Tumor Treating Fields and PULSAR for Adaptive Radiotherapy
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Solution Overview
Problem
Conventional radiotherapy treatments are rigid and lack personalization, often leading to over or under-treatment due to inflexible fractionation schedules and inadequate adaptation to tumor changes during treatment, while tumor treating fields (TTFields) have shown potential synergies with radiation but require innovative combinations for enhanced efficacy.
Innovation Solution
Combining TTFields with Personalized Ultra-fractionated Adaptive Radiotherapy (PULSAR), which involves applying TTFields at specific frequencies and intervals, along with DNA-damaging agents and immune checkpoint inhibitors, to create conditional vulnerabilities and adapt treatment based on real-time tumor and patient responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional fractionated radiotherapy is administered daily or near-daily over 4-6 weeks, then radiation doses can be delivered to control or kill malignant cells, but the treatment lacks personalization and adaptability to tumor changes
Solution Approach 1:
The patent implements dynamic treatment adaptation by allowing modification of radiation parameters (dose, fractionation schedule, target volume) based on real-time tumor response assessment. Treatment plans are no longer static but evolve throughout the 4-6 week course, with re-imaging and re-planning capabilities built into the workflow to capture tumor shrinkage or changes in morphology, thereby achieving personalization without excessive complexity
Solution Approach 2:
The system incorporates feedback mechanisms through regular tumor assessment (imaging, biomarkers) during treatment. This feedback loop enables clinicians to adjust treatment parameters based on actual tumor response, transforming the rigid conventional approach into an adaptive process that personalizes therapy to each patient's unique tumor biology and response pattern
2Object-affected harmful factors
If split-course radiotherapy with rest periods is used to reduce toxicity to normal tissue, then normal tissue can heal, but tumor control is compromised due to tumor proliferation during rest periods
Solution Approach 1:
The patent employs periodic ultra-fractionated radiation doses interspersed with brief intervals, creating a rhythm of treatment that allows normal tissue recovery while maintaining continuous pressure on tumor cells. This periodic approach with optimized timing prevents tumor repopulation during rest periods while still providing adequate normal tissue repair time, resolving the contradiction between toxicity reduction and tumor control
Solution Approach 2:
The system changes the temporal parameters of radiation delivery by using ultra-fractionated dosing schedules with variable intervals between fractions. By adjusting the timing, duration, and dose per fraction based on tumor type and location, the treatment optimizes the balance between allowing normal tissue healing and preventing tumor regrowth during treatment breaks
3Productivity
If conventional fractionated radiotherapy is delivered over short time frames, then treatment can be completed quickly, but there is insufficient time for tumor or microenvironment changes that might influence treatment adaptation
Solution Approach 1:
The patent implements periodic assessment points throughout the treatment course where tumor response is evaluated. These scheduled evaluation moments provide structured opportunities to observe tumor and microenvironment changes without significantly extending overall treatment time. The periodic nature allows accumulation of sufficient data for adaptation decisions while maintaining efficient treatment delivery
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 approach enhances radiosensitization and induces synergistic cell killing, effectively delaying tumor growth and increasing sensitivity to radiation, while allowing for personalized and adaptive treatment strategies.
Implementation Method 1
Tumor treating fields (TTFields) are low intensity alternating electric fields within the intermediate frequency range
Implementation Method 2
TTFields are induced non-invasively into a region of interest by transducers placed directly on the patient's body and applying AC voltages between the transducers
Implementation Method 3
The radiation is typically administered with a linear accelerator and is used to control or kill malignant cells that make up a tumor
Implementation Method 4
delivering agents that cause DNA damage, inhibit DNA replication fork progress or maintenance, or cause DNA replication fork collapse
Implementation Method 5
This approach enhances radiosensitization and induces synergistic cell killing, effectively delaying tumor growth and increasing sensitivity to radiation
Data Source
AI summary
A method of treating a tumor in a subject, the method comprises applying a tumor treating field to the tumor at a frequency between approximately 50 kHz and approximately 1,000 kHz; and delivering personalized ultra-fractionated adaptive radiotherapy (PULSAR) regimen.