Publications by authors named "Laurent Guy"

221 Publications

The role of CT-scan assessment of muscle mass in predicting postoperative surgical complications after renal transplantation.

Int Urol Nephrol 2021 Dec 12. Epub 2021 Dec 12.

Department of Urology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

Purpose: Despite a high rate of undernutrition in renal transplantation recipients, prognostic value of sarcopenia remains unclear. We evaluated the relation between sarcopenia and post-operative outcomes after renal transplantation.

Methods: During 7 years, each patient who underwent renal transplantation was retrospectively included. Patients with no recent pre-operative CT-scan were excluded. Sarcopenia was evaluated by measuring the muscle surface area on CT-scan section passing through the third lumbar vertebra. Main outcomes were post-operative complications at 1 month and 1 year according to the Clavien-Dindo classification.

Results: Overall, 102 patients were included. One month of complication rate was 63.9%. At 1 year, 60.8% experienced at least one medical complication and 29.4% one surgical complication. At 1 year post transplantation, low muscle density on CT scan was a surgical complication risk factor (OR = 0.6, 95% CI = [0.3-0.9], p = 0.05). The area under the curve of a 1-year complication predictive model including muscle density was 0.64. We did not observe significant relationship between CT-scan sarcopenia indicator and 1-month post-transplantation complication.

Conclusion: Although no clear link between sarcopenia and complications was exhibited in our study, low CT-scan muscle density was associated with 1-year surgical complications. The role of muscle density and its relation with sarcopenia and post-transplantation outcomes should be further explored.
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http://dx.doi.org/10.1007/s11255-021-03089-xDOI Listing
December 2021

Impact of obesity in kidney transplantation: a prospective cohort study from French registries between 2008 and 2014.

Nephrol Dial Transplant 2021 Oct 5. Epub 2021 Oct 5.

Service de Néphrologie, Dialyse et Transplantation, CHU de Clermont-Ferrand, Clermont-Ferrand, France.

Background: The access of obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis. The aim of this study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes.

Methods: We carried out a prospective cohort study using two French registries REIN and CRISTAL on 7 270 kidney transplant patients between 2008 and 2014 in France. We compared obese patients with non-obese patients and obese patients who lost more than 10% of weight before the transplant (Obese WL and Obese nWL).

Results: The mean BMI in our obese patients was 32 kg/m2. Graft survival was lower in obese patients than in non-obese patients (HR = 1.40, IC 95% [1.09; 1.78], P = 0.007) whereas patient survival was similar (HR = 0.94, IC 95% [0.73; 1.23], P = 0.66). Graft survival was significantly lower in Obese WL than in Obese nWL (HR = 2.17, CI 95% [1.02; 4.63], P = 0.045) whereas patient survival was similar in the two groups (HR = 0.79, IC 95% [0.35; 1.77], P = 0.56).

Conclusion: Grade I obesity does not seem to be a risk factor for excess mortality after kidney transplantation and should not be an obstacle to having access to a graft. Weight loss before a kidney transplant in this patients should not be essential for registration on waiting list.
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http://dx.doi.org/10.1093/ndt/gfab277DOI Listing
October 2021

Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy?

Eur Urol 2021 10 27;80(4):417-424. Epub 2021 Jun 27.

Gustave Roussy Institute, Villejuif, France.

Background: The CARMENA trial in patients with metastatic renal cell carcinoma (mRCC) demonstrated that treatment with sunitinib alone was noninferior to cytoreductive nephrectomy (CN) followed by sunitinib (nephrectomy⬜sunitinib).

Objective: The objective of this study was to provide updated overall survival (OS) outcomes of CARMENA and assess whether some subgroups may still benefit from upfront CN.

Design, Setting, And Participants: CARMENA was a phase III trial in 450 patients with mRCC enrolled from 2009 to 2017.

Intervention: Patients in the intention-to-treat population received nephrectomy⬜sunitinib (standard of care [SOC]; n = 226) or sunitinib alone (n = 224).

Outcome Measurements And Statistical Analysis: Primary endpoint was OS, assessed using an updated data cut-off (October 2018; median OS event-free follow-up, 36.6 mo). Patients were reclassified by risk using International Metastatic RCC Database Consortium (IMDC) criteria.

Results And Limitations: Sunitinib alone was noninferior to nephrectomy⬜sunitinib (hazard ratio [HR], 0.97; 95% confidence interval, 0.79⬜1.19; p = 0.8) and demonstrated longer median OS (19.8 mo vs 15.6 mo, respectively). For patients with two or more IMDC risk factors, OS was significantly longer with sunitinib alone than with nephrectomy⬜sunitinib (31.2 mo vs 17.6 mo, respectively; HR, 0.65; p = 0.03). For patients with one IMDC risk factor, OS was longer for nephrectomy⬜sunitinib versus sunitinib alone although not significantly (31.4 mo vs 25.2 mo; HR, 1.30; p = 0.2). The post hoc nature of the subgroup analyses may limit their interpretation.

Conclusions: Sunitinib alone was noninferior compared with nephrectomy⬜sunitinib, suggesting that CN should not be considered SOC in patients with mRCC requiring systemic treatment. Certain subgroups, including patients with one IMDC risk factor, may still benefit from upfront CN.

Patient Summary: We assessed the survival of patients with metastatic kidney cancer in a clinical trial. Patients treated with sunitinib on its own had the same survival as patients who had surgery before sunitinib treatment. We conclude that surgery may not be necessary for some patients with metastatic kidney cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.06.009DOI Listing
October 2021

Artificial intelligence to improve cytology performances in bladder carcinoma detection: results of the VisioCyt test.

BJU Int 2021 Mar 10. Epub 2021 Mar 10.

Anatomo and Cytopathology Department, Foch Hospital, Suresnes, France.

Objective: To explore the utility of artificial intelligence (AI) using the VisioCyt® test (VitaDX International, Rennes, France) to improve diagnosis of bladder carcinoma using voided urine cytology.

Patients And Methods: A national prospective multicentre trial (14 centres) was conducted on 1360 patients, divided in two groups. The first group included bladder carcinoma diagnosis with different histological grades and stages, and the second group included control patients based on negative cystoscopy and cytology results. The first step of this VISIOCYT1 trial focussed on algorithm development and the second step on validating this algorithm. A total of 598 patients were included in this first step, 449 patients with bladder tumours (219 high-grade and 230 low-grade) and 149 as negative controls. The VisioCyt test was compared to voided urine cytology performed by experienced uro-pathologists from each centre.

Results: Overall sensitivity was highly improved by the VisioCyt test compared to cytology (84.9% vs 43%). For high-grade tumours the VisioCyt test sensitivity was 92.6% vs 61.1% for the uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% vs 26.3% for the uro-pathologists.

Conclusion: In comparison to routine cytology, the results of the first phase of the VISIOCYT1 trial show very clear progress in terms of sensitivity, which is particularly visible and interesting for low-grade tumours. If the validation cohort confirms these results, it could lead to the VisioCyt test being considered as a very useful aid for pathologists. Moreover, as this test is in fact software based on AI, it should become more and more efficient as more data are collected.
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http://dx.doi.org/10.1111/bju.15382DOI Listing
March 2021

Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis.

Future Oncol 2021 May 5;17(14):1811-1823. Epub 2021 Feb 5.

Department of Urology, Hôpital Foch, University of Paris-Saclay, Versailles Saint-Quentin-en-Yvelines, Suresnes, France.

Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug-drug interactions and the presence of comorbidities, that affect the risk-benefit balance in individual patients.
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http://dx.doi.org/10.2217/fon-2020-1104DOI Listing
May 2021

The Functions of the Demethylase JMJD3 in Cancer.

Int J Mol Sci 2021 Jan 19;22(2). Epub 2021 Jan 19.

Department of Oncogenetics, Centre Jean Perrin, CBRV, 63001 Clermont-Ferrand, France.

Cancer is a major cause of death worldwide. Epigenetic changes in response to external (diet, sports activities, etc.) and internal events are increasingly implicated in tumor initiation and progression. In this review, we focused on post-translational changes in histones and, more particularly, the tri methylation of lysine from histone 3 (H3K27me3) mark, a repressive epigenetic mark often under- or overexpressed in a wide range of cancers. Two actors regulate H3K27 methylation: Jumonji Domain-Containing Protein 3 demethylase (JMJD3) and Enhancer of zeste homolog 2 (EZH2) methyltransferase. A number of studies have highlighted the deregulation of these actors, which is why this scientific review will focus on the role of JMJD3 and, consequently, H3K27me3 in cancer development. Data on JMJD3's involvement in cancer are classified by cancer type: nervous system, prostate, blood, colorectal, breast, lung, liver, ovarian, and gastric cancers.
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http://dx.doi.org/10.3390/ijms22020968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835890PMC
January 2021

Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses.

Eur Urol 2021 02 28;79(2):214-221. Epub 2020 Aug 28.

Department of Medical Oncology, Saint-Louis-APHP, Faculté de Paris, France.

Background: Perioperative chemotherapy (neoadjuvant or adjuvant) has been developed to increase overall survival for nonmetastatic muscle-invasive bladder cancer (MIBC). Retrospective studies or prospective phase II trials have been reported to use dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC). As dd-MVAC has shown higher response rates in metastatic disease, better efficacy is expected in the perioperative setting.

Objective: We designed a randomized phase III trial to compare the efficacy of dd-MVAC or GC in MIBC perioperative (neoadjuvant or adjuvant) setting.

Design, Setting And Participants: A total of 500 patients were randomized from February 2013 to March 2018 in 28 centers and received either six cycles of dd-MVAC every 2 wk or four cycles of GC every 3 wk.

Outcome Measurements And Statistical Analysis: The primary endpoint (progression-free survival at 3 yr) was not reported. We focused on secondary endpoints: chemotherapy toxicity and pathological responses.

Results And Limitations: In the neoadjuvant group, 218 patients received dd-MVAC and 219 received GC. Of the patients, 60% received six cycles in the dd-MVAC arm and 84% received four cycles in the GC arm; 199 (91%) and 198 (90%) patients underwent surgery, respectively. Complete pathological response (ypT0pN0) was observed in 84 (42%) and 71 (36%) patients, respectively (p=0.2). An organ-confined status (
Conclusions: The toxicity of dd-MVAC was manageable with more severe asthenia and GI side effects than that of GC in perioperative chemotherapy. A higher local control rate (complete pathological response, tumor downstaging, or organ confined) was observed in the dd-MVAC arm (p=0.021). However, such data have to be confirmed on progression-free survival, with primary endpoint data expected in mid-2021.

Patient Summary: The authors have designed a randomized phase III controlled study comparing the efficacy of gemcitabine and cisplatin, and dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) in patients for whom chemotherapy has been decided, before or after radical cystectomy. Higher toxicity regarding asthenia and gastrointestinal side effects along with a better bladder control rate were observed in the dd-MVAC arm. However, such data have to be confirmed on progression-free survival, with primary endpoint data expected in mid-2021.
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http://dx.doi.org/10.1016/j.eururo.2020.08.024DOI Listing
February 2021

Posttraumatic Stress Disorder Symptoms in Lymphoma Patients: A Prospective Study.

Front Psychiatry 2020 11;11:201. Epub 2020 Mar 11.

Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France.

The cancer experience may be marked by repeat stressors and/or traumas. The aim of our study was to assess traumatic events in a group of patients diagnosed with lymphoma and to determine which of these contribute to the development of Post-Traumatic Stress Disorder/PTSD. Two weeks after receiving a diagnosis of lymphoma, patients were referred for an assessment of peritraumatic distress (using the Peritraumatic Distress Inventory/PDI) and peritraumatic dissociation (using the Peritraumatic Dissociative Experiences Questionnaire/PDEQ). Three months after the diagnosis, we recorded the following parameters: the patients' worst experiences, the presence of PTSD symptoms, using the PTSD CheckList/PCL, as it related to the diagnosis, and symptoms of anxiety using the Hospital Anxiety and Depression/HAD scale and of depression using the Beck Depression Inventory/BDI-II. The study recruited 129 patients, with a mean age of 46 years (SD = 17.3); 70 (54%) men, 87 (67.5%) with Non-Hodgkin's lymphoma, and 42 with Hodgkin's lymphoma. Two weeks after the diagnosis, 49% of patients reported peritraumatic distress, and 20% peritraumatic dissociation, during or immediately after being informed of the lymphoma diagnosis. Three months after the diagnosis, the severity of PTSD symptoms was evaluated. At this stage none of the patients suffered PTSD, but 29 (23%) individuals exhibited partial PTSD: 13.4% correlated it to receiving the lymphoma diagnosis, 8% to telling family members, and 1.6% to adverse effects. Peritraumatic distress and dissociation as a result of receiving a lymphoma diagnosis, as well as anxiety and a mucositis within the first 3 months post-diagnosis, were factors that were significantly associated with PTSD symptoms, accounting for 35.8% in PTSD symptom load. Our study reveals that clinicians should assess the impact of a number of stressors, which are risk factors for PTSD symptoms, starting from the time point of the initial lymphoma diagnosis.
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http://dx.doi.org/10.3389/fpsyt.2020.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078238PMC
March 2020

Psychotropic drug initiation in patients diagnosed with chronic myeloid leukemia: a population-based study in France.

Fundam Clin Pharmacol 2020 Oct 3;34(5):612-622. Epub 2020 Mar 3.

Service de Pharmacologie Médicale et Clinique, CHU de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.

Psychotropic drugs (PD) are often used close to a cancer diagnosis and may be considered as a way of coping. We aimed to determine the incidence of anxiolytics, hypnotics, antidepressants, and antipsychotics initiation around a diagnosis of chronic myelogenous leukemia (CML). Population-based cohort: Data were extracted from Systeme National des données de Santé (SNDS, the French health insurance database) at the regional level (Midi-Pyrenees area, 2.9 million inhabitants). All newly diagnosed patients treated by a CML tyrosine kinase inhibitor (TKI) between 10/01/2011 and 04/01/2014 were included. Pre-CML (9 months before to 3 months before first TKI prescription-F-TKI) and CML (3 months before to 9 months after F-TKI) phases were defined. The main evaluation criterion was the initiation of PD during CML phase. Determinants associated with this incident PD use were studied through a logistic regression model. We compared pre-CML and CML healthcare consumption. The cohort included 103 patients (mean age of 60.8 years). PD initiation rate was 35.9%, anxiolytics being the most initiated PD (59.5%). Advanced age was associated with PD initiation (adjusted OR = 1.029, 95% CI = 1.001-1.056). The number of consultations during the pre-CML phase and female gender tended to be associated with increased risk of PD initiation in univariate analysis. For PD initiators, healthcare consumption was greater in CML but not in pre-CML phase. PD initiation is a frequent finding around a CML diagnosis. Its risk increases with age. It could be a way to identify a subgroup with higher healthcare consumption.
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http://dx.doi.org/10.1111/fcp.12544DOI Listing
October 2020

Real-world costs of illness of Hodgkin and the main B-Cell Non-Hodgkin lymphomas in France.

J Med Econ 2020 Mar 26;23(3):235-242. Epub 2019 Dec 26.

Unité d'Evaluation Médico-Economique, Centre Hospitalier Universitaire, Toulouse, France.

Lymphomas are costly diseases that suffer from a lack of detailed economic information, notably in a real-world setting. Decision-makers are increasing the search for Real-World Evidence (RWE) to assess the impact, in real-life, of healthcare management and to support their public decisions. Thus, we aimed to assess the real-world net costs of the active treatment phases of adult Hodgkin Lymphoma (HL), Follicular Lymphoma (FL) and Diffuse Large B Cell Lymphoma (DLBCL). We performed a retrospective cohort study using population-based data from a national representative sample of the French population covered by the health insurance system. Cost analysis was performed from the French health insurance perspective and took into account direct and sick leave compensation costs (€2,018). Healthcare costs were studied over the active treatment phase. We used multivariate modeling to adjust cost differences between lymphoma subtypes. Analyses were performed on 224 lymphoma patients and 896 controls. The mean additional monthly costs due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase. The main additional cost driver was principally inpatient stay (hospitalization costs and costly cancer-related drugs), followed by outpatient medication and productivity loss. When adjusted, DLBCL remains significantly the most costly lymphoma subtype. This study provides an accurate assessment of the main lymphoma subtypes related cost with high magnitude of details in a real-world setting. We underline where potential cost saving could be realized via the use of biosimilar medication, and where lymphoma management could be improved with the early management of adverse events.KEY POINTSThis is one of the first studies which assess the additional cost of lymphoma in Europe, according the main sub-types of lymphoma and with real-world database.The additional monthly cost due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase and the main additional cost driver was principally inpatient stay (i.e. hospitalization costs and additional inpatient medicines, notably rituximab), followed by outpatient medication and productivity loss.This study provides an accurate and detailed lymphoma subtype cost description and comparison which supply data for efficiency evaluations and will allow French health policy to improve lymphoma management.
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http://dx.doi.org/10.1080/13696998.2019.1702990DOI Listing
March 2020

Sustained degradation of quality of life in a subgroup of lymphoma survivors: a two-year prospective survey.

BMC Cancer 2019 Dec 3;19(1):1178. Epub 2019 Dec 3.

Service of Medical and Clinical Pharmacology, Center of Pharmacovigilance, Pharmaco-epidemiology and Information on Drugs, Toulouse University Hospital, 37 Allées Jules Guesde, 31000, Toulouse, France.

Background: Previous studies have suggested that lymphoma survivors commonly display altered Health-Related Quality of Life (HRQoL). Because these were predominantly cross-sectional studies, the dynamic of events as well as the factors which influence HRQoL remain to be determined.

Methods: We conducted a prospective study on a cohort of 204 Hodgkin and non-Hodgkin lymphoma survivors who remained disease-free 2 years after undergoing chemotherapy (referred to the M0-M12-M24 periods).

Results: We found that although Physical and Mental Component Scores (PCS and MCS) of HRQoL significantly improved from M0 to M24 in the vast majority of patients (favorable group), approximately 20% of patients displayed severe alterations in HRQoL (global SF-36 scores < 50) extending over the 2-year period (unfavorable group). Low M24 PCSs were associated with Post-Traumatic Stress Disorder (PTSD), depression, cardiovascular events and neuropathy. In contrast social determinants, comorbidity and infections, as well as several other parameters related to the disease or to the treatment itself were not associated with low M24 PCSs. Low M24 MCSs were associated with a low educational level, aggressive histology, infections, cardiovascular events and PTSS. However, the most predictive risk factor for low SF-36 scores at M24 was a low SF-36 score at M12. The unfavorable group also displayed a low incidence of return to work.

Conclusions: Although the HRQoL of lymphoma survivors generally improved over time, persistent and severe HRQoL alterations still affected approximately one fifth of patients, resulting in important social consequences. This specific group, which presents with identifiable risk factors, may benefit from early, targeted psycho-social support.
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http://dx.doi.org/10.1186/s12885-019-6337-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892152PMC
December 2019

Are social inequalities in acute myeloid leukemia survival explained by differences in treatment utilization? Results from a French longitudinal observational study among older patients.

BMC Cancer 2019 Sep 5;19(1):883. Epub 2019 Sep 5.

LEASP, UMR 1027, Equipe labellisée Ligue Nationale Contre le Cancer, Faculté de médecine de Purpan, Inserm-Université Toulouse III Paul Sabatier, 37 allées Jules Guesde, 31000, Toulouse, France.

Background: Evidences support social inequalities in cancer survival. Studies on hematological malignancies, and more specifically Acute Myeloid Leukemia (AML), are sparser. Our study assessed: 1/ the influence of patients' socioeconomic position on survival, 2/ the role of treatment in this relationship, and 3/ the influence of patients' socioeconomic position on treatment utilization.

Methods: This prospective multicenter study includes all patients aged 60 and older, newly diagnosed with AML, excluding promyelocytic subtypes, between 1st January 2009 to 31st December 2014 in the South-West of France. Data came from medical files. Patients' socioeconomic position was measured by an ecological deprivation index, the European Deprivation Index. We studied first, patients' socioeconomic position influence on overall survival (n = 592), second, on the use of intensive chemotherapy (n = 592), and third, on the use of low intensive treatment versus best supportive care among patients judged unfit for intensive chemotherapy (n = 405).

Results: We found an influence of patients' socioeconomic position on survival (highest versus lowest position HR: 1.39 [1.05;1.87] that was downsized to become no more significant after adjustment for AML ontogeny (HR: 1.31[0.97;1.76] and cytogenetic prognosis HR: 1.30[0.97;1.75]). The treatment was strongly associated with survival. A lower proportion of intensive chemotherapy was observed among patients with lowest socioeconomic position (OR: 0.41[0.19;0.90]) which did not persist after adjustment for AML ontogeny (OR: 0.59[0.25;1.40]). No such influence of patients' socioeconomic position was found on the treatment allocation among patients judged unfit for intensive chemotherapy.

Conclusions: Finally, these results suggest an indirect influence of patients' socioeconomic position on survival through AML initial presentation.
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http://dx.doi.org/10.1186/s12885-019-6093-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729078PMC
September 2019

Combining Ellipsometry and AFM To Probe Subnanometric Precursor Film Dynamics of Polystyrene Melts.

Langmuir 2019 Jun 4;35(24):7727-7734. Epub 2019 Jun 4.

Soft Matter Sciences and Engineering (SIMM) , ESPCI Paris, PSL University, Sorbonne Université, CNRS , F-75005 Paris , France.

We investigate the evolution over time of the space profiles of precursor films spreading away from a droplet of polymer in the poorly explored pseudo-partial wetting case. We use polystyrene melt droplets on oxidized silicon wafers. Interestingly, the film thicknesses measured by ellispometric microscopy are found in the 0.01 to 1 nm range. These thicknesses were validated by atomic force microscopy measurements performed on the textured film obtained after quenching at room temperature. From this, an effective thickness is obtained and compares well to the thicknesses measured by ellipsometry, validating the use of an optical method in this range of thickness. Ellipsometric microscopy provides a height resolution below the ångström with lateral resolution, image size, and framerate well adapted to spreading precursor films. From this, we demonstrate that precursor films of polystyrene consist of polymer chains with a surface density decreasing to zero away from the droplet. We further find that the polymer chains follow a simple diffusive law with the diffusion coefficient independent of density. This demonstrates that polystyrene chains spread independently in precursor films in pseudo-partial wetting condition. This behavior differs significantly from the case of chains spreading in total wetting for which the diffusion coefficient was found in the literature to depend on surface density or thickness.
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http://dx.doi.org/10.1021/acs.langmuir.9b00768DOI Listing
June 2019

Individual Comparison of Cholesterol Metabolism in Normal and Tumour Areas in Radical Prostatectomy Specimens from Patients with Prostate Cancer: Results of the CHOMECAP Study.

Eur Urol Oncol 2019 03 24;2(2):198-206. Epub 2018 Aug 24.

Laboratoire Génétique, Reproduction et Développement, Université Clermont Auvergne, Clermont-Ferrand, France; Centre de Recherche en Nutrition Humaine d'Auvergne, Clermont-Ferrand, France. Electronic address:

Background: Deregulation of cholesterol metabolism represents a hallmark of prostate cancer (PCa) and promotes its development.

Objective: To compare cholesterol metabolism on individual paired normal and tumour prostate tissues obtained from patients with PCa.

Design, Setting, And Participants: Between 2008 and 2012, normal and tumour paired tissue samples were collected from radical prostatectomy specimens from a cohort of 69 patients treated for localised PCa.

Outcome Measurements And Statistical Analysis: Tumour and normal tissues were subjected to gene analysis, sterol measurement, and immunohistochemistry. The Wilcoxon paired test and Spearman test were applied for comparison and correlation analyses, respectively. Principal component analysis was also carried out to investigate relationships between quantitative variables.

Results And Limitations: Overall, cholesterol concentrations were not significantly different between tissue pairs. However, tumour samples were significantly associated with downregulated de novo cholesterol synthesis, but exhibited 54.7% overexpression of SCARB1 that could increase high-density lipoprotein uptake in PCa. Tumour tissues showed different trafficking of available cholesterol, with significantly lower ACAT1, and an altered efflux via APOE. Furthermore, cholesterol metabolism in tumour tissues was characterised by higher accumulation of 7α-hydroxycholesterol (OHC), 7βOHC, and 7-ketosterol, and a lower level of 27OHC.

Conclusions: Focusing on individually paired prostate tissues, our results highlighted several differences between normal and tumour samples linked to a metabolic shift in cholesterol flux. PCa samples exhibited a specific tissue signature characterised by higher SCARB1 expression, higher accumulation of OHC species, and clear downregulation of de novo cholesterol synthesis.

Patient Summary: Comparing normal and tumour tissues from the same prostates, our study identified a set of alterations in prostate cancer samples in terms of their use of cholesterol. These included higher cholesterol uptake, accumulation of oxidised cholesterol derivatives, and autonomous cellular production of cholesterol. Together, these data provide promising clinical targets to fight prostate cancer.
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http://dx.doi.org/10.1016/j.euo.2018.08.001DOI Listing
March 2019

Work adjustments and employment among breast cancer survivors: a French prospective study.

Support Care Cancer 2020 Jan 17;28(1):185-192. Epub 2019 Apr 17.

Service des Maladies Professionnelles et Environnementales, CHU Toulouse, F-31000, Toulouse, France.

Purpose: The objective of our study was to assess the rate of work adjustments 1 year after the diagnosis in a population of female breast cancer (BC) survivors, in the context of the French system of social protection. We also characterised these adjustments and their influence on the reduction of professional exclusion of patients 1 year after the diagnosis.

Methods: This observational, prospective study was conducted from February 2015 to April 2016 among female patients with BC. Inclusion criteria were women aged between 18 and 65 years, treated for BC and integrated into the labour market at the time of diagnosis (working or on sick leave). Exclusion criteria were metastatic BC, retired patients and refusal to participate. A 1-year follow-up was scheduled, and data collection was performed with questionnaires.

Results: In total, 213 patients were included between February 2015 and April 2016. One year after the diagnosis (T1), among 185 BC survivors, 78 (42.2%) patients were working. Among them, 13 patients did not interrupt their occupational activity and 65 returned to work after a period of sick leave. Sixty-four patients returned to work after the end of chemotherapy (after 6 months), and one returned to work before this therapeutic threshold. Sixty-six patients (35.7%) benefited from at least one adjustment of their work conditions to facilitate their return to work (RTW) or maintenance at work: working hours were decreased for 43 patients, and workstation changes were performed for 22 patients. An occupational health physician was involved for some patients; work adjustments were prescribed to 42 patients, 7 patients had medical restrictions for physical reasons and 4 patients had restrictions for psychological reasons. Forty-three patients benefited from part-time work prescribed for therapeutic reasons.

Conclusions: Referral to occupational health physicians and work adjustments remain limited in the process of RTW or maintenance at work after BC in France, despite their positive impact.
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http://dx.doi.org/10.1007/s00520-019-04799-wDOI Listing
January 2020

Oncology nurse phone calls halve the risk of reduced dose intensity of immunochemotherapy: results of the randomized FORTIS study in chronic lymphocytic leukemia.

Ann Hematol 2019 Apr 18;98(4):931-939. Epub 2019 Feb 18.

University of Toulouse III Paul Sabatier, Toulouse, France.

Delivering of > 80% planned relative dose intensity (RDI) of fludarabine-cyclophosphamide-rituximab (FCR) is key to benefit from longer progression free survival (PFS) and survivals in CLL. In this randomized trial, we sought to investigate whether a telephone intervention strategy (called AMA) delivered by an oncology nurse could reduce the risk of RDI < 80% by alleviating adverse events and supporting patients' adherence. Sixty FCR patients were randomized 1:1 for AMA (stratified on Binet stage C). As per guidelines, patients received pegfilgrastim as primary prophylaxis of febrile neutropenia. At the end of therapy, RDI < 80% was reported in 31% of patients, shortening PFS (median 26 months versus not reached, P = 0.021) and OS at 3 years (100 vs 70%, P = 0.0089). Oncology nurse interventions tended to significantly reduce this event (RDI < 80%: 41.4% in non-AMA versus 20.7% in AMA patients (p = 0.09)). By adjusting our logistic regression model on published parameters exposing to RDI < 80%, we found that AMA protected significantly against the risk of reduced RDI (OR = 0.22, IC95% 0.05-0.84, p = 0.04), independently of grade 3/4 neutropenia (< 15% per cycle) and febrile neutropenia (< 5% per cycle) events. As a conclusion, we confirmed that > 20% reduction of FCR dose-intensity was detrimental for PFS/OS, but that oncology nurse interventions reduced the risk of dose concessions.
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http://dx.doi.org/10.1007/s00277-019-03631-zDOI Listing
April 2019

The impact of chronic myeloid leukemia on employment: the French prospective study.

Ann Hematol 2019 Mar 17;98(3):615-623. Epub 2018 Nov 17.

Department of Occupational Diseases, Toulouse University Hospital, Bâtiment Turiaf, Place du Dr Baylac, 31059, Toulouse Cedex 9, France.

Patients with chronic myeloid leukemia treated with breakpoint cluster region-Abelson tyrosine kinase inhibitors are likely to survive in excess of 20 years after diagnosis. New challenges appear as we consider life after the disease, including professional challenges and the social reintegration of patients. The purpose of this study was to determine the impact of chronic myeloid leukemia on employment within 2 years after diagnosis. This prospective, observational study included patients diagnosed with chronic myeloid leukemia and treated with a tyrosine kinase inhibitor. Two populations were defined as patients who reported modifications in their professional activity during the study (Acti-Pro+) and patients who did not report a modification (Acti-Pro-). Cancer survivors received a self-assessment questionnaire. The primary endpoint was to determine the professional status of patients. One hundred patients completed the questionnaire. Sixty-six patients out of 100 reported professional activity within 2 years after their diagnosis. During the 2 years after the diagnosis, 65.2% (95% confidence interval (CI), 53.7-76.7) of patients faced modifications in their professional activity due to chronic myeloid leukemia or adverse effects of drug treatments (group Acti-Pro+); in contrast, 34.8% of patients did not report any impact on their occupational activity (group Acti-Pro-). Among modifications to work organization, a change in the number of working hours was the most represented. Other modifications comprised changes in status or work pace. A majority of chronic myeloid leukemia patients face professional consequences of their disease and treatments. Our findings suggest that adverse drug reactions are a major factor affecting the occurrence of work modifications in this context.
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http://dx.doi.org/10.1007/s00277-018-3549-5DOI Listing
March 2019

Profiling Immune Escape in Hodgkin's and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining.

Cancers (Basel) 2018 Oct 31;10(11). Epub 2018 Oct 31.

Centre de Recherches en Cancérologie de Toulouse, INSERM UMR1037, 31100 Toulouse, France.

Therapeutic blockade of PD-1/PD-L1 shows promising results in Hodgkin's lymphoma (HL) and in some diffuse large B-cell lymphoma (DLBCL) patients, but biomarkers predicting such responses are still lacking. To this end, we recently developed a transcriptional scoring of immune escape (IE) in cancer biopsies. Using this method in DLBCL, we identified four stages of IE correlated with overall survival, but whether Hodgkin's lymphomas (HL) also display this partition was unknown. Thus, we explored the transcriptomic profiles of ~1000 HL and DLBCL using a comparative meta-analysis of their bulk microarrays. Relative to DLBCL, the HL co-clustered at the advanced stage of immune escape, displaying significant enrichment of both IE and T-cell activation genes. Analyses via transcriptome deconvolution and immunohistochemistry showed more CD3⁺ and CD4⁺ tumor-infiltrating lymphocytes (TILs) in HL than DLBCL. Both HL and non-GCB DLBCL shared a high abundance of infiltrating CD8⁺ T-cells, but HL had less CD68⁺CD163⁺ macrophages. The same cellular distribution of PD-1 and TIM-3 was observed in HL and DLBCL, though HL had more PD-L1 tumor cells and LAG-3 ME cells. This study illuminates the advanced stage of immune activation and escape in HL, consistent with the response to checkpoint blockade therapies for this type of lymphoma.
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http://dx.doi.org/10.3390/cancers10110415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266061PMC
October 2018

Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma.

N Engl J Med 2018 Aug 3;379(5):417-427. Epub 2018 Jun 3.

From the Departments of Urology (A.M., M.-O.T.) and Medical Oncology (S.O.), Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Descartes, and Paris Descartes Necker-Cochin Clinical Research Unit, AP-HP (S.C.), Paris, the Department of Medical Oncology, Bordeaux University Hospital (A.R.), the Department of Medical Oncology, Hôpital Saint André, Centre Hospitalier Universitaire (CHU) de Bordeaux (M.G.-G.), and the Department of Urology, CHU de Bordeaux and Université de Bordeaux (J.-C.B.), Bordeaux, Biometrics Unit, Cancer Institute of Montpellier, University of Montpellier, Montpellier (S.T.), the Department of Urology, CHU Rangueil (J.-B.B.), and the Department of Medical Oncology, Institut Universitaire du Cancer Toulouse-Oncopole (C.C.), Toulouse, the Department of Urology, University of Rennes (K.B.), and the Department of Medical Oncology, Centre Eugene Marquis (B.L.), Rennes, the Department of Medical Oncology, Institut de Cancerologie de Lorraine, Vandoeuvre lès Nancy (L. Geoffrois), the Department of Medical Oncology, CHU Besançon, Oncologie, and Université de Franche-Comte, INSERM Unité Mixte de Recherche (UMR) 1098, Structure Fédérative de Recherche Ingénierie et Biologie Cellulaire et Tissulaire, Besançon (A.T.-V.), the Department of Urology, CHU François Mitterrand, Dijon (L.C.), the Department of Urology, CHU Strasbourg, Translational Medicine Federation Strasbourg, Strasbourg (H.L.), the Department of Urology, Gabriel Montpied Hospital, and Clermont Auvergne University, Clermont-Ferrand (L. Guy), the Department of Medical Oncology, Centre de Recherche en Cancerologie de Marseille, INSERM UMR 1068, Centre National de la Recherche Scientifique UMR 7258 and Institut Paoli-Calmettes (G.G.), and the Department of Urology, Hôpital la Conception (E.L.), Aix Marseille Université, Marseille, the Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Nantes (F.R.), the Department of Medical Oncology, CHU Bretonneau, and the Department of Medicine, Université François Rabelais, Tours (C.L.), the Department of Urology, Mont de Marsan General Hospital, Mont de Marsan (J.-J.P.), the Departments of Medical Oncology (C.T.) and Urology (T.L.), Hôpital Foch, Suresnes, the Department of Urology, Imagerie Adaptative Diagnostique et Interventionnelle INSERM Unité 1254, CHU de Nancy, Brabois (J.H.), the Department of Medical Oncology, Institut Gustave Roussy and Université Paris-Saclay, Villejuif (L.A., B.E.), and Université Versailles, St.-Quentin-en-Yvelines (T.L.) - all in France; the Department of Urology, Haukeland University Hospital (C.B.), and the Department of Clinical Medicine, University of Bergen (C.B.), Bergen, Norway; and the Department of Urology, Royal Free Hospital, London (M.A.).

Background: Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies.

Methods: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival.

Results: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group.

Conclusions: Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).
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http://dx.doi.org/10.1056/NEJMoa1803675DOI Listing
August 2018

A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.

Oncotarget 2018 May 4;9(34):23413-23425. Epub 2018 May 4.

Department of Oncogenetics, Center Jean Perrin, CBRV, 63001 Clermont-Ferrand, France.

Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown to be deregulated in prostate cancer, and evidence shows H3K27me3 enrichment on gene promoters in prostate cancer. To study the impact of this enrichment, a transcriptomic analysis with TaqMan Low Density Array (TLDA) of several genes was studied on prostate biopsies divided into three clinical grades: normal ( = 23) and two tumor groups that differed in their aggressiveness (Gleason score ≤ 7 ( = 20) and >7 ( = 19)). ANOVA demonstrated that expression of the gene set was upregulated in tumors and correlated with Gleason score, thus discriminating between the three clinical groups. Six genes involved in key cellular processes stood out: , , , , and . Chromatin immunoprecipitation demonstrated collocation of EZH2 and JMJD3 on gene promoters that was dependent on disease stage. Gene set expression was also evaluated on prostate cancer cell lines (DU 145, PC-3 and LNCaP) treated with an inhibitor of JMJD3 (GSK-J4) or EZH2 (DZNeP) to study their involvement in gene regulation. Results showed a difference in GSK-J4 sensitivity under PTEN status of cell lines and an opposite gene expression profile according to androgen status of cells. In summary, our data describe the impacts of JMJD3 and EZH2 on a new gene signature involved in prostate cancer that may help identify diagnostic and therapeutic targets in prostate cancer.
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http://dx.doi.org/10.18632/oncotarget.25182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955128PMC
May 2018

[Impact of obesity in kidney transplantation: Monocentric cohort study and review of the literature].

Nephrol Ther 2018 Nov 27;14(6):454-461. Epub 2018 Mar 27.

Service de néphrologie, CHU Gabriel-Montpied, 58, rue Montalembert, BP 69, 63000 Clermont-Ferrand cedex, France.

Post-kidney transplantation outcomes in obese patients remain uncertain. The aim of this study is to compare patient and graft survival and post-transplant complications in obese patients and non-obese patients. We performed a retrospective analysis of a sample of 245kidney transplantations performed between 2008 and 2014 in Clermont-Ferrand. Obese patients and non-obese patients have been compared. Then we compared obese patients who have lost at least 5% of their weight (OPP) with obese patients who did not lose weight (OPS), and non-obese patients who have lost at least 5% of their weight (NOPP) with non-obese patients who did not lose weight (NOPS). Patient survival at 5years is similar between obese and non obese (84.06% versus 90.96%; P=0.49), between OPP and OPS (88.89% versus 81.82%; P=0.34) and between NOPP and NOPS (89.19% versus 91.05%; P=0.73). At 5years, graft survival is also comparable between obese and non obese (88.82% versus 81.86%; P=0.58), between OPP and OPS (85.56% versus 91.06%; P=0.98) and between NOPP and NOPS (88% versus 80.12%; P=0.31). The length of hospitalization and the rate of complications seem similar between obese and non obese and between OPP and OPS. Post-transplantation outcomes are similar between obese and non-obese patients and a weight loss for obese patients does not seem to decrease the risk of post-transplant complication.
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http://dx.doi.org/10.1016/j.nephro.2018.01.002DOI Listing
November 2018

DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status.

Haematologica 2018 06 22;103(6):1038-1046. Epub 2018 Mar 22.

CRCT, Université de Toulouse, Inserm, CNRS, UPS, France; Equipe Labellisée Ligue Contre le Cancer, Laboratoire d'Excellence Toulouse Cancer, France

Alteration in the DNA replication, repair or recombination processes is a highly relevant mechanism of genomic instability. Despite genomic aberrations manifested in hematologic malignancies, such a defect as a source of biomarkers has been underexplored. Here, we investigated the prognostic value of expression of 82 genes involved in DNA replication-repair-recombination in a series of 99 patients with chronic lymphocytic leukemia without detectable 17p deletion or mutation. We found that expression of the gene, encoding the specialized DNA polymerase ν (Pol ν) correlates with time to relapse after first-line therapy with fludarabine. Moreover, we found that was the only gene up-regulated in primary patients' lymphocytes when exposed to proliferative and pro-survival stimuli. By using two cell lines that were sequentially established from the same patient during the course of the disease and Pol ν knockout mouse embryonic fibroblasts, we reveal that high relative expression is important for DNA synthesis and cell survival upon fludarabine treatment. These findings suggest that Pol ν could influence therapeutic resistance in chronic lymphocytic leukemia. (Patients' samples were obtained from the CLL 2007 FMP clinical trial registered at: : 00564512).
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http://dx.doi.org/10.3324/haematol.2017.174243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058778PMC
June 2018

Aggregate Formation of Surface-Modified Nanoparticles in Solvents and Polymer Nanocomposites.

Langmuir 2018 03 20;34(9):3010-3020. Epub 2018 Feb 20.

Laboratoire Charles Coulomb (L2C) , Université de Montpellier, CNRS , F-34095 Montpellier , France.

A new method based on the combination of small-angle scattering, reverse Monte Carlo simulations, and an aggregate recognition algorithm is proposed to characterize the structure of nanoparticle suspensions in solvents and polymer nanocomposites, allowing detailed studies of the impact of different nanoparticle surface modifications. Experimental small-angle scattering is reproduced using simulated annealing of configurations of polydisperse particles in a simulation box compatible with the lowest experimental q-vector. Then, properties of interest like aggregation states are extracted from these configurations and averaged. This approach has been applied to silane surface-modified silica nanoparticles with different grafting groups, in solvents and after casting into polymer matrices. It is shown that the chemistry of the silane function, in particular mono- or trifunctionality possibly related to patch formation, affects the dispersion state in a given medium, in spite of an unchanged alkyl-chain length. Our approach may be applied to study any dispersion or aggregation state of nanoparticles. Concerning nanocomposites, the method has potential impact on the design of new formulations allowing controlled tuning of nanoparticle dispersion.
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http://dx.doi.org/10.1021/acs.langmuir.7b03932DOI Listing
March 2018

Non-cancer drug consumption during the early trajectory of lymphoma survivorship.

Therapie 2018 Sep 22;73(4):307-317. Epub 2017 Nov 22.

Medical and clinical pharmacology ward, college of medicine, university of Toulouse III Paul-Sabatier, 31000 Toulouse, France; Medical and clinical pharmacology laboratory, Toulouse university hospital, 31000 Toulouse, France; INSERM UMR1027 (French National Institute of Health and Medical Research), 31000 Toulouse, France; INSERM CIC 1436, Toulouse clinical investigation center, 31000 Toulouse, France. Electronic address:

Purpose: This study explored the use of non-cancer drugs in lymphoma survivors during the early trajectory (0 to 2 years) of cancer survivorship and determined the factors that influenced this consumption.

Methods: Between January and March 2014, a cross-sectional survey was conducted to assess drug consumption in adult lymphoma survivors at the Toulouse University Hospital. This study was based on a questionnaire consisting of ten open questions related to medical prescription and/or self-medication occurring within the last 3 months.

Results: A total of 83/103 lymphoma survivors returned the questionnaire. This study showed that 91.6% of patients were drug consumers (about twice more than the general French population). Twenty percent of patients were treated with≥5 drugs. Overall drug consumption mainly concerned analgesics, anti-inflammatory drugs and psychotropics. The presence of comorbidity, urban residence and female gender were associated with overall drug consumption. Moreover, half of survivors required at least one self-medication. Finally, only seven survivors (8.4%) reported no use of any medication.

Conclusion: This study shows that, at least during the early trajectory of cancer survivorship, lymphoma patients are heavily treated with non-cancer drug therapy. This drug consumption profile may have serious implications in terms of safety, overall benefit and health economics.
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http://dx.doi.org/10.1016/j.therap.2017.10.007DOI Listing
September 2018

Improved outcome for AML patients over the years 2000-2014.

Blood Cancer J 2017 11 29;7(12):635. Epub 2017 Nov 29.

Service d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.

Few recent studies from registries have reported an improvement in overall survival of younger patients with acute myeloid leukemia (AML). However, reasons for this improvement are not defined. We analyzed the therapeutic course and outcome of 976 patients treated by intensive chemotherapy between 2000 and 2014. The number of patients receiving allogeneic stem cell transplantation in first or second response significantly increased over time whereas autologous transplantation was progressively abandoned. In the 513 younger patients, there were no differences in first complete response, induction failure, incidence of relapse, or non-relapse mortality over time. The period of time was significantly associated with a better overall survival especially in 2010-2014. The 2010-2014 period effect was still significant in multivariate analysis and was independent of allogeneic stem cell transplantation. In the 463 older patients, there was a significant interaction between the period and leukocytosis in multivariate analysis meaning that the 2010-2014 period had only an impact in patients with white blood cell count >50 giga/L for response and overall survival. Progresses have been made in each phase of the therapeutic course of younger AML patients resulting in survival improvement. In older patients, the outcome of hyperleukocytic patients has significantly improved in 2010-2014.
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http://dx.doi.org/10.1038/s41408-017-0011-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802565PMC
November 2017
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