Chinese Lung Cancer Research Articles

Prognostic Significance of Methyl-CpG Binding Domain4 Polymorphism rs140693 and Clinical Characteristics in Chinese Lung Cancer Patients

Prognostic Significance of Methyl-CpG Binding Domain4 Polymorphism rs140693 and Clinical Characteristics in Chinese Lung Cancer Patients

P2.11C.03 Immune-Related Adverse Events are Associated with Survival in Chinese Lung Cancer Patients Treated With Immunotherapy

P2.11C.03 Immune-Related Adverse Events are Associated with Survival in Chinese Lung Cancer Patients Treated With Immunotherapy

Diagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China.

Epidemiological studies on non-small cell lung cancer (NSCLC) have noted RET fusions as an oncogenic driver. However, real-world data on RET biomarker testing and treatment patterns in China remain limited. This study aimed to examine demographics, clinical and molecular features, and RET testing and treatment patterns and outcomes in patients with RET fusion-positive NSCLC. Utilizing real-world data from the Chinese Multi-center Lung Cancer Precision Medicine Registry, this retrospective cohort study focused on Chinese patients diagnosed with RET fusion-positive NSCLC between January 1, 2016, and November 30, 2021. The cohort was divided into early-stage and advanced-stage subgroups. Demographics, clinical and molecular profiles, treatment received, and outcomes including real-world event free survival (rwEFS), real-world progression free survival (rwPFS), and overall survival (OS) were assessed. The study included 121 patients with RET fusion-positive NSCLC, comprising 80 early-stage and 58 advanced-stage patients. High biomarker testing rates were observed at diagnosis (75% for early-stage, 78% for advanced-stage). RET testing was often conducted via tissue samples (95.9%) and next-generation sequencing (89.3%). KIF5B (57.0%) and CCDC6 (20.7%) were the most common gene fusion partners. The most frequent oncogenic mutations were TP53 (15.7%) and EGFR (6.6%). Platinum-based chemotherapy was the most common first-line treatment among advanced-stage patients. Median rwPFS was 9.22months for advanced-stage patients on first-line chemotherapy, and median OS was 30.7months for all advanced-stage patients. The 2-year rwEFS rate for early-stage patients was 86.0%, with a median OS of 91.9months. The study observed high biomarker testing rates at initial diagnosis for early- and advanced-stage RET fusion-positive NSCLC patients in China. The heterogeneous treatment pattern of advanced patients suggests the need for more precise, evidence-based treatment to guide clinical decisions. Given the existing therapeutic regimens fall short of adequately addressing treatment needs, targeted therapies are essential to improve outcomes.

169P Analysis of tumor immune microenvironment with mIHC in Chinese non-small cell lung cancer

169P Analysis of tumor immune microenvironment with mIHC in Chinese non-small cell lung cancer

1045P The association of human leukocyte antigen variants in immune-related toxicity and efficacy in Chinese lung cancer patients treated with immune checkpoint inhibitors

1045P The association of human leukocyte antigen variants in immune-related toxicity and efficacy in Chinese lung cancer patients treated with immune checkpoint inhibitors

The links between symptom burden, illness perception, psychological resilience, social support, coping modes, and cancer-related worry in Chinese early-stage lung cancer patients after surgery: a cross-sectional study

ObjectivesThis study aims to investigate the links between the clinical, demographic, and psychosocial factors and cancer-related worry in patients with early-stage lung cancer after surgery.MethodsThe study utilized a descriptive cross-sectional design. Questionnaires, including assessments of cancer-related worry, symptom burden, illness perception, psychological resilience, coping modes, social support and participant characteristics, were distributed to 302 individuals in early-stage lung cancer patients after surgery. The data collection period spanned from January and October 2023. Analytical procedures encompassed descriptive statistics, independent Wilcoxon Rank Sum test, Kruskal-Wallis- H- test, Spearman correlation analysis, and hierarchical multiple regression.ResultsAfter surgery, 89.07% had cancer-related worries, with a median (interquartile range, IQR) CRW score of 380.00 (130.00, 720.00). The most frequently cited concern was the cancer itself (80.46%), while sexual issues were the least worrisome (44.37%). Regression analyses controlling for demographic variables showed that higher levels of cancer-related worry (CRW) were associated with increased symptom burden, illness perceptions, and acceptance-rejection coping modes, whereas they had lower levels of psychological resilience, social support and confrontation coping modes, and were more willing to obtain information about the disease from the Internet or applications. Among these factors, the greatest explanatory power in the regression was observed for symptom burden, illness perceptions, social support, and sources of illness information (from the Internet or applications), which collectively explained 52.00% of the variance.ConclusionsHealthcare providers should be aware that worry is a common issue for early stage lung cancer survivors with a favorable prognosis. During post-operative recovery, physicians should identify patient concerns and address unmet needs to improve patients’ emotional state and quality of life through psychological support and disease education.

Befotertinib in first-line treatment for Chinese non-small cell lung cancer patients harboring common EGFR-mutations reveals similar efficacy to other third-generation EGFR-TKIs but somewhat different safety profile.

Befotertinib in first-line treatment for Chinese non-small cell lung cancer patients harboring common EGFR-mutations reveals similar efficacy to other third-generation EGFR-TKIs but somewhat different safety profile.

Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study

BackgroundThis study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients.MethodsLung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores.ResultsForty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort.ConclusionsHA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM.Trial registrationThis study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study.

Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Noncanonical RET fusions in Chinese patients with non-small cell lung cancer from DNA-based next-generation sequencing.

e20000 Background: The FDA has approved selpercatinib and pralsetinib for the treatment of metastatic RET fusion-positive non-small cell lung cancer in adult patients. Although the overall response rate is high and the response is durable, the outcomes may vary due to different fusion types of the same driver gene. Methods: We retrospectively collected and analyzed 14062 samples (tumour tissue or plasma) from Chinese lung cancer patients who underwent tissue-based or ctDNA-based next-generation sequencing (NGS) assays at HaploX Genomic Sequencing Center from May 18, 2020, to January 11, 2024. All samples with a RET gene fusion were included and classified based on the fusion partner gene and breakpoint position. Results: A total of 157 (1.1%) samples with DNA-based NGS harbored a RET gene fusion. Among the samples with a RET gene fusion, the most common RET fusion partners at the DNA level were KIF5B (73.2%) and CCDC6 (21.0%). We categorized RET fusions into canonical fusions and noncanonical fusions based on fusion partner and breakpoint position, and the proportions of canonical fusions and noncanonical fusions were 88.5% (139/157) and 11.5% (18/157) respectively. Among the samples with a noncanonical RET fusion, 5 samples harbored a RET fusion with an uncommon fusion partner, it remains unclear whether these fusions lead to RET activation. Conclusions: In this retrospective study, we identify different types of RET fusions in Chinese lung cancer patients. The majority are canonical fusions, which can benefit from tyrosine kinase inhibitors in clinical, the rest are noncanonical fusions, and their role in precision therapy needs further verification by RNA-based NGS or other assays. All in all, our research helps guide precision therapy in clinical settings. [Table: see text]

Comparative genomic landscape of patients with lung cancer with high-load versus low-load Epstein-Barr virus infection.

e20017 Background: As the first known oncogenic virus, Epstein–Barr virus (EBV) has been proven to be associated with nasopharyngeal carcinoma, gastric cancer, and lymphomas. Its relationship with lung cancer, however, remains ambiguous. Given that over 90% of adults globally harbor EBV infections and that EBV can be detected in the tumor cells of lung cancer patients, we hypothesize that lung cancer may be associated with high-load EBV infection, whereas low-load infection is less likely. Here, we compared the genomic landscapes of lung cancer patients with high-load and low-load EBV infections. Methods: We conducted a study on 2,268 Chinese lung cancer patients, collecting tumor tissue samples for analysis. Targeted sequencing of 680 cancer-related genes and EBV genome was performed using the HapOnco StarPanel NGS Assay (HaploX Biotechnology, Shenzhen). The EBV infection load was evaluated based on the proportion of reads aligned to the EBV reference genome in the total sequenced reads for each patient. 99% of these samples could be detected with at least two EBV reads. From them, we selected a total of 32 high-load EBV cases (2.1% - 64.3%) and 35 low-load EBV cases (0.1% - 1.7%). Their genomic profiles and altered signaling pathways were subsequently analyzed. Results: In the high-load EBV group, we identified 122 somatic mutations with no recurrent mutations between cases. As for genes, the most frequently mutated were TP53 (25.0%), LRP1B (15.6%), NFKBIA (12.5%), ERBB4 (9.4%), and CNTNAP5 (9.4%), with these mutations being notably enriched in EBV infection pathways according to KEGG, and IL−7 Signal Transduction pathways as per BioCarta. The most common copy number variation events were FGFR3 (12.5%), CDKN2A (12.5%) and FOXP1 (12.5%) gene deletions. In contrast, the low-load EBV group presented with 316 somatic mutations, with the most recurrent mutations being EGFR L858R (17.1%) and E746_A750del (17.1%). The top frequently mutated genes were TP53 (55.3%), EGFR (44.7%), ARID1A (10.5%) and KRAS (10.5%). Conclusions: The genomic profiles of lung cancer patients with high-load EBV infection differ significantly from those with low-load infection. Notably, the genomic mutations in the high-load EBV group are closely associated with EBV infection, suggesting that high-load EBV infection may be linked to lung cancer, unlike low-load infection.

Classification of multiple primary lung cancer in patients with multifocal lung cancer: assessment of a machine learning approach using multidimensional genomic data.

Multiple primary lung cancer (MPLC) is an increasingly well-known clinical phenomenon. However, its molecular characterizations are poorly understood, and still lacks of effective method to distinguish it from intrapulmonary metastasis (IM). Herein, we propose an identification model based on molecular multidimensional analysis in order to accurately optimize treatment. A total of 112 Chinese lung cancers harboring at least two tumors (n = 270) were enrolled. We retrospectively selected 74 patients with 121 tumor pairs and randomly divided the tumor pairs into a training cohort and a test cohort in a 7:3 ratio. A novel model was established in training cohort, optimized for MPLC identification using comprehensive genomic profiling analyzed by a broad panel with 808 cancer-related genes, and evaluated in the test cohort and a prospective validation cohort of 38 patients with 112 tumors. We found differences in molecular characterizations between the two diseases and rigorously selected the characterizations to build an identification model. We evaluated the performance of the classifier using the test cohort data and observed an 89.5% percent agreement (PA) for MPLC and a 100.0% percent agreement for IM. The model showed an excellent area under the curve (AUC) of 0.947 and a 91.3% overall accuracy. Similarly, the assay achieved a considerable performance in the independent validation set with an AUC of 0.938 and an MPLC predictive value of 100%. More importantly, the MPLC predictive value of the classification achieved 100% in both the test set and validation cohort. Compared to our previous mutation-based method, the classifier showed better κ consistencies with clinical classification among all 112 patients (0.84 vs. 0.65, p <.01). These data provide novel evidence of MPLC-specific genomic characteristics and demonstrate that our one-step molecular classifier can accurately classify multifocal lung tumors as MPLC or IM, which suggested that broad panel NGS may be a useful tool for assisting with differential diagnoses.

Comprehensive analysis of next generation sequencing and ARMS-PCR for detecting EGFR exon 20 insertion (ex20ins) mutations in Chinese non-small cell lung cancer patients

Comprehensive analysis of next generation sequencing and ARMS-PCR for detecting EGFR exon 20 insertion (ex20ins) mutations in Chinese non-small cell lung cancer patients

Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Chinese expert consensus on refractory lung cancer

The incidence and mortality of lung cancer in China are the highest of all malignant tumors, seriously endangering people's lives and health. Refractory lung cancer is lung cancer that is unresponsive to standard treatment and is difficult to treat, or lung cancer for which a standard treatment has not yet been defined. However, there is still a lack of clear definition and consensus on the treatment of refractory lung cancer. In order to provide guidance for the clinically effective and safe treatment of refractory lung cancer, experts from Chinese Thoracic Society Lung Cancer Study Group have formulated this consensus, on the basis of the actual situation in the field of diagnosis and treatment in our country, with reference to the latest research data, relevant guidelines at home and abroad and experts' clinical practice experience. The consensus makes recommendations on the application of four aspects: refractory small cell lung cancer (SCLC), refractory driver gene-positive non-small cell lung cancer (NSCLC), refractory driver gene-negative NSCLC, and new technological solutions for precision diagnosis and treatment. It also provides references for Chinese clinicians on the use of drugs for refractory lung cancer.

Molecular and immune characterization of Chinese early-stage non-squamous non-small cell lung cancer: a multi-omics cohort study.

Albeit considered with superior survival, around 30% of the early-stage non-squamous non-small cell lung cancer (Ns-NSCLC) patients relapse within 5 years, suggesting unique biology. However, the biological characteristics of early-stage Ns-NSCLC, especially in the Chinese population, are still unclear. Multi-omics interrogation of early-stage Ns-NSCLC (stage I-III), paired blood samples and normal lung tissues (n=76) by whole-exome sequencing (WES), RNA sequencing, and T-cell receptor (TCR) sequencing were conducted. An average of 128 exonic mutations were identified, and the most frequently mutant gene was EGFR (55%), followed by TP53 (37%) and TTN (26%). Mutations in MUC17, ABCA2, PDE4DIP, and MYO18B predicted significantly unfavorable disease-free survival (DFS). Moreover, cytobands amplifications in 8q24.3, 14q13.1, 14q11.2, and deletion in 3p21.1 were highlighted in recurrent cases. Higher incidence of human leukocyte antigen loss of heterozygosity (HLA-LOH), higher tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were identified in ever-smokers than never-smokers. HLA-LOH also correlated with higher TMB, TNB, intratumoral heterogeneity (ITH), and whole chromosomal instability (wCIN) scores. Interestingly, higher ITH was an independent predictor of better DFS in early-stage Ns-NSCLC. Up-regulation of immune-related genes, including CRABP2, ULBP2, IL31RA, and IL1A, independently portended a dismal prognosis. Enhanced TCR diversity of peripheral blood mononuclear cells (PBMCs) predicted better prognosis, indicative of a noninvasive method for relapse surveillance. Eventually, seven machine-learning (ML) algorithms were employed to evaluate the predictive accuracy of clinical, genomic, transcriptomic, and TCR repertoire data on DFS, showing that clinical and RNA features combination in the random forest (RF) algorithm, with area under the curve (AUC) of 97.5% and 83.3% in the training and testing cohort, respectively, significantly outperformed other methods. This study comprehensively profiled the genomic, transcriptomic, and TCR repertoire spectrums of Chinese early-stage Ns-NSCLC, shedding light on biological underpinnings and candidate biomarkers for prognosis development.

Expert consensus on clinical practice of EGFR exon20 insertion detection in non-small cell lung cancer in China (2024 edition)

About 82% of the Chinese lung cancer population is non-small cell lung cancer(NSCLC), and the epidermal growth factor receptor (EGFR) gene is the most common driver mutation in the Chinese lung cancer population (51.7%-54.4%). In recent years, the rapid development and wide application of targeted therapies, especially EGFR tyrosine kinase inhibitors, have significantly improved the survival time and quality of life of Chinese lung cancer patients. EGFR exon20 insertion (EGFR ex20ins) accounts for 0.3%-2.9% in NSCLC patients in China. Recently, several tyrosine kinase inhibitors have been approved for the therapy of EGFR ex20ins NSCLCs. The variety variants and high molecular heterogeneity of EGFR ex20ins NSCLCs asks for more accurate detection methods, and clinical routine detection process needs to be further standardized. On account to the practical questions of EGFR ex20ins detection, this consensus was finally reached based on the combination of literature, expert experience and internal discussion among committee members, in the hope of providing the guide for standardizing the EGFR ex20ins detection.

Abstract 7618: Genomic pathogenic alterations of the SWI/SNF complex genes compromise the outcomes to immunotherapy in Chinese KRAS-mutant non-small cell lung cancer by downregulated STING

Abstract Background: Immune checkpoint inhibitors (ICIs) have been standard of care in non-small cell lung cancer (NSCLC), but lack of response to ICIs remains a major hurdle in cancer immunotherapy. Switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex mutations have been reported in KRAS-mutant cancers with debated influence to clinical outcome of ICIs, which needs further investigation. Methods: According to the OncoKB, COSMIC, and PolyPhen-2 databases, genomic pathogenic alterations (GPAs) of SWI/SNF are defined. Lung tumors were classified according to the presence or absence of mutations in six SWI/SNF genes (ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1). Lung cancer cell lines with different genotypes of SWI/SNF were used for differentially expressed genes analysis by RNA sequencing. Protein expression of STING was detected by immunohistochemistry (IHC) in tumor specimens. Results: Out of 2660 NSCLC patients (NSCLCs), the GPAs of SWI/SNF were detected in 15.0% (401/2660) patients. 23.1% (69/299) EGFRwtALKwt and 27.8% (25/90) STK11wtKEAP1wtKRASmut NSCLCs who received ICIs had SWI/SNF GPAs. Progression-free survival (mPFS) of SWI/SNF-wild type (wt) compared to SWI/SNF-mutant (mut) NSCLCs was not significantly different. However, GPAs of SWI/SNF in KRAS-mut ICI-treated NSCLCs associated with poorer clinical outcome. Patients with ARID1A, ARID1B, ARID2 or PBRM1 mutant tumors had a significantly shorter PFS (2.7 vs 6.5 months, HR=2.44 [95%CI: 1.31-4.54], P=0.004) as compared to SWI/SNF-wt patients. In STK11wtKEAP1wtKRASmut NSCLCs, all SWI/SNF mutations (4.9 vs 9.1 months, HR=2.03 [95%CI: 1.07-3.86], P=0.029) or ARID1A/ARID1B/ARID2/PBRM1 alterations (3.2 vs 9.1 months, HR=2.68 [95%CI: 1.33-5.41], P=0.004) significantly shortened the mPFS. In cell lines, SWI/SNF-mut cells had downregulated STING expression compared to SWI/SNF-wt cells. Downregulated STING protein were observed in KRAS-mut NSCLCs without benefit from the treatment of ICIs. Conclusions: In KRAS-mut NSCLCs with or without STK11/KEAP1 mutations, the presence of GPAs of DNA binding genes ARID1A/ARID1B/ARID2 could compromise the clinical outcome of immunotherapy, which might be due to the downregulated STING. Citation Format: Lingling Gao, Jie Jiang, Zhi Xie, Linlin Zhu, Yu Chen, Zhiyi Lv, Yuqing Chen, Wenbin Zhou, Ji Chen, Yumin Zhong, Li Zhang, Penghui Zeng, Xiaodan Huang, Wenqing Yan, Danxia Lu, Shuilian Zhang, Weibang Guo, Xuchao Zhang. Genomic pathogenic alterations of the SWI/SNF complex genes compromise the outcomes to immunotherapy in Chinese KRAS-mutant non-small cell lung cancer by downregulated STING [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7618.

A latent class analysis of family resilience and its relationship with fear of recurrence in lung cancer patients: a cross-sectional study.

Family resilience helps cancer-affected families overcome challenges and may influence an individual's fear of cancer recurrence (FCR). Identifying distinct classes of family resilience among lung cancer patients is crucial for tailored interventions. This study aimed to identify latent classes of family resilience in lung cancer patients and explore their relationships with FCR. Three hundred ten lung cancer patients from three hospitals in Fujian were recruited from June to September 2021. Clinical data were extracted from medical records, while sociodemographic details, family resilience, and FCR were self-reported. A latent class analysis was performed to identify family resilience classes. A 4-class solution showed the best fit. Compared to Class 1, the patients who had no comorbidities (ORs = 3.480-16.005) had an increased likelihood of belonging to Class 2 and 3, while those who were not family breadwinners (ORs = 0.118-0.176) had a decreased likelihood. Further, the patients who (1) did not lack interest/pleasure in doing things during the past 2-week period (OR = 7.057), (2) were never smokers (OR = 6.230), and (3) were urban residents (OR = 8.985) had an increased likelihood of belonging to Class 4, while those who were (1) male (OR = 0.167), (2) not the family breadwinner (OR = 0.152), and (3) had none or only one child (OR = 0.203) had a decreased likelihood of belonging to Class 4. The FCR level differed significantly among these four classes. Our study identified four distinct classes of family resilience among Chinese lung cancer patients. FCR severity decreased with increasing levels of family resilience.

Uncommon de novo EGFRT790M-Mutant NSCLC characterized with unique genetic Features: Clinical response and acquired resistance to the third-generation EGFR-TKIs treatment

IntroductionThe literature on de novo EGFRT790M-mutant patients diagnosed with lung cancer is limited, and there is currently no consensus concerning the most effective treatment protocols. This study aimed to investigate the genomic characteristics of de novoEGFRT790M-mutant non-small cell lung cancer (NSCLC) and provide insights into its clinical response and resistance mechanism to third-generation EGFR-TKIs. MethodsNext-generation sequencing was utilized to screen a substantial cohort of 4,228 treatment-naïve patients from the Mygene genomic database to identifythe de novo EGFR-T790M mutation. Meanwhile, we recruited 83 individuals diagnosed with lung cancer who harbored de novo EGFRT790M mutation in the real world. In addition, 166 patients who acquired EGFR-T790M mutation after becoming resistant to first- or second-generation EGFR-TKIs were included as a comparison cohort. ResultsDe novo EGFRT790M mutation identified by next-generation sequencing is rare (∼1.3 %) in Chinese lung cancer patients. The relative variant allele frequency (VAF) of de novo EGFRT790M mutation was either comparable to or significantly lower than those of EGFR-activating mutations. Patients with de novo-T790M mutations exhibited less favorable clinical outcomes when administered third-generation EGFR-TKIs as first-line therapy thanthose with 19del mutationsdue to a high overlap rate in EGFR p.L858R mutation. In patients with a de novo EGFRT790M mutation, no correlation was observed between T790M clonality and treatment outcomes with third-generation EGFR-TKIs. In contrast, the sub-clonality of the T790M mutation detrimentally affected the third-generation EGFR-TKI treatment efficacy in patients with acquired T790M mutation. Potential resistance mechanisms of third-generation EGFR TKIs in NSCLC patients with de novo or acquired EGFRT790M mutations included EGFR p.C797S in cis or EGFR p.E709X mutation, as well as activation of bypass pathways. ConclusionsThe present study characterized the uncommon but unique de novo EGFRT790M-mutant NSCLC and laid a foundation for designing future clinical trials in the setting of uncommon EGFR mutation.