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Dongmei Lin
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MA15 - Usage of Computer and Molecular Analysis in Treatment Selection and Disease Prognostication (ID 141)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:John Le Quesne, Noriko Motoi
- Coordinates: 9/09/2019, 15:45 - 17:15, Tokyo (1982)
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MA15.02 - Deep Learning Approach for Automated Tumor Cells Detection and Estimation of PD-L1 22C3 Assay Expression in Lung Adenocarcinoma (Now Available) (ID 577)
15:45 - 17:15 | Author(s): Dongmei Lin
- Abstract
- Presentation
Background
It is vital and challenging to assess an accurate PD-L1 expression status on tumor cells for immunotherapy in lung cancer. The purpose of this study was to set up an automated system to detect the tumor cells and estimate the tumor proportion score (TPS) of PD-L1 immunohistochemistry (IHC) expression for lung adenocarcinoma based on deep learning, and provide a potential Artificial Intelligences (AI) assistive diagnostic tool in the quantification of PD-L1 interpretation.
Method
Fifty PD-L1 22C3 IHC slides of lung adenocarcinoma samples on digitized whole-slide images (WSI) database was employed. We first designed a model with a fully convolutional neural network (FCNN) based on U-ResNet architecture to obtain the cancer segmentation. Representative regions were selected from each slide, and 100 regions were collected for manual annotations as a training set for cancer detection. Another 50 regions were used to validate the performance of automated cancer detection and TPS estimation as a test set. After the quality control, a whole model of automated cancer cell segmentation and membrane positive estimation was set up on standard PD-L1 22C3 IHC staining. TPS could be automatically predicted by AI tool and then compared with the interpretations of pathologists.
Result
The results of automated lung adenocarcinoma cells segmentation on the test set of 22C3 IHC staining showed a moderate sensitivity (71.46%) with a high specificity (95.94%) which was much more crucial for TPS counting. In rest 43 out of 50 regions after a quality control, TPS estimated by the automated PD-L1 analysis based on cancer segmentation showed a significant correlation with the average scores (r=0.9609, p<0.001) and the median scores (r=0.9523, p<0.001) of pathologists' interpretations.
Conclusion
We provide an automated tumor cells detection and TPS estimation model for lung adenocarcinoma and demonstrate the potential of using machine learning methods to access PD-L1 IHC status conveniently. A further validation of AI tool for automated scoring PD-L1 in diagnostic routine is highly recommended in the future.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-14 - Evaluation on Inter-Assay Consistency and Inter-Reader Precision for PD-L1 Assays: Ventana SP263 and Dako 22C3 in Non-Small Cell Lung Cancer (Now Available) (ID 536)
10:15 - 18:15 | Author(s): Dongmei Lin
- Abstract
Background
FDA has approved several anti-PD1/PD-L1 checkpoint inhibitors for the treatment of a variety of cancers. It has been shown the expression level of PD-L1 in NSCLC tumor cells is associated with the response to anti-PD-1/PD-L1 treatment. Currently, five anti-PD1/PD-L1 inhibitors have been approved for either as a companion diagnostic (e.g., pembrolizumab) or as complementary diagnostic (e.g., nivolumab, atezolizumab and durvalumab). The blueprint studies and several others have reported the concordance on different PD-L1 IHC assays, however, few Chinese samples were included for assay consistence study; in addition, it remains unclear how these two assays perform in inter-reader variability of pathologists in China.
Method
Surgical specimens from 48 NSCLC patients were selected for PD-L1 IHC by Ventana SP263 and Dako 22C3. Tumor proportion scores (TPS) were interpreted by three pathologists from three centers. Inter-assay consistency were evaluated by Kappa test at different cut-off value (1%, 25%, and 50%) for each pathologist; and inter-reader precision were performed by Kendall’s W test for Ventana SP263 and Dako 22C3, respectively.
Result
1) Inter-assay consistency: When TPS were categorized as <1%, 1% to 24%, ≥25% , the overall agreement percentage (OPA) between two IHC assays was 81.25% observed by Pathologist A（κ=0.710）, 89.6% observed by Pathologist B (κ=0.84) and 79.2% observed by Pathologist C （κ=0.684）; If the TPS were categorized as <1%, 1% to 50%, ≥50%, the OPA were 81.25%, 93.75% and 85.4% (κ= 0.675, 0.899 and 0.760), respectively. 2) Inter-reader precision: The interpretation results on Ventana SP263 by three pathologists were consistent, when TPS was categorized as <1%, 1% to 49%, ≥50% (p=0.017) or <1%, 1% to 24%, ≥25% (p=0.047) respectively; the consistency was not optimal, when TPS was further categorized with narrower groups as <1%, 1% to 24%, 25% to 49%, ≥50% (p=0.065). The interpretation results of Dako 22C3 were inconsistent among three observers in all categories above, with all p values greater than 0.05.
Conclusion
1) The inter-assay consistency of PD-L1 assays is high between Ventana SP263 and Dako 22C3; 2) The interpretation results of Ventana SP263 is more consistent among different observers.
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P2.09-21 - A Prospective Study of the Concordance for PD-L1 Status in Core Needle Biopsy and Corresponding Resection Specimen in NSCLC (Now Available) (ID 576)
10:15 - 18:15 | Author(s): Dongmei Lin
- Abstract
Background
Some studies have demonstrated a relatively poor concordance of PD-L1 IHC expression between biopsies and corresponding resection specimens. To address this central and relevant issue having a significant impact on treatment stratification for patients with NSCLC, we evaluated a novel method to compare and evaluate PD-L1 status in biopsies and resection samples.
Method
Randomly core needle aspiration biopsy was performed in 170 resected NSCLC samples with 1 to 2 biopsies per centimeter in longest diameter of tumor. Among these 170 cases, a total of 52 cases were selected for the study. 41 cases were characterized as PD-L1 positive as a PD-L1 TPS≥ 1%), 1 case which the TPS<1% resected specimen with obvious stained tumor area and randomly 10 specimens being PD-L1 negative. In total 221 biopsies were available for the 52 resection cases. The PD-L1 expression in resected specimens and corresponding biopsies were evaluated by the PD-L1 IHC 22C3 pharmDx assay (Agilent) on the Dako Autostainer.
Result
In our investigation, the concordance of PD-L1 status in biopsy and resection was not influenced by number of tumor cells at 1% and 50% cut-off’s. The length of biopsy improves concordance of PD-L1 status but is not statistically significant (table 1). In figure 1. under 1% cut-off, the PD-L1 status in biopsy and resection is concordant irrespective of biopsies density, whereas the density of biopsies improves the concordance for 50% cut-off. The threshold was 1 per centimeter in longest diameter of tumor.
Conclusion
The concordance between biopsy and resected specimen is related to the length, density of biopsy and the clinical cutoff. Increasing the biopsy density will improve accuracy of PD-L1 detection.
