Depression is associated with some patient-perceived cosmetic changes, but not with radiotherapy-induced late toxicity, in long-term breast cancer survivors.: Depression-associated factors in long-term breast cancer survivors

International audienceOBJECTIVE: Although depression is prevalent in long-term breast cancer survivors (LTBCS; ≥5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS. METHODS: In all, 214 patients recruited from the ARCOSEIN study were assessed for late radiotherapy toxicity (by using the LENT-SOMA scale) and patient and doctor ratings of breast cosmetic outcomes (mean = 6.7 years since the end of treatment). We reassessed 120 of these patients for depression (HAD) during a second wave of long-term assessment (mean = 8.1 years since the end of treatment). We used univariate analyses and polytomous logistic regression analyses to predict the HAD depression, which was defined as follows: normal, 0-7 points; and significant depression, ≥8 points (8-10 points, possible depression; ≥11 points, probable depression). RESULTS: The mean HAD depression score was 4.5 ± 3.6. 19. 2% of our population had significant depression, 6.7% with probable depression, and 12.5% with possible depression. Significant depression was not associated with late radiotherapy toxicity or initial cancer-related variables. Patients with probable depression reported worse cosmetic outcomes than nondepressed patients in terms of perceived breast largeness (p = 0.04), breast deformation (p = 0.02), and changes in skin pigmentation (p = 0.03). CONCLUSIONS: In LTBCS, depression seems to be more strongly associated with changes in some patients' perceived breast cosmetic outcome than late treatment toxicity or initial cancer-related variables. Copyright © 2012 John Wiley & Sons, Ltd

Integrative Oncology: An International Perspective from Six Countries.

In June 2019, a meeting was held in Paris in which experts from different countries (Israel, Spain, Belgium, Italy, USA, and France) met to discuss a selection of topics in integrative oncology (IO). The objectives were to draw on the delegates’ experience and expertise to begin an international collaboration, sharing details of differing existing models and discussing future perspectives to help define and guide practice in IO and define unmet needs. This report presents a summary of the meeting’s main presentations, and also reports on the experts’ responses to a questionnaire examining different aspects of IO service delivery, infrastructure, and utilization.post-print203 K

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

Background: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. Objective: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participants: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysis: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitations: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). Conclusions: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summary: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Evaluation globale de la qualité de vie après traitement conservateur des cancers du sein

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Résultats à long terme de la radiochimiothérapie concomitante après traitement conservateur du cancer du sein de stade I, II (résultats de l'essai randomisé multicentrique ARCOSEIN)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Visualization of ribonucleotide reductase catalytic oxidation establishes thioredoxins as its major reductants in yeast.

Thioredoxins and/or glutaredoxins assist ribonucleotide reductase, and other such enzymes that require disulfide bond reduction during their catalytic cycle. In Saccharomyces cerevisiae, the presence of either pathway is essential but which of these pathways operates in ribonucleotide reductase reduction and how this function contributes to the pathways' essential nature have not been definitively established. We have identified two in vivo redox forms of the S. cerevisiae ribonucleotide reductase R1 subunit, which correspond to catalytically reduced or oxidized enzymes. Cells lacking thioredoxins, which exhibit an elongated S phase, accumulate R1 in its oxidized form and also contain significantly decreased deoxyribonucleotide levels during the S phase. Overexpressing R1 in these cells increases both the amount of the R1 reduced form and the concentrations of deoxyribonucleotides and accelerates DNA replication. These results establish thioredoxins as the major RNR reducing system in yeast and indicate that impaired RNR reduction accounts for the S phase defects of thioredoxin-deficient cells

Biosimilar filgrastim treatment patterns and prevention of febrile neutropenia: a prospective multicentre study in France in patients with solid tumours (the ZOHé study)

Abstract Background The ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT). Methods Patients ≥ 18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines. Results Responses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ≥ 1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (< 10%) FN risk (‘over prophylaxis’). Nearly half of patients’ CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ≥ 2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed. Conclusions Use of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians’ decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of < 10%