IMPORTANCE: Chemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited. ...OBJECTIVES: To evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). The study was conducted between August 2013 and October 2014 with ongoing annual follow-up for 5 years. EXPOSURES: Use of a scalp cooling system. Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward. MAIN OUTCOMES AND MEASURES: Self-estimated hair loss using the Dean scale was assessed 4 weeks after the last dose of chemotherapy by unblinded patient review of 5 photographs. A Dean scale score of 0 to 2 (≤50% hair loss) was defined as treatment success. A positive association between scalp cooling and reduced risk of hair loss would be demonstrated if 50% or more of patients in the scalp cooling group achieved treatment success, with the lower bound of the 95% CI greater than 40% of the success proportion. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later. Median follow-up was 29.5 months. RESULTS: Among the 122 patients in the study, the mean age was 53 years (range, 28-77 years); 77.0% were white, 9.0% were black, and 10.7% were Asian; and the mean duration of chemotherapy was 2.3 months (median, 2.1 months). No participants in the scalp cooling group received anthracyclines. Hair loss of 50% or less (Dean score of 0-2) was seen in 67 of 101 patients (66.3%; 95% CI, 56.2%-75.4%) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0%) in the control group (P < .001). Three of 5 quality-of-life measures were significantly better 1 month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27.3% (95% CI, 18.0%-36.6%) reported feeling less physically attractive compared with 56.3% (95% CI, 31.9%-80.6%) of patients in the control group (P = .02). Of the 106 patients in the scalp cooling group, 4 (3.8%) experienced the adverse event of mild headache and 3 (2.8%) discontinued scalp cooling due to feeling cold. CONCLUSIONS AND RELEVANCE: Among women undergoing non–anthracycline-based adjuvant chemotherapy for early-stage breast cancer, the use of scalp cooling vs no scalp cooling was associated with less hair loss at 4 weeks after the last dose of chemotherapy. Further research is needed to assess outcomes after patients receive anthracycline regimens, longer-term measures of alopecia, and adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01831024
1553
Background: Cancer survivors receiving potentially cardiotoxic chemotherapy are at increased risk for developing left ventricular (LV) dysfunction. We implemented machine learning (ML) models to ...predict future LV dysfunction in patients with breast cancer or lymphoma scheduled to receive potentially cardiotoxic chemotherapy. Methods: We utilized prospectively collected data from NIH studies R01HL118740 (supported by the Wake Forest NCORP Research Base (UG1CA189824)) and R01CA167821. Data included measurements of LV function and demographic factors before, during, and 24 months after initiating potentially cardiotoxic chemotherapy. The two datasets were used both separately and collectively in the development of multiple ML models including penalized linear regression, support vector machine, and random forest (RF). A data preprocessing step properly handled missing information, data imbalance, and encoding. Hyperparameter tuning was performed using cross validation of training data. The final models were assessed with a 20% hold-out test dataset. Cardiotoxicity was defined as a pre- to 24-month post cancer treatment decline in LV ejection fraction (LVEF) of > 10% or to an absolute value of < 50%. Results: 276 patients were included in ML models (7% men, 93% women; age 52±13 years). The RF model based on the combined dataset had the best performance with a prediction accuracy, sensitivity, and specificity of 0.94, 0.81, and 0.98, respectively. The most important variables assessed pre-treatment as measured by the Gini impurity factor were in descending order, LVEF, global LV circumferential strain, LV end-systolic volume, body mass index, LV stroke volume, LV end-diastolic volume, and LV mass. Conclusions: Prior to cancer treatment, supervised ML methods such as RF models predicted declines in LVEF of > 10% and/or to absolute values below 50% would occur 24 months after initiating chemotherapy for breast cancer or lymphoma. With further improvement and validation using larger datasets, these models may play an important role in cardio-oncology care during and following cancer treatment.
Disparities in HER2 testing in breast cancer Paryani, Vijay; Schroeder, Mary Chen; Klepin, Heidi D. ...
Journal of clinical oncology,
05/2019, Letnik:
37, Številka:
15_suppl
Journal Article
Recenzirano
Abstract only
e13084
Background: Although targeted therapies directed at human epidermal growth factor-2 (HER2) impact breast cancer outcomes, studies have found geographic variation in testing ...rates. We report population-based patterns of HER2 testing by patient, tumor and geographic characteristics. Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) data included women diagnosed 2010-2015 with de novo breast cancer. Women were categorized by age, race, stage, year of diagnosis, and receipt of estrogen receptor (ER), progesterone receptor (PR), and HER2 testing. SEER classified lack of testing with “test ordered, results not in chart” and “test not done.” We report on cases with HER2 “test not done”. Records missing any variables were excluded. County-level measures of socioeconomic status were included for each woman. Univariate and multivariate logistic regressions identified factors associated with testing. Results: Of 281,214 new breast cancer diagnoses, 1.75% had HER2 “test not done”. ER and PR testing were “not done” in 0.57% and 0.74% of cases, respectively. HER2-testing rates improved over time: 2.54% not tested in 2010 and 1.30% in 2015 (p < 0.01). The following characteristics were associated with higher rates of “test not done”: age >70 vs < 50 (OR = 1.33, p < 0.01), blacks vs whites (OR = 1.23, p < 0.01), Stage IV vs I (OR = 2.27, p < 0.01). Regional variation was also seen, with registries reporting HER2 “test not done” ranging from 0.18%-2.89%. On multivariate analysis (Table), HER2 testing was less likely for women age ≥ 70, blacks, Stage IV disease, and those living in counties with high rates of less than high school education. Conclusions: Rates of HER2 testing have increased. However, disparities exist and are associated with age, race, stage, geography, and education. Understanding the cause of these disparities could ultimately enhance access to appropriate therapy and improve disease outcomes. Odds of not having HER2 testing (select results from multivariate analysis). Table: see text
12072
Background: Statins taken for cardiovascular (CV) indications by breast cancer (BC) and lymphoma survivors during doxorubicin (DOX) treatment may attenuate left ventricular ejection fraction ...(LVEF) decline, but statin impact among these survivors with no CV indications is unknown. Methods: In 279 patients from 31 cancer centers, we conducted a double blind, placebo-controlled, 24-month randomized trial of 40mg/day atorvastatin among those receiving DOX for BC or lymphoma. At pretreatment, six and 24 months after initiating DOX for BC or lymphoma, we assessed LV volumes, strain, mass, and LVEF (via cardiac magnetic resonance), cognitive function and serum markers of inflammation. Using a linear model adjusted for pretreatment measures, our primary analysis assessed change in LVEF over time by randomization group. Results: Participants were aged 49±12 years; 92% women, 83% white race. The mean pooled LVEF decline from pretreatment to 24 months was 62.2±6.0% to 57.6±6.3% (p < 0.001). Adjusting for pretreatment LVEF, 24-month declines in LVEF averaged 3.5±0.5% and 3.3±0.5% respectively for placebo vs statins (p = 0.83). Both randomized groups were similar for: incidence of > 10% change in LVEF, LV strain, LV mass, cognition and inflammation biomarkers, including among those > 90% study drug compliant (p > 0.05 for all). Conclusions: In BC and lymphoma survivors with no existing indication for statin therapy, prospective statin administration does not appear to impact LVEF declines two years after doxorubicin. Clinical trial information: NCT01988571. Table: see text
Abstract only
e23152
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity for breast cancer patients that leads to early treatment discontinuation and worse ...outcomes. Neuromuscular ultrasound (NMUS) is a non-invasive assessment of peripheral nerves that has not been studied in taxane CIPN. Methods: This cross-sectional study enrolled breast cancer patients with subjective complaints of CIPN symptoms during or after taxane chemotherapy and compared nerve cross-sectional area (CSA) by NMUS with historical values in 120 healthy adults. Findings were correlated with self-reported symptom scale (EORTC-QLQ CIPN20, range 0-72, higher more severe); nerve conduction studies; and skin biopsies for intraepidermal nerve fiber density (IENF). Results: We evaluated 20 participants (mean 55.4 ± 10.5 yrs) with NMUS at 74 nerve sites after median 3.7 months (IQR 1.0-6.1) since last taxane (paclitaxel 10, docetaxel 8, nab-paclitaxel 2). Participants reported moderate-to-severe CIPN symptoms which were predominantly sensory (19.1 ±4.9, max 32) as opposed to motor (15.6 ±5.8, max 32) or autonomic (3.3 ±1.6, max 8). Sural sensory nerve CSA was 1.2 mm
2
smaller than in historical controls (4.1 vs. 5.3 mm
2
, 2-sample t-test p = 0.005) and decreased with more days from last taxane (Spearman’s r -0.46, p = 0.04). Tibial motor nerve was not significantly different from controls (p = 0.35). Median nerve CSA was enlarged at the distal wrist crease entrapment site (12.5 vs 10.1, p = 0.03). Older age was associated with smaller sural CSA (r = -0.72, p < 0.001). When controlling for age and days from last taxane, for each 1mm
2
decrease in sural CSA, distal IENF reduced by 2.1 nerve/mm
2
(p = 0.04, R
2
= 0.30). Conclusions: NMUS showed expected sensory predominant distal axonopathy in taxane CIPN. Evaluation of nerve CSA by non-invasive NMUS may serve as an objective point-of-care assessment to risk-stratify women with taxane CIPN prior to the development of debilitating symptoms. Clinical trial information: NCT03139435. Table: see text
PDF
