Linear energy transfer incorporated intensity modulated proton therapy optimization. 2017

Wenhua Cao, and Azin Khabazian, and Pablo P Yepes, and Gino Lim, and Falk Poenisch, and David R Grosshans, and Radhe Mohan
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America. Author to whom any correspondence should be addressed.

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

UI MeSH Term Description Entries
D011879 Radiotherapy Dosage The total amount of radiation absorbed by tissues as a result of radiotherapy. Dosage, Radiotherapy,Dosages, Radiotherapy,Radiotherapy Dosages
D011880 Radiotherapy Planning, Computer-Assisted Computer-assisted mathematical calculations of beam angles, intensities of radiation, and duration of irradiation in radiotherapy. Computer-Assisted Radiotherapy Planning,Dosimetry Calculations, Computer-Assisted,Planning, Computer-Assisted Radiotherapy,Calculation, Computer-Assisted Dosimetry,Calculations, Computer-Assisted Dosimetry,Computer Assisted Radiotherapy Planning,Computer-Assisted Dosimetry Calculation,Computer-Assisted Dosimetry Calculations,Dosimetry Calculation, Computer-Assisted,Dosimetry Calculations, Computer Assisted,Planning, Computer Assisted Radiotherapy,Radiotherapy Planning, Computer Assisted
D012062 Relative Biological Effectiveness The ratio of radiation dosages required to produce identical change based on a formula comparing other types of radiation with that of gamma or roentgen rays. Biological Effectiveness, Relative,Effectiveness, Biologic Relative,Effectiveness, Biological Relative,Relative Biologic Effectiveness,Biologic Effectiveness, Relative,Biologic Relative Effectiveness,Biological Relative Effectiveness,Effectiveness, Relative Biologic,Effectiveness, Relative Biological,Relative Effectiveness, Biologic
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D058958 Organs at Risk Organs which might be damaged during exposure to a toxin or to some form of therapy. It most frequently refers to healthy organs located in the radiation field during radiation therapy. Organs at Risks,Risk, Organs at,Risks, Organs at,at Risk, Organs,at Risks, Organs
D061766 Proton Therapy The use of an external beam of PROTONS as radiotherapy. Proton Beam Radiation Therapy,Proton Beam Therapy,Proton Beam Therapies,Proton Therapies,Therapies, Proton,Therapies, Proton Beam,Therapy, Proton,Therapy, Proton Beam
D018499 Linear Energy Transfer Rate of energy dissipation along the path of charged particles. In radiobiology and health physics, exposure is measured in kiloelectron volts per micrometer of tissue (keV/micrometer T). Energy Transfer, Linear,LET,Transfer, Linear Energy

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