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Jie Hu
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JCSE 01 - Joint IASLC/CSCO/CAALC Session: Immunotherapy for Management of Lung Cancer: Ongoing Research from East and West (ID 630)
- Event: WCLC 2017
- Type: Joint Session IASLC/CSCO/CAALC
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:C. Bai, Fred R. Hirsch, Tony SK Mok, Yi-Long Wu
- Coordinates: 10/15/2017, 07:30 - 11:30, F203 (Annex Hall)
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JCSE 01.06 - ctDNA Based Tumor Mutation Burden Evaluation for Predicting Immunotherapy Effect (ID 8225)
07:30 - 11:30 | Presenting Author(s): Jie Hu
- Abstract
- Presentation
Abstract not provided
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MA 20 - Recent Advances in Pulmonology/Endoscopy (ID 685)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:C. Lee, S. Sasada
- Coordinates: 10/18/2017, 14:30 - 16:15, F205 + F206 (Annex Hall)
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MA 20.13 - etDNA: Tumor-Derived DNA from Pleural Effusion Supernatant as a Promising Source for NGS-Based Mutation Profiling in Lung Cancer (ID 10091)
14:30 - 16:15 | Author(s): Jie Hu
- Abstract
- Presentation
Background:
Mutation profiling of circulating tumor DNA (ctDNA) and pleural effusion sediment containing tumor cells (ETCs) were commonly applied in clinical practice. Several studies suggested that tumor-derived DNA from pleural effusion supernatant (etDNA) might be a better candidate for detecting gene alterations in lung cancer. However, little is known regarding the abundance and diversity of tumor DNA acquired among different types of liquid biopsy.
Method:
We performed targeted next generation sequencing (NGS)-based genetic profiling on tumor tissue, pleural effusion (etDNA & ETCs) and contemporaneous ctDNA from 63 lung cancer patients (58 adenocarcinoma, 2 adenosquamous carcinoma, 2 SCLC, 1 neuroendocrine carcinoma), among which 28 patients had paired tumor tissue samples. Genomic DNA from whole blood of each patient was used for germline control. Driver mutation and rearrangement profiling was validated using ARMS-PCR, FISH, or Ventana IHC assay in tumor tissue as golden standard.
Result:
We identified tumor-specific mutations in 98%, 89%, 86%, and 100% of patients in their etDNAs, ETCs, ctDNAs and tumor tissues, respectively (p<0.01). etDNAs showed a significantly higher tumor-specific mutation number per patient (Median: 5) compared to ETCs and plasma ctDNAs (Median of 3 for both), while the median number in tumor tissues is 4 per patient. The detection sensitivity for EGFR mutations in etDNAs is 95%, higher than that in ETCs and ctDNAs (89% and 63%, respectively). Two patients detected ALK fusion in tumor tissue were also positive in etDNA, only one patient was positive in ETCs and ctDNA, respectively. A total of 298 genetic alterations, including point mutations, indels, copy number variations (CNVs) and gene fusions, were identified in etDNAs from all the patients. However, only 74% and 57% of these alterations were detected in contemporaneous ETCs and ctDNA samples, with CNVs having the lowest detection sensitivity as 49% and 11%, especially in lung cancer patients without extrathoracic metastasis, as none of the CNVs detected in etDNAs were captured in plasma ctDNAs of these patients. Furthermore, driver mutations and rearrangements in etDNA showed a strong correlation to targeted therapy efficacy.
Conclusion:
This study demonstrated that etDNA had significantly higher tumor-specific mutation detection rate and sensitivity compared to ETCs and ctDNA. etDNA from supernatant of pleural effusion is a promising source for genetic testing to guide treatment-decision making in lung cancer. This study is funded by Shanghai Science and Technology Program (15ZR1406400).
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-037 - Circulating Tumor DNA Clearance During Treatment Associates with Improved Progression-Free Survival (ID 9653)
09:30 - 16:00 | Author(s): Jie Hu
- Abstract
Background:
Therapeutic selection has been shown to lead to marked clonal evolution, thus revealing limitations in imaging scan as a monitoring method, which does not reflect biological processes at a molecular level. However, currently, response assessment of patients with non-small cell lung cancer (NSCLC) primarily relies on imaging scans, necessitating the development of methodologies for dynamic monitoring of treatment response. We evaluated ctDNA as a tumor clonal response biomarker.
Method:
We screened 831 advanced NSCLC patients with a mixture of prior treatment exposure by performing capture-based ultra-deep targeted sequencing on plasma samples using a panel consisting of 168 NSCLC-related genes. Eighty-six patients with driver mutations and a minimum of 2 evaluation points in addition to baseline were included for further analysis.
Result:
At baseline, 79.9% patients harbored at least one mutation from this panel; the remaining 20.1% had no mutation detected. Sixty-nine percent of patients (570/831) harbored driver mutation. Patients harboring 2 mutations or fewer at baseline had a median progression-free survival (PFS) of 7.4 months; in contrast, patients harboring more than 2 mutations had a median PFS of 3.8 months (P=6.6x10[-5 ]HR=0.34), suggesting a significant inverse correlation between number of mutations at baseline and PFS. Next, we evaluated the ability of ctDNA as a tumor clonal response biomarker in 86 patients with a minimum of 2 follow-ups. After a median follow-up of 314 days, 64 patients (74.4%) reached disease progression. During treatment, 46 patients, treated with either matched targeted therapy (MTT) or chemotherapy, had a minimum of one time of ctDNA clearance, occurring from 1.6 months to 7.5 months after the commencement of treatment, with a median PFS of 8.07 months, an overall response rate (ORR) of 41% and a disease control rate (DCR) of 93%. Median overall survival (OS) for this group has not reached. In contrast, 40 patients who had consistent detectable ctDNA throughout the course of treatment had a median PFS of 3.47months, a median OS of 425 days, an ORR of 20% and a DCR of 53%. Our data revealed that patients with a minimum of one time ctDNA clearance are associated with a better ORR (p=0.05), DCR (p=5.9x10[-5]), a longer PFS (p=5.4x10[-10 ]HR=0.21) and OS (p=2.3x10[-5 ]HR=0.21), regardless the type of treatment commenced and the time of evaluation.
Conclusion:
This real world study comprising a heterogeneous population reveals the predictive and prognostic value of ctDNA and warrants further investigations to explore its clearance as a surrogate endpoint of efficacy.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-004 - The Underestimated Role of Bronchial Washing Fluid in the Detection of EGFR Mutation from Lung Cancer Patients (ID 7547)
09:30 - 16:00 | Presenting Author(s): Jie Hu
- Abstract
Background:
The aim of the current study was to examine the clinical application of BWF samples in detecting epidermal growth factor receptor (EGFR) mutations in a large sample set of NSCLC patients.
Method:
In diagnostic bronchoscopic examinations, before or after biopsy to target lesions, subsequent bronchial washing by saline was performed. Thereafter, EGFR mutation testing for both supernatant and sediment of BWF and histologic tissues was performed via amplification refractory mutation system real-time PCR (ARMS RT-PCR) assay.
Result:
A total of 127 cases of histologic and corresponding BWF samples of patients underwent bronchoscopy for suspected lung malignant tumor lesions on chest radiography were successfully obtained. Of these, 72 cases were pathologically confirmed to be NSCLC based on forceps biopsy samples and EGFR mutations were identified in 26 cases. In 70 of 72 cases, the results of EGFR mutation status were concordant for BWF and histologic samples, and the concordance rate was 97%. In 13 cases that were not pathologically diagnosed with NSCLC with forceps biopsy samples but other samples, five cases (38.46%) with EGFR mutated-type were detected by BWF. The overall EGFR mutation concordance rate between supernatant and sediment specimens was 100%. The detection of EGFR mutations with supernatant/sediment of BWF samples showed a sensitivity of 86.5%, a specificity of 100%.
Conclusion:
This study demonstrates a clear comparison of supernatant/sediment of BWF samples and histologic tissues for EGFR mutation testing with largest clinical samples to date. Both supernatant and sediment of BWF samples showed high credibility and concordance via highly sensitive PCR analysis. BWF is considered a simple, rapid and effective alternative for histologic samples in EGFR mutation testing.
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P3.01-052 - The Prevalence and Genotype Distribution of Dual in Cis EGFR Mutations in Chinese Advanced Non-Small Cell Lung Cancer Patients (ID 9721)
09:30 - 16:00 | Author(s): Jie Hu
- Abstract
Background:
The prevalence of EGFR mutation has been well elucidated in different ethnicities. Recently, increasing attention has been given to dual EGFR mutations. However, less attention has been invested in dual in cis EGFR mutations. Until now, none of retrospective or prospective research has focused on dual in cis EGFR mutations except case reports.
Method:
In this real world study, we performed capture-based ultra-deep targeted sequencing on circulating tumor DNA to identify and investigate the prevalence and genotype distribution of dual in cis EGFR mutations in 3,000 Chinese advanced NSCLC patients. This cohort consisted of both treatment-naïve and previously treated patients. Ten milliliter of peripheral blood was collected from every patient and a minimum of 50ng of ctDNA was needed for library construction. The panel covered critical exons and introns of 168 genes (160kb of human genomic regions).
Result:
1,266 patients harbored EGFR mutant in this cohort; among them, 501 patients harbored 19 deletions, 489 harbored L858R, and the remaining harbored other EGFR mutations. We identified 1.5% patients (19/1,266) harboring dual in cis EGFR mutations. Among them 37% (7/19）carried two rare EGFR mutations and the remaining 63% (12/19) carried EGFR L858R in combination with a rare mutation. No patient carried EGFR 19 del in combination with other rare mutations was identified in this cohort, suggesting EGFR 19del is a stronger oncogenic driver than EGFR L858R (p=0.000197, Fisher’s exact test). For patients carried two rare mutations, both mutations were either located on exon 18 or exon 21. The allelic fractions (AF) of both mutations were similar. The AF of either EGFR mutations was the maximum AF in all patients, demonstrating the clones harboring EGFR mutations were major clones. Interestingly, 1 patient carried additional KRAS mutation and 2 patients had EGFR amplification.
Conclusion:
In cis dual EGFR mutation was rare (1.5%) in EGFR mutant Chinese advanced NSCLC patients. EGFR L858R was significantly more likely to couple with a rare in cis dual mutation than 19 del. EGFR 19del might be a stronger oncogenic driver than EGFR L858R.
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P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.04-001 - Evaluate the Utility of the ProLung China Test in the Diagnosis of Lung Cancer (ID 9541)
09:30 - 16:00 | Author(s): Jie Hu
- Abstract
Background:
This Study will assess the stability of the ProLung China Test classification algorithm when used as an adjunct to CT scan. Also, we will assess whether there are any potential safety concerns of the ProLung China Test when used to evaluate patients with a positive CT scan for lung cancer.
Method:
This study is a multicentre, prospective, open, self-control study which aims to evaluate the utility of the ProLung China Test in diagnosis of lung cancer (ClinicalTrials.gov ID: NCT02726633 ). The subject whose age is between 18 and 80 years old and CT result shows a 4 ~ 50 mm nodule within 30 days is our object. In these objects, we will exclude those people who has TB, pulmonary edema, chronic lung infection, abnormal anatomy, skin disease effecting bioconductance and other tumors.The expected sensitivity and specificity of Prolung China Test are 70 % and 61%, and non-inferiority margin is 10 %. Based on these statistical information, four clinical trial centers, in the study, will enroll at least 452 samples with 20 % dropout rate. These samples must contain at least 182 effective malignant sample and 194 benign samples.
Result:
According to the inclusion and exclusion criteria, excision biopsy or follow-up examination will perform on enrolled subjects. Before these examination, a Prolung China test will be operated on these subjects. The subject in follow-up will be followed at least 24 months. The pathology result and follow-up result will be the gold standard in this study. The diagnosis result and adverse event will be recorded during the experiment.
Conclusion:
To demonstrate safety and efficacy of the ProLung China Test in the risk stratification of patients with pulmonary lesions identified by CT that are suspicious for lung cancer.
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P3.13 - Radiology/Staging/Screening (ID 729)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.13-037 - Deep Learning System for Lung Nodule Detection (ID 9503)
09:30 - 16:00 | Author(s): Jie Hu
- Abstract
Background:
Ever since its first success in large scale image recognition problem, deep convolutional neural networks (DCNNs) have shown their capabilities in solving many challenging visual perceptual tasks, such as image classification, segmentation, object detection. In some cases, DCNNs have already achieved near-human performance. In medical image analysis, DCNNs have also been successfully applied to lesion detection, segmentation, and diagnosis. The power of DCNN lies in its ability to learn a hierarchical representation of raw input data, without hand-crafted features.
Method:
The focus of this study was to improve the performance of DCNN in automatic detection of pulmonary nodule on CT scan. In particular, nodules whose size is less than 4mm were considered. A total of 171 scans were collected at Zhongshan Hospital Fudan University, which was first process by the proposed DCNN system (12Sigma). The detection results were then carefully reviewed by an experienced physician, all false positives and missed nodules were manually labeled. To refine the system, all false positives and true nodules of sizes 4mm and under were selected.
Result:
The data set was randomly split into training and test sets, where the training set consists of 90% (154 scans) and the test set consists of 10% of data (17 scans). Figure 1 shows the FROC curves on the test set before and after re-training. Overall, the detection sensitivity were improved at all false positive levels, but the improvement was most significant at low FP rate region. For example, when FP is 0.5 per scan, the detection sensitivity increased from 0.36 to 0.49. Figure 1
Conclusion:
This improvement suggests that, even with limited data, the deep neural network can learn from its mistakes and be easily tuned to be more sensitive to small nodules. We believe that when more data is colllected, more significant improve in high FP rate region will be observed.
