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Rios R.,French Institute of Health and Medical Research | Rios R.,University of Rennes 1 | Rios R.,National University of Colombia | De Crevoisier R.,French Institute of Health and Medical Research | And 13 more authors.
Medical Image Analysis | Year: 2017

In radiotherapy for prostate cancer irradiation of neighboring organs at risk may lead to undesirable side-effects. Given this setting, the bladder presents the largest inter-fraction shape variations hampering the computation of the actual delivered dose vs. planned dose. This paper proposes a population model, based on longitudinal data, able to estimate the probability of bladder presence during treatment, using only the planning computed tomography (CT) scan as input information. As in previously-proposed principal component analysis (PCA) population-based models, we have used the data to obtain the dominant eigenmodes that describe bladder geometric variations between fractions. However, we have used a longitudinal analysis along each mode in order to properly characterize patient's variance from the total population variance. We have proposed is a mixed-effects (ME) model in order to separate intra- and inter-patient variability, in an effort to control confounding cohort effects. Other than using PCA, bladder shapes are represented by using spherical harmonics (SPHARM) that additionally enables data compression without information lost. Based on training data from repeated CT scans, the ME model was thus implemented following dimensionality reduction by means of SPHARM and PCA. We have evaluated the model in a leave-one-out cross validation framework on the training data but also using independent data. Probability maps (PMs) were thus generated with several draws from the learnt model as predicted regions where the bladder will likely move and deform. These PMs were compared with the actual regions using metrics based on mutual information distance and misestimated voxels. The prediction was also compared with two previous population PCA-based models. The proposed model was able to reduce the uncertainties in the estimation of the probable region of bladder motion and deformation. This model can thus be used for tailoring radiotherapy treatments. © 2017


Rios R.,French Institute of Health and Medical Research | Rios R.,University of Rennes 1 | Rios R.,National University of Colombia | Commandeur F.,French Institute of Health and Medical Research | And 7 more authors.
Proceedings of SPIE - The International Society for Optical Engineering | Year: 2017

In radiotherapy for prostate cancer the bladder presents the largest inter-fraction shape variations during treatment resulting in random geometric uncertainties that may increase the risk of developing side-effects. In this setting, our interest is thus to propose a hierarchical population model, based on longitudinal data, to characterize bladder motion and deformation between fractions. This method is based on a principal component analysis (PCA) of bladder shapes to obtain the dominant eigenmodes that describe bladder geometric variations between fractions. However, PCA may not properly capture the latent structure of complex data like longitudinal data of organs with large inter and intra-patient shape variations. With this, we propose hierarchical modes to separate intra-and inter-patient bladder variability of the longitudinal data following a dimensionality reduction by means of spherical harmonics (SPHARM). The training data base was used to derive a top-level PCA model that describes the entire structure of the bladder surface space. This space was subsequently divided into subspaces by lower-level PCA models that describe their internal structures. The model was evaluated using a reconstruction error and compared with a conventional PCA model following leave-one-out cross validation. © 2017 SPIE.


Karayan-Tapon L.,EA3805 | Karayan-Tapon L.,University of Poitiers | Quillien V.,CRLCC Eugene Marquis | Quillien V.,University of Monastir | And 14 more authors.
Journal of Neuro-Oncology | Year: 2010

This multicenter study assesses the value of O6- methylguanine-DNA methyltransferase (MGMT) status for predicting overall survival in glioblastoma patients. Five methods are used, to identify the approach with the best prognostic value. Eighty-one tumors were obtained from patients with glioblastomas treated by surgery and radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant TMZ. MGMT promoter methylation was assessed by qualitative methyl-specific polymerase chain reaction (MSP), semiquantitative methyl-specific polymerase chain reaction (SQ-MSP), and pyrosequencing, while MGMT expression was measured at the RNA level by quantitative real-time PCR (Q-RT-PCR) and at the protein level by immunohistochemistry (IHC). MGMT promoter methylation as evaluated by MSP, SQ-MSP, and pyrosequencing was significantly correlated with overall survival. The best predictive value was obtained by pyrosequencing of one specific CpG position. Overall survival was 14 and 25 months for patients with percentages of methylation below and above the median, respectively. In contrast, MGMT status determined by Q-RT-PCR and IHC showed little or no correlation with overall survival, respectively. These results confirm the prognostic value of MGMT promoter methylation in glioblastoma patients initially treated with TMZ. SQ-MSP allowed better discrimination than classical MSP, and pyrosequencing represented a good option. © Springer Science+Business Media, LLC. 2009.


Cuggia M.,French Institute of Health and Medical Research | Cuggia M.,Rennes University Hospital Center | Campillo-Gimenez B.,French Institute of Health and Medical Research | Bouzille G.,French Institute of Health and Medical Research | And 8 more authors.
Studies in Health Technology and Informatics | Year: 2015

Recruitment of patients in clinical trials is nowadays preoccupying, as the inclusion rate is particularly low. The main identified factors are the multiplicity of open clinical trials, the high number and complexity of eligibility criteria, and the additional workload that a systematic search of the clinical trials a patient could be enrolled in for a physician. The principal objective of the ASTEC project is to automate the prescreening phase during multidisciplinary meetings (MDM). This paper presents the evaluation of a computerized recruitment support systems (CRSS) based on semantic web approach. The evaluation of the system was based on data collected retrospectively from a 6 month period of MDM in Urology and on 4 clinical trials of prostate cancer. The classification performance of the ASTEC system had a precision of 21%, recall of 93%, and an error rate equal to 37%. Missing data was the main issue encountered. The system was designed to be both scalable to other clinical domains and usable during MDM process. © 2015 IMIA and IOS Press.


Perrin C.,Center Regional Of Lutte Contre Le Cancer Eugene Marquis | Pracht M.,Center Regional Of Lutte Contre Le Cancer Eugene Marquis | Talour K.,Center Hospitalier Of Cornouaille | Adamski H.,Center Hospitalo University Pontchaillou | And 8 more authors.
Journal of Dermatological Treatment | Year: 2014

Background: Metastatic melanoma is one of the most aggressive tumours, with a median survival that does not exceed 12 months. None of the cytotoxic first-line therapies have shown survival benefit in randomised clinical trials. Objective: To describe clinical benefit of second-line cytotoxic chemotherapy in the second line of treatment for metastatic melanoma. Methods: In a retrospective study, we analyse the outcome of patients with metastatic melanoma who had received two lines or more of cytotoxic treatments in four French dermato-oncology departments between 1999 and 2009. Results:We describe the outcomes for 109 patients. Most of these patients received dacarbazine for the first line of chemotherapy and fotemustine for the second line of chemotherapy (67.0 and 64.2%, respectively). A clinical benefit was observed in 24.1% of the patients and overall survival was 4.1 months after the second-line treatment. At least 23.8% of patients suffered from grade 3 or 4 toxicities. The presence of more than two sites of metastasis and an M1c staging according to the AJCC classification represented negative predictive factors of clinical benefit. Conclusion: This study shows the modest benefit of a second line of cytotoxic chemotherapy in a nonselected population. If eligible, these patients should be proposed for ongoing clinical trials or for targeted therapies. © 2014 Informa Healthcare USA on behalf of Informa UK Ltd.


Cazoulat G.,French Institute of Health and Medical Research | Cazoulat G.,University of Rennes 1 | Simon A.,French Institute of Health and Medical Research | Simon A.,University of Rennes 1 | And 9 more authors.
IEEE Transactions on Medical Imaging | Year: 2014

This paper addresses the issue of cumulative dose estimation from cone beam computed tomography (CBCT) images in prostate cancer radiotherapy. It focuses on the dose received by the surfaces of the main organs at risk, namely the bladder and rectum. We have proposed both a surface-constrained dose accumulation approach and its extensive evaluation. Our approach relied on the nonrigid registration (NRR) of daily acquired CBCT images on the planning CT image. This proposed NRR method was based on a Demons-like algorithm, implemented in combination with mutual information metric. It allowed for different levels of geometrical constraints to be considered, ensuring a better point to point correspondence, especially when large deformations occurred, or in high dose gradient areas. The three following implementations: 1) full iconic NRR; 2) iconic NRR constrained with landmarks (LCNRR); 3) NRR constrained with full delineation of organs (DBNRR). To obtain reference data, we designed a numerical phantom based on finite-element modeling and image simulation. The methods were assessed on both the numerical phantom and real patient data in order to quantify uncertainties in terms of dose accumulation. The LCNRR method appeared to constitute a good compromise for dose monitoring in clinical practice. © 1982-2012 IEEE.


Quillien V.,CRLCC Eugene Marquis | Quillien V.,French National Center for Scientific Research | Vauleon E.,CRLCC Eugene Marquis | Vauleon E.,French National Center for Scientific Research | And 6 more authors.
Bulletin du Cancer | Year: 2011

MGMT status is now regarded as a strong predictive factor of response to standard treatment of newly diagnosed glioblastomas involving temozolomide (TMZ) and radiotherapy. MGMT promoter methylation is also a prognostic factor - independent of treatment - in anaplastic gliomas. The predictive function can be explained by the role of theDNA repair enzymeMGMT,which antagonizes the effects of alkylating agents such as TMZ. MGMT promoter methylation could also reflect a particular molecular phenotype with its own specific prognostic significance. Since MGMT status determination is becoming a crucial biological marker in new clinical glioma trials, and is beginning to be used in day-to-day clinical practice, there is currently a strong need to determine the best technique for MGMT analysis. A French multicenter study has been set up for this purpose. ©John Libbey Eurotext.


Vanpouille-Box C.,French Institute of Health and Medical Research | Lacoeuille F.,French Institute of Health and Medical Research | Lacoeuille F.,Angers University Hospital Center | Roux J.,University of Angers | And 15 more authors.
PLoS ONE | Year: 2011

Background: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC188Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC188Re-SSS in a chemically induced hepatocellular carcinoma rat model. Methodology/Principal Findings: Animals were treated with an injection of LNC188Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and 188Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC188Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC188Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. Conclusions/Significance: Overall, these results demonstrate that internal radiation with LNC188Re-SSS is a promising new strategy for hepatocellular carcinoma treatment. © 2011 Vanpouille-Box et al.


Robert A.-L.,University of Rennes 2 – Upper Brittany | Nicolas F.,University of Rennes 2 – Upper Brittany | Lavoue V.,University of Rennes 2 – Upper Brittany | Henno S.,University of Rennes 2 – Upper Brittany | And 3 more authors.
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2014

Objectives To assess whether there is a correlation between the length of a conization specimen and the length of the cervix measured by vaginal ultrasonography after the operation Patients and methods Prospective observational study including patients less than 45 years with measurement of cervical length before and the day of the conization, and measuring the histological length of the specimen. Results Among the 40 patients enrolled, the average ultrasound measurements before conization was 26.9 mm (± 4.9 mm) against 18.1 mm (± 4.4 mm) after conization with a mean difference of 8.8 mm (± 2.4 mm) (difference statistically significant P <.0001). The extent of histological specimen was 9 mm (± 2.2 mm) on average. A correlation between ultrasound and histological measurements with a correlation coefficient R = 0.85 was found statistically significant (P < 0.0001). Moreover, the rate of cervix length remove by loop-excision in our series is 33% (± 8.5%). Discussion A good correlation between the measurements of the specimen and the cervical ultrasound length before and after conization was found, as a significant reduction in cervical length after conization. The precise length of the specimen should be known in case of pregnancy and the prevention of prematurity due to conization rests on selected indications and efficient surgical technique. © 2013 Elsevier Masson SAS. Tous droits réservés.

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