Abstract
The response to radiotherapy can vary greatly among individuals, even though advances in technology allow for the highly localized placement of therapeutic doses of radiation to a tumor. This variability in patient response to radiation is biologically driven, but the individuality of tumor and healthy tissue biology are not used to create individual treatment plans. Biomarkers of radiosensitivity, whether intrinsic or from hypoxia, would move radiation oncology from precision medicine to precise, personalized medicine. Charged particle radiotherapy allows for even greater dose conformity, but the biological advantages of charged particle radiotherapy have not yet been cultivated. The development of biomarkers that would drive biologically based clinical trials, identify patients for whom charged particles are most appropriate, or aid in particle-selection strategies could be envisioned with appropriate biomarkers. Initially, biomarkers for low-linear energy transfer (LET) radiation responses should be tested against charged particles. Biomarkers of tumor radioresistance to low-LET radiations could be used to identify patients for whom the enhanced relative biological effectiveness (RBE) of charged particles would be more effective compared with low-LET radiations and those for whom specific DNA-repair inhibitors, in combination with charged particles, may also be appropriate. Furthermore, heavy charged particles can overcome the radioresistance of hypoxic tumors when used at the appropriate LET. Biomarkers for hypoxia could identify hypoxic tumors and, in combination with imaging, define hypoxic regions of a tumor for specific ion selection. Moreover, because of the enhanced RBE for charged particles, the risk for adverse healthy tissue effects may be greater, even though charged particles have greater tumor conformality. There are many validated healthy-tissue biomarkers available to test against charged particle exposures. Lastly, newer biological techniques, as well as newer bioinformatic and computational methods, are rapidly changing the landscape for biomarker identification, validation, and clinical trial design.
Highlights
In biology and medicine, biomarker describes a biological indicator of a normal or particular pathogenic biological process, such as an indicator of a disease or disease subtype, a prognostic indicator for the response to treatment irrespective of the therapy, or an indicator for choosing a specific therapy, for example
A cautionary note: because of the potential to combine immunotherapy with conventional x-ray therapy, stereotactic ablative radiotherapy, or charged particle radiotherapy—the latter 2 employing high-dose limited-fractionation schemes—it may be especially prudent to consider single-nucleotide polymorphisms (SNPs) biomarkers of adverse healthy-tissue response found in genes that are associated with or drive inflammatory and immune responses
The biologic basis for charged-particle radiotherapy trials is the physics of the interaction of charged particles with biologic materials compared with x-rays
Summary
Biomarker describes a biological indicator of a normal or particular pathogenic biological process, such as an indicator of a disease or disease subtype, a prognostic indicator for the response to treatment irrespective of the therapy, or an indicator for choosing a specific therapy, for example. Many researchers use biomarker as shorthand to describe an association with a phenotype. The regional definitions for biomarkers are similar. In the United States, biomarker is defined by the US
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