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Zhengfei Zhu
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-54 - Implementation of Fine Needle Aspiration of Supraclavicular Lymph Node as a Novel Medium for Genomic Profiling in NSCLC (Now Available) (ID 1171)
08:00 - 18:00 | Presenting Author(s): Zhengfei Zhu
- Abstract
Background
Supraclavicular lymph node (SLN) metastasis is not rare in non-small cell lung cancer (NSCLC). Palpation or B-ultrasound guided fine needle aspiration (FNA) of SLN is a very simple, rapid, and minimally invasive tool for diagnosis of these patients. With the development next generation sequencing (NGS) which has been widely used to catalogue genetic mutations in cancer, uncertainty remains if FNA of lymph node could be combined with NGS and applied in clinical practice. The aim of this study was to evaluate the clinical utility of FNA of SLN in patients with NSCLC
Method
FNA of SLN samples (stored in 10% neutral buffered formalin) and matched plasma samples from 30 patients with NSCLC were collected. Twenty-three patients (both FNA and plasma samples) were sequenced using a panel covering whole exons and critical introns of 520 cancer-related genes and seven patients (both FNA and plasma samples) were profiled using a panel of 168 lung cancer-related genes.
Result
During the procedure of next-generation sequencing library construction, the amount of extracted DNA and qualification percentage of FNA samples (n=30) from lymph nodes were similar to those of punctured lung biopsy samples (n=100, randomly selected from burning Rock database). Comparative analysis of mutation spectrums revealed that mutations were positively identified in 93.3% (28/30) FNA samples and 90.0% (27/30) plasma samples, while mutations of eight well-established lung cancer-related genes (EGFR, ERBB2, MET, BRAF, KRAS, ROS1, ALK and RET) were detected in 83.3% (25/30) FNA samples, which was higher than that in plasma samples (63.3%, 19/30). Moreover, FNA was significantly superior to plasma in detecting copy number variation (CNV) (detection frequencies, 88.9% vs 0.9%, p<0.001), both for CNVs of all genes in NGS panel (99.5% vs 10.0%) and eight well-established genes (96.0% vs 20.0%).
Conclusion
Samples from FNA of SLNs were found to be equivalent to plasma during NGS library construction. Moreover, FNA of SLNs was superior to plasma in detecting mutations of eight lung cancer-related genes, as well as CNVs in both all genes of NGS panel and the 8 key genes. This study provides knowledge for the potential use of FNA of lymph nodes in sequencing genomic profiles of patients with lung cancer, and further support its utility in clinical practice.
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EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.18-02 - Pattern of Postoperative Recurrence and Clinical Value of Adjuvant Radiotherapy in Completely Resected Stage III/N2 EGFR-Mutant NSCLC (Now Available) (ID 1006)
08:00 - 18:00 | Author(s): Zhengfei Zhu
- Abstract
Background
The pattern of postoperative recurrence among patients with stage III/N2 EGFR-mutant non-small cell lung cancer (NSCLC) is seldom reported. Moreover, the clinical value and optimal candidate of postoperative radiotherapy (PORT) for stage III/N2 NSCLC is still controversial.
Method
Consecutive patients who underwent curative resection and were pathologically confirmed EGFR-positive stage III/N2 NSCLC at Fudan University Shanghai Cancer Center from January 2007 to December 2017, were retrospectively enrolled. Serial imaging scans of each patient were intensively examined and the initial recurrence sites were categorized into five groups: thoracic recurrence, brain recurrence, neck recurrence, abdominal recurrence, and bone recurrence. Recurrence-free survival (RFS) were estimated by Kaplan-Meier curves. The Cox proportional hazards model was applied to estimate the association between RFS and clinic-pathological parameters (including age, sex, tumor size, TNM stage, tumor differentiation, tumor histology, lymphovascular invasion, visceral pleural invasion, and EGFR mutation subtypes), as well as a panel of routinely used immunohistochemical markers (including Her2, Ki67, TTF-1, CK20, CK7, CK5/6, p53, RRM1, NapsinA, p40, syn, Bcl-2, CDX2, ERCC1 and p63).
Result
Ninety-one patients were identified, all of whom received adjuvant chemotherapy and 28 of whom received PORT. After a median follow up of 28 (range, 6-103) months, disease recurrence occurred in 62 patients. Thirty-six (58.1%) patients had thoracic recurrence, 15 (24.2%) had bone recurrence, 14 (22.6%) had brain recurrence, 9 (14.5%) had neck recurrence, and 8 (12.9%) had abdominal recurrence. Nineteen patients had multiple sites of initial recurrence. In terms of thoracic recurrence, initial relapse at the resection margin occurred in 1 patients and relapse in the mediastinal or ipsilateral hilar lymph nodes was observed in 11 patients. Ki67≥45% and positive expression of ERCC1 were identified as independent predictors of postoperative recurrence in multivariate analysis. Of note, PORT was not significantly associated with RFS in the whole population (p=0.877). However, among the 62 patients who had at least one of the independent predictors of postoperative recurrence (ie: Ki67≥45%, expression of ERCC1), PORT (n=22) significantly prolonged RFS (p=0.043).
Conclusion
The majority of patients with stage III/N2 EGFR-mutant NSCLC developed their initial recurrence in the thorax. Patients with Ki67≥45% and/or positive expression of ERCC1 have a significant higher risk of postoperative recurrence, who may be the potential candidate for PORT.
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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): Zhengfei Zhu
- 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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OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Tomasz Grodzki, Kenji Suzuki
- Coordinates: 9/10/2019, 11:30 - 13:00, Toronto (1985)
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OA13.03 - Predicting Postoperative Recurrence in Completely Resected EGFR-Mutant Non-Small Cell Lung Cancer: Value of IHC Markers (Now Available) (ID 998)
11:30 - 13:00 | Presenting Author(s): Zhengfei Zhu
- Abstract
- Presentation
Background
EGFR mutations are detected in up to 50% of non-small cell lung cancer (NSCLC) and recent studies indicate that EGFR-mutant NSCLC is a heterogeneous disease with varying co-mutations, diverse histologic subtypes and distinct expression of oncoproteins. However, the risk factors and clinical patterns of postoperative recurrence among patients with completely resected EGFR-mutant NSCLC have not been fully understood. Moreover, the prognostic values of routinely used immunohistochemical (IHC) markers in NSCLC are seldom reported.
Method
Consecutive patients with curative resected NSCLC and confirmed EGFR mutations at Fudan University Shanghai Cancer Center from January 2007 to December 2017, were retrospectively enrolled. The initial recurrence sites were recorded and categorized into five groups: thoracic recurrence, brain recurrence, neck recurrence, abdominal recurrence, and bone recurrence. The indicators of overall and site-specific recurrence were identified using the Cox regression model, where a panel of routinely used IHC markers (including Her2, Ki67, TTF-1, CK20, CK7, CK5/6, p53, RRM1, NapsinA, p40, syn, Bcl-2, CDX2, ERCC1 and p63) were incorporated. A nomogram was developed based on variables selected in multivariate analysis. The bootstrapping method (1000 repetitions) was applied to internally validate the nomogram
Result
After a median follow-up of 32 (range, 5-122) months, disease recurrence was observed in 197(37.1%) out of the 531 patients, with a median recurrence-free survival (RFS) of 19 (95% CI, 16.63-21.37) months. Most patients (n=136; 69.0%) had thoracic recurrence, followed by brain recurrence (n=41; 20.8%), bone recurrence (n=41; 20.8%), abdominal recurrence (n=14; 7.1%), and neck recurrence (n=13; 6.6%). Sex, tumor size, Ki67, and N stage were independent indicators of thoracic recurrence. Tumor size, N stage, CK20, and Syn were independent indicators of brain recurrence. N stage and Ki67 were independent indicators of bone recurrence. N stage was the independent indicator of abdominal recurrence and neck recurrence. Tumor size, Ki67, CK20, and N stage were independently associated with overall recurrence, and thus a nomogram predicting the 1-, 2-, and 3-year RFS probability was developed based on these four factors. The concordance index (C-index) was 0.723 (95% confidence interval, 0.675 to 0.771) and the calibration curves displayed good agreement between the predicted RFS and the actual observation.
Conclusion
Independent prognostic indicators based on clinic-pathological parameters and routinely used IHC markers were identified to predict overall and site-specific recurrence, which may help to identify optimal candidates for adjuvant therapies and design individualized surveillance strategies among patients with completely resected EGFR-positive NSCLC
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P1.12 - Small Cell Lung Cancer/NET (ID 179)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.12-19 - Identification and Potential Application of Human Blood Exosomal RNA in Small Cell Lung Cancer (Now Available) (ID 423)
09:45 - 18:00 | Author(s): Zhengfei Zhu
- Abstract
Background
Plasma exosomes, which are nanosized endocytic vesicles that have been implicated as non-invasive diagnostic, prognostic sources, contain an abundant cargo of different RNA species that may be used as biomarkers for human cancers. Little research has been done on small cell lung cancer (SCLC) blood exosomal RNA. The aim of this study is to explore SCLC exosomal specific transcriptional profiles and to further predict efficacy of first-line chemotherapy.
Method
Pre-chemotherapy and paired post-chemotherapy plasma samples (8ml whole blood) from patients with limited or extensive disease SCLC and healthy volunteers were prospectively collected. We used exoRNeasy Serum/Plasma Kit (Qiagen, Hilden, Germany) to purify exosomes and isolate total exosomal RNAs. Exosomal RNA profiling was performed using RNA-seq. RNA-seq libraries were generated using SMART technology (Clontech). We conducted pre-experimental analysis of 8 samples from healthy volunteers and 8 samples of 4 SCLC patients before and after chemotherapy.
Result
The heat map showed that the exosomal mRNA expression profile of SCLC was significantly up-regulated compared to healthy volunteers and that the mRNA profiles before and after chemotherapy were also significantly different. Compared with healthy volunteers, SCLC had a significant up-regulation of 499 genes including the most differential gene ZNF805 (p=2.82E-05), COPS8 (p=3.20E-05), LRRC47 (p=3.54E-05), FANCE (p=1.02E-04), PGM3 (p=1.47E-04). Before and after chemotherapy, up-regulated genes with the greatest difference included KCNN4, HBB, TRAK2, TMUB2, ELF3; down-regulated genes with the greatest difference included ZBTB7C, LHFP, WNT11, VPS33B, STON1.
Conclusion
This preliminary analysis firstly identified blood exosomal RNA profiles in SCLC and highlighted the potential application of exosomal RNA based non-invasive liquid biopsy in SCLC.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-15 - Risk, Pattern and Outcome of Brain Metastases in Completely Resected Stage I (AJCC 8th Edition) Non-Squamous Non-Small Cell Lung Cancer (Now Available) (ID 1007)
09:45 - 18:00 | Author(s): Zhengfei Zhu
- Abstract
Background
Brain as the first site of recurrence after complete resection in stage I non-squamous non-small cell lung cancer (NSCLC) is occasionally encountered. However, the risk factors and clinical outcomes of this uncommon situation are not fully understood.
Method
The records of patients who underwent curative surgery at Fudan University Shanghai Cancer Center were reviewed and two cohorts with stage I non-squamous NSCLC were identified. The training cohort consisted of randomly selected patients from January 2013 to December 2017. The validation cohort included consecutive patients from January 2011 to December 2012. Brain metastasis free survival (BMFS) were calculated from the time of surgery to the documentation of brain metastasis (BM). Overall survival (OS) was measured from the documentation of BM to the time of any cause of death. A nomogram was developed based on variables selected in multivariate analysis.
Result
With a median follow-up of 28 (range, 10-69) months, 16 of the 596 patients in the training cohort had its initial relapse in the brain. The 1-year, 2-year, and 3-year cumulative incidence of BM were 0.7%, 1.9% and 4.2%, respectively. Tumor size≥2cm (HR=5.09, p=0.024), visceral pleural invasion (HR=2.79, p=0.007), expression of Syn (HR=4.24, p=0.007) and expression of CK20 (HR=14.01, p<0.001) were independent risk factors of BM. Afterwards, a nomogram predicting BMFS was developed based on these four factors. Of note, EGFR mutation was not associated with BMFS. Additionally, with a median follow-up of 75 (range, 7-98) months, 18 of the 478 patients in the validation cohort had its initial recurrence in the brain. The nomogram was validated with a concordance index of 0.93 (95%CI, 0.88-0.98) and the calibration curves displayed good agreement between the predicted BMFS and the actual observation. Among the 34 patients with BM, 10 also had extracranial recurrence, 7 were symptomatic and 24 had oligo-metastases in the brain. By the time of data cut-off, 14 patients died with a 5-year OS rate of 24.8%. Positive expression of Syn or CK20 was significantly associated with reduced OS, while upfront local therapy (surgery and/or radiotherapy) after detection of BM tended to prolong OS (p=0.068).
Conclusion
Positive expression of Syn and CK20, but not EGFR mutation, were independent risk factors of BM and reduced survival in curative resected stage I non-squamous NSCLC. The majority of patients developing BM were asymptomatic and initially having oligo-metastases, highlighting the importance of regular brain imaging for patients with high risks.
