Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity.

Background: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice. Methods: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study. Toxicity was assessed according to The Common Terminology Criteria for Adverse Events. Response assessment was performed according to RECIST 2.0 and immuno-related criteria. Descriptive and survival analyses were conducted. Degree of toxicity and response to treatment (based on treatment and histology) were assessed. LIPI and response were assessed. LIPI included dNLR (absolute neutrophil count/(white blood cell count - absolute neutrophil count)) ≥ 3 and lactate dehydrogenase (LDH) greater than the upper limit of normal. Patients were stratified into good (G), intermediate (I), and poor (P) prognostic groups. Results: A total of 168 patients were included (130 men and 38 women, mean age 64.3 years). ICI use in the first- or second-line treatment was 65% and 35%, respectively. Fifteen (9%) patients showed complete response (CR), 50 (30%) showed partial response (PR), 39 (22%) had stable disease (SD), 45 (28%) had progressive disease (PD), and 19 (11%) were not evaluated (NE). Patients with good prognostic LIPI (dNLR < 3 and normal LDH levels) showed a better response. Progression-free survival (PFS) was 19 months in G, 6 months in I, and 2 months in P. Overall survival (OS) was 27 months in G, 8 months in I, and 3 months in P. One hundred fourteen patients died (56% G, 76% I, 93% P). Patients with adenocarcinoma were 116 (77 with irAEs G1-4 (13 CR, 31 PR, 21 SD, eight PD, and four NE)), and without were 39 (three PR, six SD, 21 PD, and nine NE). Fifty-two patients had squamous carcinoma (27 with irAEs G1-4 (two CR, 12 PR, nine SD, and four PD)), and 25 did not (four PR, three SD, 12 PD, and six NE)). IrAEs appearance was observed in longer PFS (19 vs. 2 months) and OS (27 vs. 4 months; P < 0.0001). Conclusions: LIPI was a positive predictor of response to ICI. The presence of irAEs is associated with a better immune response. In contrast, the absence of toxicity predicted a worse prognosis.

Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer.

The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability.

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host-microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients' microbial gut ecosystems were rich and diverse, and the intestinal barrier's integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

Impact of antibiotics, corticosteroids, and microbiota on immunotherapy efficacy in patients with non-small cell lung cancer.

Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.

Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer.

PURPOSE: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. EXPERIMENTAL DESIGN: We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Association between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis.

Inherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS.

Factores de riesgo de deterioro cognitivo asociado a cáncer en pacientes con carcinoma de mama y colon que reciben tratamiento con quimioterapia / Risk factors for cancer-related cognitive impairment in breast and colorectal cancer patients who undergo chemotherapy

Fundamento: Nuestro estudio se plantea con el objetivo deevaluar el impacto de diferentes factores individuales sobre eldeterioro cognitivo relacionado con el cáncer en pacientes tratados con quimioterapia. Material y métodos: Estudio unicéntrico longitudinal prospectivo. Incluyó pacientes con carcinoma de mama y colon tratados con quimioterapia. Se recogieron variables clínicas y genéticas del paciente (polimorfismos de nucleótido simple, SNP). Los pacientes fueron evaluados neurocognitivamente con oncetest validados, en tres momentos: basal previo a quimioterapia(M0), entre una y cuatro semanas tras finalizar quimioterapia(M1) y entre 24-30 semanas tras finalizar quimioterapia (M2). Resultados: Se incluyeron 62 pacientes, 82% mujeres, con mediana de edad de 56 años (rango 30-74), un 64,5% con cáncer demama. La edad <55 años, tener estudios superiores, ausenciade comorbilidades y presencia de la variante CC de rs471692(TOP2A) se asociaron, en general, con mejores resultados cognitivos en M0. Se observó un empeoramiento significativo deM0 a M1 en los test RAVLT y Letras y números, y recuperaciónen M2 respecto a M0 en los test de memoria visual, FAST, clavede números, y cubos. La edad ≥55 años, la quimioterapia adyuvante, las comorbilidades, el consumo de tabaco y de alcoholy la variante GT de rs1800795 se relacionaron con el deterioroentre M0 y M1 en el modelo multivariante. Conclusiones: La edad mayor de 55 años, el sexo femenino, lapresencia de comorbilidades y el nivel básico de estudios serelacionan con un mayor riesgo de deterioro cognitivo tras eltratamiento con quimioterapia.(AU)

Background: Our study aims to evaluate the impact of differentfactors on cancer-related cognitive impairment in patients whoundergo chemotherapy.Methodology: Prospective longitudinal single-centre studythat included patients with breast and colon carcinoma whounderwent chemotherapy as part of their treatment. Clinicaland genetic characteristics of the patients (single nucleotidepolymorphisms, SNPs) were collected. Patients’ neurocognitivestatus was assessed using eleven validated tests at three timepoints: before chemotherapy (M0 - baseline), between one andfour weeks after completing chemotherapy (M1), and between24-30 weeks after completing chemotherapy (M2).Results: Sixty-two patients were included in this study; 82% werefemale, median age was 56 years (range 30-74), and 64.5% had beendiagnosed with breast cancer. Overall, better cognitive results atM0 were associated with age < 55 years, higher educational level,absence of comorbidities, and the CC variant rs471692 (TOP2A).Significant decline was found between M0 to M1 in the Rey Auditory Verbal Learning Test and the Letter and Number test, with evidence of recovery in M2 compared to M0 regarding the followingtest: Visual Memory, Functioning Assessment Short Test (FAST),Digit Symbol Substitution and Cube. In the multivariate analysis,being ≥55 years of age, adjuvant chemotherapy, presence of comorbidities, tobacco and alcohol use, and GT variant rs1800795were associated with cognitive decline between M0 and M1.Conclusion: Being ≥55 years of age, female, presence of comorbidities and basic education level are related to a higher risk ofcognitive impairment after chemotherapy.(AU)

A Delphi consensus panel about clinical management of early-stage EGFR-mutated non-small cell lung cancer (NSCLC) in Spain: a Delphi consensus panel study

Purpose This Delphi panel study assessed the level of consensus between medical oncologists on the clinical management of patients with early-stage EGFR-mutated non-small cell lung cancer (NSCLC). Methods A modified two-round Delphi approach was used. A scientific committee comprised of medical oncologists developed an online questionnaire. Delphi panel experts rated their level of agreement with each questionnaire statement on a 9-point Likert scale. The questionnaire included 36 statements from 3 domains (clinical management of early-stage NSCLC: 15 statements; role of adjuvant therapy in early-stage NSCLC: 9 statements; and role of adjuvant therapy in early-stage NSCLC with sensitizing EGFR mutation: 12 statements). Results In round 1, consensus was reached for 24/36 statements (66.7%). Nine statements that did not achieve consensus after the first round were evaluated in round 2, and none of them reached consensus. Overall, 84.4% of the panelists agreed that EGFR mutation testing should be done after surgery. Consensus was not achieved on whether the implementation of EGFR mutation testing in resected early-stage NSCLC could limit the use of adjuvant osimertinib. The panelists recognized the rationale for the use of osimertinib in the adjuvant scenario (88%) and 72% agreed that it may change the treatment paradigm in stage IB–IIIA EGFR-mutated NSCLC. Consensus was not reached on the inconvenience of prolonged duration of osimertinib. Conclusions This Delphi study provides valuable insights into relevant questions in the management of early-stage EGFR-mutated NSCLC. However, specific issues remain unresolved. The expert consensus emphasizes the role of adjuvant treatment with osimertinib in this scenario. (AU)

New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology and the Spanish Society of Medical Oncology have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice (AU)

Nueva actualización de las recomendaciones para la determinación de biomarcadores predictivos en el carcinoma de pulmón no célula pequeña: Consenso Nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica / New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

El carcinoma de pulmón de no célula pequeña (CPNCP) presenta el mayor número de dianas terapéuticas identificadas, algunas de ellas con utilidad terapéutica. En la actualidad se considera imprescindible en estos pacientes determinar las mutaciones de EGFR, BRAF, KRAS y MET, las traslocaciones de ALK, ROS1, NTRK y RET y la expresión de PD-L1. El uso de la secuenciación masiva (next-generation sequencing [NGS]) facilita el diagnóstico molecular de forma precisa y permite determinar otras mutaciones emergentes, como la mutación de HER2 y los biomarcadores predictivos de respuesta a inmunoterapia. En este consenso, un grupo de expertos en el diagnóstico y tratamiento del CPNCP seleccionado por la Sociedad Española de Anatomía Patológica (SEAP) y la Sociedad Española de Oncología Médica (SEOM) ha evaluado la información actualmente disponible y propone una serie de recomendaciones para optimizar la determinación y utilización en la práctica clínica diaria de los biomarcadores.(AU)

Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing (NGS) facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice.(AU)

Reflexiones sobre la implementación del cribado mediante tomografía computarizada de baja dosis en personas con riesgo elevado de padecer cáncer de pulmón en España / Reflections on the Implementation of Low-Dose Computed Tomography Screening in Individuals at High Risk of Lung Cancer in Spain

El cáncer de pulmón (CP) constituye un problema de salud pública de primer orden. A pesar de los recientes avances en su tratamiento, la prevención primaria y el diagnóstico precoz son las claves para reducir su incidencia y mortalidad. Un ensayo clínico reciente demostró la eficacia del cribado selectivo con tomografía computarizada de baja dosis (TCBD) en la reducción del riesgo de muerte en personas de alto riesgo, tanto por CP como global. Este artículo recoge las reflexiones de un grupo de expertos designados por la Sociedad Española de Neumología y Cirugía Torácica (SEPAR), la Sociedad Española de Cirugía Torácica (SECT), la Sociedad Española de Radiología Médica (SERAM) y la Sociedad Española de Oncología Médica (SEOM) sobre el uso de la TCBD para el diagnóstico precoz del CP en personas con riesgo elevado de padecerlo y los pasos necesarios para evaluar su implementación en nuestro país

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM)

Actualización de las recomendaciones para la determinación de biomarcadores predictivos en el carcinoma de pulmón de célula no pequeña avanzado. Consenso Nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica / Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: A National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

En el año 2011 se inició un proyecto conjunto entre la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) para establecer unas recomendaciones basadas en la evidencia actual con respecto a la determinación de biomarcadores en pacientes con carcinoma de pulmón de célula no pequeña avanzado. Al ser un área en continua evolución, estas recomendaciones se han actualizado previamente en 2012 y 2015, y ahora en 2019. Con la evidencia que existe hoy en día, las determinaciones obligatorias en cualquier paciente con este tipo de carcinoma de pulmón avanzado son las mutaciones de EGFR y BRAF, los reordenamientos de ALK y ROS1, y la expresión de PD-L1. La creciente necesidad que existe para estudiar otros biomarcadores emergentes promueve el uso de forma rutinaria de la secuenciación masiva (next-generation sequencing, NGS). Continúa siendo un reto coordinar a todos los profesionales implicados y priorizar las determinaciones y las tecnologías más adecuadas en cada caso

In 2011, the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) initiated a joint project to establish guidelines for biomarker testing in patients with advanced non-small-cell lung cancer based on the information available at the time. As this field is constantly evolving, these guidelines were updated in 2012 and 2015 and now in 2019. Current evidence suggests it should be mandatory to test all patients with this kind of advanced lung cancer for EGFR and BRAF mutations, ALK and ROS1 rearrangements and PD-L1 expression. The growing need to study other emerging biomarkers has promoted the routine use of massive sequencing (next-generation sequencing, NGS). However, the coordination of every professional involved and the prioritisation of the most suitable tests and technologies for each case remain a challenge

Actualización de las recomendaciones para la determinación de biomarcadores en el carcinoma de pulmón avanzado de célula no pequeña. Consenso Nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica / Updated guidelines for biomarker testing in advanced non-small-cell lung cancer. A national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

En el año 2011 se inició un proyecto conjunto entre la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) para establecer unas recomendaciones basadas en la evidencia actual con respecto a la determinación de biomarcadores en pacientes con carcinoma de pulmón de célula no pequeña (CPCNP) avanzado. La mayoría de estas recomendaciones siguen siendo válidas; sin embargo, existen nuevas evidencias que hacen necesaria la actualización de algunos aspectos. En concreto, se modifica la recomendación de qué biomarcadores hay que analizar y en qué pacientes, y se define el manejo óptimo de la muestra tumoral así como las características del material mínimo necesario para la determinación de biomarcadores. Además, se revisan las técnicas adecuadas para la determinación de las mutaciones de EGFR y el reordenamiento de ALK, y se consensúa en qué situaciones se debe llevar a cabo una re-biopsia (AU)

In 2011 the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) started a joint project to establish guidelines on biomarker testing in patients with advanced non-small-cell lung cancer (NSCLC) based on the current evidence. Most of these guidelines are still valid, but new evidence requires some aspects to be updated. Specifically, the recommendation about which biomarkers to test in which patients is being amended and the best way to manage tumour samples and minimum requirements for biomarker test material are defined. Suitable techniques for testing for EGFR mutations and ALK rearrangement are also reviewed, and a consensus is reached on which situations warrant re-biopsy (AU)

Recomendaciones para la determinación de biomarcadores en el carcinoma de pulmón no microcítico avanzado. Consenso nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica / No disponible

Actualmente los pacientes con cáncer de pulmón no microcítico (CPNM) avanzado portadores de mutaciones del receptor del factor de crecimiento epidérmico (EGFR), y probablemente en un futuro cercano los pacientes con reordenamientos del gen de la quinasa del linfoma anaplásico (ALK), pueden recibir un tratamiento específico basado en el resultado del análisis de biomarcadores. Esto les proporcionará mayor calidad de vida y supervivencia libre de progresión que la quimioterapia convencional. Este documento de consenso nace como una iniciativa conjunta de la Sociedad Española de Anatomía Patológica (SEAP) y de la Sociedad Española de Oncología Médica (SEOM) y propone recomendaciones diagnósticas y terapéuticas para el paciente con CPNM avanzado basadas en la evidencia científica relacionada con el uso de biomarcadores. Por tanto, supone una oportunidad para mejorar la eficiencia de la actividad asistencial y la utilización de recursos, lo que sin duda redundará en un beneficio para estos pacientes. Aunque este campo está en constante evolución, en la actualidad, con los datos disponibles, este grupo de expertos recomienda que en todos los pacientes con CPNM avanzado de células no escamosas, así como en pacientes no fumadores con independencia del subtipo histológico, se determine el estado mutacional del gen EGFR en un plazo máximo de 7 días a partir del diagnóstico anatomopatológico. Los laboratorios involucrados deben participar en programas de gestión de calidad externos. Por el contrario, los reordenamientos del gen ALK solo se deben analizar en el marco de un ensayo clínico, aunque con los datos tan prometedores que se han obtenido se justificará previsiblemente en un futuro próximo su estudio rutinario en pacientes sin mutaciones de EGFR. Por último, no se considera necesaria la determinación rutinaria de otras anormalidades moleculares en la práctica clínica actual(AU)

ingles(AU)