Virtual Library
Start Your Search
Chun-wei Xu
Author of
-
+
P23 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Esophageal Cancer and Rare Tumors (ID 137)
- Event: WCLC 2020
- Type: Posters
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P23.03 - The New Therapy on Esophageal Leiomyosarcoma in the Upper Esophagus (ID 1255)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Esophageal leiomyosarcoma (E-LM) is the commonest of all esophageal sarcomas but yet has a very low incidence. The esophageal leiomyosarcoma in the upper esophagus is extremely rare. We report a relatively rare case of E-LM in the upper esophagus enucleated by neck incision surgery.
Methods
A 31-year-old man had dysphagia for >6 months without associated weight loss or anorexia. An upper gastrointestinal endoscopy showed a huge bulge of 7.0 cm in length of the upper esophagus with intact mucosa extending to the lower margin of fourth thoracic vertebrae.
Results
Endoscopic biopsy of the distal esophagus reveal the spindle cell soft tissue tumor. Under general anesthesia, we performed left neck incision surgery. We decided to perform tumor removal as planned. The left cervical sternocleidomastoid muscle anterior incision was taken, and the esophageal outer membrane, muscle layer and mucous membrane were cut longitudinally. Tumor exploration showed the giant tumor occupying the upper mediastinum and small compressing hertrachea through the left neck space. First, the tumor adhered to the trachea. However, the trachea or re-current laryngeal nerves were not damaged in the surgery. The esophagus was encircled above and below the tumor. The tumor about 10.0×6.0×4.0cm in the esophagus was seen, the quality was tough, the affected esophageal mucosa was removed, and the mucosal layer was repaired by intermittent suture. The operation time was 65 minutes and blood loss was 25 ml. Postoperative pathology: submucosal spindle cell tumor with mucosal erosion and ulceration. Combined with immunohistochemicalization, it accorded with leiomyoma with malignant change, and evil became into leiomyosarcoma, which accounts for about 40% of tumor tissue. Our experience suggested that by neck incision surgery treatment was safety and effective for patients with E-LM. The patient was no recurrence with postoperative follow-up for one year.
Conclusion
Our experience suggested that by neck incision surgery treatment is safety and effective for patients with E-LM. The E-LM could be one-time removed and the risk is small. Moreover, the lesion was completely resected to avoid chest complications and digestive tract reconstruction.
-
+
P35 - Pathology - Genomics (ID 105)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P35.01 - Genomic Origin and Immune-related Status of Pulmonary Sarcomatoid Carcinoma (ID 1695)
00:00 - 00:00 | Author(s): Chun-wei Xu
- Abstract
Introduction
Pulmonary sarcomatoid carcinoma (PSC), composed of sarcomatous component (SaC) and carcinomatous component (CaC), is a rare and highly aggressive subtype of poorly differentiated non-small cell lung cancer (NSCLC) with poor survival compared to other type of NSCLC. Here, we explored the genetic origin, intratumor heterogeneity (ITH), driver mutations, tumor mutation burden (TMB), and PD-L1 status of PSC.
Methods
31 immunohistochemically (IHC) diagnosed PSCs were enrolled and surgical tumors were separated by laser capture microdissection to obtain SaC and CaC. Independent components were subjected to targeted sequencing with a 1021-gene-panel. Shared and private alterations were investigated to explore the genetic origin and evolutionary event. Somatic mutations were used to assess TMB and construct phylogenetic tree. PD-L1 expression level was determined by IHC. Independent cohorts of 67 lung adenocarcinomas (LUAD) and 265 sarcomas were used for genomic and PD-L1 comparison.
Results
87% of patients (pts) were male, with a median age of 58.0 years. 64.5% were smokers. The most recurrently mutated genes were TP53 (74%), MET (23%), NF1 (19%), EGFR (19%), and KRAS (19%) in SaCs, similarly, TP53 (74%), MET (19%), NF1 (19%), EGFR (19%), KRAS (19%) and MAP3K1 (19%) in CaCs. 30 (97%) cases had component-shared (trunk) alterations between SaC and CaC implying the genetically monoclonal origin of the majority of PSCs. TP53, MET, NF1, and KRAS were mostly frequently found in common mutations. Driver mutations of EGFR (L858R and 19del), KRAS (G12X), MET (amplification and exon 14 skipping), PIK3CA (E545K and amplification), and EML4-ALK fusion were tend to be located in trunk and with predominant cancer cell fraction. 27 PSCs had component-private alterations, including MET amplification, PIK3CA amplification, EGFR amplification, TP53 mutations, CDKN2A mutations, and EGFR rare mutations, suggesting the common branch evolution event and genetic ITH. Compared with LUAD, adenocarcinoma component of PSC showed the differentially mutational features, especially with lower EGFR incidence (21% vs 45%, p = 0.051). Compared with typical sarcomas, MET, EGFR, NF1 were detected with higher mutated frequently in SaCs, indicating the differentially mutational features. CaC and SaC had equivalent and proportional TMB and PD-L1 level. Compared with LUAD, SaC had significant higher TMB (p = 0.029), while CaC with not fully significant (p = 0.086). SaC possibly had more patients with high PD-L1 expression (TPS > 50%) (27% vs 12%, p = 0.080), while CaC similar (13%, p = 1.000). We found that patients with lower proportion of component-shared alterations (trunk ratio) had prolonged DFS (Log-rank test, p = 0.006). Multivariate cox regression analysis indicated that trunk ratio as an independent prognostic factor (p = 0.011).
Conclusion
The majority of PSCs share a monoclonal origin between CaC and SaC, with common branch evolutionary event leading to mutational ITH. PSC is a particular subgroup of NSCLC. Targetable trunk driver mutations, high TMB and positive PD-L1 expression may provide the treatment options. Mutational ITH may be an independently prognostic indicator.
-
+
P38 - Pathology - Pathology/Staging (ID 108)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P38.08 - Clinical Features and Survival Risk Factors of Lung Lymphoepithelioma-Like Carcinoma Based on the SEER Database Analysis (ID 682)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Primary LELC in lung (lung LELC) is a rare subtype of non-small cell lung cancer. The present study aimed to describe the demographic characteristics, clinical manifestations, treatment and outcomes of lung LELC according to 75 patients from the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
The inclusion criteria of LELC case (diagnosed from 1984 to 2016) were: with a histological type coded 8082 in ICD-O-3, the primary site was as C34, and the location of the tumor was limited to the lung. The Cox proportional hazard regression model, Kaplan-Meier method, and ROC curve were used to for survival associated data analysis.
Results
Seventy-five cases were acquired, including 33 males and 42 females. LELC has distinct features from squamous cell carcinoma in age, sex and races, and higher proportion of LELCs received surgery and chemotherapy while fewer received radiotherapy. For cases with information of tumor size, multivariable Cox proportional hazard model showed younger age, male, and non-single status were beneficial demographic factors for survival; carcinomas located on the right related to better survival; radiotherapy and chemotherapy provided significant survival benefits. Further, the 1-year and 5-year survival were predicted by the binary Logistic model, which showed satisfactory AUC levels (0.964 and 0.821, respectively). Moreover, surgery can benefit the 5-year survival. In addition, females had a higher frequency of distant metastasis at the time of diagnosis, and the tumors located on the right side or paired sides were more likely to develop distant metastasis.
Conclusion
Together, younger age, male, and non-single status were beneficial demographic factors for LELC survival, and carcinomas located on the right side mean better survival. Surgery, radiotherapy and chemotherapy can provide survival benefits in different aspects. Females and patients with carcinomas located on the right were more likely to develop distant metastasis.
-
+
P53 - Tumor Biology and Systems Biology - Basic and Translational Science - Misc. Topics (ID 213)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P53.06 - Crizotinib Induces Apoptosis of Lung Cancer Cells Through JAK-STAT Pathway (ID 671)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Effect of crizotinib on apoptosis of lung cancer cells was investigated. However, detailed mechanism is still unclear. Therefore, in this study, crizotinib was used to treat H2228 non-small cell lung adenocarcinoma cells and its effect was observed on cell apoptosis and expression of JAK and STAT protein, so as to explore the effects of crizotinib on lung cancer and the role of JAK-STAT signaling pathways.
Methods
Human non-small cell lung adenocarcinoma H2228 cells were cultured in the presence of 0, 20, 40, 80, 160 and 320 nmol/l of crizotinib for 3 days, respectively. The inhibition rate of cell proliferation was measured by MTT assay, and half maximal inhibitory concentration (IC50) was calculated. Cell apoptosis was detected by flow cytometry. Transwell assay was performed to detect cell migration. Expression of Janus protein tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) proteins was detected by western blot analysis.
Results
Crizotinib significantly inhibited the proliferation of human lung cancer H2228 cells, and the inhibitory effect was enhanced with the increase of the concentration of crizotinib (p<0.01). The IC50 value was 311.26 nnol/l. According to IC50 value, concentration of crizotinib at 300 nmol/l was selected for the study. It was found that crizotinib at 300 nmol/l significantly promoted cell apoptosis (p<0.01) and inhibited cell migration (p<0.01). Compared with pretreatment levels, crizotinib downregulated the expression of JAK and STAT (p<0.01) on the 1st day of treatment, but with the prolongation of time, no further significant difference was observed on the 1st, 2nd or 3rd day in the level of JAK protein (p=0.47); there were no statistically significant differences in the level of STAT protein (p=0.91).
Conclusion
Crizotinib can inhibit the migration and promote cell apoptosis of human lung cancer cell line H2228 by regulating the expression of JAK and STAT proteins in JAK-STAT signaling pathway.
-
+
P53.07 - Clinicopathologic Characteristics of Patients With PTPN11 Mutations in East Asian Non-Small Cell Lung Cancer Patients (ID 678)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
The PTPN11 (protein tyrosine-phosphatase non-receptor type-11) gene encodes SHP2, which is a member of ubiquitously expressed protein tyrosine phosphatase with positive regulatory roles in signalling pathways, including Ras-mitogenactivated protein kinase signaling. Somatic mutations in PTPN11 are common in histiocytic sarcoma(HS), juvenile myelomonocytic leukemia (JMML) and acute myeloid leukemia (AML), that responded to the MAPK extracellular signal-regulated kinase (MEK)-inhibitor trametinib. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring PTPN11 mutations.
Methods
A total of 724 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of PTPN11 mutations and other genes were detected by next generation sequencing.
Results
PTPN11 gene mutation rate was 0.69% (5/724) in non-small cell lung cancer, including D425N (1 patient), D425Y (1 patient), R527C (1 patient), E76Q (1 patient) and V382I (1 patient), and median overall survival (OS) for these patients was 17.0 months. Among them, all patients were PTPN11 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=2) co-occurring TP53 mutations had a median OS of 17.0 months and 10.5 months respectively (P=0.64); patients with (n=4) or without (n=1) co-occurring KRAS mutations had a median OS of 17.0 months and 4.0 months respectively (P=0.35); patients with (n=2) or without (n=3) co-occurring ATM mutations had a median OS of 10.5 months and 17.0 months respectively (P=0.64); patients with (n=2) or without (n=3) co-occurring EPHA3 mutations had a median OS of 17.0 months and 4.0 months respectively (P=0.20).
Conclusion
Our data reveal PTPN11 genetic alter occurs in a subset of NSCLC. NGS might be useful for evaluation of PTPN11 unclassified variants. Our results show that PTPN11 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through trametinib might offer new opportunities.
-
+
P55 - Tumor Biology and Systems Biology - Basic and Translational Science - Cell Cycle (ID 192)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P55.01 - Different Types of CDK4 Mutations in East Asian Non-Small Cell Lung Cancer Patients (ID 688)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, has an especially crucial role in tumorigenesis. This region harbors another important partner in the RB1-CCND1 pathway, namely, cyclin dependent kinase 4 (CDK4). The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring CDK4 mutations.
Methods
A total of 1049 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of CDK4 mutations and other genes were detected by next generation sequencing.
Results
CDK4 gene mutation rate was 0.67% (7/1049) in non-small cell lung cancer, including G13C (1 patient), D119V (1 patient), D236Y (1 patient), K282R (1 patient), K155N (1 patient), R38K (1 patient) and E7Q (1 patient), and median overall survival (OS) for these patients was 23.0 months. Among them, all patients were CDK4 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=3) co-occurring EGFR mutations had a median OS of 14.5 months and 23.0 months respectively (P=0.43); patients with (n=5) or without (n=2) co-occurring TP53 mutations had a median OS of 23.0 months and 14.5 months respectively (P=0.81); patients with (n=2) or without (n=5) co-occurring KRAS mutations had a median OS of 14.5 months and 23.0 months respectively (P=0.81); patients with (n=2) or without (n=5) co-occurring ALK mutations had a median OS of 6.0 months and 23.0 months respectively (P=0.01).
Conclusion
CDK4 mutations represent a distinct subset of NSCLC. Next generation sequencing showed that CDK4 mutations commonly co-existed with other driver genes. Our results show that CDK4 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through CDK4 inhibitior palbociclib might offer new opportunities.
-
+
P57 - Tumor Biology and Systems Biology - Basic and Translational Science - DNA Repair (ID 195)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P57.01 - Prevalence MSH6 Mutations in East Asian Non-Small Cell Lung Cancer Patients (ID 824)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
The DNA mismatch repair (MMR) pathway is one of the cell defense mechanisms by which mutations that spontaneously arise during replication and recombination are corrected to maintain genomic integrity. Defects in the MMR genes (MLH1, MSH2, MSH6 and PMS2) lead to genomic instability. MSH6 gene (HGNC_ID:7329) is located in chromosome 2 (2p16) codes for an MSH6 protein in humans. The MSH6 protein contains Walker-A/B adenine nucleotide binding motif (150 amino acids). The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring MSH6 mutations.
Methods
A total of 842 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MSH6 mutations and other genes were detected by next generation sequencing.
Results
MSH6 gene mutation rate was 3.21% (27/842) in non-small cell lung cancer, including E1163V (3 patient), S346C (3 patient), G355S (2 patient), A37G (2 patient), T1225M (2 patient), S144I (2 patient), K1358Dfs*2 (2 patient), Y642C (1 patient), A48V (1 patient), L735P (1 patient), K854M (1 patient), D116G (1 patient), Q572H (1 patient), F1088Lfs*5 (1 patient), S309Y (1 patient), N184S (1 patient), T767S (1 patient) and F1088Sfs*2 (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were MSH6 gene with co-occurring mutations. Briefly, patients with (n=5) or without (n=22) co-occurring EGFR mutations had a median OS of not up to now and 14.0 months respectively (P=0.27); patients with (n=16) or without (n=11) co-occurring TP53 mutations had a median OS of 14.0 months and 19.0 months respectively (P=0.33); patients with (n=11) or without (n=16) co-occurring KRAS mutations had a median OS of 14.0 months and 19.0 months respectively (P=0.09); patients with (n=4) or without (n=23) co-occurring KMT2C mutations had a median OS of not up to now and 14.0 months respectively (P=0.36).
Conclusion
MSH6 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to immunotherapy in patients with NSCLC.
-
+
P59 - Tumor Biology and Systems Biology - Basic and Translational Science - Genomics (ID 197)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P59.01 - AR Mutations Defines a Unique Molecular Class of Non-Small Cell Lung Cancer in East Asian Patients (ID 857)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Epidemiology of non-small-cell lung cancer (NSCLC) differs between genders and it might be partially explained by different gender hormone levels in female and male. There are some epidemiological data indicating that gender is a significant, independent prognostic factor in NSCLC with AR (Androgen receptor). The aim of this study is to investigate mutations and prognosis of NSCLC harboring AR mutations.
Methods
A total of 509 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of AR mutations and other genes were detected by next generation sequencing.
Results
AR gene mutation rate was 1.77% (9/509) in non-small cell lung cancer, including T756S (1 patient), E355K (1 patient), T919N (1 patient), Q734H (1 patient), E773Q (1 patient), A45T (1 patient) , A141T (1 patient), D840H (1 patient) and D308H (1 patient), and median overall survival (OS) for these patients was 21.0 months. Among them, all patients were AR gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=5) co-occurring EGFR mutations had a median OS of 16.5 months and 21.0 months respectively (P=0.84); patients with (n=6) or without (n=3) co-occurring TP53 mutations had a median OS of 20.5 months and 21.0 months respectively (P=0.88); patients with (n=5) or without (n=4) co-occurring SMARCA4 mutations had a median OS of 20.0 months and 21.0 months respectively (P=0.50); patients with (n=3) or without (n=6) co-occurring CDKN2A mutations had a median OS of 21.0 months and 20.0 months respectively (P=0.72).
Conclusion
Althoght EGFR, TP53, SMARCA4, CDKN2A gene accompanied may have less correlation with AR mutation in NSCLC patients, predict which patients may harbor AR mutations, could have implications in triaging toward AR variant identification for potential future targeted therapy. These data have implications for the identification of therapeutic target candidates.
-
+
P64 - Tumor Biology and Systems Biology - Basic and Translational Science - miRNA (ID 202)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P64.01 - MiRNAs in Exosomes Isolated From the Blood of Non-Small Cell Lung Cancer Patients: Biomarkers for Lung Cancer Prediction and Prognosis (ID 696)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Non-small cell lung cancer accounts for about 80% of lung cancer, and about 75% of patients have been found in advanced stages, and their survival rate is very low. However, sensitive and simple diagnostic tests for NSCLC and highly-targeted therapeutic biomarkers are still clinically unusable. The aim of this study was to investigate the expression profiles and clinical significance of miRNAs in platelet-derived exosomes in peripheral blood as biomarkers for NSCLC.
Methods
The fasting blood samples of 102 patients with NSCLC and 89 healthy people were collected. The exosomes were obtained from platelets using ExoQuick Precipitation Kit. The expression of miR-223 in exosomes from platelets were determined by QRT-PCR. Furthermore, we explored its mechanism in the tumor progress by cell migration assay.
Results
First, we found that the levels of miR-223 in platelets and P-MVs were significantly up-regulated in lung cancer patients compared with the non-cancer control group. Second, in vitro assays using qRT-PCR showed that platelet miR-223 was rapidly delivered into cancer cells by P-MVs. Third, platelet-derived exogenous miR-223 reduces the protein level of the tumor suppressor EPB41L3, thereby promoting the invasion of lung cancer cells. The effect of P-MV on the reduction and enhancement of tumor cell invasion by EPB41L3 was largely eliminated by consumption of miR-223, indicating that miR-223 plays a key role in these processes.
Conclusion
This study provides additional evidence that functional miRNAs in MVs secreted by cells can serve as biomarkers for lung cancer prediction and prognosis.
-
+
P70 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/OTHERS (ID 210)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 5
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P70.01 - Distribution of CCND1 Mutations in East Asian Patients With Non-Small Cell Lung Cancer (ID 646)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
CCND1 is a member of the cyclin D family and promotes G1-S transition in cell proliferation. In the TransATAC substudy, breast cancers with CCND1 amplification were found to have a poor prognosis. In addition, overexpression of CCND1 demonstrates resistance to chemotherapy in vitro. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring CCND1 mutations.
Methods
A total of 661 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of CCND1 mutations and other genes were detected by next generation sequencing.
Results
CCND1 gene mutation rate was 0.61% (4/661) in non-small cell lung cancer, including E280V (1 patient), E74K (1 patient), P157A (1 patient) and T120P (1 patient), and median overall survival (OS) for these patients was 13.5 months. Among them, all patients were CCND1 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=2) co-occurring EGFR mutations had a median OS of 7.5 months and 13.5 months respectively (P=0.81); patients with (n=2) or without (n=2) co-occurring TP53 mutations had a median OS of not up to now and 13.5 months respectively (P=0.88); patients with (n=2) or without (n=2) co-occurring KRAS mutations had a median OS of 7.5 months and 13.5 months respectively (P=0.81); patients with (n=2) or without (n=2) co-occurring BRCA2 mutations had a median OS of 7.0 months and not up to now respectively (P=0.09).
Conclusion
EGFR, TP53, KRAS and BRCA2 gene accompanied may have less correlation with CCND1 mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.
-
+
P70.02 - Clinicopathologic Characteristics and Outcomes of East Asian Patients With Non-Small-Cell Lung Cancer and FLT3 Mutations (ID 673)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
The FLT3 gene is located on chromosome 13, and FLT3 receptors comprise fve immunoglobulin-like structures, including a ligand-binding extracellular domain, a single transmembrane domain, a cytoplasmic domain containing the juxtamembrane domain (JMD), and two tyrosine kinase domains (TKDs; TKD1 and TKD2). FLT3-ITD results in an ITD in the JMD and is reportedly associated with signifcantly short remission periods and poor outcomes. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring FLT3 mutations.
Methods
A total of 417 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of FLT3 mutations and other genes were detected by next generation sequencing.
Results
FLT3 gene mutation rate was 1.44% (6/417) in non-small cell lung cancer, including R834Q (1 patient), I527T (1 patient), L104P (1 patient), Q115H (1 patient), R271S (1 patient) and K567E (1 patient), and median overall survival (OS) for these patients was 10.0 months. Among them, all patients were FLT3 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 10.0 months and 15.5 months respectively (P=0.60); patients with (n=2) or without (n=4) co-occurring KEAP1 mutations had a median OS of 8.0 months and 16.5 months respectively (P=0.06); patients with (n=2) or without (n=4) co-occurring NTRK3 mutations had a median OS of 9.0 months and 16.5 months respectively (P=0.26); patients with (n=3) or without (n=3) co-occurring PTPRD mutations had a median OS of 9.0 months and not up to now respectively (P=0.29).
Conclusion
FLT3 gene mutation coexists with other gene mutation in NSCLC. TP53, KEAP1, NTRK3 and PTPRD gene accompanied may have less correlation with FLT3 mutation in NSCLC patients. Analysis of FLT3 mutations shows promise as a way to refine individual patients with NSCLC, and provides more insight into effective treatment strategies for patients with FLT3 mutations.
-
+
P70.03 - Molecular Characterization of AKT1 Gene in East Asian Non-Small Cell Lung Cancer Patients (ID 685)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
The AKT1 gene provides instructions for making a protein called AKT1 kinase. This protein is found in various cell types throughout the body, where it plays a critical role in many signaling pathways. The AKT1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring AKT1 mutations.
Methods
A total of 1255 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of AKT1 mutations and other genes were detected by next generation sequencing.
Results
AKT1 gene mutation rate was 0.64% (8/1255) in non-small cell lung cancer, including E418K (1 patient), R15Q (1 patient), R25Tfs*8 (1 patient), K154Nfs*97 (1 patient), T443M (1 patient), F407L (1 patient) , G159D (1 patient) and E17K (1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were AKT1 gene with co-occurring mutations. Briefly, patients with (n=6) or without (n=2) co-occurring TP53 mutations had a median OS of 9.0 months and 12.0 months respectively (P=0.64); patients with (n=2) or without (n=6) co-occurring ERBB4 mutations had a median OS of 12.5 months and 12.0 months respectively (P=0.91); patients with (n=2) or without (n=6) co-occurring EZH2 mutations had a median OS of 9.0 months and 12.0 months respectively (P=0.52); patients with (n=2) or without (n=5) co-occurring KEAP1 mutations had a median OS of 9.0 months and 12.0 months respectively (P=0.21).
Conclusion
TP53, ERBB4, EZH2, KEAP1 gene accompanied may have less correlation with AKT1 mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.
-
+
P70.04 - Outcomes of Molecular Characteristics in East Asian IDH2-mutant Non-Small Cell Lung Cancer Patients (ID 697)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Isocitrate dehydrogenases (IDH) 2 is key metabolic enzymes that generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) to maintain a pool of reduced glutathione and peroxiredoxin, and produce-ketoglutarate, a co-factor of numerous enzymes. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring IDH2 mutations.
Methods
A total of 893 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IDH2 mutations and other genes were detected by next generation sequencing.
Results
IDH2 gene mutation rate was 0.90% (8/893) in non-small cell lung cancer, including R172G (2 patient), R140Q (2 patient), T146Lfs*15(2 patient), S371G (1 patient) and E150K (1 patient), and median overall survival (OS) for these patients was 9.5 months. Among them, all patients were IDH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=6) co-occurring EGFR mutations had a median OS of 13.5 months and 9.5 months respectively (P=0.74); patients with (n=6) or without (n=2) co-occurring TP53 mutations had a median OS of 16.5 months and 5.5 months respectively (P=0.19); patients with (n=2) or without (n=6) co-occurring RB1 mutations had a median OS of 4.5 months and 16.5 months respectively (P=0.03); patients with (n=2) or without (n=6) co-occurring CDKN2A mutations had a median OS of 9.5 months and 13.5 months respectively (P=0.64).
Conclusion
IDH2 mutations were observed in 0.90 % of cases of NSCLC. IDH2-mutated NSCLC can exhibit other driver gene alterations. RB1 accompanied mutations might play a good prognosis in IDH2 gene mutation patients.
-
+
P70.05 - The Association Between MAP2K1 Mutation Class and Clinical Features in MAP2K1‑Mutant East Asian Non‑Small Cell Lung Cancer Patients (ID 837)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
The MAP2K1 gene provides instructions for making a protein known as MEK1 protein kinase. This protein is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus. RAS/MAPK signaling helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring MAP2K1 mutations.
Methods
A total of 793 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MAP2K1 mutations and other genes were detected by next generation sequencing.
Results
MAP2K1 gene mutation rate was 1.77% (14/793) in non-small cell lung cancer, including Q56P (2 patient), D351G (2 patient), H119Y (2 patient), R160K (1 patient), R234T (1 patient), E120D (1 patient), P124L (1 patient), C207S (1 patient), A283S (1 patient), E102_I103del (1 patient) and Q354H (1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were MSH6 gene with co-occurring mutations. Briefly, patients with (n=9) or without (n=5) co-occurring TP53 mutations had a median OS of 12.0 months and not up to now respectively (P=0.41); patients with (n=3) or without (n=11) co-occurring KRAS mutations had a median OS of not up to now and 12.0 months respectively (P=0.33); patients with (n=4) or without (n=10) co-occurring KRAS mutations had a median OS of 14.5 months and 12.0 months respectively (P=0.57); patients with (n=4) or without (n=23) co-occurring STK11 mutations had a median OS of 11.5 months and 12.0 months respectively (P=0.70).
Conclusion
MAP2K1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of MAP2K1 aberrations is critical for the identification of therapeutic target candidates.
-
+
P73 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/FGFR (ID 209)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P73.01 - Clinicopathologic Characteristics and Survival Outcome in East Asian Patients With Non-Small Cell Lung Cancer and FGFR2 Mutations (ID 690)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Activation of the fibroblast growth factor receptor (FGFR) family through fusion with various partners has been described in multiple cancer types, including non-small-cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring FGFR2 mutations.
Methods
A total of 1124 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of FGFR2 mutations and other genes were detected by next generation sequencing.
Results
FGFR2 gene mutation rate was 1.69% (19/1124) in non-small cell lung cancer, including R6P(4 patient), N184Efs*16(2 patient), L753F(1 patient), G302R(1 patient), E755Q(1 patient), W72C(1 patient), A315T(1 patient), P725R(1 patient), G89W(1 patient), A362V(1 patient), V12M(1 patient), P582L(1 patient), P583(1 patient), P493L (1 patient) and N95Efs*16(1 patient), and median overall survival (OS) for these patients was 12.0 months. Among them, all patients were FGFR2 gene with co-occurring mutations. Briefly, patients with (n=15) or without (n=4) co-occurring TP53 mutations had a median OS of 8.0 months and 28.0 months respectively (P=0.23); patients with (n=7) or without (n=12) co-occurring KEAP1 mutations had a median OS of 6.5 months and 12.0 months respectively (P=0.45); patients with (n=3) or without (n=16) co-occurring STK11 mutations had a median OS of 17.5 months and 12.0 months respectively (P=0.77); patients with (n=3) or without (n=16) co-occurring SMARCA4 mutations had a median OS of 20.0 months and 12.0 months respectively (P=0.67).
Conclusion
FGFR2 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to target therapy in patients with NSCLC.
-
+
P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P76.02 - Hepatoid Adenocarcinoma of the Lung With EGFR Mutation and the Response to Tyrosine Kinase Inhibitor (ID 689)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
Hepatoid adenocarcinoma (HAC) is a rare type of tumor that frequently originates from the stomach with pathologic features indistinguishable from hepatocellular carcinoma (HCC). In addition to stomach, HAC has been found in the lung, mediastinum, gallbladder, pancreas, etc. Hepatoid adenocarcinoma of the lung (HAL) is rare with an incidence of 2.3% of all HAC cases. The biological significance of HAL is not fully elucidated, and its clinical symptoms are generally atypical.
Methods
A 53-year-old male was referred to hospital with one-month history of cough, phlegm and fever. AFP levels were 3, 296 ng/ml. A chest-CT scan demonstrated a soft-tissue mass in the upper lobe of the right lung.
Results
A right upper lobectomy with dissection of multiple lymph nodes was successfully performed. Afterwards, pathological examination of the specimen revealed adenocarcinoma. Histologically, routine paraffin sectioning and immunohistochemistry were performed and suggested that positive for TTF-1, Hepatocyte, AFP and CK and negative for NapsinA, CK5/6, P63, CD56 and Syn. The Ki-67 score was observed to be 20%. The tumor had invaded the pleura with no lymphatic metastasis. Thus, the histological type was determined to be HAC. The patient received regular adjuvant therapy with pemetrexed and cisplatin for 4 cycles. The serum AFP level gradually decreased within the normal range. 9.0 months after surgery, a regular examination with CT and enhanced computed tomography (ECT) revealed pleural effusion and multiple bone metastasis. Of note, genomic testing detected EGFR p.L747_P753delinsS. Thus, patients were given oral icotinib therapy, and had a partial response (PR) to icotinib (125 mg tid). However, the long-term efficacy was not sustained. A second analysis of gene expression was performed and revealed an EGFR exon 20 T790M mutation. Subsequently, the patient received oral osimertinib treatment (80mg qd) and obtained a 8.0 months progression free survival (PFS). After drug resistance to osimertinib occurred, anlotinib was used and a stable disease was achieved. Thus far, the disease remained stable and the patient was still alive.
Conclusion
HAL is a rare type of tumor that morphologically resembles histological features of HCC. The heterogeneity of HAL complicates the diagnosis. In addition, the poor prognosis of HAL requires the molecular profiling for potential application of targeted therapy with TKI.
-
+
P88 - Targeted Therapy - Clinically Focused - ROS1 (ID 265)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P88.02 - SDC4-ROS1 Fusion as a Mechanism of Acquired Resistance in EGFR-Mutant Lung Adenocarcinoma (ID 687)
00:00 - 00:00 | Presenting Author(s): Chun-wei Xu
- Abstract
Introduction
The enhanced understanding of the biological mechanisms underlying non-small cell lung cancer (NSCLC) development and progression has led to targeted therapies becoming an increasingly important strategy for the treatment of NSCLC. Several clinical trials have demonstrated that most NSCLC patients with specific epidermal growth factor receptor (EGFR) mutations respond significantly to EGFR tyrosine kinase inhibitors (TKIs). However, the majority of patients who initially respond to EGFR-TKI therapies eventually develop drug resistance, often within a year. The subsequent development of T790M mutations occurs in roughly half of EGFR-mutant patients who develop EGFR-TKI resistance.
Methods
Herein we present a 37-year-old never-smoker Chinese female with an EGFR exon 19 deletion who was diagnosed with lung adenocarcinoma (LADC) and initially responded to first-generation EGFR-TKI treatment, later developing acquired resistance.
Results
The subsequent biopsy specimen was subjected to next generation sequencing (NGS) and a SDC4-ROS1 rearrangement was detected. The patient received crizotinib therapy and was considered to have a partial response. The progression free survival was 16.0 months.
Conclusion
To our knowledge, SDC4-ROS1 fusion gene as a novel mechanism of acquired EGFR resistance in lung adenocarcinoma is the first reported in China. In the future, the routine use of next generation sequencing is important, more and more ROS1 fusions are identified in lung cancer by next generation sequencing.
