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Y.S. Choi
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-001 - Detection of Gene Fusions in NSCLC Using NGS Fusion Assay (ID 10033)
09:30 - 09:30 | Author(s): Y.S. Choi
- Abstract
Background:
ALK/RET/ROS and MET exon 14 skipping detection are important to guide of treatment in non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) platform has been implemented in the daily practice for the diagnosis. However, the validation of the NGS-based panel is still complicated and difficult.
Method:
We developed NGS-based fusion assay panel to detect 183 total fusion variants including ALK/RET/ROS as well as MET exon 14 skipping. The fusion call agreement between OCP-50 NGS assay and Nanostring was performed. The result was compared with the FISH and IHC results. This study describes the validation of the assay to define assay parameters, performance characteristics and reproducibility across laboratories.
Result:
For the 55 samples analyzed, the results are as follows;ALK Fusion ROS1 Fusion RET Fusion METD14 NGS(+) NGS(-) Total NGS(+) NGS(-) Total NGS(+) NGS(-) Total NGS(+) NGS(-) Total NS (+) 20 0 20 6 0 6 5 0 5 0 0 0 NS (-) 1 33 34 1 47 48 0 49 49 2 52 54 Total 21 33 54 7 47 54 5 49 54 2 52 54
Conclusion:
The results of our study will be of help in learning the process of establishing, validating and applying the fusion gene detection method in NSCLCs. Furthermore, NGS based OCP-50 assay for fusion detection is more accurate and reliable method for the diagnosis.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-082 - Surgical Rebiopsy in Advanced Non-Small Cell Lung Cancer Resistant to Previous Chemotherapy (ID 10505)
09:30 - 09:30 | Author(s): Y.S. Choi
- Abstract
Background:
To optimize the personalized medicine for advanced non-small cell lung cancer (NSCLC), sufficient tumor tissue is mandatory to analyze molecular and genetic profile. The demand for repeat biopsy in NSCLC is increasing, it is more difficult to obtain specimen after initial treatment. The aim of this study was to evaluate the impact of surgical rebiopsy in advanced NSCLC.
Method:
From Jan 2014 to Mar 2017, 146 consecutive patients underwent surgical rebiopsy for NSCLC which was resistant to prior chemotherapy. Their medical record were reviewed retrospectively.
Result:
There were 60 male and 86 female patients with mean age of 57 years (range 30-83). Adenocarcinoma was most common histologic type (n=142, 93%). Among them, 107 patients represent EGFR mutation before chemotherapy, deletion in exon 19 (n=73) was most frequently observed. Before surgical rebiopsy, 121 patients (83%) were treated with EGFR-TKIs. The mean number of change in chemotherapy regimen was 2 (range 1-6) and 24% of patients underwent more than 3 different chemotherapy before rebiopsy. The median time between initial treatment and rebiopsy was 17.4 months (IQR 9-25). Surgical rebiopsy was possible in all cases. One hundred and seven patients (73%) underwent pleura biopsy, 22 underwent lung resection and 12 patients underwent both pleural and lung resection. Most procedure underwent video-assisted thoracic surgery (n=136, 93%), 10 patients required mini-thoracotomy. Median postoperative hospital stay was 4 days (IQR, 3-6) and the 30-day mortality was 2.7%. All specimens were confirmed as NSCLC and adequate for mutational and genetic analysis except 2 patients. One patient was failed to mutational analysis, other patients was failed to genetic sequencing due to low tumor volume. After surgery, 129 patients can resume chemotherapy. Of those, 85 patients were enrolled clinical trial or treated with new target agent. Thirty nine patients were treated with cytotoxic chemotherapy and 5 patients continued with prior target agent.
Conclusion:
Surgical rebiopsy can detect changes in cancer characteristics and may be used in therapeutic decision making in advanced NSCLC resistant to previous treatment.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-011 - A Prospective Study of Serial Circulating Tumor DNA Assessment in Detecting Recurrence of Resected Early-stage Lung Cancer (ID 10062)
09:30 - 09:30 | Author(s): Y.S. Choi
- Abstract
Background:
In advanced non-small cell lung cancer (NSCLC), circulating tumor DNA (ctDNA) can be used to identify clinically actionable mutations when tissue is insufficient or unobtainable for genotyping. In early-stage NSCLC, the persistence of ctDNA after complete resection may suggest the presence of minimal residual disease and predict an increased risk of recurrence; however, data on the longitudinal use of ctDNA is very limited. The aim of this study is to assess the clinical feasibility of ctDNA assessment for the prediction of lung cancer recurrence following surgical resection.
Method:
Patients undergoing curative-intent surgery for NSCLC were prospectively enrolled. Peripheral blood samples were collected at pre-specified time points immediately prior to surgery and 2-3 weeks after surgery. Plasma cell-free DNA samples were analyzed with a novel 21-gene Digital Sequencing NGS panel (Guardant Health, Inc.) with a theoretical genomic sensitivity of > 90% for NSCLC. For each patient, the identities and quantities of somatic alterations identified in ctDNA were correlated to clinical outcomes.
Result:
Of the 55 pair-matched patients, 33 were evaluable at the time of abstract submission. The median age was 61 (18 men). The histologic type was adenocarcinoma in 19 (58%), squamous cell carcinoma in 14 (42%), and small cell lung cancer in 2 (6%). The pathologic stage was I in 20 (61%), II in 3 (9%), and IIIA in 10 (30%). Median clinical follow up was 13 months. Of the 4 patients with detectable post-operative ctDNA, 3 recurred within the follow-up period. Of the 8 total recurrences observed, the most common site was the brain (4) and lung (3). One of 4 adenocarcinoma recurrences, 1 of 2 squamous cell carcinoma recurrences, and 1 of 2 small cell recurrences were associated with detectable post-operative ctDNA. By stage, post-operative ctDNA was detected in 1 of 1 stage II and 3 of 7 stage IIIA patients. Recurrences not associated with detectable post-operative ctDNA were enriched in oligometastatic recurrence (4 of 5 unpredicted recurrences were in isolated lymph nodes or the brain).
Conclusion:
In this small pilot cohort, ctDNA detected at 2 weeks post resection was associated with recurrence (RR 9.38, p=0.038), while the absence of detectable ctDNA was not significantly associated with lack of recurrence (RR 0.65, p=0.12). Oligometastatic disease, especially in the brain, was a primary risk factor for ctDNA-negative recurrence. These findings establish proof of concept for the use of ctDNA diagnostics as a risk stratification tool in resected lung cancer.
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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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P3.04-011 - A Prospective Study to Optimize the Extent of Pulmonary Resection According to Decision-Making Algorithm in cStage IA NSCLC (ID 10047)
09:30 - 09:30 | Author(s): Y.S. Choi
- Abstract
Background:
Recent advances in imaging technology and the widespread use of low-dose computed tomography screening have greatly increased the chance of detecting small-sized non-small cell lung cancer (NSCLC) with indolent features (radiologically ground-glass opacity and histopathologically lepidic pattern adenocarcinoma). This change in the disease pattern of NSCLC has led to a resurgence of interest in sublobar resection. The purpose of this study is to determine the outcome of patients with clinical stage IA NSCLC treated by 3 types of surgical resection (wide wedge resection, segmentectomy, or lobectomy) according to the institutional decision-making algorithm.
Method:
In this study, we are planning to prospectively enroll 1,000 patients with clinical stage IA NSCLC undergoing curative-intent surgical resection. Our decision-making algorithm regarding the optimal extent of pulmonary resection has been developed based on our institutional consensus building meetings. We are planning to prospectively measure radiologic features such as tumor diameter and consolidation/tumor (CT) ratio. For ≤ 2cm tumors with CT ratio of ≤ 0.25, wide wedge resection needs to be performed. For ≤ 2cm tumors with CT ratio of 0.25 to 0.5 or 2-3cm tumors with CT ratio of ≤ 0.5, segmentectomy should be chosen. When CT ratio is larger than 0.5, lobectomy is required regardless of tumor size. When either parenchymal or bronchial resection margin is found to be insufficient during surgery, segmentectomy or lobectomy should be done even when a lesser resection was planned. Resection margins greater than the maximal tumor diameter (lesions less than 2cm) or at least 2cm gross margins (lesions larger than 2cm) should be achieved. Hilar and mediastinal lymph node dissection or at least systematic lymph node sampling is strongly recommended for any kind of pulmonary resection.
Result:
The primary objective is to determine disease-free survival following sublobar resection and lobectomy. The secondary objectives are (1) to determine overall survival following surgery, (2) to determine rates of loco-regional and systemic recurrence following surgery, (3) to compare postoperative pulmonary function between 3 different resection types, (4) to explore the relationship between radiologic parameters and pathologic subtypes, and (5) to determine the predictors of unexpected nodal involvement.
Conclusion:
This study is registered with ClinicalTrials.gov, number NCT03066297 (“OREX-IA” study) and we started recruiting patients in February, 2017 and will also be planning to follow up patients for at least 5 years to analyze their survival and recurrences.
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-012 - Clinicopathological Determinants of Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer (ID 10329)
09:30 - 09:30 | Author(s): Y.S. Choi
- Abstract
Background:
Circulating tumor DNA (ctDNA)-based liquid biopsies have recently demonstrated substantial promise in the diagnosis and monitoring of advanced non-small cell lung cancer (NSCLC); however, data regarding utility in early-stage (operable) disease are very limited. The aim of this study is to define the clinical feasibility of ctDNA assessment in operable NSCLC.
Method:
We prospectively recruited 80 patients with clinical stage I-IIIa NSCLC undergoing cruative intent tumor resection. Pre-surgical plasma cell-free DNA (cfDNA) and matched tumor genomic DNA were collected and analyzed with a novel 21-gene Digital Sequencing NGS panel (Guardant Health, Inc.) with a theoretical genomic sensitivity of > 90% for NSCLC. Genomic results, including cfDNA yields, technical sequencing information, and identity and quantity of somatic variants, were correlated with various clinicopathological characteristics, including age, sex, smoking history, clinical and pathologic stage, histological tumor type, and preoperative treatment status.
Result:
[Cohort enrollment and sample collection is complete. Sequencing and analysis have been completed for the first 20 patients. The remaining patients will be completed within 1-2 months. Results from the complete cohort will be updated as directed by the Core Program Committee and will include the data elements described in the methods above. A preliminary review of the data is included below.] Of the 18 patients with somatic variants detected in tumor tissue (18/20, 90%), pre-operative ctDNA was detected in 12 (67%). Pre-operative ctDNA detection was high in squamous cell carcinoma (8/8), small cell lung cancer (1/1) and mixed histology (1/1) relative to adenocarcinoma (2/10, 20%). Clinical stage did not influence detection of small cell or squamous cell carcinoma; however, no ctDNA was detected in stage I or II adenocarcinoma samples (0/5). Detailed data from the complete cohort will be submitted as a late-breaking abstract.
Conclusion:
[Conclusion to be updated pending full cohort data.] ctDNA demonstrates sufficient pre-operative clinical sensitivity to be a feasible recurrence monitoring tool but appears to be influenced by tumor type.
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P3.08 - Locally Advanced Nsclc (ID 724)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.08-006 - Treatment Response and Survival Outcomes Are Associated with Histologic Type in Non-Small Cell Lung Cancer Treated with Trimodal Treatment (ID 9972)
09:30 - 09:30 | Author(s): Y.S. Choi
- Abstract
Background:
Trimodal treatment incorporating neoadjuvant concurrent chemoradiotherapy (CCRT) and surgical resection is one of the treatment strategies for non-small cell lung cancer (NSCLC) patients with N2 disease. Although pathologic phenotypes as well as biological features might be different between adenocarcinoma (ADC) and squamous cell carcinoma (SqCC), histologic type has been rarely considered when selecting treatment strategy in patients with N2 disease. The aim of this study is to investigate if histologic type is associated with treatment response and survival outcomes in patients undergoing trimodal treatment for N2 disease.
Method:
A retrospective review of patients with N2 disease who underwent neoadjuvant CCRT followed by surgery at our institution was performed. Clinicopathologic features, response to CCRT, and survival outcomes were compared between ADC and SqCC.
Result:
From 2003 to 2013, 374 patients underwent curative-intent surgery after neoadjuvant CCRT for either ADC (n=233, 62.3%) or SqCC (n=141, 37.7%) with pathologically proven N2 disease. Sixty-nine patients (18.5%) had bulky and/or multi-stationed N2 diseases on pre-CCRT imaging tests. There were more male, more smokers, more advanced clinical T and N stages, and more bulky and/or multi-stationed N2 diseases in the SqCC group than in the ADC group. Conversely, the SqCC group had more radiologic responders, earlier pathologic T and N stages, more pathologic complete responders, and more frequent mediastinal downstaging than the ADC group. With a mean follow-up of 50.1 months, patients with SqCC showed significantly better 5-year recurrence-free survival than those with ADC (ADC, 22.8% vs. SqCC, 43%; p=0.001). However, there was no significant difference in the 5-year overall survival between the two groups (ADC, 57.5% vs. SqCC, 52.3%; p=0.366). This may be related to significantly better (p<0.001) post-recurrence survival in the ADC group (mean, 28 months) than in the SqCC group (mean, 14.5 months). In the ADC group, 164 patients developed recurrences and of those, 68 (41.5%) received targeted therapy. Patients who received targeted therapy for recurrences showed significant better 5-year overall survival than those who did not receive (61% vs. 45.6%, p=0.025).
Conclusion:
In this study, SqCC was associated with better treatment response and more favorable recurrence-free survival than ADC. Despite poor recurrence-free survival in ADC, its overall survival was improved by prolonged post-recurrence survival, which might be related to the use of targeted therapy for recurrence. Since treatment response and survival outcomes are different according to histologic type, individualized treatment strategy could be considered to improve outcomes of N2 disease.
