African-American Adolescents’ Weight Loss Skills Utilization: Effects on Weight Change in a Sequential Multiple Assignment Randomized Trial

Objective

Successful weight loss interventions for African-Americans adolescents are lacking. Cognitive-behavioral interventions seek to develop weight loss skills (e.g., counting calories, goal setting, managing one's environment). Little is known about how well adolescents implement such skills in their daily lives. Study aims were to (1) examine weight loss skills utilization at midpoint and end of a 6-month cognitive-behavioral/motivational interviewing weight loss sequential multiple assignment randomized trial (SMART), and (2) determine if greater skill utilization predicted weight loss at treatment end and 3 months post-treatment.

Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood–brain barrier disruption: where are we now,and where we are going

Journal of Neuro-Oncology - Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration...     

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors

This study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition. This was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD. Adverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses). Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested.     

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy,with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Background The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT).Methods 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed.Results 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017).Conclusion No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.Subject terms: Breast cancer, Breast cancer     

Development and validation of a risk calculator for post-discharge venous thromboembolism following hepatectomy for malignancy

BackgroundPost-discharge venous thromboembolism (VTE) chemoprophylaxis decreases VTEs following cancer surgery, however identifying high-risk patients remains difficult. Our objectives were to (1) identify factors available at hospital discharge associated with post-discharge VTE following hepatectomy for malignancy and (2) develop and validate a post-discharge VTE risk calculator to evaluate patient-specific risk.MethodsPatients who underwent hepatectomy for malignancy from 2014 to 2017 were identified from the ACS NSQIP hepatectomy procedure targeted module. Multivariable logistic regression identified factors associated with post-discharge VTE. A post-discharge VTE risk calculator was constructed, and predicted probabilities of post-discharge VTE were calculated.ResultsAmong 11 172 patients, 95 (0.9%) developed post-discharge VTE. Post-discharge VTE was associated with obese BMI (OR 2.29 vs. normal BMI [95%CI 1.31–3.99]), right hepatectomy/trisegmentectomy (OR 1.63 vs. partial/wedge [95%CI 1.04–2.57]), and several inpatient postoperative complications: renal insufficiency (OR 5.29 [95%CI 1.99–14.07]), transfusion (OR 1.77 [95%CI 1.12–2.80]), non-operative procedural intervention (OR 2.97 [95%CI 1.81–4.86]), and post-hepatectomy liver failure (OR 2.22 [95%CI 1.21–4.08]). Post-discharge VTE risk ranged from 0.3% to 30.2%. Twenty iterations of 10-fold cross validation identified internal validity.ConclusionsRisk factors from all phases of care, including inpatient complications, are associated with post-discharge VTE following hepatectomy. Identifying high-risk patients may allow for personalized risk-based post-discharge chemoprophylaxis prescribing.