Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). OBJECTIVE: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. DESIGN: A retrospective, cross-sectional, descriptive analysis. METHODS: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. RESULTS: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. CONCLUSIONS: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs.

Sex Differences in the Efficacy of Immune Checkpoint Inhibitors in Neoadjuvant Therapy of Non-Small Cell Lung Cancer: A Meta-Analysis.

Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13-2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97-2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence.

Complicaciones neurológicas de los inhibidores de punto de control inmunológico / Checkpoint inhibitors neurological side effects

Introducción. Los inhibidores de punto de control inmunológico han supuesto un nuevo paradigma en el tratamiento de diferentes tipos de neoplasias. Sin embargo, con el uso creciente de estos fármacos, se están observando diferentes efectos adversos. Entre ellos destacan los neurológicos, puesto que su frecuencia parece haberse infraestimado en los ensayos aprobatorios. Objetivo. Revisar la fisiopatología y la incidencia de los efectos adversos neurológicos por inhibidores de punto de control neurológicos, así como el abordaje basándose en diferentes guías clínicas. Desarrollo. Se revisan los casos que se han publicado desde la aprobación de los fármacos y añadimos la experiencia de nuestro centro. A su vez, se hace un resumen de las diferentes guías publicadas de forma reciente. Conclusiones. Las complicaciones derivadas del uso de los inhibidores de punto de control inmunológico son frecuentes. Incluyen múltiples cuadros de diferente gravedad, y pueden afectar a cualquier parte del sistema nervioso central y periférico. Además, en tumores del sistema nervioso, puede observarse un fenómeno de pseudoprogresión derivado de la inflamación asociada. Queda pendiente realizar nuevos estudios para conocer en detalle estos efectos adversos y desarrollar guías clínicas con las que optimizar el manejo

Introduction. Checkpoint inhibitors have dramatically transformed cancer treatment. However, due to the increasing number of tumors in which they are used, there is a high number of reported adverse effects. Among them, we highlight neurological side effects. In the approbatory clinical trials, they were thought to be sparse, but they may have been underestimated. Aim. To review the physiopathology and the incidence of neurological side effects due to the use of checkpoint inhibitors, as well as the clinical practice guidelines published in the last years. Development. To review the published case reports of neurological side effects since the approval of checkpoint inhibitors, and our own experience. Moreover, we summarize the main clinical practice guidelines. Conclusions. Checkpoint inhibitors neurological side effects are frequent. A wide variety of central or peripheral nervous system symptoms may develop. In the setting of brain tumors, inflammation due to immune system activation might lead to pseudoprogression. Further studies are needed to better describe these neurological side effects, and to implement clinical guidelines

Dural arteriovenous fistula at the foramen magnum: Report of a case and clinical-anatomical review / Fístula dural arteriovenosa en el agujero occipital: caso clínico y revisión clínico-anatómica

Arterial supply and venous drainage at the foramen magnum is variable. Two main forms of clinical presentation, intracranial and spinal, can be differentiated when a dural arteriovenous fistula (DAVF) is found at this level. We describe a case of a 68-year-old patient with a progressive paraparesis, diagnosed of dural arteriovenous fistula located at the posterior lip of foramen magnum. We review, in this setting, the vascular radiological anatomy of those fistulas and its important correlation with neurologic clinical symptoms

El aporte arterial y el drenaje venoso en el agujero magno son variables. Dos formas principales de presentación clínica, intracraneal y medular pueden ser diferenciadas en las fístulas durales arteriovenosas encontradas a este nivel. Se presenta el caso de un paciente de 68 años que, tras un cuadro de paraparesia progresiva, se diagnostica de una fístula dural arteriovenosa dural localizada en el borde posterior del agujero magno. A propósito de este caso se revisa la anatomía radiológica y vascular de estas fístulas y su importante correlación con los síntomas neurológicos

Dural arteriovenous fistula at the foramen magnum: Report of a case and clinical-anatomical review.

Arterial supply and venous drainage at the foramen magnum is variable. Two main forms of clinical presentation, intracranial and spinal, can be differentiated when a dural arteriovenous fistula (DAVF) is found at this level. We describe a case of a 68-year-old patient with a progressive paraparesis, diagnosed of dural arteriovenous fistula located at the posterior lip of foramen magnum. We review, in this setting, the vascular radiological anatomy of those fistulas and its important correlation with neurologic clinical symptoms.