[Clinical research in general hospital centres in France, strengths and weaknesses]. / Recherche clinique au sein des centres hospitaliers généraux en France, forces et faiblesses.

Clinical research is an essential activity in cancer care. Both for patients, who can gain access to innovative therapies, and for practitioners, who can maintain their skills and stay at the forefront of new treatment approaches. First developed in university hospitals, clinical research is now established in general hospitals and private health institutions. The number of patient inclusions in clinical trials has doubled over the last ten years, thus reflecting the dynamism of it. Strengths and weaknesses, opportunities and threats concerning clinical research, and more specifically clinical research in general hospitals, are exposed in this article.

Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: An ancillary study of the PROstate fractionated irradiation trial - PROFIT.

PURPOSE: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa). METHODS: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap. RESULTS: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099). CONCLUSIONS: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.

[Intermediate-risk prostate cancer treated with exclusive external irradiation: Focus on anatomical sites of recurrence in two French trials]. / Cancer de la prostate de risque intermédiaire traité par irradiation externe exclusive : focus sur les sites anatomiques de récidive dans deux essais français.

PURPOSE: Retrospective description of anatomical sites of relapse based on (18F)-choline PET-CT, (68Ga)-prostatic specific-membrane antigen PET-CT, bone scan, and prostate magnetic resonance imaging (MRI) data. MATERIALS AND METHODS: From two French prospective cohorts, patients treated with exclusive radiotherapy for an intermediate-risk cancer were identified during their follow-ups. They were included if they presented a rising of the prostate-specific antigen (PSA) associated with the realization of an imaging showing the sites of recurrences. RESULTS: Two hundred and sixty-three patients were included. After a median follow-up of 76 months (interquartile range [IQR] 67-95), 65 patients had biochemical recurrence and positive imaging. The median nadir PSA was 0.6ng/mL and the median PSA at recurrence was 3.4ng/mL. A single lesion was found in 48% of cases, 2 to 4 lesions in 43% of cases and more than 4 lesions in 9% of cases. The sites of relapse identified were prostate (37/65), prostate only (19/65), seminal vesicles (9/65) Pelvic nodes (35/65), extrapelvic nodes (15/65) and bone (13/65). CONCLUSIONS: The majority of relapses presented as a single lesion localized in the pelvis.

Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method.

Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.

Are Gadolinium-Enhanced MR Sequences Needed in Simultaneous 18F-FDG-PET/MRI for Tumor Delineation in Head and Neck Cancer?

BACKGROUND AND PURPOSE: PET/MRI with 18F-FDG has demonstrated the advantages of simultaneous PET and MR imaging in head and neck cancer imaging, MRI allowing excellent soft-tissue contrast, while PET provides metabolic information. The aim of this study was to evaluate the added value of gadolinium contrast-enhanced sequences in the tumor delineation of head and neck cancers on 18F-FDG-PET/MR imaging. MATERIALS AND METHODS: Consecutive patients who underwent simultaneous head and neck 18F-FDG-PET/MR imaging staging or restaging followed by surgery were retrospectively included. Local tumor invasion and lymph node extension were assessed in 45 head and neck anatomic regions using 18F-FDG-PET/MR imaging by 2 rater groups (each one including a radiologist and a nuclear medicine physician). Two reading sessions were performed, one without contrast-enhanced sequences (using only T1WI, T2WI, and PET images) and a second with additional T1WI postcontrast sequences. The results were compared with the detailed histopathologic analysis, used as reference standard. The κ concordance coefficient between the reading sessions and sensitivity and specificity for each region were calculated. RESULTS: Thirty patients were included. There was excellent agreement between the contrast-free and postgadolinium reading sessions in delineating precise tumor extension in the 45 anatomic regions studied (Cohen κ = 0.96, 95% CI = [0.94-0.97], P < .001). The diagnostic accuracy did not differ between contrast-free and postgadolinium reading sessions, being 0.97 for both groups and both reading sessions. For the 2 rater groups, there was good sensitivity for both contrast-free (0.83 and 0.85) and postgadolinium reading sessions (0.88 and 0.90, respectively). Moreover, there was excellent specificity (0.98) for both groups and reading sessions. CONCLUSIONS: Gadolinium chelate contrast administration showed no added value for accurate characterization of head and neck primary tumor extension and could possibly be avoided in the PET/MR imaging head and neck workflow.

Baseline data for distribution of contaminants by natural disasters: results from a residential Houston neighborhood during Hurricane Harvey flooding.

Hurricane Harvey made landfall in Texas August 25, 2017, bringing massive rains and flooding that impacted soils in a residential neighborhood in East Houston. Trace elements, organochlorine pesticides, polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ether fire retardants (PBDEs) and polychlorinated biphenyls (PCBs) were determined in 24 soil samples. The highest concentrations found in soils were total PAHs, which ranged from 1,310 µg/kg to 85,700 µg/kg with a mean of 12,600 µg/kg. Analysis of specific PAH ratios indicate the source of the PAHs were dominated by pyrogenic rather than petrogenic sources. Chlordanes were detectable in the area where the likely local source is for ant control. The trace metal concentrations were below any environmental health concern concentrations but As, Cd, Hg, Pb, Se, Ag, Zn were enriched over the crustal abundance. While Hurricane Harvey was responsible for the redistribution of many contaminants, the large volume of rain and floodwater likely transported contaminants from the land areas and into the Houston Ship Channel and Galveston Bay. The findings from this study will serve as baseline data for determining the mobilization of contaminants caused by natural disasters.

Vibrational spectra of Pb2Bi2Te3, PbBi2Te4, and PbBi4Te7 topological insulators: temperature-dependent Raman and theoretical insights from DFT simulations.

Herein, using Raman spectroscopy, we have presented the investigation of a temperature-dependent frequency shift and the line broadening of phonon modes by inserting the atomic layers of Pb and PbTe in the prototype 3D topological insulator Bi2Te3. Good quality single crystals of Pb2Bi2Te3, PbBi2Te4, and PbBi4Te7 were grown using the modified Bridgman technique. The Raman modes show progressive blue-shift with the decrease in temperature from 298 K to 93 K in Pb2Bi2Te3, PbBi2Te4, and PbBi4Te7 due to the anharmonic vibrations of the lattice as well as the increase in the strength of Bi-Te covalent interactions. The experimental results were complemented by extensive first principles calculations, where a reasonable matching between the experimental and computational data was found. Chemical pressure, induced by the insertion of Pb and PbTe layers in Bi2Te3, modified the interactions at the boundaries of the quintuple-layers, which was evident from the evolution of the A21u mode. The enhancement in the out-of-plane Bi-Te vibrations with respect to the in-plane Bi-Te vibrations was observed at low temperatures. The temperature coefficients of the Raman modes were useful in determining the thermal conductivity, which is a key design parameter for the fabrication of spintronic devices using topological insulators. The estimated first order temperature coefficient (χ') for Pb2Bi2Te3 signified the decrease in the thermal conductivity relative to Bi2Te3, which was caused by the insertion of the Pb layers in the van der Waals gaps of Bi2Te3.

Electronic, magnetic and spectroscopic properties of doped Mn(1-x) A x WO4 (A = Co, Cu, Ni and Fe) multiferroic: an experimental and DFT study.

The influence of dopants (Co, Cu, Fe and Ni) on the optical, electronic and magnetic properties of multiferroic MnWO4 was studied using Raman spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), magnetization measurements and density functional theory (DFT) calculations. The evolution of Raman spectra with different elemental substitutions at the Mn site was also studied, where the peak width increased with doping of higher mass elements (Co, Cu, Fe and Ni). UV-Vis diffuse reflectance spectroscopy on polycrystalline Mn(1-x) A x WO4 (A = Co, Cu, Fe and Ni) (0 ⩽ [Formula: see text] ⩽ 0. was performed. The evaluated electronic band gap decreasing with successive Co, Cu and Fe doping reflected the lower ionic radius of the substituted element, and for Ni-doped MnWO4 the band gap increased slightly compared to the parent MnWO4. Bader charge transfer and a partial density of states (PDOS) analysis from DFT simulations predict the appearance of impurity states in the band gap region (of pure MnWO4) from the d orbital of the dopant (Co, Cu and Fe) hybridized with the p orbital of the bonded O atoms due to charge transfer from O to the dopant, and reduced the band gap of Co, Cu and Fe-doped MnWO4. On the other hand, for Ni-doped MnWO4 strong W-O hybridization occurring due to large charge transfer from oxygen to tungsten leads to an increase in the band gap. The band gap, computed using the GGA + U method, is close to the experimental value. The signature of the d-d transition observed in the UV spectra is explained in terms of the crystal field stabilization energy caused by the octahedral distortion present in the lattice. Three different antiferromagnetic phases (AF1, AF2 and AF3) are identified in MnWO4 and also for the Co (18.75%)-doped sample. For Cu-doped samples, suppression of the AF1 phase and stabilization of the AF2 phase is observed up to 2 K. Successive doping of Cu leads to the diminution of magnetic frustration. A new magnetic order is identified for Ni-doped MnWO4 in the temperature range 13.7-20 K.

A simplified CT-based definition of the supraclavicular and infraclavicular nodal volumes in breast cancer.

PURPOSE: The available contouring guidelines for the supraclavicular and infraclavicular lymph nodes appeared to be inadequate for their delineation on non-enhanced computed tomography (CT) scans. For this purpose, we developed delineation guidelines for the clinical target volumes (CTV) of these lymph nodes on non-enhanced CT-slices performed in the treatment position of breast cancer. MATERIALS AND METHODS: A fresh female cadaver study as well as delineation and an anatomical descriptions review were performed to propose a simplified definition of the supra- and infraclavicular lymph nodes using readily identifiable anatomical structures. This definition was developed jointly by breast radiologists, breast surgeons, and radiation oncologists. To validate these guidelines, the primary investigator and seven radiation oncologists (observers) independently delineated 10 different nodal CTVs. The primary investigator contours were considered to be the gold standard contours. Contour accuracy and concordance were evaluated. RESULTS: Written guidelines for the delineation of supra- and infraclavicular lymph nodes CTVs were developed. Consistent contours with minimal variability existed between the delineated volumes; the mean kappa index was 0.83. The mean common contoured and additional contoured volumes were 84.6% and 18.5%, respectively. The mean overlap volume ratio was 0.71. CONCLUSIONS: Simplified CT-based atlas for delineation of the supra- and infraclavicular lymph nodes for locoregional irradiation of the breast on non-enhanced CT-scan, have been developed in this study. This atlas provides a consistent set of guidelines for delineating these volumes.

[Oligometastatic bone disease. Can limited metastatic bone disease be cured? Is there room for local ablative treatments?]. / Traitement local ablatif de la maladie oligométastatique osseuse (hors chirurgie).

Solitary metastases have been reported in up to 30% of cases in imaging series. Local treatment aims at consolidating the injured bone and to prevent neurologic complications. Since the prognosis of bony metastatic disease is about 30 months and includes some long survivors, the multisdisciplinary committee in charge of the patient should ask the question and decide on the type of radical/ablative intervention in case of oligometastases. A literature search was performed using MESH terms (bone, metastases, radiotherapy, radiology, cement, radiofrequency ablation, chemoembolisation). Local ablative treatments can yield symptomatic relief and local control rates of about 90%. Stereotactic hypofractionated irradiation and cementoplasty are increasingly used. In conclusion, local ablative treatment of bony oligometastases is an efficient treatment. Its potential impact on survival remains to be demonstrated prospectively in clinical trials.

[Idiopathic sudden deafness: a report of 96 patients]. / Surdité brusque idiopathique: mise au point a propos de 96 patients.

OBJECTIVES: Evaluation of the management of idiopathic sudden deafness indicating the usefulness of biological assessments and the pronostic factors of hearing recovery. PATIENTS AND METHODS: This is a retrospective study of 96 patients with idiopathic sudden deafness referred to a tertiary centre between 2005 and 2009 treated with corticosteroids intravenously at a daily dose of 1 mg/kg. Mean tonal thresholds were assessed (PTA = [500 Hz + 1000 Hz + 2000 Hz + 4000 Hz]/4). Each audiogram was classified as five classes according to its frequency profile. RESULTS: The hearing recovery is significant between D0-D5 and D5-M1 for the frequencies 0.5, 1 and 2 kHz. For 4 kHz, the recovery is significant between 0 and J5. There is no statistically significant correlation between the presence of associated signs (tinnitus, vertigo) and hearing recovery. Hearing recovery according to the five types of audiograms has the same evolution in the follow-up time but with audiograms type E (cophosis or subcophosis) often associated with an hyporeactivity at the videonystagmography. The presence of cardiovascular disease is a predictor of poor hearing recovery. The usefullness of systematic extensive blood tests is low. CONCLUSION: In sudden deafness, the maximum hearing recovery takes place in the month following the onset of symptoms. The predictors of poor hearing recovery are an initial mean threshold > 70 dB, the existence of an associated cardiovascular disease.

[Automatic image segmentation for treatment planning in radiotherapy]. / Segmentation automatique des images pour la planification dosimétrique en radiothérapie.

One drawback of the growth in conformal radiotherapy and image-guided radiotherapy is the increased time needed to define the volumes of interest. This also results in inter- and intra-observer variability. However, developments in computing and image processing have enabled these tasks to be partially or totally automated. This article will provide a detailed description of the main principles of image segmentation in radiotherapy, its applications and the most recent results in a clinical context.

[Esophageal cancer]. / Cancer de l'œsophage.

Esophageal cancers are highly malignant tumours with often a poor prognostic, except for minimal lesions treated with surgery. Radiation therapy, or combined radiation and chemotherapy is the most used therapeutic modality, alone or before oesophagectomy. The delineation of target volumes is now more accurate owing the possibility to use routinely the new imaging techniques (mainly PET). The aim of this work is to precise the radio-anatomical particularities, the pattern of spread of esophageal cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case.

[Normal tissue tolerance to external beam radiation therapy: esophagus]. / Dose de tolérance à l'irradiation des tissus sains: l'oesophage.

The esophagus is a musculo-membranous tube through which food passes from the pharynx to the stomach. Due to its anatomical location, it can be exposed to ionizing radiation in many external radiotherapy indications. Radiation-induced esophageal mucositis is clinically revealed by dysphagia and odynophagia, and usually begins 3 to 4 weeks after the start of radiation treatment. With the rise of multimodality treatments (e.g., concurrent chemoradiotherapy, dose escalation and accelerated fractionation schemes), esophageal toxicity has become a significant dose-limiting issue. Understanding the predictive factors of esophageal injury may improve the optimal delivery of treatment plans. It may help to minimize the risks, hence increasing the therapeutic ratio. Based on a large literature review, our study describes both early and late radiation-induced esophageal injuries and highlights some of the predictive factors for cervical and thoracic esophagus toxicity. These clinical and dosimetric parameters are numerous but none is consensual. The large number of dosimetric parameters strengthens the need of an overall analysis of the dose/volume histograms. The data provided is insufficient to recommend their routine use to prevent radiation-induced esophagitis. Defining guidelines for the tolerance of the esophagus to ionizing radiation remains essential for a safe and efficient treatment.

[Automatic segmentation using atlases in head and neck cancers: Methodology]. / Outils de contourage, utilisation et construction d'atlas anatomiques : exemples des cancers de la tête et du cou.

Highly conformal irradiation techniques are associated with steep gradient doses. Accuracy and reproducibility of delineation are required to avoid geometric misses and to properly report dose-volume effects on organs at risk. Guidelines of the International Commission on Radiation Units have largely contributed to high quality treatments. The ICRU endeavors to collect and evaluate the latest data and information pertinent to the problems of radiation measurement and dosimetry. There remains a need for delineation guidelines and automatic segmentation tools in routine practice. Among these tools, atlas-based segmentation has been shown to provide promising results. The methodology used for head and neck cancer patients is illustrated.

[Help for delineation: what kind of tools?]. / Aide à la délinéation: quels outils pratiques?

The planning of radiotherapy has known major developments during the last years. With the emergence of news techniques such as conformational radiotherapy, intensity modulated radiation therapy or stereotactic radiation therapy, the definition of target volumes was of great importance. The recommendations for the target volumes definition have been defined in the ICRU 50 and 62 reports, without any guidelines for volume delineation. Among the uncertainties that may influence the outcome after irradiation, the intra- and interobservers variations in delineation are the most important. Many teams have offered guidelines or atlases to homogenize these volumes and reduce these variations related to medical intervention. The aim of this paper is to present the main recommendations.

Induced electric and magnetic fields due to wave propagation in a tubular bone.

Electric and magnetic fields in tubular bones induced due to the propagation of travelling axisymmetric torsional waves, are determined in the paper by accounting for the piezoelectricity, inhomogeneity and anisotropy of osseous tissues. Using the derived expressions and experimentally determined values of the involved physical constants, numerical values of the displacement and stress fields, and also the induced fields are computed for points at different locations of the bone specimen.