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P.A. Russell
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-047 - Intra- and Inter-Observer Reproducibility Study of PD-L1 Biomarker in Non-Small Cell Lung Cancer (NSCLC) - The DREAM STUDY (ID 4297)
14:30 - 14:30 | Author(s): P.A. Russell
- Abstract
Background:
PD-L1 expression in NSCLC correlates with increased response to pembrolizumab, supporting its role as a predictive biomarker but the reproducibility of pathologists’ scoring of PD-L1 requires further investigation. The primary objective of the DREAM study was to assess the reproducibility of scoring PD-L1 staining by evaluating intra- and inter-observer reproducibility for the assessment of PD-L1 expression in NSCLC. The secondary objective was to assess the impact of training on reproducibility.
Methods:
The study was a blinded, pathologist reproducibility study of scoring PD-L1 expression in NSCLC cases stained with PD-L1 22C3 pharmDx™ kit using the Dako Automated Link 48 Platform. Two pathologists previously trained and certified by Dako scored 789 specimens to form the gold standard. From these specimens 60 were randomly selected to evaluate a 1% cut-point and 60 for a 50% cut-point. Both sample sets were designed to include 50% positive/negative specimens and 20-30 close to each cut-point. Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all samples on two consecutive days. Subgroup 2 performed the same assessments, except they received a one hour training session prior to the second assessment.
Results:
The overall percent agreement (OPA) for the analysis of the intra-observer reproducibility was 89.7% (95% CI: 85.7; 92.6) for the 1% cut-point sample set and 91.3% (95% CI: 87.6; 94.0) for the 50% cut-point. The OPAs for inter-observer reproducibility of all ten pathologists were 84.2% (95% CI: 82.8; 85.5) and 81.9% (95% CI: 80.4; 83.3) for the 1% and 50% cut-point sample sets, respectively. There was substantial agreement at both the 1% cut-point (prevalence-adjusted bias-adjusted kappa 0.68 (95% CI: 0.65; 0.71)) and the 50% cut-point (prevalence-adjusted bias-adjusted kappa 0.64 (95% CI: 0.61; 0.67)). Training was found to have no or very little impact on the inter- or intra-observer reproducibility in subgroup 2. The OPAs for the inter-observer reproducibility assessments were 82.0% and 82.3% for the first and second assessments of the 1% cut-point sample set, respectively, and 78.3% and 81.7% for the first and second assessments of the 50% cut-point sample set, respectively. The exploratory analyses showed that the sensitivity and specificity of the pathologists assessments, compared with the gold standard assessment, were 84.3% and 91.3%, respectively, for the 1% cut-point and 56.3% and 94.0%, respectively, for the 50% cut-point.
Conclusion:
There is high intra-observer reproducibility and substantial inter-observer agreement in pathologists’ assessment of PD-L1 expression in NSCLC at 1% and 50% cut-points.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-021 - Reproducibility of Comprehensive Histologic Assessment and Refining Histologic Criteria in P Staging of Multiple Tumour Nodules (ID 5365)
14:30 - 14:30 | Author(s): P.A. Russell
- Abstract
Background:
Multiple tumor nodules (MTNs) are being encountered, with increasing frequency with the 8[th] TNM staging system recommending classification as separate primary lung cancers (SPLC) or intrapulmonary metastases (IM). Pathological staging requires assessment of morphological features, with criteria of Martini and Melamed supplanted by comprehensive histologic assessment of tumour type, predominant pattern, other histologic patterns and cytologic features. With publication of the 2015 WHO classification of lung tumours, we assessed the reproducibility of comprehensive histologic assessment and also sought to identify the most useful histological features.
Methods:
We conducted an online survey in which pathologists reviewed a sequential cohort of resected multifocal tumours to determine whether they were SPLC, IM, or a combination. Specific histological features for each nodule were entered into the database by the observing pathologist (tumour type, predominant adenocarcinoma pattern, and histological features including presence of lepidic growth, intra-alveolar cell clusters, cell size, mitotic rate, nuclear pleomorphism, nucleolar size and pleomorphism, nuclear inclusions, necrosis pattern, vascular invasion, mucin content, keratinization, clear cell change, cytoplasmic granules¸ lymphocytosis, macrophage response, acute inflammation and emperipolesis). Results were statistically analyzed for concordance with submitting diagnosis (gold standard) and among pathologists. Consistency of each feature was correlated with final determination of SPLC vs. IM status (p staging) by chi square analysis and Fisher exact test.
Results:
Seventeen pathologists evaluated 126 tumors from 48 patients. Kappa score on overall assessment of primary v. metastatic status was 0.60. There was good agreement as measured by Cohen’s Kappa (0.64, p<0.0001) between WHO histological patterns in individual cases with SPLC or IM status but proportions for histology and SPT or IM status were not identical (McNemar's test, p<0.0001) and additional histological features were assessed. There was marked variation in p values among the specific histological features. The strongest correlations (<0.05) between p staging status and histological features were with nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intra-alveolar clusters and necrosis pattern. Correlation between lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization and emperipolesis did not reach a p value of 0.05.
Conclusion:
Comprehensive histologic assessment shows good reproducibility between practicing lung pathologists. In addition to main tumour type and predominant patterns, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate appear to be useful in distinguishing between SPLC and IM.
