[Role of radiotherapy in the management of node-positive prostate cancer]. / Place de la radiothérapie dans la prise en charge des cancers de prostate avec atteinte ganglionnaire pelvienne initiale sans métastase à distance.

Node-positive prostate cancer patients represent a small proportion of all prostate cancers for whom limited prospective information is available. Most retrospective or cohort data strongly suggest however that radiotherapy combined with androgen-depriving therapies is the preferable treatment in this setting. Only randomized clinical trials would be able to better define both radiotherapy (dose? volume? fractionation?) and androgen-depriving therapies (duration? role of novel androgen-depriving therapy?) modalities.

[Use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the upper urinary tract]. / Quelle place pour la radiothérapie et la chimiothérapie dans le traitement adjuvant des carcinomes urothéliaux des voies excrétrices urinaires supérieures ?

Urothelial carcinomas of the upper urinary tract are rare entities. Surgery remains the mainstay of the management. The use of others therapeutic modalities is not clearly defined yet. However, the frequency of local recurrence and locoregional encourage us to evaluate the indication of adjuvant therapies. We conducted a synthesis of key data in the literature on the use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and ureter. A literature search on PubMed was performed using the following keywords (MeSH) "urothelial carcinoma", "upper urinary tract", "radiation", "chemotherapy", and adjuvant.

[Recurrence sites following definitive intensity-modulated conformational radiotherapy of squamous-cell carcinomas of the upper aerodigestive tract]. / Sites de récidive après radiothérapie conformationnelle avec modulation d'intensité des carcinomes épidermoïdes des voies aérodigestives supérieures.

PURPOSE: The implementation of intensity-modulated radiotherapy (IMRT) in a centre requires regular critical review of medical practices and feedback to optimize the subsequent management of patients. PATIENTS AND METHODS: We reviewed and determined through a retrospective single-centre study recurrence sites of 167 consecutive patients treated for head and neck squamous cell carcinoma excluding skin or sinuses. Patients had mostly stage III or IV locally advanced cancer (n=123). RESULTS: Locoregional control rates at 1 and 2 years were respectively 87.9% (95% confidence interval [95%CI]: 81.6%-92.1%) and 77.6% (95%CI: 70.1%-83.5). Among 55 relapses, 20 patients (36.4%) had treatment failures. Patients treated with 70 Gy relapsed mainly in high risk volume (78%). Those treated with 66 Gy recurred regionally outside the irradiated volume (n=4) or in the irradiated high risk volume (n=3) or had isolated metastatic failure (n=3). Those irradiated with 50 Gy had regional relapse outside the irradiated volume (n=2) or isolated metastatic relapse (n=2). We noticed respectively 5.4%, 10.2% and 4.2% isolated metastatic, local, cervical lymph node relapse. CONCLUSION: Our results are consistent with data from the literature. Corrective actions were performed to enhance our practices.

Fracture incidence after 3 years of aromatase inhibitor therapy.

BACKGROUND: The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. RESULTS: Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. CONCLUSION: This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women.

[Adjuvant treatment of keloid scars: electrons or brachytherapy?]. / Traitement postopératoire des cicatrices chéloïdes : électrons ou irradiation interstitielle ?

PURPOSE: Evaluation of perioperative treatment of keloid scars with electron beam therapy or iridium 192 low dose rate brachytherapy. PATIENTS AND METHODS: From 1994 to 2010, 95 patients with 142 keloid scars have been treated by immediate perioperative irradiation and retrospectively reviewed in our institute: 116 scars were treated by electrontherapy and 26 by brachytherapy. RESULTS: In the electrontherapy group treated locations were: earlobe (n=88, 76%), thorax (n=14, 12%), neck (n=9, 8%), limbs (n=5, 4%). The median size of lesions was 3cm (range [R]: 0.5-18cm). In 95.6% of cases, a dose of 15Gy was delivered in five fractions of 3Gy. The median follow-up was 70 months (R: 7-161 months). The 2-year and 5-year local control were respectively 69% (95% confidence interval [95% CI]: 59-76%) and 55% (95% CI: 45-64%). In the brachytherapy group treated locations were: neck (n=3, 11%), earlobe (n=8, 32%), abdomen (n=3, 11%), thorax (n=2, 8%), limbs (n=10, 38%). The median size of lesions was 6.6cm (R: 1.7-28cm). The median dose delivered at 5mm from the source was 20Gy (R: 15-20.69). The median follow-up was 113 months (R: 21-219 months). The 2-year and 5-year local control were respectively 84.6% (95% CI: 64-94%) and 73.5% (95% CI: 49-87%). So far, no radiation-induced cancer has occurred. A trend to a better local control with brachytherapy was noted (compared to electrontherapy, 2-year relapse is halved with brachytherapy) though this difference did not reach the significance (P=0.0991), probably due to the reduced number of patients in the brachytherapy group. CONCLUSION: Brachytherapy seems to provide better local control compared to electrontherapy, and should be proposed as first line treatment. However, electrontherapy is an interesting alternative in case of difficulty to realize brachytherapy. There is probably a dose effect: according to published data, 25 to 30Gy should at least be proposed.

[Esophageal cancer: outcome according to therapeutic strategy]. / Évolution des cancers de l'œsophage : impact de la stratégie thérapeutique.

PURPOSE: To assess the outcome of esophageal cancer according to therapeutic strategy. PATIENTS AND METHODS: One-hundred and twenty patients with esophageal cancer treated by an association of radiotherapy and chemotherapy and possibly surgery, between 2004 and 2010, were retrospectively studied. The first site of relapse was classified as follows: local (tumour), locoregional (tumour and/or nodal: celiac, mediastinal, sus-clavicular) or metastatic. RESULTS: With a 15.7-months (1.4-62) median follow-up, there were 89 deaths and 79 recurrences. Three types of treatments were performed: 50Gy exclusive chemoradiotherapy (47 patients) or 50 to 65Gy exclusive chemoradiotherapy (44 patients) or chemoradiotherapy followed by surgery (27 patients). The local first relapse was as much frequent as distant relapse (50 patients). With a-5cm margin up and down to the tumour, there was only one nodal relapse. Two-year survival was 39.5% (95% confidence interval [IC]: 30.5-40.8) and relapse-free survival was 26.5% (CI: 18.6-35). Multivariate analysis revealed that treatment type and disease stage had a significant impact on survival, relapse-free survival and locoregional control. Compared to exclusive chemoradiotherapy, surgery improved locoregional control (40.2 versus 8.7 months, P=0.0004) but in a younger population. Despite postoperative mortality, the gain was maintained for distance relapse-free survival (40.2 versus 10 months, P=0.0147) and overall survival (29.3 versus 14.2 months, P=0.0088). Compared to 50Gy chemoradiotherapy, local control was improved if high dose chemoradiotherapy was performed (13.8 versus 7.5 months, P=0.05) but not overall survival (14.0 versus 15.4 months, P=0.24). CONCLUSION: More than one-third relapse is local. Locoregional control is better with high dose chemoradiotherapy. In this study, surgery performed in selected patients only, improved locoregional control, relapse-free disease and overall survival.

[Are there any dosimetric advantages in using VMAT for treatment of locally advanced non-small cell lung cancer?]. / La radiothérapie avec modulation d'intensité rotationnelle apporte-t-elle un avantage dosimétrique dans le traitement du cancer bronchique localement évolué ?

PURPOSE: To analyse the dosimetric differences between the conventional conformal radiation therapy (CR) and the volumetric modulated arc therapy (VMAT) for non-small-cell locally advanced lung cancer (NSCLC). PATIENTS AND METHODS: Two plans (CR and VMAT) were calculated for ten NSCLC patients. Dose to PTV, organs at risk and external contours (body), conformity index (PTV volume/volume of the 95% reference isodose) and homogeneity index ([maximal dose-minimal dose]/dose prescription) were compared. RESULTS: Doses delivered to PTV (homogeneity index, maximal, minimal and mean dose) are similar with both techniques but conformity index is improved by 60% with VMAT: from 0.55±0.07 with CR to 0.89±0.07 with VMAT (P=0.002). Pulmonary protection is improved with VMAT: with CR and VMAT, respectively, the mean lung dose is 14.1±5.2Gy and 12.2±4.5Gy, the lung volume which receives at least 30Gy (V30) is 20±8% and 14±5%, and the V20 is 24±11% and 20±10% (P=0.002). The mean dose received by the body is also 9% lower (P=0.004) and V5 is 13% higher (P=0.004) with VMAT. V10 and V15 were similar with both modalities. From 20Gy and higher, irradiated body volume is larger with CR than with VMAT. The relative difference increases with the dose: from 10% for 20Gy (P=0.014) up to 39% for 62.7Gy (P=0.002). CONCLUSION: Compared to CR, VMAT greatly improves conformity and reduces mean dose and dose delivered from 20Gy and higher to the lungs and the body.

[Dosimetric study of the different techniques to deal with respiratory motion for lung stereotactic radiotherapy]. / Étude dosimétrique des différentes techniques de gestion du mouvement respiratoire pour l'irradiation thoracique en conditions stéréotaxiques.

PURPOSE: To evaluate the different respiratory movement management techniques during irradiation of lung tumours. PATIENTS AND METHODS: Seven patients with one or more primary or secondary lung lesions less than 5 cm (11 tumours in total) had three computed tomographies (CT): free-breathing, deep-inspiration breath-hold using a spirometer, and 4-dimensional (4D). From these three acquisitions, five treatment plans were performed: free-breathing (reference method), deep-inspiration breath-hold, and three from the 4D CT: two breathing synchronized treatments (inspiration and expiration) and one treatment taking into account all the tumour motions (definition of the internal target volume [ITV]). Planning target volume (PTV) size and dose delivered to the lungs were compared. RESULTS: Mean PTV with the free-breathing modality was 83 ± 28 cm(3), which was significantly greater than any of the other techniques (P<0.0001). Compared to the free-breathing PTV, PTV defined with the ITV was reduced by one quarter (63 ± 31 cm(3)), and PTV with the deep-inspiration breath-hold, breathing synchronized inspiration and breathing synchronized expiration techniques were reduced by one third (50 to 54 ± 24 to 26 cm(3)). Deep-inspiration led to significantly increase the healthy lung volume compared to other methods (mean volume of 5500 ± 1500 cm(3) versus 3540 to 3920 cm(3), respectively, P<0.0001). The volume of healthy lungs receiving at least 5 and 20 Gy (V5 and V5) were significantly higher with the free-breathing method than any of the other methods (P<0.0001). The deep-inspiration breath-hold modality led to the lowest lung V5 and V20. CONCLUSION: Deep-inspiration breath-hold technique provides the most significant dosimetric advantages: small PTV and large lung volume. However, patients must be able to hold 20 seconds of apnea. Respiratory gating also reduces the PTV, but its application often requires the implantation of fiducial, which limit its use. A 4-dimensional CT allows for a personalized and reduced PTV compared to free-breathing CT.

NitroScape: a model to integrate nitrogen transfers and transformations in rural landscapes.

Modelling nitrogen transfer and transformation at the landscape scale is relevant to estimate the mobility of the reactive forms of nitrogen (N(r)) and the associated threats to the environment. Here we describe the development of a spatially and temporally explicit model to integrate N(r) transfer and transformation at the landscape scale. The model couples four existing models, to simulate atmospheric, farm, agro-ecosystem and hydrological N(r) fluxes and transformations within a landscape. Simulations were carried out on a theoretical landscape consisting of pig-crop farms interspersed with unmanaged ecosystems. Simulation results illustrated the effect of spatial interactions between landscape elements on N(r) fluxes and losses to the environment. More than 10% of the total N(2)O emissions were due to indirect emissions. The nitrogen budgets and transformations of the unmanaged ecosystems varied considerably, depending on their location within the landscape. The model represents a new tool for assessing the effect of changes in landscape structure on N(r) fluxes.

Assessing the ability of mechanistic volatilization models to simulate soil surface conditions: a study with the Volt'Air model.

Ammonia and pesticide volatilization in the field is a surface phenomenon involving physical and chemical processes that depend on the soil surface temperature and water content. The water transfer, heat transfer and energy budget sub models of volatilization models are adapted from the most commonly accepted formalisms and parameterizations. They are less detailed than the dedicated models describing water and heat transfers and surface status. The aim of this work was to assess the ability of one of the available mechanistic volatilization models, Volt'Air, to accurately describe the pedo-climatic conditions of a soil surface at the required time and space resolution. The assessment involves: (i) a sensitivity analysis, (ii) an evaluation of Volt'Air outputs in the light of outputs from a reference Soil-Vegetation-Atmosphere Transfer model (SiSPAT) and three experimental datasets, and (iii) the study of three tests based on modifications of SiSPAT to establish the potential impact of the simplifying assumptions used in Volt'Air. The analysis confirmed that a 5 mm surface layer was well suited, and that Volt'Air surface temperature correlated well with the experimental measurements as well as with SiSPAT outputs. In terms of liquid water transfers, Volt'Air was overall consistent with SiSPAT, with discrepancies only during major rainfall events and dry weather conditions. The tests enabled us to identify the main source of the discrepancies between Volt'Air and SiSPAT: the lack of gaseous water transfer description in Volt'Air. They also helped to explain why neither Volt'Air nor SiSPAT was able to represent lower values of surface water content: current classical water retention and hydraulic conductivity models are not yet adapted to cases of very dry conditions. Given the outcomes of this study, we discuss to what extent the volatilization models can be improved and the questions they pose for current research in water transfer modeling and parameterization.

Effects of farm heterogeneity and methods for upscaling on modelled nitrogen losses in agricultural landscapes.

The aim of this study is to illustrate the importance of farm scale heterogeneity on nitrogen (N) losses in agricultural landscapes. Results are exemplified with a chain of N models calculating farm-N balances and distributing the N-surplus to N-losses (volatilisation, denitrification, leaching) and soil-N accumulation/release in a Danish landscape. Possible non-linearities in upscaling are assessed by comparing average model results based on (i) individual farm level calculations and (ii) averaged inputs at landscape level. Effects of the non-linearities that appear when scaling up from farm to landscape are demonstrated. Especially in relation to ammonia losses the non-linearity between livestock density and N-loss is significant (p > 0.999), with around 20-30% difference compared to a scaling procedure not taking this non-linearity into account. A significant effect of farm type on soil N accumulation (p > 0.95) was also identified and needs to be included when modelling landscape level N-fluxes and greenhouse gas emissions.

Sensitivity analysis for models of greenhouse gas emissions at farm level. Case study of N(2)O emissions simulated by the CERES-EGC model.

Modelling complex systems such as farms often requires quantification of a large number of input factors. Sensitivity analyses are useful to reduce the number of input factors that are required to be measured or estimated accurately. Three methods of sensitivity analysis (the Morris method, the rank regression and correlation method and the Extended Fourier Amplitude Sensitivity Test method) were compared in the case of the CERES-EGC model applied to crops of a dairy farm. The qualitative Morris method provided a screening of the input factors. The two other quantitative methods were used to investigate more thoroughly the effects of input factors on output variables. Despite differences in terms of concepts and assumptions, the three methods provided similar results. Among the 44 factors under study, N(2)O emissions were mainly sensitive to the fraction of N(2)O emitted during denitrification, the maximum rate of nitrification, the soil bulk density and the cropland area.

High-resolution inventory of NO emissions from agricultural soils over the Ile-de-France region.

Arable soils are a significant source of nitric oxide (NO), a precursor of tropospheric ozone, and thereby contribute to ozone pollution. However, their actual impact on ozone formation is strongly related to their spatial and temporal emission patterns, which warrant high-resolution estimates. Here, we combined an agro-ecosystem model and geo-referenced databases to map these sources over the 12,000 km2 administrative region surrounding Paris, France, with a kilometric level resolution. The six most frequent arable crop species were simulated, with emission rates ranging from 1.4 kg N-NO ha(-1) yr(-1) to 11.1 kg N-NO ha(-1) yr(-1). The overall emission factor for fertilizer-derived NO emissions was 1.7%, while background emissions contributed half of the total NO efflux. Emissions were strongly seasonal, being highest in spring due to fertilizer inputs. They were mostly sensitive to soil type, crops' growing season and fertilizer N rates.

[Towards global security in radiation oncology. Using event notification feed-back]. / Vers une "politique sécurité" en oncologie-radiothérapie. La mise en oeuvre du retour d'expérience.

Large modifications are on going in our medical practice in oncology (cancer incidence, ageing, rules, authorizations, billings...). To obtain the best results as possible implies a quality control of the equipments (drugs, machines...), of the professionals (certification) and of the organisations (accreditations). Radiation oncology plays a key role in the multidisciplinary treatment of cancer ant is very sensitive to quality assurances due to its specificities: different tumours, various patients, multiple sequences of treatment with high tech machines and information systems. From 2003, a progress policy has been developed with the MeaH (Mission d'évaluation et d'audit hospitalier). Rapidly, the transfer of security policies from industry to medicine has been considered. This paper will present the first results and their potential implications in the field of oncology.

Challenges in quantifying biosphere-atmosphere exchange of nitrogen species.

Recent research in nitrogen exchange with the atmosphere has separated research communities according to N form. The integrated perspective needed to quantify the net effect of N on greenhouse-gas balance is being addressed by the NitroEurope Integrated Project (NEU). Recent advances have depended on improved methodologies, while ongoing challenges include gas-aerosol interactions, organic nitrogen and N(2) fluxes. The NEU strategy applies a 3-tier Flux Network together with a Manipulation Network of global-change experiments, linked by common protocols to facilitate model application. Substantial progress has been made in modelling N fluxes, especially for N(2)O, NO and bi-directional NH(3) exchange. Landscape analysis represents an emerging challenge to address the spatial interactions between farms, fields, ecosystems, catchments and air dispersion/deposition. European up-scaling of N fluxes is highly uncertain and a key priority is for better data on agricultural practices. Finally, attention is needed to develop N flux verification procedures to assess compliance with international protocols.

Measurement of trifluralin volatilization in the field: Relation to soil residue and effect of soil incorporation.

Volatilization may represent a major dissipation pathway for pesticides applied to soils or crops. A field experiment (September, 2002), consisted in volatilization fluxes measurements during 6 days, covering the periods before and after soil incorporation carried out 24 h after trifluralin spraying on bare soil. Evolution of concentration in soil was measured during 101 days, together with soil physical and meteorological variables. Volatilization fluxes were very high immediately after application (1900 ng m(-2) s(-1)), decreased down to 100 ng m(-2) s(-1) in the following 24 h. Soil incorporation strongly abated trifluralin concentration in the air. 99% of the total volatilization losses recorded over the 6 days following application occurred before incorporation. Volatilization fluxes evidenced a diurnal cycle driven by environmental conditions. Soil trifluralin residues could still be quantified 101 days after application. Our results highlight the caution required when using soil degradation half-life values in the field for volatile compounds.

[The role of hyperbaric oxygen therapy in radiation-induced digestive disorders. 36 cases]. / Intérêt de l'oxygènothérapie hyperbare dans la pathologie digestive post-radique. 36 observations.

OBJECTIVES: Study the effect of hyperbaric oxygen on chronic irradiation induced digestive disorders. PATIENTS AND METHODS: A retrospective study was conducted in 36 patients (mean age 66 +/- 11 years) with chronic digestive tract necrosis which had developed a mean 42 months after irradiation therapy. Hyperbaric oxygen therapy was given a mean 17 months after symptom onset: failing healing (n = 9), rectal bleeding (n = 19), profuse diarrhea (n = 9), recurrent anal abscess (n = 1). The severity of the digestive tract radionecrosis was quantified using the Soma-Lent scale. Hyperbaric oxygen therapy was grade 1 (n = 1), grade 2 (n = 11), grade 3 (n = 16), grade 4 (n = 8). RESULTS: Thirty-six patients underwent a mean 67 hyperbaric sessions (100% O2, 2.5 atm, 90 min). Three patients died within one month of the first session due to radiation enteritis, a neoplastic process or another concomitant cause. Immediate outcome after hyperbaric oxygen therapy was cure (n = 3) or improvement (n = 16) in 19 patients (53%) and failure in 17 (47%). Long-term results evaluated in 32 subjects with a mean 52 months follow-up were: cure (n = 9) or improvement (n = 12) in 21 patients (66%) and failure in 11 (34%). Nine patients died within a mean 25 months after the end of the hyperbaric sessions. Death was related to digestive tract radionecrosis in 1 case and neoplasia in 5. CONCLUSION: Hyperbaric oxygen therapy provides clinical relief in 2 out of 3 patients and can be a useful alternative to conventional treatment in patients with chronic radiation-induced necrosis of the digestive tract.

[Parietal tumor seeding after thoracoscopic surgery: apropos of a case]. / Greffe tumorale pariétale après chirurgie thoracoscopique: à propos d'une observation.

The authors report one case of port site recurrence 5 months after thoracoscopic resection of a pulmonary metastasis in a 68-year-old woman.

[Bone metastases of colorectal cancers: apropos of 8 cases]. / Métastases osseuses des cancers colorectaux: à propos de huit cas.

Having found, in the same medical centre, an abnormally high (15%) frequency of bone metastases from colorectal carcinoma, the authors report a series of 8 cases and review what is now known of this reputed rare (4%) metastases. Their clinical and imaging features are not very different from secondary bone lesions of other origins. They usually appear approximately 5 years after the primary tumour has been diagnosed; and they are rarely isolated, being part of a diffuse metastatic disease; their prognosis is in fact conditioned by visceral metastases (liver, lung, peritoneum). Concerning treatment, pain relieving radiotherapy is crucial, as witnesses by the authors. Chemotherapy must always be prescribed for its proven effectiveness against visceral lesions. The other medicinal treatments (e.g. analgesics, bisphosphonates) are very useful. Surgery must be reserved to emergency situations (spinal cord compression) and to patients in good general condition. To our 8 patients these treatments brought comfort and increased survival. Survivals of at least 6 to 9 months were obtained, and one patient is still alive 14 months after the diagnosis of bone metastasis. These results compare favourably with the 4 months median survival observed in other series.