During the First Year of Endocrine Therapy for Early Breast Cancer Using Patient-Reported Outcomes Collected via Smartphone App.

PURPOSE: Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. METHODS: Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. RESULTS: Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. CONCLUSION: Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers.

OBJECTIVES: Single-agent heat shock protein 90 (HSP90) inhibition has demonstrated activity in oncogene-driven non-small cell and small cell lung cancers. SNX-5422 is an oral HSP90 inhibitor with increased activity in vitro with the addition of carboplatin and paclitaxel. Therefore, we conducted a phase 1, open-label, multicenter study to evaluate SNX-5422, carboplatin and paclitaxel followed by SNX-5422 maintenance in patients with advanced lung cancers. MATERIALS AND METHODS: In part 1 (3 + 3 dose escalation), SNX-5422 (50/75/100-mg/m2) was dosed every other day (qod) for 21 days (28-day cycle) for ≤4 cycles; carboplatin (AUC 5)-paclitaxel (175 mg/m2) was administered once every 3 weeks for ≤6 courses. In part 2 (maintenance), subjects who achieved at least stable disease in part 1 received 100 mg/m2 SNX-5422 monotherapy qod for 21 days (28-day cycle). RESULTS: Twenty-three patients with advanced non-small cell lung cancer (NSCLC, n = 20) and small cell lung cancer (SCLC, n = 3) were enrolled. The median age was 60 years and 61% (n = 14/23) had ≥1 prior treatment regimens. The maximum tolerated dose of SNX-5422 was 100 mg/m2 qod in combination with carboplatin-paclitaxel. The most common treatment-related grade 3/4 adverse events (part 1/part 2) were diarrhea (26%/15%) and nausea (9%/0%). In response-evaluable patients with NSCLC, 33% (6/18) had a partial response, 56% (10/18) stable disease, and 11% (2/18) progressive disease. Patients who remained on single-agent SNX-5422 maintenance therapy ≥2 months (n = 9) had cancers enriched for oncogenic drivers (n = 3 KRAS mutation, n = 1 EGFR exon 20 mutation, n = 1 HER2 mutation, and n = 1 RET fusion). CONCLUSIONS: The triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity. Cancers for which disease control on single-agent SNX-5422 maintenance was observed were enriched for oncogene-driven NSCLCs.

The use of adjuvant radiation therapy in male breast cancer and its impact on outcomes.

BACKGROUND: Male breast cancer (MBC) accounts for 1% of all breast cancers and there is a paucity of data on factors impacting the treatment strategies and outcomes. We sought to use a large national database to examine trends and predictors of the use of adjuvant radiation (Adj-RT), as well as any association with outcome. METHODS: We queried the National Cancer Database (NCDB) for patients with stages I-III MBC treated with surgery (breast conservation surgery-BCS or mastectomy-MS) within 180 days of diagnosis (years 2004-2015). Multivariable logistic regression identified predictors of adj-RT receipt. Multivariable Cox regression evaluated predictors of survival. Propensity matching for adj-RT was used to account for indication biases. RESULTS: We identified 6,217 patients meeting the eligibility criteria (1457 BCS vs. 4760 MS). The majority of patients were Caucasian (85%) and in an age range of 50-80 years (74%). Although adj-RT was omitted for 30% of BCS patients, the utilization was higher compared to MS (OR=26, p-value=0.001). The predictors of adj-RT use included African-American race, more advanced stage, higher grade, presence of lymphovascular invasion, and ER/Her-2 positivity for the entire cohort and increased age, urban location and higher income for BCS. Adj-RT was associated with lower mortality in the propensity matched model (overall HR for BCS=0.28, p-value<0.001; overall HR for MS=0.62, p-value=0.001). CONCLUSION: This study demonstrates that while adj-RT after BCS is associated with decreased mortality in MBC patients, adj-RT is omitted in up to a third of cases of MBC after BCS despite being standard of care.

Trastuzumab and pertuzumab in hemodialysis: A case report.

INTRODUCTION: Trastuzumab and pertuzumab are recombinant humanized monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2). Currently, six reported cases on the use of trastuzumab in dialysis, and one on the use of pertuzumab, have been identified in the literature. This case is one of the first to describe the use of pertuzumab, and adds to currently available reports on the use of trastuzumab, in hemodialysis. CASE REPORT: A female receiving hemodialysis three times per week was diagnosed with a clinical T2N1M0, hormone receptor-negative, HER2-positive, invasive ductal carcinoma of the breast. She received six cycles of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab, with left ventricular ejection fraction (LVEF) remaining stable throughout. Following surgery, she continued dual HER2 blockade with trastuzumab and pertuzumab, after six cycles of which she was found on routine echocardiogram to have an asymptomatic decline in LVEF.Management & outcome: Following the decline in LVEF, trastuzumab and pertuzumab were held, and cardio-oncology was consulted. LVEF recovered within one month, after which she continued on single-agent trastuzumab to complete one year of HER2-directed therapy. DISCUSSION: To our knowledge, this is one of the first published cases describing the use of pertuzumab in a patient receiving hemodialysis. Though our patient did experience a reversible decline in LVEF following twelve cycles of combination trastuzumab and pertuzumab, this case demonstrates the relatively safe and effective use of pertuzumab in a patient with end-stage renal disease undergoing hemodialysis, and lends additional support to the use of trastuzumab in this particular patient population.

Melanoma brain metastases: is it time to eliminate radiotherapy?

PURPOSE: Immunotherapy has demonstrated efficacy in treatment of intracranial metastasis from melanoma, calling into question the role of intracranial radiotherapy (RT). Herein, we assessed the utilization patterns of intracranial RT in patients with melanoma brain metastasis and compared outcomes in patients treated with immunotherapy alone versus immunotherapy in addition to intracranial RT. METHODS: We queried the National Cancer Database (NCDB) for patients with melanoma brain metastases treated with immunotherapy and intracranial RT or immunotherapy alone. Multivariable logistic regression identified variables associated with increased likelihood of receiving immunotherapy alone. Multivariable Cox regression was used to identify co-variates predictive of overall survival (OS). Propensity matching was used to account for indication bias. RESULTS: We identified 528 and 142 patients that were treated with combination therapy and immunotherapy alone, respectively. Patients with lower comorbidity score were more likely to receive immunotherapy alone. Extracranial disease and treatment at a non-academic center were associated with worse OS. Median OS for all patients was 11.0 months. Treatment with stereotactic radiosurgery (SRS) in addition to immunotherapy was superior to immunotherapy alone, median OS of 19.0 versus 11.5 months (p = 0.006). Whole brain radiation therapy (WBRT) in combination with immunotherapy performed worse than immunotherapy alone, median OS of 7.7 versus 11.5 months (p = 0.0255). CONCLUSIONS: For melanoma patients requiring WBRT, immunotherapy alone may be reasonable in asymptomatic patients. For those eligible for SRS, combination therapy may provide better outcomes. Results of ongoing prospective studies will help provide guidance regarding the use of radioimmunotherapy in this population.

Improving the use of the 'COUGH' bundle in Surgical High Dependency Unit, Ninewells Hospital, Dundee.

Developing respiratory complications postoperatively is one of the major determinants of longer hospital stay, morbidity, mortality and increased healthcare costs. The incidence of postoperative respiratory complications varies from 1% to 23%. Given that postoperative respiratory complications are relatively common and costly, there have been various studies which look at ways to reduce the risk of these occurring. One such protocol is the ICOUGH bundle which stands for Incentive spirometry, Coughing and deep breathing, Oral care, patient Understanding, Getting out of bed and Head of bed elevation. This has been adapted locally to the Coughing and deep breathing, Oral care, patient Understanding, Getting out of bed and Head of bed elevation (COUGH) bundle which consists of these components excluding incentive spirometry. Within our surgical high dependency unit (HDU), the COUGH bundle should be implemented in patients who have a moderate or high risk of developing postoperative respiratory complications with an Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score of 26 or above. Studies have shown that the ICOUGH bundle has reduced rates of pneumonia and unplanned intubation in general surgical and vascular patients. Baseline data taken from surgical HDU showed that the COUGH bundle was not well implemented. One out of eight patients who had an ARISCAT score greater than 26 had the COUGH bundle implemented on admission to the unit. Three out of eight patients had the ARISCAT score documented in their admission medical review. One patient who should have received the bundle, but did not, developed a hospital acquired pneumonia postoperatively. To address this issue, we aimed to increase awareness surrounding the COUGH bundle and to increase the number of patients who had the COUGH bundle started on admission. This quality improvement project had four cycles (plan, do, study, act) and after these, 100% of patients who had an ARISCAT score of 26 or more had the COUGH bundle implemented.

Management trends and outcomes of breast angiosarcoma: Is breast conservation feasible?

We queried the National Cancer Database for nonmetastatic breast angiosarcoma, yielding 808 patients (202 de novo, 606 secondary). The median survival was 53.7 months. Secondary tumors were more likely to undergo mastectomy than de novo lesions (OR = 3.99, P < 0.001). Treatments included lumpectomy (10%), lumpectomy/radiation (3%), mastectomy alone (73%), or mastectomy/radiation (14%), with no difference in survival (P = 0.68). Lumpectomy correlated with positive margin rate (OR 3.29), which was a predictor for death (HR = 2.37, P < 0.01), along with older age, higher comorbidity scores, size >5 cm, and high-grade disease (P < 0.05). While breast angiosarcoma is usually treated with mastectomy, lumpectomy may be feasible for well-selected tumors.

Surveillance Mammography After Breast Conservation Therapy: Is Tomosynthesis Worth It?

INTRODUCTION: We investigated the downstream workup and costs associated with digital breast tomosynthesis (DBT) compared with 2-dimensional full field digital mammogram (FFDM) when employed as initial follow-up imaging in breast conservation therapy. METHODS: Between the years 2015 and 2017, 450 consecutive breast conservation therapy patients, ages 32 to 89, with a follow-up DBT (n=162) or FFDM (n=288) were retrospectively reviewed. The primary endpoints were further workup after follow-up mammogram and associated health care costs at 1 year. A single DBT costs an estimated $149 compared with $111 for FFDM, based on Centers for Medicare claims data from the Oncology Care Model. RESULTS: The first posttreatment mammogram was received within 3 (20%), 3 to 6 (32%), or after 6 months (48%) following radiation. Younger patients and those undergoing hypofractionated radiation were more likely to get DBT. There were no differences in stage, receptor status, or mammogram timing between those in the FFDM and DBT groups.The following downstream workup ensued for DBT compared with FFDM imaging: 18% versus 29% short-interval (6-mo) mammogram (odds ratio=1.83, P=0.01), 6% versus 11% breast magnetic resonance imaging (odds ratio=1.90, P=0.08), 4% ultrasound for each, and 3% biopsy for each (1 positive in the FFDM group). Including downstream workup, the estimated cost per patient in the DBT group was $216.14 compared with $237.83 in the FFDM group. Independent predictors for reduced downstream workup per multivariable analysis were the use of DBT and first follow-up mammogram at least 6 months after radiation (P<0.05). DISCUSSION: Excess workup was reduced with DBT compared with FFDM in the posttreatment setting, which translated to an improvement in cost efficiency in this study.

Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) patients aged ≥ 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13-724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML.