Search

International audience; The origins of diffuse low-grade gliomas (DLGG) are unknown. Beyond some limited data on their temporal and cellular origins, the mechanisms and risk factors involved are poorly known. First, based on strong relationships between DLGG development and the eloquence of brain regions frequently invaded by these tumors, we propose a "functional theory" to explain the origin of DLGG. Second, the biological pathways involved in DLGG genesis may differ according to tumor location (anatomo-molecular correlations). The cellular and molecular mechanisms of such "molecular theory" will be reviewed. Third, the geographical distribution of diffuse WHO grade II-III gliomas within populations is heterogeneous, suggesting possible environmental risk factors. We will discuss this "environmental theory". Finally, we will summarize the current knowledge on genetic susceptibility in gliomas ("genetic predisposition theory"). These crucial issues illustrate the close relationships between the pathophysiology of gliomagenesis, the anatomo-functional organization of the brain, and personalized management of DLGG patients.

The improved understanding of the natural course of diffuse low-grade gliomas (DLGG) has allowed a paradigmatic shift in their management, from a “wait-and-see” attitude to an early, individualized and dynamic therapeutic strategy. However, optimization of this management requires a better understanding the origins of DLGG. To date, the origins and etiologic factors of DLGG are mostly unknown. Beyond some data, yet limited, regarding the temporal and the cellular origins of DLGG, the mechanisms and risk factors involved in DLGG are poorly known. A way to better understand the mechanisms involved in the genesis of DLGG is to study their spatial distribution, both within the brain and at the geographical level. Indeed, some hypotheses regarding the mechanisms involved may be speculated from these distributions. It is interesting to note that DLGG have preferential locations within the brain, mostly within the so-called “functional areas”. On the basis of strong relationships between DLGG development and the eloquence of brain regions frequently invaded by these tumors, we propose a “functional theory” to explain the origin of DLGG. In addition, it can be hypothesized that the biological pathways involved in the genesis of DLGG may differ according to the tumor location, as anatomo-molecular studies showed significant correlations between the DLGG locations and tumor genetics, with a higher rate of IDH mutation and 1p19q codeletion in frontal tumors. The cellular and molecular mechanisms of such “molecular theory” will be reviewed in the present chapter. It is also interesting to note that the geographical distribution of diffuse WHO grade II and grade III gliomas is heterogeneous at the international and national levels, suggesting possible environmental risk factors. We will thus also discuss this “environmental theory". Finally, we will briefly summarize the current knowledge on genetic susceptibility in gliomas. All of these crucial issues very well illustrate the close relationships between the pathophysiology of gliomagenesis, the anatomo-functional organization of the brain, and personalized management of DLGG patients.

Diffuse WHO grade II and III gliomas (DGII/IIIG) are rare tumors, with few specific epidemiological studies. We aimed at describing the geographical distribution of a homogeneous series of histologically confirmed DGII/IIIG, over a four-year period (2006-2009), at a national level. The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase and data collected directly from every neuropathology department. Personal home addresses were collected for confirmed cases. For each region, the incidence of DGII/IIIG was analyzed and standardized on the age and sex distribution of the French population. The number of patients with newly diagnosed, histologically confirmed DGII/IIIG was 4,790. The overall crude rate was 19.4/10(6). To enable international comparisons, standardized rates were calculated as follows: 19.8/10(6), 18.8/10(6) and 16.0/10(6) (reference population, Europe, US and world, respectively). The geographical distribution by region showed significant differences, with higher incidence rates in Northeast and central parts of France. This work is the first studying the geographical distribution of a pure series of DGII/IIIG at a national level. It demonstrates significant heterogeneity in the distribution, and raises the question of the role of environmental and/or genetic risk(s) factor(s) for DGII/IIIG.

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155–280]; B-CRC n = 21, 318[166–480]; B-RT n = 37, 149[130–214]; RS-CT n = 11, 245[211–na]; RS-CRC n = 18, 372[349–593]; RS-RT n = 39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients

The involvement of eloquent brain areas may preclude the total/subtotal surgical resection of diffuse low-grade gliomas (DLGGs). The feasibility and functional tolerance of neoadjuvant chemotherapy have been demonstrated in such cases. The present study assesses the clinical and radiological impact of neoadjuvant chemotherapy on the natural course of DLGG. Seventeen patients without feasible surgical resection (infiltration of functional areas and/or large contralateral extension) were retrospectively selected. Temozolomide based neoadjuvant chemotherapy was initiated, inducing a tumor volume decrease and allowing a functional based maximal surgical resection. The median follow-up since initial radiological diagnosis was 5.9 years (range, 1.4–11). The median time to malignant transformation was 5.9 years. Six patients (35 %) had 1p19q codeletion, 12 patients (70 %) with IDH mutation and MGMT promoter methylation, and eight patients (47 %) had p53 overexpression. Chemotherapy reduced tumor volume (median −35.6 %, range −61.6 to −5.1 %) in contralateral hemisphere through the corpus callosum in seven cases (41 %) and in ipsi-lesional functional areas in ten cases (59 %). Chemotherapy significantly decreased the imaging tumor growth (measured by the velocity of diametric expansion VDE) with a median of −3.2 mm/year (range, −29.8 to −0.9 mm/year) (p < 0.001). A tumor volume decrease of more than 20 % was correlated with a lower postoperative residual tumor (median 2 cc, p = 0.04), a greater extent of resection (93.1 vs. 89.5 %), a higher probability of total/subtotal removal. Neoadjuvant chemotherapy with Temozolomide could optimize the surgical resection of DLGGs and could impact their natural history. Further large prospective studies with long-term follow-up are needed.

International audience; Breast cancer (BC) is the second most common cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM. Elevated serum S100ß protein and neuron-specific enolase (NSE) could reflect the brain damages induced by BM. Matrix metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Also, HER2-amplified BC were shown to have a particular tropism for central nervous system (CNS). This study evaluated the correlation of these biomarkers with the presence of BM in metastatic BC patients. In this case-control study, 88 consecutive metastatic BC patients with BM (BM group) treated in our institution (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor marker determination. Patients were matched by age, tumor biology and number of previous metastatic chemotherapy lines to 162 metastatic BC patients without CNS involvement (control group). Serum NSE, MMP-9 and HER2 extracellular domain (ECD) levels were significantly higher in the BM group (p = 0.0051, p = 0.0062 and p = 0.0057, respectively). In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated patients with BM: odds ratios 4.4 (p < 0.001; 95%CI: 1.9-9.6) for HER2 ECD and 3.5 (p = 0.005; 95%CI: 1.5-8.4) for MMP-9. In multivariate analysis, HER2 ECD and NSE serum levels were independent prognostic factors in patients with BM. Serum HER2 ECD and MMP-9 appear to be associated with BM in metastatic BC patients. Their predictive value for BM still needs to be evaluated in further prospective studies.

International audience; Cet article s’intéresse au rôle de la conscience autonoétique, celle qui permet le voyage mental dans le temps. Cette conscience joue un rôle central dans la qualité de vie de patients souffrant de métastases cérébrales (MC). L’article explore deux déclinaisons du voyage mental, la mémoire prospective et la perspective temporelle, à travers un regard neuropsychologique et psychologique. L’article propose des perspectives de recherches cliniques et de prises en charge pour ces patients.

International audience; Diffuse WHO grade II gliomas are diffusively infiltrative brain tumors characterized by an unavoidable anaplastic transformation. Their management is strongly dependent on their location in the brain due to interactions with functional regions and potential differences in molecular biology. In this paper, we present the construction of a probabilistic atlas mapping the preferential locations of diffuse WHO grade II gliomas in the brain. This is carried out through a sparse graph whose nodes correspond to clusters of tumors clustered together based on their spatial proximity. The interest of such an atlas is illustrated via two applications. The first one correlates tumor location with the patient's age via a statistical analysis, highlighting the interest of the atlas for studying the origins and behavior of the tumors. The second exploits the fact that the tumors have preferential locations for automatic segmentation. Through a coupled decomposed Markov Random Field model, the atlas guides the segmentation process, and characterizes which preferential location the tumor belongs to and consequently which behavior it could be associated to. Leave-one-out cross validation experiments on a large database highlight the robustness of the graph, and yield promising segmentation results.

Resume Les manifestations d’origine hypothalamique sont rares dans la sclerose en plaques (SEP). Nous rapportons deux cas d’hypothermie associee a une thrombopenie et a une cytolyse hepatique chez des patients avec une longue histoire de SEP. Plusieurs cas de dysregulation thermique (hypothermie ou hyperthermie) chez des patients atteints de SEP ont deja ete rapportes dans la litterature. Ces manifestations pourraient etre en lien avec une atteinte hypothalamique, notamment dans la region preoptique. Cependant, d’autres localisations anatomiques semblent egalement impliquees dans la thermoregulation et peuvent etre atteintes dans la SEP. Par ailleurs, des cas d’hyponatremie par syndrome de secretion inappropriee d’hormone antidiuretique (SIADH) ont ete rapportes dans la litterature. Enfin, certains troubles du sommeil, et notamment l’hypersomnie ou la narcolepsie, pourraient etre en lien avec des lesions hypothalamiques, via une diminution du taux d’hypocretine-1, neuropeptide secrete par certaines cellules hypothalamiques et implique dans le rythme veille-sommeil. Nous rapportons un cas de narcolepsie avec cataplexie precedant l’apparition des signes de SEP. Si les manifestations d’origine hypothalamique sont rares chez les patients atteints de SEP, plusieurs series autopsiques ont pourtant mis en evidence une incidence elevee des lesions demyelinisantes dans la region hypothalamique. Parmi ces lesions, la proportion de lesions actives semble elevee. Cependant, peu d’entre elles presentent une expression clinicobiologique sous la forme d’un dysfonctionnement de la thermoregulation, de troubles du sommeil ou d’anomalies de la natremie. Il semble donc peu probable qu’une atteinte inflammatoire hypothalamique, meme bilatetale, puisse a elle seule expliquer la survenue de tels symptomes. Un nombre suffisant de lesions inflammatoires demyelinisantes, comme on peut le voir chez des patients avec une charge lesionnelle importante et un handicap deja severe, est sans doute necessaire pour developper une symptomatologie aussi rare. Il est possible que la survenue d’une manifestation hypothalamique, et notamment d’un episode d’hypothermie, soit un facteur de mauvais pronostic vis a vis de l’evolution de la maladie et du handicap.

Background and purposeThis 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.MethodsThe 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.ResultsFrom 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/conclusionMany 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.RésuméObjectifCe travail a pour objectif de recenser de manière prospective l’ensemble des cas de tumeurs primitives du système nerveux central (TPSNC), ayant un diagnostic histologique, en France. Les buts sont de créer une base de données et un réseau national pour favoriser la mise en place d’études épidémiologiques, biologiques et cliniques, et d’harmoniser la prise en charge des patients atteints de TPSNC.MéthodeLa méthodologie est basée sur l’existence d’un réseau national multidisciplinaire déjà établi par le Recensement national histologique des tumeurs primitives du système nerveux central (RnhTPSNC) (French Brain Tumor DataBase [FBTDB]), et la participation active des sociétés savantes impliquées en neuro-oncologie.RésultatsDe 2004 à 2009, 43 929 cas incidents de TPSNC ayant une confirmation histologique ont été recensés : gliomes (42,4 %), ensemble des autres tumeurs neuroépithéliales (4,4 %), tumeurs des méninges (32,3 %), tumeurs des nerfs intracrâniens et/ou intrarachidiens (9,2 %), lymphomes (3,4 %), et autres (8,3 %). La cryopréservation a été notée pour 9603 cas de TPSNC. Une intervention d’exérèse a été réalisée dans 78 % des cas, et une biopsie dans 22 %. L’âge médian au diagnostic, le sexe, le pourcentage de tumeurs réséquées, et le nombre de cas cryopréservés sont détaillés pour chaque histologie.Discussion/conclusionLes principales applications actuelles et futures du RnhTPSNC sont présentées dans la discussion. À notre connaissance, ce travail constitue la première base de données en Europe, dédiée aux TPSNC, qui recense des données cliniques, chirurgicales et histologiques (incluant la cryopréservation), et ses applications et perspectives sont très nombreuses.

BACKGROUND: The assessment of Bevacizumab efficacy in high-grade gliomas (HGG) depends on the response criteria used, with discrepancies between T1 Gadolinium-enhanced sequences, T2 sequences and neurological outcome. The aim was to compare McDonald's, RANO and RECIST 1.1 criteria to the clinical outcome in a consecutive series of HGG patients. METHODS: HGG patients treated at the Montpellier Cancer Institute were retrospectively selected. Patients with a Performance Status (PS) 20% of the product of perpendicular diameters. CONCLUSIONS: The high correlation between McDonald's and RANO criteria demonstrates the importance of accurately assessing changes in steroids and neurological state, as well as imaging response, in order to avoid concluding to a false efficacy on imaging only, when using the McDonald's criteria. These results raise the question of the value of the FLAIR assessment when McDonald's criteria are rigorously applied.

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.

This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research.

Glioblastoma (GBM) is the most common malignant primary brain tumor. Its incidence continues to increase in the elderly because the older segment of the population is growing faster than any other age group. Most clinical studies exclude elderly patients, and "standards of care" do not exist for GBM patients aged >70 years. We review epidemiology, tumor biology/molecular factors, prognostic factors (clinical, imaging data, therapeutics), and their assessments as well as classic and specific endpoints plus recent and ongoing clinical trials for elderly GBM patients. This work includes perspectives and personal opinions on this topic. Although there are no standards of care for elderly GBM patients, we can hypothesize that (i) Karnofsky performance status (KPS), probably after steroid treatment, is one of the most important clinical factors for determining our oncological strategy; (ii) resection is superior to biopsy, at least in selected patients (depending on location of the tumor and associated comorbidities); (iii) specific schedules of radiotherapy yield a modest but significant improvement; (iv) temozolomide has an acceptable tolerance, even when KPS

Radiotherapy with concomitant and adjuvant temozolomide (six cycles) is the standard treatment after surgery in glioblastoma patients. Few studies have assessed the impact of additional cycles of temozolomide on survival.We conducted a bi-centric retrospective study comparing survival and toxicity according to the number of cycles of adjuvant temozolomide.Fifty-eight patients were included. All patients received radiotherapy with concomitant temozolomide. Thirty-eight patients received six cycles, while 20 received nine or more (median=14) cycles. The risk of recurrence was significantly higher in the group receiving six cycles compared to the other group. Prolonged treatment improved progression-free survival (p=0.03) and overall survival (p=0.01) in multivariate analysis without a significant increase in toxicity.Prolonged administration of temozolomide seems to improve progression-free and overall survival, without increased toxicity. Prospective studies in larger populations are needed to better-define the population to whom it can be proposed and its optimal duration.

BACKGROUND: Breast cancer (BC) is the second leading cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM in this population. Serum levels of protein S100, an astrocytic marker, are associated with stroke severity. Neuron Specific Enolase (NSE), a neuronal marker, has been associated with BM prognosis in lung cancer. Elevated serum levels of these markers could reflect the brain damages induced by BM. Matrix Metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Finally, it has been shown that HER2-amplified breast tumors have a particular tropism for central nervous system. This study evaluates the predictive value of these four markers for BM in a population of metastatic BC patients. METHODS: In this case-control study, 88 consecutive BC patients with BM (cases) treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor markers determination. Cases were matched by age, tumor biology and number of previous metastatic treatment lines to 162 patients with metastatic BC but without CNS involvement (controls). RESULTS: Serum HER2, NSE and MMP-9 levels were significantly higher in cases than in controls (p= 0.0057, p = 0.0051 and p = 0.0062, respectively). Median HER2 (ng/ml) was 21.1 in cases compared to 12.3 in controls; median NSE (µg/l) was 10.8 compared to 8.70 in controls; median MMP-9 (ng/µl) was 422.9 in cases compared to 320.5 in controls. In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated cases from controls: odd ratio 4.4 (p = 0.000; 95%CI 1.9-9.6) for HER2 and 3.5 (p = 0.005; 95%CI 1.5-8.4) for MMP-9. CONCLUSIONS: Serum HER2 and MMP-9 seem to be predictive of BM in metastatic BC patients. These results need to be validated in further larger prospective studies.

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 T2-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.

e13005 Background: This work describes oncological patterns of care and survival for all patients (pts) with newly diagnosed histologically confirmed glioblastoma (GB) in metropolitan France in 200...

e13051 Background: National brain tumor registries exist only in few countries, and systematic brain tumor declaration is not mandatory in many countries. Here we propose an easy method to build a ...

Introduction Dans les pays industrialises, l’incidence du glioblastome (GB) chez le sujet âge ( > 70 ans) est importante (environ 14/100 000 habitants/an) et en forte augmentation, principalement due au vieillissement de la population. Un doublement du nombre de cas est attendu avant l’annee 2050. Or, chez ces patients, aucun standard de prise en charge n’existe actuellement et les attitudes therapeutiques et/ou palliatives varient considerablement d’un pays ou d’une region a l’autre. L’objectif de la presentation est de proposer et de discuter un arbre decisionnel de prise en charge oncologique chez ces patients. Patients et methode Les auteurs ont effectue une revue de la litterature portant sur les facteurs epidemiologiques, biologiques, neuroradiologiques, cliniques et therapeutiques, ainsi qu’une synthese des essais cliniques recents et des etudes en population concernant les patients âges atteints de GB. Resultats L’index de Karnofsky et une evaluation geriatrique semblent etre les elements les plus pertinents sur le plan clinique, et la topographie et les caracteristiques neuroradiologiques de la tumeur les plus pertinents sur le plan neurochirurgical. Il sera presente et discute un premier arbre decisionnel (choix entre biopsie, exerese ou abstention chirurgicale) et un deuxieme arbre decisionnel, une fois le diagnostic histologique de GB confirme (choix entre les differentes modalites de radiotherapie et/ou de chimiotherapie et prise en charge palliative). Conclusion Si certains elements cliniques, neuroradiologiques et biologiques permettent des maintenant de proposer une medecine personnalisee a ces patients, il n’en demeure qu’une evaluation rigoureuse en population est necessaire et indispensable pour optimiser nos prises en charge actuelles et futures.

2067 Background: Diffuse WHO grade II and III gliomas (DGII/IIIG) are rare tumors (incidence ≤ 2/105person-years). Specific epidemiological studies are very rare. The main objective of this work is to study the geographical distribution of all newly diagnosed and histologically confirmed DGII/IIIG in metropolitan France. Methods: The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase. Personal addresses at the moment of the surgical procedure for all DGII/IIIG cases were collected for the years 2006-2009. For each area, the incidence of DGII/IIIG was analyzed and standardized on age and sex distribution of the French population (pop). Results: The total number of patients with newly diagnosed and histologically confirmed DGII/IIIG was 4790 (1220, 1190, 1228, and 1152 for years 2006-2009). The Table shows the number of tumors by histology, sex and median age at diagnosis. The overall crude rate was 19.4/106. To enable international comparisons, standardized rates were calculated as follows: 19.8/106 (reference pop, Europe), 18.8/106 (reference pop, US 2000), and 16.0/106 (reference pop, world). The geographic distribution by regions in France showed significant differences. For example, the standardized rates (for 106person-years, 95% confidence intervals, reference pop: France) for Auvergne, Champagne-Ardenne, and Basse-Normandie, were 30.9 (26.4-35.5), 28.5 (24.0-33.0), and 13.9 (10.9-17.0), respectively. Conclusions: To our knowledge, this work is the first to study the geographical distribution of DGII/IIIG across one entire country, and it shows significant heterogeneity. These results will enable to look for different environmental and genetic factors in these different regions. [Table: see text]

Background Metastatic breast cancer (MBC) prognosis is highly variable, depending on various factors such as the biological subtype, the performance status, disease extension…. A better evaluation of a patient’s prognostic factors could allow for a more accurate choice of treatments. The role of serum tumor markers remains, however, unclear in this population. Considering the recent interest in phenotypic changes and tumor heterogeneity during breast cancer progression, additional tumor markers could be interesting in this setting. Methods Two hundred fifty MBC patients treated at the Montpellier Cancer Institute (2008–2015) were retrospectively selected, based on the availability of frozen serum samples. The usual MBC clinical and pathological variables were collected, altogether with Cancer Antigen 15-3 (CA15-3), Carcinoembryonic Antigen (CEA), HER2 extra-cellular domain (ECD), Neuron Specific Enolase (NSE), S100ß protein and Matrix Metalloproteinase 9 (MMP-9) serum levels in order to determine their prognostic value. Results With a median follow-up of 40.8 months, median overall survival was 16.2 months (95 % CI 12.4–20.6). In multivariate analysis, the performance status, brain or subcutaneous metastases, the number of previous metastatic chemotherapy lines and the tumor biological subtype were independent prognostic factors. Elevated CA 15-3 (HR = 1.95, IC 95 % 1.31–2.93, p = 0.001), HER2 ECD (regardless of tumor HER2 status, HR = 2.51, IC 95 % 1.53–4.12, p