Abstract 3456
Background
Tumor pathologists classify tumors according to cell-level and tissue-level criteria, using molecular markers in addition to morphological patterns, as reported in WHO tumor classifications. Their work describes to some extent both inter-tumor and intra-tumor heterogeneity, but it is a tedious task with potential reproducibility issues. The molecular subtyping of tumors represents a sometimes parallel and sometimes convergent effort to describe the heterogeneity of tumors. It is automated, which attenuates the limitations of pathological scoring mentioned above, but so far it is poorly adapted to describe intra-tumor heterogeneity.
Methods
We propose a novel method, WISP (Weighted In Silico Pathology), which finely measures intra-tumor heterogeneity by automatically estimating the proportions of cell types present in a bulk tumor sample, these cell types being predefined based on histological or high-throughput molecular criterions.
Results
We illustrate the relevance of our approach in several tumor types including lung cancer, glioblastoma and pancreatic cancer. We show that the cell types that describe tumors for a given cancer type can fairly well recapitulate existing molecular classifications and are very consistent with an independent pathological scoring. We show that our method offers a more standardized and finer-grained solution for describing tumor heterogeneity than either pathological scoring or molecular subtyping. More importantly, we show that the proportion of certain cell types is strongly associated to prognosis and drug response.
Conclusions
This study provides a framework for standardized molecular pathology and fully reshapes the way in which we think about pathology or molecular subtyping. We believe that our results are a proof of concept demonstrating the importance of considering cell types intra-tumor proportions for personalized clinical care.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
CIT Program - Ligue Contre le Cancer.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2045 - The analysis of treatment sequences and clinical outcomes of thymic carcinoma
Presenter: Arakaki Motoko
Session: Poster Display session 1
Resources:
Abstract
4785 - Transcriptomic Difference of Thymoma and Thymic Carcinoma
Presenter: Naixin Liang
Session: Poster Display session 1
Resources:
Abstract
2864 - A Phase II Trial of Preoperative Chemoradiotherapy and Pembrolizumab for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Presenter: Seoyoung Lee
Session: Poster Display session 1
Resources:
Abstract
5015 - The study of tumor associated exosomes in crosstalk between esophageal carcinoma and lymphatic endothelial cells
Presenter: Weimin Mao
Session: Poster Display session 1
Resources:
Abstract
1339 - Up-regulation of IBSP expression predicts poor prognosis of Esophageal Squamous Cell Carcinoma patients
Presenter: Mingyue Wang
Session: Poster Display session 1
Resources:
Abstract
4083 - PD-L1 expression in primary tumour vs metastatic samples in the Phase 3 MYSTIC study in first-line metastatic (m) NSCLC
Presenter: Niels Reinmuth
Session: Poster Display session 1
Resources:
Abstract
5113 - Assessing the impact of subsequent checkpoint inhibitor (CPI) treatment on overall survival: post hoc analyses from the phase 3 JAVELIN Lung 200 study of avelumab vs docetaxel in platinum-treated locally advanced/metastatic non-small cell lung cancer (NSCLC)
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
4256 - Long-term avelumab treatment in patients with advanced non-small cell lung cancer (NSCLC): post hoc analyses from JAVELIN Solid Tumor
Presenter: Borys Hrinczenko
Session: Poster Display session 1
Resources:
Abstract
4305 - Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
5128 - IO-Synthesise NSCLC: A pooled analysis of real-world survival outcomes for non-small cell lung cancer patients treated with nivolumab in France and Germany
Presenter: Adrien Dixmier
Session: Poster Display session 1
Resources:
Abstract