A Long-Term Extension Study of Bevacizumab in Patients With Solid Tumors.

BACKGROUND: Bevacizumab has been studied in numerous clinical trials in multiple types of cancer; however, patients may receive bevacizumab over an extended period of time. This study assessed the long-term safety and tolerability of bevacizumab among patients with solid tumors. MATERIALS AND METHODS: Patients enrolled in a Roche/Genentech-sponsored trial who had derived benefit from bevacizumab therapy as monotherapy or in combination with anticancer drugs were eligible for continuation of bevacizumab in this long-term extension (LTE) study. The primary endpoints were the incidence of adverse events (AEs) of Common Terminology Criteria for AEs (CTCAE) grade ≥3 related to bevacizumab treatment, serious AEs (SAEs), and deaths. RESULTS: Ninety-five patients with the following cancer types were enrolled in the LTE: ovarian cancer or peritoneal carcinoma (n = 41), non-small cell lung cancer (n = 16), glioblastoma multiforme (n = 14), breast cancer (n = 11), colorectal cancer (n = 7), or renal cell carcinoma (n = 6). The median (range) duration of bevacizumab treatment was 15.6 (0.0-81.0) months during the LTE and 57.5 (16.4-134.9) months overall (parent trial + LTE), with three patients receiving bevacizumab for >10 years. Overall, 17 patients (17.9%) experienced SAEs, and 21 (22.1%) had a bevacizumab-related AE of CTCAE grade ≥3 (proteinuria and hypertension were the most common). Four patients died: three from disease progression and one from an AE considered unrelated to bevacizumab. CONCLUSION: The safety outcomes observed support the tolerability of long-term bevacizumab in patients with various solid tumors, with a median extended treatment duration of almost 5 years overall and >10 years in some individual patients. ClinicalTrials.gov identifier: NCT01588184. IMPLICATIONS FOR PRACTICE: In this long-term extension study of patients with solid tumors, the median duration of bevacizumab treatment (including parent trials) was just under 5 years, with a long-term exposure in some patients of 7 to >10 years. Grade ≥3 adverse events related to bevacizumab were consistent with the established safety profile, with proteinuria and hypertension being the most common. Patients received bevacizumab over an extended period of time (beyond the length of most clinical trials), and the overall safety outcomes observed support the tolerability of long-term bevacizumab treatment in patients with solid tumors, with clinical benefit achieved over an extended period.

Lomustine and Bevacizumab in Progressive Glioblastoma.

BACKGROUND: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. METHODS: We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients). The methylation status of the promoter of O6-methylguanine-DNA methyltransferase (MGMT) was assessed. Health-related quality of life and neurocognitive function were evaluated at baseline and every 12 weeks. The primary end point of the trial was overall survival. RESULTS: A total of 437 patients underwent randomization. The median number of 6-week treatment cycles was three in the combination group and one in the monotherapy group. With 329 overall survival events (75.3%), the combination therapy did not provide a survival advantage; the median overall survival was 9.1 months (95% confidence interval [CI], 8.1 to 10.1) in the combination group and 8.6 months (95% CI, 7.6 to 10.4) in the monotherapy group (hazard ratio for death, 0.95; 95% CI, 0.74 to 1.21; P=0.65). Locally assessed progression-free survival was 2.7 months longer in the combination group than in the monotherapy group: 4.2 months versus 1.5 months (hazard ratio for disease progression or death, 0.49; 95% CI, 0.39 to 0.61; P<0.001). Grade 3 to 5 adverse events occurred in 63.6% of the patients in the combination group and 38.1% of the patients in the monotherapy group. The addition of bevacizumab to lomustine affected neither health-related quality of life nor neurocognitive function. The MGMT status was prognostic. CONCLUSIONS: Despite somewhat prolonged progression-free survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with lomustine alone in patients with progressive glioblastoma. (Funded by an unrestricted educational grant from F. Hoffmann-La Roche and by the EORTC Cancer Research Fund; EORTC 26101 ClinicalTrials.gov number, NCT01290939 ; Eudra-CT number, 2010-023218-30 .).

Adapting Logic to Physics: The Quantum-Like Eigenlogic Program.

Considering links between logic and physics is important because of the fast development of quantum information technologies in our everyday life. This paper discusses a new method in logic inspired from quantum theory using operators, named Eigenlogic. It expresses logical propositions using linear algebra. Logical functions are represented by operators and logical truth tables correspond to the eigenvalue structure. It extends the possibilities of classical logic by changing the semantics from the Boolean binary alphabet { 0 , 1 } using projection operators to the binary alphabet { + 1 , - 1 } employing reversible involution operators. Also, many-valued logical operators are synthesized, for whatever alphabet, using operator methods based on Lagrange interpolation and on the Cayley-Hamilton theorem. Considering a superposition of logical input states one gets a fuzzy logic representation where the fuzzy membership function is the quantum probability given by the Born rule. Historical parallels from Boole, Post, Poincaré and Combinatory Logic are presented in relation to probability theory, non-commutative quaternion algebra and Turing machines. An extension to first order logic is proposed inspired by Grover's algorithm. Eigenlogic is essentially a logic of operators and its truth-table logical semantics is provided by the eigenvalue structure which is shown to be related to the universality of logical quantum gates, a fundamental role being played by non-commutativity and entanglement.

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma.

BACKGROUND: We assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV. PATIENTS AND METHODS: TAMIGA (NCT01860638) was a phase II, randomized, double-blind, placebo-controlled, multicenter trial in adult patients with glioblastoma. Following surgery, patients with newly diagnosed glioblastoma received first-line treatment consisting of radiotherapy plus temozolomide and BEV, followed by six cycles of temozolomide and BEV, then BEV monotherapy until disease progression (PD1). Randomization occurred at PD1 (second line), and patients received lomustine (CCNU) plus BEV (CCNU + BEV) or CCNU plus placebo (CCNU + placebo) until further disease progression (PD2). At PD2 (third line), patients continued BEV or placebo with chemotherapy (investigator's choice). The primary endpoint was survival from randomization. Secondary endpoints were progression-free survival in the second and third lines (PFS2 and PFS3) and safety. RESULTS: Of the 296 patients enrolled, 123 were randomized at PD1 (CCNU + BEV, n = 61; CCNU + placebo, n = 62). The study was terminated prematurely because of the high drop-out rate during first-line treatment, implying underpowered inferential testing. The proportion of patients receiving corticosteroids at randomization was similar (BEV 33%, placebo 31%). For the CCNU + BEV and CCNU + placebo groups, respectively, median survival from randomization was 6.4 versus 5.5 months (stratified hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.69-1.59), median PFS2 was 2.3 versus 1.8 months (stratified HR, 0.70; 95% CI, 0.48-1.00), median PFS3 was 2.0 versus 2.2 months (stratified HR, 0.70; 95% CI, 0.37-1.33), and median time from randomization to a deterioration in health-related quality of life was 1.4 versus 1.3 months (stratified HR, 0.76; 95% CI, 0.52-1.12). The incidence of treatment-related grade 3 to 4 adverse events was 19% (CCNU + BEV) versus 15% (CCNU + placebo). CONCLUSION: There was no survival benefit and no detriment observed with continuing BEV through multiple lines in patients with recurrent glioblastoma. IMPLICATIONS FOR PRACTICE: Previous research suggested that there may be value in continuing bevacizumab (BEV) beyond progression through multiple lines of therapy. No survival benefit was observed with the use of BEV through multiple lines in patients with glioblastoma who had progressed after first-line treatment (radiotherapy + temozolomide + BEV). No new safety concerns arose from the use of BEV through multiple lines of therapy.

CSF CA 15-3 in breast cancer-related leptomeningeal metastases.

UNLABELLED: The sensitivity of CSF cytology, the standard method for diagnosis of leptomeningeal metastases (LM), is low. Serum cancer antigen 15-3 (CA 15-3) is frequently used for the monitoring of patients with breast cancer (BC) and is a laboratory test available in most centers. The aim of the current study was to determine the feasibility of measuring CSF CA 15-3 and CA 15-3 CSF/serum ratio in patients with BC-related LM. Serum and CSF CA 15-3 values were evaluated in 20 BC patients with LM (Group 1), 20 patients with LM from other primary cancers (Group 2), 20 BC patients with parenchymal brain metastases only (Group 3) and 20 controls (Group 4). CSF and serum were collected on the same day. Serum and CSF CA 15-3 were assessed by an automatized immuno-enzymatic technology (TRACE(®) technology, KRYPTOR Automate, Brahms Society, France). In univariate analysis, BC patients with LM (Group 1) compared to other groups, a significantly elevated serum CA 15-3 (median 51 U/ml, range 12-2819) and CSF CA 15-3 (median 8.7 U/ml, range 0.1-251) was observed. Additionally, the CSF/serum ratio of CA 15-3 was significantly higher in this group of patients (median 0.18, range 0.002-4.40). Multivariate analysis identified a cut-off for CSF CA15-3 with 80 % sensitivity and 70 % specificity. CONCLUSIONS: The current study confirms the feasibility of determining CSF CA 15-3 using a widely available technology. Evaluation of the CSF CA 15-3 may be useful in the diagnosis and management of BC-related LM but further studies are needed.

Salvage intracerebrospinal fluid thiotepa in breast cancer-related leptomeningeal metastases: a retrospective case series.

There is currently a paucity of data on salvage intracerebrospinal fluid (intra-CSF) chemotherapy in leptomeningeal metastases (LM). This report is a single-institution experience with salvage treatment in patients with breast cancer (BC) and LM. This retrospective cohort describes 24 consecutive patients with BC selected for a second-line of treatment for LM. The first line of LM treatment consisted of intra-CSF liposomal cytarabine in all patients combined with systemic therapy in 18 cases and radiotherapy in four cases. Second-line (salvage) treatment utilized intra-CSF thiotepa in all and systemic chemotherapy in nine patients. No patient received CNS-directed radiotherapy. The median Eastern Cooperative Oncology Group performance status at initiation of intra-CSF thiotepa treatment was 3 (range 1-4). The median progression-free survival and median survival following intra-CSF thiotepa was 3.1 months (range 3 days-2 years) and 4.0 months (range 6 days-2.5 years), respectively. The median overall survival from LM diagnosis was 9.5 months (range 1.3 months-2.7 years). No grade 3 or higher toxicity was observed. Recognizing the limits of a retrospective study, intra-CSF thiotepa has an acceptable toxicity profile and appears to be a reasonable option for selected BC patients.

Stereotactic biopsy for brainstem tumors: comparison of transcerebellar with transfrontal approach.

BACKGROUND: An important aspect of evaluating patients submitted to stereotactic biopsy of the brainstem is the trajectory used. The literature describes two principal approaches: the suboccipital transcerebellar and the transfrontal; however, no studies exist comparing these two techniques. OBJECTIVE: The purpose of this study was to compare diagnosis success rates and complications between the suboccipital transcerebellar and transfrontal trajectories. METHODS: The study evaluated 142 patients submitted to stereotactic biopsy. The patients presented brainstem tumors in the following areas: pons (n = 31), midbrain (n = 36), medulla (n = 2), pons-medulla (n = 30), pons-midbrain (n = 33), and midbrain-pons-medulla (n = 10). On 123 patients, the transfrontal approach was used, and on 19 the suboccipital transcerebellar approach. RESULTS: Comparing success rates between the two approaches, it was observed that in the group of patients submitted to the transfrontal approach, 95.1% (117 cases) were successful, while in those submitted to the suboccipital transcerebellar approach, 84.2% (16 cases) were successful. Despite a higher success rate among patients in the first group, the difference was not statistically significant. Regarding complications, in patients who were biopsied via the transfrontal trajectory, the morbidity rate was 9.8% (12 cases), while in patients submitted to the suboccipital transcerebellar approach, the morbidity rate was 5.3% (1 case) and the mortality rate 5.3% (1 case). CONCLUSIONS: This study verified a higher diagnosis rate in patients submitted to the transfrontal approach than in those submitted to the suboccipital transcerebellar approach (95.1 vs. 84.2%); however, the difference was not statistically significant. Regarding complications, the rate was similar in both groups of patients.

[Pre-hospital management of adults with life-threatening emergencies]. / Prise en charge pré-hospitalière des urgences vitales de l'adulte en pratique civile.

In France, acute life-threatening situations are handled by the French Secours a Personne (assistance to persons) and emergency medical facilities. An unequivocal success, this early management of life-threatening emergency situations relies upon centralized call reception, medical dispatching, and immediate on-site emergency medical care. We describe the different emergency care providers and steps involved in the response to emergency situations. Each call centre (Samu, phone number 15; Sapeurs-Pompiers, 18) provides a response tailored to the nature of incoming calls for assistance. A check-list of grounds for an "automatic response" by the SDIS (Service Départemental d'Incendie et de Secours--the French fire brigade) is in use, ensuring that firefighters are often the first on the spot, while the knowledge and skills of the dispatching physician are essential to ascertain the patient's needs, to preserve life and vital functions, and to ensure the patient is sent to the appropriate emergency healthcare facility. In life-threatening emergency situations, patients must be brought straight to the appropriate reference emergency healthcare facility, as quickly as possible, without prior admittance to an emergency department. This is the procedure for extremely acute emergency situations in the following areas: trauma (multiple trauma and/or uncontrolled bleeding, spinal cord trauma), delivery bleeding, other life-threatening situations such as ischemic heart disease, cardiac arrest (sudden death), cerebrovascular stroke and ensuing brain damage, some acute respiratory situations such as anaphylactic shock, foreign-body inhalation, electrocution, drowning, drug overdose, certain forms of poisoning, and conditions requiring initial hyperbaric oxygen (diving accidents, acute carbon monoxide and smoke poisoning). The reasons for suboptimal emergency care in life-threatening situations are currently a major issue, with medical facilities being reduced in some areas, fewer voluntary firemen, hospital reorganization, tight funding, difficulties of medical dispatching, and the varying skills of "first-on-the-scene "emergency workers. Grievances include late emergency responses, inappropriate medical care, and dispatching to the wrong facility. This raises the question of equal opportunity for all in a country with widely varying geographic features and population density. Improvement in the system's efficiency will require a series of objectives to be met in varied and complementary--Enhanced functional coordination, by speeding up the deployment of the ANTARES digital radio-frequency transmission network (Adaptation Nationale des Transmissions Aux Risques Et aux Secours).--Implementation of a network of emergency services with varying degrees of emergency healthcare management related to the technical nature of the facilities. Three levels of emergency healthcare must be made available: level 1 is provided by local hospitals, level 2 includes support facilities available in general hospitals (not necessarily the nearest hospital), and level 3 provides specialized healthcare in large and/or training hospitals with specialized departments. Life-threatening emergency situations are to be handled by level 2 or 3 facilities. Specific facilities must be selected as reference centers. In France, the ARS (Agences Régionales de Santé) is in charge of this procedure, as it provide funding for healthcare continuity--Reducing inequalities in access to emergency care. This will involve improving the network of SDIS brigades, making local medical facilities more responsive, delegating more medical procedures, on-site telemedicine, providing more helicopters equipped with healthcare facilities, more automated external defibrillators, and more dedicated neuro-vascular units.--First aid training must be made widely available. The French National Academy of Medicine has approved ten recommendations regarding organization and facilities.

Clinicopathological features of breast cancers predict the development of leptomeningeal metastases: a case-control study.

The incidence of leptomeningeal metastases (LM) in patients with breast cancer (BC) is increasing as a result of increased screening and improved patient survival. However, the median survival time after diagnosis of LM is between 5 weeks (without any treatment) and 5 months (for aggressively treated patients). In an attempt to identify clinicopathological risk factors for LM, we carried out a case-control study of 100 women with BC. Fifty patients with BC and LM were enrolled and an additional 50 patients with BC and no CNS metastases including leptomeningeal spread were selected as controls. Patients who had developed LM were selected between December 2006 and August 2008. The control group was matched for: age at diagnosis, year of diagnosis, and initiation of chemotherapy at BC diagnosis. The ILC type (P = 0.03), ER-negative (P = 0.01) and PR-negative status (P = 0.03), and initial M+ status at BC diagnosis (P = 0.008) tended to be more frequent in LM patients. These characteristics should lead to early appropriate assessments being performed in this targeted population when a neurological complaint appears, in order to detect LM as soon as possible.

Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache.

Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located <2 mm from the centres of effective contacts were: the mesencephalic grey substance (5/5), the red nucleus (4/5), the fascicle retroflexus (4/5), the fascicle longitudinal dorsal (3/5), the nucleus of ansa lenticularis (3/5), the fascicle longitudinal medial (1/5) and the thalamus superficialis medial (1/5). The contact coordinates (Wilcoxon test) and the structures (Fisher's exact test) were not significantly different between responders and non-responders. These findings suggest that failure of deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems.

[Virtual endoscopic navigation and body transparency based on computed tomography. A step towards in vivo imaging]. / Navigation endoscopique et transparences corporelles par scanner à RX, une étape en imagerie in vivo.

Progress in HR-CTdata processing has led to lower X-ray exposure and to better diagnostic performance. We describe 19 adult patients (among 5000) examined by HR CT with 64 detectors, acquisition and exposure protocols in mSv, spiral, 0.6-mm slices, 5To PACS. After the two usual processing steps (60 gray values, 5122 and 10242 matrices, dedicated workstations for coronaroscopy and virtual coloscopy, 2D multiplanar reformation, surfacic, 3D volumes with dissection and navigation), a third original data processing step on additional workstations was added. Variable matrix extrapolated images, flexible colored curves (different from anatomical conventions), lighting (sources) and transparencies (unavailable with traditional endoscopy) were used. The digital film is a 16-minute "journey "consisting of 19 endo-body navigations in 5 regions, from the head to the bronchi, from the heart to the coronary arteries, and from the digestive tract to the abdomen and pelvis. One possible application is post-operative verification of an aortic graft. The movie is illustrated here with ten plates. This new approach is cost-effective and beneficial for the patient, in terms of early diagnosis and therapeutic follow-up. Ethical issues are also examined.

Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension.

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity,sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions.During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation(weekly frequency of attacks decrease [50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial.

OBJECTIVE: To determine the efficacy of the thrombopoietin receptor agonist romiplostim for the prevention of temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma. METHODS: In the PLATUM phase II open-label, multicenter, single-arm trial, patients diagnosed with Common Terminology Criteria for Adverse Events grade 3 or 4 thrombocytopenia during chemoradiotherapy received weekly subcutaneous romiplostim injections. PLATUM aimed at demonstrating that the percentage of thrombocytopenic patients treated with romiplostim able to complete 6 cycles of maintenance temozolomide chemotherapy exceeded 10% (p0 = 0.10; pA = 0.35). Using type I error equal to 0.05% and 95% power, 31 patients had to be recruited. According to a Fleming 2-step design with a preplanned interim analysis after recruitment of 20 patients (step 1), the trial was terminated early for success. RESULTS: Twenty patients were enrolled in step 1. Median age was 61 years (range 33-73). Twelve patients received 6 temozolomide cycles, corresponding to a success rate of 60% (95% confidence interval 36%-81%). Four patients discontinued temozolomide because they did not respond to romiplostim, 2 for progression, and 2 for adverse events unrelated to romiplostim. CONCLUSION: The thrombopoietin receptor agonist romiplostim improves exposure to chemotherapy in patients with glioblastoma experiencing temozolomide-induced thrombocytopenia. CLINICALTRIALSGOV IDENTIFIER: NCT02227576. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with glioblastoma and thrombocytopenia, romiplostim is effective for the secondary prophylaxis of temozolomide-induced thrombocytopenia.

Clinical outcomes after Gamma Knife surgery for idiopathic trigeminal neuralgia: review of 76 consecutive cases.

OBJECT: Stereotactic radiosurgery is an increasingly used, and the least invasive, surgical option for patients with trigeminal neuralgia (TN). In this study, the authors performed a retrospective evaluation of the safety and efficacy of this method for idiopathic TN. METHODS: The authors reviewed data from 76 patients with idiopathic TN who underwent Gamma Knife surgery (GKS). The mean age of the patients was 64 years (range 27-83 years). All patients had typical features of TN. Thirty patients (39.5%) had previously undergone surgery. The intervention consisted of GKS on the retrogasserian cisternal portion of the fifth cranial nerve. The mean maximum GKS dose used was 85.1 Gy (range 75-90 Gy). RESULTS: Patients were followed-up from 6 to 42 months (mean 20.3 months) after GKS. Complete pain relief was achieved in 83.1% of the patients within 1 year, 70.9% within 2 years, and 62.5% within 3 years. Patients who underwent previous surgery demonstrated a lower rate of pain relief (p < 0.05). Twenty patients (26.3%) reported pain recurrence between 6 and 42 months after treatment. New or worsened persistent trigeminal dysfunction developed after GKS in 16 patients (21%); 8 of these patients described some facial numbness/not bothersome, and 8 reported some facial numbness/somewhat bothersome. None of the patients developed troublesome dysesthesia or anesthesia dolorosa. CONCLUSIONS: Gamma Knife surgery for idiopathic TN proved to be safe and effective and was associated with a particularly low rate of complications.

99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent, primary brain tumors.

BACKGROUND: Malignant brain tumors carry a pejorative prognosis and necessitate aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With limited response rate and potential toxicity to chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. AIM: To define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy response in recurrent primary brain tumors. METHODS: In a retrospective analysis, thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT system. A MIBI uptake index (UI) was computed as the ratio of counts in the lesion to those in contralateral region. For all patients, we compared changes over time in UI with MRI and clinical data. RESULTS: The changes in UI agreed well with the clinical and MRI-based assessments in 97% of cases. In 44% of these cases, the scintigraphic response appeared before the MRI response. In instances of treatment failure or rebound, the concordance between scintigraphy and MRI was 52%, and the scintigraphic response appeared before the MRI response in 48% of cases. CONCLUSION: This study confirms our previous results obtained on a short series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT in prediction of chemotherapy response. Moreover, in cases of tumor progression, we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an average 4 months before MRI changes.

[Surgical procedures improvements thanks to navigators and robots]. / L'aide au geste chirurgical par les navigateurs et les robots.

Navigator is a three-dimensional C-T scan image localization device, which supplies the surgeon with a real time relationship of surgical instruments with pathological lesion and vital organs. Robot controls surgical devices movements according to a various sophisticated programming, in order to palliate the imperfection of their manual use. Navigators and robots, frequently connected, allow a precise control of the instruments course, improving accuracy and efficiency of most surgical procedures. It is necessary to contribute to their improvement and development, taking in count the economic, ethic and legal problems which may be encountered.

[Symptomatic management of brain metastasis]. / Prise en charge symptomatique des métastases cérébrales.

Indications and choice of antiepileptic drugs (AED), treatments for cerebral edema and prophylactic and curative treatments of thromboembolic complications of brain metastasis are discussed.

Prolonged survival of patients with breast cancer-related leptomeningeal metastases.

BACKGROUND/AIM: Prolonged overall survival (OS) has been reported for selected patients with leptomeningeal metastases (LM). The management and treatment of such patients is poorly-described. We report our experience on breast cancer (BC)-associated LM and patients with prolonged survival. PATIENTS AND METHODS: Eleven patients with BC and LM had an OS >12 months in which treatment is described. RESULTS: Combined intra-cerebro spinal fluid (CSF) and systemic treatment were administered until disease progression or toxicity in all but two patients. Involved-field radiotherapy was administered to two patients. Median OS in this selected cohort following LM diagnosis, was 21.0 (range=13-33.3) months. CONCLUSION: Prolonged OS but also prolonged responses can be observed in BC with LM. An individualized and multi-disciplinary approach is advised for the management of these patients.