Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database.

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

Altered Position Sense after Submaximal Eccentric Exercise-inducing Central Fatigue.

PURPOSE: The purpose of this study was to concomitantly investigate the acute and delayed effects of a submaximal eccentric-induced muscle fatigue on the position sense and the neuromuscular function of the right knee extensor muscles. METHODS: Thirteen young and physically active participants performed a unilateral isokinetic eccentric exercise of their right lower limb until a decrease in maximal voluntary isometric contraction (MVIC) of 20% was reached. Neuromuscular (i.e., MVIC, voluntary activation (VA) level, and evoked contractile properties [DB100 and DB10]) and psychophysical evaluations (i.e., bilateral position-matching task, perceived muscle soreness, and perceived fatigue) were performed at four time points: before (PRE), immediately after (POST), 24 (POST24), and 48 (POST48) the exercise. RESULTS: The acute 20% MVIC reduction (P < 0.001) was associated with both central (i.e., -13% VA decrease, P < 0.01) and peripheral (i.e., -18% and -42% reduction of DB100 and DB10, respectively, P < 0.001) fatigue. In the following days (POST24 and POST48), VA levels had recovered despite the presence of a persisting peripheral fatigue and delayed-onset muscle soreness. Knee position sense, as revealed by position errors, was significantly altered only at POST (P < 0.05) with participants overestimating the length of their knee extensor. Position errors and VA deficits were significantly correlated at POST (r = -0.60, P = 0.03). Position errors returned to nonsignificant control values in the following days. CONCLUSION: The acute central fatigue induced by the eccentric exercise contributes to the position sense disturbances. Central fatigue might lead to alterations in the sensory structures responsible for the integration and the processing of position-related sensory inputs.

[Techniques from EMDR Psychotherapy : a tool against disruptive psycho-behavioural disorders?] / Techniques issues de la psychothérapie EMDR : un outil contre les troubles psycho-comportementaux ?

Behavioural disorders in residential care facilities for dependent seniors are particularly common in residents with Alzheimer's and related diseases. Verbal agitation is one of the most disruptive behavioural disorders. The use of techniques from Eye Movement Desensitisation and Reprocessing therapy in gerontology, its applications and research perspectives may be illustrated.

[Protein supplementation to prevent loss in muscle mass and strength in frail older patients: a review]. / Quels bénéfices attendre de la supplémentation en protéines pour limiter la perte de masse et de fonction musculaire chez le sujet âgé fragile ?

Minimum levels of protein intake are essential for the preservation of muscle mass and function, which is a major preventive issue of successful aging. Epidemiological studies suggest strong associations between protein intake and the different elements of sarcopenia, namely maintenance of lean mass and muscle strength. Most often, protein intakes among older patients are below requirements, independently from situations of under nutrition. This opens the path for nutritional interventions to prevent the consequences of sarcopenia in older patients. Isolated amino-acids such as leucine have shown positive effects in the short term only. The positive effects of protein supplementations on muscle strength and function are currently not established in the absence of concomitant exercise training. The highest level of evidence supports interventions combining exercise and nutrition.

Hyperthermic intraperitoneal chemotherapy for the treatment of recurrent ovarian cancer in elderly women.

Our aim was to evaluate the morbidity and survival associated with combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of recurrent ovarian cancer for patients aged 70 years and older. We conducted a monocentric study in a French university hospital and collected data on 15 women aged ≥ 70 years, treated by cytoreduction and HIPEC for ovarian cancer relapse. The median overall survival was 35 months, with a median disease-free survival of 15.6 months. When a Peritoneal Cancer Index subgroup analysis was performed, a statistically significant difference in the disease-free survival could be observed for a Peritoneal Cancer Index ≤ 13 (p = 0.036). A trend towards improvement of disease-free survival was observed when the Completeness of Cytoreductive Score was equal to 0 (p = 0.0915).