Cambios en el perfil inmunohistoquímico tras tratamiento neoadyuvante en pacientes con cáncer de mama

El cáncer de mama constituye un importante problema de salud. Aunque su incidencia está aumentando, la supervivencia ha mejorado gracias al avance en los métodos diagnósticos y los tratamientos. En el cáncer de mama localmente avanzado la supervivencia a 5 años es mayor al 80% y el tratamiento se basa en QT neoadyuvante con combinaciones de antraciclinas y taxanos, terapia anti-­‐HER2 (tumores con sobreexpresión/amplificación de HER2), terapia hormonal (tumores hormono-­‐ sensibles) y RT adyuvante en pacientes de alto riesgo de recaída local. Actualmente las decisiones terapéuticas se basan en los resultados de la determinación de RE, RP, ki67 y HER2, marcadores estudiados en la biopsia inicial mediante técnicas de IHQ y/o FISH (HER2). Tras el tratamiento con QT se producen variaciones en estos cuatro marcadores en la pieza quirúrgica. La determinación de estos marcadores mediante técnicas de IHQ y/o FISH debe seguir un protocolo riguroso para minimizar las variaciones dependiente de la técnica. En los últimos años, han sido varios los estudios publicados en los que a través del estudio de 50 genes (PAM50) se han definido 4 subtipos intrínsecos de cáncer de mama: Luminal A, Luminal B, HER2-­‐enriched y Basal-­‐like. Un último subtipo denominado Claudin-­‐low ha sido descrito recientemente. Los subtipos intrínsecos son factores predictivos de respuesta a la QT y tienen valor pronóstico..

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononu-clear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), an-alyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each bi-omarker, defined as those above the 55th or below the 45th percentile of the overall marker expres-ion within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patientsProjects PIE15/00068, PI17/01865, and PI20/01458 (Instituto de Salud Carlos III) awarded to R.C.; Projects FIS PI19/01491 and CIBER Cardiovascular (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III with co-funding from the Fondo Europeo de Desarrollo Regional FEDER) awarded to A.A.; CNIO Bioinformatics Unit is supported by the Instituto de Salud Carlos III (ISCIII); Project RETOS RTI2018-097596-B-I00 (AEI/10.13039/501100011033 MCI/FEDER, UE); Projects PI17/00801 and PI21/01111 grants from Instituto de Salud Carlos III and JR17/00007 awarded to N.R.-L., and Project Molecular Analysis of the Exhaled Breath Condensate in the Management of Solitary Pulmonary Nodule (ideas semilla AECC 2019), from Asociación Española Contra el Cáncer (AECC), awarded to J.

Consensus of experts from the Spanish pharmacogenetics and pharmacogenomics society and the Spanish society of medical oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidinesThis project has been financed with SEOM and SEFF resource

Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study

[Purpose] To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine.[Methods] In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.) nab-paclitaxel at a dose of 125 mg/m2, followed by i.v. injections of gemcitabine at a dose of 1000 mg/m2 on days 1, 8 and 15 until disease progression or unacceptable toxicity was observed. The primary outcome was the HRQoL (deterioration-free rate at 3 months as evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30.[Results] Eighty patients (median age: 74.6 years) were enrolled (56 with mPC, 24 with LAPC). The percentage of patients who had not experienced deterioration at 3 months was 54.3% (95% CI 41.6–67.0%). The median (interquartile range) time until definite deterioration was 1.6 (1.1–3.7) months. The objective response rate and clinical benefit rate were achieved by 11 (13.8%, 95% CI 6.2–21.3%) and 54 patients (67.5%, 95% CI 57.2–77.8%), respectively. The median overall survival was 9.2 months (95% CI 6.9–11.5), and the median progression-free survival was 7.2 months (95% CI 5.8–8.5). Only fatigue and neutropenia demonstrated a grade 3–4 toxicity incidence > 20%.[Conclusions] Our study confirms the clinical benefit of the combination of nab-paclitaxel and gemcitabine in an elderly population with pancreatic cancer in terms of improved survival and clinical response. However, we were unable to confirm a benefit in terms of quality-of-life.The BIBABRAX study was funded by Celgene. Medical writing assistance in the preparation of this paper was provided by Apices with financial support from Celgene.Peer reviewe