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Purpose The assessment of quality of life (QOL) among ovarian cancer (OC) patients has mainly focused on the acute phase of treatment. This systematic review examines studies measuring QOL in patients who survived OC after treatment and synthesizes results in order to assess QOL and patient-reported outcome (PRO) data at long-term follow-up. Methods Articles published in English between 1990 to November 2014 were identified with the databases MEDLINE and PubMed, using the specific keywords “OC survivors” combined with the terms, “QOL,” “health-related QOL,” and “PROs.” Data were reviewed for design, time since end of treatment, measurement tools, and outcomes (categorized in three topics: global QOL compared to controls, treatment sequelae, and intervention strategies). Results The initial search strategy provided 148 articles of which 31 were considered eligible. Most studies focused on epithelial OC, and only a few studies investigated survivors of ovarian germ cell tumor. More than 60 instruments of QOL measures were used in the corpus. Despite the persistence of psychological and physical symptoms, treatment sequelae, sexual problems, and fear of recurrence in some survivors, most studies demonstrated that OC survivors generally have good QOL compared to healthy women. Studies proposing interventions are lacking. Conclusions and Implications for Cancer Survivor OC survivors experience a wide range of sequelae that may persist for a long time and negatively impact QOL. Further large-scale research is needed to fully understand problems that have significant effects on QOL, in order to develop interventions and treatments suitable for women at need.

Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Clovis Oncology.

Background: Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients. Methods: In this multicenter, open-label, phase 2 study, patients with advanced or metastatic endometrial cancer refractory to one or two previous chemotherapy regimens received everolimus 10 mg per day until progression or unacceptable toxicity. Primary end point was the non-progressive disease rate at 3 months. Secondary end points included duration of response, progression-free, and overall survival (OS), and safety. Results: Forty-four patients were enrolled (median age, 65 years); 66% received one previous chemotherapy regimen. The 3-month non-progressive disease rate was 36% (95% confidence interval 22–52%), including two patients (5%) with partial response (PR). At 6 months, two additional patients experienced PR. Median duration of response was 3.1 months. Median progression-free and OS were 2.8 months and 8.1 months, respectively. The most common adverse events were anaemia (100%), fatigue (93%), hypercholesterolaemia (81%), and lymphopenia (81%). Conclusion: Everolimus demonstrated efficacy and acceptable tolerability in patients with chemotherapy-refractory advanced or metastatic endometrial cancer. These results support the further development of phosphatidylinositol 3-kinase-targeted therapies in endometrial cancer.

Complaints of sleep disturbance are prevalent among breast cancer (BC) patients and are predictors of quality of life. Still, electrophysiological measures of sleep are missing in patients, which prevents from understanding the pathophysiological consequences of cancer and its past treatments. Using polysomnography, sleep can be investigated in terms of macro- (e.g. awakenings, sleep stages) and micro- (i.e. cortical activity) structure. We aimed to characterize sleep complaints, and macro- and microstructure in 33 BC survivors untreated by chemotherapy and that had finished radiotherapy since at least 6 months (i.e. out of the acute effects of radiotherapy) compared to 21 healthy controls (HC). Compared to HC, BC patients had a larger number of awakenings ( p  = 0.008); and lower Delta power ( p  < 0.001), related to sleep deepening and homeostasis; greater both Alpha ( p  = 0.002) and Beta power ( p  < 0.001), related to arousal during deep sleep; and lower Theta power ( p  = 0.004), related to emotion regulation during dream sleep. Here we show that patients have increased cortical activity related to arousal and lower activity related to sleep homeostasis compared to controls. These results give additional insights in sleep pathophysiology of BC survivors and suggest sleep homeostasis disruption in non-advanced stages of BC.

Backround: Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. Methods: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. Results: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8–6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. Conclusions: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

Objective : Faecal bifidobacteria and lactobacilli, perceived as exerting health-promoting properties, may be increased by ingestion of high-dose lactulose in humans. The effects of low and well-tolerated doses of lactulose are not well known. The aim of the study was to assess the effects of prolonged low-dose lactulose administration on faecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis. Subjects and methods : In all, 16 healthy volunteers were included in this controlled, randomised, double-blind, parallel group trial. Participants ingested lactulose or placebo (sucrose) at a dose of 5 g b.i.d. for 6 weeks. Stools were regularly collected at baseline (d0), and after 3 (d21) and 6 (d42) weeks of sugar ingestion. Tolerance was evaluated using a daily chart. Results : Faecal bifidobacterial counts were higher in lactulose than in sucrose group ( P =0.03). Lactulose ingestion led to a significant increase in faecal bifidobacteria counts from d0 to d21 and d42 (( m ±s.e.m.) 8.25±0.53, 8.96±0.40 and 9.54±0.28 log colony-forming units/g wet wt (CFU/g), respectively ( P =0.048)). Placebo ingestion did not lead to any faecal bifidobacterial count change. Total anaerobes, Lactobacillus and pH were not significantly changed throughout the study in the two groups. Neither faecal bile acids nor neutral sterols were modified by lactulose. Excess flatus was more common in the lactulose group ( P =0.03), but was very mild. Bloating and borborygmi did not differ between both the groups. Conclusions : A measure of 10 g lactulose/day increases faecal bifidobacterial counts, and lactulose fulfils the criteria requested to be considered as a prebiotic.

Purpose Impairment of cognitive function, a common complaint in patients receiving chemotherapy, is usually measured through neuropsychological tests. Patient self-evaluation of cognitive difficulties is an important complement to those tests. The Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) is a self-report questionnaire with potential to be used in standard clinical practice as a tool for evaluating patient's cognitive function before, during, and after chemotherapy. The purpose of our study was to conduct linguistic validation of the French version of the FACT-Cog. Methods Both qualitative and quantitative methods were used in this study. After undergoing a rigorous translation methodology, the French FACT-Cog version was pretested in France with 35 cancer patients undergoing chemotherapy treatment. Interviews were conducted with all patients to ascertain their understanding of each item. The validation of the final version was conducted among 63 cancer patients, and sociodemographic information was collected as well as brief measure of cognitive function and depression score. Results Patient comments obtained through the cognitive debriefing interviews indicated that patients understand the French FACT-Cog items as they are intended and that the measure is culturally appropriate. Internal consistency reliability of the subscales, evaluated using Cronbach's coefficient alpha, was high for all four subscales: Perceived Cognitive Impairments  = 0.93, Impact On QOL  = 0.85, Comments From Others  = 0.70, and Perceived Cognitive Abilities  = 0.89. All item-total correlations for each subscale were greater than 0.20, and most were greater than 0.50. Conclusions Results from this study effectively demonstrate that the French FACT-Cog is a reliable instrument for the self-reporting of cognitive abilities in patients undergoing chemotherapy.

Mongolia is subject to regular peaks of livestock winter mortality called dzuds. Several kinds of dzud exist and the ‘white dzud’, characterized by heavy stochastic snowfalls preventing livestock to access forage, is considered the most common. Droughts and high livestock densities are thought to be part of the dzud process by affecting body condition, which increases vulnerability to snowfalls. Guided by the equilibrium/nonequilibrium framework, we studied how rainfall, animal numbers and pasture health (defined as the integrity of ecological processes sustaining grass growth) impact livestock body condition in a case study of West Mongolia. We studied this parameter through livestock productivity (LP) as a proxy, defined as the annual number of newborns per breeding-age female. We found no significant impact of rainfall or livestock numbers, alone or combined. We found through the study of pasture use, defined as the ratio forage consumed/forage available, an impact of the combined effect of rainfall, animal numbers and pasture health. We observed in addition sharp LP decreases prior to dzuds, which suggests that the above-mentioned drivers interact to weaken livestock which increases its vulnerability to winter hazards. This tends to show that in our case study, dzuds are not the simple consequence of stochastic hazards striking randomly, but instead, the final stage of a chain of events that involves dry years, high livestock densities and pasture degradation. This also indicates that dzud early warning indicators could be designed based on LP monitoring.

Background: The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma. Methods: A multicentre, single-arm phase II trial was conducted. The primary objective was to determine the non-progression rate (RECIST) at 24 weeks for patients receiving sorafenib at a dose of 800 mg per day. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and HRQoL. Results: Thirty-two patients were included. Ten patients showed non-progression at 24 weeks (31.2%) without objective tumour responses. The estimated 24-week PFS was 31.2% (95% CI: 14.8%–47.6%) and the estimated 24-week OS was 62.5% (95% CI: 45.4%–79.6%). Ten patients (34.3%) had at least one grade 3 or 4 adverse reaction and 12 patients (41.4%) required dose modifications due to toxicity. At 24 weeks, no patient had an improvement in global HRQoL and 87.5% experienced a permanent increase in physical fatigue. Conclusions: Sorafenib demonstrated non-progression at 24 weeks in 31.2% of patients. However, 41.4% of patients required dose modifications due to toxicity and no improvement in HRQoL was demonstrated.

PurposeOral anticancer therapies have an important place in the therapeutic arsenal, but factors influencing adherence to oral treatment are poorly documented in oncology. The objective of this study was to assess the impact of anxio-depressive symptoms and cognitive functioning on oral medication adherence.MethodsThis prospective study included cancer patients initiating a first oral therapy. Before initiation of treatment, an assessment of depression, anxiety, and cognition was performed. Using self-report questionnaires, we collected information on socio-demographic conditions and the non-adherence at 1 (M1) and 3 months (M3) after the beginning of treatment.ResultsAmong 129 patients enrolled, median age was 70 years and 81% of patients were treated for metastatic cancer. Before initiating treatment, 16% and 8% of patients presented respectively depression and anxiety symptoms. Global cognitive impairment was observed in 51% of patients. Ten percent of the patients were non-adherent at M1 and 13% at M3. Depression was strongly associated with non-adherence at M1 (P = 0.046) and M3 (P = 0.014), but not anxiety. Non-adherence was associated with lower working memory (P = 0.037) and digit memory (P = 0.018) at M1 and short-term memory (P = 0.04) at M3. Patients with more than eight co-medications were more often non-adherents (P = 0.055).ConclusionsNon-adherence to oral anticancer therapies was mainly associated to depression. Focusing on depressive symptoms before initiation of oral anticancer therapy could help to identify patient profiles more likely to fail self-management. Working memory, digit memory, and short-term memory also seem to play a role in non-adherence. Further studies should include a more specific population, especially according to age.