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Wenhua Liang
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MA21 - Non EGFR/MET Targeted Therapies (ID 153)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Benjamin Besse, Michael Thomas
- Coordinates: 9/10/2019, 14:30 - 16:00, Vienna (2016)
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MA21.02 - Genomic Origin and EGFR-TKI Efficacy of Pulmonary Adenosquamous Carcinoma (Now Available) (ID 578)
14:30 - 16:00 | Author(s): Wenhua Liang
- Abstract
- Presentation
Background
Lung adenosquamous carcinoma (ASC) is a heterogeneous disease that comprises of both adenocarcinoma (AC) and squamous cell carcinoma (SCC) components. Their genomic profile, evolutionary origin, and clinical management remain controversial. Objective of this study is to define the genomic origin of this heterogeneous tumor by independent genomic analyses of the AC and SCC components.
Method
Surgical ASCs were collected. AC component and SCC component were obtained separately by microdissection, and Lymph node (LN) metastases were gathered. Targeted sequence was performed for the two components using a 1021-gene panel, independently. Evolutionary relationship of the two components was analyzed. The independent cohorts of adenocarcinoma (n=170) and squamous cell carcinomas (n=62) were used for comparison. EGFR and concomitant mutations with response to EGFR-TKI were analyzed. Retrospective 517 ASCs underwent EGFR detections were collected from 11 centers. Objective response rate (ORR), disease control rate (DCR) and progression free survival (PFS) were analyzed in EGFR-positive patients received EGFR-TKIs.
Result
28 ASCs were collected. NGS was performed on AC component and SCC component samples, respectively. The most frequent alterations in 28 ASCs were EGFR mutation (79%), TP53 mutation (68%), MAP3K1 mutation (14%), EGFR amplification (32%), and MDM2 amplification (18%). 27 patients had trunk variations in the both components suggesting the monoclonal origin of ASCs. The prevalence of trunk mutations was correlated to those of AC, indicating that ASC might originate from AC. Only one patient did not carry any trunk variations between AC and SCC components, which were clearly and geographically distinguishable under the microscope. 22 had AC component or/and SCC component specific variations suggesting the common event of branch evolution. The 23 LNs of 13 patients mainly contained AC and ASC components (AC, SCC, and ASC: 11, 1, and 11, respectively), and each of the LNs carried the trunk mutations of the primary ASC. Like pure AC, the alterations of L858R and Exon 19 Dels of EGFR were common in the 28 ASCs. Unfortunately, these patients have not been treated with TKIs. Further, of 517 retrospective ASCs from 11 centers, 51.8% were EGFR-positive. For the 129 EGFR-positive ASCs who had received TKIs, the ORR and DCR were 56.6% and 89.1%, respectively. The median PFS was 10.1 months (95% CI: 9.0-11.2).
Conclusion
The AC and SCC components share a monoclonal origin, and a majority have branching evolution. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR-TKIs.
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-39 - Intra-Tumoral CD61+ Megakaryocytes Predicts Poor Prognosis in Non-Small Cell Lung Cancer (ID 1663)
09:45 - 18:00 | Presenting Author(s): Wenhua Liang
- Abstract
Background
Lung is a reservoir for MKs to produce platelets. The aim is to investigate relationship between intra-tumoral MK with the recurrence of NSCLC.
Method
The tissue sections of 629 patients with resected NSCLC were stained with hematoxylin, anti-CD61, anti-CD34 and stromal cell-derived factor-1 (SDF-1). CD61+ giant cells localized in CD34+ capillaries were identified as MKs. The impact of MKs and DFS was investigated.
Result
Overall, 18.9% of patients were positive for the presence of MKs. In univariate analysis, the median DFS of the MK+ group was shorter than the median DFS of the MK- group (69.1 vs. 80.5 months; P=0.021). Multivariate analysis indicated that MKs in tumor tissue was an unfavorable prognostic factor for DFS (HR 1.351, P=0.065), the impact of which was more significant in non-squamous cell carcinoma (NSCC) (HR 1.710, P=0.008) and in patients with N0 (HR 1.883, P=0.009). Although systemic platelet count of the MK+ group was significantly higher than the MK- group (270.6 vs. 243.6 ×109/L, P=0.007), the stratified subgroup DFS curves (P=0.003) showed that the effect of MKs on prognosis was independent of the blood platelet count. In addition, the positive association of SDF-1, CD61 and microthrombi indicated a potential mechanism by which increased MKs facilitate blood metastasis.
Conclusion
CD61+ MKs in tumor tissue predict unfavorable prognosis in NSCLC. The prognostic impact of MKs in addition to that of systemic platelet count implies that regional MK-producing platelets in tumors might contribute to NSCLC metastasis.
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P1.11 - Screening and Early Detection (ID 177)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.11-23 - The Impact of the Family History of Different Cancers on Lung Cancer (ID 2542)
09:45 - 18:00 | Author(s): Wenhua Liang
- Abstract
Background
The definition of the high-risk population of lung cancer screening remains controversial. People with a family history of lung cancer will have a distinctly increase risk of lung cancer, but the influence of family history of other cancers it is still unclear.
Method
We performed a case-control study to compare the exposure of different cancer family history between lung cancer and other cancers. All cancer patients who were hospitalized in our center between 2007 and 2018 were included and records of each patient’s family history were retrieved. Logistic regression analysis was conducted after excluding the patients with a family history of non-lung cancer who had diagnosed the corresponding system cancer.
Result
This study enrolled 23,977 cancer patients including 15,120 lung cancer and 8,857 non-lung cancer. Lung cancer patients had a higher exposure to a family history of lung cancer compared with non-lung cancer patients（OR=2.418, P< 0.001）, and had a potential higher exposure to the patients with the family history of pancreatic cancer（OR=1.769，P=0.597）and kidney cancer（OR=1.326，P=0.596）without statistical difference. Sex had no significantly impact on the association between cancer family history and lung cancer risk (interaction P >0.05).
Conclusion
Patients with a family history of lung cancer should be considered a high-risk population for lung cancer screening, whereas there is no strong evidence to support that family history of other cancer will influence the risk of lung cancer. More researches are required to determine the relationship between lung cancer risk and family history of pancreatic and kidney cancers.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-26 - Epithelial Growth Factor Receptor Mutation Pattern in Non-Small Cell Lung Cancer of Xuanwei Region in Southwestern China (Now Available) (ID 131)
09:45 - 18:00 | Author(s): Wenhua Liang
- Abstract
Background
The incidence and mortality rate of lung cancer in Xuanwei region are among the highest in China. A previous study reported that non-smoking female lung cancer patients in Xuanwei exhibit different EGFR mutation patterns compared with the patterns seen elsewhere in Asia. A unique environment, ethnic group and certain susceptible population may have certain genetic background. Investigating EGFR mutation distribution of NSCLC patients in Yunnan province especially in Xuanwei region is meaningful.
Method
A meta-analysis was conducted to identify the distinctive pattern of EGFR mutations in NSCLC patients in Xuanwei. Electronic databases were comprehensively searched and relevant literature with data were retrieved. The odds ratios (OR) for each EGFR mutation between Xuanwei and other regions were calculated, and the absolute incidence of EGFR mutations in Xuanwei was pooled. Subgroup analyses were performed for different EGFR mutation subtypes.
Result
Five relevant studies with a total of 1,058 NSCLC patients from Yunnan province in southwestern China were conducted. 337 were from Xuanwei and 721 were from other regions; The overall EGFR mutation rate across studies ranged from 34.90% to 55.56%（Table 1）. The results revealed a higher incidence of uncommon EGFR mutations (p<0.001), but a lower incidence of common EGFR mutations (p<0.001) in Xuanwei region compared with other regions. The pooled incidence of uncommon and common EGFR mutations in Xuanwei were 62.7% and 37.3%, respectively (Table 2). More specifically, compared with other areas, patients from Xuanwei harbored a higher frequency of exon 20 S768I (P<0.001) and exon 18 G719X + 20 S768I mutations (P<0.05), but had a lower frequency of 19 deletion (p<0.001)(Table 3).
Conclusion
To summarize, Xuanwei patients carrying EGFR mutations exhibit distinct EGFR mutation spectrum compared with other regions, with higher uncommon mutations but lower common mutations. The Xuanwei pattern provides an important model to study the etiology or risk factor for EGFR uncommon mutations.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-50 - Stromal BTK Expression Predicts Poor Prognosis in NSCLC Patients (ID 1665)
10:15 - 18:15 | Presenting Author(s): Wenhua Liang
- Abstract
Background
Bruton's tyrosine kinase (BTK) is a kinase that plays a crucial role in B-cell development and widely involves cancer biology. We sought to explore the relationship between BTK expression and NSCLC.
Method
We firstly used a cohort of 1,249 consecutive NSCLC patients who underwent surgical resection in our center between Apr 2018 and Sep 2018 with fresh tissue to examine the presence of BTK (cohort 1). Another cohort of 681 patients with resected NSCLC between 2009-2014 with stored paraffin sections and survival information were also retrieved to assess the prognostic value of BTK (cohort 2). All samples were stained by IHC for BTK (EPR20445) and PD-L1 (SP142).
Result
The overall expression rates of BTK expression on tumor and stromal cells were 11.9% and 87.1% respectively in cohort 1, which did not differ across histological types or other clinical features. Both tumoral expression (Chi2=8.84, P<0.01) and stromal expression (Chi2=3.96, P=0.047) of BTK were positively correlated with tumoral PDL1 expression. In cohort 2, we found that the stromal (HR=1.49, P=0.03) but not tumoral (HR=0.74, P=0.20) BTK expression was significantly correlated with poorer prognosis, after adjusting for tumoral PDL1 expression (HR=0.58, P<0.01) and other covariates.
Conclusion
This is the first study showing the presence of BTK expression and its positive correlation with PDL1 expression in NSCLC. Stromal BTK expression predicts poor prognosis in NSCLC patients. This study shed light on the biological effect of BTK-expressing cells and treatment potential of targeting relevant pathways.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-01 - Characteristics of Driver Mutations in Early Lung Adenocarcinoma: From Preinvasive/Minimally invasive to Invasive Adenocarcinoma (Now Available) (ID 1743)
10:15 - 18:15 | Author(s): Wenhua Liang
- Abstract
Background
It is still unclear when the gene mutation occurs during the carcinogenetic process, which progresses from preinvasive to invasive adenocarcinoma. We aim to investigate the driver gene alterations profile of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC).
Method
A total of 1219 patients with pulmonary nodes smaller than 3 cm were selected for this study. Driver mutation testing was performed with NGS in all resected tumor tissues. The incidence of mutations was calculated and compared among different subtypes. Logistic regression was used to further identify factors that may independently correlate with IAC.
Result
In all 1219 patients with lung adenocarcinoma, 62 were diagnosed as AIS, 208 as MIA and 949 as IAC. Mutations were found in 809 (66.4%) patients. The frequency of mutations increased with the progression of tumor invasiveness: AIS (32.3%), MIA (45.2%) and IAC (73.2%)(P<0.001 between IAC and AIS, P<0.001 between IAC and MIA). The results (Figure 1) also showed an increasing trend towards more driver mutations from AIS to MIA, and to IAC. Multivariate analysis revealed that driver mutations was a factor associated with IAC (OR: 2.39, P<0.001). Of the genetic factors, EGFR, KRAS and ALK alterations were significant indicators of IAC (all P<0.020), and were found increased in IAC compared with AIS/MIA.
Conclusion
Genetic alterations occurs early in the development of lung adenocarcinoma and can be detected even before tumor have acquired malignant potential. Driver mutations gradually increase in tumorigenesis and progression from AIS to MIA, and finally to overt IAC. A better understanding of carcinogenesis in preinvasive/minimally invasive cases may allow the development of effective preventive, screening, and treatment strategies.
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P2.09-04 - The Clinicopathological Characteristics and Prognosis of Lung Cancer with Tumor Spread Through Air Spaces: A Meta-Analysis (Now Available) (ID 1652)
10:15 - 18:15 | Author(s): Wenhua Liang
- Abstract
Background
Background: The clinicopathological characteristics of lung cancer with tumor spread through air spaces (STAS) has not been clearly characterized yet. Also, it is still not clear whether the presence of STAS correlated with worse prognosis in patients with lung cancer. Thus, we aim to systematically evaluate the clinicopathological characteristics and prognosis of the patients with or without STAS undergoing surgical resection for lung cancer.
Method
Materials and Methods: A comprehensive search of online databases was performed. Clinicopathological characteristics, 5-year RFS and OS rate were compared between 2 groups. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups according to different types of lung cancer are examined.
Result
Results: A total of 25 eligible studies including 8494 patients were recruited. STAS occurred in 2881 patients (34%) while non-STAS occurred in 5613 patients (66%). Overall, patients with STAS manifested significantly more aggressive characteristics, including lymphatic invasion (SMD=2.935; P=0.000), pleural invasion (SMD=2.329; P=0.000), vascular invasion (SMD=2.306; P=0.000) as well as lymph node metastasis (OR=3.510; P=0.000). Patients with STAS also correlated with significantly higher pathological stage (OR=2.216; P=0.003), T stage (OR=1.756; P=0.000), N stage (OR=2.395; P=0.000) and larger tumor size (OR=0.275; P=0.001). Meanwhile, the incidence of STAS was significantly associated with the micropapillary (OR=9.792; P=0.000) and solid patterns (OR=2.451; P=0.000). Moreover, the presence of STAS was related to male sex (OR=1.493; P=0.000), smoking history (OR=1.637; P=0.000) and necrosis (OR=2.300; P=0.000). As for the outcomes of the prognosis, patients with STAS linked with significant worse prognosis than those without STAS, including both 5-year RFS (HR=0.585; 95% CI: 0.486–0.684; P=0.000) and 5-year OS rate (HR=0.788; 95% CI: 0.596–0.980; P=0.000).
Conclusion
Conclusions: The presence of STAS was associated with several invasive pathological characteristics, which might explain the worse prognosis in patients with STAS compared with those without STAS.
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-29 - Diagnosis and Surveillance of Solitary Pulmonary Nodules with ctDNA Methylation Sequencing: Protocol for a Prospective Multicenter Study (ID 1666)
10:15 - 18:15 | Presenting Author(s): Wenhua Liang
- Abstract
Background
LDCT screening can identify early-stage lung cancers yet introduces excessive false positives , which calls for better non-invasive diagnostic tools. We previously established a diagnostic model of early stage lung cancer based on high-throughput DNA methylation sequencing of ctDNA (Theranostics 2019; 9(7)). The aim of the present study is to assess the role of ctDNA methylation markers in differential diagnosis and surveillance of pulmonary nodules.
Method
A prospective cohort of 10,560 patients from 20 centers in China with non-calcified nodules range from 0.5 to 3 cm in diameter indicated by LDCT or CT will be included and followed up for 2 to 3 years. Each patient will undergo LDCT/CT follow-up and their information as well as blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. Blood samples will be subjected to ctDNA methylation test. Sensitivity, specificity, positive predictive value and negative predictive value are used to measure the diagnostic value of ctDNA methylation test in differentiating benign and malignant pulmonary nodules.
Result
This study is registered in clinicaltrials.gov (NCT03651986, BELL study) and has launched since Oct 2018. Upon submission, 975 cases had been enrolled from 13 centers who had begun recruiment. Completion of data collection is anticipated by March 2023.
Conclusion
To the best of our knowledge, this is the first and largest study worldwide to test the efficacy of ctDNA methylation markers in differential diagnosis and surveillance of pulmonary nodules.
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P2.17 - Treatment of Early Stage/Localized Disease (ID 189)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.17-36 - Molecular Markers, Therapeutic and Prognostic Analysis of Lung Sarcomatoid Carcinomas (ID 2973)
10:15 - 18:15 | Presenting Author(s): Wenhua Liang
- Abstract
Background
Several molecular markers have been established for therapeutic intervention and prognostic prediction of lung cancer. Less is known about their therapeutic potential and prognostic significance in less common lung cancer subtypes. The present study was therefore designed to assess a set of well-defined molecular markers in patients with lung sarcomatoid carcinomas and their therapeutic and prognostic significance.
Method
This is a single-center retrospective study of lung cancer patients with histologic types of the sarcomatoid carcinomas who underwent surgical resection at our center during August 2008 to August 2018. The molecular markers analyzed were driver mutations in EGFR, ERBB2, PIK3CA, C-MET, RAS, BRAF, EML4-ALK, RET and ROS1 by ARMS-PCR or NGS, protein expressions of PD-L1 (clone SP-142) in tumors and/or associated lymphocytes by immunohistochemistry. Log-rank test was used to compare the overall survival of patients.
Result
A total of 74 (1.18%) patients with sarcomatoid carcinomas were identified from 6,285 patients underwent surgical resection. Of the 35 patients underwent mutation testing (including 14 test EGFR and RAS by ARMS), 17 (48.57%) harbored driver mutations (12 RAS, 4 EGFR L859R and 4 EGFR 19del). Proteins expressions of PD-L1 were found in 67.86% of patients. No prognostic significance (DFS and OS) was noted regarding to any driver mutations and PD-L1 expression. Half of the patients (37/74, 50.00%) received adjuvant therapy, 27 of whom used platinum-based chemotherapy (72.97%). Platinum-based adjuvant chemotherapy showed improved DFS (P=0.011) but similar OS (P=0.079).
Conclusion
A part of lung sarcomatoid carcinomas harbor driver mutation or PD-L1 expression, although they are not prognostic. Platinum-based chemotherapy was preferable in these patients. The role of targeted or immune agents as adjuvant therapy needs further study.
