CHU Hautepierre

Strasbourg, France

CHU Hautepierre

Strasbourg, France
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Background: Intensity modulated radiotherapy is an efficient radiotherapy technique to increase dose in target volumes and decrease irradiation dose in organs at risk. This last objective is mainly relevant in children. However, previous results suggested that IMRT could increase low dose, factor of risk for secondary radiation induced cancer. This study was performed to compare dose distributions with 3D-radiotherapy (3D-RT) and IMRT with tomotherapy (HT) in children with neuroblastoma. Seven children with neuroblastoma were irradiated. Treatment plans were calculated for 3D-RT, and for HT. For the volume of interest, the PTV-V95% and conformity index were calculated. Dose constraints of all the organs at risk and integral dose were compared.Results: The conformity index was statistically better for HT than for 3D-RT. PTV-V95% constraint was reached in 6 cases with HT compared to 2 cases with 3D-RT. For the ipsilateral kidney of the tumor, the V12 Gy constraint was reached for 3 patients with both methods. The values were lower with HT than with 3D-RT in two cases and higher in one case. The threshold was not reached for one patient with either technique, but the value was lower with HT than with 3D-RT. For the contralateral kidney of the tumors, the V12 Gy constraint was reached for all patients with both methods. The values were lower with HT than with 3D-RT in 5 of 7 children, equal in one patient and higher in one patient. The organ-at-risk volumes receiving low doses were significantly lower with 3D-RT but larger for the highest doses, compared to those irradiated with HT. The integral doses were not different.Conclusions: IMRT with HT allows a better conformity treatment, a more frequently acceptable PTV-V95% than 3D-RT and, concomitantly, a better shielding of the kidneys. The integral doses are comparable between both techniques but consideration of differences in dose distribution between the two techniques, for the organs at risk, has to be taken in account when validating treatment. © 2012 Beneyton et al; licensee BioMed Central Ltd.

Soussan M.,University of Paris 13 | Guetz G.D.,University of Paris 13 | Barrau V.,Center Cardiologique du Nord | Aflalo-Hazan V.,University of Paris 13 | And 8 more authors.
European Radiology | Year: 2012

Objectives To assess the accuracy of FDG-PET/CT and MRwith diffusion-weighted imaging (MR-DWI) for diagnosing peritoneal carcinomatosis (PC) from gastrointestinal malignancies. Methods Thirty consecutive patients referred for staging of gastrointestinal malignancy underwent FDG-PET/CT and MR-DWI in this retrospective study. Extent of PC was characterised by dividing the peritoneal cavity into three sites in each patient: right and left supramesocolic areas and inframesocolic level (total 90 sites). Presence of PC was confirmed either by surgery (18/30) or by follow-up (12/30). Results PC was confirmed in 19 patients (19/30). At a total of 90 sites, 27 showed proven PC. On a patient-based analysis, sensitivity, specificity, PPV, NPV and accuracy were respectively 84%, 73%, 84%, 73% and 80% for PET/ CT and 84%, 82%, 89%, 75% and 83% for MR-DWI. On a site-based analysis, overall sensitivity and specificity of PET/ CT (63%, 90%) and MR-DWI (74%, 97%) were not statistically different (P00.27). In the supramesocolic area, MR-DWI detected more sites involved than PET/CT (7/9 vs. 4/9). The sensitivities of PET and MR were lower for subcentimetre tumour implants (42%, 50%). Interobserver agreement was very good for PET/CT and good for MR-DWIConclusions FDG-PET/CT and MR-DWI showed similar high accuracy in diagnosing PC. Both techniques underestimated the real extent of PC because of decreased sensitivity for subcentimetre lesions. Key Points ̇ FDG-PET/CT and MR-DWI showed similar high accuracy for diagnosing peritoneal carcinomatosis. ̇ In the supramesocolic area, MR-DWI could be more sensitive than PET/CT. ̇ Both techniques showed lower sensitivity for subcentimetre lesions. ̇ Interobserver agreement was very good for PET/CT and good for MR-DWI. © European Society of Radiology 2012.

Borrione F.,Center Phocea | Bonnevialle P.,Toulouse University Hospital Center | Mabit C.,Limoges University Hospital Center | Guingand O.,Institute Mutualiste Montsouris | And 4 more authors.
International Orthopaedics | Year: 2011

Purpose: Our goal was to evaluate the five-year follow-up results of the Scorpio single radius total knee arthroplasty. Method: We performed a retrospective study based upon a multicentre database to evaluate the minimum five-year follow-up clinical and radiological results of 747 patients (831 knees) who underwent primary Scorpio single radius total knee arthroplasty. Results: The mean age of the patients was 71.9 years. At a minimal five-year follow-up, 141 patients were lost to follow-up, 83 patients had died, eight patients had undergone revision of a component, and the remaining 589 patients (602 knees) had a complete clinical and radiological evaluation after a median of six years (range, 5-8). The mean clinical component of the knee score was 92.2 points, and the mean functional component of the knee score was 76.9 points. At last follow-up, 530 of the 602 knees were rated as excellent or good. Only four knees developed patellar complications requiring revision. The survival rate at six years was 95.2% ± 1.9% and 98.3% ± 0.6 with revision for any reason and revision for mechanical failure as the end point, respectively. Conclusion: This medium-term study indicates favourable clinical and radiological results for this single flexion-extension radius design arthroplasty, with a low complication rate on the patellar side. © 2011 Springer-Verlag.

PubMed | Hopital Mere enfant, Marseille University Hospital Center, Besancon University Hospital Center, Institute Gustave Roussy and 8 more.
Type: | Journal: BMC cancer | Year: 2015

The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry.All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed.Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR)= 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively.Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.

PubMed | University of Rochester, hopital Pasteur, Center Paul Strauss and CHU Hautepierre
Type: Journal Article | Journal: Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique | Year: 2016

Bevacizumab and stereotactic treatment are efficient combined or alone in relapse glioma. However, patterns of relapse after this kind of salvage treatment have never been studied. The purpose of this unicentric retrospective analysis was to assess and understand the patterns of relapse of high grade glioma treated with stereotactic radiation, with or without bevacizumab.Twenty patients with high grade glioma relapse received a stereotactic radiation; among them two patients received temozolomide and eight patients received bevacizumab; among the latter, four received also irinotecan. We matched the stereotactic radiation treatment planning scan with the images of the first treatment and of the second relapse in order to determine the patterns of failure and associate dosimetric profile.For the total population, median follow-up from the first diagnosis and relapse were 46.1 and 17.6 months, respectively. Among the 13 patients who relapsed, ten did not receive chemotherapy and three received it (P<0.05), two received temozolomide and one bevacizumab. Patients who received bevacizumab had no out-of-field recurrences. Among the 32 irradiated relapses, 15 were in-field recurrences; among them two were treated with bevacizumab and 13 were not (P<0.05). For the 32 lesions, a favourable prognostic factor of control was the association of a high-dose of irradiation and the use of bevacizumab.For patients with relapsed high grade glioma, local control was higher with combined bevacizumab and high-dose stereotactic radiation.

PubMed | CHU Hautepierre, CHRU de Besancon and University of Monastir
Type: Journal Article | Journal: Gynecologie, obstetrique & fertilite | Year: 2015

Health-related quality of life (QoL) in patients treated for ovarian cancer is directly and heavily impacted by the natural history of cancer, its evolution and its therapeutic modalities. The evaluation and consideration of various parameters of QoL seems to be a major issue. Indeed, on the one hand, it is essential to take into account the opinion of patients in the choice of therapeutic strategies for this cancer with a poor prognosis and, on the other hand, more and more studies show that QoL is an independent prognostic factor in ovarian cancer. Improvement in this case, in addition to being an endpoint by itself, would potentially improve the overall survival of patients. To date there are several tools to assess QOL of patients with ovarian cancer. The 2 questionnaires most commonly used are: FACT-O and the EORTC QLQ-OV28. The aim of our study was to evaluate from a review of the literature, the reciprocal effects of ovarian cancer on QoL and QoL on ovarian cancer survival, as well as specificities of each of the 2 questionnaires most commonly used in assessing the QoL.

PubMed | Toulouse University Hospital Center, Hopital Necker Enfants Malades, Unicancer, Institute Bergonie and 14 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2016

Based on preclinical data for the antitumour effect of zoledronate in osteosarcoma, we assessed whether zoledronate combined with chemotherapy and surgery improved event-free survival in children and adults with osteosarcoma.In this randomised, multicentre, open-label, phase 3 trial (OS2006), patients aged between 5 years and 50 years with newly diagnosed high-grade osteosarcoma were randomly assigned to receive standard chemotherapy with or without ten zoledronate intravenous infusions (four preoperative and six postoperative). Adults older than 25 years received 4 mg zoledronate per infusion, patients aged 18-25 years received 005 mg/kg for the first two infusions and 4 mg for the remaining eight infusions, and younger patients received 005 mg/kg per infusion. Chemotherapy comprised high-dose methotrexate based chemotherapy in patients younger than 18 years, and doxorubicin, ifosfamide, and cisplatin in adults older than 25 years; patients aged 18-25 years were treated with either regime at the discretion of the treating centre. Balanced randomisation between the two groups was done centrally with online randomisation software, based on a minimisation algorithm taking into account centre, age, combined with chemotherapy regimen, and risk group (resectable primary and no metastasis vs other). Patients and investigators were not masked to treatment assignment, but the endpoint adjudication committee members who reviewed suspected early progressions were masked to group allocation. The primary endpoint was event-free survival, estimated from the randomisation to the time of first failure (local or distant relapse, progression, death) or to the last follow-up visit for the patients in first complete remission, analysed on a modified intention-to-treat population, which excluded patients found not to have a malignant tumour after central review. Three interim analyses were planned. This trial is registered with, number NCT00470223.Between April 23, 2007, and March 11, 2014, 318 patients, median age 155 years (range 58-509), were enrolled from 40 French centres; of whom 158 were assigned to the control group (chemotherapy alone) and 160 to the zoledronate group, including 55 (17%) patients with definite metastases. The trial was stopped for futility after the second interim analysis. With a median follow-up of 39 years (IQR 27-51), 125 events occurred (55 in the control group and 70 in the with zoledronate group). Event-free survival at 3 years for all 315 randomly assigned patients was 603% (95% CI 645-659); 3-year event-free survival was 634% (552-709) for the control group and 571% (488-650) for the zoledronate group. The risk of failure was not reduced and was even marginally higher in the zoledronate group than in the control group (hazard ratio [HR] 136 [95% CI 095-196]; p=0094). No major increase in severe toxic effects of grade 3 or higher associated with zoledronate, barring expected hypocalcaemia (45 [29%] of 153 participants in the zoledronate group vs ten [6%] of 155 participants in the control group; p<00001) and hypophosphataemia (61 [40%] of 151 in the zoledronate group vs 26 [17%] of 156 in the control group; p<00001). No significant difference in orthopaedic complications was noted between the two groups (27 in the control group and 29 in the zoledronate group). Two treatment-related deaths were reported (one from cardiomyopathy in the control group and one from multiorgan failure in the zoledronate group before the first zoledronate infusion).From the results observed in this study, we do not recommend zoledronate in osteosarcoma patients. Further biological studies are required to understand the discordance between the results of OS2006 trial and preclinical data.French National Cancer Institute (INCa), Novartis, Chugai, Ligue Nationale contre le Cancer, Fdration Enfants et Sant, Socit Franaise des Cancers et Leucmies de lEnfant.

PubMed | University Hospital Gasthuisberg, University Hospital, Service dHematologie Greffe, French Institute of Health and Medical Research and 13 more.
Type: Comparative Study | Journal: Bone marrow transplantation | Year: 2015

Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA-identical sibling donors aged 55 years or more should not be excluded because of age for patients aged 55 years and older with AML in CR1.

PubMed | University of Texas Health Science Center at San Antonio, University of Houston, University of California at Irvine, Hospital Pontchaillou and 8 more.
Type: Clinical Trial, Phase II | Journal: Clinical lymphoma, myeloma & leukemia | Year: 2016

Long-term disease-free survival in adult patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory, and the treatment options are limited for those patients with relapse or a failure to respond after initial therapy. We conducted a dose-escalation/expansion phase II, multicenter, single-arm study to determine the optimal dose of coltuximab ravtansine (SAR3419), an anti-CD19 antibody-drug conjugate, in this setting.The dose-escalation part of the study determined the selected dose of coltuximab ravtansine for the evaluation of efficacy and safety in the dose-expansion phase. Patients received coltuximab ravtansine induction therapy ( 8 weekly doses). The responding patients were eligible for maintenance therapy (biweekly administration for 24 weeks). Three dose levels of coltuximab ravtansine were examined: 55, 70, and 90 mg/m(2). The primary endpoint was the objective response rate (ORR). The secondary endpoints included the duration of response (DOR) and safety.A total of 36 patients were treated: 19 during dose escalation and 17 during dose expansion. One dose-limiting toxicity was observed at 90 mg/m(2) (grade 3 peripheral motor neuropathy); therefore, 70 mg/m(2) was selected for the dose-expansion phase. Five patients discontinued therapy because of adverse events (AEs). The most common AEs were pyrexia, diarrhea, and nausea. Of the 17 evaluable patients treated at the selected dose, 4 had a disease response (estimated ORR using the Bayesian method: 25.5% (80% confidence interval, 14.2%-39.6%). The DOR was 1.9 months (range, 1-5.6 months). Because of these results, the study was prematurely discontinued.Coltuximab ravtansine was well tolerated but was associated with a low clinical response rate in patients with relapsed or refractory ALL.

Bykerk V.P.,Hospital for Special Surgery | Bykerk V.P.,Mount Sinai Hospital | Kstr A.J.,Addenbrookes Hospital | Alvaro-Gracia J.,Hospital Universitario Of La Princesa | And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis). Methods: Patients-categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout)-received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses. Results: Overall, 1681 (976 TNF-naive, 298 TNFiprevious and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFiprevious) and 50.4% (TNFi-recent) patients achieved DAS28 remission. Conclusions: In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.

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