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
1613 - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: initial Phase 1b results
Presenter: David Berz
Session: Poster Display session 1
Resources:
Abstract
2853 - Real-world implementation of sequential targeted therapies for EGFR-mutated NSCLC
Presenter: Petros Christopoulos
Session: Poster Display session 1
Resources:
Abstract
1974 - A Phase II Open-Label, Multicentre Study to Assess the Anti-tumour Activity of Afatinib in Patients with Activating Epidermal Growth Factor Receptor mutation (EGFRm) from Circulating Tumor DNA (CtDNA)
Presenter: Young-Chul Kim
Session: Poster Display session 1
Resources:
Abstract
3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients
Presenter: Geerten Veerman
Session: Poster Display session 1
Resources:
Abstract
5900 - PTEN loss as Predictor of Tumor Heterogeneity (TH) and Poor Prognosis in EGFR-mutant Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients (pts) Receiving Tyrosine-Kinase Inhibitors (TKIs).
Presenter: Miriam Ferrara
Session: Poster Display session 1
Resources:
Abstract
1302 - Safety of lorlatinib in subgroups of patients from a phase 1/2 trial
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
1497 - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase 2 ALTA trial
Presenter: Dae Ho Lee
Session: Poster Display session 1
Resources:
Abstract
2349 - The safety assessment of crizotinib and alectinib from real world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L).
Presenter: Kei Kunimasa
Session: Poster Display session 1
Resources:
Abstract
1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study
Presenter: Silvia Novello
Session: Poster Display session 1
Resources:
Abstract
5239 - Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in US clinical practice
Presenter: Matthew Krebs
Session: Poster Display session 1
Resources:
Abstract