Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database.

BACKGROUND: Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. METHODS: The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan-Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. RESULTS: Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. CONCLUSIONS: MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used.

Descriptive epidemiology of 13,038 newly diagnosed and histologically confirmed meningiomas in France: 2006-2010.

PURPOSE: This work describes the clinical epidemiology and pathology for patients undergoing surgery for newly diagnosed meningiomas in France between 2006 and 2010. METHODS: The methodology is based on a multidisciplinary national network previously established by the French Brain Tumor DataBase (FBTDB) (in French: Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the scientific societies involved in neuro-oncology in France. RESULTS: From 2006 to 2010, 13,038 incident cases of meningioma with histological validation were identified and analyzed (9769 women, 3269 men, resection 98.2%, cryopreservation 20.5%). For each histological subtype of meningioma (meningothelial, fibrous, transitional, psammomatous, angiomatous, rare variety, microcystic, secretory, lymphoplasmacyte-rich, clear-cell, chordoid, rhabdoid, metaplastic, atypical, papillary, anaplastic and not otherwise specified), number of cases, sex, median age, cryopreservation and surgery were reported. Among the various histological subtypes, atypical meningioma (grade II) slightly, but significantly, increased after 2007. Headache, sensory-motor impairments and seizures were the most frequent clinical symptoms. Time between the first clinical symptom and surgery ranged from 0 to 314 months, and was <3 months in 37% of cases. At the time of surgery, 9% of patients were asymptomatic. DISCUSSION/CONCLUSION: Given the number of meningiomas not histologically-validated, we can estimate that the gross incidence rate for meningiomas operated in France is about 4.2 per 100,000 person/year. To our knowledge, this work is the most important study evaluating the different subtypes of meningiomas and it validates the relevance of histological databases for central nervous system tumors.

Paroxysmal hypothermia in two patients with multiple sclerosis.

BACKGROUND: Hypothermia is a rare condition in patients with multiple sclerosis (MS). Only 17 patients have been reported so far. CASE REPORT: We report 2 patients with a long history of MS who presented with severe acute hypothermia associated with thrombocytopenia and hepatic cytolysis. Both patients presented with an aggravation of their neurological status, psychomotor slowing and confusion. There was no clinical or biological sign of infection. Magnetic resonance imaging (1.5 T) revealed bilateral preoptic T(2)-weighted lesions for 1 patient. The neurological status of one patient was worse after the episode of hypothermia than before, which suggests that hypothermia could be a factor of poor prognosis concerning disease progression.

[French brain tumor database: general results on 40,000 cases, main current applications and future prospects]. / Recensement national histologique des tumeurs primitives du système nerveux central : résultats généraux sur 40 000 cas, principales applications actuelles et perspectives.

BACKGROUND AND PURPOSE: This work aimed at prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis was available. The objectives were to (i) create a national database and network to perform epidemiological studies, (ii) implement clinical and basic research protocols, and (iii) harmonize the health care of patients affected by PCNST. METHODS: The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase (FBTDB) (Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the Scientific Societies involved in neuro-oncology in France. RESULTS: From 2004 to 2009, 43,929 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included gliomas (42,4%), all other neuroepithelial tumors (4,4%), tumors of the meninges (32,3%), nerve sheath tumors (9,2%), lymphomas (3,4%) and others (8,3%). Cryopreservation was reported for 9603 PCNST specimens. Tumor resections were performed in 78% cases, while biopsies accounted for 22%. Median age at diagnosis, sex, percentage of resections and number of cryopreserved tumors were detailed for each histology, according to the WHO classification. DISCUSSION/CONCLUSION: Many current applications and perspectives for the FBTDB are illustrated in the discussion. To our knowledge, this work is the first database in Europe, dedicated to PCNST, including clinical, surgical and histological data (with also cryopreservation of the specimens), and which may have major epidemiological, clinical and research implications.

[Hypothalamic involvement in multiple sclerosis]. / Atteintes hypothalamiques dans la sclérose en plaques.

Hypothalamic involvement is a rare condition in patients with multiple sclerosis (MS). We report two patients with a long history of MS who presented with severe acute hypothermia with associated thrombocytopenia and elevated transaminase levels. Several cases of hypothermia or hyperthermia in patients with MS have been reported in the literature. They could be linked with hypothalamic lesions, in particular in the pre-optic area. However, other anatomical locations seem to be involved in thermoregulation and can be affected by MS. Besides, some cases of syndrome of inappropriate antidiuretic hormone secretion have been reported in patients with MS. Finally, some sleep disorders, particularly hypersomnia or narcolepsy, could be related to hypothalamic lesions, through the fall in hypocretin-1 in the cerebrospinal fluid. Hypocretin-1 is a neuropeptide that is secreted by some hypothalamic cells. It plays a role in the sleep-awake rhythm. We report one patient with narcolepsy and cataplexy before the first symptoms of MS appeared. Hypothalamic signs are rare in MS. However, several series of autopsies have shown a high frequency of demyelinating lesions in the hypothalamic area. Among these lesions, the proportion of active lesions seems elevated. Yet only few of them have a clinical or biological translation such as thermoregulation dysfunction, sleep disorders or natremia abnormalities. Thus, it seems unlikely that inflammatory hypothalamic lesions alone, even when bilateral, could be the explanation of these signs. A sufficient number of inflammatory demyelinating lesions, which we can observe in patients with a long history of MS and an already severe disability, is probably necessary to develop such a rare symptomatology. Hypothalamic signs might be a factor of poor prognosis for the disease course and progression of the disability.

Supportive care in neurooncology.

The quality of life of patients treated for brain tumor is, in all cases, deeply altered by the tumor and the treatments. Optimizing the symptomatic management is a key objective for all care givers. We present in this paper a very pragmatic focus concerning the management of intracranial hypertension (and/or neurological deficits), venous thromboembolism, confusion, epilepsy and symptoms more directly associated with the end of life.