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PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-mutant, metastatic non-small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum-based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837). METHODS: Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS. RESULTS: Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients. CONCLUSION: Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.
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In practical visual search fields, observers often encounter errors that result from an unknown number of targets, which may induce reduced accuracy and speed. Our current study addresses the potential enhancement of collaborative search efficiency as a dyad to mitigate such incurred search costs. Utilizing the capacity coefficient, we evaluated search efficiency and explored the interplay of task difficulty and termination rule in collaborative visual search. Our prediction that collaborative benefits increased with elevated task difficulty was not supported in Experiment 1, where participants were tasked with judging the presence of any target. In contrast, Experiment 2 demonstrated that dyads exhibited greater search efficiency during exhaustive searches for multiple targets with elevated task difficulty. Notably, our findings indicated an advantage in dyad searches compared to baseline predictions from individual searches. Our results underscored the significance of task difficulty and termination rules in leveraging human resources for improved collaborative visual search performance.
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The 2023 consensus from the Taiwanese Dermatological Association (TDA) and Taiwan Lung Cancer Society (TLCS) addresses the management of tyrosine kinase inhibitor (TKI)-induced skin toxicities in non-small cell lung cancer (NSCLC). Providing a comprehensive overview, the consensus reflects recent advances in understanding causes and developmental processes of TKI-related skin toxicities. Aimed at guiding clinicians in Taiwan, the consensus integrates new treatment perspectives while incorporating experiences from local dermatology experts. Recommendations underwent a voting process, achieving consensus when 75% or more of experts agreed, leading to their inclusion. Approved by over 90% of participants, the recommended treatment algorithms for major skin toxicities offer valuable insights for clinicians managing TKI-associated effects in NSCLC patients.
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This study delves into expressing primary emotions anger, happiness, sadness, and fear through drawings. Moving beyond the well-researched color-emotion link, it explores under-examined aspects like spatial concepts and drawing styles. Employing Python and OpenCV for objective analysis, we make a breakthrough by converting subjective perceptions into measurable data through 728 digital images from 182 university students. For the prominent color chosen for each emotion, the majority of participants chose red for anger (73.11%), yellow for happiness (17.8%), blue for sadness (51.1%), and black for fear (40.7%). Happiness led with the highest saturation (68.52%) and brightness (75.44%) percentages, while fear recorded the lowest in both categories (47.33% saturation, 48.78% brightness). Fear, however, topped in color fill percentage (35.49%), with happiness at the lowest (25.14%). Tangible imagery prevailed (71.43-83.52%), with abstract styles peaking in fear representations (28.57%). Facial expressions were a common element (41.76-49.45%). The study achieved an 81.3% predictive accuracy for anger, higher than the 71.3% overall average. Future research can build on these results by improving technological methods to quantify more aspects of drawing content. Investigating a more comprehensive array of emotions and examining factors influencing emotional drawing styles will further our understanding of visual-emotional communication.
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Emotions , Facial Expression , Humans , Emotions/physiology , Male , Female , Young Adult , Happiness , Anger/physiology , Adult , Fear/psychology , SadnessABSTRACT
Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC.
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Acrylamides , Aniline Compounds , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Mutation , Protein Kinase Inhibitors , Humans , Acrylamides/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Aniline Compounds/therapeutic use , Female , ErbB Receptors/genetics , ErbB Receptors/antagonists & inhibitors , Male , Middle Aged , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Aged , Adult , Protein Kinase Inhibitors/therapeutic use , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Neoplasm Metastasis , Progression-Free Survival , Indoles , PyrimidinesABSTRACT
Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25-8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12-17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).
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Antibodies, Monoclonal, Humanized , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Male , Female , Treatment OutcomeABSTRACT
Prior research has highlighted the potential impact of aerobic exercise on cognitive functioning, particularly in situations demanding heightened cognitive control. However, the mechanism underlying this cognitive enhancement has remained unknown. To address this issue, this study examined the impact of a 4-week aerobic exercise program on cognitive control processes in young male adults (aerobic exercise group: n=36, aged 21.42±1.13years) in comparison to a control group that received no treatment (n=33, aged 21.82±1.76years). We employed the redundant-target Stroop task to investigate inhibition processes at both perceptual and semantic stages. Utilizing systems factorial technology and the drift diffusion model, we assessed changes in resilience capacity and the underlying cognitive mechanisms. Our primary findings revealed a significant reduction in mean response times (RTs) in the aerobic exercise group, accompanied by a decrease in RT variability when inhibiting semantic processing. Resilience capacity significantly declined in both groups at similar levels. Notably, the aerobic exercise group exhibited an enhanced drift rate during automatic response inhibition and reduced non-decision time in the condition involving the inhibition of perceptual information. This study deepens our understanding of how a 4-week aerobic exercise program enhances cognitive control, affecting distinct cognitive processes, including processing speed, information accumulation during automatic response inhibition, and sensory and motor processes in perceptual conflicts. Our research underscores the potential of aerobic exercise as a means to boost cognitive control among young adults.
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Cognition , Exercise , Humans , Male , Young Adult , Exercise/physiology , Cognition/physiology , Exercise Therapy , Reaction Time/physiologyABSTRACT
Introduction: Pulse harmonic analysis is a quantitative and objective methodology within traditional Chinese medicine (TCM) used to evaluate pulse characteristics. However, interpreting pulse wave data is challenging due to its inherent complexity. This study aims to provide a comprehensive review and comparison of existing human pulse wave harmonic analysis methods to elucidate their patterns and characteristics. Methods: A systematic review of clinical research reports published from 1990 to 2021 was conducted, focusing on variations in harmonic characteristics across different medical conditions and physiological states. Keyword searches included terms related to analysis methods (e.g., "Pulse Spectrum," "harmonic analysis," "harmonic index") and measured indicators (e.g., "vascular response," "PPG," "Photoplethysmography," "aortic," "arterial," "blood pressure"). Supplementary research using PubMed's Mesh terms specifically targeted "Pulse wave analysis" within the methods and statistical analysis domain. Articles were filtered based on predefined criteria, including human participants and research related to pulse pressure or vascular volume changes. Conference papers, animal studies, and irrelevant research were excluded, with literature evaluation scales selected based on the retrieved research reports. Results: Initially, 6487 research reports were identified, and after screening, 50 reports were included in the review. The analysis revealed that low-frequency harmonics increase following vigorous activity or sympathetic excitation but decrease during rest or parasympathetic excitation. Cardiovascular patients exhibited elevated first harmonics associated with the liver meridian, while diabetes patients displayed weakened third harmonics related to the spleen meridian. Liver dysfunction was linked to changes in the first harmonic, and cancer patients showed signs of liver and kidney yin deficiency in the first and second harmonics. These findings underscore the potential of harmonic analysis for TCM disease diagnosis and organ assessment. Moreover, individuals with conditions such as liver dysfunction, cancer, and gynecological disorders displayed distinct intensity patterns across harmonics one through ten compared to healthy controls, albeit with some variations. Heterogeneity in these studies mainly stemmed from differences in measurement methods and study populations. Additionally, research suggested that factors like blood circulation and cognitive activity influenced harmonic intensity. Conclusions: In summary, this report consolidates prior research on pulse wave harmonics analysis, revealing unique patterns associated with various physiological conditions. Despite limitations, such as limited sample sizes in previous studies, the observed associations between physiological states and harmonics hold promise for potential clinical applications. This study lays a solid foundation for future applications of arterial wave harmonics analysis, promoting wider adoption of this analytical approach.
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Physical activity has been viewed as a potential non-pharmacological therapeutic strategy to improve the clinical symptoms and neurocognitive deficits in patients with schizophrenia. However, there are various types of physical activities, and different exercise prescriptions might produce inconsistent benefits. Thus, this study aimed to conduct a systematic review of exercise interventions for patients with schizophrenia, clarifying the benefits of these interventions on cognitive function and clinical symptoms. This review encompasses six electronic databases, with inclusion criteria including randomized controlled trial designs, participants with schizophrenia, and a comprehensive exercise intervention program. Twenty-seven studies met the inclusion criteria, incorporating data from 1549 patients with schizophrenia. The results highlight that when comparing the exercise intervention group to the non-intervention control group, patients with schizophrenia showed significant improvement in negative symptoms. Structured exercise interventions can help improve the negative symptoms of schizophrenia, filling the gaps where medication falls short. Regarding functional outcomes, exercise interventions aid in enhancing the overall functionality (psychological, social, occupational) of individuals with schizophrenia. The improvement is largely tied to the boost in physical fitness that exercise provides. Based on current findings, exercise interventions assist in enhancing cognitive function in patients with schizophrenia. Notably, significant improvements are observed in higher-order cognitive functions, including processing speed, attention, and working memory. It is recommended to engage in moderate-intensity exercises at least three times a week, with each session lasting a minimum of 30min. Well-structured exercise interventions contribute to enhancing the negative symptoms and cognitive functions in patients with schizophrenia.
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Exercise Therapy , Randomized Controlled Trials as Topic , Schizophrenia , Humans , Schizophrenia/therapy , Schizophrenia/complications , Cognition/physiology , Exercise/physiology , Schizophrenic PsychologyABSTRACT
Background: Encountering challenges and stress heightens the vulnerability to mental disorders and diminishes well-being. This study explores the impact of psychological resilience in the context of adverse events, considering age-related variations in its influence on well-being. Methods: A total of 442 participants (male vs. female =48% vs. 52%) with a mean age of 41.79 ± 16.99 years were collected and completed the following questionnaires Brief Betrayal Trauma Survey (BBTS), Brief Resilience Scale (BRS), Peace of Mind (PoM), The World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Social Support Questionnaire (SSQ). They all underwent structural and resting-state functional magnetic resonance imaging (MRI) scans. Results: Participants were categorized based on adversity levels: 34.39% faced one, 26.24% none, and 19.91, 9.50, and 8.14% encountered two, three, and four adversities, respectively. This categorization helps assess the impact on participants' experiences. As adversity factors increased, PoM decreased. Controlling for age improved PoM model fit (ΔR2 = 0.123, p < 0.001). Adversity factors and age explained 14.6% of PoM variance (df = 2, F = 37.638, p < 0.001). PoM decreased with more adversity and increased with higher age. Conclusion: The study found most participants faced at least one adversity. Adversity negatively affected PoM scores, while resilience acted as a protective factor. Resilience plays a crucial role in buffering the impact of adversities on well-being. Among those with high adversity, higher resilience correlated with stronger DMN-right frontal pole connectivity. Brain volume showed no significant differences, but the quality of life and social support varied between subgroups, with no differences in personal demographic and biophysical features.
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BACKGROUND: This study aimed to investigate the factors associated with prolonged progression-free survival (PFS) (>36 months) of advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first-line afatinib. METHODS: We performed a retrospective analysis of data of patients with advanced EGFR-mutated NSCLC receiving first-line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022. RESULTS: The data of 546 treatment-naïve EGFR-mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067-0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log-rank test, p < 0.001). CONCLUSIONS: We found that EGFR-mutated NSCLC patients receiving first-line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis.
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Carcinoma, Non-Small-Cell Lung , Liver Neoplasms , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Afatinib/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Progression-Free Survival , Retrospective Studies , ErbB Receptors/genetics , Mutation , Protein Kinase Inhibitors/therapeutic useABSTRACT
BACKGROUND: In real-world practice, most patients with lung cancer are diagnosed when they are aged ≥65 years. However, clinical trials tend to lack data for the elderly population. Therefore, we aimed to describe the effectiveness and safety of afatinib, gefitinib, and erlotinib for elderly patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: Treatment-naïve patients with EGFR-mutated advanced NSCLC were enrolled at many hospitals in Taiwan. Patient characteristics and the effectiveness and safety of afatinib, gefitinib, and erlotinib were compared. RESULTS: This study enrolled 1,343 treatment-naïve patients with EGFR-mutated advanced NSCLC, of whom 554 were aged <65 years, 383 were aged 65-74 years, 323 were aged 75-84 years, and 83 were aged ≥85 years. For elderly patients, afatinib was more effective, with a median progression-free survival (PFS) of 14.7 months and overall survival (OS) of 22.2 months, than gefitinib (9.9 months and 17.7 months, respectively) and erlotinib (10.8 months and 18.5 months, respectively; PFS: p = 0.003; OS: p = 0.026). However, grade ≥3 adverse events, including skin toxicities, paronychia, mucositis, and diarrhea, were more frequently experienced by patients receiving afatinib than those receiving gefitinib or erlotinib. CONCLUSIONS: This large retrospective study provides real-world evidence of the effectiveness and safety of EGFR-TKIs for elderly patients with EGFR-mutated advanced NSCLC, a population that is often underrepresented in clinical trials and real-world evidence. Afatinib was more effective as a first-line treatment than gefitinib or erlotinib for elderly patients with EGFR-mutated advanced NSCLC.
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Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Humans , Afatinib/adverse effects , Afatinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Erlotinib Hydrochloride/adverse effects , Erlotinib Hydrochloride/therapeutic use , Gefitinib/adverse effects , Gefitinib/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Retrospective StudiesABSTRACT
PURPOSE: The phase III CheckMate 722 trial (ClinicalTrials.gov identifier: NCT02864251) evaluated nivolumab plus chemotherapy versus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (NSCLC) after disease progression on EGFR tyrosine kinase inhibitors (TKIs). METHODS: Patients with disease progression after first- or second-generation EGFR TKI therapy (without EGFR T790M mutation) or osimertinib (with/without T790M mutation) were randomly assigned 1:1 to nivolumab (360 mg once every 3 weeks) plus platinum-doublet chemotherapy (once every 3 weeks) or platinum-doublet chemotherapy alone (once every 3 weeks) for four cycles. Primary end point was progression-free survival (PFS). Secondary end points included 9- and 12-month PFS rates, overall survival (OS), objective response rate (ORR), and duration of response (DOR). RESULTS: Overall, 294 patients were randomly assigned. At final analysis (median follow-up, 38.1 months), PFS was not significantly improved with nivolumab plus chemotherapy versus chemotherapy (median, 5.6 v 5.4 months; hazard ratio [HR], 0.75 [95% CI, 0.56 to 1.00]; P = .0528), with 9- and 12-month PFS rates of 25.9% versus 19.8%, and 21.2% versus 15.9%, respectively. Post hoc PFS subgroup analyses showed a trend favoring nivolumab plus chemotherapy in patients with tumors harboring sensitizing EGFR mutations (HR, 0.72 [95% CI, 0.54 to 0.97]), one line of previous EGFR TKI (0.72 [95% CI, 0.54 to 0.97]), or both (0.64 [95% CI, 0.47 to 0.88]). Median OS was 19.4 months with nivolumab plus chemotherapy versus 15.9 months with chemotherapy, while ORR was 31.3% versus 26.7%, and median DOR was 6.7 versus 5.6 months, respectively. Grade 3/4 treatment-related adverse events occurred in 44.7% and 29.4% of patients treated with nivolumab plus chemotherapy and chemotherapy alone, respectively. CONCLUSION: Nivolumab plus chemotherapy did not significantly improve PFS versus chemotherapy in patients with EGFR-mutated metastatic NSCLC previously treated with EGFR TKIs. No new safety signals were identified.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Nivolumab/therapeutic use , Platinum/therapeutic use , Protein Kinase Inhibitors/adverse effectsABSTRACT
Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32-0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47-2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10-5). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44-2.57); p = 0.897]. Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.
Different prognostic meaning of tumor resistant gene detected from tumor or blood in patients with EGFR-mutant lung cancer The study demonstrates that patients with EGFR-mutant lung cancer who develop resistance due to a secondary T790M mutation, defined by tumor or blood T790M positivity, achieve better survival than patients without secondary T790M mutation; this association was mainly contributed by tumour T790M positivity. Oismertinib and chemotherapy led to similar survival in tumour T790M-positive patients. However, compared to osimertinib, chemotherapy was associated with longer survival in blood T790M-positive patients.
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Managing contradictions and building resilience help us overcome life's challenges. Here, we explored the link between attitudes towards contradictions and psychological resilience, examining the role of cortical conflict resolution networks. We enlisted 173 healthy young adults and used questionnaires to evaluate their cognitive thinking styles and resilience. They underwent structural and functional magnetic resonance imaging scans. Our results revealed that contrasting attitudes toward contradictions, formal logic, and naïve dialecticism thinking styles corresponded with varying degrees of resilience. We noted structural and functional differences in brain networks related to conflict resolution, including the inferior frontal and parietal cortices. The volumetric variations within cortical networks indicated right-hemispheric lateralization in different thinking styles. These findings highlight the potential links between conflict resolution and resilience in the frontoparietal network. We underscore the importance of frontoparietal brain networks for executive control in resolving conflicting information and regulating the impact of contradictions on psychological resilience.