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E.K. Verbeken
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-025 - Evaluation of NGS and RT-PCR Methods for ALK Assessment in European NSCLC Patients: Results from the ETOP Lungscape Project (ID 5001)
14:30 - 14:30 | Author(s): E.K. Verbeken
- Abstract
Background:
The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%, depending on population and detection method. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been advocated and most recently the advent of targeted Next-Generation Sequencing (NGS) for ALK and other fusions has become possible. This is one of the first studies comparing all 4 techniques in resected NSCLC from the large ETOP Lungscape cohort.
Methods:
96 cases from the ETOP Lungscape iBiobank (N=2709) selected based on any degree of IHC staining (clone 5A4 antibody, Novocastra, UK) were examined by FISH (Abbott Molecular, Inc.; Blackhall, JCO 2014), central RT-PCR and NGS. H-score 120 is used as cutoff for IHC+. For both RT-PCR and NGS, RNA was extracted from the same formalin-fixed, paraffin-embedded tissues. For RT-PCR, primers were used covering the most frequent ALK translocations. For NGS, the Oncomine™ Solid Tumour Fusion Transcript Kit was used, allowing simultaneous sequencing of 70 ALK, RET and ROS1 specific fusion transcripts associated with NSCLC, as well as novel ALK translocations using 5’-3’ ALK gene expression ‘Imbalance Assay’.
Results:
NGS provided results for 90 cases, while RT-PCR for 77. Overall, 70 cases have results for all 4 methods, with fully concordant 60 (85.7%) cases (49 ALK-, 11 ALK+). Before employing the ‘Imbalance Assay', in 5 of the remaining 10 cases, NGS differs from the other methods (3 NGS-, 2 NGS+), while in the other 5, NGS agrees with RT-PCR in all, IHC in 2, and FISH in 1. Using the concordant result of at least two of the three methods as true negative/positive, the specificity and sensitivity of the fourth is 96/94/100/96% and 94/94/89/72% for IHC/FISH/RT-PCR/NGS, respectively (incorporating imbalance: NGS sensitivity=83%). Imbalance scores are presented here for 18 NGS- cases: 9 ‘NGS-/FISH+/IHC+’, 9 ‘NGS-/FISH-/IHC-‘. Among the ‘NGS-/FISH+/IHC+’, there is strong evidence of imbalance in 4 cases (score’s range: 0.0144-0.0555), uncertain in 5 (range: 0.0030-0.0087), and no evidence (scores≤0.0004) in the 9 negative cases.
Conclusion:
NGS is a useful screening tool for ALK rearrangement status, superior to RT-PCR when RNA yield is limited. When using NGS, it is critically important to integrate the 5’-3’ imbalance assay and to confirm with one or more additional methods in the ‘imbalance’ cases. Data further highlight the possibility of missing actionable rearrangements when only one screening methodology is available.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-055 - Pathologic Mediastinal Nodal and Metabolic Tumor Response to Predict Overall Survival in Stage IIIA-N2 NSCLC after Neoadjuvant Chemotherapy (ID 5098)
14:30 - 14:30 | Author(s): E.K. Verbeken
- Abstract
Background:
Neoadjuvant chemotherapy (NCT) is a therapeutic option that is used in patients with resectable stage IIIA-N2 NSCLC. We previously hypothesized that combined major histopathological mediastinal nodal response (≤10% residual tumor cells in nodal tissue) and metabolic FDG-PET response (ΔSUVmax ≥60%) on the primary tumor could be regarded as a powerful surrogate of overall survival (OS) in stage IIIA-N2 NSCLC given NCT and confirmed mediastinal nodal disease at diagnosis. This phase II prospective multicenter study aimed to validate the predictive power for OS of our restaging algorithm.
Methods:
Patients with resectable stage IIIA-N2 NSCLC having mediastinal nodal disease proven by endosonography and primary tumor SUVmax at least 2.5 were eligible. All patients were scheduled for 3 cycles of NCT followed by video-assisted mediastinoscopy (VAM). A standardized PET/CT was performed at baseline, after one and three cycles. The primary endpoint was the predictive power for longer OS of a major histopathological mediastinal nodal response at VAM combined with a pre-defined primary tumor SUVmax ≥60% at PET (good prognosis group) compared to all other situations (poor prognosis group). Under an assumption of a 2-year OS of 80% compared to 30% for the good versus poor prognosis group, respectively, 48 patients were required to have 80% power with 2-sided alpha of 0.05.
Results:
We enrolled 32 patients between 2009 and 2014. Two patients demonstrated stage IV at PET/CT after cycle one. All 3 cycles were given to 30 patients of whom 29 underwent VAM and 22 underwent surgical resection. Objective response rate (RECIST 1.1) was 44%. Complete pathological response occurred in 2 patients. Median OS was 26 months (all 2-year events occurred). In ITT, combined major histopathologic nodal and metabolic tumor response was associated with a trend towards longer OS (HR 0.29, 95%CI 0.14-1.09, P=0.07). Major histopathologic mediastinal nodal response was significantly associated with longer OS (HR 0.25, 95%CI 0.02-0.51, P=0.006), while metabolic ΔSUVmax ≥60% primary tumor response was only associated with a trend towards better OS (HR 0.41, 95%CI 0.17-1.27, P=0.14).
Conclusion:
Complete pathological response to NCT in stage IIIA-N2 NSCLC is infrequent and therefore not useful as a surrogate for OS. Combined major pathologic nodal and metabolic tumor response was associated with a trend towards longer OS. By contrast, a major histopathologic mediastinal nodal response with ≤10% residual tumor cells at VAM is well suited to be adopted as a surrogate of OS.
