Chinese Lung Cancer Research Articles

Integrated investigation of the prognostic role of HLA LOH in advanced lung cancer patients with immunotherapy.

Although multiple studies have shown that loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus is one of the mechanisms of immune escape, the effect of HLA LOH on the immunotherapy response of patients is still unclear. Based on the data of 425 Chinese lung cancer patients, the genomic characteristics with different HLA LOH statuses were analyzed. The driver genes mutation frequency, oncogenic signaling pathways mutation frequency, tumor mutational burden (TMB) and chromosomal instability (CIN) score in the HLA LOH high group was significantly higher than in the HLA LOH negative group. Transcriptome analyses revealed that pre-existing immunologically active tumor microenvironment (TME) was associated with HLA LOH negative patients. Non-small cell lung cancer (NSCLC) patients, especially for lung squamous cell carcinomas (LUSC), with HLA LOH negative have a longer survival period than those with HLA LOH. In addition, the combination of HLA LOH with TMB or programmed cell death-Ligand 1 (PD-L1) expression can further distinguish responders from non-responders. Furthermore, a comprehensive predictive model including HLA LOH status, TMB, PD-L1 expression and CD8+ T cells was constructed and exhibited a higher predictive value, which may improve clinical decision-making.

A Novel TP53 Gene Mutation Sustains Non-Small Cell Lung Cancer through Mitophagy.

Lung cancer is the leading cause of cancer death in the world. In particular, non-small-cell lung cancer (NSCLC) represents the majority of the lung cancer population. Advances in DNA sequencing technologies have significantly contributed to revealing the roles, functions and mechanisms of gene mutations. However, the driver mutations that cause cancers and their pathologies remain to be explored. Here, we performed next-generation sequencing (NGS) on tumor tissues isolated from 314 Chinese NSCLC patients and established the mutational landscape in NSCLC. Among 656 mutations, we identified TP53-p.Glu358Val as a driver mutation in lung cancer and found that it activates mitophagy to sustain cancer cell growth. In support of this finding, mice subcutaneously implanted with NSCLC cells expressing TP53-p.Glu358Val developed larger tumors compared to wild-type cells. The pharmaceutical inhibition of autophagy/mitophagy selectively suppresses the cell proliferation of TP53-null or TP53-p.Glu358Val-expressing lung cancer cells. Together, our study characterizes a new TP53 mutation identified from Chinese lung cancer patients and uncovers its roles in regulating mitophagy, providing a new insight into NSCLC treatment.

Relationships Among Perceived Social Support, Family Resilience, and Caregiver Burden in Lung Cancer Families: A Mediating Model

ObjectivesTo identify the factors associated with caregiver burden in Chinese lung cancer families and to detect whether family resilience mediates the effect of perceived social support on caregiver burden. Data SourcesFrom October 2021 to March 2022, a total of 213 family caregivers of patients with lung cancer from a public hospital in Sichuan Province, China, completed the Zarit Burden Interview (ZBI), the Perceived Social Support Scale (PSSS), and the Family Resilience Assessment Scale (FRAS). The Mann-Whitney U test and the Kruskal-Wallis H test were used to identify the influencing factors of family caregiver burden, and the bootstrapping method was conducted to detect the mediating role of family resilience. ConclusionIn this study, family caregiver burden could be influenced by caregiver age, caregivers’ relationships with patients, and patients’ self-care degree; family resilience was found to mediate the relationship between caregivers’ perceived social support and caregiver burden. Implication for Nursing PracticeOur study manifested that factor from both the patients’ and caregivers’ sides could influence caregiver burden of lung cancer family caregivers. The results provide further evidence that lung cancer care should be family-centered, and relevant family-supportive systems should be further developed in this field.

Real-world clinical treatment outcomes in Chinese non-small cell lung cancer with EGFR exon 20 insertion mutations.

Background EGFR exon 20 insertions (EGFR ex20ins) constitute a heterogeneous subset of EGFR-activating alterations. However, the effectiveness of standard therapy in patients with EGFR ex20ins remains poor.MethodsIn our study, we retrospectively collected next-generation sequencing (NGS) data from 7,831 Chinese NSCLC patients and analyzed the relationship between EGFR ex20ins variations and medical records.ResultsOur data showed that EGFR ex20ins account for up to 3.5% of all EGFR mutation non-small-cell lung cancer (NSCLC) patients and 1.6% of all NSCLC patients in China. Thirty-eight different variants of EGFR ex20ins were identified in 129 NSCLC patients. We observed that the patients with EGFR ex20ins may benefit from the anti-angiogenesis agents significantly (P = 0.027). In the EGFR ex20ins near-loop group, patients who received second-/third-generation EGFR-TKI therapy treatment as first-line treatment had a longer median progression-free survival (PFS) than those who initiated treatment with first-generation EGFR-TKI or chemotherapy. Patients with co-mutations of EGFR ex20ins near-loop and TP53 tended to have a shorter OS in second-/third-generation EGFR-TKI therapy (P = 0.039). Additionally, median PFS was significantly longer in patients harboring EGFR ex20ins far-loop variants who received chemotherapy as a first-line setting (P = 0.037).ConclusionsOverall survival was significantly longer in EGFR ex20ins patients with anti-angiogenesis agents. For the choice of first-line strategy, NSCLC with EGFR ex20ins near-loop variants may benefit from second-/third-generation EGFR-TKI, while patients harboring EGFR ex20ins far-loop variants might have better outcomes from chemotherapy. TP53 could serve as a potential predictive marker in poor prognosis for EGFR ex20ins near-loop patients.

‘It’s not within my control’: local explanations for the development of lung cancer in China

ABSTRACT Rates of lung cancer in China are rising rapidly, creating an urgent need for prevention. Effective prevention measures require understanding local beliefs and perceptions about the risk for developing lung cancer. This article explores the explanations that Chinese lung cancer patients and their families give about the aetiology of their disease. Fifty-three interviews were conducted among lung cancer patients and their family members at a large tumour hospital in southern China. Participants presented a complex multifactorial explanation of lung cancer associating their disease with risks like tobacco use, occupational exposures, environmental pollution, lifestyle changes, and personal characters. While these are all standard risk factors commonly associated with lung cancer, participants presented them within a larger contextual frame of structural issues that impede their ability to change their behaviours. Using a social ecological model, we demonstrate how China’s socio-cultural environment shapes assumptions about the risk of lung cancer with particular reference to work, home, social situations, and the natural environment.

EP10.01-010 Real-world Study of the Incidence and Risk Factors of Venous Thromboembolism in Chinese Lung Cancer (RIVAL)

Patients with lung cancer have high incidence of venous thromboembolism (VTE), which might aggravate the overall survival. This prospective real-world study aims to investigate the incidence of VTE and determine the VTE-high-risk population of lung cancer.

EP16.03-006 Genetic Characteristics of EGFR Concurrent Variants with RB1 and TP53 in NCSLC Patients

EGFR-TKIs (tyrosine kinase inhibitor) can effectively improve the survival rate of NSCLC patients with EGFR sensitive mutations. However, concomitant alterations along with EGFR mutations often affect the effect of EGFR-TKIs. The genome characteristic of EGFR co-mutation is of great significance for guiding clinical treatment. In this study, we first reported the genetic characteristics of EGFR/RB1/TP53 co-variation in the Chinese non-small cell lung cancer (NSCLC) cohort.

EP01.01-012 Clinical and Molecular Features of Chinese Early-stage Multiple Primary Lung Cancer Patients

The incidence of early-stage multiple primary lung cancer (MPLC) has been increasing in recent years, while the ideal strategy for its diagnosis and treatment remains controversial. Moreover, the difference between MPLC and intrapulmonary metastasis (IM) in patients with lung cancer is vital but controversial.

1125P Real-world molecular testing and treatment patterns in epidermal growth factor receptor (EGFR) mutation-positive, locally advanced or metastatic Chinese non-small cell lung cancer patients failing first-line EGFR-tyrosine kinase inhibitors

Epidermal Growth Factor Receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) patients failing first-line (1L) EGFR- tyrosine kinase inhibitors (TKI) can benefit from subsequent targeted therapies. However, the real world data on the testing patterns and subsequent treatment patterns among patients failing 1L EGFR-TKI are lacking.

1102P Genomic alterations correlated with the expression of PD-L1 based on the next-generation sequencing in Chinese non-small cell lung cancer

Blockade of programmed cell death protein-1 (PD1)/programmed cell death ligand-1 (PD-L1) interaction is one of important immunotherapies in lung cancers. Current research also focused on the relationship between genomic alterations and the expression of PD-L1. Therefore, we analyzed the molecular characteristics and its correlation with the expression of PD-L1, which may help to establish a reasonable tumor classification strategy to improve immunotherapy. Tissue specimens were obtained from 391 cases suffered from lung cancer. Frequencies of gene alterations were detected and analyzed using next-generation sequencing(152 or 603 genes). All specimens were also performed for PD-L1 (22C3) by immunohistochemistry (IHC) with PD-L1 tumor proportion score (TPS) reported for further analysis. In 391 lung cancer samples, 113 (28.9%) cases had comutations in both TP53 and EGFR, 110 (28.1%) cases had alterations in EGFR only, 94 (24.0%) cases had alterations in TP53 only, and 74(18.9%) cases were wild-type of TP53 and EGFR. Two major alterated genes were TP53 (57.0%) and EGFR (52.9%), both of whose frequencies were significantly higher than the other tested genes (P < 0.05). Groups with alterations in EGFR, APC (3.3%) or RBM10 (4.1%) were significantly associated with the decreased expression of PD-L1 (P < 0.05), while alterations in TP53 were significantly associated with the increased expression of PD-L1 (P < 0.05). Comparative analysis revealed that alterations (single or compound mutation) occured in either EGFR or TP53 affect the PD-L1 expression in this Chinese cohort. Although alterations in either EGFR or TP53 has independent and synergistic effects on the PD-L1 expression, there is limited evidence for those alterations serving as predictive biomarkers for the PD-L1 status. Furthermore, whether patients with both high PD-L1 expression and alterations in EGFR or TP53 can benefit from immunotherapies is still in question, and this subgroup is still worthy of clinical molecular recognition by further study.

EP16.03-043 Comprehensive Genomic Profiling of Tumor Mutational Burden-high in Chinese Lung Cancer Patients

Tumor mutational burden-high (TMB-H) is the indication biomarker for pan-cancer immunotherapy approved by FDA. However, the understanding of the molecular and clinical characteristics of TMB-H lung cancer still limited, especially in Chinese patients.

Prognostic value of GPC5 polymorphism rs2352028 and clinical characteristics in Chinese lung cancer patients.

Background: GPC5 rs2352028 is associated with the risk of lung cancer, but its relationship with lung cancer prognosis is unclear. Materials & methods: The authors collected blood samples from 888 patients with lung cancer and used a Cox proportional hazards model to analyze the association between prognosis and GPC5polymorphism rs2352028. Results: GPC5 rs2352028C> Twas associated with a better prognosis. Patients with CT genotype had longer overall survival than those with CC genotype. Additionally, older and early-stage patients with CT+TT genotype had a lower risk of death than those with CC genotype. Conclusion: GPC5rs2352028C > T may play a protective role in patients with lung cancer and GPC5 rs2352028 may be a potential genetic marker for lung cancer prognosis.

EP16.03-008 The Landscape of NFE2L2 Alteration in Chinese Lung Cancer Patients

NFE2L2 encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. NFE2L2 variations were detected in many tumors, such as lung cancer, esophageal cancer, renal cell carcinoma and other cancer types. The landscape of NFE2L2 gene in lung cancer of Chinese population has not been descripted.

EP16.02-016 Exploration of Factors Affecting the Performance of MRD Tumor-Informed Assay in Chinese Lung Cancer Patients

Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) is predictive for post-operative recurrence in lung cancer. However, the suitable approach for sensible MRD monitoring remains controversial. Currently, whole-exome sequencing (WES) is widely used to design the customized monitoring panels of tumor-informed assay for MRD monitoring. We investigated the potential factors which may affect the performance of whole-exome sequencing (WES) for monitoring panels’ design.

Analysis of the Effcacy and Safety of Amivantamab in Non-small Cell Lung Cancer Patients with EGFR/MET Gene Abnormalities: A Single Center's Experience

背景与目的表皮生长因子受体（epidermal growth factor receptor, EGFR）和细胞间质上皮转换因子（cellular-mesenchymal to epithelial transition factor, c-Met）是非小细胞肺癌（non-small cell lung cancer, NSCLC）中常见的变异基因，都是受体酪氨酸激酶，在下游信号转导方面具有协同作用。针对EGFR和c-Met通路的靶向药物联合应用后，能够阻断PI3K/AKT/mTOR途径和Ras/Raf/Mek途径，限制补偿通路激活，发挥抗肿瘤作用。以Amivantamab为代表的EGFR和c-Met双特异性抗体新型药物能同时阻断两条信号通路，在肺癌临床研究中展现出良好前景。然而目前国内应用较少，相关经验缺乏。本研究将介绍我中心Amivantamab疗效数据和不良反应处理经验，探讨此类药物对我国EGFR/MET基因异常NSCLC的应用价值。方法收集2020年8月-2021年12月于我院接受Amivantamab治疗的晚期NSCLC病例的临床数据，分析其治疗反应率、生存和不良反应。结果本研究共纳入15例患者，其中Amivantamab单药治疗6例，Amivantamab联合Lazertinib治疗9例。治疗后7例（46.7%）达部分缓解（partial response, PR），7例（46.7%）达疾病稳定（stable disease, SD），1例（6.7%）达疾病进展（progressive disease, PD），总体客观缓解率（objective response rate, ORR）为46.7%，总体疾病控制率（disease control rate, DCR）为93.3%。7例EGFR外显子20插入突变患者中，2例（28.6%）达PR，5例（71.4%）达SD，DCR为100.0%，中位缓解持续时间（duration of response, DOR）未成熟，2例PR者仍持续缓解。5例奥希替尼耐药的患者中，2例（40.0%）达PR，3例（60.0%）达SD，DCR为100.0%，中位DOR未成熟，1例PR者仍持续缓解。中位随访时间为8.7个月（0.9个月-18.6个月），截至最后一次随访，共有6例患者发生疾病进展，3例患者死亡，中位无进展生存期和中位总生存期未成熟。常见的不良事件为皮疹（86.7%），甲沟炎（80.0%）和输液反应（60.0%），多为1级-2级。3级及以上不良反应包括皮疹（33.3%），转氨酶升高（13.3%）、水肿（6.7%）、血栓栓塞（6.7%）、间质性肺炎（6.7%）和血小板减低（6.7%）。结论Amivantamab对EGFR外显子20插入突变和奥希替尼耐药的中国晚期NSCLC治疗有效，与国外疗效数据相仿。整体安全性可耐受，需重点关注皮疹、甲沟炎、输液反应等不良反应。

Increasing Trends of Polypharmacy and Potentially Inappropriate Medication Use in Older Lung Cancer Patients in China: A Repeated Cross-Sectional Study.

Objectives: Polypharmacy and potentially inappropriate medication (PIM) use are frequent in older lung cancer patients. This study aimed to examine the trends of polypharmacy and PIM use and explore risk factors for PIM use based on the 2019 Beers criteria in older Chinese lung cancer outpatients with multimorbidity. Methods: A repeated cross-sectional study was conducted using electronic medical data consisting of the prescriptions of older lung cancer outpatients in China from January 2016 to December 2018. Polypharmacy was defined as the use of five or more medications. The 2019 Beers criteria were used to evaluate the PIM use of older cancer outpatients (age ≥65 years), and multivariate logistic regression was used to identify the risk factors for PIM use. Results: A total of 3,286 older lung cancer outpatients and their prescriptions were included in the study. The prevalence of polypharmacy was 14.27% in 2016, 16.55% in 2017, and 18.04% in 2018. The prevalence of PIM use, according to the 2019 Beers criteria, was 31.94% in 2016, 35.78% in 2017, and 42.67% in 2018. The two most frequently used PIMs in older lung cancer outpatients were estazolam and tramadol. The logistic regression demonstrated that age 75 to 79, polypharmacy, irrational use of drugs, and lung cancer accompanied by sleep disorders, anxiety or depression, or pain were positively associated with PIM use in older lung cancer outpatients. Conclusion: The prevalence of polypharmacy and PIM use in older lung cancer outpatients with multimorbidity was high in China, and polypharmacy and PIM use increased over time. Further research on interventions rationing PIM use in the older lung cancer patient population is needed.

Abstract 5774: Investigating the characteristics of BRAF Mutations and its potential relationship with therapy in a large Chinese Lung Cancer cohort

Abstract Background: In lung cancer, the proportion of BRAF mutations is low. Rare specific studies have evaluated the BRAF mutation characteristics in lung cancer. Currently, there are some studies suggesting that patients with BRAF mutations may be benefit from immunotherapy, while patients with BRAF V600E may benefit from targeted therapy. Here, the characteristics of BRAF mutation, including BRAF V600E, in a lung cancer cohort of Chinese were analyzed. The characteristics of BRAF mutation with PD-L1 expression were also analyzed. Method: BRAF mutant samples were extracted from 12,051 our cohort samples of lung cancer that from Onco Panscan࣪ (Genetron Health) based sequencing of tissue. The characteristics of them were then investigated. Co-mutations of PD-L1 expressed BRAF samples were also analyzed. Results: 684 samples (5.68%) in our cohort had BRAF mutations. Only 134 (19.59%) of them were V600E mutation, maybe good response to BRAF inhibitors. 550 (80.41%) of samples were BRAF non-V600E mutation, maybe benefit from immunotherapy. BRAF mutations were more happened in male (58.3%), while female patients were increased in V600E mutation group when compared with non-V600E group (49.25% vs. 39.82%, P=0.0509). BRAF mutations were more likely to occur in LUAD than in LUSC (6.37% vs. 3.89%, P=0.0022), especially BRAF V600E mutation. The mean age of BRAF mutant patients was 61.56 ± 10.32 years. BRAF V600E patients was significantly older than BRAF non-V600E patients on average (63.01 ± 9.76 years vs. 61.20 ±10.43, P=0.0129). BRAF mutations were distributed across all exons but concentrated on exon 15 (269/684, 39.33%). Moreover, BRAF V600E mutation accounted for 49.81% (134/269) of exon 15. In our data, there were 108 samples with BRAF mutation and PD-L1 positive (TPS≥1%). Among them, 95 samples (87.96%), including samples with BRAF V600E or non-V600E mutation, had no co-mutations or without other medication targets, may be benefit from BRAF inhibitors, or may be good response to immunotherapy, especially the 20 samples with TMB-high. Interestingly, 13 samples had EGFR sensitive co-mutation or EML4-ALK fusion. These 13 patients may be benefit from TKI firstly, then immunotherapy can be considered. Conclusions: Most of BRAF mutations in Chinese lung cancer samples were non-V600E mutations (80.26%). BRAF mutations were more occurred in male and LUAD patients whose age around 61.56 ± 10.32 years. BRAF V600E patients were much older. Among PD-L1 positive and BRAF mutant samples, most BRAF mutations (87.96%), including V600E, were mutually exclusive with driver mutations of other genes. These patients will most likely benefit from BRAF inhibitors or immunotherapy. For the samples with co-mutation of BRAF and EGFR or ALK, may be treated EGFR or ALK TKI firstly. Citation Format: Jianqing Zhang, Jiagang Feng, Ling Liu, Man Jia, Tong Liu, Jiaqiang Zhang, Zehua Liao, Jianmei Zhao, Yu Fang, Jing Chen, Xiaoyan Zhang, Tonghui Ma. Investigating the characteristics of BRAF Mutations and its potential relationship with therapy in a large Chinese Lung Cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5774.

Abstract 5292: Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC)

Abstract BackgroundCurrently, BRAF inhibitors are primarily effective in LC patients with BRAF V600E mutation, while with limited benefit for patients with BRAF non-V600E mutation. Additionally, it is unclear whether immunotherapy is effective in LC patients with BRAF mutations, and the relationship between BRAF mutations and immune biomarkers, such as TMB, is also unclear. Here, we retrospectively investigated the relationship with BRAF mutation and TMB in Chinese LC patients.MethodsSamples were extracted from 3,136 our cohort samples of LC, which from OncoPanscan࣪ (Genetron Health) based sequencing of tissue. Because of the significantly different cohort characteristics, propensity score matching was used to resolve potential confounding by a nearest neighbor algorithm. The use of a multivariable logistic regression model to estimate the propensity score was based on age, sex, cancer type and detail panels. The samples after propensity score matching was used to investigate the relationship with TMB. ResultsIn our cohort, 171 samples had BRAF mutations and 2,965 samples had non-BRAF mutations. After propensity score analysis, 165 samples of BRAF mutations were screened with 165 paired samples of non-BRAF mutations.In the 165 samples of BRAF mutations, 83 samples of them had TMB information, while 83 samples of the 165 paired samples of non-BRAF mutations had TMB information. Patients with BRAF mutation had a higher median TMB than the patients with non-BRAF mutation (9.39 vs. 7.51 Muts/Mb, p=0.0545). Similarly, in these two groups, there was slightly higher ratio of samples with TMB ≥10muts/Mb (43.37% vs. 31.32%, P=0.0788). Among BRAF mutation group, when compared to BRAF V600E group (N=26), the median TMB was much higher in non-V600E group (N=57) (7.38 vs. 9.86 muts/Mb, P=0.0270). The proportion of TMB ≥10muts/Mb in BRAF non-V600E group was much higher than V600E group (49.12% vs. 30.77%, P=0.0094). Additionally, we analyzed the samples that had high TMB (TMB≥10 muts/Mb) and high PD-L1 (TPS≥50%). The BRAF mutation group had more proportion than non-BRAF mutation (14.46% vs.6.02%, p=0.0593), and the BRAF non-V600E group was higher than BRAF V600E group (15.79% vs. 11.54%, P=0.4150).ConclusionsCompared with non-BRAF mutation, BRAF mutation was associated with higher TMB, and it was also higher in BRAF non-V600E than BRAF V600E. These results suggested that patients with driver mutation of BRAF V600E had lower TMB and they always had good response to BRAF inhibitors. While LC patients with BRAF non-V600E always with higher TMB, thus, they may be more suitable for immunotherapy. However, more clinical research are needed to evaluate the effectiveness of immunotherapy. Citation Format: Jian Zhang, Yu Fang, Lei Sun, Hongling Yuan, Mao Shang, Xiaoyan Zhang, Honglin Zhu, Tonghui Ma. Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5292.

Abstract 5771: The refined stratification of receptor tyrosine kinase fusions in lung cancer

Abstract Background: The overall survival of patients with the actionable receptor tyrosine kinase (TRK) fusions can be significantly prolonged after taking targeted kinase inhibitors. However, the outcomes are variable due to the different fusion types of the same driver gene. Method: Formalin fixed paraffin embedded tissues from patients with lung cancer between March 2018 and September 2021 were performed by using next generation sequencing (NGS) at Genetronhealth, a laboratory accredited by College of American Pathologists and Clinical Laboratory Improvement Amendments. Results: In a large cohort of 3768 patients with lung cancer, 348 cases harboring the actionable TKR fusions, including ALK, ROS1, RET, EGFR, MET, BRAF, NTRK1/2/3. TRK fusions can be divided into three types based on the breakpoints, partners and fusion models: single 3’ fusions, nonreciprocal fusions with the intact tyrosine kinase domain (TKD); single 5’ fusions, reciprocal fusions with the incomplete TKD; complex fusions, nonreciprocal/reciprocal fusions or nonreciprocal fusions with different partners. At the gene level, 58% (203 of 348) of TRK fusions were ALK, among which 71% of single 3’ ALK (144 of 203), 3% of single 5’ ALK (6 of 203) and 26% of complex fusions (53 of 203) were included. ROS1 fusions accounted for 14% (50 of 348) of all TRK fusions, and the proportions of single 3’ fusions, single 5’ fusions and complex fusions were 60% (30 of 50), 6% (3 of 50) and 34% (17 of 50), respectively. RET captured 19% (66 of 348) TRK fusions with 70% of single 3’ RET (46 of 66), 5% of single 5’ RET (3 of 66) and 26% of the complex fusions (17 of 66). EGFR owned 3% (9 of 348) with 33% of single 3’ EGFR (3 of 9), 33% of single 5’ EGFR (3 of 9) and 33% of the complex (3 of 9). MET, BRAF and NTRK1/2/3 shared the rest 5% of total fusions without complex type. Conclusion: Our research shows different types of TRK fusions in Chinese lung cancer patients, which can help guide the precise treatment in clinical. Citation Format: Chaoyang Liang, Lin Li, Xiaofang Liu, Qiuhua Liu, Baoming Wang, Chunyang Wang, Tonghui Ma, Fanlu Meng. The refined stratification of receptor tyrosine kinase fusions in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5771.

Prognostic features and comprehensive genomic analysis of NF1 mutations in EGFR mutant lung cancer patients.

NF1 is a tumor suppressor gene that encodes the neurofibromin protein and negatively regulates Ras signaling. This study was aimed to investigate the molecular, clinical characteristics, and prognostic features of NF1 gene in EGFR mutant lung cancer patients. The next-generation sequencing (NGS) was used to analyze the data from lung cancer patients in the Guangdong Lung Cancer Institute (GLCI) from June 2016 to December 2020. Somatic NF1 mutations were present in 4.2% (135/3220) of Chinese lung cancer patients. NF1 mutations where clearly enriched in older (p < 0.001), male (p < 0.001), and smoking (p < 0.001) patients. Patients with NF1 mutations were more likely to have TP53 (p=0.003), BRAF (p =0.001) and RASA1 (p=0.026) mutations and mutually exclusive with EGFR mutations (p=0.006). TP53 mutation had worsen prognosis in cases of NF1 mutant (p=0.026) or EGFR/NF1 co-mutant (p=0.031) lung adenocarcinomas (LUAD) patients. There was no effect on overall survival (OS) in LUAD patients with and without NF1 mutations, even in LUAD driver-gene negative patients. NF1/EGFR co-mutation patients had a longer OS than a single mutation of either the EGFR gene (median OS: 47.7m vs. 30.2 m, hazard ratio [95% CI], 0.47 [0.30-0.74], p=0.004) or NF1 gene (47.7m vs. 19.0 m, 0.44 [0.27-0.73], p=0.003). Furthermore, NF1 mutations significantly prolonged OS in EGFR mutant/TP53 wild-type LUAD patients (106.5m vs. 25.5 m, 0.28 [0.13-0.59], p=0.003) but not in patients with EGFR/TP53 co-mutations (36.8m vs. 30.2 m, 0.70 [0.39-1.26], p=0.280). Our results indicated NF1 mutations served as a good prognostic factor in EGFR mutant/TP53 wild-type lung cancer patients in this single-center study. TP53 mutation was obviously enriched in NF1 mutant patients and had shorter OS.