Chinese Lung Cancer Patients Research Articles

Relationships among Social Support, Coping Style, Perceived Stress, and Psychological Distress in Chinese Lung Cancer Patients

Objective:Social support is associated with improved psychological distress in cancer patients. This study investigates the impact of social support on Chinese lung cancer patients' psychological distress and further clarifies the mediating role of perceived stress and coping style.Methods:A cross-sectional survey study examined social support and psychological distress in 441 patients diagnosed with lung cancer from seven hospitals in Chongqing, China, between September 2018 and August 2019. Coping style and perceived stress were considered to be potential mediators of adjustment outcomes.Results:We found a detection rate of 17.7% for psychological distress among Chinese lung cancer patients. Social support was in significantly negative association with psychological distress, which was partially mediated by confrontation coping and perceived stress.Conclusions:Social support appears to contribute to ameliorate psychological distress by enhancing confrontation coping with cancer and enhancing perceived stress. There is a need for the development and evaluation of psychological intervention program to enhance the buffering effects of social support in lung cancer patients.

P86.14 Next-Generation Sequencing Guided the Gene Mutations Associated with mTOR-Inhibitors in Chinese Lung Cancer Patients

P86.14 Next-Generation Sequencing Guided the Gene Mutations Associated with mTOR-Inhibitors in Chinese Lung Cancer Patients

P89.09 The Landscape of Kinase Domain Duplication (KDD) in Chinese Lung Cancer Patients

P89.09 The Landscape of Kinase Domain Duplication (KDD) in Chinese Lung Cancer Patients

P76.37 Comprehensive Investigation of Uncommon EGFR Mutations in 14,429 Chinese Lung Cancer Patients

Uncommon EGFR mutations are thought to be in only 10 to 20 percent of EGFR mutation cases. Most of them harbor heterogeneous molecular alterations within exons 18-21, and some of them are sensitive to EGFR TKI. However, rare specific studies have evaluated uncommon EGFR mutations in detail.

P02.22 Identification of FGFR Mutations in Chinese Lung Cancer Patients by Next-Generation Sequencing

P02.22 Identification of FGFR Mutations in Chinese Lung Cancer Patients by Next-Generation Sequencing

P35.27 Next Generation Sequencing Reveals the Genetic Landscape of JAK Family in Chinese Lung Cancer Patients

P35.27 Next Generation Sequencing Reveals the Genetic Landscape of JAK Family in Chinese Lung Cancer Patients

P57.03 Pathogenic Germline Mutations of Homologous Recombination Deficiency (HRD) Genes in Chinese Lung Cancer Patients

P57.03 Pathogenic Germline Mutations of Homologous Recombination Deficiency (HRD) Genes in Chinese Lung Cancer Patients

P88.01 Comprehensive Profiling of ROS1 Fusions in Chinese Non-Small Cell Lung Cancer Patients

P88.01 Comprehensive Profiling of ROS1 Fusions in Chinese Non-Small Cell Lung Cancer Patients

P89.01 Clinical and Genomic Features of EGFR-KDD/EGFR Rearrangements of Chinese Lung Cancer Patients

P89.01 Clinical and Genomic Features of EGFR-KDD/EGFR Rearrangements of Chinese Lung Cancer Patients

P37.16 Alterations in HRR Related Genes as Potential Markers of Clinical Benefit from PARP Inhibitor and PD-1/PD-L1 Blockade in Advanced Lung Cancer

Homologous recombination repair (HRR) related gene alteration are associated with PARP inhibitor and increased tumor mutation burden (TMB). However, in lung cancer the detection of HRR gene is unclear, and its correlation with TMB has not been reported. We systematically investigated alteration genes in 578 Chinese lung cancer patients all samples were detected by hybridization capture-based NGS 1021-gene panel, which includes 36 HRR-related genes (see the gene list in below). We also evaluate the TMB of each patients. TMB analysis interrogated single nucleotide variants, small insertion and deletion, with VAF (variant allele frequency) ≥3 % (tissue) and ≥0.5 % (blood), respectively. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus). In this study, HRR related gene is the mainly germline mutation, percentage being about 66% (4). The percentage of HRR related gene somatic alteration in lung cancer is about 29% (168). Interesting, there 32% HRR alteration cases were found co-occurrence EGFR mutation but no significantly difference with non-EGFR cases(p=0.13). And also the percentage of BRCA1/2 mutation co-occurrence with EGFR mutation is no significantly difference with non-EGFR (14% vs 17%, p=0.44). On the other hand, TMB-high percentage in the case with HRR gene alteration is higher than the case without HRR related gene (49% vs 13%, p˂0.0001). In non-EGFR patients, the percentage of TMB-H is about 25% (92/365), and 51% (59/114) HRR alterations case without EGFR were TMB-H. So 20% (114/578) lung cancer patients who without EGFR mutation but with HRR related gene alteration could have a chance to consider medication of PARP inhibitor, and also 10% patients with TMB-high (59/578), maybe with higher efficacy of PD-1/PD-L1 blockade .

P53.09 Molecular Alterations of KIT Oncogene in a Large Cohort of Chinese Pan-Lung Cancer Patients

KIT was identified as a proto-oncogene mutated or up-regulated in different types of cancers. However, it is unlikely that KIT inhibitors will be effective for lung cancer patients. Analysis of activating KIT mutations in lung cancer will be helpful to explain the above issue. Furthermore, previous studies showed that an activating KIT mutation could induce crizotinib resistance in ROS1-positive lung cancer. To assess the probability of tyrosine kinase inhibitors (TKIs) resistance induced by activating KIT mutations, we explored co-occurring activating alterations of KIT with other tyrosine kinase genes in a large cohort of Chinese lung cancer patients.

P85.06 Clinical and Genomic Features of Middle Intensity cMET Stain of Chinese Lung Cancer Patients

P85.06 Clinical and Genomic Features of Middle Intensity cMET Stain of Chinese Lung Cancer Patients

The positive effect of social support on psychological distress among Chinese lung cancer patients: The mediating role of self-esteem.

AimTo investigate the effect of social support on psychological distress among Chinese lung cancer patients and clarify the mediating role of self‐esteem.DesignA cross‐sectional descriptive correlational survey of 441 Chinese lung cancer patients was designed.MethodsSelf‐esteem was supposed to play a mediating role in the association between social support and psychological distress. We collected demographic information, the Distress Thermometer, Multidimensional Scale of Perceived Social Support and Rosenberg Self‐Esteem Scale.ResultsOur revised model demonstrated an acceptable fit to the data (χ 2 = 37.489, comparative fit index (CFI) = 0.965, Tucker‐Lewis index (TLI) = 0.926, root mean square error of approximation [RMSEA] = 0.099). Social support had a direct effect on self‐esteem and psychological distress, and self‐esteem had also a direct effect on psychological distress. Meanwhile, self‐esteem also partially mediated the relationship between social support and psychological distress among Chinese lung cancer patients.

Combined Effect of MTHFR C677T and PAI-1 4G/5G Polymorphisms on the Risk of Venous Thromboembolism in Chinese Lung Cancer Patients.

Venous thromboembolism (VTE) is a common and potentially fatal complication in cancer patients. Although several genetic risk factors related to thrombophilia have been identified, their contributions for the occurrence of VTE in cancer patients have conflicting results. The aim of this study was to evaluated the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G in lung cancer patients, with and without VTE, and the combined effect on the risk of VTE. 92 lung cancer patients diagnosed with VTE (VTE group) and 122 lung cancer patients without VTE (non-VTE group) were enrolled in the study. The gene polymorphisms were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism. Gene mutation of factor V Leiden was not detected both in non-VTE group and VTE group. The frequency of MTHFR C677T homozygous mutation in VTE group was 25.00%, higher than that in the non-VTE group without statistical difference. It was found that the PAI-1 4G4G genotype is associated with a higher risk of VTE (OR: 2.62, 95%CI: 1.19-5.75). Interestingly, the interaction between MTHFR C677T and PAI-1 4G/5G polymorphisms showed that the coexistence of the 2 homozygous mutation could further increase the risk of VTE. In conclusion, PAI-1 4G/5G polymorphism may be an increased risk factor for VTE among lung cancer patients in Chinese population. The homozygous MTHFR C677T mutation may be not a risk factor for VTE but increases the risk, accompanied with PAI-1 4G5G genotype.

Genomic and clinical characteristics of MET exon14 alterations in a large cohort of Chinese cancer patients revealed distinct features and a novel resistance mechanism for crizotinib

Background: Alterations in MET exon 14 (METex14) and its flanking intronic regions have been identified in a variety of cancers. Patients with METex14 alterations often benefit from MET inhibitors such as crizotinib. Given the unique mutation profiles of Chinese lung cancer patients, it is necessary to investigate the prevalence of METex14 alterations in a large cohort of cancer patients.Patients and methods: Cases carrying METex14 alterations were screened from 26,391 Chinese cancer patients by next-generation sequencing (NGS), and the clinicopathologic and molecular characteristics were reviewed.Results: Compared to Western population (~3%), the frequency of METex14 alterations is much lower in Chinese cancer patients (0.7%, n=184) and lung cancer patients (1.1%, n=175). Seventy-eight distinct METex14 alterations, including several novel alteration types were detected. Concurrent MET copy gain and non-exon14 MET mutations were also found. EGFR copy gain (11%) and mutations (8%), KRAS (5%) and PIK3CA (5%), appeared in a mutually exclusive pattern. Female patients contain much less TP53 mutations than male patients (65% vs. 24%, FDR = 0.01). Co-amplification of CDK4 and MDM2, CDK6 and EGFR were identified, which indicated cell cycle dysregulation and EGFR alteration are important co-occurring features in patients with METex 14 alteration. Of 9 tissue specimens having PD-L1 immunohistochemistry (IHC) results, 5 of them (55.5%) were found PD-L1 positive, which is comparable to other types of tumor. In 14 crizotinib-treated patients, the median progression free survival (mPFS) was 7 months. Upon resistance to crizotinib, two patients acquired secondary mutations in MET and one patient acquired BRAF p.K601E that can be a novel resistance mechanism.Conclusion: Chinese cancer patients have a relatively lower frequency of METex14 alterations compared to Western patients. Patients with METex14 alterations showed distinct molecular characteristics and the representative case study showed responses to MET tyrosine kinase inhibitor (TKI).

Osimertinib for Chinese advanced non-small cell lung cancer patients harboring diverse EGFR exon 20 insertion mutations

ObjectivesEpidermal growth factor receptor (EGFR) exon 20 insertion (ex20 ins) mutations are generally associated with de novo resistance to first- or second-generation EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the real efficacy of osimertinib for this subset remains elusive. We performed this study to investigate the real efficacy of osimertinib for Chinese advanced NSCLC patients harboring EGFR ex20 ins mutations. Materials and methodsWe retrospectively collected data of metastatic NSCLC patients with EGFR ex20 ins mutations who were treated with osimertinib 80 mg or 160 mg once daily in our center from June 2017 to May 2020. Progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. ResultsA total of 62 cases with EGFR ex20 ins mutations were included, and the major insertion variant was D770_N771insSVD and V769_D770insASV (45.1 %). Concurrent TP53 mutation was most commonly observed (59.7 %). Four patients showed partial response, 29 cases with stable disease and 29 showed progressive disease as best response to osimertinib (ORR: 6.5 %, DCR: 53.2 %). The median PFS (mPFS) in total patients was 2.3 (95 %CI, 1.5–3.1) months. Patients harboring A763_Y764insFQEA/D770delinsGY variants showed numerically longer mPFS than those with other variants (4.2 vs. 2.2 months, P = 0.164). Patients who failed to osimertinib and occurred extracranial progression showed similar mPFS to those with intracranial progression (2.3 vs. 1.9 months, P = 0.142). Median PFS was not significantly different between patients who received osimertinib 80mg or 160mg once daily (2.5 vs. 1.3 months, P = 0.161), either with no significance when it used in fist-line setteing or bove (3.0 vs. 2.2 months, P = 0.639). ConclusionThe unique insertion variant A763_Y764insFQEA and D770delinsGY might better respond to osimertinib than other ex20 ins subtypes. Osimertinib either 80 mg or 160 mg once daily showed less activity in Chinese NSCLC patients harboring diverse EGFR ex20 ins mutations.

The landscape of kinase domain duplication in Chinese lung cancer patients.

BackgroundKinase domain duplication (KDD) is a special type of large genomic rearrangement (LGR), occurring in the kinase domain of protein kinase genes. KDD of some lung cancer driver genes, such asEGFRKDD, has been identified and implicated to be oncogenic in non-small cell lung cancer (NSCLC). The present study aims to interrogate the spectrum of KDD occurring on classic driver genes in Chinese lung cancer patients without the presence of classic lung cancer driver mutations.MethodsWe retrospectively enrolled 10,525 Chinese lung cancer patients who met the following inclusion criteria; (I) do not carry classic lung cancer driver mutations in any of the 8 driver genes and (II) tyrosine kinase inhibitor (TKI)-naïve. Capture-based targeted sequencing was performed on tissue or plasma samples. LGR and KDD were identified by using in-house analysis scripts. The prevalence and distribution of LGR and KDD in our cohort were analyzed.ResultsThe median age of the cohort was 64 years with 68.7% being male. Among all patients, 23.2% and 51.8% were diagnosed with stage III and IV disease respectively. We identified 43 cases (0.41%) harboring LGR in one of the driver genes (EGFR/ERBB2/ALK/RET/ROS1/MET/BRAF), with 24 (0.23%) patients harboring KDD. Of the patients harboring KDD, a majority (n=19) harbored canonical EGFR-KDD involving exons 18–25, whilst one patient harbored duplications of EGFR exons 18–26. There were three MET-KDD patients; in two, the alteration occurred in exons 15–21 and in one, the alteration occurred in exons 3–21. One patient harbored RET-KDD involving exons 12–18. KDD showed a comparable prevalence in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (0.33% vs. 0.11%, P=0.118). Nineteen non-KDD LGRs, spanning six genes including EGFR (n=6), MET (n=3), ALK (n=4), ROS1 (n=2), ERBB2 (n=2) and BRAF (n=2), were found, each occurring in one patient. The prevalence of LGR in LUADs and LUSCs was comparable (0.55% vs. 0.38%, P=0.452).ConclusionsWe observed a prevalence of 0.41% and 0.23% for LGR and KDD, respectively. Twenty-four different LGR alterations, including 5 KDDs and 19 non-KDD LGRs, were observed. KDDs mainly occurred in EGFR involving exons 18–25 and non-KDD LGRs were distributed more randomly. The prevalence of LGR/KDD in LUSCs and LUADs was comparable.

66P Tislelizumab plus chemotherapy as first-line treatment for lung cancer in Chinese patients

66P Tislelizumab plus chemotherapy as first-line treatment for lung cancer in Chinese patients

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

Lung cancer is the leading causes of cancer-related death worldwide. Precise treatment based on next-generation sequencing technology has shown advantages in the diagnosis and treatment of lung cancer. This cohort study included 371 lung cancer patients. The lung cancer subtype was related to the smoking status and sex of the patients. The most common mutated genes were TP53 (62%), EGFR (55%), and KRAS (11%). The mutation frequencies of EGFR, TP53, PIK3CA, NFE2L2, KMT2D, FGFR1, CCND1, and CDKN2A were significantly different between lung adenocarcinoma and lung squamous cell carcinoma. We identified the age-associated mutations in ALK, ERBB2, KMT2D, RBM10, NRAS, NF1, PIK3CA, MET, PBRM1, LRP2, and CDKN2B; smoking-associated mutations in CDKN2A, FAT1, FGFR1, NFE2L2, CCNE1, CCND1, SMARCA4, KEAP1, KMT2C, and STK11; tumor stage-associated mutations in ARFRP1, AURKA, and CBFB; and sex-associated mutations in EGFR. Tumor mutational burden (TMB) is associated with tumor subtype, age, sex, and smoking status. TMB-associated mutations included CDKN2A, LRP1B, LRP2, TP53, and EGFR. EGFR amplification was commonly detected in patients with acquired lcotinib/gefitinib resistance. DNMT3A and NOTCH4 mutations may be associated with the benefit of icotinib/gefitinib treatment.

Checkpoint inhibitor pneumonitis in Chinese lung cancer patients: clinical characteristics and risk factors.

Checkpoint inhibitor pneumonitis (CIP) may be accompanied by lung cancer in patients treated with immune checkpoint inhibitors (ICI). This study aimed to test the risk factors, genetic and clinical characteristics of CIP in a cohort of Chinese patients with lung cancer. We retrospectively reviewed the medical records of eligible patients who received ICI treatment from December 2017 to September 2020 in our hospital. Patient characteristics, ICI protocols, and mutation frequencies of related genes are compared between the CIP group and the non-CIP group. A total of 94 patients were recruited. Of them, 16 (17.0%) patients developed CIP. Multivariate logistic regression analysis suggested Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 [odds ratio (OR) =6.53; 95% confidence interval (CI), 1.74-24.46; P=0.005] and previous pulmonary fibrosis (OR =20.13; 95% CI, 3.64-111.44; P=0.001) were independently associated with a higher incidence of CIP. There was an increasing trend, although not statistically significant, in the risk of CIP in patients with TP53 mutation (P=0.280). Most CIP patients were managed successfully following the current guideline. However, serious events (including one death) were still observed. ECOG PS ≥2 and earlier pulmonary fibrosis were closely correlated to the occurrence of CIP in Chinese lung cancer patients after ICI treatment. Early screening and prompt intervention are necessary for the management of CIP.