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A. Spatz
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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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P2.02-040 - Cytology Cell Block Is Suitable for Immunohistochemical Testing for PD-L1 in Lung Cancer (ID 10132)
09:30 - 16:00 | Author(s): A. Spatz
- Abstract
Background:
PD-L1 immunohistochemistry (IHC) testing is usually performed on core needle biopsy or surgical resection tissue blocks, and tumor proportion score (TPS) ≥50% is used to select patients to treat with Pembrolizumab immunotherapy. In this study, we evaluate the results using cytology cell block for PD-L1 IHC assay.
Method:
A total of 1423 consecutive cases of non-small cell lung cancer (NSCLC), including 368 cytology cell blocks, 813 small biopsies and 242 surgical resections, were included in the study. 151 cytology cell blocks had known fixation status, which were either directly fixed in formalin, or in alcohol first then refixed in formalin. IHC used Dako PD-L1 IHC 22C3 pharmDx. The TPS of ≥ 50% tumor cells was defined as positive. A total of 100 viable tumor cells were required for adequacy.
Result:
Of the cytology cell blocks, 93% of the specimens had sufficient numbers of tumor cells, and the rate was equivalent to the rate of small biopsies (93%). All resection specimens were shown to be adequate for testing. PD-L1 expression was positive in 42.1% of cytology cell blocks, statistically comparable to small biopsies (36.3%, P>0.05), but higher than in surgical resections (28.5%, p<0.05). The fixative methods did not affect the immunostaining, since the PD-L1 positive rate was of 41.9% in formalin only group, vs 40.4% in alcohol plus formalin fixed cell blocks (p>0.05). The PD-L1 positive rate appeared lower in cell blocks from bronchoalveolar lavage (BAL) (27%) as compared to fine needle aspiration (FNA, 42%) and pleural/pericardial fluid (45%), although the difference did not reach statistical significance (P>0.05).
Conclusion:
Our results demonstrate that PD-L1 IHC performs well with cytology cell blocks. The rate of positive PD-L1 was comparable between cytology blocks and small biopsies. As cytology cell blocks are commonly available from lung cancer patients, they can provide valuable resource for PD-L1 testing and can help to avoid rebiopsies. However additional correlation with clinical response will be helpful to further validate the cytology specimens.
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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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P3.01-019 - Canadian Multicentre Validation Study of Plasma Circulating Tumour DNA for Epidermal Growth Factor (EGFR) T790M Testing (ID 8878)
09:30 - 16:00 | Author(s): A. Spatz
- Abstract
Background:
Plasma detection of EGFR T790M mutations in circulating tumour DNA (ctDNA) of advanced lung cancer patients with acquired resistance to EGFR tyrosine kinase inhibitor (TKI) has been proposed as alternative to tumor re-biopsy. This national validation study across Canadian centres aimed to establish the sensitivity and specificity of plasma detection of T790M as a clinical test using digital droplet (dd)PCR and next generation sequencing (NGS) assays.
Method:
Canadian patients at 7 centres undergoing screening for ASTRIS (NCT02474355) were invited to participate in this companion blood-based study. Patients with acquired resistance to EGFR TKI consented to collection of blood samples and demographic data. Samples were analysed using ddPCR and/or NGS platforms available at 4 molecular diagnostic laboratories across Canada. Concordance between the results of plasma T790M assayed in these 4 laboratories with reference tissue/plasma testing conducted for ASTRIS was assessed.
Result:
63 patients participated; the median age was 64 years (range 31-87), 69%(40/58) were Asian; 55%(33/60) were male. All patients received prior EGFR TKI, 17%(10/60) also received prior chemotherapy. Reference testing for EGFR T790M for ASTRIS eligibility identified positive T790M(+) results for 31(49%), negative(-) for 30(48%) and indeterminate(i) results for 2(3%) patients. One laboratory tested all 63 patient samples using both ddPCR and NGS (Oncomine Lung cfDNA assay), another laboratory tested 18 samples using ddPCR and NextSeq, a third tested 10 samples using ddPCR and COBAS EGFRv2, and a fourth tested 6 samples using Ion Torrent PGM. A total of 188 tests were performed including 91 by ddPCR, 87 NGS and 10 COBAS assays. Combining test results for each patient, 60%(38/63) of patient plasma samples were T790M+, 23(37%) were T790M-, and 2(3%) were inconclusive. Of 31 patients with reference T790M+ results from ASTRIS, 23(74%) had T790M detected in plasma, 6(19%) did not (T790M-), and 2(7%) had indeterminate (T790Mi) plasma results. For 30 patients with T790M- reference results from ASTRIS, 13(43%) had plasma T790M+ and 17 plasma T790M- results. The 2 patients with T790Mi by reference testing both had T790M+ results from plasma. Altogether, 47%(15/32) of patients deemed to have T790M-/i tumours by reference testing were found to have T790M+ results by plasma in this multicentre study. Combining results from both tissue and plasma testing, 73%(46/63) of study patients had T790M+ results.
Conclusion:
Plasma ctDNA testing in this multicentre Canadian study identified a significant number of additional patients eligible for osimertinib therapy beyond routine biopsy tissue testing for EGFR T790M.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-055 - Detecting ALK, ROS1 and RET Gene Translocations in Non-Small Cell Lung Cancer (NSCLC) with the NanoString Platform (ID 9976)
09:30 - 16:00 | Author(s): A. Spatz
- Abstract
Background:
Identification of ALK, ROS1 and RET fusions is critical for guiding target therapy of lung cancers. In this study, we evaluated the transcript-based nanoString assay for detection of ALK fusions compared to immunohistochemistry (IHC) and FISH methods, and the simultaneous detection of ROS1 and RET transcripts in formalin-fixed and paraffin embedded tissues (FFPE).
Method:
A total of 44 patients with NSCLC were selected for this non-consecutive case study. Samples included 24 cases of non-smokers or patients younger than 50 years with negative EGFR/ALK results that are more likely to contain a ROS1 or RET translocation. Eight cases with a discrepancy between ALK IHC and FISH results or equivocal IHC ALK results, as well as 12 cases previously confirmed positive for ALK by IHC were also included. The specimens were assessed for ALK, ROS1 and RET fusion transcripts by nanoString nCounter profiling.
Result:
While nanoString demonstrated 94.9% concordance with IHC and 84.2% concordance with FISH, it detected unknown ALK active transcripts in 3 of 7 cases that showed a discrepancy between IHC and FISH, or which were negative for ALK by IHC and FISH (see table 1). The three equivocal ALK IHC cases were scored negative by the 2 other methods. In addition to ALK, 3 cases of ROS1 and 2 cases of RET fusions were detected by nanoString. ALK, ROS1 and RET fusions were found mutually exclusive. Table 1. Discrepancy of ALK findings by IHC, FISH and nanoString, and crizotinib responseCase IHC FISH FISH positive nuclei (%) nanoString Crizotinib response 1 Positive Negative 3.9 Unknown ALK active fusion Positive 2 Negative Negative 3.3 Unknown ALK active fusion Positive 3 Negative Negative 8.6 Unknown ALK active fusion Unknown 4 Negative Borderline 17.3 Negative Not treated 5 Negative Borderline 15.1 Negative Not treated 6 Negative Borderline 19.7 Negative Not treated 7 Negative Positive 24 Inconclusive Unknown
Conclusion:
NanoString performed well in lung cancer FFPE tissue including cytology materials. The results are highly concordant with the current standard methods of ALK-1 IHC and FISH. As a single test, it detected ALK, ROS1 and RET fusions simultaneously. NanoString profiling can be an alternative for a one tube test for ALK, ROS1 and RET translocations in a selected NSCLC patient group.
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P3.02-097c - Detection of the EGFR P.(T790M) Mutation by Different Methods: A Small Comparison Case Study (ID 10260)
09:30 - 16:00 | Author(s): A. Spatz
- Abstract
Background:
About 50-60% of non-small cell lung cancer (NSCLC) patients with a Tyrosine Kinase Inhibitor (TKI) sensitizing EGFR mutation can develop therapy resistance via the acquisition of the additional p.(T790M) mutation. The identification of this group of patients is important because they can be treated with a 3[rd] line TKI: Osimertinib. Analysis of plasma samples has become a minimally invasive alternative to repeat tissue biopsy for the detection of the EGFR p.(T790M) mutation. The mutation can be detected in plasma and tissue by various methods including the FDA approved Roche COBAS® EGFR v2 test, the EntroGen® EGFR test and digital droplet PCR (ddPCR). In this study, we compared the detection of the EGFR p.(T790M) mutation by ddPCR and COBAS in plasma specimens, and ddPCR and EntroGen in tissue specimens.
Method:
Blood from 14 NSCLC was collected in STRECK™ blood collection tubes. Plasma was prepared and circulating cell-free (ccf) DNA extracted with the COBAS and Qiagen method. DNA was analyzed for the presence of the EGFR TKI sensitizing and p.(T790M) mutation by COBAS, or the p.(T790M) mutation only by ddPCR on a Biorad QX200 platform. In addition, 26 biopsies from EGFR-positive patients who progressed on TKI, and which were tested p.(T790M) negative by Entrogen were re-analyzed by ddPCR.
Result:
Nine out of fourteen plasma samples were found to contain DNA with the sensitizing EGFR mutation by COBAS. The p.(T790M) mutation was found in four of these nine cases. ddPCR revealed one additional p.(T790M)-positive plasma sample that was tested negative by COBAS. ddPCR detected ten p.(T790M)-positive cases in the 26 EntroGen p.(T790M) negative samples, and suggests a 38% of false negative rate of the EntroGen method in this small cohort of samples.
Conclusion:
ddPCR for the detection of the EGFR p.(T790M) mutation in plasma and tissue appears to be associated with a higher sensitivity compared to the COBAS and EntroGen methods, respectively.
