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Irradiator Commissioning and Dosimetry for Assessment of LQ α and β Parameters, Radiation Dosing Schema, and in vivo Dose Deposition
Published on: March 11, 2021
Is there a selection bias in radiotherapy dose-escalation protocols?
Elisabeth Weiss1, Viswanathan Ramakrishnan, Paul J Keall
1Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298, USA. eweiss@mcvh-vcu.edu
Summary
Radiotherapy dose escalation trials can have selection bias. Patients eligible for higher doses in this virtual trial showed better outcomes, suggesting a need for bias mitigation strategies in clinical research.
Area of Science:
- Radiation oncology
- Clinical trial design
- Cancer treatment optimization
Background:
- Dose-escalation trials in radiotherapy aim to increase tumor dose while maintaining normal tissue constraints.
- Increasing tumor dose can conflict with normal tissue tolerance, potentially introducing selection bias.
- Investigating selection bias is crucial for accurate interpretation of dose-escalation trial results.
Purpose of the Study:
- To investigate the presence and impact of selection bias in a virtual radiotherapy dose-escalation trial.
- To compare outcomes between patients eligible for all dose levels and those eligible only for lower doses.
- To identify methods for mitigating selection bias in dose-escalation studies.
Main Methods:
- A virtual dose-escalation trial was conducted for 9 non-small-cell lung cancer patients.
- Tumor dose was escalated from 66 Gy to 78 Gy using intensity-modulated radiotherapy.
- Dosimetric and radiobiologic parameters were compared between patients eligible for all dose levels (Group E) and those eligible only for lower doses (Group I).
Main Results:
- Seven patients (Group E) were eligible for all dose levels, while two (Group I) were not.
- Group E had smaller planning target volumes, significantly lower monitor units per fraction, and better plan quality scores.
- Group E demonstrated higher predicted tumor control probabilities and lower predicted normal tissue complication probabilities compared to Group I.
Conclusions:
- Patients eligible for higher radiation doses in dose-escalation trials exhibit superior estimated outcome parameters.
- This suggests a significant selection bias that can influence trial interpretation.
- A methodology to eliminate this source of error in dose-escalation trials is proposed.
