Intratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor

Intratumoral heterogeneity has been suggested to be an important resistance mechanism leading to treatment failure. We hypothesized that radiologic images could be an alternative method for identification of tumor heterogeneity. We tested heterogeneity textural parameters on pretreatment FDG-PET/CT in order to assess the predictive value of target therapy. Recurred or metastatic non-small cell lung cancer (NSCLC) subjects with an activating EGFR mutation treated with either gefitinib or erlotinib were reviewed. An exploratory data set (n = 161) and a validation data set (n = 21) were evaluated, and eight parameters were selected for survival analysis. The optimal cutoff value was determined by the recursive partitioning method, and the predictive value was calculated using Harrell's C-index. Univariate analysis revealed that all eight parameters showed an increased hazard ratio (HR) for progression- free survival (PFS). The highest HR was 6.41 (P< 0.01) with co-occurrence (Co) entropy. Increased risk remained present after adjusting for initial stage, performance status (PS), and metabolic volume (MV) (aHR: 4.86, P< 0.01). Textural parameters were found to have an incremental predictive value of early EGFR tyrosine kinase inhibitor (TKI) failure compared to that of the base model of the stage and PS (C-index 0.596 vs. 0.662, P = 0.02, by Co entropy). Heterogeneity textural parameters acquired from pretreatment FDG-PET/CT are highly predictive factors for PFS of EGFR TKI in EGFR-mutated NSCLC patients. These parameters are easily applicable to the identification of a subpopulation at increased risk of early EGFR TKI failure. Correlation to genomic alteration should be determined in future studies.

Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non-small-cell lung carcinoma

Malignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non-small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulated GNB2L1 and CAV1 expression were enriched in the EGFR TKI-resistant group. Moreover, GZMK upregulated transitional effector T cells, and plasmacytoid dendritic cells were significantly enriched in the EGFR TKI-resistant patients. Our results suggest that cellular plasticity and immunosuppressive microenvironment in MPEs are potentially associated with the TKI response of patients with EGFR-mutated NSCLC

Mechanizace svařování uskladňovacích nádrží velkých objemů na montáži

Import 20/04/2006Prezenční výpůjčkaFakulta strojní a elektrotechnická VŠB (Ostrava). Katedra mechanické technologie (345

Mapování procesu objemového tváření se zaměřením na zápustkové kování

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta strojní. Katedra (345) mechanické technologi

Metody měření zrychlení v technické diagnostice

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Fakulta strojní. Katedra (352) automatizační techniky a řízen

Additional file 5: Table S3. of Characterization of genetic aberrations in a single case of metastatic thymic adenocarcinoma

Occurrences of the TP53 p.C176F variant in the COSMIC database (version 68). (DOCX 12 kb

Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations?

Approximately 10% of the epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are uncommon EGFR mutations. Although the efficacy of second (2G) or third generation (3G) EGFR tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon EGFR mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon EGFR mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon EGFR mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon EGFR mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major EGFR mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8&ndash;13.5), 11.7 months (95% CI: 6.6&ndash;16.7), 7.7 months (95% CI: 4.9&ndash;17.4), and 5.0 months (95% CI: 3.7&ndash;6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9&ndash;34.2), 28.8 (95% CI: 24.4&ndash;33.4), 13.5 months (95% CI: 7.4&ndash;27.8), and 9.4 months (95% CI: 3.4&ndash;10.5) for major uncommon EGFR mutation (G719X), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6&ndash;16.9), and 37.5 months (95% CI: 35.4&ndash;39.6) for common EGFR mutation-positive NSCLC. After failing 1L EGFR-TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G EGFR-TKI after failing the first-line EGFR-TKI, the ORR and PFS for 3G EGFR-TKI were 80% and 8.9 months (95% CI: 8.0&ndash;9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8&ndash;39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common EGFR mutations. T790M was detected in 28.6% of the uncommon EGFR mutation-positive patients for whom prior 1G/2G EGFR-TKIs failed and underwent repeat biopsy at the time of progression

Additional file 11: Table S6. of Characterization of genetic aberrations in a single case of metastatic thymic adenocarcinoma

Two fusion transcripts detected by deFuse (DOCX 13 kb

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations

Background/Aims: Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. Methods: A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. Results: In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. Conclusions: Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.