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Buge Aysim Oz
MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 2
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
MA26.06 - Crizotinib-Treated ALK Immunopositive Metastasized NSCLC is Associated with an Unfavorable Prognosis when FISH Negative (ID 13179)
14:05 - 14:10 | Author(s): Buge Aysim Oz
Metastasized NSCLC with an ALK fusion are sensitive to a range of tyrosine kinase inhibitors. ALK-positive NSCLC has been identified in the pivotal phase III trial with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC+ FISH-. The aim of this study was to collect ALK IHC+ cases and compare within this group response to crizotinib treatment of ALK FISH+ cases with ALK FISH- cases.a9ded1e5ce5d75814730bb4caaf49419 Method
A prospective multicenter investigator initiated research study was started in Europe. Stage IV ALK IHC+ NSCLC cases treated with crizotinib were collected centrally. Slides were validated centrally for ALK IHC (with 5A4 ETOP and D5F3 Ventana protocol) and ALK FISH (Vysis probes).4c3880bb027f159e801041b1021e88e8 Result
The study started April 1, 2014 and closed in November 2017. Fifteen centers participated. Registration of 3523 ALK IHC tests revealed prevalence of 2.6% ALK IHC+ cases. Local ALK FISH analysis resulted in 46 concordant (ALK IHC+/FISH+) and 18 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 6 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The time to treatment failure did not differ for concordant nor discordant cases, and neither for local nor validated ALK testing (HR=0.78; 95% CI= 0.27-2.3; p=0.64) and (HR=2.2; 95% CI= 0.72-6.5; p=0.16), respectively). However, overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010), but not according to local testing (HR=1.7; 95% CI= 0.45-6.2; p=0.44).8eea62084ca7e541d918e823422bd82e Conclusion
ALK IHC+ FISH- NSCLC cases are an infrequent finding. We recommend such cases to be validated carefully because our data indicate that ALK IHC+ FISH- cases have a worse survival when treated by crizotinib compared to ALK IHC+ FISH+ cases.
This study was funded by an independent research grant by Pfizer6f8b794f3246b0c1e1780bb4d4d5dc53
MA26.07 - ROS1 (SP384) Immunohistochemistry Inter-Reader Precision Between 12 Pathologists (ID 12387)
14:10 - 14:15 | Author(s): Buge Aysim Oz
ROS1 positive non-small cell lung cancer (NSCLC) patients can be treated with specific tyrosine kinase inhibitors including crizotinib. ROS1 positivity is often clinically detected by fluorescence in situ hybridization (FISH), however ROS1 IHC can be used to screen samples prior to FISH confirmation of ROS1 status. The ROS1 (SP384) antibody detects ROS1 with high sensitivity, specificity, and consistency. Consistent interpretation of a ROS1 IHC assay between pathologists is important patient evaluation. Here we present inter-reader precision of 12 pathologists across 60 FFPE cases stained with ROS1 (SP384).a9ded1e5ce5d75814730bb4caaf49419 Method
A retrospective cohort of 60 FFPE NSCLC cases stained with H&E, Rabbit Monoclonal Negative Control Ig, and ROS1 (SP384) were selected to represent positive, negative, and borderline ROS1 IHC status. Twelve practicing lung pathologists independently scored the cases as positive or negative around a cutoff of cytoplasm staining in > 30% tumor cells at a ≥2+ intensity level using Pathotrainer software (Pathomation bvba). Scoring was blinded to other readers and ROS1 status of the cases. Overall percent agreement (OPA), negative percent agreement (NPA), and positive percent agreement (PPA) were calculated in comparison to the group mode. Average overall percent agreement (AOPA), average positive agreement (APA), and average negative agreement (ANA) were calculated pairwise for each reader pair. Following independent assessment, participating pathologists conducted a discordant case review establishing consensus reads for all 60 cases and compared 44 cases to available FISH results.4c3880bb027f159e801041b1021e88e8 Result
OPA of each of the 12 readers to the mode was 96.4% (95% CI 93.9-98.6) with PPA of 96.3% (95% CI 92.7-99.4) and NPA of 96.5% (95% CI 92.8-99.5). Pairwise AOPA between each of the 12 readers was 94.5% (95%CI 91.2-97.7) with APA 94.0% (95% CI 89.5-97.6) and ANA 95.0% (95%CI 91.2-97.9).
Consensus IHC scores were concordant with FISH 90.0% (40/44 cases).8eea62084ca7e541d918e823422bd82e Conclusion
Inter-reader precision around a cutoff of >30% tumor cells with cytoplasmic staining at a ≥2+ intensity level was high in interpreting ROS1 (SP384) in NSCLC samples. Case review highlighted confirmation with FISH in questionable cases and staining patterns to be considered when interpreting ROS1 (SP384) IHC.6f8b794f3246b0c1e1780bb4d4d5dc53
P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
P1.09-06 - The Incidence of PD-L1 in NSCLC and its Correlation with Driver Mutations in Turkish Patients; A Single Center Experience. (ID 12506)
16:45 - 18:00 | Presenting Author(s): Buge Aysim Oz
PD-L1 testing have become the new standard of care for patient diagnosis in advance Non-Small Cell Lung Carcinoma (NSCLC). NSCLC also is characterized by driver mutations in epidermal growth factor receptor (EGFR), alterations anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1). This study aimed to evaluate and to compare with immunotherapy related biomarker PD-L1 and driver mutations biomarkers (EGFR, ALK, and ROS1) in Turkish patients with NSCLC retrospectively. PD-L1 positivity also was examined whether related to some clinico-pathological parameters in NSCLC patients.a9ded1e5ce5d75814730bb4caaf49419 Method
A retrospective cohort composed of 650 consecutive patients diagnosis with NSCLC were tested for PD-L1 between November of 2016 and February of 2018. PD-L1 immunostaining was performed using and 22c3 (DAKO platform) or SP263 (Ventana platform). Pathology report were reviewed to collect patient demographic data, smoking status, tumor sup-types, and specimen types. For EGFR mutational analysis were examined using a real time assay (The cobas v2 ® EGFR Mutation Test). ALK and ROS1 translocations were evaluated by IHC + FISH method. For statistical analysis Pearson chi -square test was used.4c3880bb027f159e801041b1021e88e8 Result
Clinico-pathological characteristics of NSCLC patients (n=650) and their relationships with PD-L1 expression were presented on Table I.8eea62084ca7e541d918e823422bd82e Conclusion
This is the first study to compare PD-L1 expression with clinico-pathological parameters in Turkish NSCLC patients (n=650).
The majority of Turkish patients were smokers (85.6%). Although there was no statistical significance between PD-L1 positivity and smoking status, smoker patients showed more PD-L1 high tumor proportion score (H-TPS = ≥50%) than non-smoker patients; 29.4% to 16.9% respectively.
The majority of patients were Adenocarcinoma patients (63.8%).
PD-L1 positivity was higher in Non-adenocarcinoma patients than Adenocarcinomas (p=0.018).
This study demonstrated that PD-L1 positivity in lung adenocarcinoma, was strongly associated with EGFR wild-type status (p=0.002) which was parallel to literature.
There was no correlation between ALK and ROS1 translocation with PD-L1 status.6f8b794f3246b0c1e1780bb4d4d5dc53