Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Celiac Disease Diagnosed through Screening Programs in At-Risk Adults Is Not Associated with Worse Adherence to the Gluten-Free Diet and Might Protect from Osteopenia/Osteoporosis

Screening strategies to detect celiac disease (CD) in at-risk subjects are of paramount importance to prevent the possible long-term complications of this condition. It is therefore of strategic relevance to understand whether patients diagnosed through screening follow a strict gluten-free diet (GFD), as the non-compliance to this diet can make screening efforts pointless. Currently, no studies have verified whether CD patients diagnosed in their adulthood are adhering to the GFD years after the diagnosis. We retrospectively evaluated the medical records of 750 CD patients diagnosed in our center during January 2004⁻December 2013 to verify differences between screening detected and clinically diagnosed patients. The groups shared a similar adherence to the GFD (91.2 versus 89.8%, p = 0.857). Moreover, the rates of non-responsive CD, GFD-induced metabolic alterations, and persistence in controls were also similar. Instead, screening-detected patients had a significantly lower rate of osteopenia/osteoporosis at diagnosis (31.3 versus 46%, p < 0.001). In conclusion, screening strategies for CD in at-risk groups should be encouraged even in the adult population. Patients diagnosed through these strategies had no additional problems compared to those diagnosed for clinical suspicion and might benefit from a protective effect against metabolic bone disease

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059–1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and “Bread and bakery” (p = 0.002), “salty convenience” (p = 0.005), and “sweet convenience” (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas

Risk of Drop-Out from Follow-Up Evaluations for Celiac Disease: Is It Similar for All Patients?

Background: Celiac disease (CD) follow-up is a relatively underevaluated topic. However, correct adherence to follow-up procedures is central to the early recognition of complicated CD and other conditions typically associated with CD. Establishing whether patients at increased risk of complications follow clinicians’ recommendations has multiple repercussions. Methods: We retrospectively analyzed the records of patients consecutively diagnosed with CD in our outpatient clinic between January 2004 and October 2017 to investigate the factors associated with drop-out from follow-up procedures. Results: Among the 578 patients analyzed, 40 (6.9%) dropped out during the first six months and 272 (50.6%) during the observation period. The median time to drop-out was 7.4 years (95% confidence interval: 6.8–8.0). No factors were associated with early drop-out. Instead, age at diagnosis >40 years (40–59 years, p < 0.001; ≥60 years, p = 0.048) and classical clinical presentation (p = 0.016) were significantly associated with a lower risk of later drop-out. Conclusions: Patients at increased risk of complicated CD are more compliant with follow-up procedures than patients at lower risk, despite being prescribed the same controls. These results indirectly support the hypothesis of tailored follow-up strategies, differentiated according to the risk of complications

Presurgical window of opportunity trial design as a platform for testing anticancer drugs: Pros, cons and a focus on breast cancer

The high attrition rate is a major issue in anticancer drug development. Among the alternative trial designs, presurgical window of opportunity trials envision a short course treatment in the time window between diagnostic biopsy and surgery in a moderately-sized patient population. This approach allows testing therapeutics when pre- and post-treatment tumor tissues are available for comprehensive molecular analyses. The emerging evidence may help define the ability of a given agent to modulate its target(s) and help obtain a broader picture of the molecular changes operated by the treatment. The resulting gain may outweigh the potential harms for patients in the early disease setting. Window of opportunity trials have been extensively applied to breast cancer. Overall, a wider use of these trial designs might lead to the identification of potential responders, ineffective drugs or combinations, and ultimately contribute to enhance the efficiency of the clinical developmental process

Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc