Systemic Treatment Initiation in Classical and Endemic Kaposi's Sarcoma: Risk Factors and Global Multi-State Modelling in a Monocentric Cohort Study.

BACKGROUND: Although several studies described the clinical course of epidemic and post-transplant Kaposi's Sarcoma (KS), the lack of large cohorts of classic/endemic KS, precluded such characterization. METHODS: We used multi-state modelling in a retrospective monocentric study to evaluate global disease evolution and identify risk factors for systemic treatment (ST) initiation. 160 classic/endemic KS patients consecutively diagnosed between 1990 and 2013 were included. RESULTS: 41.2% of classic/endemic KS patients required ST. Cumulative incidence of ST after 2 years of follow-up was 28.4% [95% CI: 20.5; 35.5]. Multivariate analysis identified six risk factors for ST initiation: time between first symptoms and diagnosis ≥1 year, endemic KS, total number of lesions ≥10, visceral, head or neck localization and presence of edema. Type of ST, type of KS, age and time between diagnosis and ST were not associated with response. Mean treatment-free time during the first 5 years following ST was 44 months for interferon and 44.6 months for chemotherapy treated patients (Mean difference: -0.5 months [95% CI: -9.5; 4.9]). CONCLUSIONS: Our study reveals ST risk factors in classic/endemic KS and highlights the clinical aggressiveness of the endemic KS subtype. No efficacy difference was observed between standard of care treatments, enabling treatment choice based on patient's fitness.

Immunotherapy and patients treated for cancer with microsatellite instability.

Microsatellite instability (MSI) is a tumor phenotype linked to somatic or germline (Lynch syndrome) inactivating alterations of DNA mismatch repair genes. A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer. MSI tumors are characterized by dense immune infiltration and high load of tumor neo-antigens. Growing evidence is accumulating on the efficacy of immune checkpoint inhibition for patients treated for MSI solid tumors. We present a comprehensive overview of MSI phenotype, its biological landscape and current diagnostic methods. Then we focus on MSI as a predictive biomarker of response to immune checkpoint inhibition in the context of colorectal cancer and non-colorectal tumors.

[ESMO ECCO 2015: The highlights of immunotherapy and targeted therapies]. / ESMO ECCO 2015 : les temps forts de l'immunothérapie et des thérapies ciblées.

The ESMO/ECC congress (European Society for Medical Oncology/European Cancer Congress) took place in Vienna, Austria, September 25-29. The main topic of the conference was immunotherapies especially in advanced kidney cancer with nivolumab in phase III and in metastatic lung cancer with atezolizumab in phase II. Targeted therapies were also highlighted with cabozantinib proposed in advanced renal cancer or everolimus in differenciated neuroendocrine tumors grade 1 or 2. Furthermore the current challenges remain unchanged: improving patients' care through better selection and finding biomarkers using simple samples (blood or urine). Also early phases and personalized medicine found their place in the different presentations and were highlighted largely bringing new approaches in the treatment of metastatic patients.

[Intrathecal methotrexate in breast cancer meningeal carcinomatosis - Experience with a new administration schedule]. / Méthotrexate intrathécal dans les méningites carcinomateuses du cancer du sein - Expérience avec le protocole utilisé à l'hôpital Saint-Louis.

Methotrexate represents the standard intrathecal treatment of breast cancer meningeal carcinomatosis. However, its optimal schedule remains undefined. The aim of the present study was to evaluate results obtained with the methotrexate schedule used in Saint-Louis hospital (Paris). Patients followed in Saint-Louis hospital for breast cancer and who received intrathecal methotrexate were included in this retrospective monocentric study. Intrathecal treatment received contained methotrexate 12 mg/day (days: 1-5) and then 15 mg/week until progression or toxicity. Between 2003 and 2015, 41 patients were included. Primitive tumours were RH+/HER2-, HER2+ and triple-negative in respectively 66%, 14%, 5% and 15% of patients, 22% of them had meningeal carcinomatosis as metastatic disease initial manifestation. Objective response rate was 54%, median overall survival was 4.0 mois [CI 95%: 3-7.3] and 1-year survival rate was 15.2% (11.4%, 50% et 0% in RH+/HER2-, HER2+ and triple-negative subgroups; HR=0.45 [0.21-0.97] between HER2+ and RH+/HER2-). In univariate analysis, prognostic factors were brain involvement (p=0.049), initial cerebrospinal fluid protein level (p=0.0002) and concomitant systemic treatment received (p=0.049). This intrathecal methotrexate schedule demonstrates a similar median overall survival as the one obtained with a dose-dense schedule and an improved quality of life. Nevertheless, as the objective response and 1-year survival rates are slightly inferior, a dose-dense schedule remains still preferred in HER2+ patients or in those harboring a mainly meningeal progression.

Vaccine knowledge in students in Paris, France, and surrounding regions.

INTRODUCTION: In France, young adults are legally freed from parental authority at the age of 18 years and are, thus, responsible for their own vaccine record. This young adult population is more frequently exposed to vaccine-preventable infectious diseases. OBJECTIVE: To determine the factors associated with students' knowledge of the interval between two antitetanus boosters and their report of having up-to-date vaccinations. METHODS: In April 2009, a survey was conducted involving a random sample of students between 18 and 25 years of age eating lunch at university dining facilities in Paris and its suburbs (Ile de France). RESULTS: Among the 677 students approached, 583 agreed to participate. Only 207 (36%) of respondents knew the recommended dosing interval between two doses of tetanus vaccine booster (10 years). The majority of students (69%) reported having up-to-date vaccinations. Declaring having up-to-date vaccinations was significantly associated with having a general practitioner (OR 3.03 [95% CI 1.69 to 5.55]). Health care students were significantly more likely to know the decennial interval between two antitetanus boosters (OR 2 [95% CI 1.28 to 3.25]). Most of responding students (n=519 [89%]) believed that vaccines were very useful. CONCLUSIONS: An overall lack of knowledge of vaccines was observed among this student population. Health care providers, such as GPs and university medical practice staff, who interact with these young individuals have an essential role to promote better vaccination coverage in this population.

INTRODUCTION: En France, les jeunes adultes sont légalement libérés de l'autorité parentale à 18 ans et deviennent donc responsables de leur dossier de vaccination. La population de jeunes adultes est davantage exposée aux maladies infectieuses évitables par la vaccination. OBJECTIF: Déterminer les facteurs associés aux connaissances des étudiants sur l'intervalle entre les deux doses de rappel du vaccin contre le tétanos et sur leur déclaration d'avoir une couverture vaccinale. MÉTHODOLOGIE: En avril 2009, un sondage a été mené auprès d'un échantillon aléatoire d'étudiants de 18 à 25 ans qui, le midi, mangent aux cafétérias universitaires de Paris et des banlieues (Île de France). RÉSULTATS: Sur les 677 étudiants abordés, 583 ont accepté de participer. Seulement 207 des répondants (36 %) connaissaient l'intervalle recommandé entre deux doses de rappel du vaccin contre le tétanos (dix ans). La majorité des étudiants (69 %) déclarai avoir une couverture vaccinale à jour. Cette déclaration s'associait de manière significative au fait d'avoir un praticien général (RC 3,03 95 % IC 1,69 à 5,55]). Les étudiants du milieu de la santé étaient considérablement plus enclins à connaître l'intervalle de dix ans entre deux doses de rappel du vaccin antitétanique (RC 2 [95 % IC 1,28 à 3,25]). La plupart des étudiants répondants (n=519 [89 %]) croyaient en l'utilité des vaccins. CONCLUSIONS: Les chercheurs ont constaté une ignorance globale des vaccins au sein de cette population de patients. Les dispensateurs de soins, tels que les praticiens généraux et le personnel médical en milieu universitaire, qui dialoguent avec ces jeunes, ont un rôle essentiel à jouer pour promouvoir une meilleure couverture vaccinale au sein de cette population.

Rationale and efficacy of CD52 targeting in HTLV-1-associated myositis.

We retrospectively analysed two selected patients, referred to our Haematology Department for refractory HTLV-1 associated myositis with circulating pathologic T-cell population with ATL phenotype. They respectively presented also HTLV-1 associated Crohn-like disease and myelopathy. Muscle biopsy of both patients was analysed to determine the pathologic infiltrate. Alemtuzumab was proposed as salvage therapy. Targeting CD52 with alemtuzumab showed good efficacy on myopathy of both patients for respectively 11 and 10 months. Interestingly, this treatment showed also efficacy on circulating pathologic T-cell population and on concomitant digestive and neurological diseases. The double infected cells ablation and immunosuppressive propriety of alemtuzumab probably explains its interest in this infectious and dysimmunitary disorder. Even though alemtuzumab probably remains a suspensive treatment, its place should be assessed in controlled trial in this difficult to treat rare disease.