Frequently mutated genes in predicting the relapse of stage I lung adenocarcinoma

Purpose Approximately, 45–65% stage I non-small cell lung cancer (NSCLC) patients with surgical resection relapse within 5 years. Therefore, it is urgent to identify the predictors involved in the relapse of stage I NSCLC. Methods/patients Targeted sequencing was used to examine the mutation of tumor tissues and matched adjacent normal tissues from 35 patients with stage I lung adenocarcinoma (LUAD). Then, tissue microarrays containing tumor tissues from 149 stage I LUAD patients were used to assess protein expression of frequently mutated genes by immunohistochemistry. COX regression model was used to evaluate the impacts of frequently mutated genes and their protein expression on relapse-free survival (RFS) in stage I LUAD. Results and conclusions Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15–1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54–6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance (AU)

ADAM12 promotes gemcitabine resistance by activating EGFR signaling pathway and induces EMT in bladder cancer

Background Gemcitabine (GEM)-based chemotherapy regimens is widely used in bladder cancer (BC) patients. However, GEM resistance may occur and result in treatment failure and disease progression. A disintegrin and metalloprotease 12 (ADAM12) plays a critical role in many cancers. However, the role of ADAM12 in GEM resistance of BC remains unclear. Methods We analyzed the relationship between ADAM12 expression and tumor characteristics using the data downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Then, we established GEM resistant BC cell lines and used quantitative real-time PCR, western blot, cell counting kit-8, immunohistochemistry, and xenograft mouse model to investigate the role of ADAM12 in GEM resistance. Results In general, ADAM12 was found to be upregulated in GEM resistant BC cells. ADAM12 knockdown increased the chemosensitivity of BC cells. We further proved that ADAM12 could promote GEM resistance by activating the epidermal growth factor receptor (EGFR) signaling pathway in BC. Furthermore, the epithelial–mesenchymal transition (EMT) phenotype was observed in GEM resistant BC cells. ADAM12 induced EMT process and promotes tumor progression in BC. Conclusion Our findings suggested that ADAM12 was a key gene for GEM resistance and positively correlated with malignancy of BC. It might serve as a novel and valuable therapeutic target for BC (AU)

Methylation detection of circulating tumor cell miR-486-5p/miR-34c-5p in the progression of colorectal cancer

Aims This study set out to examine the expression and methylation levels of miR-486-5p/miR-34c-5p and its mechanism of action based on the microRNA methylation level of circulating tumor cells (CTCs) in colorectal cancer (CRC) through clinical data and tissue detection. Methods EGFR and EpCAM immunophospholipid magnetic spheres (EpCAM-IML/EGFR-IML) were synthesized by the thin film method to capture CTCs in peripheral blood. The expression of miR-486-5p/miR-34c-5p was detected via real-time fluorescent quantitative PCR (RT-PCR). Methylation-specific PCR was implemented to detect the methylation level of miR-486-5p/miR-34c-5p, and 5-Aza-dC was used for demethylation treatment to detect the effect of changes in methylation levels on the tumor cells development. Cell Counting Kit-8 (CCK-8) analysis, transwell assay, and flow cytometry were used to determine the effects of demethylation and overexpression on the proliferation, invasion, migration, and apoptosis of CRC cells. Results The results showed that the expression and methylation levels of the miR-486-5p/miR-34c-5p isolated from CTCs were low and the methylation level was high in tumor cells and tissues. In CRC cell lines, demethylation and overexpression of miR-486-5p/miR-34c-5p could effectively inhibit the proliferation, invasion and migration of tumor cells, and facilitate tumor apoptosis (p < 0.05). Conclusion The constructed CTCs sorting system has characteristics of high specificity and high sensitivity, is a supplement to tissue samples, and has guiding significance for the clinical rational use of drugs and personalized therapy (AU)

Asparaginyl endopeptidase contributes to cetuximab resistance via MEK/ERK signaling in RAS wide-type metastatic colorectal cancer

Background Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), is effective for RAS wild-type metastatic colorectal cancer (mCRC) patients. However, cetuximab resistance often occur and the mechanism has not been fully elucidated. The purpose of this study was to investigate the role of asparaginyl endopeptidase (AEP) in cetuximab resistance. Methods Differentially expressed genes between cetuximab responders and non-responders were identified by analyzing the gene expression profile GSE5851, retrieved from Gene Expression Omnibus (GEO). The potential genes were further validated in cetuximab-resistant CRC cell lines. The expression of AEP in the peripheral blood and tumor tissues of mCRC patients in our hospital were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The survival analysis was carried out by Kaplan–Meier method. The function and associated pathways of AEP were further investigated by lentivirus transfection, CCK8 assay, colony formation assay, real-time polymerase chain reaction (qPCR) and western blot. Results Through bioinformatics analysis, we found that the expression of AEP gene was related to progress free survival (PFS) of mCRC patients treated with cetuximab alone (P = 0.00133). The expression of AEP was significantly higher in the cetuximab-resistant CRC cell lines, as well as in mCRC patients with shorter PFS treated with cetuximab-containing therapy. Furthermore, AEP could decrease the sensitivity of CRC cells to cetuximab in vitro. And the phosphorylation level of MEK and ERK1/2 was increased in AEP overexpression cells (AU)

Pre-radiotherapy systemic immune inflammation index associated with overall survival in patients with advanced EGFR mutant non-small cell lung cancer receiving thoracic radiotherapy

Purpose This study aimed to investigate the prognostic potential of the pre-radiotherapy systemic immune-inflammation index (SII) for the survival of advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations, which might provide a basis for optimizing the comprehensive treatment scheme. Methods A total of 111 lung adenocarcinoma patients with EGFR mutations, who received thoracic radiotherapy, were included in this retrospective study. The primary endpoint of the study was based on the overall survival (OS) of patients. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of each immune inflammation index. Kaplan–Meier analysis was performed for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate regression analyses to determine the correlations of prognostic factors with the disease. Results SII was divided into the high SII group (≥ 620.2; 45.95%) and the low SII group (SII < 620.2; 54.05%) based on the optimal cutoff values. The median OS rates were 53.3 and 33.3 months in the low and high SII groups, respectively, showing statistically significant differences ( hazard ratio (HR) = 0.459; 95% CI 0.286–0.736; P < 0.001). The multivariate analysis showed that, after adjusting for the significant covariates, the SII values were independently associated with the improved OS of the patients (adjusted HR = 0.444; 95% CI 0.279–0.709; P = 0.001). The low NLR values were associated with the better OS of patients (HR = 0.509; 95% CI 0.326–0.792; P = 0.005) and vice versa (HR = 0.422; 95% CI 0.213–0.836; P < 0.001). The patients in the low LMR group before radiotherapy exhibited longer OS as compared to those in the high LMR group (HR = 0.497; 95% CI 0.308–0.802; P = 0.001) (AU)

Expression and potential role of CCL4 in CD8+T cells in NSCLC

Purpose Under the continuous stimulation of tumor antigen in the tumor microenvironment, CD8+T cells will enter a state of functional defect or failure, which cannot effectively prevent the progression of lung cancer. Therefore, finding potential targets for immunotherapy in lung cancer has broad prospects. Methods In the early stage of this study, the genes related to immune infiltration in lung cancer were found through the analysis on multiple datasets (GSE116959, GSE139032 and GSE111894). Characteristics of candidate genes were identified from transcriptome, methylation, single cell sequencing and other dimensions, respectively. Moreover, the correlation between candidate genes and immunotherapy-related genes and mutated genes of lung cancer was further identified. Finally, the expression of the candidate genes was detected with an online immunohistochemistry database. Results According to the above research, it was found that CCL4 (chemokine (C–C motif) ligand 4) was abnormally highly expressed in samples from patients with NSCLC and had certain methylation characteristics. In addition, CCL4 was also closely associated with infiltration of immune cells, such as B cells and CD8+T cells. Interestingly, the aberrant expression of CCL4 affected the survival of CD8+T cells. Single cell sequencing results also showed that CCL4 was highly expressed in CD8+T cells and was involved in biological functions such as generation cycle. Finally, CCL4 expression was positively associated with PD-1 and PD-L1, and also with mutant genes, such as EGFR, ALK and ROS1, associated with the treatment for lung cancer. Conclusion CCL4 may be a potential target for immunotherapy in patients with NSCLC (AU)

Sensitivity analysis of EGFR L861Q mutation to six tyrosine kinase inhibitors

Purpose: Lung cancer is one of the most common carcinomas with the highest mortality in the world. Non-small cell lung carcinoma has a large proportion of epidermal growth factor receptor (EGFR) mutations, of which rare EGFR mutations account for about 10%–20%. Currently, tyrosine kinase inhibitors (TKIs) therapy is a standard treatment for patients with non-small cell lung carcinoma with EGFR mutations. To date, the toxicological effects of the EGFR L861Q variant (less than 2%) have been rarely reported, so further investigation of its sensitivity to six first-in-class TKIs is of great clinical interest.MethodsIn this study, two EGFR L861Q variants cell lines (EGFR L861Q variant and EGFR L861Q + exon 19 deletion variant) were established by CRISPR-Cas9 gene-editing technology. The steady-state plasma concentrations of six TKIs (gefitinib/erlotinib/icotinib, the first generation; dacomitinib/afatinib, the second generation; and osimertinib, the third generation) were tested, respectively. The change of cell viability, proliferation, cloning ability, mitochondrial membrane potential and apoptosis were detected by MTT assay, EdU staining assay, colony formation assay, mitochondrial membrane potential and apoptosis test. TUNEL and Annexin V / PI staining were used to detect cell apoptosis, and flow cytometry was employed to explore the sensitivity of two variants to six TKIs.ResultsOur study indicated that the six TKIs inhibited the viability of the two cell lines in a time-dependent manner, and the inhibitory time of six TKIs on proliferation was different between the two cell lines. The proliferation and cloning ability of two cell lines were inhibited by six TKIs. The cytoskeleton morphology, microfilament structure and distribution of the two cell lines were changed by six TKIs. (AU)

LncRNA ABHD11-AS1 promotes tumor progression in papillary thyroid carcinoma by regulating EPS15L1/EGFR signaling pathway

ObjectiveslncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11‐AS1 could be helpful in therapeutic targeting for PTC treatment.MethodsDifferentially expressed lncRNAs were selected from TCGA database. qRT‐PCR analysis was applied to examine the expression of ABHD11‐AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan–Meier analysis.Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo.ResultsHigh expression of ABHD11‐AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated.ConclusionABHD11‐AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.

Resistencia a los anticuerpos monoclonales anti-EGFR en el tratamiento del carcinoma de cabeza y cuello / Resistance to anti-EGFR monoclonal antibodies in the treatment of head and neck carcinoma

Introducción: Los anticuerpos monoclonales dirigidos al receptor del factor de crecimiento epidérmico (EGFR) han demostrado beneficio clínico en el carcinoma de cabeza y cuello en estadios avanzados, sin embargo, a pesar de los alentadores resultados iniciales, los estudios clínicos evidencian que hay pacientes que presentan tasas de respuesta muy pobres o nulas con su uso. Método: Se realizó una revisión de la bibliografía científica en las fuentes especializadas Medline, Cochrane Library y Google académico sobre los mecanismos moleculares de resistencia que pueden estar involucrados en la reducción de la eficacia de los anticuerpos monoclonales cetuximab y nimotuzumab. Resultados: En el caso del cetuximab, se exponen los mecanismos de resistencia intrínseca y adquirida tales como: la presencia de los polimorfismos EGFR-K521 y AURKA Phe31-Ile, la activación de puntos calientes de mutaciones en PIK3CA y KRAS/HRAS, la pérdida de expresión de PTEN, las mutaciones en el dominio extracelular del EGFR, la sobreexpresión de MET e inducción de la transición epitelial-mesenquimal, así como algunos mecanismos que involucran las vías AKT/PI3K, RAS/RAF/MEK/ERK y JAK/STAT. Con respecto al nimotuzumab, la literatura refiere que los mejores resultados clínicos con su uso se han asociado con la sobreexpresión del EGFR. Conclusiones: Los mayores desafíos en el carcinoma de cabeza y cuello son comprender la resistencia a estas terapias e identificar biomarcadores predictivos de respuesta para la selección adecuada de los pacientes. Aunque son múltiples las propuestas de biomarcadores que se publican, requieren su validación en ensayos clínicos prospectivos para su introducción en la práctica clínica habitual. Se sugiere la necesidad de incrementar los estudios sobre los mecanismos de resistencia al nimotuzumab. (AU)

Introduction: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefit in advanced stages of head and neck carcinoma; however, despite encouraging initial results, clinical stud-ies show that there are patients who present rates very poor or null response with its use. Method: A review of the scientific literature was carried out in the specialized sources Medline, Cochrane Library and academic Google on the molecular mechanisms of resistance that may be involved in reducing the efficacy of the monoclonal antibodies cetuximab and nimotuzumab. Results: In the case of cetuximab, the mechanisms of intrinsic and acquired resistance are exposed, such as: the presence of the EGFR-K521 and AURKA Phe31-Ile polymorphisms, the hot spots activating PIK3CA and KRAS/HRAS mutations, the loss of PTEN protein expression, mutations in the extracellular domain of EGFR, overexpression of MET and induction of epithelial–mesenchymal transition, as well as some mechanisms involving the AKT/PI3K, RAS/RAF/MEK/ERK and JAK/STAT pathways. About nimotuzumab, the literature refers that the best clinical results with its use have been associated with EGFR overexpression. Conclusions: The greatest challenges in head and neck carcinoma are understanding resistance to these therapies and identifying predictive biomarkers of response for proper patient selection. Although there are multiple propos-als for biomarkers that are published, they require their validation in prospective clinical trials for their introduction into routine clinical practice. The need to increase studies on the mechanisms of resistance to nimotuzumab is suggested. (AU)

Preparation of a novel EGFR specific immunotoxin and its efficacy of anti-colorectal cancer in vitro and in vivo

Objectives Epithelial growth factor receptor (EGFR), as a malignancy marker, is overly expressed in multiple solid tumors including colorectal neoplasms, one of the most prevalent malignancies worldwide. The main objective of this study is to enhance the efficacy of anti-tumor therapy targeting EGFR by constructing a novel EGFR-specific immunotoxin (C-CUS245C) based on Cetuximab and recombinant Cucurmosin (CUS245C). Methods E. coli BL21 (DE3) PlysS (E. coli) was used to express CUS245C with a cysteine residue inserting to the C-terminus of Cucurmosin. Then immobilized metal ion affinity chromatography (IMAC) was used to purify CUS245C. The chemical conjugation method was used for the preparation of C-CUS245C. Then dialysis and IMAC were used to purify C-CUS245C. Western blot as well as SDS-PAGE was carried out to characterize the formation of C-CUS245C. At last the anti-colorectal cancer activity of C-CUS245C was investigated in vitro and in vivo. Results CUS245C with high purity could be obtained from the prokaryotic system. C-CUS245C was successfully constructed and highly purified. The cytotoxicity assays in vitro showed a significant proliferation inhibition of C-CUS245C on EGFR-positive cells for 120 h with IC50 values less than 0.1 pM. Besides, the anti-tumor efficacy of C-CUS245C was remarkably more potent than that of Cetuximab, CUS245C, and C + CUS245C (P < 0.001). Whereas the cytotoxicity of C-CUS245C could hardly be detected on EGFR-null cell line. Our results also showed that C-CUS245C had efficacy of anti-colorectal cancer in mouse xenograft model, indicating the therapeutic potential of C-CUS245C for the targeted therapy of colorectal neoplasms. Conclusions C-CUS245C exhibits potent and EGFR-specific cytotoxicity. Insertional mutagenesis technique is worthy to be adopted in the preparation of immunotoxin. Immunotoxin can be highly purified through dialysis followed by IMAC (AU)

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus

Aim To stablish a consensus on the treatment strategy for advanced non–small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. Methods After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1–9 range scale (1–3 = disagree, 7–9 = agree). Consensus was reached if 2/3 of the participants are in the median range. Results In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. Conclusions A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations (AU)

Osimertinib for the Treatment of EGFR Mutation-Positive Lung Adenocarcinoma Complicated With Dermatomyositis / El osimertinib como tratamiento del adenocarcinoma de pulmón con mutación positiva del EGFR complicado con dermatomiositis

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ASTRIS, a large real-world study to evaluate the efficacy of osimertinib in epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer patients: Clinical characteristics and genotyping methods in a Spanish cohort / ASTRIS, un gran estudio en el mundo real para evaluar la eficacia de osimertinib en pacientes de cáncer de pulmón no microcítico positivo a la mutación de T790M del receptor del factor de crecimiento epidérmico: características clínicas y métodos de genotipificación en una cohorte española

PURPOSE: Osimertinib has proven efficacy in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients; however, its benefits have not been evaluated in a real-world setting. METHODS: ASTRIS is a single-arm, open-label, multinational study to evaluate the efficacy and safety of osimertinib for the treatment of EGFR T790M mutation-positive NSCLC. We present the study design and preliminary cut-off analysis results (as of October 2017) describing the baseline characteristics and methodology for T790M mutation detection in the Spanish cohort. RESULTS: The Spanish cohort included 131 patients from a total 3014 patients. Forty patients (28.1%) were still undergoing therapy at the time of cut-off; 68.7% were women and 97.7% were Caucasian, with a mean age of 64.8 (SD 11.7) years. The most common type of sample for evaluating T790M mutations was tissue (55.0%), and samples were obtained from the primary tumor in 61.1% of cases. Mutation analysis was performed by the local laboratory in 60.3% of cases and using the Roche Cobas® EGFR assay in 43.5% of cases. CONCLUSIONS: ASTRIS is expected to confirm the benefits of osimertinib in a real-world setting. Data on real-world practices for the detection of the EGFR T790M mutation may provide additional information for the designing of guidelines for best practices

OBJETIVO: Osimertinib ha probado su eficacia en los pacientes de cáncer de pulmón no microcítico (CPNM) positivo a la mutación de EGFR T790M; sin embargo, sus beneficios no han sido evaluados en el mundo real. MÉTODOS: ASTRIS es un estudio de brazo único, abierto y multinacional para evaluar la eficacia y la seguridad de osimertinib para el tratamiento del CPNM positivo a la mutación de EGFR T790M. Presentamos el diseño del estudio y los resultados del análisis del punto de corte (octubre de 2017), que describe las características basales y la metodología de la detección de la mutación de T790M en la cohorte española. RESULTADOS: La cohorte española incluyó 131 pacientes de entre un total de 3.014 sujetos. Cuarenta pacientes (28,1%) seguían en terapia en el momento del punto de corte, el 68,7% eran mujeres y el 97,7% eran caucásicos, con una edad media de 64,8 (DE: 11,7) años. El tipo más común de muestra para evaluar las mutaciones de T790M fue tisular (55%), habiéndose obtenido las muestras del tumor primario en el 61,1% de los casos. El análisis de la mutación fue realizado por parte del laboratorio local en el 60,3% de los casos, utilizando el ensayo Roche Cobas® EGFR en el 43,5% de los casos. CONCLUSIONES: Se espera que ASTRIS confirme los beneficios de osimertinib en el mundo real. Los datos sobre las prácticas en el mundo real para la detección de la mutación de EGFR T790M podrían proporcionar información adicional para aportar directrices sobre las mejores prácticas

Los parámetros volumétricos de la PET pueden predecir la supervivencia global en el adenocarcinoma pulmonar avanzado / Volumetric PET parameters can predict overall survival in advanced lung adenocarcinoma

OBJETIVO: El presente estudio evalúa el valor pronóstico de los parámetros metabólicos relacionados con el tumor primario en el 18F-FDG PET/TC pretratamiento en pacientes con adenocarcinoma pulmonar en fase avanzada. MATERIALES Y MÉTODOS: Este estudio retrospectivo incluyó 258 pacientes con adenocarcinoma pulmonar en fase avanzada a los que se les realizó un escáner PET/TC del pretratamiento y para quienes estaba disponible el receptor del factor de crecimiento epidérmico (EGFR)/cinasa de linfoma anaplásico (ALK). Se registraron el valor máximo de captación estándar (SUVmáx), SUVmean, el volumen tumoral metabólico (MTV) y la glucólisis total de la lesión (TLG) relacionados con el tumor primario en la PET basal y diversos factores clínicos. Se evaluó la relación entre estos factores y la supervivencia global (OS) y la supervivencia libre de progresión (PFS). RESULTADOS: El estudio incluyó a 258 pacientes con adenocarcinoma pulmonar en fases IIIB-IV (72 mujeres, 186 hombres, de edad media 60,4 +/- 10,4 años), 210 de los cuales murieron y 243 progresaron en el momento del análisis. La OS y PFS media de los pacientes fue de 16 +/- 1,9 y 5 +/- 0,5 meses respectivamente. El presente estudio no reveló una relación significativa entre la OS o PFS y el sexo, el estatus de fumador, la presencia de metástasis a distancia, la edad y el tamaño del tumor. No hubo una diferencia significativa en la OS y PFS de los pacientes que dieron resultados negativos en mutaciones EGFR/reorganizaciones ALK y los que dieron resultados positivos para ambos o para las mutaciones EGFR o las reorganizaciones ALK. La OS fue significativamente más larga en pacientes con MTV bajo (p = 0,011) y en aquellos con TLG bajo (p = 0,012) que en los que los tenían altos. No obstante, no se encontró una relación significativa entre los valores SUVmáx y SUVmean y la OS, ni entre todos los parámetros del PET y la PFS. CONCLUSIÓN: Los MTV y TLG que reflejen la carga tumoral metabólica pueden predecir la OS en pacientes con adenocarcinoma pulmonar avanzado

OBJECTIVE: The present study evaluates the prognostic value of metabolic parameters related to the primary tumor on pretreatment 18F FDG PET/CT in patients with advanced stage lung adenocarcinoma. MATERIAL AND METHODS: This retrospective study included 258 patients with advanced stage lung adenocarcinoma who underwent pretreatment PET/CT scan, and for whom epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) status was available. The maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) related to the primary tumor at the baseline PET and various clinical factors were recorded. The relation between these factors and overall survival (OS) and progression-free survival (PFS) was evaluated. RESULTS: The study included 258 patients with stage IIIB-IV lung adenocarcinoma (72 female, 186 male, mean age 60.4+/-10.4 years), 210 of which died and 243 of which progressed at the time of analysis. The median OS and PFS of the patients were 16+/-1.9 and 5+/-0.5 months, respectively. The present study revealed no significant relation between OS or PFS and gender, smoking status, presence of distant metastasis, age and tumor size. There was no significant difference in the OS and PFS of patients testing negative for EGFR mutations/ALK rearrangements and those testing positive for both or either of the EGFR mutations and ALK rearrangements. OS was significantly longer in patients with low MTV(p = 0.011) and those with low TLG(p = 0.012) than high ones. However, no significant relation was found between SUVmax and SUVmean values and OS, and between all PET parameters and PFS. CONCLUSION: MTV and TLG reflecting the metabolic tumor burden can predict OS in patients with advanced lung adenocarcinoma

Acquired T790M-positive Squamous Cell Lung Carcinoma that Responded to Osimertinib / Carcinoma pulmonar de células escamosas con mutación T790M adquirida que respondió a osimertinib

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FR - Inhibidores del factor de crecimiento epidérmico y toxicidad cutánea: en busca de un protocolo de manejo / RF - Epidermal Growth Factor Receptor Inhibitors and Skin Toxicity: The Search for a Management Protocol

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Accurate Identification of Predictive Biomarkers of Response to Targeted Therapies in Lung Cancer With Next Generation Sequencing / Identificación precisa de biomarcadores predictivos de respuesta a terapias dirigidas en cáncer de pulmón con secuenciación de nueva generación

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Clinical and Mutational Aspects of Non-small Cell Lung Cancer in a Latin American Reference Center / Aspectos clínicos y mutacionales del cáncer de pulmón de célula no pequeña en un Centro de Referencia de Latinoamerica

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Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS

Purpose: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. Methods: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. Results: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. Conclusions: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable

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