Cellular Damage in the Target and Out-Of-Field Peripheral Organs during VMAT SBRT Prostate Radiotherapy: An In Vitro Phantom-Based Study.

Hypo-fractionated stereotactic body radiation therapy (SBRT) is an effective treatment for prostate cancer (PCa). Although many studies have investigated the effects of SBRT on the prostate and adjacent organs, little is known about the effects further out-of-field. The aim of this study was to investigate, both in vitro and in a quasi-humanoid phantom, the biological effects (using a dose-scaling approach) of radiation in the out-of-field peripheral organs delivered by 6 MV volumetric modulated arc therapy (VMAT) SBRT in a prostate cancer model. Healthy prostate cells were irradiated in a phantom at locations corresponding to the prostate, intestine, lung, thyroid, and brain. Seven 10 Gy fractions of VMAT SBRT were delivered to the target in a single session without intermission (scaled-up method). Radiochromic films were used to measure the doses. The radiobiological response was assessed by measuring DNA breaks, the cell survival fraction, and differences in gene expression profile. Our results showed a strong, multiparametric radiobiological response of the cells in the prostate. Outside of the radiation field, the highest doses were observed in the intestine and lung. A small increase (not statistically significant) in DNA damage and cell death was observed in the intestines. Several gene groups (cell cycle, DNA replication) were depleted in the lung and thyroid (DNA replication, endocytosis), but further analysis revealed no changes in the relevant biological processes. This study provides extensive evidence of the types and extent of radiobiological responses during VMAT SBRT in a prostate cancer model. Additional research is needed to determine whether the radiobiological effects observed in the peripheral organs are validated in a clinical context.

Nontarget and Out-of-Field Doses from Electron Beam Radiotherapy.

In clinical radiotherapy, the most important aspects are the dose distribution in the target volume and healthy organs, including out-of-field doses in the body. Compared to photon beam radiation, dose distribution in electron beam radiotherapy has received much less attention, mainly due to the limited range of electrons in tissues. However, given the growing use of electron intraoperative radiotherapy and FLASH, further study is needed. Therefore, in this study, we determined out-of-field doses from an electron beam in a phantom model using two dosimetric detectors (diode E and cylindrical Farmer-type ionizing chamber) for electron energies of 6 MeV, 9 MeV and 12 MeV. We found a clear decrease in out-of-field doses as the distance from the field edge and depth increased. The out-of-field doses measured with the diode E were lower than those measured with the Farmer-type ionization chamber at each depth and for each electron energy level. The out-of-field doses increased when higher energy megavoltage electron beams were used (except for 9 MeV). The out-of-field doses at shallow depths (1 or 2 cm) declined rapidly up to a distance of 3 cm from the field edge. This study provides valuable data on the deposition of radiation energy from electron beams outside the irradiation field.

Influence of Specific Treatment Parameters on Nontarget and Out-of-Field Doses in a Phantom Model of Prostate SBRT with CyberKnife and TrueBeam.

The aim of the study was to determine the influence of a key treatment plan and beam parameters on overall dose distribution and on doses in organs laying in further distance from the target during prostate SBRT. Multiple representative treatment plans (n = 12) for TrueBeam and CyberKnife were prepared and evaluated. Nontarget doses were measured with anionization chamber, in a quasi-humanoid phantom at four sites corresponding to the intestines, right lung, thyroid, and head. The following parameters were modified: radiotherapy technique, presence or not of a flattening filter, degree of modulation, and use or not of jaw tracking function for TrueBeam and beam orientation set-up, optimization techniques, and number of MUs for CyberKnife. After usual optimization doses in intestines (near the target) were 0.73% and 0.76%, in head (farthest from target) 0.05% and 0.19% for TrueBeam and CyberKnife, respectively. For TrueBeam the highest peripheral (head, thyroid, lung) doses occurred for the VMAT with the flattening filter while the lowest for 3DCRT. For CyberKnife the highest doses were for gantry with caudal direction beams blocked (gantry close to OARs) while the lowest was the low modulated VOLO optimization technique. The easiest method to reduce peripheral doses was to combine FFF with jaw tracking and reducing monitor units at TrueBeam and to avoid gantry position close to OARs together with reduction of monitor units at CyberKnife, respectively. The presented strategies allowed to significantly reduce out-of-field and nontarget doses during prostate radiotherapy delivered with TrueBeam and CyberKnife. A different approach was required to reduce peripheral doses because of the difference in dose delivery techniques: non-coplanar using CyberKnife and coplanar using TrueBeam, respectively.

Development of a quasi-humanoid phantom to perform dosimetric and radiobiological measurements for out-of-field doses from external beam radiation therapy.

Our understanding of low dose, out-of-field radiation and their radiobiological effects are limited, in part due to the rapid technological advances in external beam radiotherapy, especially for non-coplanar and dynamic techniques. Reliable comparisons of out-of-field doses produced by advanced radiotherapy techniques are difficult due to the limitations of commercially available phantoms. There is a clear need for a functional phantom to accurately measure the dosimetric and radiobiological characteristics of out-of-field doses, which would in turn allow clinicians and medical physicists to optimize treatment parameters. We designed, manufactured, and tested the performance of a quasi-humanoid (Q-H) adult phantom. To test the physics parameters, we used computed tomography (CT) scans of assembled Q-H phantom. Static open field and dynamic techniques were measured both in- and out-of-field with ionization chambers and radiochromic films for two configurations (full solid and with water-filled containers). In the areas simulating soft tissues, lung, and bones, median Hounsfield units and densities were, respectively: 129.8, -738.7, 920.8 HU and 1.110, 0.215, 1.669 g/cm3 . Comparison of the measured to treatment planning systems (TPS) in-field dose values for the sample volumetric arc therapy (VMAT) (6 MV flattening filter-free (FFF)) plan, 96.4% of analyzed points passed the gamma evaluation criteria (L2%/2 mm, threshold (TH) 10%) and less than 1.50% for point dose verification. In the two phantom configurations: full poly(methyl) methacrylate (PMMA) and with water container, the off-axis median doses for open field, relative to the central axis of the beam (CAX) were similar, respectively: 0.900% versus 0.907% (15 cm distance to CAX); 0.096% versus 0.120% (35 cm); 0.018% versus 0.018% (52 cm); 0.009% versus 0.008% (74 cm). For VMAT 6 MV FFF, doses relative the CAX were, respectively: 0.667% (15 cm), 0.062% (35 cm), 0.019% (52 cm), 0.016% (74 cm). The Q-H phantom meets the International Commission on Radiation Units and Measurements (ICRU) and American Association of Physicists in Medicine (AAPM) recommended phantom criteria, providing medical physicists with a reliable, comprehensive system to perform dose calculation and measurements and to assess the impact on radiobiological response and on the risk of secondary tumor induction.