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Artificial Intelligence-Powered Human Epidermal Growth Factor Receptor 2 Quantification and Clinical Outcomes in
Hongsik Kim1, Chiyoon Oum2, Soo Ick Cho2
1Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea.
Purpose:
Despite recent advances in anti-human epidermal growth factor receptor 2 (HER2) treatments for HER2-positive biliary tract cancer (BTC), current guidelines lack clear thresholds for defining HER2 positivity in BTC. This study investigated the use of artificial intelligence (AI) to analyze HER2 expression and immune phenotypes (IP) in patients with HER2-positive BTC treated with anti-HER2 therapy.
Materials And Methods:
We conducted a post hoc analysis of a phase II trial (KCSG HB19-14) of trastuzumab plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) for HER2-positive BTC. AI-powered HER2 quantification and IP analyses were performed on whole-slide images of pretreatment samples. Clinical outcomes were analyzed on the basis of HER2 positivity using a continuous AI-based HER2 immunohistochemistry scoring system. Additionally, we evaluated the spatial distribution of tumor-infiltrating lymphocytes using AI-based IP analysis.
Results:
Among 29 patients, the overall concordance rate between pathologists and the HER2-AI analyzer was 79.1%. AI-defined HER2-positivity status, characterized by a ≥30% H3 tumor cell proportion threshold, significantly predicted improved outcomes with trastuzumab plus FOLFOX (progression-free survival: 6.7 v 4.9 months, P = .039; overall survival: not reached v 8.4 months, P = .018). By contrast, traditional pathologist-based scoring did not stratify outcomes. AI-powered immune profiling revealed that HER2 3+ tumors predominantly exhibited immune-desert phenotypes, whereas HER2 2+ tumors displayed more inflamed phenotypes, potentially limiting the efficacy of current immunotherapy regimens for HER2 3+ BTC.
Conclusion:
AI-powered HER2 quantification provides a refined biomarker for predicting the response to HER2-targeted therapies in BTC, proposing a ≥30% HER2 3+ tumor cell proportion threshold. Our findings highlight the potential of combining anti-HER2 therapy with immune checkpoint inhibitors on the basis of IP profiles.
Insights
Artificial intelligence (AI) can precisely define human epidermal growth factor receptor 2 (HER2) positivity in biliary tract cancer (BTC), improving treatment outcomes. This AI approach offers a better biomarker than traditional methods for predicting response to HER2-targeted therapies.
Area of Science:
- Oncology
- Biomarker Discovery
- Artificial Intelligence in Medicine
Background:
- Current guidelines lack clear thresholds for human epidermal growth factor receptor 2 (HER2) positivity in biliary tract cancer (BTC).
- Anti-HER2 therapies have advanced treatment for HER2-positive BTC, but precise patient selection remains a challenge.
Purpose of the Study:
- To investigate the utility of artificial intelligence (AI) in analyzing HER2 expression and immune phenotypes (IP) for HER2-positive BTC patients receiving anti-HER2 therapy.
- To establish AI-driven thresholds for HER2 positivity to predict treatment response.
Main Methods:
- Post hoc analysis of a phase II trial (KCSG HB19-14) involving trastuzumab plus FOLFOX for HER2-positive BTC.
- AI-powered quantification of HER2 expression and immune profiling on whole-slide images of pretreatment tumor samples.
- Evaluation of clinical outcomes based on AI-defined HER2 positivity and spatial distribution of tumor-infiltrating lymphocytes.
Main Results:
- AI-defined HER2 positivity (≥30% tumor cell proportion) significantly predicted improved progression-free survival (6.7 vs 4.9 months) and overall survival (not reached vs 8.4 months) with trastuzumab plus FOLFOX.
- Traditional pathologist-based scoring did not stratify outcomes, unlike the AI-based continuous scoring system.
- AI immune profiling indicated distinct immune phenotypes between HER2 3+ (immune-desert) and HER2 2+ (inflamed) tumors, suggesting implications for immunotherapy efficacy.
Conclusions:
- AI-powered HER2 quantification offers a refined biomarker for predicting response to HER2-targeted therapies in BTC, proposing a ≥30% HER2 3+ tumor cell proportion threshold.
- Findings suggest potential for combining anti-HER2 therapy with immune checkpoint inhibitors, guided by AI-derived immune profiling.
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