Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

IMPORTANCE: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. OBJECTIVE: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. DESIGN, SETTING, AND PARTICIPANTS: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. INTERVENTIONS: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. MAIN OUTCOMES AND MEASURES: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). RESULTS: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01042379.

Value, Access, and Cost of Cancer Care Delivery at Academic Cancer Centers.

Key challenges facing the oncology community today include access to appropriate, high quality, patient-centered cancer care; defining and delivering high-value care; and rising costs. The National Comprehensive Cancer Network convened a Work Group composed of NCCN Member Institution cancer center directors and their delegates to examine the challenges of access, high costs, and defining and demonstrating value at the academic cancer centers. The group identified key challenges and possible solutions to addressing these issues. The findings and recommendations of the Work Group were then presented at the Value, Access, and Cost of Cancer Care Policy Summit in September 2015 and multi-stakeholder roundtable panel discussions explored these findings and recommendations along with additional items.

Web-based self-monitoring for weight loss among overweight/obese women at increased risk for breast cancer: the HELP pilot study.

OBJECTIVE: Excess weight and physical inactivity are modifiable risk factors for breast cancer. Training women to use self-help resources over the internet has potential for reducing intervention costs and enhancing maintenance. METHODS: A total of 50 overweight/obese women at increased breast cancer risk were randomized to a 12-week intervention or a comparison group. Telephone-based sessions trained participants to use web-based self-monitoring tools to set goals and track diet and exercise. The comparison group received dietary information but no training. At baseline and 12 weeks, participants were weighed and wore an accelerometer. RESULTS: Participants were aged 60.9 ± 0.8 years with a BMI of 33.1 ± 0.6 kg/m(2). The intervention group lost 3.3 ± 4.0 kg, whereas the comparison group gained 0.9 ± 3.4 kg (p < 0.0001). Intervention participants who found the website helpful lost 5.6 ± 0.7 kg; those who did not lost 0.8 ± 0.9 kg (p < 0.001). Change in physical activity was +70 ± 140 min/week among those who found the website helpful, -6 ± 75 min/week among those who did not, and -34 ± 207 min/week in the comparison group (p < 0.01). CONCLUSIONS: A program to train women to use web-based weight loss tools achieved a substantial short-term weight loss among the majority of participants. Further follow-up is needed to assess weight loss maintenance over time.

Food intake and ageing--the role of the gut.

Healthy ageing is associated with decreased appetite and energy intake and this is generally associated with weight loss after about 70 years of age. The mechanisms responsible for this 'physiological' anorexia are not well understood, but it may predispose to the development of protein-energy malnutrition in older people, which is associated with increased morbidity and mortality. Many sensory and social factors, including olfactory changes and economic status, contribute to under-nutrition in older people; however, normal ageing is associated with a number of significant changes in gastrointestinal function. The control of appetite is complex but it is clear that gastrointestinal signals are important in the regulation of appetite and food intake. This review examines the role of small intestinal hormones and gastrointestinal motor function in the observed changes to appetite and food intake in older people.