Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial.

PURPOSE: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status. METHODS: Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity. RESULTS: Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9-85.4) vs. 71.9% (95%CI: 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8-83.2) vs. 61.5% (95%CI: 42.5-77.6), 82.4% (95%CI: 62.2-93.6) vs. 100% (95%CI: 74.1-100), and 90% (95%CI: 69.8-98.3) vs. 100% (95%CI: 74.1-100). Toxicity profile was consistent with previous reports. CONCLUSION: Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned. TRIAL REGISTRATION NUMBER: NCT02339532 (registered on 14/12/14).

Survival outcomes of metastatic breast cancer patients by germline BRCA1/2 status in a large multicenter real-world database.

The outcomes and best treatment strategies for germline BRCA1/2 mutation (gBRCAm) carriers with metastatic breast cancer (MBC) remain uncertain. We compared the overall survival and the first line progression free survival (PFS1) of patients with a gBRCAm identified at initiation of first-line treatment with those of BRCA wild-type (WT) and not-tested (NT) individuals in the ESME real-world database of MBC patients between 2008 and 2016 (NCT03275311). Among the 20 624 eligible patients, 325 had a gBRCAm, 1138 were WT and 19 161 NT. Compared with WT, gBRCAm carriers were younger, and had more aggressive diseases. At a median follow-up of 50.5 months, median OS was 30.6 (95%CI: 21.9-34.3), 35.8 (95%CI: 32.2-37.8) and 39.3 months (95% CI: 38.3-40.3) in the gBRCAm, WT and NT subgroups, respectively. Median PFS1 was 7.9 (95%CI: 6.6-9.3), 7.8 (95%CI: 7.3-8.5) and 9.7 months (95%CI, 9.5-10.0). In the multivariable analysis conducted in the whole cohort, gBRCAm status had however no independent prognostic impact on OS and PFS1. Though, in the triple-negative subgroup, gBRCAm patients had better OS and PFS1 (HR vs WT = 0.76; 95%CI: 0.60-0.97; P = .027 and 0.69; 95% CI: 0.55-0.86; P = .001, respectively). In contrast, in patients with HR+/HER2 negative cancers, PFS1 appeared significantly and OS non significantly lower for gBRCAm carriers (PFS1: HR vs WT = 1.23; 95%CI: 1.03-1.46; P = .024; OS:HR = 1.22, 95% CI: 0.97-1.52, P = .089). In conclusion, gBRCA1/2 status appears to have divergent survival effects in MBC according to IHC subtype.

Baseline quality of life and chemotherapy toxicities in patients with early breast cancer.

BACKGROUND: The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose-reductions (CDRs) or postchemotherapy-toxicities (PCTs). METHODS: In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associations between baseline physical functioning (PF) and fatigue measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30, and two endpoints-CDRs during adjuvant or neoadjuvant chemotherapy; and selected PCTs were estimated with odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) using logistic regression models. RESULTS: Among the 3079 patients from the CANTO cohort who were included, 718 (33.0%) received chemotherapy in the neoadjuvant setting, and 2361 (67.0%) received chemotherapy as adjuvant treatment. The chemotherapy included taxanes in 94.2% of patients and anthracyclines in 90.5% of patients. Overall, 15.5% of patients experienced CDRs and, 31.0% developed PCTs. Women with low baseline PF scores (<83) had higher multivariate odds of developing CDRs compared with those who had PF scores ≥83 (OR, 1.54; 95% CI, 1.13-2.09). The corresponding OR for PCTs was 1.50 (95% CI, 1.13-2.00). Women with high baseline fatigue scores had higher odds of CDRs (OR, 1.43; 95% CI, 1.13-1.76) and PCTs (OR, 1.32; 95% CI, 1.10-1.59). CONCLUSIONS: By using the national CANTO cohort, baseline PF and fatigue were independently associated with CDRs and PCTs.

Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort.

OBJECTIVE: The aim was to evaluate the impact of local surgery performed during the year after MBC diagnosis on patients' outcomes from a large reallife cohort. SUMMARY BACKGROUND DATA: Locoregional treatment for patients with MBC at the time of diagnosis remains debated. METHODS: Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis. RESULTS: Out of 16,703 patients in the ESME database, 1977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, P < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, P < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, P < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61-0.92] and 0.72 [0.63-0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype, and age. CONCLUSIONS: In the large ESME cohort, surgery within 1 year after de novo MBC diagnosis was associated with a significantly better OS and PFS.

Pattern and risk factors of isolated local relapse among women with hormone receptor-positive and HER2-negative breast cancer and lymph node involvement: 10-year follow-up analysis of the PACS 01 and PACS 04 trials.

PURPOSE: We aimed to determine the pattern of isolated local recurrences (ILR) in women with stage II-III hormone receptor-positive and human epidermal growth factor receptor 2 breast cancer (HR + /HER2-BC) after 10-year follow-up. METHODS: UNICANCER-PACS 01 and PACS 04 trials included 5,008 women with T1-T3 and N1-N3 to evaluate the efficacy of different anthracycline ± taxanes-containing regimens after modified mastectomy or lumpectomy plus axillary lymph node dissection. We analyzed the data from 2,932 women with HR + /HER2- BC to evaluate the cumulative incidence of ILR and describe the factors associated with ILR. RESULTS: After a median follow-up of 9.1 years (95% CI 9.0-9.2 years), the cumulative incidence of ILR increased steadily between 1 and 10 years from 0.2% to 2.5%. The multivariable analysis showed that older age (subhazard ratios [sHR] = 0.95, 95% CI 0.92-0.99) and mastectomy (sHR = 0.39, 95% CI 0.17-0.86) were associated with lower risk of ILR, and no adjuvant endocrine therapy (sHR = 2.73, 95% CI 1.32 7-5.67) with increased risk of ILR. CONCLUSION: In this population of high-risk patients with localized HR + /HER2- BC, the risk of ILR was low but remained constant over 10 years. Younger age at diagnosis, breast-conserving surgery, and adjuvant endocrine therapy were independent risk factors of ILR.

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.

Assessment of quality of life after laparoscopic GERD surgery in children: a prospective study.

The purpose of this study is to assess quality of life (QoL) after laparoscopic anti-reflux surgery (LARS) in children with gastroesophageal reflux disease (GERD) and to evaluate GERD symptoms and their impact on daily life and school. From June 2016 to June 2019, all children with GERD from 2 to 16 years of age, without neurologic impairment or malformation-related reflux, were prospectively included in a monocentric study. Patients (or their parents according to the age of the child) answered the Pediatric Questionnaire on Gastroesophageal Symptoms and QoL (PGSQ) before surgery and 3 and 12 months after surgery. Variables were compared by paired, bilateral Student t-test. Twenty-eight children (16 boys) were included. The median age at surgery was 77 months (IQR: 59.2-137) with median weight of 22 kg (IQR: 19.8-42.3). All had a laparoscopic Toupet fundoplication. Median duration of follow-up was 14.7 months (IQR: 12.3-22.5). One patient (4%) had a recurrence of GERD symptoms without abnormalities on follow-up examinations. Preoperative total PGSQ score was 1.42 (± 0.7) and decreased significantly 3 months (0.56 ± 0.6; p < 0.001) and 12 months after surgery (0.34 ± 0.4; p < 0.001). PGSQ subscale analysis revealed a significant decrease at 3 and 12 months for GERD symptoms (p < 0.001), impact on daily life (p < 0.001), and impact on school (p = 0.03). CONCLUSION: There was a significant improvement in symptoms and their frequency after LARS in children, as well as an improvement of QoL, in the short and medium term. The impact of GERD should be taken into consideration in the treatment decision, given that surgery clearly improves the QoL. WHAT IS KNOWN: • Laparoscopic anti-reflux surgery (LARS) is an established and effective treatment option in pediatric patients with severe GERD refractory to medical treatment. • Effect of LARS on the quality of life (QoL) has been mainly investigated in the adult population but there is very little data on the effect of LARS on the QoL in pediatric patients. WHAT IS NEW: • Our prospective study was the first to analyze the effect of LARS on QoL in pediatric patients without neurologic impairment using validated questionnaires at two postoperative time points with a significant improvement in postoperative QoL at 3 and 12 months. • Our study emphasizes the importance of evaluating QoL and impact of GERD on all the aspects of daily life and of taking these into consideration in the treatment decision.

Evaluation of quality of care in neonatal anesthesia using a bundle of intraoperative parameters.

BACKGROUND: Maintenance of physiological homeostasis is key in the safe conduct of pediatric anesthesia. Achieving this goal is especially difficult in neonatal surgery. AIMS: The first aim was to document the absolute number of seven intraoperative parameters monitored during anesthesia in neonates undergoing gastroschisis surgery. The second aims were to determine the frequency of monitoring of each of these intraoperative parameters as well as the proportion of cases in which each parameter was both monitored and maintained within a pre-defined range. METHODS: This retrospective observational analysis includes data from 53 gastroschisis surgeries performed at Caen University Hospital (2009-2020). Seven intraoperative parameters were analyzed. First, we assessed if the intraoperative parameters were monitored or not. Second, when monitored, we assessed if these parameters were maintained within a pre-defined range, based on the current literature and on local agreement. RESULTS: The median [first-third Q], range (min-max) number of intraoperative parameters monitored during the 53 gastroschisis surgeries was 6 [5-6], range (4-7). There were no missing data for the automatically recorded ones such as arterial blood pressure, heart rate, end-tidal CO2, and oxygen saturation. Temperature was monitored in 38% of the patients, glycemia in 66%, and natremia in 68% of the cases. Oxygen saturation and heart rate were maintained within the pre-defined range in 96% and 81% of the cases respectively. The blood pressure (28%) and temperature (30%) were instead the least often maintained within the pre-defined range. CONCLUSION: Although a median of six out of the seven selected intraoperative parameters were monitored during gastroschisis repair, only two of them (oxygen saturation and heart rate) were maintained within the pre-defined range more than 80% of the time. It might be of interest to extend physiologic age- and procedure-based approach to the development of specific preoperative anesthetic planning.

Progression-free survival on endocrine therapy, before or after chemotherapy, in hormone receptor-positive HER2-negative metastatic breast cancer.

PURPOSE: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. METHODS: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2- MBC who received ET or CT first. RESULTS: We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9-13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1-13.4), HR 0.96 (95% CI 0.90-1.01, P = 0.1277). CONCLUSIONS: PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance.

Unhealthy behaviors after breast cancer: Capitalizing on a teachable moment to promote lifestyle improvements.

BACKGROUND: This study assessed the prevalence and risk factors of unhealthy behaviors among survivors of early-stage breast cancer. METHODS: Women (n = 9556) from the CANcer TOxicity cohort (NCT01993498) were included. Physical activity (PA), tobacco and alcohol consumption, and body mass index were assessed at diagnosis and at years 1 and 2 after diagnosis. A behavior was defined as unhealthy if patients failed to meet PA recommendations (≥10 metabolic equivalent task hours per week), reduce/quit tobacco, or decrease alcohol consumption to less than daily, or if they gained substantial weight over time. Multivariable-adjusted generalized estimating equations explored associations with unhealthy behaviors. RESULTS: At diagnosis, 41.7% of patients were inactive, 18.2% currently used tobacco, 14.6% consumed alcohol daily, and 48.9% were overweight or obese. At years 1 and 2, unhealthy PA behavior was reported among 37.0% and 35.6% of patients, respectively, unhealthy tobacco use behavior was reported among 11.4% and 9.5%, respectively, and unhealthy alcohol behavior was reported among 13.1% and 12.6%, respectively. In comparison with the previous assessment, 9.4% and 5.9% of underweight and normal-weight patients had transitioned to the overweight or obese category at years 1 and 2, respectively, and 15.4% and 16.2% of overweight and obese patients had gained ≥5% of their weight at years 1 and 2, respectively. One in 3 current tobacco smokers and 1 in 10 daily alcohol users reported improved behaviors after diagnosis. Older women (5-year increment) were more likely to be inactive (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.01-1.05) and report unhealthy alcohol behavior (aOR, 1.28; 95% CI, 1.23-1.33) but were less likely to engage in unhealthy tobacco use (aOR, 0.81; 95% CI, 0.78-0.85). Being at risk for depression (vs not being at risk for depression) was associated with reduced odds of unhealthy tobacco use (aOR, 0.67; 95% CI, 0.46-0.97) and with a higher likelihood of unhealthy alcohol behavior (aOR, 1.58; 95% CI, 1.14-2.19). Women with a college education (vs a primary school education) less frequently reported an unhealthy PA behavior (aOR, 0.61; 95% CI, 0.51-0.73) and were more likely to report unhealthy alcohol behavior (aOR, 1.85; 95% CI, 1.37-2.49). Receipt of chemotherapy (vs not receiving chemotherapy) was associated with higher odds of gaining weight (aOR, 1.51; 95% CI, 1.23-1.87) among those who were overweight or obese at diagnosis. CONCLUSIONS: The majority of women were adherent to healthy lifestyle behaviors at the time of their breast cancer diagnosis, but a significant subset was nonadherent. Unhealthy behaviors tended to persist after the breast cancer diagnosis, having varying clinical, psychological, sociodemographic, and treatment-related determinants. This study will inform more targeted interventions to promote optimal health.

Multicenter evaluation of breast cancer patients' satisfaction and experience with oncology telemedicine visits during the COVID-19 pandemic.

INTRODUCTION: During the COVID-19 pandemic, teleconsultation was implemented in clinical practice to limit patient exposure to COVID-19 while monitoring their treatment and follow-up. We sought to examine the satisfaction of patients with breast cancer (BC) who underwent teleconsultations during this period. METHODS: Eighteen centres in France and Italy invited patients with BC who had at least one teleconsultation during the first wave of the COVID-19 pandemic to participate in a web-based survey that evaluated their satisfaction (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) with teleconsultation. RESULTS: Among the 1299 participants eligible for this analysis, 53% of participants were undergoing standard post-treatment follow-up while 22 and 17% were currently receiving active anticancer therapy for metastatic and localised cancers, respectively. The mean satisfaction scores were 77.4 and 73.3 for the EORTC OUT-PATSAT 35 and TSQ scores, respectively. In all, 52.6% of participants had low/no anxiety. Multivariable analysis showed that the EORTC OUT-PATSAT 35 score correlated to age, anxiety score and teleconsultation modality. The TSQ score correlated to disease status and anxiety score. CONCLUSION: Patients with BC were satisfied with oncology teleconsultations during the COVID-19 pandemic. Teleconsultation may be an acceptable alternative follow-up modality in specific circumstances.

Risk Factors of Early Mortality and Morbidity in Esophageal Atresia with Distal Tracheoesophageal Fistula: A Population-Based Cohort Study.

OBJECTIVE: To identify the risk factors for early mortality and morbidity in a population with distal esophageal atresia (EA)-tracheoesophageal fistula. STUDY DESIGN: Cohort study from a national register. Main outcomes and measures included early mortality, hospital length of stay (LoS), need for nutritional support at 1 year of age as a proxy measure of morbidity, and complications during the first year of life. RESULTS: In total, 1008 patients with a lower esophageal fistula were included from January 1, 2008, to December 31, 2014. The survival rate at 3 months was 94.9%. The cumulative hospital LoS was 31.0 (17.0-64.0) days. Multivariate analysis showed that intrahospital mortality at 3 months was associated with low birth weight (OR 0.52, 95% CI [0.38-0.72], P < .001), associated cardiac abnormalities (OR 6.09 [1.96-18.89], P = .002), and prenatal diagnosis (OR 2.96 [1.08-8.08], P = .034). LoS was associated with low birth weight (-0.225 ± 0.035, P < .001), associated malformations (0.082 ± 0.118, P < .001), surgical difficulties (0.270 ± 0.107, P < .001), and complications (0.535 ± 0.099, P < .001) during the first year of life. Predictive factors for dependency on nutrition support at 1 year of age were complications before 1 year (OR 3.28 [1.23-8.76], P < .02) and initial hospital LoS (OR 1.96 [1.15-3.33], P < .01). CONCLUSIONS: EA has a low rate of early mortality, but morbidity is high during the first year of life. Identifying factors associated with morbidity may help to improve neonatal care of this population.

Clinicopathological characterization of a real-world multicenter cohort of endometrioid ovarian carcinoma: Analysis of the French national ESME-Unicancer database.

BACKGROUND: Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes. METHODS: We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features. RESULTS: Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p < 0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p < 0.001). CONCLUSIONS: Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management.

New insights in Cercopithecinae spermatozoa.

Sperm morphometric and morphologic data have been shown to represent useful tools for monitoring fertility, improving assisted reproduction techniques and conservation of genetic material as well as detecting inbreeding of endangered primates. We provide here for the first time sperm morphologic and morphometric data from Cercopithecus neglectus, Cercopithecus cephus, Papio papio and critically endangered Cercopithecus roloway, as well as comparative data from other Cercopithecinae species, i.e. Allochrocebus lhoesti, Mandrillus sphinx and Papio anubis. Following collection from the epididymis, spermatozoa were measured for each species for the following parameters: head length, head width, head perimeter, head area, midpiece length and total flagellum length, and the head volume, ellipticity, elongation, roughness and regularity were then calculated. Our data are consistent with both the general morphology and the morphometric proportions of Cercopithecinae sperm. Some specificities were observed, with C. cephus displaying a narrow head (width = 2.76 ± 0.26 µM) and C. roloway displaying a short midpiece (6.65 ± 0.61 µM). This data set represents an important contribution, especially for Cercopithecus roloway, one of the most endangered monkeys in the world, and further data on additional specimens coupled to data on mating systems and reproductive ecology should allow a better understanding of the mechanisms underlying these morphological differences across primate species.

ANTIBODY RESPONSE TO EPSILON TOXIN OF CLOSTRIDIUM PERFRINGENS IN CAPTIVE ADULT SPRINGBOK (ANTIDORCAS MARSUPIALIS), IMPALA (AEPYCEROS MELAMPUS), ALPACA (VICUGNA PACOS), AND RED-NECKED WALLABY (MACROPUS RUFOGRISEUS) OVER A YEAR.

Enterotoxemia is an important issue in various zoological taxa. In this study, serologic responses over a 1-yr period after vaccination with a multivalent clostridial vaccine were evaluated in 10 adult springboks (Antidorcas marsupialis), 12 impalas (Aepyceros melampus), seven alpacas (Vicugna pacos), and five red-necked wallabies (Macropus rufogriseus). Antibody production to the Clostridium perfringens type D epsilon toxin component of the vaccine was measured using an indirect enzyme-linked immunosorbent assay and determined as the percentage of inhibition (% inhib). Initial % inhib was (0.01-18.9)%. All animals received initial vaccination with a booster vaccine 4 weeks apart. Serum samples were collected at T0 (nonvaccinated), 15, 30, 60, 180, and 360 days postvaccination (dpv) for analysis. The vaccine induced a high antibody response that peaked at 15, 30, and 60 dpv in springboks, 30 and 60 dpv in impalas (P < 0.01), and 60 dpv in alpacas and wallabies (P < 0.01). The booster vaccine was followed by a high antibody response, which slowly decreased with time. The antibody response was significantly higher at 360 dpv than at T0 in wallabies and alpacas (P < 0.01). In impalas and springboks, it appeared that a booster every 6 mo might be required to maintain an antibody response above baseline (P < 0.01). Because no challenge studies were performed, it is unknown whether the measured humoral immune responses would have been protective. Further research is warranted to investigate protective effects of antibodies to inoculation challenge in nondomestic species.

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial.

BACKGROUND: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab. METHODS: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251. FINDINGS: Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin-gemcitabine-bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3-21·7) in the experimental group and 11·3 months (8·0-18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7-14·2) in the experimental group versus 11·6 months (11·0-12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68-0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (<1%; large intestine perforation) and two patients in the standard group (1%; one case each of osmotic demyelination syndrome and intracranial haemorrhage). INTERPRETATION: Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer. FUNDING: F Hoffmann-La Roche.

Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial.

BACKGROUND: There is no treatment for cancer-related cognitive impairment, an important adverse effect that negatively impacts quality of life (QOL). We conducted a 3-arm randomized controlled trial to evaluate the impact of computer-assisted cognitive rehabilitation (CR) on cognition, QOL, anxiety, and depression among cancer patients treated with chemotherapy. METHODS: Patients who reported cognitive complaints during or after completing chemotherapy were randomly assigned to 1 of 3 12-week CR programs: computer-assisted CR with a neuropsychologist (experimental group A), home cognitive self-exercises (active control group B), or phone follow-up (active control group C). Subjective cognition was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), objective cognition was assessed by neuropsychological tests, QOL was assessed by the FACT-General, and depression and anxiety were assessed by psychological tests. The primary endpoint was the proportion of patients with a 7-point improvement in the FACT-Cog perceived cognitive impairment (PCI) score. RESULTS: Among the 167 enrolled patients (median age, 51 years), group A had the highest proportion of patients with a 7-point PCI improvement (75%), followed by groups B (59%) and C (57%), but the difference was not statistically significant (P = .13). Compared with groups B and C, the mean difference in PCI score was significantly higher in group A (P = .02), with better perceived cognitive abilities (P < .01) and a significant improvement in working memory (P = .03). Group A reported higher QOL related to cognition (FACT-Cog QOL) (P = .01) and improvement in depression symptoms (P = .03). CONCLUSIONS: These results suggest a benefit of a computer-based CR program in the management of cancer-related cognitive impairment and complaints.

Fulvestrant and palbociclib combination in heavily pretreated hormone receptor-positive, HER2-negative metastatic breast cancer patients.

PURPOSE: We report the results of a retrospective analysis of the fulvestrant and palbociclib combination within a temporary authorization of use (TAU) program in 77 heavily pretreated patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. METHODS: All patients who received the fulvestrant and palbociclib combination within this TAU program were included. Toxicities were graded using the CTCAE v5 scale. RESULTS: The majority of patients (62.3%) were previously treated with the mTOR inhibitor everolimus. The median number of previous treatments for their metastatic disease was 4. With a median follow-up of 14 months, the median progression-free survival (PFS) was 7.6 months. The median PFS significantly (p < 0.0001) decreased with the number of previous treatment lines in the metastatic setting. The median PFS was 5.5 months in patients who had previously progressed on everolimus compared to 9.3 months in the everolimus non-pretreated subgroup. No significant difference in median PFS was detected in patients according to age. The median overall survival rate was not reached. The clinical benefit rate was 64%, including 4% of complete responses, 26% partial responses, and 34% stable diseases for the entire cohort. CONCLUSIONS: The fulvestrant and palbociclib combination exerts an appreciable effect on metastatic heavily pretreated patients with a tolerable toxicity profile.

Persistent taxane-induced neuropathy in elderly patients treated for localized breast cancer.

Breast cancer is the most common cancer among women. Localized breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. A monocenter historical cohort study including all women over 65 years of age treated between 2001 and 2016 with a taxane-based chemotherapy for localized breast cancer was carried out at the Paul Strauss Regional Comprehensive Cancer Center. All cases included were followed up for at least 2 years, deaths from causes unrelated to TIPN were excluded. We report on the frequency and risk factors and establish a prognostic score of persistent Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9% developed persistent TIPN of grade 2 and 3, respectively. Two patients died from complications of grade 3 TIPN. Risk factors of persistent grade 2 and higher neuropathy included age (P < .0001), body mass index (P < .0001), and diabetes (P = .0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (OR = 5.43; P < .0001). Patients presenting all four major risk factors had a 97.2% probability of developing long-term symptoms against 1.2% for patients showing no risk factor. We therefore identified 3 prognostic groups. TIPN is a frequent and sometimes severe persistent side effect of breast cancer treatment among elderly women with a major impact on health-related quality of life. Chemotherapy regimens without taxane could therefore be a valid option in elderly patients with neurotoxicity risk factors.

Real-life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program.

Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth-line). No significant difference was reported in second-line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2- patients, a significant difference was seen for all lines, including 2nd-line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real-world database, HER2-negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2-targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti-HER2 therapies addition in this setting still needs to be defined.