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Bevacizumab is a monoclonal antibody, which neutralizes the effect of vascular endothelium growth factor (VEGF) allowing regression of tumour vessels and a decrease in the permeability of the blood-brain barrier. Already used in oncology as adjuvant treatment for certain metastatic cancers and in second line for high-grade gliomas, it has been recently used as a treatment of cerebral radionecrosis resisting conventional drug treatment and hyperbaric oxygen. This article presents three patients with cerebral radionecrosis and treated by monthly infusions of bevacizumab (10 mg/kg per month). The patients had developed cerebral radionecrosis after radiation therapy for a malignant brain tumour. The radionecrosis was proved by magnetic resonance imaging and spectroscopy. The first patient received only one perfusion of bevacizumab, as the development of a lymphopenia prevented the patient from continuing with the treatment. The second patient received four infusions, but the absence of improvement of the clinical symptoms and progression of the radiolesion led to discontinuation of the treatment. The third patient developed several severe side effects, a transient ischemic accident and a perforated corneal ulcer, resulting again in premature discontinuation of treatment. The development of severe side effects, combined with the absence of notable clinical and radiologic improvements resulting from the use of bevacizumab as a treatment resulted in the premature interruption of such treatment, in all three patients., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: We review the indications and limitations of chemotherapy in glioblastoma multiform (GBM), including the role played by alkylating and other cytotoxic agents and the increased input of clinical research on targeted agents in GBM management., Methods: In 2005, a phase III study clearly concluded in the benefit of adding temozolomide during and after radiotherapy treatment in GBM and thus defined the new standard of treatment in this devastating disease. This schedule increased the median survival from 12.1 to 14 months and the two- and five-year survival rates from 8 to 26%, and 3 to 10%, respectively, with a good tolerance profile. Moreover, methylation of the promoter of the O6 methylguanine DNA transferase (MGMT) gene exhibits a prognostic impact independently of therapeutic schedule but may also predict the benefit of adding temozolomide to radiotherapy. However, pitfalls in MGMT determination and lack of prospective validation have to be solved before considering MGMT as a decisional marker. More recently, antiangiogenic agents including enzastaurin, cediranib, bevacizumab, and others that target mainly the VEGF pathway, have been evaluated in this highly angiogenic disease. Among them, only bevacizumab has been associated with clear anti-tumor activity, although the lack of control studies limits the impact of the results to date., Conclusions: Recent studies conducted in GBM, both in the adjuvant and recurrent setting, have changed the natural course of the disease and opened a new area of clinical research, including imaging and response evaluation, predictive markers, and other targeted therapies., (Copyright © 2010. Published by Elsevier Masson SAS.)

Some cancers are involved in inherited genetic syndromes. These genetic diseases are suspected of being involved in approximately 1% of gliomas. Few data are available on glioblastomas and their characteristics among these diseases. Familial syndromes known to predispose individuals to glioblastoma are neurofibromatosis type 1, Li-Fraumeni's syndrome, tuberous sclerosis, and Turcot's syndrome. This review discusses glioblastomas related to these diseases and the current knowledge on the statistical, clinical, and molecular biology data. Non-syndromic glioma families are discussed: a better understanding of molecular abnormalities in these groups should help understand the mechanisms of gliomagenesis. A case of malignant glioma requires the physician to actively search for the possibility of inherited factors and eventually suggest genetic counseling., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Damage to the nervous system is a common side effect of antineoplastic therapy. The improvements in treating systemic malignancies have been accompanied by the reports of neurological toxicity that has important impact on quality of life and may even limit the use of the treatment. Neurotoxicity can be induced by synergistic or additive effects of cytotoxic drugs and nervous system exposure is related to routes and doses of administered drugs. Neurological toxicity may be a dose-limiting factor that prevents the more aggressive use of cytotoxic drugs. With the increasing use of multiple modality therapy, dose-intensive therapy and experimental therapy, the incidence of neurological toxicity is still rising. Early diagnosis is essential. Indeed, when neurological complications are diagnosed with delay, they are rarely reversible. Neuroprotective agents are still evaluated. The neurologic complications of the more commonly used chemotherapeutic agents, hormones and targeted molecular agents are discussed., (Copyright 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose: Stereotactic radiotherapy using the CyberKnife has become a key treatment in the multidisciplinary management of secondary tumours, as well as primary benign or malignant tumours located within or adjacent to vertebral bodies and the spinal cord. The aim of this treatment is to improve local control and clinical response, including previously irradiated cases., Patients and Methods: In this study, we present the first patients treated with CyberKnife between December 2006 and December 2007 for spinal or paraspinal tumours. The primary aim was to assess the feasibility and tolerance of stereotactic radiotherapy using the CyberKnife. Secondary aims were to establish the short-term local control, to calculate the local progression-free survival and overall survival. Clinical examination and imaging procedures were performed every three months. Response was assessed according to RECIST criteria., Results: During that period, 16 patients were treated with CyberKnife. Thirteen patients had been pre-treated, three of whom had received spinal cord doses considered to be maximal. Three patients did not receive previous irradiation. The median age was 59 (36-74). The most frequent symptoms were pain (n = 8) and motor weakness (n = 4). The median dose was 30 Gy (16-50). The median number of fractions was 3 (1-5). No patient developed acute myelitis. Three patients developed acute reaction. Overall survival at 18 months was 72.4%, with a mean survival of 18.2 months (95% CI: 15.4-20.9). Local progression-free survival at 18 months was 58.4%, with a mean value of 16.9 months (95% CI: 13.6-20.2)., Conclusion: The use of stereotactic radiotherapy with CyberKnife represents a major progress in the management of paraspinal tumours. The main advantages are better sparing of the spinal cord and the possibility of increasing the dose to the tumour target volume., (2009 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Losses of chromosomes 1p and 19q are deemed correlated with diagnosis of oligodendroglioma, higher chemosensitivity and better prognosis. We reviewed the literature to evaluate the usefulness of these correlations in daily clinical practice. The rates of deletions relative to histology (WHO classifications) were extracted from 33 studies, including 2666 patients. The 1p deletions and 1p19q codeletion mean rates were respectively 65.4 and 63.3% in oligodendrogliomas, 28.7 and 21.6% in oligoastrocytomas, 13.2 and 7.5% in astrocytomas, 11.6 and 2.9% in glioblastomas. The presence of 1p deletion and 1p19q codeletion were strongly correlated with the histological diagnosis corresponding to oligodendroglioma. Calculation of specificity, sensitivity, predictive positive values and false negative rates suggests that presence of deletion 1p or codeletion represents a strong argument in favor of the diagnosis of oligodendroglioma. However, considering the high false negative rate, absence of such deletions does not rule out the diagnosis. In grade 3 oligodendroglial tumors, the probability of responding to chemotherapy, and the duration of response, were higher when codeletions were present. This suggests that, in these tumors, the presence of codeletion is a strong argument in favor of adjuvant chemotherapy. However, chemotherapy should not be systematically excluded when codeletions are absent, as the chances of response are about 33% in this situation. Data concerning low-grade gliomas were more controversial. Oligodendroglial tumors with 1p deletion or 1p19q codeletion seemed to have a better prognosis, as five-year survival rates were 50% higher than in tumors without deletion. This might be explained by the correlation between 1p deletion and other identified prognosis factors: (1) higher chemosensitivity, (2) tumor location more frequently in the frontal lobe, leading to better resection and lower risk of neurological deficit, (3) slower growth rate, (4) higher risk of epilepsy, leading to an early detection.

Introduction: Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and a familial adenomatous polyposis or a hereditary nonpolyposis colorectal cancer., Observation: We report a case of a 45-year-old woman who underwent in 1995 neuro-oncological treatment for an anaplastic astrocytoma (grade III according to the World Health Organization classification). Treatment included complete surgery, radiotherapy, a first-line nitrosourea-based chemotherapy regimen and a second-line platinium salt-based regimen. It was then noted that the patient's brother had colorectal cancer. A genetic study detected a germ-line mutation on the hMSH2 gene specific of HNPCC syndrome (Human Non Polyposis Colorectal Cancer). Colonoscopy was normal. Eight years after the diagnosis, the patient developed a gliomatosis cerebri and died., Conclusion: Relevant personal and familial history can provide the clue to the diagnosis of Turcot's syndrome. Molecular diagnosis may contribute to appropriate care of affected patients.

Not uncommonly, damage to the nervous system occurs as a complication of antineoplastic therapy. Neurotoxicity can be induced by synergistic or additive effects of cytotoxic treatments and nervous system exposure is related to routes and doses. Improvements in treating systemic malignancy have been accompanied by reports of neurologic toxicity that has important impact on quality of life and may even limit use of the treatment. Neurological toxicity may be a dose-limiting factor that prevents more aggressive use of that form of treatment. With the increasing use of multi-modality therapy, dose-intensive therapy and experimental therapy, the incidence of neurological toxicity continues to rise. It points out the need for continuous clinical evaluation to detect their appearance. When neurological complications are diagnosed late, they are rarely reversible. Neuroprotective agents are still under evaluation.

Systemic metastases from ovarian carcinoma are frequent, but they seldom affect the central nervous system. We present here the case of a patient treated for an ovarian cancer by surgery and chemotherapy. Three months after the end of chemotherapy, the patient developed cerebral metastases from ovarian carcinoma (CMOC) treated by iterative surgery and and whole brain irradiation. As the frequency of solitary cerebral metastasis of ovarian cancer is higher than with other cancers, it is likely that they behave slightly differently. Literature analysis reveals an increase in the incidence of CMOC since the middle of the nineties. CMOC can occur during or after adjuvant chemotherapy and the best management strategies to better define determinants of survival for patients are not well known. It appears that a better outcome of CMOC may be obtained by an aggressive treatment, if possible, including surgery, radiotherapy, and chemotherapy. Taking into account the increase in the incidence of the CMOC and their early occurrence, some authors have proposed a prophylactic brain radiotherapy in patients who receive adjuvant chemotherapy.

One hundred forty-four patients with breast cancer and osteolytic bone metastases were randomized to receive either oral clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either chemotherapy or hormonal therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as: hypercalcemia (> 3 mmol/l), increase in, or onset of new bone pain due to metastases, requirement of radiotherapy for bone pain relief, pathological fractures (including vertebral collapse, spinal cord compression) or death due to bone metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral clodronate and 68 placebo. Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05). Hypercalcemia did not occur in the clodronate group but was observed in four placebo-treated patients. Clodronate-treated patients had a significant reduction in pain intensity compared to placebo (p = 0.01; measured using a visual pain scale) and significantly fewer patients receiving clodronate required analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups. Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone metastases from breast cancer and adds to treatment of malignant osteolysis.

Efficiency of chemotherapy (CT) on non removable HGG has not been proven and neoadjuvant brain irradiation (RT) following biopsy is the standard treatment. We aimed to define whether combination of polychemotherapy and radiotherapy is synergistic in non removable HGG. It has been proven that F, CDDP and VP16 can reach therapeutic levels in brain after intravenous standard dose injections. The aim of this study was to assess that (i) neoadjuvant CT is safe; (ii) feasibility and efficacions of F (100 mg/m2.d1)/CDDP (100 mg/m2.d1-3 TD)/VP16 (75 mg/m2.d1-3) q21-28d regimen; (iii) Delayed RT is not unsafe: RT was performed when tumor progression or toxicity appeared. This study included 16 patients with symptomatic non removable HGG. Two of them had anaplastic gliomas and 14 glioblastomas multiforme. None of them had a prior chemotherapy regimen. Objective response was evaluated with CT scan or MRI during chemotherapy. Toxicity was moderate and mainly hematological (grade III-IV thrombopenia = 10/67 cycles; leukopenia = 13/67). Objective response rates were 5/16 (31 p. 100) (CR = 1; PR = 4; Median duration of response: 20 weeks). Median survival was 55 weeks in the 14 grade IV patients. Three/16 patients are still alived with respectively 22, 30, 40 months survival: These results confirm the neoadjuvant chemotherapy efficacy. It may be a useful tool before RT for non removable HGG.

Introduction: Neurotoxicity can be induced by the synergistic or additive effects of cytotoxic treatments, and nervous system exposure is related to routes and doses., Current Knowledge and Key Points: The improvements in treating systemic malignancy have been accompanied by reports of neurologic toxicity, which has an important impact on the quality of life and may even limit the use of the treatment., Perspectives and Future Projects: It demands out a continuous clinical evaluation to detect their appearance. When neurological complications are diagnosed later, they are rarely reversible. Neuroprotective agents are still being evaluated.

Introduction: The epidemiology of brain or central nervous system metastases is poorly documented. Retrospective studies based on autopsies that were aimed at investigating the incidence and prevalence of brain metastases have revealed the shortfalls in tumour registers. The exact role of cerebral metastases has not been addressed within the scope of cancer considered as a public health issue., Current Knowledge and Key Points: The prognosis of brain metastases should not be considered either on general or a priori basis as being poorer than that of other metastatic sites. Evaluation of the role of focal radiation therapy and chemotherapy is still in progress. Appropriate use of therapeutical strategies directed at brain tumors generally improves the condition of most patients. It also usually increases survival and enhances the quality of life., Future Prospects and Projects: The role of chemotherapy in current therapeutical strategies has not yet been defined and should be investigated and developed.

Introduction: Seizures are common in patients presenting with intracranial tumors. Nevertheless, the incidence of cancer is not higher in patients with seizures. We attempted to summarize situations that can lead to the diagnosis or treatment of seizures in patients presenting with cancer., Current Knowledge and Key Points: Focal neurological signs on clinical examination when seizures occur for the first time in patients with cancer lead to brain imaging. As a result of recent advances in neuro-imaging techniques, the presence of a tumor is now more frequently observed in patients with seizures., Perspectives and Future Projects: As it may have irritating effects on the cerebral cortex, chemotherapy is able to either increase or induce seizures in patients presenting with cancer. Potential pharmacological interactions between antiepileptic and cytotoxic drugs thus require close surveillance in patients with cancer.

Adjuvant tamoxifen (TAM) has been proved to reduce recurrence and mortality in early breast cancer, nevertheless many patients did not receive TAM as adjuvant therapy after local treatment. In order to study the efficacy of delayed TAM therapy in patients who were not given immediate adjuvant hormonal treatment, a multicenter randomized trial has been conducted by the French National Cancer Centers (FNCLCC). According to eligibility criterias all women with breast cancer who received curative local treatment at least 2 years before (surgery +/- radiotherapy) with or without adjuvant chemotherapy but no hormonal treatment could have been included. Between September 1986 and October 1989, 494 women were randomized to receive either TAM 30 mg/day for 5 years or no treatment. Patients' characteristics such as age, tumoral stage, number of positive nodes, receptors status and time from local treatment were equally distributed in the 2 groups. An improvement in the disease free survival in the TAM treated patients can be observed with a significative difference (p = 0.05), nevertheless the overall survival is not improved in the TAM group. In the same way, in nodes positive patients although no significative improvement in the overall survival can be observed, a significative improvement in the disease free survival (p = 0.05) can be noted. In estradiol receptors positive patients tamoxifen gives a significative reduction in the odds of death (p = 0.04) and recurrence (p = 0.03). The disease free improvement seems to be limited to 50 and more years old patients. The first results of this trial lead to prescribe tamoxifen to all postmenopausal women previously treated for an early breast cancer without adjuvant tamoxifen treatment.

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.

The most frequent brain metastasis originates from a lung cancer. About half of them are unique. We report a series of 36 patients with lung cancer, operated for a single brain lesion. The mean age was 57.6 years, most (83.3%) were male. Most of the metastases originated from a primary adenocarcinoma (52.8%), in 10 patients (27.8%) from an epidermoid carcinoma, in 4 patients (11.1%) from a small cell carcinoma and in 3 patients from a mixed lesion. The metastatic lesion was detected before the primary lesion in 20 cases (55.5%). The mean post-operative survival was 9.6 months. 36% were alive one year after surgical treatment. We evaluated our clinical findings, histopathological studies and the type of surgical and medical post-operative management, at the cerebral and pulmonary level, in order to make a possible prognosis. In our series we found that only post-operative clinical status (Karnofsky score) and the post-operative neurological grading (Order classification) were significant factors (p < 0.001) to determine survival time.

Bone metastases are frequent in the evolution of breast cancer. Bone scan is the best method for early detection. At initial presentation the frequency of bone metastases is low, and it is usefulness to recommend this exam except for old people or patients with risks factors. During the follow-up, the utility of repeated bone scan is discussed. For the majority of authors, it may be reserved for symptomatic patients or when biological modifications appeared. The follow-up of these patients must be essentially clinical. This strategy delay the diagnosis of bone metastases of only a few weeks; and it don't seem to affect the prognosis of these patients.

The aim of this study was to test cisplatinum and 5-FU chemotherapy. Thirty-five patients with epidermoid or undifferentiated lung carcinoma were entered in a multicentric phase II trial, in an attempt to further define the activity and toxicity of this association. None of them had been previously treated by chemotherapy. The dosage schedule was cisplatinum 100 mg/m2 D1 and 5-FU 1 g/m2 D1 to D5 every 3 weeks for 3 courses before evaluation. There were CR: 2, PR: 10, for a total response rate of 35%. Median survival was 7 months. Tolerance was acceptable. We conclude that this association can be safely administered, but that the results are not superior to others previously reported. Further studies are required to define the activity of a cisplatinum, 5-FU and radiotherapy association.

A retrospective study with an 18 month follow-up period was conducted on 184 patients (with 172 epithelial ovarian tumors) to compare the value of ultrasonography and CT for detection of pelvic masses, adenopathies, urinary stasis, hepatic metastasis and peritoneal or intestinal involvement. Ultrasound and CT findings were compared with histology data for 47 patients; ultrasound and CT data were compared with the clinical course for 53 patients. Ultrasonography was better than CT for the detection of pelvic masses, and was also slightly better for liver metastases and urinary stasis. CT was more effective for the diagnosis of lumbo-aortic and pelvic adenopathies, and peritoneal and intestinal involvement, but the sensitivity of imaging techniques remains insufficient for both of these lesion types. Combined examination by ultrasonography and CT every 6 months suffices for follow-up of patients who have undergone surgery and can evaluate tumoral response in patients treated by first-line chemotherapy.

CA 125 is today the best tumour marker to follow up the evolution of epithelial cancers of the ovary where it is elevated in about 80% of cases (as compared with a positive finding in only 20% for CEA and CA 19,9): it is no use as a screening test, it does reflect the quality of the first debulking operation, it makes it possible to follow the clinical evolution of the disease and thus to modify the adjuvant treatment, it helps to indicate whether a second look operation should be carried out; but it does not dispense altogether with the second look operation because even when CA 125 returns to normal the disease is sometimes still not eradicated, finally, it gives an opportunity to look early for any recurrences.