Subventricular zones: new key targets for glioblastoma treatment.

BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment.

Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation.

OBJECTIVE: To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. METHODS: Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was tend; MR acquisitions performed at tend-2M, tend-4M and tend-6M (respectively 2, 4 and 6 months before tend) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∆B from tend-4M to tend-2M and ∆B from tend-6M to tend-4M. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. RESULTS: The fraction of hypoperfused tumor volume (F_hPg) was a relevant biomarker. A ratio R(F_hPg) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (≥0.61) was associated with more relapse at tend compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). CONCLUSION: Iterative analysis of F_hPg from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. KEY POINTS: • Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. • Biomarkers were assessed through their patterns of variation during the follow-up. • The fraction of hypoperfused tumour volume (F_hP g ) seemed to be a relevant biomarker. • An innovative ratio R(F_hP g ) could be an early surrogate marker of relapse. • A significant time gain could be achieved in the management of GBM patients.

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET.

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm2. A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm2. The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm2. The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm2. Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm2 were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm2 and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.

An optimized calibration method for surface measurements with MOSFETs in shaped-beam radiosurgery.

Nowadays MOSFET dosimeters are widely used for dose verification in radiotherapy procedures. Although their sensitive area satisfies size requirements for small field dosimetry, their use in radiosurgery has rarely been reported. The aim of this study is to propose and optimize a calibration method to perform surface measurements in 6 MV shaped-beam radiosurgery for field sizes down to 18 × 18 mm(2). The effect of different parameters such as recovery time between 2 readings, batch uniformity and build-up cap attenuation was studied. Batch uniformity was found to be within 2% and isocenter dose attenuation due to the build-up cap over the MOSFET was near 2% irrespective of field size. Two sets of sensitivity coefficients (SC) were determined for TN-502RD MOSFET dosimeters using experimental and calculated calibration; the latter being developed using an inverse square law model. Validation measurements were performed on a realistic head phantom in irregular fields. MOSFET dose values obtained by applying either measured or calculated SC were compared. For calibration, optimal results were obtained for an inter-measurement time lapse of 5 min. We also found that fitting the SC values with the inverse square law reduced the number of measurements required for calibration. The study demonstrated that combining inverse square law and Sterling-Worthley formula resulted in an underestimation of up to 4% of the dose measured by MOSFETs for complex beam geometries. With the inverse square law, it is possible to reduce the number of measurements required for calibration for multiple field-SSD combinations. Our results suggested that MOSFETs are suitable sensors for dosimetry when used at the surface in shaped-beam radiosurgery down to 18 × 18 mm(2).

[Radiosurgery for brain arteriovenous malformations]. / Radiochirurgie stéréotaxique des malformations artérioveineuses cérébrales.

Radiosurgery as treatment for arteriovenous malformations has shown a good efficacy in reducing intracranial bleeding due to rupture. The choice of therapeutic modalities is based on evolutive risk and arteriovenous malformations volume, patient profile and risks stratification following therapeutic techniques (microsurgery, radiosurgery, embolization). Nidus size, arteriovenous malformations anatomical localization, prior embolization or bleeding, distributed dose are predictive factors for radiosurgery's good results and tolerance. This review article will highlight arteriovenous malformations radiosurgery indications and discuss recent irradiation alternatives for large arteriovenous malformation volumes.

[Stereotactic and diagnostic imaging in radiosurgery]. / Imagerie stéréotaxique et diagnostique en radiochirurgie.

Constant progress in medical imaging and particularly magnetic resonance imaging has profound impact in planning for stereotactic radiosurgery and radiotherapy. The purpose of this paper is to discuss the integration of medical imaging modalities in the planning process. Principles of generic algorithms to calculate stereotactic coordinates are treated for tomographic imaging and digital substraction angiography, and their accuracies are analyzed in a review of the literature. The algorithmic foundations and performance of automatic intermodality co-registration methods are developed. Finally, the MRI sequences useful in planning and follow-up are discussed and the role of MR angiographic sequences compared to conventional X-ray angiography in the particular case of the arteriovenous malformation planning.

[Dosimetric stereotactic radiosurgical accident: Study of 33 patients treated for brain metastases]. / Traitement des métastases cérébrales par radiochirurgie stéréotaxique : étude de 33 cas liés à un accident de "surexposition".

The consequences of a dosimetric radiosurgery accident are not the same as a conventional radiotherapy accident. The objective of this study was to estimate the clinical and radiological outcome of patients treated by radiosurgery for metastasis during the period of the overexposure accident that occurred in the Toulouse Radiosurgery Unit. Between April 2006 and March 2007, 33 patients with 57 metastases were treated in the Toulouse Radiosurgery Unit (Novalis(®), BrainLab). An initial error in the estimation of the scatter factors led to an overexposure to radiation. The median age was 55 years [range, 35-85]. Twenty-one patients (64%) harbored a single metastasis. The primary tumor location was lung (16 cases), kidney (nine cases), breast (four cases), and others (four cases). The mean tumoral volume was 3.2cm(3) [0.04-14.07]. The mean prescribed dose at the isocenter was 20 Gy [range, 10-23], the mean delivered dose was 31.5 Gy [range, 13-52], and the mean overdose was 61.2% [range, 5.6-226.8]. In order to evaluate the consequences of the overdose, three parameters were analyzed: a risk index using dose and volume, the volume of parenchyma that received more than 12 Gy, and the mean dose in a sphere of 20cm(3) surrounding the target volume. Median actuarial survival was 14.1 months, the survival rate was 79.4 % at six months, 59.1% at 12 months, and 27.2% at 24 months. The rate of tumor control was 80.7%. No morbidity was observed. There was no correlation between death and the parameters studied. The survival rates and times observed in our study of the patients treated for brain metastases by radiosurgery and overexposed were among the good results of the international literature. Deaths were not related to the overdose and no side effect was noted. This dosimetric accident has not had worse consequences in this population.

Good recovery from aphasia is also supported by right basal ganglia: a longitudinal controlled PET study. EJPRM-ESPRM 2008 award winner.

AIM: It has long been a matter of debate whether recovery from aphasia after left perisylvian lesion is mediated by perilesional left hemispheric regions or by right homologous areas. To investigate the neural substrates of aphasia recovery, a longitudinal study in patients after a left single perisylvian stroke was performed. METHODS: Thirteen aphasic patients were H2(15)O PET-scanned twice at a one year interval during a word generation task. Patients are divided into two groups according to language performance for the word generation task at PET2. For the Good Recovery (GR) group, patients' performances are indistinguishable from those of normal subjects, while patients from the Poor Recovery (PR) group keep language disorders. Using SPM2, Language-Rest contrast is computed for both groups at both PET stages. Then, Session Effect contrast (TEP2-TEP1>0) is calculated for both groups. RESULTS: For the GR group, the Session Effect contrast shows an increase of activations in the left Postero-Superior Temporal Gyrus PSTG but also in the right thalamus and lenticular nuclei; for PR patients, the right lenticular nucleus activation is more important at PET1 than PET2. CONCLUSIONS: The crucial role of the left temporal activation is confirmed and its increase is linked to behavioural recovery. The role of the right basal ganglia to support good recovery from aphasia is a new finding. Their activation may be more task-dependant and related to inhibition of the right frontal cortex.

[Identification of viable myocardium in ischemic heart disease with severe left ventricular contractile dysfunction: comparison of myocardial scintigraphy with 99mTc-sestamabi and with 201-thallium]. / Identification du myocarde viable dans les cardiopathies ischémiques avec atteinte sévère de la fonction contractile du ventricule gauche: comparaison de la scintigraphie myocardique <> au 99mtechnétium-sestamibi et de la scintigraphie myocardique au 201thallium.

The aim of this study was to compare quantitatively uptake of 99mTc-Sestamibi at rest and that of late redistribution of 201Tl in the same patients with severe ischaemic left ventricular dysfunction, and to correlate the uptake of the tracer to regional ventricular dysfunction studied by ECG grated 99Tc-Sestamini. A double isotope myocardial scintigraphy, 201 Thallium at rest/redistribution and 99Tc-Sestamibi at rest and on exercise, was performed in 28 patients with severe postinfarction ischaemic cardiomyopathy (EF= 29 +/- 4%). Quantitative analysis for each patient and each isotope were performed with respect to the number of hits expressed in percentage of the activity of a normal zone in 17 circumferential profiles distributed in 4 zones, that is to say in 476 segments. A score allowed counting of viable and non-viable segments and evaluation of contractile function of the 17 segments with respect to wall motion and systolic thickening. Total concordance of global uptake of the two isotopes was observed in 430 of the 476 segments (90.3%) (r= 0.814, p< 0.0001), but the 99mTc-Sestamibi uptake was less than 201 Th (71 +/- 23% vs 73 +/- 21%, p= 0.0001). With respect to left ventricular wall motion, uptake of 99mTc-Sestamibi was greater than that of 201Tl in normal or hypokinetic segments but less in akinetic and dyskinetic segments. The difference between the two isotopes was most marked in segments with very severe contractile dysfunction. The authors conclude that the uptake of 99mTc-Sestamibi is correlated with that of late distribution of 201Tl when left ventricular contraction is not too poor and should no longer be considered as only a marker of perfusion but can also be useful in the investigation of myocardial viability.

Perimetric visual field and functional MRI correlation: implications for image-guided surgery in occipital brain tumours.

OBJECTIVE: To compare the results of visual functional MRI with those of perimetric evaluation in patients with visual field defects and retrochiasmastic tumours and in normal subjects without visual field defect. The potential clinical usefulness of visual functional MRI data during resective surgery was evaluated in patients with occipital lobe tumours. METHODS: Eleven patients with various tumours and visual field defects and 12 normal subjects were studied by fMRI using bimonocular or monocular repetitive photic stimulation (8 Hz). The data obtained were analyzed with the statistical parametric maps software (p<10(-8)) and were compared with the results of Goldmann visual field perimetric evaluation. In patients with occipital brain tumours undergoing surgery, the functional data were registered in a frameless stereotactic device and the images fused into anatomical three standard planes and three dimensional reconstructions of the brain surface. RESULTS: Two studies of patients were discarded, one because of head motion and the other because of badly followed instructions. On the remaining patients the functional activations found in the visual cortex were consistent with the results of perimetric evaluation in all but one of the patients and all the normal subjects although the results of fMRI were highly dependent on the choices of the analysis thresholds. Visual functional MRI image guided data were used in five patients with occipital brain tumours. No added postoperative functional field defect was detected. CONCLUSIONS: There was a good correspondence between fMRI data and the results of perimetric evaluation although dependent on the analysis thresholds. Visual fMRI data registered into a frameless stereotactic device may be useful in surgical planning and tumour removal.

Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies.

Chronic motor cortex stimulation (CMCS) has provided satisfactory control of pain in patients with central or trigeminal neuropathic pain. We used this technique in 3 patients with intractable phantom limb pain after upper limb amputation. Functional magnetic resonance imaging (fMRI) correlated to anatomical MRI permitted frameless image guidance for electrode placement. Pain control was obtained for all the patients initially and the relief was stable in 2 of the 3 patients at 2 year follow-up. CMCS can be used to relieve phantom limb pain. fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication.

[Therapeutic indications of symptomatology: fatigue, pain, abnormal movements and reeducation]. / Indications thérapeutiques à visée symptomatique: fatigue, douleur, mouvements anormaux et rééducation.

Multiple Sclerosis is a chronic progressive and handicapping pathology of the central nervous system. Despite the recent progress no curative molecule has fundamentally modified its prognosis. Within this context symptomatic treatments are inevitable. As part of this consensus conference we have made a systematic critical and objective review about the literature relating how to take care symptomatically of "fatigue", pain, movement disorders and rehabilitation.