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Stefania Izzo
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EP1.09 - Pathology (ID 199)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.09-13 - Clinic-Pathological and Molecular Features of PD-L1 Analyses in Advanced NSCLC: A Real Life Single Center Experience (Now Available) (ID 2559)
08:00 - 18:00 | Author(s): Stefania Izzo
- Abstract
Background
Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is the most rapid, less expensive and routinely applied predictive assay for treatment with immune checkpoint inhibitors (ICI) in advanced non small cell lung cancer (NSCLC). We analyzed a real-life single center activity of PD-L1 characterization together with pathological features, molecular status determination and patients’ clinical response to ICI.
Method
From January 2017 to July 2018 all advanced NSCLC tumor tissue analyzed for PD-L1 expression and molecular status determination in the Pathology Unit of San Luigi Hospital, Orbassano (Turin) were selected. PD-L1 analysis was performed using 22C3 PharmDX on Dako Autostainer, while ALK rearrangement was assessed by FISH and EGFR mutations by direct pyrosequencing. Furthermore in a majority of cases (60%) a 22-gene panel was evaluated by Ion Torrent PGMTM Next Generation Sequencing (NGS). The PD-L1 IHC assay results were analyzed with cut-off values of >50% (strong positive), 1-49% (weak positive), and <1% (negative). Clinical data of response to ICI were acquired for 65 patients.
Result
510/532 (96%) cases were adequate for PD-L1 determination and molecular analyses; 169 (33%) were histological, 269 (53%) core biopsies and 72 (14%) cytological samples; 375 (74%) were from primitive lesion, while 135 (26%) were from metastatic sites. Of the 22 inadequate samples for PD-L1 analysis half of them were cytological specimens. PD-L1 was strong positive in 91 (18%) cases, weak positive in 137 (27%) cases and negative in 285 (56%) cases. Specimens with higher expression (>50%) derived preferentially from histological samples (e.g. surgical specimens) and from external hospitals referred to our Central Hub. EGFR and ALK positive cases were more frequently PD-L1 negative or weak positive (13% and 2%, respectively), although not reaching statistical significance. Instead, KRAS and TP53 mutated cases were significantly associated with negative or weak positive PD-L1 expression (14% and 22%, chi-square p=0.0006 and p=0.01, respectively). Among the 65 patients with clinical data of response to ICI, 37/65 (57%) were responders (partial response + stable disease) while 28/65 (43%) had progressive disease. No significant differences in terms of clinic-pathological or molecular features were found between these two groups, maybe due to the limited number of cases.
Conclusion
Our analyses suggest that integration of PD-L1 testing in the pathological and molecular characterization of advanced NSCLC is feasible with a very high adequacy, enabling a wide ICI administration to these patients.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-18 - Lymphocyte Infiltration Pattern and STING Expression Identify Different Prognostic Groups in Early Stage NSCLC (ID 2536)
10:15 - 18:15 | Author(s): Stefania Izzo
- Abstract
Background
Lymphocyte infiltration has been described has a potential biomarker of lung cancer patients’ survival. Different studies de-convoluted immune cell compartment (i.e. stromal CD8 density) trying to identify clinically relevant immune patterns.
Method
A series of 178 early-stage (IB-IIIA) NSCLC has been retrospectively collected at Department of Oncology, San Luigi Hospital (Orbassano, Italy). From Formalin-Fixed and Paraffine-Embedeed (FFPE) tumor blocks, Tissue Microarrays (TMA) were constructed (4 cores were selected for each case). Lymphocyte infiltration pattern was determined by light-microscopy on Hemathoxylin-Eosin (HE) whole slides. Immunohistochemistry was performed as follow: CD8 (SP57) and STING (D2P2F) antibodies were tested with Ventana Benchmark and PD-L1 (22C3) with Dako Autostainer. Infiltration pattern has been clustered in 4 different categories: brisk-diffuse, non-brisk multifocal, non-brisk focal and none. CD8 was quantified as positivity percentage, PD-L1 through TPS (<1%, 1-49% and ≥50%) and STING taking advantage of H-score. Overall survival (OS) and Progression Free Survival (PFS) were estimated using the Kaplan-Meier method and compared using log-rank test.
Result
Most represented patients had following features: male (119-71%), current or previous smokers (145-82%), stage II (94-53%) and adenocarcinoma histology (119-67%). Distribution of lymphocyte infiltration pattern was: 110 cases with brisk-diffuse (62%), 56 with non-brisk (multi-focal and focal) (31%) and 12 with none pattern (7%). CD8 positivity was distributed in 3 categories: high (66 - 37%), intermediate (75 - 42%) and low (37 -21%) density. For PD-L1 TPS analyses 111 cases (62%) had <1%, 39 cases (22%) 1-49% and 28 cases (16%) >50%. STING high-expressors were 88 (49%) and low-expressors 90 cases (51%). Lastly, were identified 81 samples (45%) with STING positivity at high-density on immune cells (IC) and 97 samples (55%) with low-density. As expected, Brisk-infiltrated samples presented an higher CD8 density (p=0.015). At PFS analyses, STING IC resulted associated (p=0.05) with a worse PFS for high-density patients. At OS analyses, brisk lymphocyte infiltration pattern appeared to have a negative impact (p=0.05) and STING higher-expressors on tumor cells had a worse prognosis (p=0.04).
Conclusion
NSCLC with wider lymphocyte infiltration and expression of immune activation markers (as STING) appeared to be associated with a worse prognosis (PFS and OS). These date need further validation at multivariate analyses.