Search tips
Search criteria

Results 1-13 (13)

Clipboard (0)

Select a Filter Below

Year of Publication
author:("pallid, Johan")
1.  Long-term results of carmustine wafer implantation for newly diagnosed glioblastomas: a controlled propensity-matched analysis of a French multicenter cohort 
Neuro-Oncology  2015;17(12):1609-1619.
The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care.
Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted.
The median progression-free survival was 12.0 months (95% CI: 10.7–12.6) in the implantation group and 10.0 months (9.0–10.0) in the standard group and the median overall survival was 20.4 months (19.0–22.7) and 18.0 months (17.0–19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63–0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60–0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80–1.13], P = .574; HR, 1.06 [0.87–1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44–0.76], P < .0001; HR, 0.54 [0.41–0.70], P < .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40–0.78], P < .0001; HR, 0.46 [95% CI: 0.33–0.64], P < .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival.
Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit.
PMCID: PMC4633930  PMID: 26185110
carmustine wafers; chemoradiotherapy; glioblastoma; surgery; survival
2.  Imaging of gliomas at 1.5 and 3 Tesla - A comparative study 
Neuro-Oncology  2014;17(6):895-900.
Glioma follow-up is based on MRI parameters, which are correlated with survival. Although established criteria are used to evaluate tumor response, radiological markers may be confounded by differences in instrumentation including the magnetic field strength. We assessed whether MRIs obtained at 3 Tesla (T) and 1.5T provided similar information.
We retrospectively compared imaging features of 30 consecutive patients with WHO grades II and III gliomas who underwent MRI at 1.5T and 3T within a month of each other, without any clinical changes during the same period. We compared lesion volumes on fluid attenuation inversion recovery (FLAIR), ratio of cerebral blood volume (rCBV) on perfusion-weighted imaging, contrast-to-noise ratio (CNR) on FLAIR, and on post-gadolinium 3D T1-weighted sequences between 1.5T and 3T using intraclass correlation coefficient (ICC). Concordance between observers within and between modalities was evaluated using weighted-kappa coefficient (wκ).
The mean ± SD delay between modalities (1.5T and 3T MRI) was 8.6 ± 5.6 days. Interobserver/intraobserver concordance for lesion volume was almost perfect for 1.5T (ICC = 0.96/0.97) and 3T (ICC = 0.99/0.98). Agreement between observers for contrast enhancement was excellent at 1.5T (wκ = 0.92) and 3T (wκ = 0.92). The tumor CNR was significantly higher for FLAIR at 1.5T (P < .001), but it was higher at 3T (P = .012) for contrast enhancement. Correlations between modalities for lesion volume (ICC = 0.97) and for rCBV values (ICC = 0.92) were almost perfect.
In the follow-up of WHO grades II and III gliomas, 1.5T and 3T provide similar MRI features, suggesting that monitoring could be performed on either a 1.5 or a 3T MR magnet.
PMCID: PMC4483120  PMID: 25526734
glioma; MRI; neuroimaging; observer variation; reproducibility of results
3.  Is a prospective trial necessary to suggest a clinical relevance? 
Neuro-Oncology  2014;16(9):1295-1296.
PMCID: PMC4136901  PMID: 25096190
4.  Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas 
Neuro-Oncology  2014;16(8):1100-1109.
We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults.
One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied.
Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81–9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19–4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42–185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15–200.1, respectively).
The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults.
PMCID: PMC4096178  PMID: 24847087
isocitrate dehydrogenase 1; low-grade glioma; prognosis; velocity of tumor expansion
5.  Cortical GABAergic excitation contributes to epileptic activities around human glioma 
Science translational medicine  2014;6(244):244ra89.
Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study.
We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities.
Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas.
Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients.
PMCID: PMC4409113  PMID: 25009229
6.  Quantitative characterization of the imaging limits of diffuse low-grade oligodendrogliomas 
Neuro-Oncology  2013;15(10):1379-1388.
Supratentorial diffuse low-grade gliomas in adults extend beyond maximal visible MRI-defined abnormalities, and a gap exists between the imaging signal changes and the actual tumor margins. Direct quantitative comparisons between imaging and histological analyses are lacking to date. However, they are of the utmost importance if one wishes to develop realistic models for diffuse glioma growth.
In this study, we quantitatively compared the cell concentration and the edema fraction from human histological biopsy samples (BSs) performed inside and outside imaging abnormalities during serial imaging-based stereotactic biopsy of diffuse low-grade gliomas.
The cell concentration was significantly higher in BSs located inside (1189 ± 378 cell/mm2) than outside (740 ± 124 cell/mm2) MRI-defined abnormalities (P = .0003). The edema fraction was significantly higher in BSs located inside (mean, 45% ± 23%) than outside (mean, 5 %± 9%) MRI-defined abnormalities (P < .0001). At borders of the MRI-defined abnormalities, 20% of the tissue surface area was occupied by edema and only 3% by tumor cells. The cycling cell concentration was significantly higher in BSs located inside (10 ± 12 cell/mm2), compared with outside (0.5 ± 0.9 cell/mm2), MRI-defined abnormalities (P = .0001).
We showed that the margins of T2-weighted signal changes are mainly correlated with the edema fraction. In 62.5% of patients, the cycling tumor cell fraction (defined as the ratio of the cycling tumor cell concentration to the total number of tumor cells) was higher at the limits of the MRI-defined abnormalities than closer to the center of the tumor. In the remaining patients, the cycling tumor cell fraction increased towards the center of the tumor.
PMCID: PMC3779035  PMID: 23771168
edema; gliomas; histology; magnetic resonance imaging; quantification
7.  Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas 
Neuro-Oncology  2013;15(5):595-606.
Supratentorial diffuse low-grade gliomas present a slow macroscopic tumor growth that can be quantified through the measurement of their velocity of diametric expansion. We assessed whether spontaneous velocity of diametric expansion can predict long-term outcomes as a categorical variable and as a continuous predictor.
A total of 407 adult patients with newly diagnosed supratentorial diffuse low-grade gliomas in adults were studied.
The mean spontaneous velocity of diametric expansion before first-line treatment was 5.8 ± 6.3 mm/year. During the follow-up (mean, 86.5 ± 59.4 months), 209 patients presented a malignant transformation, and 87 died. The malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (median, 103 and 249 months, respectively) than in cases of fast velocity of diametric expansion (median, 35 and 91 months, respectively; P < .001). In multivariate analyses, spontaneous velocity of diametric expansion as a categorical variable (<4, ≥4 and <8, ≥8 and <12, ≥12 mm/year) was an independent prognostic factor for malignant progression-free survival (P < .001; hazard ratio, 3.87; 95% confidence interval [CI], 2.67–5.52) and for overall survival (P < .001; hazard ratio, 4.62; 95% CI, 2.58–7.97). Velocity of diametric expansion was also an independent prognostic factor for overall survival as a continuous predictor, showing a linear relationship between overall survival and spontaneous velocity of diametric expansion (hazard ratio, 1.09 per one unit increase; 95% CI, 1.06–1.12; P < .001).
Independent of the molecular status, the spontaneous velocity of diametric expansion allows the identification of rapidly growing diffuse low-grade gliomas (at higher risk of worsened evolution) during the pretherapeutic period and without delaying treatment.
PMCID: PMC3635513  PMID: 23393207
diffuse low-grade gliomas; kinetics; malignant transformation; overall survival; velocity of diametric expansion
8.  Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography☆ 
NeuroImage : Clinical  2013;2:549-557.
A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of full-field optical coherence tomography (FF-OCT) in brain tumor diagnosis.
FF-OCT captures en face slices of tissue samples at 1 μm resolution in 3D to a penetration depth of around 200 μm. A 1 cm2 specimen is scanned at a single depth and processed in about 5 min. This rapid imaging process is non-invasive and requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications.
Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low-grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells such as astrocytes (normal or reactive) or oligodendrocytes were not observable.
This study reports for the first time on the feasibility of using FF-OCT in a real-time manner as a label-free non-invasive imaging technique in an intraoperative neurosurgical clinical setting to assess tumorous glial and epileptic margins.
•Demonstration of full-field optical coherence tomography imaging of human brain samples•Potential as an intraoperative tool for determining tissue architecture and content in minutes•Myelin fibers, neurons, microcalcifications, tumor cells, microcysts, and vessels identified•Good correspondence with histological slides, allowing clinical use for tissue selection
PMCID: PMC3778248  PMID: 24179806
FF-OCT, full field optical coherence tomography; OCT, optical coherence tomography; Optical imaging; Digital pathology; Brain imaging; Brain tumor; Glioma
9.  Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas 
Neuro-Oncology  2012;14(4):496-505.
Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, −16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm3), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at −10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than −10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.
PMCID: PMC3309865  PMID: 22416109
growth rates; low-grade glioma; prognosis; radiation therapy
10.  Symptomatic Extensive Thoracolumbar Epidural Hematoma Following Lumbar Disc Surgery Treated by Single Level Laminectomy 
Asian Spine Journal  2012;6(2):152-155.
Spinal epidural hematomas (SEHs) are rare complications following spine surgery, especially for single level lumbar discectomies. The appropriate surgical management for such cases remains to be investigated. We report a case of an extensive spinal epidural hematoma from T11-L5 following a L3-L4 discectomy. The patient underwent a single level L4. A complete evacuation of the SEH resulted in the patient's full recovery. When presenting symptoms limited to the initial surgical site reveal an extensive postoperative SEH, we propose: to tailor the surgical exposure individually based on preoperative findings of the SEH; and to begin the surgical exposure with a limited laminectomy focused on the symptomatic levels that may allow an efficient evacuation of the SEH instead of a systematic extensive laminectomy based on imaging.
PMCID: PMC3372553  PMID: 22708022
Epidural; Hematoma; Spine; Surgery; Management; Emergency; Postoperative
11.  Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas 
Neuro-Oncology  2010;12(10):1078-1082.
Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated.
PMCID: PMC3018918  PMID: 20488959
growth kinetics; low-grade glioma; PCV chemotherapy
12.  Prognostic significance of imaging contrast enhancement for WHO grade II gliomas 
Neuro-Oncology  2009;11(2):176-182.
In this study, we investigated the prognostic value of MRI contrast enhancement (CE) at the time of histological diagnosis specifically in a selected population of WHO grade II gliomas. We reviewed 927 histologically proven WHO grade II gliomas for which contrast-enhanced MR images were available at the time of histological diagnosis. CE patterns were classified into three categories: “patchy and faint,” “nodular-like,” and “ring-like.” CE progression over time was recorded before oncological treatment on successive MR images, when available. CE was present in 143 cases (15.9%), with 93 patchy and faint, 50 nodular-like, and no ring-like patterns. CE areas were time progressive before oncological treatment in 35 of the 56 available cases (62.5%). Regardless of its pattern, the presence of CE was not significantly associated with a worsened prognosis (p = 0.415) by univariate analysis. Only the nodular-like pattern of CE (p < 0.01) and the time-progressive CE (p < 0.001) in the available subgroup proved to be statistically associated with survival since first oncological treatment. The present results show the necessity, in cases of WHO grade II gliomas, to study CE at the time of histological diagnosis and, whenever possible, to follow its progression over time before oncological treatment. Nodular-like CE and time- progressive CE are associated with a worsened prognosis, both suggesting malignant transformation, even though histopathological examination cannot initially disclose signs of malignancy in those areas.
PMCID: PMC2718989  PMID: 18697954
contrast enhancement; histology; magnetic resonance imaging; prognosis; WHO grade II glioma
13.  Successfull Management of a Life Threatening Cerebellar Haemorrhage Following Spine Surgery - A Case Report - 
Asian Spine Journal  2009;3(1):32-34.
Cerebellar haemorrhages are rare life-threatening complications following spine surgery that present challenges for their diagnostic and their therapeutic management. Their patho-physiology remains unclear.
We report a case of a life-threatening cerebellar haemorrhage secondary to an occult dural tear following a planned L5-S1 laminectomy. The patient was treated with emergent external ventriculostomy following by a posterior fossa decompressive craniectomy. Cerebellar haemorrhages have to be suspected systematically when unexpected neurological signs occur after spine surgery since their rapid management lead to favourable outcomes. The present imaging findings allow us proposing that cerebellar haemorrhages result primarily from superior cerebellar venous stretching and tearing, and that cerebellar infarction and swelling occur secondarily.
PMCID: PMC2852039  PMID: 20404944
Cerebellar haemorrhage; Dural tear; Spine surgery

Results 1-13 (13)