Genomic Alterations in Head and Neck Squamous Cell Carcinoma: Level of Evidence According to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT).

Development of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes. HRAS-activating mutations were ranked in tier IB because of the efficacy of tipifarnib (farnesyltransferase inhibitor) in HRAS-mutated patients with HNSCC (nonrandomized clinical trial). Microsatellite instability (MSI), high tumor mutational burden (TMB), and NTRK fusions were ranked in tier IC because of PD-1 and TRK tyrosine kinase inhibitors tissue-agnostic approvals. CDKN2A-inactivating alterations and EGFR amplification were ranked in tier IIA because of the efficacy of palbociclib (CDK4/6 inhibitor) and afatinib (tyrosine kinase inhibitor) in these respective molecular subgroups in retrospective analyses of clinical trials. Molecular alterations in several genes, including PIK3CA gene, were ranked in tier IIIA because of clinical benefit in other tumor types, whereas molecular alterations in IGF1R and TP53 genes were ranked in tier IVA and tier V, respectively. The most compelling actionable molecular alterations in HNSCC according to ESCAT include HRAS-activating mutations, MSI, high TMB, NTRK fusions, CDKN2A-inactivating alterations, and EGFR amplification.

Fine-needle aspiration as an alternative to core needle biopsy for tumour molecular profiling in precision oncology: prospective comparative study of next-generation sequencing in cancer patients included in the SHIVA02 trial.

High-throughput molecular profiling of solid tumours using core needle biopsies (CNB) allows the identification of actionable molecular alterations, with around 70% success rate. Although several studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to the sensitivity of the less invasive fine-needle aspiration (FNA) compared to CNB to detect molecular alterations. We aimed to prospectively evaluate the potential of FNA to detect such alterations in various tumour types as compared to CNB in cancer patients included in the SHIVA02 trial. An in-house amplicon-based targeted sequencing panel (Illumina TSCA 99.3 kb panel covering 87 genes) was used to identify pathogenic variants and gene copy number variations (CNV) in concomitant CNB and FNA samples obtained from 61 patients enrolled in the SHIVA02 trial (NCT03084757). The main tumour types analysed were breast (38%), colon (15%), pancreas (11%), followed by cervix and stomach (7% each). We report 123 molecular alterations (85 variants, 23 amplifications and 15 homozygous deletions) among which 98 (80%) were concordant between CNB and FNA. The remaining discordances were mainly related to deletions status, yet undetected alterations were not exclusively specific to FNA. Comparative analysis of molecular alterations in CNB and FNA showed high concordance in terms of variants as well as CNVs identified. We conclude FNA could therefore be used in routine diagnostics workflow and clinical trials for tumour molecular profiling with the advantages of being minimally invasive and preserve tissue material needed for diagnostic, prognostic or theranostic purposes.

Uso de biocidas y mecanismos de respuesta bacteriana / Use of biocides and bacterial response mechanisms

La constante aparición de microorganismos que incrementan su tolerancia a sustancias utilizadas para su control como los biocidas está generando atención en salud pública y debe ser estudiado, teniendo en cuenta los diversos riesgos que se pueden enfrentar principalmente en pacientes con alta susceptibilidad a las infecciones asociadas a la atención en salud, dado que estos biocidas son utilizados cotidianamente lo que ha generado mecanismos bacterianos como lo son la formación de biopelículas y aquellos que incrementan su tolerancia como la generación de bombas de flujo. Esta respuesta bacteriana a la presión de los biocidas se potencia por la aparición de microorganismos resistentes a los antimicrobianos de uso en el tratamiento y control de las infecciones lo que hace difícil el control de estos. Se realizó una revisión de literatura disponible en las bases de datos Proquest, ovid, Science direct, PubMed, donde se encontraron un total de 103 artículos y se seleccionaron 73, de acuerdo con el año de publicación en los idiomas español e inglés, que incluyeron estudios descriptivos y de revisión. El objetivo de este artículo fue realizar una revisión acerca de los principales mecanismos de acción de biocidas y la respuesta de tolerancia que presentan los microorganismos frente a estos; lo que conlleva a la reflexión sobre las implicaciones del uso de estas sustancias sobre la salud humana.

The constant appearance of microorganisms that increase their tolerance to substances used for their control such as biocides is generating attention in public health and should be studied, taking into account the various risks that can be faced mainly in patients with high susceptibility to infections associated with health care, given that these biocides are used on a daily basis, which has generated bacterial mechanisms such as the formation of biofilms and those that increase their tolerance, such as the generation of flow pumps. This bacterial response to the pressure of the biocides is enhanced by the appearance of microorganism's resistant to the antimicrobials used in the treatment and control of infections, which makes their control difficult. A literature review was made available in the databases Proquest, ovid, Science direct, PubMed, where a total of 103 articles were found and 73 were selected, according to the year of publication in the Spanish and English languages, which included Descriptive and review studies. The objective of this article is to carry out a review about the main action mechanisms of biocides and the tolerance response presented by microorganisms against them; which leads to reflection on the implications of the use of these substances on human health.