Skin dose distributions between Stanford and rotational techniques in total skin electron therapy (TSET).

PURPOSE: Total skin electron therapy (TSET) has proven to be one of the most effective treatments for advanced-stage cutaneous T-cell lymphoma. Two most used techniques are the Stanford six-field and rotational techniques. This study compares patient skin dose distributions as a function of depth between these two techniques. METHODS: The EGSnrc system was used to simulate electron beams and calculate patient dose distributions. The calculations assumed the same patient standing on a platform, and the patient's different postures were ignored for the Stanford technique in the comparison of dose distributions. The skin doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms (DVH). The comparisons were performed in three realistic clinical settings in which dual-field were used for patients treated at extended distances of 316 and 500 cm, and a single field was used at 700 cm. In all cases the realistic patient treatment beam delivery geometry was simulated. RESULTS: Although small dose differences were observed in some local areas, no clinically significant differences were found in the patient 3D dose distributions between the Stanford and rotational techniques. Virtually the same DVH curves between two the techniques were observed for mean dose to skin depth of 0-5, 5-10, and 10-15 mm from the skin surface, respectively. It is found that the skin depth dose coverage is 2 mm shallower for patient treatment at 500 cm compared to at 316 cm due to the additional air attenuation. However, very similar dose coverage and uniformity can be achieved at these two different extended treatment distances by adjusting the thickness of acrylic scatter plate. Adequate thickness of a scattering plate improves the skin dose uniformity. CONCLUSION: Both the Stanford and rotational techniques deliver very similar skin dose coverage in DVH plots, and only small differences are seen in local areas. It is worth to emphasize that the DVH is a graphical representation of the distribution of dose within a structure, and it does not contain spatial information. Therefore, comparison of entire skin dose using DVH may mask some variations at different locations of the surface area. In addition, the comparison did not consider different patient postures of the Stanford technique. Including the different patient postures in the calculation may affect the result of doses to the limbs.

A general-purpose Monte Carlo particle transport code based on inverse transform sampling for radiotherapy dose calculation.

The Monte Carlo (MC) method is widely used to solve various problems in radiotherapy. There has been an impetus to accelerate MC simulation on GPUs whereas thread divergence remains a major issue for MC codes based on acceptance-rejection sampling. Inverse transform sampling has the potential to eliminate thread divergence but it is only implemented for photon transport. Here, we report a MC package Particle Transport in Media (PTM) to demonstrate the implementation of coupled photon-electron transport simulation using inverse transform sampling. Rayleigh scattering, Compton scattering, photo-electric effect and pair production are considered in an analogous manner for photon transport. Electron transport is simulated in a class II condensed history scheme, i.e., catastrophic inelastic scattering and Bremsstrahlung events are simulated explicitly while subthreshold interactions are subject to grouping. A random-hinge electron step correction algorithm and a modified PRESTA boundary crossing algorithm are employed to improve simulation accuracy. Benchmark studies against both EGSnrc simulations and experimental measurements are performed for various beams, phantoms and geometries. Gamma indices of the dose distributions are better than 99.6% for all the tested scenarios under the 2%/2 mm criteria. These results demonstrate the successful implementation of inverse transform sampling in coupled photon-electron transport simulation.

A PHASE II TRIAL OF BALLOON-CATHETER PARTIAL BREAST BRACHYTHERAPY OPTIMIZATION IN THE TREATMENT OF STAGE 0, I AND IIA BREAST CARCINOMA.

OBJECTIVES: (a) To prospectively determine if multidwell position dose delivery can decrease skin dose and resultant toxicity over single dwell balloon-catheter partial breast irradiation, and (b) to evaluate whether specific skin parameters could be safely used instead of skin-balloon distance alone for predicting toxicity and treatment eligibility. METHODS: A single-arm phase II study using a Simon two-stage design was performed on 28 women with stage 0-II breast cancer. All patients were treated with multiple dwell position balloon-catheter brachytherapy. The primary endpoint was ≥ grade 2 skin toxicity. Initial entry required a balloon-skin distance ≥ 7 mm. Based on the toxicity in the first 16 patients, additional patients were treated irrespective of skin-balloon distance as long as the Dmax to 1 mm skin thickness was < 130%. RESULTS: Compared to the phantom single dwell plans, multidwell planning yielded superior PTV coverage as per median V90, V95 and V100, but had slightly worse V150, V200 and DHI. Dmax to skin was decreased by multidwell planning at multiple skin thicknesses. The most common acute toxicity was grade 1 erythema (57%), and only two patients (7%) developed acute grade 2 toxicity (erythema). Late grade 1 fibrosis was seen in 32%. No patients experienced grade 3, 4, or 5 toxicity. CONCLUSIONS: Multidwell position planning for balloon-catheter brachytherapy results in lower skin doses with equal to superior PTV coverage and an overall low rate of initial skin toxicity. Our data suggest that limiting the Dmax to < 130% to 1 mm thick skin is achievable and results in minimal toxicity.

A molecular dynamics simulation of DNA damage induction by ionizing radiation.

We present a multi-scale simulation of the early stage of DNA damages by the indirect action of hydroxyl ((•)OH) free radicals generated by electrons and protons. The computational method comprises of interfacing the Geant4-DNA Monte Carlo with ReaxFF molecular dynamics software. A clustering method was employed to map the coordinates of (•)OH-radicals extracted from the ionization-track-structures onto nano-meter simulation voxels filled with DNA and water molecules. The molecular dynamics simulation provides the time-evolution and chemical reactions in individual simulation voxels as well as the energy-landscape accounted for the DNA-(•)OH chemical reaction that is essential for the first-principle enumeration of hydrogen abstractions, chemical bond breaks, and DNA-lesions induced by collection of ions in clusters less than the critical dimension which is approximately 2-3 Å. We show that the formation of broken bonds leads to DNA-base and backbone damages that collectively propagate to DNA single and double-strand breaks. For illustration of the methodology, we focused on particles with an initial energy of 1 MeV. Our studies reveal a qualitative difference in DNA damage induced by low energy electrons and protons. Electrons mainly generate small pockets of (•)OH-radicals, randomly dispersed in the cell volume. In contrast, protons generate larger clusters along a straight-line parallel to the direction of the particle. The ratio of the total DNA double-strand breaks induced by a single proton and electron track is determined to be ≈4 in the linear scaling limit. In summary, we have developed a multi-scale computational model based on first-principles to study the interaction of ionizing radiation with DNA molecules. The main advantage of our hybrid Monte Carlo approach using Geant4-DNA and ReaxFF is the multi-scale simulation of the cascade of both physical and chemical events which result in the formation of biological damage. The tool developed in this work can be used in the future to investigate the relative biological effectiveness of light and heavy ions that are used in radiotherapy.

Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia.

PURPOSE: Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. METHODS AND MATERIALS: A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. RESULTS: Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 µm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. CONCLUSIONS: Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia.

A novel modified dynamic conformal arc technique for treatment of peripheral lung tumors using stereotactic body radiation therapy.

PURPOSE: To describe and compare a novel, modified dynamic conformal arc (MDCA) technique for lung stereotactic body radiation therapy with the standard noncoplanar beam (NCB) technique based on stereotactic body radiation therapy (SBRT) coverage, dose conformality, normal tissue constraints, and treatment time. MATERIALS AND METHODS: Twenty consecutive medically inoperable patients with early stage, peripheral, non-small cell lung cancer treated with SBRT using an NCB technique were re-planned with a novel MDCA technique. Treatment plans were compared based on Radiation Therapy Oncology Group (RTOG) 0236 criteria for planning treatment volume (PTV) coverage and normal tissue dose constraints, as well as high- and moderate-dose conformality. Treatment times necessary to deliver the NCB plans were compared with the times of a separate group of 12 consecutive patients treated with the MDCA technique at our institution. RESULTS: The MDCA technique resulted in improved coverage of the cranial and caudal regions of the PTV and generated plans that were significantly more conformal by all high-dose criteria proposed by the RTOG protocol. In terms of moderate-dose criteria, MDCA plans had a significantly lower maximum dose (2 cm from the PTV), whereas the ratio of the 50% dose volume to the volume of the PTV was equivalent between the 2 techniques. All normal tissue dose constraints proposed in the RTOG 0236 protocol were met by each plan, although the median lung V20 and mean lung dose were slightly higher in the MDCA plans, whereas the chest wall dose was slightly lower. A 42% reduction in treatment time was observed when patients treated with the NCB technique were compared with a separate cohort of 12 patients treated with the MDCA technique (P < .0001). CONCLUSIONS: The new MDCA technique described in this study resulted in enhanced PTV coverage, improved high- and moderate-dose conformality, simplified treatment planning, and reduced treatment time compared with results using the standard NCB technique.