Metronomic Four-Drug Regimen Has Anti-tumor Activity in Pediatric Low-Grade Glioma; The Results of a Phase II Clinical Trial

Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC has shown its efficacy in adult tumor types such as breast and ovarian cancer and has to some extent been studied in pediatrics.Objective: To assess the anti-tumor activity and toxicity of a four-drug metronomic regimen in relapsing/refractory pediatric brain tumors (BT) with progression-free survival (PFS) after two cycles as primary endpoint.Methods: Patients ≥4 to 25 years of age were included with progressing BT. Treatment consisted of an 8-week cycle of celecoxib, vinblastine, and cyclophosphamide alternating with methotrexate. Kepner and Chang two-steps model was used with 10 patients in the first stage. If stabilization was observed in ≥2 patients, 8 additional patients were recruited. Assessment was according WHO criteria with central radiology review.Results: Twenty-nine patients (27 evaluable) were included in two groups: ependymoma (group 1, N = 8), and miscellaneous BT (group 2): 3 medulloblastoma (MB), 5 high grade glioma (HGG), 11 low grade glioma (LGG), 2 other BT. After first stage, recruitment for ependymoma was closed [one patient had stable disease (SD) for 4 months]. Cohort 2 was opened for second stage since 1 HGG and 3 LGG patients had SD after two cycles. Recruitment was limited to LGG for the second stage and 2 partial responses (PR), 6 SD and 2 progressive disease (PD) were observed after two cycles. Of these patients with LGG, median age was 10 years, nine patients received vinblastine previously. Median number of cycles was 6.8 (range: 1–12). Treatment was interrupted in five patients for grade 3/4 toxicity.Conclusion: This regimen is active in patients with LGG, even if patients had previously received vinblastine. Toxicity is acceptable.Trial Registration: This study was registered under clinicaltrials.gov – NCT01285817; EUDRACT nr: 2010-021792-81

Neuroimaging Differential Diagnoses to Abusive Head Trauma

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Rickettsia mongolitimonae Encephalitis, Southern France, 2018

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Can metronomic maintenance with weekly vinblastine prevent early relapse/progression after bevacizumab-irinotecan in children with low-grade glioma?

International audienceThe association of bevacizumab and irinotecan has been shown to display a quick efficacy in low- grade glioma (LGG), but most patients relapse within months after cessation of therapy. From October 2012 to March 2014, four patients have been treated with irinotecan–bevacizumab followed by a metronomic maintenance with weekly vinblastine to try to prevent relapses. After a median follow- up of 23 months after the end of the bevacizumab–irinotecan induction, no patient relapsed. These observations suggest that maintenance chemotherapy with weekly vinblastine after an induction by irinotecan–bevacizumab can improve progression-free survival in children with LGG

Multimodal MR Imaging (Diffusion, Perfusion, and Spectroscopy): Is It Possible to Distinguish Oligodendroglial Tumor Grade and 1p/19q Codeletion in the Pretherapeutic Diagnosis?

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Distal cerebral vasospasm treatment following aneurysmal subarachnoid hemorrhage using the Comaneci device: technical feasibility and single-center preliminary results

International audienceBackground Balloon-assisted mechanical angioplasty for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) has a number of limitations, including transient occlusion of the spastic blood vessel. Comaneci is an FDA-approved device for temporary coil embolization assistance which has recently also been approved for the treatment of distal symptomatic refractory vasospasm. We aimed to report the feasibility, efficacy and safety of our experience with Comaneci angioplasty for refractory distal vasospasm (up to the second segment of the cerebral arteries) following aSAH. Methods This is a retrospective analysis of a prospective series of 18 patients included between April 2019 and June 2021 with aSAH and symptomatic vasospasm refractory to medical therapy, who were treated using Comaneci-17-asssisted mechanical distal angioplasty. Immediate angiographic results, procedure-related complications, and clinical outcomes were assessed. Inter-rater reliability of the scores was determined using the intraclass correlation coefficient. Results Comaneci-assisted distal angioplasty was performed in 18 patients, corresponding to 31 target arteries. All distal anterior segments were easily accessible with the Comaneci-17 device. Vasospasm improvement after Comaneci mechanical angioplasty was seen in 22 distal arteries (71%) (weighted Cohen’s kappa (κ w ) 0.73, 95% CI 0.69 to 0.93). Vasospasm recurrence occurred in three patients (16.67%) and delayed cerebral infarction in three patients (16.67%), with a mean±SD delay between onset of symptoms and imaging follow-up (MRI/CT) of 32.61±8.93 days (κ w 0.98, 95% CI 0.88 to 1). Conclusion This initial experience suggests that distal mechanical angioplasty performed with the Comaneci-17 device for refractory vasospasm following aSAH seems to be safe, with good feasibility and efficacy

Recanalization Treatments for Pediatric Acute Ischemic Stroke in France

International audienceImportance: There is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS).Objectives To report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS.Design, Setting, and Participants The KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018. Data analysis was performed from January 1, 2015, to May 31, 2019.Exposure: IVT and/or EVT.Main Outcomes and Measures Primary outcome was day 90 favorable outcome (modified Rankin Scale [mRs] 0-2, with 0 indicating no symptoms and 6 indicating death). Secondary end points included 1-year favorable outcome (mRs, 0-2), mortality, and symptomatic intracerebral hemorrhage. Other measures included the Pediatric National Institutes of Health Stroke Scale (pedNIHSS), with pedNIHSS 0 indicating no symptoms, 1 to 4 corresponding to a minor stroke, 5 to 15 corresponding to a mild stroke, greater than 15 to 20: severe stroke, and the adult Alberta Stroke Program Early CT Score (ASPECTS), which provides segmental assessment of the vascular territory, with 1 point deducted from the initial score of 10 for every region involved (from 10 [no lesion] to 0 [maximum lesions]).Results: Overall, 68 children were included in 30 centers (IVT [n = 44]; EVT [n = 40]; 44 boys [64.7%]; median [IQR] age, 11 [4-16] years; anterior circulation involvement, 57 [83.8%]). Median (IQR) pedNIHSS score at admission was 13 (7-19), higher in the EVT group at 16 (IQR, 10-20) vs 9 (6-17) in the IVT only group (P < .01). Median time from stroke onset to imaging was higher in the EVT group at 3 hours and 7 minutes (IQR, 2 hours and 3 minutes to 6 hours and 24 minutes) vs 2 hours and 39 minutes (IQR, 1 hour and 51 minutes to 4 hours and 13 minutes) (P = .04). Median admission ASPECTS score was 8 (IQR, 6-9). The main stroke etiologies were cardioembolic (21 [30.9%]) and focal cerebral arteriopathy (17 [25.0%]). Median (IQR) time from stroke onset to IVT was 3 hours and 30 minutes (IQR, 2 hours and 33 minutes to 4 hours and 28 minutes). In the EVT group, the rate of postprocedure successful reperfusion (≥modified Treatment in Cerebral Infarction 2b) was 80.0% (32 of 40). Persistent proximal arterial stenosis was more frequent in focal cerebral arteriopathy (P < .01). Death occurred in 3 patients (4.4%). Median pedNIHSS reduction at 24 hours was 4 (IQR, 0-9) points. Intracerebral hemorrhage occurred in 4 patients and symptomatic intracerebral hemorrhage occurred in 1 patient, all in the EVT group. The median mRS was 2 (IQR, 0-3) at day 90 and 1 (IQR, 0-2) at 1 year, which was not significantly different between EVT and IVT only groups, although different in initial severity.Conclusions and Relevance: The findings of this cohort study suggest that use of EVT and/or IVT is safe in children with AIS

Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak

International audienceBackground and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P <0.001) in MT case volumes during the epidemic period, and a significant increase in delays between imaging and groin puncture, overall (mean 144.9±SD 86.8 minutes versus 126.2±70.9; P <0.001 in 2019) and in transferred patients (mean 182.6±SD 82.0 minutes versus 153.25±67; P <0.001). After the instatement of strict epidemic mitigation measures, there was a significant negative correlation between the number of hospitalizations for COVID and the number of MT cases ( R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P <0.05). Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution