[Understanding/acceptance of radiotherapy: An ethical dilemma resolved by an ethics of care]. / Compréhension/acceptation de la radiothérapie : un dilemme éthique résolu par une éthique de la considération et de la sollicitude.

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.

[French organization of paediatric radiation treatment: Results of a survey conducted by the radiotherapy Committee of the French Society of Paediatric Cancers (SFCE)]. / Organisation française de la radiothérapie pédiatrique : résultats d'une enquête du comité radiothérapie de la Société française des cancers de l'enfant (SFCE).

PURPOSE: Radiotherapy is a rare indication in paediatric oncology, with 800 to 900 children in treatment per year in France. Child cancers represent approximately 1% of cancers in France and half occur before the age of 5 years. Paediatric radiation requires appropriate tools, local, time and specific training. In France, in 2015, 18 centres are accredited by the French National Cancer Institute (INCa) for this activity. MATERIAL AND METHODS: Survey conducted in February 2015 on the care of children (0 to 18 years) in radiotherapy departments in France. The survey was sent to the radiation oncologists involved in the 18 centres. The questions concerned the qualitative and quantitative aspect, medical and organizational aspects, and the involvement of assistant practitioners in the management of this activity. RESULTS: Seventeen centres responded. In 2014, 889 children under 18 were treated in radiotherapy departments. These departments are working together with one to four paediatric oncology departments. Regarding access to general anaesthesia: three centres perform one to seven treatment(s) under anaesthesia per year, three centres eight to ten treatments under anaesthesia per year, three centres ten to 24 treatments under anaesthesia per year and nine centres out of 17 use hypnosis techniques. In terms of human resources, in 2015, 29 radiation therapists have a paediatric radiotherapy activity. Involvement of assistant practitioners is growing and specific training are desired. Regarding treatment preparation and delivery, 13 centres have specific paediatric contentions, 14 of 16 centres employ radiation intensity modulated if dosimetry is more satisfying with 11 regularly to the craniospinal irradiation. Radiotherapy on moving areas with respiratory gating or hypofractionation is under developed. CONCLUSION: Paediatric radiation therapy is a specific activity requiring a dedicated management, both in human, organizational, medical and scientific aspects.

[French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)]. / Expérience française de l'irradiation corporelle totale en pédiatrie : étude du comité de radiothérapie de la Société française des cancers de l'enfant (SFCE).

A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults.

[Benefit of a pretreatment planning library-based adaptive radiotherapy for cervix carcinoma?]. / Bénéfice de la radiothérapie adaptative par bibliothèque de plans de traitement pour les cancers du col utérin ?

PURPOSE: In case of intensity-modulated radiotherapy (IMRT) for locally advanced cervix carcinoma, the objectives were to quantify the difference between the planned and the delivered doses by a standard irradiation, and to estimate the dosimetric benefit of a pretreatment planning library-based adaptive radiotherapy. MATERIAL AND METHODS: Ten patients with locally advanced cervix carcinoma had three planning CTs corresponding to three bladder volumes: empty, intermediate (vi) and full. On each CT, two IMRT plans were generated to deliver 45 Gy to the planning target volume (PTV), with two different margins: clinical target volume (CTV)+10mm and CTV+15 mm. Using bi-weekly CBCTs, three scenarios of treatment have been simulated and compared: standard IMRT (one vi planning) with 10 and 15 mm margins and adaptive radiotherapy with 10mm margin. The cumulated dose in the organs at risk was estimated by elastic registration. RESULT: In case of standard IMRT, the cumulated dose was significantly different than the planning dose, with an under-dose of the CTV and the bladder, and an over-dose of the rectum and the peritoneal cavity. For 54% of the fractions, the adaptive radiotherapy planning was not based on vi. Considering the cumulated dose and compared to IMRT with 10-mm margin, adaptive radiotherapy increased the dose to the CTV (1.4 Gy for D98%) and decreased slightly the dose to the rectum and the peritoneal cavity. Compared to a standard IMRT with 15 mm margin, adaptive radiotherapy decreased significantly the dose to the rectum (20% for V40), the bladder (13% for V40) and the peritoneal cavity (2% for V35). CONCLUSION: A pretreatment planning library-based adaptive radiotherapy in cervix carcinoma decreases the dose to the organs at risk and increases the dose to the CTV.

[Mid-ventilation position planning: optimal model for dose distribution in lung tumour]. / Planification selon la position moyenne du cycle respiratoire : modèle de planification optimale pour une distribution de dose dans les tumeurs pulmonaires.

PURPOSE: The dose distribution for lung tumour is estimated using a 3D-CT scan, and since a person breathes while the images are captured, the dose distribution doesn't reflect the reality. A 4D-CT scan integrates the motion of the tumour during breathing and, therefore, provides us with important information regarding tumour's motion in all directions, the motion volume (ITV) and the time-weighted average position (MVP). PATIENT AND METHODS: Based on these two concepts, we have estimated, for a lung carcinoma case a 3D dose distribution from a 3D-CT scan, and a 4D dose distribution from a 4-D CT scan. To this, we have applied a non-rigid registration to estimate the cumulative dose. RESULTS: Our study shows that the 4D dose estimation of the GTV is almost the same when made using MVP and ITV concepts, but sparring of the healthy lung is better done using the MPV model (MVP), as compared to the ITV model. This improvement of the therapeutic index allows, from a projection on the theoretical maximal dose to PTV (strictly restricted to doses for the lungs and the spinal cord), for an increase of about 11% on the total dose (maximal dose of 86 Gy for the ITV and 96 Gy for the MVP). CONCLUSION: Further studies with more patients are needed to confirm our data.

[From image-guided radiotherapy to dose-guided radiotherapy]. / De la radiothérapie guidée par l'image à la radiothérapie guidée par la dose.

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.

[((18)F)-fluorodeoxyglucose PET/CT in cervix cancer: lymph node assessment and prognostic/predictive value of primary tumour analysis]. / Tomographie par émission de positons au ((18)F)-fluorodésoxyglucose dans les cancers du col utérin : évaluation ganglionnaire et valeur pronostique/prédictive des données de la tumeur primitive.

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<0.05). CONCLUSION: PET has high sensitivity in detecting pelvic and para-aortic lymph nodes. Some primary cervical tumour PET parameters are useful as prognostic and predictive factors.

Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active ß-catenin.

Constitutive activation of Wnt/ß-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 ß-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 ß-catenin to show that V3Nter and SFRP-1 decrease baseline and Wnt3a-induced ß-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 ß-catenin target gene expression signature in vivo. Moreover, experiments with ß-catenin allele-targeted cells showed that the ΔS45 ß-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 ß-catenin signaling in SW480 cells carrying nonfunctional Adenomatous polyposis coli. Thus, SFRP-1 and the SFRP-like molecule V3Nter can inhibit tumor growth of ß-catenin-activated tumor cells in vivo.

[Intensity-modulated radiotherapy for cancers in childhood]. / Radiothérapie conformationnelle par modulation d'intensité des tumeurs pédiatriques.

Approximately 40-50% of children with cancer will be irradiated during their treatment. Intensity-modulated radiotherapy (IMRT) by linear accelerator or helical tomotherapy improves dose distribution in target volumes and normal tissue sparing. This technology could be particularly useful for pediatric patients to achieve an optimal dose distribution in complex volumes close to critical structures. The use of IMRT can increase the volume of tissue receiving low-dose radiation, and consequently carcinogenicity in childhood population with a good overall survival and long period of life expectancy. This review will present the current and potential IMRT indications for cancers in childhood, and discuss the benefits and problems of this technology aiming to define recommendations in the use of IMRT and specific doses constraints in pediatry.

[Image-guided radiotherapy: rational, modalities and results]. / Radiothérapie guidée par l'image : pourquoi, comment et résultats.

The objective of Image-Guided Radiotherapy (IGRT) is to take in account the inter- or/and intrafraction anatomic variations (organ motion and deformations) in order to improve treatment accuracy. The IGRT should therefore translate in a clinical benefit the recent advances in both tumor definition thanks to functional imaging, and dose distribution thanks to intensity modulated radiotherapy. The IGRT enables direct or indirect tumor visualization during radiation delivery. If the tumor position does not correspond with the theoretical location of target derived from planning system, the table is moved. In case of important uncertainties related to target deformation, a new planning can be discussed. IGRT is realized by different types of devices which can vary in principle and as well as in their implementation: from LINAC-integrated-kV (or MV)-Cone Beam CTs to helicoidal tomotherapy, Cyberknife and Novalis low-energy stereoscopic imaging system. These techniques led to a more rational choice of Planning Target Volume. Being recently introduced in practice, the clinical results of this technique are still limited. Nevertheless, until so far, IGRT has showed promising results with reports of minimal acute toxicity. This review describes IGRT for various tumor localizations. The dose delivered by on board imaging should be taken in account. A strong quality control is required for safety and proper prospective evaluation of the clinical benefit of IGRT.

[The effect of gentamicin on rat kidney lysosomes]. / Influence de la gentamicine sur les lysosomes de reins chez le rat

The in vitro action of gentamicin on kidney lysosomes gives rise to an increase in free acid phosphatase activity compared with total activity which points to a modification in the lysosomal membrane. These effects are more marked in pregnant rats, probably due to progesterone, but reduced in vitro by chloroquine.