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Biomedical subjects

Sophie Taillibert

Publications and source records attributed to Sophie Taillibert.

18 recordsLinked to original sources
PubMed2006

Gliomatosis cerebri: a review of 296 cases from the ANOCEF database and the literature.

Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic glial cell infiltration of the brain. Diagnosis and management of GC are difficult. This study analyzed 296 individual cases (90 patients followed through the ANOCEF network, and 206 cases from the literature), aged 1 month to 85 years (median 42), sex ratio=1.31. Median survival was 14.5 months. It was higher for patients younger than 42 years (17 months vs. 13 months), with performance status>or=80 (27 months vs. 9 months), low grade gliomatosis (grade 2=20 months, grade 3=11.5 months, grade 4=8.5 months), oligodendroglial subtype (36 months compared to 14 months for mixed GC and 11 months for astrocytic GC). Male population was younger (median 39 years vs. 45), had a higher incidence of oligodendroglial GC (22% vs. 13%), which may explain their better prognosis (median survival 17 months vs. 11.5 months) than female population. Despite a high rate of stabilization, the impact on survival of whole brain radiotherapy, which carries the risk of severe toxicity, is still unclear. Up-front chemotherapy benefit to some patients and may be preferred to whole brain radiotherapy. However, the many bias of such retrospective heterogeneous data claim for multicentric clinical trials in this rare disease.

Adolescent↗
PubMed2006

Treatment of central nervous system metastases: parenchymal, epidural, and leptomeningeal.

PURPOSE OF REVIEW: With prolonged survival from systemic therapies in the adjuvant and salvage setting, and because these agents cannot cross the intact blood-brain barrier, central nervous system metastases are becoming a therapeutic challenge in oncology. RECENT FINDINGS: Recent therapeutic achievements include an extended use of surgery and radiosurgery. Although each of these treatment modalities has its own indications, in patients eligible for both treatments the upfront comparison of these two techniques has not been performed yet. Systemic chemotherapies and biotherapies may be effective in the management of central nervous system metastases as they may act on both neurologic and extra-central nervous system lesions. In the treatment of epidural metastases, a surgical procedure providing immediate direct circumferential decompression of the spinal cord followed by local irradiation has been demonstrated in a prospective randomized trial. The management of leptomeningeal metastases remains controversial and of limited efficacy especially in chemoresistant tumours and still relies on the combination of chemotherapy (intrathecal and intravenous) and focal radiotherapy. SUMMARY: Aggressive treatments in patients with early diagnosis and in whom central nervous system metastases are the life-threatening location may provide a substantial increase in survival and favourably affect quality of life.

Antineoplastic Agents↗
PubMed2006

Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma.

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was 80% (range, 60%-100%). Adverse effects possibly or probably related to the studied drug were moderate and consisted mainly in worsening of neurological conditions (four patients), fever above 38 degrees C that disappeared within a few days (five patients), and reversible grade 3 lymphopenia (seven patients). Only one patient experienced a dose-limiting toxicity. Preliminary evidence of activity was suggested by a minor response observed in two patients and an overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main side effects were limited to transient worsening of neurological condition and fever.

Adjuvants, Immunologic↗
PubMed2005

Dural metastases.

Dural metastases are found at autopsy in 8-9% of patients with advanced systemic cancer. They arise either by direct extension from skull metastases or by hematogeneous spread. Dural metastases are often clinically asymptomatic but they may produce progressive neurological deficits and sometimes subdural hematomas. MRI may be misleading when the metastasis simulates a meningioma or when a subdural hematoma masks the underlying tumor. Whenever possible, surgical removal is the most appropriate treatment. The prognosis is poor because of the progressive systemic cancer but prolonged survival has been reported in operated patients, when the systemic cancer was controlled.

Dura Mater↗
PubMed2005

Skull-base metastases.

Metastasis to the skull-base particularly affects patients with carcinoma of the breast and prostate. Clinically, the key feature is progressive ipsilateral involvement of cranial nerves. Five syndromes have been described according to the metastatic site including the orbital, parasellar, middle-fossa, jugular foramen and occipital condyle syndromes. Magnetic resonance imaging (MRI) is nowadays the most useful examination to establish the diagnosis but plain films, CT scans with bone windows and isotope bone scans remain helpful to demonstrate bone erosion. Normal imaging studies do not exclude the diagnosis. The treatment depends on the nature of the underlying tumor. Radiotherapy is generally the standard treatment, while some patients with chemosensitive or hormonosensitive lesions benefit from chemotherapy or hormonotherapy and selected patients from surgical removal. Gamma Knife radiosurgery is sometimes a useful alternative, particularly for previously irradiated skull-base regions, and for small tumors (diameter < 30 mm). The overall prognosis is poor, with an overall median survival of about 2.5 years, probably because skull-base metastases appear late in the course of the disease.

Humans↗
PubMed2005

Leptomeningeal metastases from solid malignancy: a review.

Leptomeningeal metastases (LMM) consist of diffuse involvement of the leptomeninges by infiltrating cancer cells. In solid tumors, the most frequent primary sites are lung and breast cancers, two tumors where the incidence of LMM is apparently increasing. Careful neurological examination is required to demonstrate multifocal involvement of the central nervous system (CNS), cranial nerves, and spinal roots, which constitute the clinical hallmark of the disease. Cerebro-spinal fluid (CSF) analysis is almost always abnormal but only a positive cytology or demonstration of intrathecal synthesis of tumor markers is diagnostic. T1-weighted gadolinium-enhanced sequence of the entire neuraxis (brain and spine) plays an important role in supporting the diagnosis, demonstrating the involved sites and guiding treatment. Radionuclide CSF flow studies detect CSF compartmentalization and are useful for treatment planning. Standard therapy relies mainly on focal irradiation and intrathecal or systemic chemotherapy. Studies using other therapeutic approaches such as new biological or cytotoxic compounds are ongoing. The overall prognosis remains grim and quality of life should remain the priority when deciding which treatment option to apply. However, a sub-group of patients, tentatively defined here, may benefit from an aggressive treatment.

Breast Neoplasms↗
PubMed2005

Palliative care in patients with brain metastases.

PURPOSE OF REVIEW: With improvements in systemic therapy, central nervous system metastases have increased in incidence in patients with cancer. Patients with brain metastases from solid tumors often have a dismal prognosis, and supportive measures are often critical in improving patient outcome. They include treatments against vasogenic edema, seizures, symptomatic venous thrombosis, and pain, and the management of iatrogenic side effects. This article reviews all the supportive care measures in patients with brain metastases, with the exception of tumor-specific chemotherapy treatments that are also used in this patient population. RECENT FINDINGS: Recently, improvement has been made in the management of the following complications of brain metastases: epilepsy and antiepileptic drug side effects, thromboembolic complications, fatigue and cognitive disorder of mixed (tumoral and/or iatrogenic) origin, pain, hematological side effects of chemotherapy, and steroids complications. SUMMARY: Patients with brain metastases are particularly prone to develop severe side effects, increased fatigue, and cognitive deteriorations following apparently minor changes in symptomatic treatments. Palliative management of brain metastasis requires a multidisciplinary approach, and it is important to avoid any treatment that is useless or harmful or has a poor toxicity/efficacy ratio.

Adrenal Cortex Hormones↗
PubMed2004

[The genetics of glioma: molecular classification].

Gliomas result from specific genetic alterations--such as activation of specific oncogenes and/or inactivation of specific tumor suppressor genes. These alterations affect specific pathways involved in either signal transduction or cell cycle control, leading to phenotypic changes such as uncontrolled proliferation, inhibition of apoptosis, genetic instability, invasive properties. Tumoral progression includes multiple molecular pathways of clinical relevance: early alterations (p53 mutations for astrocytomas, 1p and 19q loss for oligodendrogliomas) and late alterations (EGF-R amplification, PTEN and P16/CDKN2A inactivation). Genetic profile is not only of diagnostic--but also prognostic relevance, as shown by 1p associated to 19q loss in oligodendrogliomas which is predictive of better prognosis and higher response rate.

Brain Neoplasms↗
PubMed2004

[Current classification of gliomas].

The histologic classification of gliomas, which is based on oligodendroglial- or astrocytic-like morphology distinguishes gliomas in astrocytic tumors (grade 1- pilocytic astrocytoma to grade 4- glioblastoma), oligodendroglial and mixed tumors (grade 2 and 3) according to cell differenciation, cellularity, nuclear atypia, mitotic activity, necrosis and microvascular proliferation. Prognosis is correlated to grade. Based on interobserver variability, the histological diagnosis is often highly subjective and should be interpreted within the context of clinical and radiological data. Newly identified good prognostic markers (1p and 19q loss in oligodendrogliomas) and new molecular techniques such as microarray may further refine the existing classification.

Brain Neoplasms↗
PubMed2004

[Therapeutic strategies and prospects of gliomas].

The prognosis and the treatment of gliomas depend on age, performance status and histological grade. Symptomatic treatment relies on steroids against cerebral edema, anti-epileptic drugs for seizures and perioperatively, prevention of thrombo-embolism and digestive complications, physiotherapy. Specific therapies include surgery, radiotherapy and chemotherapy. Surgery is necessary for histological diagnosis. In low grade gliomas, it has a significant impact in terms of survival. In malignant gliomas, surgery provides symptomic relief without clearly improving survival. Radiation therapy has been shown to improve survival in malignant glioma, but not in asymptomatic low grade tumors. Chemotherapy has a modest efficacy in glioblastomas, whereas oligodendrogliomas with 1p 19q deletion are chemosensitive tumors.

Age Factors↗
PubMed2004

Analysis of the bHLH transcription factors Olig1 and Olig2 in brain tumors.

In the absence of specific markers, the histological diagnosis of oligodendroglial tumors is based on subjective qualitative criteria and remains controversial. Recently, two bHLH transcription factors involved in oligodendroglial specification, Olig1 and Olig2 have been proposed as potential markers of oligodendrogliomas. Expression of Olig1/2 was analyzed by in situ hybridization on 78 samples including 47 glial, 29 non-glial tumors, and two non-tumoral brain tissues. Both genes had a similar pattern of expression. Olig1 and Olig2 were expressed in 26/30 (87%) and 28/30 (93%) of oligodendroglial tumors respectively but in only 9% of glioblastomas (1/11). Olig genes were also expressed in the low-grade fibrillary astrocytomas (4/4) and anaplastic astrocytomas (2/2). No expression was found in non-glial tumors, except for one primary cerebral lymphoma. Double staining with PLP, NFH, GFAP showed that olig genes were expressed by mature, non-tumoral oligodendrocytes, but not by normal astrocytes or neurones. This study indicates that Olig1/2 expression clearly distinguishes pure Olig-negative glioblastomas from a wide spectrum of Olig-positive tumors including traditional oligodendrogliomas and oligoastrocytomas, glioblastomas with an oligodendroglial component (GBMO), and WHO grade 2 and 3 astrocytomas. Because Olig genes have a crucial role in oligodendroglial determination, our data could be of help in defining the real spectrum of oligodendroglial tumors.

Astrocytes↗
PubMed2004

Loss of 14q chromosome in oligodendroglial and astrocytic tumors.

Loss of chromosome 14q has been investigated in 142 gliomas. Loss of heterozygosity (LOH) at one or more microsatellite has been found in 8/30 grade II (27%) and 2/21 grade III (10%) oligodendrogliomas, 3/9 grade II (33%) and 5/15 grade III (33%) oligoastrocytomas, 0/9 grade II (0%) and 1/7 grade III (14%) astrocytomas, 11/51 glioblastomas (22%). Two minimal regions were identified on 14q21.2-14q24.3 (between D14S288 and D14S74) and 14q31.3-14q32.1 (between D14S74 and D14S65). Loss of 14q was not correlated to survival, histological grading and subtype or other genetic alterations, except for 1p deletions. Taken together, these data suggest that LOH14q is an early alteration involving 20% of glioma.

Astrocytoma↗
PubMed2004

Palliative care in patients with primary brain tumors.

PURPOSE OF REVIEW: Because patients with primary brain tumors often present severe functional impairment as well as behavioral/cognitive dysfunction, they suffer from greater dependency and hopelessness than other cancer patients. Optimal management should not only focus on symptom relief through medication and physiotherapy, but should also take into account the psychosocial burden of the disease on the patients and their caregivers. This review updates available data on supportive care in patients with brain tumor. RECENT FINDINGS: Recent improvements have been made in the management of several complications of brain tumor: pain, epilepsy, and side effects of antiepileptic drugs; disability and related thromboembolic complications; cognitive disorders of mixed (tumoral and/or iatrogenic) origin; side effects of steroids; fatigue; and psychological consequences of the disease. SUMMARY: Avoiding useless "overtreatment" is the governing idea. A very thorough evaluation of the benefit/risk ratios is needed each time a new treatment is being considered. Brain tumor patients are particularly prone to develop severe side effects, increased fatigue, and cognitive deterioration following apparently minor changes in symptomatic treatments. Care is also needed to avoid useless prolongation of a burdensome situation. Another issue is that patients and their caregivers should benefit from the support of a multidisciplinary team to maintain realistic hopes and to anticipate critical decisions. Finally, guidelines from the literature are proposed to improve physicians' communication skills when treating these patients.

Brain Neoplasms↗
PubMed2004

Oxaliplatin plus irinotecan and FU-FOL combination and pharmacokinetic analysis in advanced colorectal cancer patients.

This phase I-II trial was designed to assess the effect of irinotecan on oxaliplatin pharmacokinetics and to determine the MDT of both drugs when administered in combination. Treatment was repeated every 2 weeks. Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best sequence and detect any interaction between the two drugs. Thirty-four patients with advanced colorectal cancer were enrolled; 28 of them (82%) had liver involvement. The main toxicities were neutropenia and delayed diarrhea; 5 patients (14%) experienced febrile neutropenia. Dose-limiting toxicity was experienced at levels 1/2/3/4/5 by 4/10, 1/6, 3/6, 3/8, and 3/4 patients, respectively. Fifteen patients responded (2 CR; 13 PR) for an ORR of 44%. No pharmacokinetic interactions between irinotecan and oxaliplatin were detected. The recommended dose for future phase II trials is oxaliplatin 85 mg/m and irinotecan 180 mg/m2 on day 1 combined with 5FU/leucovorin according to the de Gramont regimen at days 2 and 3. Twenty-nine percent of patients underwent secondary hepatectomy with curative intent, and two of them are long-term disease-free survivors. It would appear that the dose and schedule defined by this trial could be proposed as front-line therapy for advanced colorectal carcinoma to establish rapid disease control and to permit patients to proceed to surgery.

Adult↗
PubMed2004

Prognostic value of allelic losses and telomerase activity in meningiomas.

OBJECT: The goal of this study was to examine allelic losses and telomerase activity in meningiomas to determine whether they could be used to predict disease recurrence. METHODS: To identify predictive markers of recurrence, a cohort of high-grade (24 World Health Organization [WHO] Grade II and six WHO Grade III) and low-grade (21 WHO Grade I) meningiomas was investigated for losses of heterozygosity (LOHs) on chromosomes 1p, 9p, 10q, 14q, and 22q, a deletion of CDKN2A, and telomerase activity. Results of molecular analyses were compared with radiological and histological findings and progression-free survival (PFS). Losses of heterozygosity on chromosomes 22q, 1p, and 10q, as well as telomerase activity were related to the WHO histological grades of the lesions (p < 0.01, p < 10(-5), p < 10(-4), and p = 0.002, respectively). In the absence of an LOH on 22q, the other alterations were found infrequently. Overall, the number of molecular alterations was closely related to the histological grades of the lesions (p < 10(-6)). An LOH on 22q occurred much more frequently in convexity or falx (33 [87%] of 38 lesions) than in skull base or spinal meningiomas (four [31%] of 13 lesions) (p < 0.001). The histological grade; Simpson grade; an LOH on chromosome 1p, 9p, or 10q; and telomerase activity were correlated with a shorter PFS time (p < 10(-4), p = 0.02, p = 0.000365, p = 0.022, p = 0.00027, and p = 0.000512, respectively). CONCLUSIONS: On the basis of these data the authors suggest that LOH analysis and a telomerase activity assay could be useful to determine molecular predictors of outcome in patients with meningiomas.

Adult↗
PubMed2002

Metastatic melanoma: chemotherapy.

The incidence of cutaneous melanoma has been rapidly increasing, with an estimate of 47,700 new cases diagnosed in 2000 in the United States. In the early phase of its natural history, melanoma is cured in most cases by surgery, but once the metastatic phase develops, it is almost always fatal. The treatment of metastatic melanoma remains unsatisfactory. Systemic therapy has not been successful up to now, with very low response rates to single-agent chemotherapy. Polychemotherapy has increased the response rate (RR), without a significant improvement in overall survival. Immunotherapy alone is able to induce only a few durable complete responses (CRs). New chemotherapeutic and biologic agents are now available and promising combined approaches targeting the tumor by several different mechanisms are desirable and will probably represent the future modality of treatment.

Antineoplastic Agents↗