[Limits of dose constraint definition for organs at risk specific to stereotactic radiotherapy]. / Limites de la définition des contraintes de dose pour les organes à risque spécifiques à la radiothérapie stéréotaxique.

Stereotactic radiotherapy is a very hypofractionated radiotherapy (>7.5Gy per fraction), and therefore is more likely to induce late toxicities than conventional normofractionated irradiations. The present study examines four frequent and potentially serious late toxicities: brain radionecrosis, radiation pneumonitis, radiation myelitis, and radiation-induced pelvic toxicities. The critical review focuses on the toxicity scales, the definition of the dose constrained volume, the dosimetric parameters, and the non-dosimetric risk factors. The most commonly used toxicity scales remain: RTOG/EORTC or common terminology criteria for adverse events (CTCAE). The definition of organ-at-risk volume requiring protection is often controversial, which limits the comparability of studies and the possibility of accurate dose constraints. Nevertheless, for the brain, whatever the indication (arteriovenous malformation, benign tumor, metastasis of solid tumors...), the association between the volume of brain receiving 12Gy (V12Gy) and the risk of cerebral radionecrosis is well established for both single and multi-fraction stereotactic irradiation. For the lung, the average dose received by both lungs and the V20 seem to correlate well with the risk of radiation-induced pneumonitis. For the spinal cord, the maximum dose is the most consensual parameter. Clinical trial protocols are useful for nonconsensual dose constraints. Non-dosimetric risk factors should be considered when validating the treatment plan.

Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. METHODS: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. RESULTS: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months). CONCLUSION: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Independent 6D quality assurance of stereotactic radiotherapy repositioning on linacs.

PURPOSE: A high level of accuracy while positioning the patient is mandatory for frameless stereotactic radiotherapy (SRT), as large doses in multiple fractions can be delivered near organs at risk. The objective of this study is to propose an end-to-end quality assurance method to verify that submillimetre alignment can be achieved with stereotactic conventional linacs. METHODS: We used a TrueBeam® linear accelerator equipped with a 6DOF robotic couch. The "ISO Cube" phantom was used with a homemade stand designed to generate known translational and rotational offsets. A reference CT scan was performed with straight alignment of the phantom. The procedure introduced 1.6° angular offset for the couch pitch and roll, at various gantry angles. The couch base was also moved between 0° and 270°. We compared the results with the daily machine performance check tests (MPC, Varian). RESULTS: The mean isocentre size, MV and kV imager offsets were found to agree to within 0.1mm, 0.1mm and 0.3mm respectively, and were in close agreement between the methods. For a total four months data collection period, the mean deviation between requested and measured 6DOF couch shifts was 0.6mm and 0.2°. Errors on field size were smaller than 1mm for 97.7% of the 324 data points. CONCLUSION: Results demonstrate that the linac equipped with a 6DOF robotic positioner and CBCT imaging satisfies requirements for SRT. Our methodology, based on a modified Winston-Lutz quality control, allowed us to quantitatively assess end-to-end accuracy of a linac in order to safely deliver SRT.

[Technical aspects and indications of extracranial stereotactic radiotherapy]. / Place de la radiothérapie stéréotaxique extracrânienne dans la prise en charge des patients atteints de cancer.

Extracranial stereotactic radiotherapy has developed considerably in recent years and is now an important part of the therapeutic alternatives to be offered to patients with cancer. It offers opportunities that have progressively led physicians to reconsider the therapeutic strategy, for example in the case of local recurrence in irradiated territory or oligometastatic disease. The literature on the subject is rich but, yet, there is no real consensus on therapeutic indications. This is largely due to the lack of prospective, randomized studies that have evaluated this technique with sufficient recoil. We propose a review of the literature on the technical aspects and indications of extracranial stereotactic radiotherapy.

Production of Highly Polarized Positrons Using Polarized Electrons at MeV Energies.

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-Z target. Positron polarization up to 82% have been measured for an initial electron beam momentum of 8.19 MeV/c, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.

[Are the patients not carrying protections after radical prostatectomy really continent?]. / Les patients ne portant pas de protection après prostatectomie radicale sont-ils vraiment continents?

AIM: To analyse urinary continence and related quality of life in patients not wearing any pad after robotic assisted radical prostatectomy (RARP). METHOD: Two hundred and sixteen patients operated consecutively by RARP between January 2009 and June 2011 were evaluated by the ICS (International Continence Society) Male Self-questionnaire. The questionnaires were sent by mail and mailed back by patients with a minimum of 14 months following surgery. The ICS questionnaire contains a symptom score (ICS 1) and a quality of life score (ICS 2). RESULTS: Out of 216 sent questionnaires, 145 (67%) were received. The subgroup of 121 patients who replied that they were not wearing any pad was analysed. Fifty-three (43,8%) of them reported not having leakage when coughing or sneezing, 65 (53,7%) reported not having spontaneous leakage, and 102 (84,3%) reported not having leakage when sleeping. The ICS 1 and ICS 2 scores were strongly correlated (Pearson correlation coefficient 0.96). CONCLUSION: Within a group of patients not wearing any pad following RARP, the continence as assessed by self-questionnaires remains altered. This analysis might help counselling patients who are about to choose a surgical treatment for their prostate cancer.

[Is nocturnal polyuria more frequent among patients with Parkinson's disease?]. / La polyurie nocturne est-elle plus fréquente chez les patients parkinsoniens?

OBJECTIVE: Nocturia is a frequent complaint in the population of idiopathic Parkinson's disease patients (IPD). The consequences of nocturia in the IPD population are at high importance as these patients have motor problems and therefore a risk of nocturnal fall. The aim of the study was to determine the mechanism of nocturia in patients with MPI, by determining the prevalence of nocturnal polyuria (NP) in this population. METHOD: A prospective study by bladder diary was conducted on 70 consecutive IPD patients consulting for regular neurological follow-up at a non-severe stage. Nocturia was defined as 1 or more awakenings to urinate. Two definitions of NP were used: nocturnal diuresis 33% or higher of the total diuresis (NUV33), which is the ICS (International Continence Society) definition, and nocturnal diuresis 90 mL/h or higher (NUP90). RESULTS: The mean patient age was 71 years (45-86, sex ratio 33/30). On average, patients were diagnosed for IPD 6.76 years earlier. The prevalence of NP was 64.5% according to NUV33 definition, and 17.7% according to NUP90 definition. Among patients with nocturia, the prevalence of NP was 66% (NUV33) and 21.5% (NUP90). No association was observed between disease duration of the IPD and the prevalence of nocturia and NP. Patients 70 years and older were more likely to have NP as defined by NUV33 than those less than 70 years (72.7% versus 55.17%, P=0.015). Men had more frequently nocturia (33.3% versus 20.7%, P=0.027). CONCLUSIONS: The prevalence of NP and nocturia was analyzed in patients with IPD at a non-severe stage. This prevalence was not higher than in the general population of the same age. The mechanism of nocturia in patients with IPD is not unambiguous and therefore requires to be explored by a bladder diary.

Image-guided IMRT for localized prostate cancer with daily repositioning: inferring the difference between planned dose and delivered dose distribution.

INTRODUCTION: To investigate the dosimetric impact of daily on-line repositioning during a full course of IMRT for prostate cancer. MATERIALS AND METHODS: Twenty patients were treated with image-guided IMRT. Each pre-treatment plan (Plan A) was compared with a post-treatment plan sum (Plan B) based on couch shifts measured. The delivered dose to the prostate without a daily repositioning was inferred by considering each daily couch shift during the whole course of image-guided IMRT (i.e., plan B). Dose metrics were compared for prostate CTV (P-CTV) and PTV (P-PTV) and for organs at risk. Ten patients were treated with a 5 mm margin and 10 patients with a 10 mm margin. RESULTS: For plan A vs. plan B: the average D95, D98, D50, D mean and EUD were: 76.4 Gy vs. 73.9 Gy (p = 0.0007), 75.4 Gy vs. 72.3 Gy (p = 0.001), 78.9 Gy vs. 78.4 Gy (p = 0.014), 78.7 Gy vs. 77.8 Gy (p = 0.003) and 78.1 Gy vs. 75.9 Gy (p = 0.002), respectively for P-CTV, and 73.2 Gy vs. 69.3 Gy (p = 0.0006), 70.7 Gy vs. 66.0 Gy (p = 0.0008), 78.3 Gy vs. 77.5 Gy (p = 0.001), 77.8 Gy vs. 76.4 Gy (p = 0.0002) and 74.4 Gy vs. 69.2 Gy (p = 0.003), respectively for P-PTV. Margin comparison showed no differences in dose metrics between the two plans except for D98 of the rectum in plan B which was significantly higher with a 10 mm margin. CONCLUSIONS: The absence of daily image-guided IMRT resulted in a significantly less uniform and less homogeneous dose distribution to the prostate. A reduction in PTV margin showed neither a lower target coverage nor a better spare of OAR with and without daily image-guided IMRT.

Evaluation of a computer-assisted navigation system for anterior cruciate ligament reconstruction: prospective non-randomized cohort study versus conventional surgery.

BACKGROUND: Conventional reconstruction of the anterior cruciate ligament (ACL) is associated with a 15% failure rate. Computer-assisted navigation systems (CANS) have been developed to improve the accuracy of tunnel positioning. HYPOTHESIS: The use of a CANS for ACL reconstruction decreases the rate of failure, defined as IKDC grade C or D, compared to conventional ACL reconstruction. MATERIALS AND METHODS: This prospective multicentre observational non-randomised open study compared two groups of patients requiring arthroscopic ACL reconstruction: one group was managed with a CANS and the other (control group) without a CANS. The primary evaluation criterion was based on the subjective and objective IKDC scores. Inclusion criteria were age older than 18 years and first ACL reconstruction procedure using autologous semitendinosus and gracilis tendons or an autologous bone-patellar tendon-bone graft. Of the 272 included patients, 214 were analysed; 100 were in the control group and 114 in the CANS group. RESULTS: No significant between-group differences were found for the fraction of patients having an IKDC grade A or B (P=0.953), the subjective IKDC score (P=0.77), differential knee laxity at 150 N (1.38 ± 1.79 mm in the control group and 1.77 ± 2.06 mmin the CANS group, P=0.384), graft-type, or graft positioning. DISCUSSION: Our results establish the large-scale feasibility of computer-assisted navigation for ACL reconstruction. However, the main outcomes at 1 year showed no significant differences between patients managed with and without computer-assisted navigation.

[Magnetic resonance imaging for delineation of prostate in radiotherapy: monocentric experience and review of literature]. / Imagerie par résonance magnétique et délinéation de la prostate en radiothérapie : expérience monocentrique et revue de la littérature.

PURPOSE: To assess the benefits of magnetic resonance imaging (MRI) in the dosimetric treatment planning for prostate radiotherapy. PATIENTS AND METHODS: Ten consecutive patients have been enrolled. They were treated for a low risk prostate adenocarcinoma. A rigid superimposition was performed between MRI and scan slides obtained at time of virtual simulation, then prostate volume was delineated by four to five physicians, on TDM slides and on MRI/TDM superimposition. For each treatment plan, we assessed the impact of MRI in terms of planned treatment volume (PTV) position, individual variability of prostate delineation and doses delivered to the critical organs. The prescribed dose was 74 Gy in 37 fractions to the PTV. RESULTS: PTV delineated on TDM (V(TDM)) were 1.15 (SD 3.71) larger than volumes delineated on MRI. Prostate apex was 4.6 mm (SD 2.87) lower on TDM than on MRI. Posterior limit of the prostate was in mean 4 mm more posterior on TDM. The variability between physicians in terms of prostate delineation was lower using MRI. For apex, these variations were 6.8 mm using TDM, versus 3.3 mm using MRI. Mean rectal dose was 8 % lower with MRI, compared to delineation using TDM. CONCLUSION: Superimposition TDM/MRI improves accuracy, decreases delineation variability, and allows to spare anterior part of the rectum from irradiation. It remains unknown whether this strategy translates into clinical benefit.

[Management of patients with long term indwelling catheter: Survey of Limousin general practitioners]. / Prise en charge des patients avec sonde vesicale à demeure au long cours : enquête auprès des médecins généralistes du Limousin.

OBJECTIVE: To evaluate the management of patients with long-term (>1 month) indwelling catheter by general practitioners (GP). PATIENTS AND METHODS: A self-questionnaire was sent to 603 regional GP, between March and May 2010. It was composed of 12 multiple-choice questions and one open question, about management of their patients with indwelling catheter. RESULTS: Two hundred and twenty-eight self-questionnaires were analyzed: 126 (55%) from urban GP and 102 (45%) from rural GP. On average, each GP managed 1.3 patients with long term indwelling catheter (>1 month). The catheters were changed by the GP, urologists, and nurses in 23.2, 23.7, and 53.1%, respectively. In a majority of cases, catheters were changed every 4 weeks (59%). Nursing cares were prescribed by 64.5% of GP. Prescribed drainage bags were sterile in 42.5%. Most of GP reported to prescribe a daily change of drainage bag (56.1%). Urine analysis as performed only in case of symptomatic urine infection by 58% of respondents. Fifty percent of GP required guidelines for the management of patients with long term indwelling catheter. Rural GP managed significantly more patients with indwelling catheter, prescribed fewer sterile drainage bags, made change the drainage bag less often, and required the help of urologist less frequently. CONCLUSION: Management of long term indwelling catheter was heterogeneous among GP, and varied according to rural or urban practice. Some used significantly differed from available practice guidelines. This survey could be a basis for the preparation of an informative document aimed at GP.

Is a hip distractor useful in the arthroscopic treatment of femoroacetabular impingement?

INTRODUCTION: There is increasing interest in using hip arthroscopy for the treatment of femoroacetabular impingement (FAI). However, the distraction is typically done with a traction table, which can lead to complications. Our working hypothesis was that a hip-specific distractor could be used to perform arthroscopic treatment of FAI without the complications associated with traction. MATERIAL AND METHODS: Twenty-three patients were included in this prospective study with an average follow-up of 21 months (range 12-28 months). The average age was 34 ± 4 years. The technical feasibility, complications, quality of the distraction and early clinical results were evaluated. RESULTS: None of the arthroscopy procedures had to be converted to an arthrotomy. In all cases, the procedures planned for the central and peripheral compartments were fully executed. One patient (4%) had a grade 1 cartilage iatrogenic injury of the femoral head. The distraction was determined to be effective in all the patients, with an average of 15 mm of distraction achieved (range 12-21 mm). The average Merle d'Aubigne score went from 11 (range 9-18) preoperatively to 16 (range 14-18) postoperatively; the average Harris score went from 76 (range 46-80) to 91 (range 87-100); the average Christensen score went from 64 (range 48-88) to 84 (range 72-100); the average Womac score went from 58 (range 42-96) to 84 (range 74-100). No neurological, infectious or bone complications were recorded. DISCUSSION: The use of a distractor during hip arthroscopy appears to be a reliable and reproducible technique that allows FAI to be treated. Early results are consistent with those reported in the literature, and the risks associated with the use of a traction table are reduced. This technique makes hip arthroscopy safer and contributes to advances in labrum and cartilage repair, without additional complications. LEVEL OF EVIDENCE: Level III prospective study.

SEISM: a 60 GHz cusp electron cyclotron resonance ion source.

LPSC has been involved for several years in a challenging research and development program on the production of pulsed ions beams with high ionization efficiency primarily dedicated to radioactive ion beams. The generation of the high magnetic field requires the use of helix techniques developed at Laboratoire National des Champs Magnétiques Intenses. As a first approach, a cusp structure has been chosen. 3D simulations were used to define the geometry of the helices. The computer aided design of the mechanical parts of the magnetic structure has been performed at LPSC and was optimized to decrease the total volume of the source. The first 60 GHz magnetic structure (helices coils in their tanks, electrical, and water cooling environment) should be available before the end of 2009.

[MRI features of spinal neurosarcoidosis associed with cervical spondylosis]. / Myélopathie sarcoïdosique associée à un canal cervical rétréci : aspects IRM.

INTRODUCTION: Spinal neurosarcoidosis is rare and exceptionally inaugural. OBSERVATION: A 49-year-old African woman developed a progressive left Brown-Sequard syndrome. Magnetic resonance imaging (MRI) scans of the cervical spinal cord revealed an intramedullary lesion from C2 to T1 with intense pial enhancement after administration of contrast material associated with cervical spondylosis. The diagnostic of sarcoidosis was confirmed by liver biopsy which demonstrated noncaseating granulomas. CONCLUSIONS: MRI features of spinal neurosarcoidosis were reviewed by the authors with focus on differential diagnosis.

Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjogren syndrome: a case-control study.

OBJECTIVES: To assess subclinical central nervous system (CNS) involvement in primary Sjögren syndrome (pSS), by comparing standard brain MRI, in-depth neuropsychological testing and (99m)Tc-ECD brain single-photon emission computed tomography (SPECT) of patients with pSS with matched controls. METHODS: 10 women (<55 years old), with pSS defined using European-American criteria, presence of anti-SSA and/or anti-SSB antibodies and no history of neurological involvement were prospectively investigated, and compared with 10 age- and sex-matched controls. All subjects underwent, within 1 month, brain MRI, neuropsychological testing, including overall evaluation and focal cognitive function assessment, and (99m)Tc-ECD brain SPECT. RESULTS: (99m)Tc-ECD brain SPECT abnormalities were significantly more common in patients with pSS (10/10) than controls (2/10; p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial disorders, were also significantly more common in patients with pSS (8/10) than controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant correlation to be established between neuropsychological assessment and (99m)Tc-ECD brain SPECT abnormalities in patients with pSS (r(s) = 0.49, p<0.01). MRI abnormalities in patients and controls did not differ significantly. CONCLUSIONS: Neuropsychological testing and (99m)Tc-ECD brain SPECT seem to be the most sensitive tools to detect subclinical CNS dysfunction in pSS. The strong correlation between cortical hypoperfusion in (99m)Tc-ECD brain SPECT and cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS. These data should be confirmed in a larger study.

Compact vibration isolation and suspension for Australian International Gravitational Observatory: performance in a 72 m Fabry Perot cavity.

This paper describes the first demonstration of vibration isolation and suspension systems, which have been developed with view to application in the proposed Australian International Gravitational Observatory. In order to achieve optimal performance at low frequencies new components and techniques have been combined to create a compact advanced vibration isolator structure. The design includes two stages of horizontal preisolation and one stage of vertical preisolation with resonant frequencies approximately 100 mHz. The nested structure facilitates a compact design and enables horizontal preisolation stages to be configured to create a superspring configuration, where active feedback can enable performance close to the limit set by seismic tilt coupling. The preisolation stages are combined with multistage three-dimensional (3D) pendulums. Two isolators suspending mirror test masses have been developed to form a 72 m optical cavity with finesse approximately 700 in order to test their performance. The suitability of the isolators for use in suspended optical cavities is demonstrated through their ease of locking, long term stability, and low residual motion. An accompanying paper presents the local control system and shows how simple upgrades can substantially improve residual motion performance.