Effectiveness, Safety, and Appropriateness in the Use of the Fixed-Ratio Combination of Insulin Glargine and Lixisenatide in Type 2 Diabetes: The ENSURE Retrospective Real-World Study

Introduction Pivotal trials documented glycemic benefits of fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi), with no weight gain and low hypoglycemia risk in type 2 diabetes (T2D). This study aimed at assessing effectiveness and patterns of use of iGlarLixi in a real-world setting. Methods This was a retrospective, multicenter, study, based on electronic medical records. All patients initiating iGlarLixi from May 2018 to July 2020 were considered. Results Overall, 25 centers provided data on 675 patients initiating iGlarLixi with the following characteristics: age 66.4 +/- 10.1 years, 54.2% men, T2D duration 15.5 +/- 11.5 years, HbA1c 8.6 +/- 1.4%, body mass index (BMI) 30.8 +/- 5.3 kg/m(2), 45.1% already treated with basal insulin, and 21.9% with basal bolus (+/- oral hypoglycemic agents). Metformin and sodium-glucose cotransporter-2 inhibitors were used in 76.0% and 0.9% of patients, respectively. Combinations of iGlarLixi with other glucose-lowering drugs such as sulfonylureas or short-acting insulin were found in 32.4% of patients. Effectiveness of iGlarLixi (N = 184) showed that HbA1c declined by 0.77% [95% confidence interval (CI) -1.00, -0.54] after 6 months. In combination with metformin and/or SGLT-2i (N = 117), HbA1c declined by -0.92% (95% CI -1.22, -0.62) and weight significantly decreased by 1.21 kg. iGlarLixi dose was suboptimally titrated. Safety data (N = 171) showed incidence rates of blood glucose <= 70 and < 54 mg/mL of 0.26 and 0.05 events per person-month during 6 months, respectively, with a risk reduction of about 75% with respect the 6 months before iGlarLixi initiation. No severe hypoglycemia was reported. Conclusion In adults with T2D, effectiveness and safety of iGlarLixi were documented in a real-world setting; appropriateness of use and adequate titration should be urgently improved so that clinical practice outcomes become more comparable to clinical trials results. Further real-world studies on the effect of iGlarLixi therapy are warranted

Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis

Background: Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. Methods: All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. Results: Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. Conclusion: This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women

Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis.

Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P &lt; 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women

Recurrence and Survival after Minimally Invasive and Open Esophagectomy for Esophageal Cancer: A Post Hoc Analysis of the Ensure Study

Objective: To determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. Background: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. Methods: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS). Results: In total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates (P = 0.005) and nodal yield (P < 0.001) were independently increased after TMIE, but not HMIE (P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE. Conclusion: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer

Effect of reduced follow-up care on patient satisfaction with care among patients with endometrial cancer: The ENSURE randomized controlled trial

Background: Evidence on the optimal follow-up schedule after endometrial cancer is lacking. The study aim was to compare satisfaction with care between women who received reduced follow-up care and women who received usual guideline-directed follow-up care for three years after surgery. Methods: The ENSURE (ENdometrial cancer SURvivors' follow-up carE) trial was a non-inferiority randomized controlled multicenter trial in 42 hospitals in the Netherlands. The intervention arm received reduced follow-up care (4 visits/3 years), while the control group received usual follow-up care (8–11 visits/3 years). Primary outcome was overall satisfaction with care, PSQIII score, over three years follow-up, with a non-inferiority margin of 6. Mixed linear regression, intention-to-treat and per-protocol analyses (presented below) were used. Results: Among 316 women included, overall satisfaction with care was not lower in the reduced follow-up (mean 82; SD = 15) compared with the usual follow-up group (mean 80; SD = 15) group (B = 1.80(−2.09;5.68)). At 6, 12 and 36 months, more women (93/94/90%) in the reduced follow-up group were satisfied with their follow-up schedule than in the usual follow-up group (79/79/82%; p < 0.001; p < 0.001; p = 0.050). Conclusions and relevance: Women with low-risk, early-stage endometrial cancer who received reduced follow-up care were no less satisfied with their care than women receiving usual follow-up care. Compared with usual follow-up, women in the reduced follow-up group had fewer clinical visits and, at the same time, more often reported being satisfied with their follow-up schedule. Findings suggest that reduced follow-up care may be the new standard, but should be tailored to meet additional needs where indicated

An International Multicenter Study Exploring Whether Surveillance After Esophageal Cancer Surgery Impacts Oncological and Quality of Life Outcomes (ENSURE)

OBJECTIVE: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer. SUMMARY BACKGROUND DATA: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence. METHODS: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed. RESULTS: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL. CONCLUSIONS: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding