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International audience; Purpose: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. Materials and methods: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. Results: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. Conclusion: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.

Survey about LTFU care and specific questions about second cancers. (DOCX 13 kb)

List of involved centers or hospitals. (DOCX 12 kb)

International audience; The ability to predict tumor recurrence after chemoradiotherapy of locally advanced cervical cancer is a crucial clinical issue to intensify the treatment of the most high-risk patients. The objective of this study was to investigate tumor metabolism characteristics extracted from pre- and per-treatment F-18-FDG PET images to predict 3-year overall recurrence (OR). A total of 53 locally advanced cervical cancer patients underwent pre-and per-treatment F-18-FDG PET (respectively PET1 and PET2). Tumor metabolism was characterized through several delineations using different thresholds, based on a percentage of the maximum uptake, and applied by region-growing. The SUV distribution in PET1 and PET2 within each segmented region was characterized through 7 intensity and histogram-based parameters, 9 shape descriptors and 16 textural features for a total of 1026 parameters. Predictive capability of the extracted parameters was assessed using the area under the receiver operating curve (AUC) associated to univariate logistic regression models and random forest (RF) classifier. In univariate analyses, 36 parameters were highly significant predictors of 3-year OR (p < 0.01), AUC ranging from 0.72 to 0.83. With RF, the Out-of-Bag (OOB) error rate using the totality of the extracted parameters was 26.42% (AUC=0.72). By recursively eliminating the less important variables, OOB error rate of the RF classifier using the nine most important parameters was 13.21% (AUC=0.90). Results suggest that both pre-and per-treatment F-18-FDG PET exams provide meaningful information to predict the tumor recurrence. RF classifier is able to handle a very large number of extracted features and allows the combination of the most prognostic parameters to improve the prediction.

International audience; Cervical cancer is one of the most common cancer to affect women worldwide. Despite the efficiency of radiotherapy treatment, some patients present post-treatment tumor recurrence which increases the risk of death. Early outcome prediction could help oncologists to adapt the treatment. Several studies suggest that quantification of tumor activity using F-18-FDG PET imaging could be used to predict post-treatment tumor recurrence. In this paper we study the predictive value of weighted quantification of tumor metabolism extracted by fuzzy-thresholding for tumor recurrence of locally advanced cervical cancer. Fifty-three patients with locally advanced cervical cancer treated by chemo-radiotherapy were considered in our study. For each patient, a coregistered F-18-FDG PET/CT scan was acquired before the treatment and was segmented using different hard and fuzzy segmentations methods. The tumor activity was extracted through the total lesion glycolysis and through a weighted analog of the total lesion glycolysis using the probability maps provided by the fuzzy segmentations. Outcomes prediction was performed using the area under the receiver operating characteristic curve (AUC) and the Harrell's C-index. Results suggest that weighted quantification of tumor activity seems to be strongly informative and could be used to predict post-treatment tumor recurrence in cervical cancer

International audience; PURPOSE: In case of tumour displacement, image-guided radiotherapy (IGRT) based on the use of cone beam CT (tomographie conique) allows replacing the tumour under the accelerator by rigid registration. Anatomical deformations require however replanning, involving an estimation of the cumulative dose, session after session. This is the objective of this study. PATIENTS AND METHODS: Two examples of arc-intensity modulated radiotherapy are presented: a case of prostate cancer (total dose=80 Gy) with tomographie conique (daily prostate registration) and one head and neck cancer (70 Gy). For the head and neck cancer, the patient had a weekly scanner allowing a dose distribution calculation. The cumulative dose was calculated per voxel on the planning CT after deformation of the dose distribution (with trilinear interpolation) following the transformation given by a non-rigid registration step (Demons registration method) from: either the tomographie conique (prostate), or the weekly CT. The cumulative dose was eventually compared with the planned dose. RESULTS: In cases of prostate irradiation, the "cumulative" dose corresponded to the planned dose to the prostate. At the last week of irradiation, it was above the planned dose for the rectum and bladder. The volume of rectal wall receiving more than 50 Gy (V50) was 20% at the planning and 26% at the end of treatment, increasing the risk of rectal toxicity (NTCP) of 14%. For the bladder wall, V50 were 73% and 82%, respectively. In head and neck, the "cumulative" dose to the parotid exceeded the planned dose (mean dose increasing from 46 Gy to 54 Gy) from the 5th week of irradiation on, suggesting the need for replanning within the first 5 weeks of radiotherapy. CONCLUSION: The deformable registration estimates the cumulative dose delivered in the different anatomical structures. Validation on digital and physical phantoms is however required before clinical evaluation.

National audience; PURPOSE: In cervix carcinoma: (a) to evaluate the ability of ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the lymph node detection; (b) to investigate the prognostic and predictive value of the primary cervical PET parameters. PATIENTS AND METHODS: Ninety patients treated for cervix carcinoma and evaluated initially by MRI and FGD PET were included. The performances of FDG-PET for lymph node detection (relatively to the lymph node dissection) have been described (sensitivity, specificity, positive predictive value and negative predictive value). PET tumour parameters analyzed were: maximum standard uptake value (SUVmax), the volume and the maximum diameter. The prognostic and predictive values of these parameters were investigated. The tumour response was evaluated on surgical specimens. RESULTS: PET detected the cervical tumour with a sensitivity of 97% (mean values: SUVmax=15.8, volume=27 mm(3), maximum diameter=47). For the detection of the lymph nodes, the values of sensibility, specificity, positive predictive value and negative predictive value were: 86, 56, 69 and 78% in the pelvic, and 90, 67, 50 and 95% for the para-aortic area, respectively. The SUVmax was correlated with histologic response (P=0.04). The frequency of partial histological response was significantly higher for tumour SUVmax>10.9 (P=0.017). The maximum PET diameter and pathologic response had an impact on disease-free survival and overall survival in multivariate analysis (P

International audience; Constitutive activation of Wnt/β-catenin signaling in cancer results from mutations in pathway components, which frequently coexist with autocrine Wnt signaling or epigenetic silencing of extracellular Wnt antagonists. Among the extracellular Wnt inhibitors, the secreted frizzled-related proteins (SFRPs) are decoy receptors that contain soluble Wnt-binding frizzled domains. In addition to SFRPs, other endogenous molecules harboring frizzled motifs bind to and inhibit Wnt signaling. One of such molecules is V3Nter, a soluble SFRP-like frizzled polypeptide that binds to Wnt3a and inhibits Wnt signaling and expression of the β-catenin target genes cyclin D1 and c-myc. V3Nter is derived from the cell surface extracellular matrix component collagen XVIII. Here, we used HCT116 human colon cancer cells carrying the ΔS45 activating mutation in one of the alleles of β-catenin to show that V3Nter and SFRP-1 decrease baseline and Wnt3a-induced β-catenin stabilization. Consequently, V3Nter reduces the growth of human colorectal cancer xenografts by specifically controlling cell proliferation and cell cycle progression, without affecting angiogenesis or apoptosis, as shown by decreased [(3)H]-thymidine (in vitro) or BrdU (in vivo) incorporation, clonogenesis assays, cell cycle analysis and magnetic resonance imaging in living mice. Additionally, V3Nter switches off the β-catenin target gene expression signature in vivo. Moreover, experiments with β-catenin allele-targeted cells showed that the ΔS45 β-catenin allele hampers, but does not abrogate, inhibition of Wnt signaling by SFRP-1 or by the SFRP-like frizzled domain. Finally, neither SFRP-1 nor V3Nter affect β-catenin signaling in SW480 cells carrying nonfunctional Adenomatous polyposis coli. Thus, SFRP-1 and the SFRP-like molecule V3Nter can inhibit tumor growth of β-catenin-activated tumor cells in vivo.