In Euro‐EWING99‐R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard‐risk Ewing sarcoma (SR‐EWS) after a common induction with VIDE ...(vincristine‐ifosfamide‐doxorubicin‐etoposide). We present the results of the late effects analysis of VAC (vincristine‐dactinomycin‐cyclophoshamide) vs VAI (vincristine‐dactinomycin‐ifosfamide) conducted in Euro‐EWING99‐R1 French cohort. Of 267 French randomized patients, 204 were alive and free‐of‐relapse at 5‐years including 172 with available long‐term follow‐up data concerning cardiac, renal and/or gonadal functions (sex‐ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2, ifosfamide = 59.4 g/m2) and 88 in VAI (ifosfamide = 97.1 g/m2). With a median follow‐up of 10 years (range = 5‐17), five late relapses and five second malignancies were recorded. The 10‐year event‐free survival among 5‐year free‐of‐relapse survivors was similar between VAC and VAI (93% vs 95%, P = .63). We estimated the 10‐year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval 95% CI = 1.1%‐7.6%) and 34.8% (95% CI = 26.8%‐42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P = .02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P < .01). At 10 years, gonadal toxicity was observed in 27% and 28% of pubertal men and women, respectively, without significant difference between VAC and VAI. Kidney and gonadal toxicities represent major issues in Euro‐EWING99‐R1, with significantly higher risk of kidney toxicities with VAI, without significant gonadal toxicity reduction. These results support the need to limit cumulative doses of both alkylating agents and to use mixed regimen as in VIDE‐VAC or VDC/IE (vincristine‐doxorubicin‐cyclophoshamide/ifosfamide‐etoposide).
What's new?
The Euro‐EWING99‐R1 trial compared the alkylating agents cyclophosphamide with ifosfamide in combination treatment for Ewing sarcoma. Here, the authors compare the late events between the two combination treatments using data from 172 patients enrolled in Euro‐EWING99‐R1. The combination containing ifosfamide carried a higher risk of kidney toxicity, but both regimens carried high rates of gonadal toxicity. Some of this toxicity could be avoided, they suggest, by using a mixed regimen to limit the dose of both alkylating agents.
Thromboembolic events are frequent and serious complications of acute lymphoblastic leukaemia treatment. The importance of chemotherapy in the pathogenesis of this increased risk is enhanced by the ...fact that thrombosis rarely occurs at diagnosis. Our study aims at investigating the effect of chemotherapy on pro-coagulant activity (PCA), phosphatidylserine (PS) exposure, tissue factor (TF) activity and derived extracellular vesicles (EV) of Jurkat cells. Jurkat cells were treated with two commonly used chemotherapeutics: Vincristine (VCR) or Daunorubicin (DNR), at relevant concentrations. PCA of cells and derived EV were evaluated using Thrombin generation Assay (TGA). Cells or EV were incubated with annexin V or anti TF antibodies to assess the respective contribution of TF and PS. PS exposure on cells was analysed by flow cytometry. Derived EV were evaluated in fluorescence microscopy and flow cytometry. Untreated Jurkat cells and EV support thrombin generation. Thrombin generation was abolished when PS activity was inhibited by annexin V. VCR treatment resulted in a time dependent increase of thrombin generation. After VCR exposure, TF activity increased as well as PS exposure increased on the cell surface. The increase in TF activity was abolished by annexin V indicating that PS was required. A spontaneous release of EV from Jurkat cells was observed and VCR treatment increased the number of generated EV. Our results indicate that VCR increased the PCA of Jurkat cells predominantly through PS exposure and increased EV generation. Lymphoid blasts derived EV could be biomarkers to determine high thrombotic risk ALL patients.
Nodular lymphocyte predominant Hodgkin disease (NLPHL) differs clearly from classical Hodgkin lymphoma (cHL) by clinical presentation and more favorable outcome. Patients often present with early ...stage IA or IIA. Extranodal disease and B-symptoms are uncommon. Histologically, NLPHL is characterized by the presence of atypical "lymphocyte predominant cells" (LP cells) or "pop-corn" cells in a non-neoplastic and reactionnal nodular background of small mature B-lymphocytes. LP cells are negative for CD30 and positive for CD20, BCL6 and EMA (in half of the cases). FDG-PET plays an important role in evaluation of cHL and NLPHL for staging, therapy assessment and relapse. Historically, patients with NLPHL have been treated like patients with cHL, but their very favorable prognosis and the risk of late complications of chemotherapy and/or radiotherapy have led to a de-escalation in recent years. Patients with early stage could be treated by surgical adenectomy alone or associated with not intensive chemotherapy. Currently, there is no consensus regarding to the optimal treatment of patients with advanced stage. Rituximab used as monotherapy or in association with chemotherapy has achieved complete or partial responses. The outcome of NLPHL is singular by the frequent occurrence of late relapses and the risk of transformation into aggressive B lymphoma justifying an extended follow-up. Further prospective studies are needed to optimize treatment of these advanced and recurrent forms.
Acute lymphoblastic leukaemia (ALL) is the most common type of cancer diagnosed in children. Improvement in the treatment has resulted in survival rates of nearly 85% with modern intensive ...chemotherapy. However, intensive treatment imposes morbidity and mortality. Thromboembolic events are among the more frequent and serious complications of acute lymphoblastic leukaemia. They represent a potentially reversible cause of morbidity and mortality. In the largest study, the rate of thrombosis was 5.2% and half of thrombotic events occurs in the central nervous system. The pathogenesis of this increased thrombotic risk is not fully understood, but probably includes a combination of variables related to the disease itself, its treatment, and the host. In literature, there are few studies about the role of lymphoid blasts and of derived microparticules (MP) in these complications.
JURKAT ALL cell line was exposed to Vincristine (VCR) or Doxorubicin (DOX) at the therapeutic concentrations of respectively 300ng/ml and 20ng/ml during 4 or 24 hours (h). Cells viability was studied with MTT tetrazolium reduction assay. Tissue factor (TF) expression was studied by RT PCR and Western Blot. Thrombin generation was estimated by Thrombin generation assay (TGA). Antibody (Ab) against TF and Annexin V (AV) were used to assess respectively the role of TF and of phosphatidylserine. MP derived from JURKATT cells were isolated by two centrifugations (15 minutes at 1500x g and 45 minutes at 15000x g). MP were observed and quantified by fluorescence microscopy after a labelling with AV Alexa. TGA was used to evaluate MP thrombin generation.
After 4h and 24h of incubation with VCR, cells viability was respectively of 109% and 42%. JURKAT cell line expressed TF mRNA and protein. This expression did not vary with chemotherapy. JURKAT cell line was able to support thrombin generation. After a treatment during 24h with VCR, thrombin generation was significantly higher with a significant modification of all parameters of TGA. AV induced a complete inhibition of thrombin generation whereas TF Ab induced a delay in the initiation of thrombin generation. This delay was significantly higher after 24h incubation with VCR (182%) than after 4h (114%). At baseline, JURKAT cell line released MP which were observed and quantified by florescence microscopy. MP induced thrombin generation. After 4 and 24h of incubation with VCR, the number of MP increased significantly (respectively 74% and 142%). The size of MP was significantly smaller after an incubation of 24h. 24h exposure to VCR significantly increased MP thrombin generation. AV induced a complete inhibition of thrombin generation. TF Ab induced a delay in the initiation of thrombin generation. Despite its effect on cells viability (115% after 4h and 38% after 24h), DOX treatment during 4h or 24h did not induce statistically significant variations in thrombin generation by JURKAT cells or by derived MP.
The role of blasts in thromboembolic events has been mostly studied in acute myeloid leukaemia but only rarely in ALL. The role of high levels of MP has been studied in various diseases complicated by thrombosis but not in ALL. According to the results of this study, lymphoid blasts could play a role in thrombosis events at the initiation of treatment in ALL. When exposed to VCR, JURKAT cell line is able to support thrombin generation with a time-dependant effect of VCR. Pro-coagulant phospholipids exposure on blasts and derived MP plays a major role in thrombin generation.TF has a role in the initiation of coagulation. Inhibition of TF effect by Ab is also time-dependant, suggesting that despite the absence of modification in TF expression, VCR may induce modifications in TF activity, maybe by a mechanism of decryption via interactions with phosphatidylserine. Our data also suggest that MP could be potential markers and targets in the prevention of thrombosis in ALL patients.
No relevant conflicts of interest to declare.
Three-dimensional conformal RT (3D-RT) techniques are gold standard for post-operative flank radiotherapy (RT) in paediatric renal tumours. Recently, highly conformal RT (HC-RT) techniques have been ...implemented without comparative clinical data. The main objective of this multicentre study was to compare locoregional control (LRC) in children treated either with HC-RT or 3D-RT techniques.
Patients treated with post-operative flank RT for renal tumour registered in the national cohort PediaRT between March 2013 and September 2019 were included. Treatment and follow-up data, including toxicities and outcomes, were retrieved from the database. LRC was calculated, and dose reconstruction was performed in case of an event.
Seventy-nine patients were included. Forty patients were treated with HC-RT and 39 with 3D-RT. Median follow-up was 4.5 years. Three patients had locoregional failure (LRF; 4%). HC-RT was not associated with a higher risk of LRF. Three-year LRC were 97.4% and 94.7% in the HC-RT and 3D-RT groups, respectively. The proportion of planning target volumes receiving 95% or more of the prescribed dose did not significantly differ between both groups (HC-RT 88%; 3D-RT 69%; p = .05). HC-RT was better achieving dose constraints, and a significant mean dose reduction was observed in the peritoneal cavity and pancreas associated with lower incidence of acute gastrointestinal toxicity.
LRF after post-operative flank RT for renal tumours was rare and did not increase using HC-RT versus 3D-RT techniques. Dose to the pancreas and the peritoneal cavity, as well as acute toxicity, were reduced with HC-RT compared to 3D-RT.
La qualité de vie Alaphilippe, Daniel; Bacro, Fabien; Botella, Marion ...
2014
Book
Qualité de vie et bien-être sont des concepts en plein développement dans les différents domaines de la psychologie. Cet ouvrage, issu du 32e symposium de l'Association de psychologie scientifique de ...langue française (APSLF), examine les enjeux conceptuels et méthodologiques liés à l'essor des recherches sur la qualité de vie, et fait le point sur les connaissances issues de ces travaux pour mieux saisir quelles peuvent être leurs applications dans les domaines de l'éducation et de la santé. Comment parvenir à une définition claire de la qualité de vie ? Quelle place accorder à la subjectivité des personnes interrogées ? Comment appréhender la qualité de vie à différents âges et dans divers contextes de vie (scolaire, institutionnel, médical) ? Comment les enfants peuvent-ils évaluer leur qualité de vie ? Quels facteurs influencent la qualité de vie des personnes atteintes de maladies chroniques ? En quoi est-il utile d'évaluer la qualité de vie dans le cadre d'un suivi thérapeutique ? Le vieillissement s'accompagne-t-il d'une diminution de la qualité de vie ? Cet ouvrage tente de répondre à ces différentes questions. Les thèmes abordés relèvent de la psychologie cognitive, du développement et de l'éducation, de la psychologie du handicap, de la psychopathologie, de la psychologie de la santé et du vieillissement.
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