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  • American Society of Clinical Oncology (ASCO)  (3)
  • Ma, Minuk  (3)
  • 2020-2024  (3)
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Publisher
  • American Society of Clinical Oncology (ASCO)  (3)
Language
Years
  • 2020-2024  (3)
Year
Subjects(RVK)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e13578-e13578
    Abstract: e13578 Background: The MET proto-oncogene is involved in tumorigenesis and progression and has emerged as an attractive targetable genomic alteration in NSCLC. However, it has not been actively tested in NSCLC due to the lack of a cost-effective screening tool. We developed a deep-learning based model to predict genomic profiles from H & E WSI and applied it to MET pathologic mutations in NSCLC. The prediction model is based on an ensemble model trained not solely on H & E images but also on multi-layered semantic contents that were produced by a pre-trained AI analyzer, Lunit SCOPE IO. Methods: The model was trained on the MET aberration (exon 14 skipping, n=191; pathogenic mutation, n=109) and paired wild-type dataset (n=500). To extract deep features from raw H & E images, a self-supervised vision transformer was used, and an AI-based pathology profiling analyzer extracted semantic contents such as the spatial information of tumor cells, lymphocytes, cancer epithelium, and cancer stroma. A set of classifiers was trained based on the two features, and the ensemble of these features was used to improve robustness. Following cross-validation, the model was applied to an independent clinical dataset with MET sequencing results from The Cancer Genome Atlas (TCGA) LUAD and LUSC datasets (n=914), Samsung Medical Center (SMC, n=361), and Chonnam National University Hospital (CNUH, n=54). Results: The best cross-validation performances of the models predicting MET aberration measured by mean area under the receiver operating characteristic curve (AUROC) were 0.772 when trained by only H & E images (HE-only), 0.788 by AI semantic content with MLP classifier (AISC-MLP), and 0.803 by AISC with random forest (AI-RF), respectively. An ensemble of the three models showed an increased AUROC of 0.837 in the training dataset by cross-validation. These models were applied to the external validation dataset (n=1,329), including 20 (1.5%) MET exon 14 skipping and known pathologic mutations. The mean AUROC to predict MET aberration by the ensemble model was 0.817 with 95% sensitivity, 64.7% specificity. The AUROC of TCGA, SMC, and CNUH cohorts were 0.815, 0.802, and 0.812, respectively. Conclusions: An AI-based ensemble model combining H & E images with semantic contents extracted from pre-developed AI models significantly improved the accuracy and robustness of MET pathogenic mutation prediction using an H & E sample in NSCLC. These findings allow for cost-effective screening for MET alterations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 17 ( 2022-06-10), p. 1916-1928
    Abstract: Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI). METHODS We have developed an artificial intelligence (AI)–powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non–small-cell lung cancer (NSCLC). RESULTS Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists ( P 〈 .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at 〈 1%, 1%-49%, and ≥ 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP. CONCLUSION The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e21179-e21179
    Abstract: e21179 Background: PD-L1 tumor proportion score (TPS) is the only biomarker for clinical decision-making regarding immunotherapy (IO) in advanced NSCLC. Currently, there is uncertainty when selecting treatment options between IO monotherapy (IO-only) and in combination with chemotherapy (Chemo-IO) when solely based on PD-L1, in patients with PD-L1 TPS ≥ 50%. Here, we explored a novel biomarker, immune phenotype as assessed by artificial intelligence (AI)-powered spatial tumor infiltrating lymphocytes (TIL) analysis to provide additional information in determining first-line treatment for advanced NSCLC, using a real-world dataset. Methods: A total of 349 whole-slide images (WSIs) of H & E-stained slides for advanced/metastatic NSCLC patients without actionable EGFR mutation and ALK translocation treated with IO-only or Chemo-IO as their first-line were retrospectively collected from Samsung Medical Center. An AI-powered spatial TIL analyzer, Lunit SCOPE IO classified inflamed immune phenotype (IIP, the proportion of inflamed area ≥ 33.3% in tumor microenvironment) versus non-inflamed IP (non-IIP). PD-L1 TPS was assessed based on PD-L1 pharmDx 22C3 staining. Progression-free survival (PFS) was measured by the investigators per RECIST v1.1. Results: In the analysis set, all IO-only group (n = 84) had TPS ≥ 50%, but Chemo-IO group (n = 265) consisted of 21.1%, 29.8%, and 49.1% of TPS ≥ 50%, 1-49%, and 〈 1%, respectively. Proportions of squamous cell carcinoma were not significantly different between IO-only and Chemo-IO (32.1% vs 27.5%, p = 0.5008). Proportions of IIP were significantly correlated with the TPS group, as they were 33.6%, 19.0%, and 13.1% in TPS ≥ 50%, 1-49%, and 〈 1%, respectively (p = 0.0002). In the merged dataset (n = 349), PFS was significantly increased in IIP (22.6%) compared to non-IIP (median PFS [mPFS] 14.6 vs 6.0 m, 6-m PFS rate 72.1% vs 49.9%, hazard ratio [HR, 95% confidence interval] 0.57 [0.39-0.82], p = 0.0014). In TPS ≥ 50% group, IIP was significantly correlated with favorable PFS in IO-only group (IIP vs non-IIP; mPFS 14.6 vs 4.6 m, 6-m rate 65.5 vs 45.2%, HR 0.55 [0.31-0.98] , p = 0.0375), however, it was not statistically different in Chemo-IO (n = 56, mPFS not reached [NR] vs 8.3 m, 6-m rate 88.5 vs 65.3%, HR 0.45 [0.15-1.33] , p = 0.1185). Interestingly, in the subgroup of TPS ≥ 50% with IIP (n = 47), PFS was not significantly different based on treatment regimen (Chemo-IO vs IO-only, mPFS NR vs 14.6 m, 6-m rate 88.5 vs 65.5%, HR 0.52 [0.17-1.59], p = 0.2263), but Chemo-IO was significantly superior to IO-only in TPS ≥ 50% with non-IIP group (n = 93, mPFS 8.3 vs 4.6 m, 6-m rate 65.3 vs 45.2%, HR 0.53 [0.30-0.94] , p = 0.0255). Conclusions: Immune Phenotype based on AI-powered spatial TIL analysis may provide complementary information for clinical decision-making between IO-only and Chemo-IO in advanced NSCLC patients with TPS ≥ 50%.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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