The management of brain metastases remains a challenging issue due to the detrimental impact on the patient quality of life and the wide range of clinical situations. The question is not a local treatment or WBRT but when and how to use the different modalities for each patient. Survival, an endpoint often used, is probably not the best way to evaluate the local efficacy: most patients will die from progressive extracranial disease. The brain tumor control (local or freedom from new brain metastases) is a better way to assess the impact of WBRT or SBRT. Another major problem is the great heterogeneity of the primary tumors and clinical situations. First, we should remember that most patients are not candidate for a local treatment (SBRT or surgery (S)) due to the number of lesions, locations, performance status, meningeal infiltration…and WBRT remains the standard treatment if a brain irradiation is needed. For patients with an "oligo metastatic disease," many studies have clearly showed the superiority of a form of local treatment (S or SBRT) compared to WBRT at least in term of progression or control at the primary brain site (Table1).1-5 Another issue is to control the disease within the brain: new brain metastases are very common. WBRT has been tested either after S or SBRT to prevent the development of those new lesions: indeed adding WBRT let to a better brain tumor control but this did not translate in any major survival benefit. One major drawback of WBRT is its possible toxicity: the impact on the quality of life, the neurocognitive toxicity, the fatigue and the hair loss. In the EORTC trial, WBRT had a transitory negative impact on the physical or cognitive functioning and more fatigue in the early period of observation compared to the group of patients in the observation arm.6 A current approach is to follow the patient after SBRT and in case of relapse to propose a salvage treatment which may be a new course of SBRT or even WBRT. Another question was to improve the local control after S adding SBRT. Postoperative SBRT has been proposed and several retrospective studies have shown the feasibility results. Two recently published randomized trials have compared postoperative SBRT to either WBRT or observation. The two main conclusions were less cognitive deterioration with SBRT compared to WBRT (15% vs 48%) and less local relapse at the primary site compared to no treatment (at 1 year 43% vs 72%) but no difference in overall survival.4,5 An intriguing observation was the better local control at one year after postoperative WBRT compared to SBRT.4 Is there a group of patients benefiting from WBRT? In a new analysis of the Aoyama trial, patients with NSCLC were divided according to a graded prognostic assessment: a statistically significant benefit was observed only in the favorable group with a 6 months gain in median survival.7 A similar observation was reported in the RTOG trial testing the role of adding SBRT to WBRT with a median survival of 14 vs 21 months.8 Is it possible to reduce WBRT toxicity? The hippocampus region play an important role in the preservation of the neurocognitive functions: techniques have been developed to spare the hippocampus region keeping the dose below 7 Gy with a better quality of life and a very low risk of new brain metastases occurring in this spared regions.9 This approach should be tested in large scale phase III trial. Last but not least, the timing of the treatment should be individualized based on the patient needs, and in asymptomatic patients, SBRT may be safely postponed if a systemic treatment is to be administered. Estimated from figures.

Introduction. - Grade II intramedullary astrocytomas are rare tumors. Despite a well-defined role of adjuvant temozolomide chemotherapy for brain gliomas, the contribution of this therapy for intramedullary gliomas is not yet clearly defined.Method. - We retrospectively analyzed the data of 5 adult patients treated with temozolomide between 2008 and 2015 for a grade II intramedullary astrocytoma with progression after surgery.Results. - Five patients from 19 to 70 years of age (median, 37 years) underwent a second surgery for the progression of a grade II intramedullary astrocytoma (median progression-free survival 26 months [8-901). All tumors remained grade II. Due to a second clinical or/and radiological tumor progression, the patients were treated with temozolomide after a 37 months median progression-free survival (5-66). All patients received at minimum 12 cycles (mean 14 5; range 12-24) of temozolomide (150-200 mg/m(2)/day, 5 days/28 days). All patients were alive after a 10-year median follow-up after diagnosis (6-13). All patients were able to walk except one, who was previously in McCormick autonomy grade IV before chemotherapy. The McCormick autonomy rating after temozolomide was stable for 4 patients and improved for 1 patient. The treatment was delayed once for hematological toxicity.Conclusion. - Temozolomide stabilized all 5 patients without any major toxicity. Based on this experience that needs to be confirmed, we consider that temozolomide should be envisaged within the therapeutic arsenal for progressive intramedullary grade II astrocytomas. (C) 2017 Elsevier Masson SAS. All rights reserved.

Grade II intramedullary astrocytomas are rare tumors. Despite a well-defined role of adjuvant temozolomide chemotherapy for brain gliomas, the contribution of this therapy for intramedullary gliomas is not yet clearly defined.We retrospectively analyzed the data of 5 adult patients treated with temozolomide between 2008 and 2015 for a grade II intramedullary astrocytoma with progression after surgery.Five patients from 19 to 70 years of age (median, 37years) underwent a second surgery for the progression of a grade II intramedullary astrocytoma (median progression-free survival 26months [8-90]). All tumors remained grade II. Due to a second clinical or/and radiological tumor progression, the patients were treated with temozolomide after a 37months median progression-free survival (5-66). All patients received at minimum 12 cycles (mean 14 ± 5; range 12-24) of temozolomide (150-200mg/m2/day, 5days/28days). All patients were alive after a 10-year median follow-up after diagnosis (6-13). All patients were able to walk except one, who was previously in McCormick autonomy grade IV before chemotherapy. The McCormick autonomy rating after temozolomide was stable for 4 patients and improved for 1 patient. The treatment was delayed once for hematological toxicity.Temozolomide stabilized all 5 patients without any major toxicity. Based on this experience that needs to be confirmed, we consider that temozolomide should be envisaged within the therapeutic arsenal for progressive intramedullary grade II astrocytomas.

CONCLUSION: In this study we validated both the M-GPA and Chowdhury OS score.The Chowdhury OS score proved to be the most accurate score to categorize patients with MBM in risk groups with corresponding statistically significant median overall survival time.Contrary to Chowdhury et al the follow-up time in our study was sufficient for the low-risk group to reach the median overall survival time which was 13 months.P13.

Les métastases cérébrales sont une complication fréquente des épithéliomas bronchiques à petites cellules et représentent un défithérapeutique au vu des conséquences neurologiques. Les différents traitements seront envisagés ainsi que la prévention de ces métastases par une irradiation cérébrale prophylactique.

PURPOSE: To prospectively validate our basic score for brain metastases (BSBM) classification in patients treated by Gamma Knife radiosurgery (GKRS) for brain metastases (BM) METHODS AND MATERIALS: Between January 2003 and December 2007, we treated more than 1000 BM in 283 patients by RS. We followed these patients prospectively since January 2003 using the BSBM classification, which is based on 3 prognostic factors: no extracranial metastatic disease (ECMD), KPS ≥80, primary tumor controlled. A score of 0 to 1 point was attributed to each factors, with a total from 0 to 3 points; the patients had a BSBM score 0, 1, 2 and 3 in 2.5%, 13%, 60% and 24%, respectively. RESULTS: The median survival (MS) was 12 months (95% CI, 10-14 months); the 2-years and 5-years survival were respectively 27 and 10 %. The MS was 2.5, 6, 12 and 20.5 months respectively for the BSBM scores 0, 1, 2 and 3 (p < 0.001); the MS was respectively 13 and 11 months with an ECMD absent or present (p < 0.001), 4 and 13 months according a KPS <80 or ≥80 (p < 0.001) and finally, 13 and 7 months with a primary tumor controlled or not (p < 0.001). All 3 prognostic factors used in the BSBM classification were found statistically significant in univariate and multivariate analysis. CONCLUSIONS: We have validated prospectively our BSBM prognostic model which we developed retrospectively in 2004. The strenghts of our classification is the ease to use as we consider only 3 prognostic factors.

Hearing preservation and tumour control after radiosurgery for NF2-related vestibular schwannomas. Objectives: We analyzed the effects of stereotactic radiosurgery on tumour control and cranial nerve function in patients with vestibular schwannomas (VS) secondary to neurofibromatosis type 2 (NF2). Irradiation was performed with a Gamma Knife, model C equipped with a high-precision, robotized positioning system (APSTM). Methodology: This study included 18 patients with 25 VSs secondary to NF2 that were treated from 2001 to 2010 with radiosurgery at our Gamma Knife Center. The radiosurgical procedure included high-resolution conformational doseplanning with multiple, small-diameter isocenters, a single-fraction, low-dose irradiation prescription, and highly accurate gamma rays delivery to the target with the APSTM. Results: The median follow-up time was 4.4 y. For 16 tumours in 12 patients with available follow-up data, we observed an actuarial tumour control of 87.5% at 2 y and 80.2% at 5 y, based on the Kaplan-Meier method. No patient developed facial weakness. Serviceable hearing was preserved in 78% of cases. Patients treated for bilateral and unilateral tumours had similar outcomes. Conclusions: Radiosurgery could control tumour growth and preserve hearing function and facial weakness in patients with VS secondary to NF2. The enhanced techniques of radiosurgical irradiation provided with the Gamma Knife model C have improved the results of this treatment alternative to microsurgery.

The authors present the activity of Mrs. Sofia Ionescu, the one female surgeon who was nominated as the first woman neurosurgeon in the world. Sofia Ionescu worked in the field of neurosurgery for 47 years, performing all the known neurosurgical procedures of the time. She made herself known through her incredible surgical skill and her enormous work power. Due to her incredible modesty and workload, she never participated at international congresses or manifestations. The nomination as first woman neurosurgery took place in Marrakech, Morocco, during the 2005 WFNS Congress. Although some claim that Diana Beck was the first woman neurosurgeon in the world, our theory suggests otherwise. The first documented surgical intervention performed by Diana Beck dates to 1952. Sofia Ionescu operated for the first time on a human brain as early as 1944. Furthermore, Diana Beck's actions surfaced in the year 1947, long after the war had ended and Sofia Ionescu had become a neurosurgeon.

BACKGROUND Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. METHODS Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. RESULTS The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. CONCLUSIONS The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.

Hearing outcome after gamma knife radiosurgery for vestibular schwannoma: a prospective Belgian clinical study.Introduction: Leksel Gamma Knife(R) (LGK) radiosurgery is a safe and efficient therapeutic approach for vestibular schwannoma (VS) with low side effects. The goal of radiosurgery is not necessarily to cause significant tumour necrosis or to obtain a complete radiographic response, but to halt the tumour's growth permanently through its biological elimination. The 2 major aims of radiosurgery for VS are long-term tumour control and functional hearing preservation. The purpose of this study is to report our experience with LGK radiosurgery in the management of VS and to evaluate the hearing preservation rate after a minimum one-year follow-up.Material and methods: Between January 2000 and January 2011, 415 patients with unilateral VS underwent LGK radiosurgery at the University Erasmus Hospital of Brussels. There were 349 patients with previously untreated VS (86 grade I, 96 grade II, 141 grade III, 9 grade IVa, 17 unknown grades, according to Koos) and 66 patients with post-operative residual tumour. All patients in our series underwent evaluation with high resolution neurodiagnostic imaging including computed tomography and magnetic resonance imaging, and clinical evaluation as well as audiological tests that included tonal and speech audiometries. The Gardner Robertson (OR) classification is used to report the results of this study. We identified 276 patients treated for VS with LGK, tested and retested with speech and tonal audiometries by the same team, and followed for a minimum of one year.Results: Before LGK, 144 patients had serviceable (85 GR class I and 59 GR class II) hearing; 95 (65.97%) of these patients had preservation of serviceable hearing (Pure tone average <= 50 db and Speech discrimination >= 50%) at minimum one-year audiological follow-up. It was observed that 44 of the 85 OR class I patients (51.76%) maintained their level of audition and 66 of these (74.64%) preserved serviceable hearing. In the 34 patients with preradiosurgery non-serviceable hearing (GR class III-IV) 25 of these patients (73.52%) maintained their hearing. The tumour was stable or declining in size in 90.44% of cases.Conclusion: LGK radiosurgery provides excellent tumour control in vestibular schwannomas and has low toxicity even after long-term follow-up.

570 Background: Previous trials have suggested the efficacy of either L or T for the treatment of brain metastases. This study was designed to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of L + T in pts with BM from HER2+ metastatic breast cancer. Methods: Eligible pts had HER2+ breast cancer and recurrent or progressive BM. Previous chemotherapy, trastuzumab, L and brain RT/surgery/radiosurgery were allowed. Measurable brain disease was required (> 5mm by volumetric MRI). Adequate cardiac, renal, bone marrow and hepatic functions prior to study entry were required. Patients were enrolled in one of the cohorts and treated as per the table. The primary endpoint was the determination of the MTD, defined as the dose level below that dose in which ≥ 2/3 or ≥ 2/6 pts experience DLT in the first cycle. Volumetric brain MRI was performed at baseline and every two cycles during therapy. Secondary endpoints included objective response, clinical benefit and duration of response. The protocol was amended to allow treatment (only 1 cycle) to be given prior to surgery/gamma knife. This trial is registered at NCT00614978. Results: 17 pts were enrolled from Jan 2008 to Jan 2011. A DLT was observed in cohort 5 (L 1500 mg/d and T 200 mg/m2 D1-5) with an extension to 6 patients in this cohort. The last patient in cohort 5 will be enrolled in Feb 2011 and the study will be finalized in Q2 2011. The most common toxicities were fatigue, diarrhea, thrombocytopenia, and liver enzymes alterations. Conclusions: The study is ongoing at the last dose level (full doses of both agents). The combination of L + T seems well tolerated. Final results on safety and efficacy data, including volumetric MRI, will be available for this meeting. Dose group (No. of patients) Lapatinib (mg/day) days 1-28 Temozolomide (mg/m2/day) days 1-5 DLT observed (first cycle) 1 (3 pts) 1,000 100 None 2 (3 pts) 1,250 100 None 3 (3 pts) 1,500 100 None 4 (3 pts) 1,500 150 None 5 (5 pts) 1,500 200 Thrombocytopenia > 7 days

2044 Background: The standard treatment of GBM is curently maximal surgical resection followed by 6 weeks of radiochemotherapy and 6 months of adjuvant temozolomide (TMZ). Nevertheless, nearly half of the patients who have completed this treatment will relapse within 6 months. In some cases where TMZ was continued beyond 6 months, a further clinical and radiologic improvement has been observed. Therefore some physicians propose to extend adjuvant TMZ, although this approach is not validated by a trial demonstrating a clinical benefit. Methods: Progression-free patients were randomized after completion of the 6 cycles adjuvant TMZ in a Belgian academic multicenter phase II trial. In the experimental arm, treatment was continued until progression (TMZ Arm). The patients randomized in the observation arm discontinued TMZ and were retreated upon progression. The presence of residual tumor and MGMT status were used as stratification factors. 42 patients out of the 62 planned are included. Tumor evaluation was performed by MRI every 3 months and centrally reviewed. An interim analysis was planned and performed 6 months after the inclusion of the twentieth patient. Results: Half of the patients included in this interim analysis were randomized in the TMZ arm. The well-known prognostic factors were equally balanced between the TMZ arm and the observation arm: median age 55 vs. 56 yrs, Karnovsky index 84 vs. 92%, residual tumor 8 vs. 9 pts, and steroids use 5 vs. 2 pts. The median follow-up was 12.3 and 6.5 months, respectively. The progression-free survival (PFS) at 6 months was 70% vs 57%, respectively. The median number of TMZ cycles received in the TMZ arm was 6 and 4 patients progressed. In the observation arm, 5 patients were rechallenged and 3 cycles were given without any response. The toxicities of TMZ were limited to grade 1-2 and 3 patients with an asymptomatic grade 3 lymphopenia. Conclusions: Continued treatment with TMZ is well tolerated in this selected population. The interim analysis is in line with a potential benefit of the experimental arm in terms of PFS. Accrual continues and the final analysis will be reported later. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough

The microwave hydrothermal method was employed for the synthesis of Ni doped Barium trimolybdate (Ni–BaMo3O10) tripod microcrystals. The photocatalyst, BaMo3O10 and Ni–BaMo3O10 have tendency to degrade the Indigo Carmine (IC) about 40 and 98% under visible light irradiation, respectively in 180 min. The photocatalyst revealed the excellent photodegradation stability up to five cycles. The active species (OH•, O2•-, and h+) were responsible for IC degradation on the basis of scavenger test. Effect of pH on IC degradation was also investigated. The enhancement of photocatalytic efficiency for IC degradation is related to increase in visible light absorption/oxygen vacancy and efficient separation of electron-hole pairs on the surface of photocatalyst. The suppression of charge recombination explained by transient photocurrent response and EIS measurements. The IC degradation was analyzed by ultra-performance liquid chromatography-photodiode array (UPLC-PDA) and high resolution-quadruple time of flight electrospray ionization mass spectroscopy (HR-QTOF ESI/MS). The four degradation pathways of IC in water were proposed on the basis of degraded products. Hydroxylation, oxidation, methylation, decarboxylation, and desulfonation reactions were observed during IC degradation. The efficient mineralization of IC occurred according to total organic carbon (TOC) investigation. Therefore, this research article presents removal of dyes pollutants from polluted water and in-depth analysis of IC pathways.