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MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
MA 05.07 - Whole Body PD-1 and PD-L1 PET in Pts with NSCLC (ID 9219)
15:45 - 17:30 | Author(s): I. Bahce
Tumor PD-L1 IHC relates moderately with treatment outcome following anti-PD1 therapy in pts with NSCLC and single biopsies do not account for tumor heterogeneity. Aim: 1. Assess safety of the PET procedures. 2. Quantify Zirconium-labeled nivolumab (Zr-nivo) and F-labeled BMS-986192 (F-PD-L1) uptake. 3. Assess tracer uptake heterogeneity. 4. Correlate tracer uptake with PD-1/PD-L1 IHC in tumor, stroma and with treatment outcome.
NSCLC pts eligible for treatment with nivolumab were included. Pts received whole body F-PD-L1 and Zr-nivo PET scans. Baseline tumor biopsy was required to assess PD-(L)1 IHC status (28.8 assay). SUV~peak~ was calculated for delineable lesions and correlated to PD-(L)1 IHC and response after 12 wks of nivolumab treatment.
10 pts (3 ≥50%, 5 ≥1%, 5 negative by PD-L1 IHC) were enrolled and 37 lesions analysed. No toxicity related to radiotracer was observed. Tumor uptake of both tracers was visualized in all pts, but not in all lesions. Tracer uptake varied among pts with mean F-PD-L1 SUV~peak~ 4.6, range 0.5 - 14.4 and mean Zr-nivo SUV~peak~ 5.0, range 1.6 – 11 (p=0.03) and within pts with mean SUV~peak~ difference 3.6-fold (±2.1) and 2.4-fold (±0.77) between lesions for F-PD-L1 and Zr-nivo, respectively. For lesions with ≥50% PD-L1 IHC, mean F-PD-L1 SUV~peak~ was 8.0 (±4.7) as compared to 3.5 (±1.6) for lesions with <50% PD-L1 IHC (p=0.03). For tumors with high TIL/ stromal PD-1 expression, mean Zr-nivo SUV~peak~ was 8.6 (±2.4) as compared to 6.1 (±2.1) for lesions with low PD-1 expression (p=0.1). Mean SUV~peak ~for F-PD-L1 was 8.4 (±5.4) for pts with PR and 4.5 (±2.9) for pts with PD/SD (p=0.3). Mean SUV~peak~ for Zr-nivo was 7.8 (±1.8) for pts with PR and 5.4 (±2.2) for pts with PD/SD (p=0.2).
1. PET-imaging with both tracers is safe and feasible, with good tumor-to-normal tissue contrast. 2. Tumor uptake showed heterogeneity among pts and among tumors within pts. 3. Pts with ≥50% tumor PD-L1 expression showed higher F-PD-L1 uptake. 4. Pts with high PD-1 expression showed higher Zr-nivo uptake, and pts with PR demonstrated higher F-PD-L1 and Zr-nivo tracer uptake than pts with PD/SD, although these are without statistical significance which may be due to the small dataset.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P2.02-024 - False Positivity Due to Polysomy in Fluorescence in Situ Hybridization (ID 10523)
09:30 - 16:00 | Author(s): I. Bahce
Pathologists may recognize the phenomenon of polyploidy in FISH, which may be misleading in interpretation of break apart fluorescence in-situ hybridization (FISH). The chance for single or split probe signals is likely to increase with the degree of polysomy. The aim of this study was to explore whether false positivity due to polyploidy occurs in practice.
A cohort of cases referred for study or patient care was collected from the archives. From the cases where the ALK and/or ROS1 in-situ hybridization test was repeated in our hospital the outcome of testing was compared. Additionally tumor DNA of an occasional case was tested by an orthogonal method (Ion Torrent Oncomine Focus Assay) for translocations.
Three cases with ALK FISH rearrangement elsewhere were diagnosed with polyploidy in the referral center. One case was reported with rearrangements in both the ALK and the ROS1 gene detected by FISH analysis. In the repeated FISH analysis the average number of co-localization signals in the tumor cell nuclei was 7.6 for ALK and 9.5 for ROS1 respectively (range 1 - 30). Moreover, the morphology of this case was a giant cell carcinoma, variant of pleomorphic carcinoma of the lung. Examination with an orthogonal method (Ion Torrent Oncomine Assay) revealed no translocations and the tumor cells were negative for ALK and ROS1 by immunohistochemistry proving the original report as false positive, supported by absence of response on crizotinib. In break apart FISH the 15% threshold for positivity was obtained in cells emphasizing that in cross sections of normal nuclei occasionally split signals or 3’ probe signals may be present even in diploid nuclei. In the range of 15-20% the chance of false positive FISH is >1%. However, in polyploid tumors the higher number of probe signals within one nucleus comes with an increased chance of split or 3’ signals and a higher rate of false-positive results when maintaining a uniform threshold 15% irrespective of ploidy. Moreover, this may in case of ALK be an additional reason for discordancy with ALK immunohistochemistry, explaining the lack of response on targeted therapy in these patients. 1. vLaffert Lung cancer. 2015;90:465 2. vdWekken. Clin Cancer Res.epub.
In case of polysomy there is a increased chance of false positive in break apart FISH results. An addition technique should be used to confirm a positive FISH status in tumors with highly increased gene copy number due to polysomy.