Jean-Christophe Sol

αvβ3 Integrin and Fibroblast growth factor receptor 1 (FGFR1): Prognostic factors in a phase I–II clinical trial associating continuous administration of Tipifarnib with radiotherapy for patients with newly diagnosed glioblastoma

BACKGROUNDnBased on our previous results showing the involvement of the farnesylated form of RhoB in glioblastoma radioresistance, we designed a phase II trial associating the farnesyltransferase inhibitor Tipifarnib with radiotherapy in patients with glioblastoma and studied the prognostic values of the proteins which we have previously shown control this pathway.nnnPATIENTS AND METHODSnPatients were treated with 200mg Tipifarnib (recommended dose (RD)) given continuously during radiotherapy. Twenty-seven patients were included in the phase II whose primary end-point was time to progression (TTP). Overall survival (OS) and biomarker analysis were secondary end-points. Expressions of αvβ3, αvβ5 integrins, FAK, ILK, fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) were studied by immuno-histochemistry in the tumour of the nine patients treated at the RD during the previously performed phase I and on those of the phase II patients. We evaluated the correlation of the expressions of these proteins with the clinical outcome.nnnRESULTSnFor the phase II patients median TTP was 23.1 weeks (95%CI = [15.4; 28.2]) while the median OS was 80.3 weeks (95%CI = [57.8; 102.7]). In the pooled phase I and II population, median OS was 60.4 w (95%CI = [47.3; 97.6]) while median TTP was 18.1 w (95%CI = [16.9; 25.6]). FGFR1 over-expression (HR = 4.65; 95%CI = [1.02; 21.21], p = 0.047) was correlated with shorter TTP while FGFR1 (HR = 4.1 (95% CI = [1.09-15.4]; p = 0.036)) and αvβ3 (HR = 10.38 (95%CI = [2.70; 39.87], p = 0.001)) over-expressions were associated with reduced OS.nnnCONCLUSIONnAssociation of 200mg Tipifarnib with radiotherapy shows promising OS but no increase in TTP compared to historical data. FGFR1 and αvβ3 integrin are independent bad prognostic factors of OS and TTP.

French guidelines on stereoelectroencephalography (SEEG)

Stereoelectroencephalography (SEEG) was designed and developed in the 1960s in France by J.xa0Talairach and J.xa0Bancaud. It is an invasive method of exploration for drug-resistant focal epilepsies, offering the advantage of a tridimensional and temporally precise study of the epileptic discharge. It allows anatomo-electrical correlations and tailored surgeries. Whereas this method has been used for decades by experts in a limited number of European centers, the last ten years have seen increasing worldwide spread of its use. Moreover in current practice, SEEG is not only a diagnostic tool but also offers a therapeutic option, i.e., thermocoagulation. In order to propose formal guidelines for best clinical practice in SEEG, a working party was formed, composed of experts from every French centre with a large SEEG experience (those performing more than 10 SEEG per year over at least a 5 year period). This group formulated recommendations, which were graded by all participants according to established methodology. The first part of this article summarizes these within the following topics: indications and limits of SEEG; planning and management of SEEG; surgical technique; electrophysiological technical procedures; interpretation of SEEG recordings; and SEEG-guided radio frequency thermocoagulation. In the second part, those different aspects are discussed in more detail by subgroups of experts, based on existing literature and their own experience. The aim of this work is to present a consensual French approach to SEEG, which could be used as a basic document for centers using this method, particularly those who are beginning SEEG practice. These guidelines are supported by the French Clinical Neurophysiology Society and the French chapter of the International League Against Epilepsy.

Primary sellar neuroblastoma. A new case and review of literature.

The primary intracranial development of olfactory neuroblastomas, outside olfactory epithelium, is rare. We report a case of primary sellar neuroblastoma without any aggressive histopathological features, managed solely surgically without adjuvant therapy, with good outcomes at 3 years. Primary sellar neuroblastomas mostly occur in women in the 4th decade with a context of a non-secreting pituitary tumour. Diagnosis is made on histopathological examination (small cells, fibrillary intercellular background, strong immunoreactivity for neurons markers, negative immunoreactivity for anterior pituitary hormones). Management is based on surgery. Adjuvant treatment is not consensual, largely depends on patients conditions and aggressive histopathological features.

Bilateral ophthalmic origin of the middle meningeal artery.

The origin of the middle meningeal artery (MMA) may vary although it can arise from the ophthalmic artery (OA) with a 0.5% prevalence. We report the exceptional bilateral asymmetric origin from the OAs that has not previously been reported in the literature. Surgeons should be aware of this variation as it could be crucial in the setting of an endovascular approach for meningeal lesions, as in our observation. A 50-year-old male underwent a preoperative cerebral digital subtracted angiography that incidentally revealed MMAs arising from the OA on both sides. In fact, the origin was asymmetric because it was complete on the right side with the anterior and posterior branches of the MMA arising from the OA, whereas it was partial on the left side, with only the anterior branch arising from the OA. The CT scan showed the absence of the foramen spinosum only on the right side. This paper discusses the unique anatomic variation in the light of MMA embryology and its different origins. Knowledge of this variation may have a practical impact in cases of cerebral embolization.

Is there any benefit from short-term perioperative antiepileptic prophylaxis in patients with chronic subdural haematoma? A retrospective controlled study.

BACKGROUNDnChronic subdural haematoma is a common pathology, which can be complicated by seizures. Seizures may worsen the outcome of patients presenting with a chronic subdural haematoma. However, since the overall and postoperative incidence of seizures and their impact on patients outcome has been diversely appreciated in the literature, the interest of routine antiepileptic prophylaxis remains a controversial question.nnnMETHODSnWe retrospectively investigated 99 patients who were surgically treated for a chronic subdural haematoma in two French academic hospitals: 48 patients received antiepileptic prophylaxis (group A) and were compared with a group of 51 patients who did not receive any antiepileptic prophylaxis (group B). Incidence of perioperative seizures was determined, and potential risk factors for epilepsy were analysed.nnnRESULTSnOverall postoperative seizure incidence was 5.1%. There was a slight trend towards a lower incidence of seizures in patients who had received antiepileptic prophylaxis, but no significant difference was found between the two groups (4.2% in group A versus 5.9% in group B, P=0.697). Seizures were not correlated with increased death. No risk factor for seizures was identified.nnnCONCLUSIONSnOur retrospective data showed there is no benefit of perioperative antiepileptic prophylaxis in patients surgically treated for chronic subdural haematoma. Since other authors have shown conflicting results, sufficiently powered prospective randomized study should be conducted in order to confirm these results.

Subventricular zone involvement at recurrence is a strong predictive factor of outcome following high grade glioma reirradiation

We aimed to assess the efficacy of stereotactic irradiation for patients with recurrent high-grade glioma (HGG) and identify predictive factors of progression-free survival (PFS) and overall survival (OS) following reirradiation. We identified 32 patients with recurrent brain HGG who had been treated with either single-dose (stereotactic radiosurgery) or fractionated stereotactic radiotherapy between April 2008 and October 2015. Median follow up was 21.4 months (range 12.9–23.2) and median PFS was and 3.3xa0months (95% CI [2.3–4.7]), respectively. OS was 90.40% (95% CI [73.09–96.80]) at 6xa0months and 79.55% (95% CI [59.9–90.29]) at 12xa0months. Univariate analysis showed that biological effective dose at isocenteru2009≤u200976xa0Gy was a poor prognostic factor for both OS (83.33 vs. 100% at 6xa0months, pu2009=u20090.032) and median PFS (2.7 vs. 4.7xa0months, pu2009=u20090.025), as was gross tumor volume (GTV) above 1xa0cm3 for OS (86.15 vs. 94.12% at 6xa0months, pu2009=u20090.043). Contact with the subventricular zone (SVZ) was also a poor prognostic factor for median PFS (2.3 vs. 4.7 months, pu2009=u20090.002). Multivariate analysis showed that SVZ contact remained a poor prognostic factor for PFS (hazard ratiou2009=u20093.44, 95% CI [1.21–9.82], pu2009=u20090.021). Results suggest that reirradiation is a safe and effective treatment option for recurrent HGG in patients with a good Karnosfsky Performance Scale score, a long progression-free interval since first radiation and limited GTV, and that contact to SVZ is a strong prognostic factor for PFS.

A prospective video-based observational and analytical approach to evaluate management during brain tumour surgery at a university hospital

The operating room (OR) is a high-risk complex setting, where patient safety relies on the coordinated efforts of multiple team members. However, little attention has been paid to evaluating the strategies employed by OR practitioners to prevent and correct incidents that inevitably occur during surgery. Therefore, we were prompted to investigate human factor (HF) engineering methods that have been used in an innovative way in order to systematically observe and analyze the management of incidents in the neurosurgical OR of a French university hospital. A technical case report illustrates our approach that associates the following procedures: the recording of OR team member activities and behaviour by video cameras and direct observation of a HF researcher, with the description and the explicit demonstration of safety related procedures in self- and cross-confrontation interviews of OR team members. This technical report emphasizes complementary aspects of clinical performance related to safety skills. Moreover, individual and team performances rely on complementary abilities that associate practical knowledge, skills, and attitudes, which are engaged at various degrees to prevent and manage incidents. This report also enlightens new quality-improvement opportunities as well as further objectives for future studies.