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Angelica Rigutto
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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): Angelica Rigutto
- 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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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-26 - ALK Fusion Variant Detection by Targeted RNA-Seq in TKIs Treated ALK-Positive Lung Adenocarcinoma (ID 1860)
09:45 - 18:00 | Author(s): Angelica Rigutto
- Abstract
Background
Clinical outcomes of ALK positive (ALK+) Non-Small-Cell Lung Cancer (NSCLC) and the identification of the most effective anaplastic lymphoma kinase inhibitor (ALKi) according to the specific ALK fusion variants are not well assessed. We retrospectively characterized fusion variant distribution in a cohort of ALK+ lung adenocarcinomas (ADC) with paired clinical data about treatments and outcomes.
Method
Diagnostic tumor tissue from advanced ALK+ (by FISH and/or IHC) ADC diagnosed from 2010 to 2018 and treated with single or multiple ALKis were collected (expanded cohort from Gobbini et al. Lung Cancer, 2017). The OncomineTM Solid Tumor Fusion Transcript Kit on an Ion PGM™ system and the Ion Reporter™ software were used to identify targeted ALK fusion gene products (ThermoFisher).
Result
Specific fusion variant transcripts were found in 34/55 (62%) of collected samples. As expected, EML4-ALK fusion transcripts were the most common (31/34 samples, 91%), but HIP-ALK transcripts were also detected (3/34 - 9%). Among EML4-ALK fusions the following variants were detected: V1 (n=11); V2 (n=2); V3a/b (n=12 ) V5a/b (n=5 ) and E6A19 (n=1). Patient median age was 60 year [range 36-85], 22 were male and 12 female. Three patients were current, 11 former and 20 never smokers. Crizotinib, alectinib, ceritinib, brigatinib and lorlatinib were the ALKis used. Independently of the therapy line, 12 patients received crizotinib only, while 22 patients received crizotinib followed by one or two other ALKis. Regardless of the type of transcript, those patients who received more than one ALKi had a better median overall survival compared to those receiving crizotinib only, as expected (74 vs 21 months, HR: 5.31; 95%CI: 1.464-19.26, log rank p=0.0006). Furthermore, a significant difference in the mean duration of the different ALKi treatment was found according to the ALK variants (Chi-square p<0.0001), suggesting a private ALKi efficacy profile for specific fusion variants. Finally, the 3 HIP-ALK cases showed a better outcome with respect the EML4-ALK variants (not reached vs 51 months).
Conclusion
Our analysis suggests that different ALK fusion variant might affect ALKi treatment duration in ALK+ lung ADC.
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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): Angelica Rigutto
- 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.
