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Aim Cabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for ‘unfit’ mCRPC patients after docetaxel failure. Methods In this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m2 to eligible ‘unfit’ patients; oral prednisone (5 mg) was administered twice a day. Circulating tumour cells (CTCs) were also collected. New treatment scheme was considered effective if at least 65% of patients met a clinical benefit criteria based on prostate-specific antigen (PSA)-progression-free survival (PFS) values at week 12. Results Seventy patients (median age: 73.9 years) were enrolled; overall, 71.4% had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2; and 84%, 16% and 11% had bone, liver and lung metastases, respectively. Objective partial response or stable disease was achieved in 61% of patients, while PSA responses of ≥50% and ≥80% were observed in 34.8% and 10.6%, respectively. The median PSA-PFS was 4.8 months; and 68.6% of patients had no progression at week 12. The most frequent grade 3/4 toxicities were neutropenia (2.8%), leukopenia (5.7%) and thrombocytopaenia (9%); no cases of febrile neutropenia were reported. Early CTC response was significantly correlated with PSA-PFS. Conclusions CBZ/prednisone administered weekly to ‘unfit’ mCRPC patients appears to be as effective as classical standard 3-week scheme (TROPIC study) but with significantly lower toxicities and better tolerance. Early CTC response appears to be valuable as an early end-point of therapeutic efficacy.

Objectives: In the PAOLA-1/ENGOT-ov25 primary analysis (NCT02477644), adding the PARP inhibitor olaparib to maintenance bevacizumab (bev) after first-line platinum-based chemotherapy with bev led to a significant progression-free survival (PFS) benefit vs placebo (pbo) + bev in patients (pts) with advanced high-grade ovarian cancer (HGOC), using modified RECIST v1.1 criteria (HR 0.59; 95% CI 0.49-0.72; P Methods: Pts with newly diagnosed, FIGO stage III-IV HGOC in response after platinum-based chemotherapy plus bev received bev (15 mg/kg q3w for 15 months) + olaparib (300 mg bid for 24 months) or pbo. Scans were performed every 24 weeks, or every 12 weeks if there was evidence of clinical or CA-125 progression. CA-125 levels were assessed every 12 weeks. Time to RECIST or CA-125 progression or death was a secondary endpoint; RECIST/CA-125 progression by biomarker status, response to initial therapy and CA-125 level at baseline were explored. Results: 537 pts were randomized to olaparib + bev and 269 to pbo + bev with median follow-up for PFS by RECIST/CA-125 of 24.2 vs 24.7 months (DCO 22 March 2019). In the ITT population, the benefit provided by olaparib + bev vs pbo + bev for PFS by RECIST/CA-125 (HR 0.58; 95% CI 0.48-0.70; P Download : Download high-res image (258KB) Download : Download full-size image Conclusions: Median PFS and HRs were consistent when progression was assessed by either RECIST or RECIST/CA-125 in PAOLA-1. Scans appear particularly important for detecting progression in HRD-positive pts, tBRCAm pts or pts with normal CA-125 levels at baseline as CA-125 levels did not seem to predict relapse in these pts. Results suggest that CA-125 surveillance alone may be sufficient to detect progression in most pts with abnormal baseline CA-125 levels when starting maintenance therapy.

Resumen El Grupo de Trabajo de Neurooncologia (GTNO) de la SENEC ha encargado a los miembros del comite de neurooncologia del Hospital Universitario Donostia de San Sebastian (Espana) la elaboracion del presente documento, para que sirva como Guia del consenso establecido en el seno del GTNO y recomendacion propuesta en todos los hospitales, publicos o privados, que manejan esta patologia. Es obligado la constitucion y funcionamiento normalizado de comites de neurooncologia en todos los centros con servicio de neurocirugia, y lo expuesto a continuacion debe contemplarse a la luz de las condiciones particulares de los mismos, con las variaciones pertinentes segun los recursos diagnosticos y terapeuticos. Nos presentan a continuacion el ejemplo de la constitucion, funcionamiento y experiencia que han contraido en mas de 8 anos de trabajo multidisciplinar en pacientes con tumores cerebrales.

Neurodegenerative diseases that course with dementia represent a public health problem that is growing in importance, mostly due to the aging of the population. Imaging techniques provide essential diagnostic and prognostic information. Some classifications of these diseases have recently been modified through the incorporation of histological, immunohistochemical, and genetic criteria. This article reviews the different radiological and pathological aspects of the most common diseases that course with dementia. We studied brains from our community's tissue bank with postmortem MRI and posterior histological examination and illustrate this exposition with images from the radiopathologic correlation.

At advanced stages, Alzheimer’s disease (AD) is characterized by an extensive neuronal loss. However, the early neurodegenerative deficiencies have not been yet identified. Here we report an extensive, selective and early neurodegeneration of the dendritic inhibitory interneurons (oriens-lacunosum moleculare, O-LM, and hilar perforant path-associated, HIPP, cells) in the hippocampus of a transgenic PS1 × APP AD model. At 6 months of age, from 22 different pre- and postsynaptic mRNA markers tested (including GABAergic, glutamatergic and cholinergic markers), only the expression of somatostatin (SOM) and NPY neuropeptides (O-LM and HIPP markers) displayed a significant decrease. Stereological cell counting demonstrated a profound diminution (50–60%) of SOM-immunopositive neurons, preceding the pyramidal cell loss in this AD model. SOM population co-expressing NPY was the most damaged cell subset. Furthermore, a linear correlation between SOM and/or NPY deficiency and Abeta content was also observed. Though the molecular mechanism of SOM neuronal loss remains to be determined, these findings might represent an early hippocampal neuropathology. Therefore, SOM and NPY neuropeptides could constitute important biomarkers to assess the efficacy of potential early AD treatments.

Fundamento y objetivo La inestabilidad de microsatelites derivada del fallo en la reparacion de los falsos emparejamientos del ADN es la alteracion caracteristica de los tumores de la via mutadora o inestables (MSI). Tales casos parecen presentar diferencias desde el punto de vista clinicopatologico con los tumores de la via supresora o estables (MSS). Los tumores con alto grado de inestabilidad (MSI-H) parecen constituir una nueva entidad de tumores con diferencias en determinadas caracteristicas anatomopatologicas y clinicas con respecto a los tumores estables (MSS) e inestables de bajo grado (MSI-L). En el presente estudio se valora la posible asociacion entre el alto grado de inestabilidad de microsatelites con la localizacion, contenido mucinoso, grado de diferenciacion, estadio, asi como el intervalo libre de enfermedad y supervivencia. Pacientes y metodo Se clasifica a 117 pacientes con cancer de colon esporadico en las poblaciones MSS/MSI-L y MSI-H (siguiendo las recomendaciones del National Cancer Institute) ediante reaccion en cadena de la polimerasa y electroforesis de 7 microsatelites. Resultados Los tumores MSI-H tendieron a localizarse en el colon derecho (p = 0,022) y a presentar contenido mucinoso (p = 0,04). El conjunto de pacientes MSI-H de estadios II y III no presento intervalos libres de enfermedad ni periodos de supervivencia mas prolongados (p = 0,54, p = 0,37, respectivamente). Los tumores MSI-H de estadio II presentaron periodos de supervivencia mas prolongados que los tumores MSS/MSI-L (p = 0,027). No observamos diferencias en la respuesta a quimioterapia con 5-fluorouracilo y leucovorin entre los grupos MSS/MSI-L y MSI-H (p = 0,38). Conclusiones El alto grado de inestabilidad de microsatelites se asocia con determinadas caracteristicas patologicas, asi como con periodos de supervivencia mas prolongados para los tumors de estadios II.

Three naturally occurring ajugarins and seven semisynthetic derivatives of them, possessing different functionalities in the decalin part, together with two natural furoneoclerodane diterpenes, have been assessed as feeding behavior modifying agents of larvae of the generalist Spodoptera exigua and a specialist like Leptinotarsa decemlineata. Ajugarin I and some of its derivatives exhibited a significant antifeedant activity against larvae of S. exigua in both choice and no-choice assays. Conversely, the furoneoclerodane diterpenes only presented antifeedant activity against larvae of L. decemlineata. These results indicate that the biological action of the tested substances is strongly modulated by minimal structural variations, which are also responsible for the specificity of action.

SUMMARY The hydrogen peroxide is a liquid widely used as germicide and disinfectant in the sanitary and medical practice. Nevertheless, severe effects can not be ruled out. We present the case of a 47 year-old man with a hydatid cyst of the liver who died in the surgical procedure in order to deactivate the cyst by using hydrogen peroxide at high pressure. A lethal massive oxygen gas embolism secondary to the use of hydrogen peroxide was found in the necropsy. The involvement of the hydrogen peroxide in the patogenesis of the case is reviewed.

Aim: Cabazitaxel (C), a novel taxane developed to overcome docetaxel (D) resistance, showed an overall survival improvement after D in mCRPC in a three-weekly dose schedule. We aimed to evaluate efficacy and safety of a weekly C/prednisone (P) schedule in "unfit" mCRPC patients previously treated with D. Methods: Unfit pts (ECOG 2, dose reduction due to febrile neutropenia during treatment with D or radiation therapy affecting more than 25% of bone marrow reserve) with mCRPC progressing after D treatment with adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15 and 22 of 5-week cycles with P (5 mg b.i.d.). Radiological and PSA responses were evaluated according to the PCWG2 (Scher H, 2008) criteria and toxicity according NCI-CTC AE. Results: To date 69 pts have been enrolled and data are available for 54. Median age was 73 y (range 54-83); 59% pts had ECOG 2, 83% had bone, 19% liver and 9% lung metastases. 50% had Gleason > 7. Twenty three pts (43%) achieved ≥50% PSA response and 19 (35.2%) ≥80% PSA response. Response was evaluable in 28 pts. PR was observed in 1 pt (3.6%) and SD in 18 pts (64.3%). Median PSA PFS was 5.9 months. Median overall survival was 8.3 months. Most frequent toxicities of all grades as percentage of pts were: anemia (44.4%), asthenia (22.2%), thrombocytopenia (27.8%), leukopenia (18.5%), diarrhea (11.1%), nauseas (11.1%), neutropenia (5.6%), peripheral neuropathy (5.6%), and anorexia (3.7%). Grade 3-4: thrombocytopenia (20.4%), anemia (7.5%), leucopenia (3.8%), neutropenia (1.9%), asthenia (1.9%), diarrhea (1.9%), anorexia (1.9%), and peripheral neuropathy (1.9%). No grade IV diarrhea nor febrile neutropenia was observed. Conclusions: Administration of weekly C (10 mg/m2) plus P to unfit pts seems efficacious and safe with no grade 4 neutropenia, diarrhea or febrile neutropenia reported. Funding: Sanofi. Disclosure: All authors have declared no conflicts of interest.