[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.

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.

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.

[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.

[Dosimetric impact of the 2D motion of a platform simulating breathing during a dynamic mode treatment]. / Impact dosimétrique du mouvement 2D d'une plateforme simulant la respiration lors d'un traitement en mode dynamique.

Breathing-adapted techniques in external radiotherapy lead to the improvement of the taken into account of the tumour motion during the patient treatment. Indeed, this motion involves dosimetric uncertainties, in particular during a dynamic treatment (intensity-modulated radiation therapy, dynamic wedge...). As tumoral movement is complex and is carried out in various directions of space, a dynamic platform moving in one or two plans was conceived. This article approaches the technical aspects of design and functioning of this prototype. A study of the dosimetric effects of the respiratory movement on one and two plans during a dynamic treatment without gating will be presented. Films were irradiated while varying the rates with wedged fields at various speeds. The penumbra of beams were compared with the static case and appeared twice broader in the majority of the cases. The results highlighted the contributions of the longitudinal and the axial components of the motion on the form of the dose distribution. These results were completed with gamma index measurements to determine an internal margin. Moreover, this platform proves to be a promising tool for breathing-adapted treatment, in particularly to test the synchronisation of RPM system in fluoroscopic mode in board imaging system.

[Practical recommendations for breathing-adapted radiotherapy]. / Bonnes pratiques pour la radiothérapie asservie à la respiration.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath-hold techniques or respiration synchronized gating techniques. Breath-hold techniques can be achieved with active techniques, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily holds his/her breath. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. This work summarizes the different experiences of the centers of the STIC 2003 project. It describes the different techniques, gives an overview of the literature and proposes a practice based on our experience.

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

BACKGROUND AND PURPOSE: The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. MATERIALS AND METHODS: We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. RESULTS: We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. CONCLUSION: We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

Esophageal cancer: determination of internal target volume for conformal radiotherapy.

BACKGROUND AND PURPOSE: To evaluate esophageal tumor and OAR movement during the respiratory cycle in order to obtain optimal values for ITV and PRV. To correlate tumor motion with chest wall displacement - information of value in the free-breathing gating system. MATERIAL AND METHOD: Inclusion criteria were: histologically proven squamous-cell carcinoma (SCC) or adenocarcinoma at stage T3 - T4 NX or TX N1 M0 according to the UICC 1997 classification. Two spiral scans were performed with breath-hold respiration under spirometric control: one at end expiration (EBH) and the other at end inspiration (IBH). Displacements between exhalation and inhalation were calculated according to ICRU report 42 recommendations. For the correlation study, CT-scan acquisition was performed at the isocenter over a 20 - 40 s period. After Fourier Transform, frequency spectra for amplitude and phase of tumor and chest wall motions were performed for each patient. RESULTS: Cumulative distribution of CTV motion in absolute values showed that 95% of data ranged from 0 to 1 cm. Cumulative distribution of GTV motion in absolute values showed that 95% of data ranged from 0 to 0.8 cm. The correlation study demonstrated no specific relationship between respiratory and esophageal motions. CONCLUSION: The ITV margin for 3D conformal radiotherapy in esophageal cancer was 1 cm when 95% of motions were taken into account in this clinical study involving eight patients. Before using a free-breathing gating system, the correlation between external markers and target displacement during irradiation must be established for each patient.

Dosimetric consequences of breath-hold respiration in conformal radiotherapy of esophageal cancer.

The objective of this paper is to study the dosimetric impact of respiratory gated radiotherapy in locally advanced esophageal carcinomaand to define the optimal respiratory phase for this treatment. The study included 8 consecutive patients with squamous-cell carcinoma (SCC) or histologically proved adenocarcinoma, for both at least T3-T4 NX or TX N1 M0 stage. Informed consent was obtained before beginning the study. Three spiral scans were performed in breath-hold respiration: one acquisition in end expiration (EBH), one in end inspiration (IBH) and one in deep inspiration breathhold (DIBH); and one acquisition was performed in Free Breathing (FB). A 3 mm-margin was defined as Internal Target Volume (ITV) on FB CT-scan. No ITV was applied on EBH, IBH and DIBH CT-scan. Target volumes were analyzed and we performed dosimetric comparisons on DVH data of each CT-scan for PTV and Organs at Risk (OAR) (Conformity Index, V(dose), D(mean), Equivalent Uniform Dose). DIBH and IBH correlated with a 32% (p=0.77) and 20% (p=0.52) decrease in lung V(20) respectively as compared to FB (13.5%and 15.6% respectively versus 19.9%). DIBH and IBH correlated with a 25% (p=0.25) and 17% (p=0.39) decrease in cardiac V(40) respectively, as compared with FB (16.9% and 18.9% respectively versus 22.7%). For spinal cord irradiation, the minimum dose was obtained in IBH (36.5 Gy). Conformal radiotherapy with respiratory gating for esophageal cancer decreases the irradiated dose to OAR. We suggest that DIBH technique should be used when irradiation is performed using the spirometric system. In the Tidal Volume, the inspiration phase is the most favourable and should be chosen for irradiation with a free breathing gating system.

Evaluation of trimethoprim and sulphamethoxazole as monotherapy or in combination in the management of toxoplasmosis in murine models.

The combination of trimethoprim (TMP) and sulphamethoxazole (SMX) is commonly used for the prevention of cerebral toxoplasmosis although there is no firm experimental basis to support this regimen. We used strain RH tachyzoites for challenge in the acute murine model of toxoplasmosis and found that TMP administered as a single agent, failed to eradicate toxoplasma even at the highest dose (70 mg/kg per day). SMX alone at 600 mg/kg per day, protected ten out of ten mice, although inoculation of brain from surviving animals to naive mice resulted in the development of an encephalitis. When combined, TMP (60 mg/kg per day) and SMX (300 mg/kg per day) protected ten out of ten mice and gave a 'cure' in four out of four mice. In the chronic cystogenic murine models, the combination TMP plus SMX administered from day 5 for 15 days or from day 28 for 288 days, gave protection and even apparent toxoplasmal eradication ('cure') at the highest dosing (60/300 mg/kg per day). However, microscopic severe encephalitis was found in mice classified as 'cured' after reinoculation. This result makes the interpretation of 'cure' very difficult. In conclusion TMP and SMX act synergistically, SMX being the more active arm of the combination. The combination was efficient in preventing the lethal development of chronic toxoplasma encephalitis, but did not guarantee complete recovery.

[Sarcoidosis of the central nervous system]. / Sarcoïdose du système nerveux central.

PURPOSE: Current knowledge on central nervous system sarcoidosis. CURRENT KNOWLEDGE AND KEY POINTS: Sarcoidosis is localized in the central nervous system in 5 to 16% of the cases. Various neurological manifestations are observed, including: seizures, cognitive or psychic manifestations, hypothalamic and pituitary involvement, local pseudotumors, and hydrocephalus very frequently associated with asymptomatic lymphocytic meningitis and with cranial nerve palsy, particularly palsy of the seventh nerve, occurring less regularly. CNS localization is most often an early manifestation of the disease, unmasking sarcoidosis. It is often part of primary or secondary systemic polyvisceral sarcoidosis. The diagnosis is mainly based on two arguments: confirmation of the existence of systemic sarcoidosis and clinical and paraclinical compatibility of neurological abnormalities (particularly at magnetic resonance imaging [MRI]). Neurological histopathology is rarely necessary to confirm the diagnosis. Corticotherapy is indicated in all symptomatic cases and most often leads to a more or less complete clinical response evidenced by regression of active lesions identified on MRI. The treatment must often be prolonged for several years, and clinical and MRI evolution help guide therapeutical choices for dosages and threshold doses. CNS involvement is potentially severe with mortality and morbidity rates that are not insignificant. Limiting of iatrogenic risks requires adequate follow-up. PERSPECTIVES AND PROJECTS: Multicenter studies are necessary to determine factors influencing the incidence and long-term prognosis of CNS sarcoidosis treated with corticotherapy. The efficacy of treatments other than corticotherapy must be evaluated.

Parenchymal neurocysticercosis: follow-up and staging by MRI.

We describe the evolution of parenchymal cerebral cysticerci on MRI, to assess signs of early cyst degeneration. We studied 15 lesions in four treated and one untreated patient. MRI was performed before therapy and repeated in the 1st month after each course of anticysticercus drugs, every 4 months during the 1st year and then annually; the follow-up period was 8-48 months. Lesions were classified according to changes in four features: cyst content and capsule signal, gadolinium enhancement and oedema signal. We were able to recognise each of the pathological phases; five MRI stages were identified. Stage 1 showed oedema and/or nodular gadolinium enhancement in the tissue invasion phase; stage 2 was cerebrospinal fluid-like signal within a cyst in the vesicular phase; stage 3 showed a thick capsule with an impure liquid content signal and surrounding oedema, in the cystic phase; stage 4 showed the disappearance of the cyst fluid content signal in the degenerative phase; stage 5 showed a calcified lesion in the residual phase. Stage 1 lesions disappeared after therapy; the other progressed from one stage to another. Stage 4 indicated the end of viability of the parasite and determined the point after which treatment was useless. On T2-weighted images changes in the cyst content differed according to the history of the lesion; nodular low intensity followed the natural degeneration of the parasite and a mixed fluid signal with punctate low signal seemed to represent the specific result of therapy. MRI staging can help in the evaluation of indications for treatment and facilitate clinical therapeutic trials.

The abdominal linea alba: an anatomo-radiologic and biomechanical study.

Traditionally, the linea alba represents the principal route of approach in abdominal surgery and in consequence it is the commonest site of incisional hernia. The aim of this study was to review its morphology and to study its mechanical parameters of resistance, deformation and elasticity in order to compare these with the prosthetic materials most often used in the treatment of incisional hernia. Forty fresh cadavers were dissected and tests with a dynamometer and "bursting strength tester" were performed on samples taken from the linea alba at three levels: supra-umbilical, subumbilical and umbilical. Forty abdomino-pelvic scans were analysed. The morphologic results allowed definition of diastasis of the rectus mm. in terms of subject age: below 45 years of age diastasis was considered as a separation of the two rectus mm. exceeding 10 mm above the umbilicus, 27 mm at the umbilical ring and 9 mm below the umbilicus; above 45 years of age the corresponding values were 15 mm, 27 mm and 14 mm respectively. In the biomechanical study the subumbilical region exhibited a coefficient of elasticity greater than that of the supra-umbilical portion, but no significant difference in resistance was found between the different parts studied. The biomechanical results are compared with the corresponding data for prosthetic materials.

Pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroid alone: first case report.

We report the first case of pseudotumoral lymphocytic hypophysitis successfully treated by corticosteroids without surgery. A 27-year-old woman had been monitored for chronic headache 13 months after giving birth, associated with amenorrhea and galactorrhea. Cranial magnetic resonance imaging revealed a markedly enlarged pituitary gland with a suprasellar extension; the only biochemical abnormality was a mild hyperprolactinemia. Because of a putative diagnosis of prolactinoma, bromocriptine was prescribed at a dose of 5 mg daily, soon followed by the transitory appearance of menstruation. Two years later, panhypopituitarism was present and was revealed by acute adrenal insufficiency. Magnetic resonance imaging revealed that the pituitary mass was the same as previously described, but hormonal investigation showed evidence of complete hypopituitarism and no hyperprolactinemia. Nuclear antibodies were negative as well as other autoantibodies. Human leukocyte antigen serological Class II typing was DR3/DR4. Lymphocytic hypophysitis was then suspected; in the absence of visual complication and because this patient refused surgery, corticosteroids were attempted at a daily dose of 60 mg of prednisone for 3 months, progressively decreased for the next 6 months. Under this treatment, a gradual recovery of all pituitary hormones was observed and magnetic resonance imaging showed a reduction of two-thirds in pituitary mass. Five months after the end of corticoid treatment, our patient relapsed with panhypopituitarism and an increase of pituitary volume. She underwent steroid treatment, and a biopsy was performed and confirmed the diagnosis of autoimmune hypophysitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis.

The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Radioanatomic study of the gastrocolic venous trunk.

The mode of formation, measurements and frequency of occurrence of the gastrocolic venous trunk were studied by the injection-corrosion technique in a series of 54 anatomic specimens and by the analysis of 50 CT studies in patients without hepatic or pancreatic disease. The gastrocolic trunk was found in 51 of the 54 anatomic specimens and in 27 of the 50 CT studies. The great variability in its formation, whether bipodal, tripodal or quadripodal, was noted. With a mean diameter of 4.9 mm, it opened into the anterior, right or antero-left aspects of the superior mesenteric v. at a mean distance of 15 mm below the inferior border of the spleno-mesenteric confluence. The value of preliminary CT assessment before an operation for portal hypertension or a pancreatic tumor or in the diagnosis of a splenic thrombosis is emphasised.

[Meningoradiculitis disclosing T-lymphocyte leukemia in HTLV-1 infection]. / Méningo-radiculite révélatrice d'une leucémie à lymphocytes T au cours d'une infection à HTLV1.

A case of HILV1-associated adult T cell leukaemia/lymphoma (ATLL) in à 21-year olf African woman is reported. The patient presented with lymphomatous meningoradiculopathy. The usual clinical features of ATLL were absent. Lumbar MRI showed a pial enhancement by DTPA-gadolinium of the conus medullaris which extended to the proximal cauda equina. Under systemic chemotherapy coupled with intrathecal chemotherapy the patient progressively improved, and at the second MRI examination complete disappearance of the lumbar enhancement was observed. MRI of the brain using axial and coronal T2-weighted sequences detected multifocal lesions of high-intensity signal in the subcortical white matter. ATLL is unusual in people of African origin. The ATLL-strongyloïdes infestation association has previously been reported, suggesting that parasitic infestation may be an important co-factor leading to the development of ATLL.