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In-Jae Oh
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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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P1.01-014 - Feasibility of Liquid Biopsy Using Plasma and Platelets for Detection of ALK Rearrangements in Non-Small Cell Lung Cancer (ID 9301)
09:30 - 16:00 | Author(s): In-Jae Oh
- Abstract
Background:
Fluorescence in situ hybridization (FISH) using tissue biopsy specimen is the gold standard for detection and confirmation of ALK rearrangement in non-small cell lung cancers (NSCLC), but it is time-consuming and labor-dependent procedure. Liquid biopsy using reverse-transcriptase polymerase chain reaction (RT-PCR) is expected to overcome these limitations, and provide an easy accessibility and frequent assessment of biomarkers. The aim of this study is to investigate the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement.
Method:
FISH was performed in 664 patients between January 2015 and May 2017. We retrospectively analyzed the formalin-fixed paraffin-embedded (FFPE) tissue and blood sample to detect ALK rearrangement using multiplex RT-PCR from 30 advanced NSCLC patients who had available tissue specimen and agreed with venous sampling. Total RNA were extracted from FFPE cell blocks, plasma and platelets, respectively. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK, the most common translocation, fusion RNA was detected using PANAqPCR[TM] EML4-ALK fusion gene detection kit.
Result:
Twenty-eight patients were FISH positive and two were negative. In a validation data compared with FISH, RT-PCR using FFPE tissue demonstrated 57.1% sensitivity and 69.2% accuracy. Liquid biopsy (plasma or platelets-positive) had higher sensitivity (96.4%) and accuracy (93.3%). Among the specimen of liquid biopsy, platelets showed slightly higher sensitivity and accuracy than plasma (82.1 and 83.3% vs 78.6 and 76.7%). Compared with FFPE tissue using RT-PCR, liquid biopsy showed 100% sensitivity, 20.0% specificity and 69.2% accuracy. Median proportion of positive cells in FISH was higher in subgroups of liquid biopsy with positive result (Plasma, 30.0 vs 15.0%; Platelets 30.0 vs 20.0%), but it was not statistically significant (p=0.062 and 0.104). In 18 patients with crizotinib treatment, platelets-positive subgroup showed a tendency of longer duration of treatment (7.2 vs 1.5 months) and higher response rate (57.1 vs 0.0 %), but the difference was not significant (p=0.071 and 0.100). However, platelets-positive subgroup showed significantly higher disease control rate than platelets-negative subgroup when they were treated with crizotinib (85.7 vs 25.0%, p=0.044).
Conclusion:
Plasma and platelets are a valuable source for liquid biopsy using RT-PCR technique in detection of ALK rearrangement, and they could play a supplementary role in diagnosis of ALK-positive NSCLC. Furthermore, platelets, especially, may be useful for predicting the treatment outcome of crizotinib.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-024 - Phase II Trial of AZD9291 in Second-Line Treatment after Acquired Resistance with T790M Mutation Detected From Circulating Tumor DNA (ID 8736)
09:30 - 16:00 | Author(s): In-Jae Oh
- Abstract
Background:
Administering the best treatment after acquiring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) requires the knowledge of the resistance status. In this trial, the treatment efficacy of osimertinib (AZD9291) was assessed in patients with non-small-cell lung carcinoma (NSCLC) harboring T790M resistance mutation, which was detected in the circulating tumor DNA (CtDNA) without re-biopsy of the tumor tissue.
Method:
To prove 60% response rate of osimertinib compared to 30% as null hypothesis, and considering 10% drop out rate, 19 subjects were recruited. To extract CtDNA, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas® v2 RUO (Roche diagnostics) and PANA mutyper® (Pangene, Korea) were used to detect the EGFR mutations from CtDNA. Osimertinib was prescribed as an 80 mg tablet once in a day irrespective of the food intake.
Result:
Eighty patients with acquired resistance to prior EGFR TKIs were screened for T790M resistance mutation, and the CtDNA of 21 subjects (26.3%) showed T790M mutation. T790M mutation was detected by both PANA mutyper® and Cobas® in 13 cases, T790M was detected only by PANA mutyper® in 4 cases, and only by Cobas® in 4 cases. Nineteen subjects (age: 64.4 ± 11.6 years old, 14 women, 5 men) were enrolled in this prospective single arm trial from September 2016 to April 2017. Prior EGFR TKIs were afatinib (n=3), erlotinib (n=4), gefitinib (n=10), erlotinib and afatinib (n=1), and gefitinib and afatinib (n=1). Twelve subjects had exon 19 deletion of EGFR gene, 4 had L858R point mutation, one showed exon 19 deletion and L858R, 1 had G719X, and 1 case showed no activating mutation. The response to osimertinib was evaluable in 15 subjects; 4 subjects dropped out from this trial before response evaluation. Among the 15 subjects (efficacy analysis set), partial remission was observed in 10 cases (66.7%).
Conclusion:
Assuming 40% of screened patients are harboring T790M mutation, sensitivity of CtDNA testing is 65% using both tests, and 53% with either test. Toxicity and survival analyses will be followed. (ClinicalTrials.gov Identifier: NCT02769286)
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P2.14 - Radiotherapy (ID 715)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.14-017 - Postoperative Radiotherapy in Completely Resected Stage IIIA-N2 Non-Small Cell Lung Cancer (ID 9641)
09:30 - 16:00 | Author(s): In-Jae Oh
- Abstract
Background:
Use of postoperative radiotherapy (PORT) in completely resected (R0) pathologic stage IIIA-N2 non-small cell lung cancer (NSCLC) remains controversial. To assess the impact of PORT, we analyzed on the patterns of failure and survival difference in these patients.
Method:
Consecutive 50 patients with pathologic stage ⅢA-N2 NSCLC who underwent surgery with complete resection (R0) between Apr. 2004 and Dec. 2013 were retrospectively reviewed. Thirty-five(70%) patients were male and median age was 63 years (range, 35 - 82 years). Thirty-nine(78%) patients underwent lobectomy, 7(14%) bilobectomy, and 4(8%) pneumonectomy. Postoperative adjuvant therapy consisted of chemotherapy (ChT) alone in 26(52%) patients, ChT + PORT in 10(20%), PORT alone in 4(8%), and none in 10(20%). Radiation dose was ranged from 34 to 60 Gy with the median 55 Gy. Follow-up period was ranged from 4 to 132 months with median 42 months. Survival was calculated from the date of surgery. Kaplan-Meier method was used for survival calculation and their comparison was done using log-rank test.
Result:
The 3 and 5-year overall survival (OS) rate of all 50 patients was 70% and 58%, respectively and the median survival time was not yet reached. Both univariate and multivariate analysis showed age (> 70 yrs old) and ratio of node positive (LNR > 17%) were correlated with the poor OS. The locoregional recurrence was appeared in 19(38%) patients and distant metastasis in 27(54%). The median time to recurrence was 16 months (range, 1 - 87 months) in locoregional failure and that of distant metastasis was 20 months (range, 6 - 60 months). Lymphovascular space invasion (LVSI) was the only statistically significant factor correlating to the locoregional recurrence-free survival (LRFS) both in univariate and multivariate analysis. PORT did not improve both OS and LRFS. Three and 5-years OS in patients with PORT were 56% and 40%, in a while 76% and 68% in patients without PORT (P=0.166), respectively. Three and 5-years LRFS in patients with or without PORT was 80% and 80% versus 54% and 50% (P=0.105), respectively. We could find that the LNR over 17% (p=0.003), tumor extension (p=0.006), and LVSI (p=0.01) were more prevalent in patients group with PORT.
Conclusion:
In this analysis, the most important prognostic factor in the pathologic stage IIIA-N2 (R0) NSCLC patients was the age and positive lymph node ratio. Risk of locoregional recurrence was decreased with the use of PORT. However, this benefit was not leaded to the overall survival benefit.
