Molecular and clinical diversity in primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.

Characteristics of IDH-mutant gliomas with non-canonical IDH mutation.

BACKGROUND: Approximately 10% of IDH-mutant gliomas harbour non-canonical IDH mutations (non-p.R132H IDH1 and IDH2 mutations). OBJECTIVE: The aim of this study was to analyse the characteristics of non-canonical IDH-mutant gliomas. MATERIALS AND METHODS: We retrospectively analysed the characteristics of 166 patients with non-canonical IDH mutant gliomas and compared them to those of 155 consecutive patients with IDH1 p.R132H mutant gliomas. RESULTS: The median age at diagnosis was 38 years in patients with non-canonical IDH mutant gliomas and 43 years in glioma patients with IDH1 p.R132H-mutant tumours. Family history of cancer was more frequent among glioma patients harbouring non-canonical IDH mutations than in patients with IDH1 p.R132H mutations (22.2% vs 5.1%; P < 0.05). Tumours were predominantly localised in the frontal lobe regardless of the type of IDH mutation. Compared to IDH1 p.R132H-mutant gliomas, tumours with non-canonical IDH mutations were more frequently found in the infratentorial region (5.5% vs 0%; P < 0.05) and were often multicentric (4.8% vs 0.9%; P < 0.05). Compared to IDH1 P.R132H-mutant gliomas, tumours with non-canonical IDH1 mutations were more frequently astrocytomas (65.6% vs 43%, P < 0.05), while those with IDH2 mutations were more frequently oligodendrogliomas (85% vs 48.3%; P < 0.05). The median overall survival was similar in patients with IDH1 p.R132H-mutant gliomas and patients with non-canonical IDH-mutant gliomas. CONCLUSION: Gliomas with non-canonical IDH mutations have distinct radiological and histological characteristics. The presence of such tumours seems to be associated with genetic predisposition to cancer development.

Advanced multiparametric magnetic resonance imaging of multinodular and vacuolating neuronal tumor.

BACKGROUND AND PURPOSE: Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare brain lesion with suggestive imaging features. The aim of our study was to report the largest series of MVNTs so far and to evaluate the utility of advanced multiparametric magnetic resonance (MR) techniques. METHODS: This multicenter retrospective study was approved by our institutional research ethics board. From July 2014 to May 2019, two radiologists read in consensus the MR examinations of patients presenting with a lesion suggestive of an MVNT. They analyzed the lesions' MR characteristics on structural images and advanced multiparametric MR imaging. RESULTS: A total of 64 patients (29 women and 35 men, mean age 44.2 ± 15.1 years) from 25 centers were included. Lesions were all hyperintense on fluid-attenuated inversion recovery and T2-weighted imaging without post-contrast enhancement. The median relative apparent diffusion coefficient on diffusion-weighted imaging was 1.13 [interquartile range (IQR), 0.2]. Perfusion-weighted imaging showed no increase in perfusion, with a relative cerebral blood volume of 1.02 (IQR, 0.05) and a relative cerebral blood flow of 1.01 (IQR, 0.08). MR spectroscopy showed no abnormal peaks. Median follow-up was 2 (IQR, 1.2) years, without any changes in size. CONCLUSIONS: A comprehensive characterization protocol including advanced multiparametric magnetic resonance imaging sequences showed no imaging patterns suggestive of malignancy in MVNTs. It might be useful to better characterize MVNTs.

Progestin-associated shift of meningioma mutational landscape.

Background: Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated. Patients and methods: We identified 40 female patients operated for a meningioma after long-term progestin therapy and performed targeted next generation sequencing to decipher the mutational landscape of hormone-related meningiomas. A published cohort of 530 meningiomas in women was used as a reference population. Results: Compared with the control population of meningiomas in women, progestin-associated meningiomas were more frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001]. Conclusion: This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma.

BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. RESULTS: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. CONCLUSION: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.

Descriptive epidemiology and risk factors of primary central nervous system tumors: Current knowledge.

Although comparisons are difficult due to differences in methodologies, the annual incidence rates of central nervous system (CNS) tumors range from 8.5 to 21.4/100,000 population according to cancer registries, with a predominance of neuroepithelial tumors in men and meningiomas in women. An increase in the incidence of CNS tumors has been observed during the past decades in several countries. It has been suggested that this trend could be due to aging of the population, and improvements in diagnostic imaging and healthcare access, but these factors do not explain differences in incidence by gender and histological subtypes. Several etiological hypotheses related to intrinsic (sociodemographic, anthropometric, hormonal, immunological, genetic) and exogenous (ionizing radiation, electromagnetic fields, diet, infections, pesticides, drugs) risk factors have led to analytical epidemiological studies to establish relationships with CNS tumors. The only established environmental risk factor for CNS tumors is ionizing radiation exposure. However, for other risk factors, studies have been inconsistent and inconclusive due to systematic differences in study design and difficulties in accurately measuring exposures. Thus, the etiology of CNS tumors is complex and may involve several genetic and/or environmental factors that may act differently according to histological subtype.

[Prospective longitudinal study on the evolution of autobiographical memory in patients irradiated for benign skull base tumour]. / Étude prospective longitudinale sur l'évolution de la mémoire autobiographique de patients irradiés pour une tumeur bénigne de la base du crâne.

PURPOSE: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory. PATIENTS AND METHODS: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability. RESULTS: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study. CONCLUSION: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

Molecular cytogenetic aberrations in Tunisian patients with multiple myeloma identified by cIg-FISH in fixed bone marrow cells.

Cytogenetic studies in multiple myeloma (MM) are hampered by the hypo-proliferative nature of plasma cells. In order to circumvent this problem, we have used a combination of immunolabeling of cytoplasmic Ig light chains (λ or κ) and FISH (cIg-FISH), which allowed a comprehensive detection of the most common and/or recurrent molecular cytogenetic aberrations on fixed bone marrow cells of 70 Tunisian patients. Translocations involving the chromosome 14q32 region were observed in 32 cases (45.7%), including 18 cases with a t(11;14), 8 cases with a t(4;14), and 2 cases with a t(14;16). Deletions of the 13q14 region (D13S319/RB1) were detected in 18.6%, and deletions of the 17p13 region (TP53) in 5.7% of the cases, respectively. Of all patients with a D13S319/RB1 deletion, 61.5% also carried a 14q32 translocation, whereas TP53 deletions were associated with a t(11;14) in 2 cases (50%) and a D13S319 deletion in 1 case (25%). Our results suggest that there is a correlation between the presence of 14q32 translocations and chromosome 13q14 deletions in MM patients and that cIg-FISH is more sensitive as compared to conventional karyotyping in detecting molecular cytogenetic abnormalities in this disease.

[Performance evaluation of hospital claims database for the identification of incident central nervous system tumors compared with a cancer registry in Gironde, France, 2004]. / Évaluation des performances du PMSI pour l'identification des tumeurs incidentes du système nerveux central par rapport à un registre spécialisé en Gironde, France, en 2004.

BACKGROUND: Cancer registries cover 18% of the French population. A national surveillance might be warranted for some potentially environment-related cancers such as tumors of the central nervous system (CNS) to detect abnormal incidence variations. The PMSI database provides an interesting source of comprehensive, standardized and mandatory data collected from all health facilities. The aim of this work was to develop methods to identify incident CNS tumors using the PMSI database. METHODS: A selection of patients living in Gironde was made in the 2004 PMSI database of the hospital of Bordeaux, using the CNS tumors codification. Cases were validated via the CNS primary tumor registry of Gironde taken as the reference, or medical records. Various combinations of criteria were defined and tested. RESULTS: The first selection based on diagnoses identified patients with a sensitivity of 84% and a positive predictive value (PPV) of 34%. Patients wrongly identified by the PMSI were non-incident cases (49%) or patients without a CNS tumor (45%). Patients with a tumor not identified by the PMSI had been hospitalized in 2005 (44%) or had no code for CNS tumor (42%). According to the algorithms, the sensitivity ranged from 64% to 84%, and the PPV from 34% to 69%. The best combination had a sensitivity of 67% and a PPV of 69% and was obtained with codes for CNS tumor in 2004 associated with a diagnostic or therapeutic code for persons under 70 years without code for CNS tumor in previous years or code for metastasis in 2004. CONCLUSION: According to these results, the PMSI database cannot be used alone to calculate the incidence of these complex tumors. However the PMSI database plays an important role in cancer surveillance, in combination with other information sources and the expertise of cancer registries. This role could increase with further reflection and improvement of data quality.

Second Impact Syndrome. Myth or reality?

INTRODUCTION: Second impact syndrome (SIS) is a devastating condition occurring in sport-induced mild brain injury. SIS is drastically defined by anamnestic, clinical and radiological criteria, which is unusual in the field of cranial traumatology. The purpose of this study was to provide a literature review of this syndrome. MATERIAL AND METHODS: We conducted a literature review of all published studies on PubMed. The keywords were "second impact syndrome and catastrophic head injury", "second impact syndrome and sport", "repeat concussion and catastrophic brain injury", "catastrophic head injury and concussion", "catastrophic head injury", "concussion and second impact syndrome", "concussion and repetitive head injury". RESULTS: Eighty-two full-text articles were assessed for eligibility. Finally, 41 studies were included in qualitative synthesis and 21 were included in quantitative synthesis. DISCUSSION: The number of cases reported in the literature was extremely small compared to the population at risk, i.e., the number of athletes exposed to repeated concussions. SIS was similar to talk and die syndrome, with which it shares certain characteristics. If we consider SIS according to "talk and deteriorate tables", it opens up interesting perspectives because they are specific in children and adolescents. Taking into account the scarcity of this syndrome, one may question whether athlete-intrinsic features may be involved in at least some cases of SIS. On a pathophysiological level, many explanations remained unsatisfactory because they were unable to explain all the clinical phenomena and observed lesions. Triggering the trigeminocardiac reflex is a crucial element in explaining the sequence of clinical events. Its association with a state of neurogenic inflammation provides an almost complete explanation for this particular condition. Finally, on a practical level, a concussion occurring during the playing of a sport must be considered as any other injury before allowing a return to play.

WHO grade II meningioma: Epidemiology, survival and contribution of postoperative radiotherapy in a multicenter cohort of 88 patients.

BACKGROUND: Meningioma is the most common primary intracranial tumor, representing 13-36.6% of all primary central nervous system tumors. Meningiomas are benign in about 90% of cases. World Health Organization (WHO) grade II meningioma is associated with a high rate of recurrence and poorer survival than in grade I. The reference treatment is surgery, which should be as complete as possible. Currently, in grade II, there are no recommendations for systematic adjuvant treatment such as radiotherapy. We studied a homogeneous series of grade II meningiomas treated by surgery in two university hospital centers to analyze use of radiotherapy and its efficacy. METHODS: We retrospectively analyzed patients in our database with WHO grade II meningioma, operated on between 2007 and 2010 in the university hospitals of Montpellier and Bordeaux, France. Clinical and radiological data, treatments and survival were analyzed. RESULTS: Eighty-eight patients were included. Five-year overall survival was 89.7%. Nineteen patients received radiotherapy during follow-up, without significant impact on survival (P=0.27). CONCLUSION: In WHO grade II meningioma, it is currently difficult to establish clear recommendations for radiotherapy. The present study is in accordance with the literature that early postoperative radiotherapy is not mandatory in grade II meningioma with macroscopically total resection.

[Epidemiology of primary brain tumor]. / Epidémiologie des tumeurs cérébrales primitives.

Two main approaches are generally used to study the epidemiology of primary brain tumors. The first approach is to identify risk factors, which may be intrinsic or related to external causes. The second main approach is descriptive. Intrinsic factors potentially affecting risk include genetic predisposition and susceptibility, gender, race, birth weight and allergy. Radiation exposure is the main extrinsic factor affecting risk. A large body of work devoted, among others, to electromagnetic fields and especially cellular phones, substitutive hormonal therapy, pesticides, and diet have been published. To date, results have been discordant. Descriptive epidemiological studies have reported an increasing annual incidence of primary brain tumors in industrialized countries. The main reasons are the increasing age of the population and better access to diagnostic imaging. Comparing incidences from one registry to another is difficult. Spatial and temporal variations constitute one explanation and evolutions in coding methods another. In all registries, weak incidence of primary brain tumors constitute a very important limiting factor. Renewed interest from the neuro-oncological community is needed to obtain pertinent and essential data which could facilitate improved knowledge on this topic.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

[Radiation therapy for glial tumors: technical aspects and clinical indications]. / Radiothérapie des tumeurs gliales: techniques et indications.

Radiotherapy of glial tumors is rapidly evolving with the recent technical and therapeutic progress. About technical aspects, progress in technical imaging and development of non-coplanar conformal and IMRT techniques provide new possibilities for sparing healthy tissue while increasing dose in tumoral volume. Furthermore, functional and molecular imaging are helpful for delineation and for prediction of relapse. Even modest, the actual improvement of survival with radiochemotherapy leads now to new and important developments for clinical research according to clinical data (age, general status), biological data (MGMT promotor methylation and cytogenetic modifications) and technical data (quality of surgery and radiotherapy). Understanding of molecular mechanisms allows for rational targeting or specific pathways of repair, signaling angiogenesis associated with surgery and radiotherapy in a multidisciplinary approach.

[Spinal meningioma surgery after 75 years of age]. / La chirurgie des méningiomes rachidiens après 75 ans.

BACKGROUND AND PURPOSE: Spinal meningioma surgery is usually not difficult and is commonly associated with good outcome. However, advanced age and severe neurological deficit have been considered to be predictors of poor surgical outcome. Therefore, we attempted to assess the surgical outcome of spinal meningiomas in the elderly and to analyze the role of outcome predictors. METHODS: From 1990 to 2006, 32 patients 76 years or older with spinal meningiomas were operated on in our Neurosurgery Departments. All patients had MRI. Neurological status was assessed using the Solero score. Neurological evaluations were conducted three months and one year after surgery. The mean follow-up was 36 months. A multiple logistic regression was applied to establish the relationship between the risk factors and outcome. RESULTS: The median age was 79.3 years. The mean duration of symptoms until surgery was 12.7 months. One patient was rated Solero grade I, 11 grade II, 17 grade III and three patients were rated grade IV. Radical tumor removal was performed in 30 patients (94%). All meningiomas were benign. There was no recurrence, morbidity was 9%, and 1-year mortality was 0%. One year after surgery, all patients had improved, 56 % had recovered completely. Among 20 patients with severe paraparesis or paraplegia, 30 % had recovered completely. There was no statistical correlation between outcome and various risk factors: age, gender, ASA, tumor size, quality of tumor removal, and location. Only preoperative Solero score and duration of symptoms before surgery were statistically significant. CONCLUSIONS: Surgery is the only treatment of symptomatic spinal meningioma. Advanced age did not seem to contraindicate surgery, even in those with severe preoperative neurological deficits, because quality of life can be improved in the vast majority of cases. There was a correlation between duration and severity of deficit and outcome.

Epidemiology of meningiomas.

Although they represent about a third of all the tumors of the central nervous system, knowledge concerning meningioma epidemiology (including incidence data and exploration of the risk factors) remains scarce compared to that of gliomas. A limited number of cancer registries worldwide only record malignant brain tumors, however their completeness and accuracy have been questioned. Even if comparisons are made difficult due to differences in methodologies, available annual incidence rates (sex- and age-standardized, generally on US or World standard population), provided by population-based registries range from 1.3/100,000 to 7.8/100,000 for cerebral meningiomas. An increase in the incidence of primary brain tumors in general and of meningiomas in particular has been observed during the past decades in several countries. It has been suggested that this trend could be artefactual and could be the resultant of an ageing population, improvement in health access and in diagnostic procedures, changes in coding classification for tumors recorded in registries, and/or an increase in the rate of histological confirmation, even in the elderly. All these factors are likely to play a role but they might not fully explain the increase in incidence, observed in most age groups. In addition to intrinsic risk factors (gender, ethnic groups, allergic conditions, familial and personal history, genetic polymorphisms), some exogenous risk factors have been suspected to play a role in the etiology of meningiomas and their changes with time is likely to impact incidence trends. A causal link has been established only for ionising radiation but the role of many other factors have been hypothesised: electromagnetic fields, nutrition, pesticides, hormonal as well as reproductive factors. Considering the serious or even lethal potentiality of some meningiomas and the apparent rise in their incidence, all practitioners involved in neuro-oncology should feel concerned today of the necessity to better assess their public health burden and to study their epidemiological features.

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.

Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients.

Novel anti-myeloma agents have improved patient response rates, which are historically based on reductions of the M-protein. These methods can be inaccurate for quantifying M-proteins at low concentrations. We compared the consistency and clinical impact of response assignment by electrophoretic and heavy+light chain (HLC) immunoassays post-consolidation in 463 newly diagnosed patients. The two methods gave similar assignments in patients with partial (PR; 79% agreement) or complete response (⩾CR; 92%). However, in patients achieving very good PR (VGPR) there was poor concordance between methods (45%). Median progression-free survival (PFS) for standard VGPR patients was 34.5 months; HLC responses stratified these patients further into PR, VGPR and ⩾CR, with median PFS of 21.3, 28.9 months and not reached, respectively; P<0.001. At this time, abnormal HLC ratios had better concordance with multiparametric flow cytometry (sensitivity 10-4) (37 and 34% positive, respectively), compared to immunofixation (62% positive). In addition, HLC-pair suppression was identified in 38% of patients and associated with shorter PFS (30.6 months vs not reached; P<0.001). We conclude that HLC monitoring could augment electrophoretic assessments in patients achieving VGPR. The prognostic significance of HLC responses might partly depend on the patients' ability to recover their immune system, as determined by normalisation of HLC measurements.