Organotypic Slice Radiation Toxicity Assessment

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Solution Overview

Problem

Current methods for assessing radiation-induced toxicity in radiotherapy are inefficient and lack effective tools for predicting normal tissue reactions, leading to variations in treatment efficacy and limitations in radiation doses that can be administered, particularly due to the inability to accurately measure adverse reactions in healthy tissues.

Innovation Solution

The use of organotypic slices from healthy tissues, irradiated using various radiation therapies, with cell proliferation measured via assays like EdU incorporation to determine radiation-induced toxicity, allowing for personalized treatment planning and selection of suitable subjects for radiotherapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If radiation therapy is administered to treat tumors, then tumor control is improved, but normal tissue toxicity increases

Engineering Contradiction:
Improvetumor controlVSAvoidnormal tissue toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by performing ex vivo irradiation tests on patient-derived organoids before actual radiotherapy treatment. This pre-treatment assessment allows prediction of normal tissue toxicity responses, enabling clinicians to adjust treatment plans in advance to minimize harmful effects while maintaining tumor control efficacy.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If radiation dose is increased to improve tumor control, then treatment efficacy is improved, but normal tissue damage increases

Engineering Contradiction:
Improvetreatment efficacyVSAvoidnormal tissue damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by using ex vivo irradiation tests to determine individual patient sensitivity parameters. By measuring the actual response of patient-derived organoids to radiation at different doses, the system identifies optimal dose parameters that maximize tumor control while minimizing normal tissue damage for each patient-specific case.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If comprehensive normal tissue reaction assessment is performed, then personalized treatment accuracy is improved, but testing complexity increases

Engineering Contradiction:
Improvepersonalized treatment accuracyVSAvoidtesting complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies copying by creating ex vivo replicas (organoids) of patient-specific normal tissues. These copied tissue models allow comprehensive toxicity assessment in a controlled laboratory setting without requiring complex in vivo testing, thereby achieving high measurement precision for personalized treatment while reducing overall testing complexity.

Inventive Principle:
Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This method provides a rapid, reproducible, and sensitive assessment of radiation-induced toxicity, enabling personalized radiotherapy regimens that minimize harm to healthy tissues while maintaining treatment effectiveness, overcoming the limitations of existing methods by directly measuring cell proliferation in irradiated organotypic slices.

Implementation Method 1

RT is not specific to cancer cells, and radiation-induced cytotoxic effects occur both in the tumor and in normal tissues

Methodology Applied
Scientific EffectIonizing radiation: Radiation

Implementation Method 2

measuring cell proliferation after irradiation

Methodology Applied
Scientific EffectDNA synthesis:

Data Source

PatentEP4187245A1Methods for assessing the toxicity and efficacity of radiation therapy
Publication Date: 2023.05.31 INSTITUT CURIE
  • EP4187245A1 patent drawingFigure 1A~1B
  • EP4187245A1 patent drawingFigure 2A~2B
  • EP4187245A1 patent drawingFigure 3

AI summary

The invention relates to the field of radiotherapy and cancer prognosis, diagnosis and therapeutics. More particularly, the invention relates to methods for assessing radiation-induced toxicity and to methods for identifying and selecting subjects for treatment with radiation therapy. Also provided herein are methods for treating subjects who respond to radiation therapy and for determining the efficacy of such radiation therapy.