Thyroid Cancer Classification Algorithm Using BRAF V600E Mutation Testing

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Solution Overview

Problem

Current methods for diagnosing thyroid cancer, particularly for rare conditions like Hurthle cell adenomas and carcinomas, often result in inaccurate diagnoses leading to unnecessary surgeries and treatment complications due to the lack of efficient and accurate diagnostic tools.

Innovation Solution

A method involving the identification of the BRAFV600E mutation in fine needle aspiration samples using a trained algorithm, which is trained on expression levels of specific biomarkers, allowing for classification with a statistical confidence level of at least 95% to predict the presence or absence of thyroid cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional diagnostic methods are used for thyroid cancer, then the diagnostic process is simple, but the diagnosis accuracy is low leading to unnecessary surgeries

Engineering Contradiction:
Improvediagnosis accuracyVSAvoiddiagnostic method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The diagnostic process is segmented into multiple independent testing steps: initial cytology assessment, followed by selective molecular marker testing (BRAF V600E mutation, TERT promoter mutation, or integrated genomic classifier) only for indeterminate cases. This segmentation maintains simplicity for clear cases while providing high accuracy for ambiguous cases through targeted additional testing.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Molecular markers serve as intermediaries between cytology assessment and surgical decision-making. The BRAF V600E mutation test, TERT promoter mutation test, or integrated genomic classifier act as mediator tests that provide additional diagnostic information for indeterminate thyroid nodules, enabling more accurate classification without immediate surgery.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If more diagnostic tests are performed to improve accuracy, then unnecessary surgeries are reduced, but the time and cost of diagnosis increase

Engineering Contradiction:
Improvediagnosis reliabilityVSAvoiddiagnostic time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The diagnostic algorithm is dynamic and adaptive, adjusting the number and type of tests based on initial cytology results. Benign cases require only initial testing (minimal time), while indeterminate cases proceed to additional molecular marker testing (increased time for higher reliability). This dynamic approach ensures that diagnostic time is proportional to the uncertainty and potential risk of the case.

Inventive Principle:
Principle #15Dynamics

3Object-affected harmful factors

If traditional diagnostic methods are used, then the process is quick and simple, but unnecessary surgeries and treatment complications occur

Engineering Contradiction:
Improveunnecessary surgeries and complicationsVSAvoiddiagnostic algorithm complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The diagnostic process is segmented into multiple independent testing steps: initial cytology assessment, followed by selective molecular marker testing (BRAF V600E mutation, TERT promoter mutation, or integrated genomic classifier) only for indeterminate cases. This segmentation maintains simplicity for clear cases while providing high accuracy for ambiguous cases through targeted additional testing.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Molecular markers serve as intermediaries between cytology assessment and surgical decision-making. The BRAF V600E mutation test, TERT promoter mutation test, or integrated genomic classifier act as mediator tests that provide additional diagnostic information for indeterminate thyroid nodules, enabling more accurate classification without immediate surgery.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP2971164B1Methods and compositions for classification of samples
Publication Date: 2023.07.26 VERACYTE INC
  • EP2971164B1 patent drawingFigure 1A
  • EP2971164B1 patent drawingFigure 1B
  • EP2971164B1 patent drawingFigure 1C

AI summary

Disclosed herein are kits, compositions, and methods relating to the classification of samples. Methods disclosed herein can also be used to diagnose conditions or to support treatment-related decisions.