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P. Meldgaard
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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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P3.02-005 - Applicability of Ion Torrent Colon and Lung Sequencing Panel on Circulating Cell-Free DNA (ID 8925)
09:30 - 09:30 | Author(s): P. Meldgaard
- Abstract
Background:
Identifying tumor-specific mutations in plasma from cancer patients serves as a non-invasive supplement to taking biopsies. Targeted sequencing of the circulating cell-free DNA (cfDNA) is an efficient method, for screening for a number of relevant mutations. Different approaches of targeted sequencing have been optimised for clinical use on FFPE, e.g. the Ion Torrent Colon and Lung panel. The size of DNA extracted from FFPE tissue is comparable with that from cfDNA. We therefore investigated the performance of the clinically relevant Ion Torrent Colon and Lung panel on cfDNA.
Method:
We used the Horizon multiplex cfDNA standard with eight known mutations at concentrations of 5 % (5-6.3 %), 1 % (1-1.3 %) , 0.1 % (0.1-0.13 %) and no mutations (wild type), respectively, to test the reproducibility of the panel. We obtained plasma from healthy donors from the danish Blood Bank to set a baseline for the panel. Lastly, the panel was tested on 52 patient samples. Patient plasma samples are from a previously collected cohort of EGFR wild-type non-small cell lung cancer patients (: NCT02043002) All samples were sequenced using the Ion Torrent Oncomine Solid Tumor DNA kit (Colon and Lung panel) from Thermo Fisher. Sample preparation was performed using the Ion Torrent Chef and sequencing was performed on the Personal Genome Machine (PGM) system. Data was analyzed using the Torrent Suite software, and variants called by Ion Reporter.
Result:
No somatic mutations were identified in neither the Horizon multiplex wild type nor the cfDNA from healthy donors. The Horizon multiplex samples were sequenced three times in different runs, to test the reproducibility of the panel. For the 5 % sample all mutations were detected in all runs. For the 1 % sample the four mutations at 1.3 % where detected in all runs, while two out of three runs missed one mutation at 1 %. In both cases the mutation could be identified by visualization of the reads, but was not called. For the 0.1 % sample, no mutations were detected. After finishing the validation the panel was used for sequencing patient samples. Of the 52 samples, 47 were successfully sequenced (90 %), and COSMIC-verified mutations were identified in 32 samples.
Conclusion:
The panel reliably and reproducibly detects mutations down to 1.3 %. Mutations present in lower concentration can also be detected, but for reliable detection higher coverage is needed. Sequencing was successfully performed on a range of patient samples.
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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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P3.13-014 - Prediction of Survival with 18F-FDG-PET/CT Early during Erlotinib Treatment in NSCLC Patients – a Comparison of Four Evaluation Methods (ID 8902)
09:30 - 09:30 | Author(s): P. Meldgaard
- Abstract
Background:
Erlotinib treatment is offered to NSCLC patients in a palliative setting also in EGFR wildtype (EGFR-wt) patients because we know that some of these patients will benefit, However, in order to evaluate the effect of treatment, we wait for 8-12 weeks before performing a CT scan, since the effect is rather subtle especially in EGFR-wt patients. The purpose of this study was to evaluate which method for evaluating change in 18F-FDG uptake is the best predictor for survival.
Method:
18F-FDG-PET/CT scans from 56 NSCLC patients (48 EGFR-wt and 8 EGFR mutated) performed before and after 7-10 days of erlotinib treatment were analysed with four different methods for response to treatment including visual evaluation, and three semi quantitative methods measuring % change in SULpeak, SULmax and TLG, with a range of cut-off levels determining response, stable disease and progression. A direct comparison of the semi-quantitative parameters was performed using univariate cox regression, linear regression and ROC analysis for progression free survival (PFS) and overall survival (OS) < the median. Kaplan-Meier analysis was used to estimate PFS and OS for the response categories.
Result:
Both %SULpeak, % SULmax and %TLG were correlated to PFS and OS. The strongest linear correlation was found for %TLG (R=0.51, p< 0.001). The ROC analysis showed the highest AUC for predicting OS for %TLG (0.70 (0.56-0.85) with a sensitivity of 0.68 and a specificity of 079. All the semi-quantitative methods showed a statistical overall difference in PFS for the three response categories at some cut-off levels for %SULmax both at 15 and 25%, for %SULpeak at 20 and 25% and for %TLG at 45/75, 50, 30, 25 and 20% cut-off. Visual evaluation failed to differentiate between response categories. For OS %TLG at 4 different cut-off levels and SULpeak at the three lowest cut-off levels showed a statistical overall difference in OS, both visual and %SULmax did not.
Conclusion:
The choice of method for analysis is not clear-cut, but %TLG as suggested by the PERCIST 1.0 is not inferior to other methods, and visual evaluation seems to be the least sensitive at this very early time-point. A lower cut-off level for discriminating between response categories seems to be relevant, we find that 20-25% change for both response and progression is optimal.
