Continuous Immune Context Scoring for Stage III Colorectal Cancer
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Solution Overview
Problem
Existing methods for assessing immune cell infiltrate in colorectal cancer are not quantitative, relying on binary scoring systems that compromise accuracy and lead to mis-prognosis and missed treatment opportunities.
Innovation Solution
A method using a continuous scoring function, such as a Cox proportional hazard model, to calculate an immune context score (ICS) based on the density of CD3+ cells in tumor tissue sections, allowing for a more accurate assessment of immune cell infiltration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If binary scoring systems (Jass score, Klintrup-Mäkinen grade, Galon IMMUNOSCORE) are used to assess immune cell infiltrate, then the assessment process is simplified and easier to perform, but measurement precision and prognostic accuracy deteriorate
Solution Approach 1:
The patent transforms the assessment from discrete binary categories (present/absent, low/high) to continuous quantitative parameters by counting actual immune cell densities per high-power field and calculating standardized scores. This parameter change enables precise measurement while maintaining operational feasibility through automated or semi-automated counting methods.
Solution Approach 2:
The patent replaces manual binary scoring with automated image analysis systems that digitally quantify immune cell infiltrate. This substitution uses computer vision and algorithms to objectively count cells and generate continuous scores, eliminating subjectivity and improving measurement precision while reducing operational complexity.
2Measurement precision
If continuous scoring function (Cox proportional hazard model) is used to calculate immune context score, then prognostic accuracy and treatment selection precision are improved, but device complexity and computational requirements increase
Solution Approach 1:
The patent segments the complex continuous scoring process into distinct manageable components: (1) immune cell detection and counting in specific tumor regions, (2) calculation of cell densities per high-power field, (3) application of standardized scoring formulas, and (4) integration into prognostic models. This segmentation makes the complex system more manageable and implementable.
Solution Approach 2:
The patent introduces standardized intermediate scoring metrics (immune cell density per high-power field, standardized immune score) that serve as mediators between raw cell counts and final prognostic predictions. These intermediaries simplify the computational process and make the system more interpretable while maintaining prognostic accuracy.
Data Source
AI summary
Immune context scores are calculated for stage III colorectal tumor tissue samples using continuous scoring functions. Feature metrics for at least one immune cell marker are calculated for a region or regions of interest, the feature metrics including at least a density of human CD3+ cells in a region of interest including an invasive margin. A continuous scoring function is then applied to a feature vector, the output of which is an immune context score. The immune context score may then be plotted as a function of a diagnostic or treatment metric, such as a prognostic metric (e.g. overall survival, disease-specific survival, progression-free survival) or a predictive metric (e.g. likelihood of response to a particular treatment course). The immune context score may then be incorporated into diagnostic and/or treatment decisions.