Rene Gauducheau Cancer Center

Saint-Herblain, France

Rene Gauducheau Cancer Center

Saint-Herblain, France
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Perrier L.,Leon Berard Cancer Center | Morelle M.,Leon Berard Cancer Center | Pommier P.,Leon Berard Cancer Center | Lagrange J.-L.,APHP University | And 12 more authors.
Radiotherapy and Oncology | Year: 2013

Purpose: This cost analysis aimed to quantify the cost of IGRT in relation to IGRT frequency and modality with Cone Beam Computed Tomography (CBCT) or orthogonal electronic portal imaging with fiducial markers (EPI-FM). Material and methods: Patients undergoing IGRT for localized prostate cancer were randomized into two prostate control frequencies (daily or weekly). Costs were calculated based on the micro-costing results according to hospitals' perspectives (in Euros, 2009) and the time horizon was radiation therapy. Results: A total of 208 patients were enrolled in seven French cancer centers. A total of 6865 fractions were individually analyzed. The mean total treatment fraction duration was 21.0 min for daily CBCT and 18.3 min for daily EPI-FM. Increasing the control frequency from weekly to daily increased the mean treatment fraction duration by 7.3 min (+53%) for CBCT and 1.7 min (+10%) for EPI-FM (p ≤ 0.01). The mean additional cost per patient of daily controls compared with weekly controls was 679 and 187 for CBCT and EPI-FM, respectively (p < 0.0001). Conclusions: The incremental costs due to different prostate IGRT strategies are relatively moderate, suggesting that daily IGRT combined with intensity-modulated RT (IMRT) could be administered in cases of high-dose radiation delivery to the prostate. © 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology.

PubMed | Lorraine Institute of Oncology, Institute Claudius Regaud, Montpellier Cancer Institute, Clinique Pasteur and 9 more.
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2016

This cost analysis aimed to prospectively assess differences in costs between TomoTherapy and volumetric modulated arc therapy (VMAT) in patients with head and neck cancer.Economic data were gathered from a multicenter study. However, randomization was not possible due to the availability of equipment. Costs were calculated using the microcosting technique from the hospitals perspective (in 2013 euros), and the time horizon was radiation therapy. Only resources that entered the hospital production process and which were likely to vary between the strategies being compared were considered. Acute adverse events observed within the time horizon were also assessed.The cost analysis was based on a total of 173 patient treatments given between 2010 and 2012 in 14 French cancer centers: 73 patients were treated with TomoTherapy, 92 with VMAT RapidArc, and 8 with VMAT SmartArc. Estimated costs of SmartArc were removed from the comparison due to the small sample size. The meanSD cost per patient of the treatment planning phase was 314 (214) for TomoTherapy and 511 (590) for RapidArc. Mean costsSD per patient of irradiation reached 3144 (565) for TomoTherapy and 1350 (299) for RapidArc. The most sensitive parameter of irradiation was the annual operating time of accelerators. Ninety-five percent confidence intervals for the mean costs of irradiation were 3016 to 3272 for TomoTherapy and 1281 to 1408 for RapidArc. The number of acute adverse events during radiation therapy was not significantly different between strategies.TomoTherapy appeared to be more expensive than RapidArc mainly due to the higher price of the accelerator, the higher costs of maintenance, and the longer duration of treatment sessions. Because strategies were not significantly different in clinical effect, RapidArc appeared to be the strategy to be recommended at this stage of knowledge.

Cassier P.A.,Center Leon Berard | Gelderblom H.,Leiden University | Stacchiotti S.,Italian National Cancer Institute | Thomas D.,Peter MacCallum Cancer Center | And 10 more authors.
Cancer | Year: 2012

BACKGROUND: Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. METHODS: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi-institutional retrospective study to assess the activity of IM in patients with locally advanced/metastatic PVNS/TGCT. RESULTS: Twenty-nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n = 17; 59%). Two patients had metastatic disease to the lung and/or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. CONCLUSIONS: IM displayed interesting activity in patients with PVNS/TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/TGCT must be balanced against the potential toxicity of chronic drug therapy. © 2011 American Cancer Society.

Descotes F.,Lyon University Hospital Center | Jezequel P.,Rene Gauducheau Cancer Center | Spyratos F.,Institute Curie Hopital Rene Huguenin | Campion L.,Biostatistics Unit | And 14 more authors.
International Journal of Oncology | Year: 2012

We used a 2D-electrophoresis (2-DE) proteomic approach to identify novel biomarkers in node-negative breast cancers. This retrospective study focused on a population of patients with ductal pN0M0 tumours. A subset of patients who developed metastases and in whose tumours were found high levels of uPA and PAI-1 (metastatic relapse, MR: n=20) were compared to another subset in whom no metastatic relapse occurred and whose tumours were found to have low levels of uPA and PAI-1 (no relapse, NR: n=21). We used a 2-DE coupled with MS approach to screen cytosol fractions using two pH-gradient scales, a broad scale (3.0-11.0) and a narrower scale focussing in on a protein rich region (5.0-8.0). This study was conducted on 41 cytosol specimens analyzed in duplicate on two platforms. The differential analysis of more than 2,000 spots in 2-DE gels, obtained on the two platforms, allowed the identification of 13 proteins which were confirmed by western blotting. Two proteins, GPDA and FABP4 were down-regulated in the MR subset whereas all the others were up-regulated. An in silico analysis revealed that GMPS (GUAA), GAPDH (G3P), CFL1 (COF1) and FTL (FRIL), the most informative genes, displayed a proliferation profile (high expression in basal-like, HER2 + and luminal B molecular subtypes). Inversely, similar to FABP4, GPD1 [GPDA] displayed a high expression in luminal A subtype, a profile characteristic of tumour suppressor genes. Despite the small size of our cohort, the 2-DE analysis gave interesting results which were confirmed by the in silico analysis showing that some of the corresponding genes had a strong prognostic impact in breast cancer, mostly because of their link with proliferation: GMPS, GAPDH, FTL and GPD1. A validation phase on a larger cohort is now needed before these biomarkers could be considered for use in clinical practice.

Kraeber-Bodere F.,University of Nantes | Kraeber-Bodere F.,Rene Gauducheau Cancer Center | Bodet-Milin C.,University of Nantes | Niaudet C.,University of Nantes | And 10 more authors.
Journal of Nuclear Medicine | Year: 2010

A significant antitumor effect was previously observed with radioimmunotherapy using anti-carcinoembryonic antigen 131I-F6 monoclonal antibody in medullary thyroid cancer-bearing nude mice. Nevertheless, no complete response was observed. As seen with chemotherapy, drugs targeting the tumor microenvironment might improve radioimmunotherapy efficacy. This study evaluated the toxicity and efficacy of combining radioimmunotherapy with thalidomide or a cyclopeptidic vascular endothelial growth inhibitor (CBOP11) in mice grafted with the TT human medullary thyroid cancer cell line. Methods: Six to 10 nude mice treated with 92.5 MBq of 131I-F6 in association with 200 mg/kg/d of oral thalidomide during 20 d by force-feeding or 0.45 mg/kg/d of CBOP11 during 25 d using subcutaneous minipumps were compared with control mice receiving either treatment or naked F6 or nonspecific 131I-734. Combined therapies included 131I-F6 at day 0 followed by thalidomide between days 20 and 40, thalidomide between days 0 and 20 followed by 131I-F6 at day 25, 131I-F6 at day 0 and CBOP11 between days 0 and 25, CBOP11 between days 0 and 25 followed by 131I-F6 at day 25, and 131I-F6 at day 0 followed by CBOP11 between days 20 and 45. Animal weight, hematologic toxicity, tumor volume, and serum calcitonin were monitored for the following 3 mo. Improvement of 125I-F6 tumor biodistribution by antiangiogenic drug was studied after pretreatment by thalidomide. Follow-up of the tumor after combined antiangiogenic and radioimmunotherapy therapies was performed by histology studies. Results: Combined associations, as compared with radioimmunotherapy alone, increased leukopenia but not thrombocytopenia. Tumor volume-quadrupling time (TVQT) was 22.8 ± 3.3 d in the control group, 29.9 ± 3.6 d in the group treated with thalidomide, 34.6 ± 4.4 d in the group treated with CBOP11, and 51.0 ± 2.8 d after radioimmunotherapy alone. As compared with radioimmunotherapy, TVQT was significantly longer (P<0.01) after thalidomide followed by radioimmunotherapy (69.83 ± 3.9), CBOP11 followed by radioimmunotherapy (71.3 ± 6.1), and CBOP11-radioimmunotherapy in concomitance (64.2 ± 6.1). Nevertheless, TVQT was not increased after radioimmunotherapy followed by thalidomide (48.8 ± 4) and radioimmunotherapy followed by CBOP11 (56.8 ± 4.8). Surprisingly, pretreatment by CBOP11 or thalidomide sensitized larger tumors (>300 mm 3) to radioimmunotherapy. Change in calcitonin levels confirmed morphologic tumor response. Tumor uptake 24 h after injection of 125I-F6 was 4.5 ± 0.6 percentage injected dose per gram(%ID/g) without pretreatment and 8.7 ± 1.3%ID/g with pretreatment by thalidomide. An increase of the antitumor effect observed using the antiangiogenic drug combined with radioimmunotherapy was correlated with a decrease of blood vessels shown by von Willebrand immunostaining. Conclusion: Pretreatment with antiangiogenic therapies improved radioimmunotherapy efficacy, with acceptable toxicity. Future investigations will be performed to understand how antiangiogenic agents sensitize large tumors to radioimmunotherapy. Copyright © by the Society of Nuclear Medicine, Inc.

Cherel M.,University of Nantes | Cherel M.,Rene Gauducheau Cancer Center | Gouard S.,University of Nantes | Gaschet J.,University of Nantes | And 12 more authors.
Journal of Nuclear Medicine | Year: 2013

New multiple myeloma (MM) treatments-such as high-dose melphalan therapy plus autologous stem cell transplantation or regimens incorporating bortezomide, thalidomide, and lenalidomide- substantially increase the rate of complete response that is associated with longer patient survival. Thus, maintaining the complete response status by improving the minimal residual disease after induction therapy is a key goal for MM management. Here, we address the question of radioimmunotherapy efficacy in MM minimal residual disease treatment in mice with a low tumor burden. a-emitters are particularly well adapted to this approach because the short range of a-particles enables localized irradiation of tumor cells within the bone marrow and a cytotoxic effect on isolated cells due to the high LET (linear energy transfer) of a-particles. The CD138 antigen was used as a target because of its strong expression on myeloma cells in 100% of patients. Method: Intravenous injection of 106 5T33 mouse myeloma cells into the Syngeneic mouse strain C57BL/KaLwRij resulted in a rapid invasion of the marrow and limb paralysis, as illustrated by bioluminescence imaging with luciferase-transfected 5T33 cells. Radioimmunotherapy was performed 10 d after 5T33 cell engraftment with an intravenous injection of an antimouse CD138 antibody radiolabeled with 213Bi at activities of 1.85, 3.7, 7.4, and 11.1 MBq. A blood cell count was performed weekly to monitor hematologic toxicity. The levels of blood Flt3 ligand were also measured to evaluate the radioimmunotherapy-related myelotoxicity. Disease progression was monitored by titrating the monoclonal IgG2b antibody produced by 5T33 cells. Results: The groups treated with 3.7 and 7.4 MBq exhibited a median survival greater than 300 and 227 d, respectively, compared with 45.5 d in the control untreated group. The highest activity (11.1 MBq) showed short-term toxicity whereas the lowest activity (1.85 MBq) gave results similar to those of the controls. With activities of 3.7 and 7.4 MBq, mice exhibited a transient hematologic toxicity whereas only temporary and moderate myelotoxicity was observed with 7.4 MBq. Conclusion: This study demonstrates promising therapeutic efficacy of 213Bi-labeled antimCD138 for the treatment of residual disease in the case of MM, with only moderate and transient toxicity. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Harousseau J.L.,Rene Gauducheau Cancer Center
Oncology (Williston Park, N.Y.) | Year: 2010

Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.

Harousseau J.-L.,Rene Gauducheau Cancer Center
Clinical Lymphoma, Myeloma and Leukemia | Year: 2010

In 2000, the most important therapeutic improvement in multiple myeloma (MM) had been the introduction of high-dose therapy (HDT) supported by autologous stem cell transplantation, but this strategy was proposed only to younger patients without comorbidities. In the past decade, progress in the management of MM has been dramatic and more rapid than in the four previous decades. The main reason for this has been the introduction of three novel agents in less than five years. These three agents, two immunomodulatory agents (IMIDs; thalidomide and lenalidomide) and one proteasome inhibitor (bortezomib) have been initially used in relapsed or refractory patients and rapidly added to frontline therapy both in younger and older patients. They have already increased overall survival but are also changing the objectives of treatment and the therapeutic strategy; other important advances have been made during these ten years with new diagnostic and staging procedures and new prognostic factors. These clinical improvements have been possible mostly by a better understanding of the disease pathophysiology, including genetic changes, and by the development of preclinical in vitro and vivo tests to better evaluate the potential clinical activity of new agents. © 2011 CIG Media Group, lp.

Salaun P.-Y.,French Institute of Health and Medical Research | Bodet-Milin C.,French Institute of Health and Medical Research | Bodet-Milin C.,University of Nantes | Frampas E.,French Institute of Health and Medical Research | And 10 more authors.
Cancer | Year: 2010

BACKGROUND: Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anticarcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells. METHODS: Groups of 4-6 nude mice were treated with 5 μg/g bevacizumab twice weekly during 4 weeks and/or 100 MBq of 131IF6. For combined therapy, bevacizumab was given at Day 0 followed by 131I-F6 at Day 30. The control group received no treatment. Animal weight, hematological toxicity, tumor volume, and serum calcitonin were monitored for 2 or 4 months. RESULTS: Bevacizumab alone induced no cytopenia and no significant weight loss. A weight loss of 12 ± 1% and 15 ± 2% was observed in mice treated by RIT alone or bevacizumab + RIT, respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT alone and RIT plus bevacizumab induced tumor responses with minimum relative tumor volume of 0.38 ± 0.24 and 0.15 ± 0.07%, respectively, and time to progression of 35 ± 5 and 56 ± 11 days, respectively. CONCLUSIONS: Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as compared as RIT alone. © 2010 American Cancer Society.

Pallardy A.,Rene Gauducheau Cancer Center | Bodet-Milin C.,University of Nantes | Oudoux A.,University of Nantes | Campion L.,Rene Gauducheau Cancer Center | And 11 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2010

Purpose: The aim of this retrospective study was to evaluate the contribution of 18F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival. Methods: A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard. Results: The final diagnosis was established pathologically (n=25) or by median clinical follow-up for 48 months after the PET (n=15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (>3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings with ≤1 focus for which the median survival was not attained (p=0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (>3 foci) was the most significant factor (p<0.03) for death from cervical cancer. Conclusion: FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome. © Springer-Verlag 2010.

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