期刊
MEDICAL PHYSICS
卷 45, 期 7, 页码 3466-3474出版社
WILEY
DOI: 10.1002/mp.12988
关键词
dosimetry planning; normal tissue complication probability; normal tissue toxicity reduction; temporally feathered radiation therapy; therapeutic ratio
资金
- German Federal Ministry of Education and Research (BMBF) [01ZX1308D]
- Helmholtz Association of German Research Centers - Initiative and Networking Fund for the project on Reduced Complexity Models [ZT-I-0010]
- NIH Loan Repayment Program
- Andrew Sabin Family Foundation
- Sabin Family Foundation
- National Institutes of Health (NIH), the National Institute for Dental and Craniofacial Research Award [1R01DE025248-01/R56DE025248-01]
- National Science Foundation (NSF), Division of Mathematical Sciences, Joint NIH/NSF Initiative on Quantitative Approaches to Biomedical Big Data (QuBBD) [NSF 1557679]
- NIH Big Data to Knowledge (BD2K) Program of the National Cancer Institute (NCI) Early Stage Development of Technologies in Biomedical Computing, Informatics, and Big Data Science Award [1R01CA214825-01]
- NCI Early Phase Clinical Trials in Imaging and Image-Guided Interventions Program [1R01CA218148-01]
- NIH/NCI Cancer Center Support Grant (CCSG) Pilot Research Program Award from the UT MD Anderson CCSG Radiation Oncology and Cancer Imaging Program [P30CA016672]
- NIH/NCI Head and Neck Specialized Programs of Research Excellence (SPORE) Developmental Research Program Award [P50 CA097007-10]
- Elekta AB
PurposeIntensity-modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy temporally feathered radiation therapy (TFRT). MethodsTemporally feathered radiotherapy plans were generated as a composite of five simulated treatment plans each with altered constraints on particular hypothetical organs at risk (OARs) to be delivered sequentially. For each of these TFRT plans, OARs chosen for feathering receive higher doses while the remaining OARs receive lower doses than the standard fractional dose delivered in a conventional fractionated IMRT plan. Each TFRT plan is delivered a specific weekday, which in effect leads to a higher dose once weekly followed by four lower fractional doses to each temporally feathered OAR. We compared normal tissue toxicity between TFRT and conventional fractionated IMRT plans by using a dynamical mathematical model to describe radiation-induced tissue damage and repair over time. ResultsModel-based simulations of TFRT demonstrated potential for reduced normal tissue toxicity compared to conventionally planned IMRT. The sequencing of high and low fractional doses delivered to OARs by TFRT plans suggested increased normal tissue recovery, and hence less overall radiation-induced toxicity, despite higher total doses delivered to OARs compared to conventional fractionated IMRT plans. The magnitude of toxicity reduction by TFRT planning was found to depend on the corresponding standard fractional dose of IMRT and organ-specific recovery rate of sublethal radiation-induced damage. ConclusionsTFRT is a novel technique for treatment planning and optimization of therapeutic radiotherapy that considers the nonlinear aspects of normal tissue repair to optimize toxicity profiles. Model-based simulations of TFRT to carefully conceptualized clinical cases have demonstrated potential for radiation-induced toxicity reduction in a previously described dynamical model of normal tissue complication probability (NTCP).
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