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
2273 - High performance of serial tumor biopsies in first in human (FIH) phase I trials.
Presenter: Jun Sato
Session: Poster Display session 1
Resources:
Abstract
5933 - Response rates and lesion-level progression patterns of solid tumor patients in an academic phase 1 program: implications for tumor heterogeneity
Presenter: Christopher Chen
Session: Poster Display session 1
Resources:
Abstract
3569 - Clinical Benefit and Response Rate in Early Phase Clinical Trials: First Report from a Single-Institution Study
Presenter: Antonio Marra
Session: Poster Display session 1
Resources:
Abstract
4139 - Patient (pt) selection for immunotherapeutic early-phase clinical trials (ieCTs): a single Phase I Unit experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
4451 - Improving patient selection for immuno-oncology phase 1 trials: an external validation of five prognostic scores at Claudius Regaud Institute of Toulouse, Oncopôle (IUCT-O).
Presenter: Ghassan Al Darazi
Session: Poster Display session 1
Resources:
Abstract
1696 - Demonstrating the Changing Trends in Phase 1 Clinical Trials
Presenter: Christina Guo
Session: Poster Display session 1
Resources:
Abstract
3202 - Participation of Women in phase 1 oncology clinical trials
Presenter: Laura Vidal
Session: Poster Display session 1
Resources:
Abstract
4518 - Predictors for early trial discontinuation of patients with cancer participating in phase I clinical trials
Presenter: Joeri Douma
Session: Poster Display session 1
Resources:
Abstract
4368 - Safety of Tumor Treating Fields delivery to the torso: Meta analysis from TTFields clinical trials
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract