Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons and protons remain elusive. We compared the differences in DNA double strand break (DSB) repair and survival of cells compromised in non-homologous end joining (NHEJ), homologous recombination repair (HRR) or both, after irradiation with an equal dose of X-ray photons, entrance plateau (EP) protons, and mid spread-out Bragg peak (SOBP) protons. We used super-resolution microscopy to investigate potential differences in spatial distribution of DNA damage foci upon irradiation. While DNA damage foci were equally distributed throughout the nucleus after X-ray photon irradiation, we observed more clustered DNA damage foci upon proton irradiation. Furthermore, deficiency in essential NHEJ proteins delayed DNA repair kinetics and sensitized cells to both, X-ray photon and proton irradiation, whereas deficiency in HRR proteins sensitized cells only to proton irradiation. We assume that NHEJ is indispensable for processing DNA DSB independent of the irradiation source, whereas the importance of HRR rises with increasing energy of applied irradiation.

Purpose/objective Quantification of surface dose within the first few hundred water equivalent µm is challenging. Nevertheless, it is of large interest for the proton therapy community to study dose effects in the skin. The experimental determination is affected by the detector properties, such as the detector volume and material. The International Commission on Radiation Units and Measurements in its report 39 recommends assessing the skin dose at a depth of 0.07 mm. The aim of this study is the estimation of the absorbed dose at and around a depth of 70 µm. We used various dosimetric approaches in conjunction with proton pencil beam scanning delivery to determine the skin dose in a clinical setting. Material/methods Five different detectors were tested for determining the surface dose in water: EBT3 and HD‐V2 GAFCHROMIC™ radiochromic film, LiF:Mg,Ti thermoluminescent dosimeter, IBA PPC05 plane‐parallel ionization chamber, and PTW 23391 extrapolation chamber. The irradiation setup consisted of quasi‐monoenergetic scanned proton pencil beams with kinetic energies of 100, 150, and 226.7 MeV, respectively. Radiochromic films were placed within a vertical stack and in wedge geometry and were analyzed with FilmQA Pro™ adopting triple channel dosimetry. The extrapolation chamber PTW 23391, which served as a reference in the current work, was used in a conventional ionization chamber setup with a fixed electrode gap of 2 mm. Three Kapton® entrance windows with thicknesses of 25, 50, and 75 µm were employed. Thermoluminescent dosimeters were provided as powder and were pressed onto a sheet of aluminum. Furthermore, the Monte Carlo code TOol for PArticle Simulation (TOPAS) in version 3.1.p2 was used to model an IBA pencil beam scanning nozzle and score dose to water in a water phantom. Results The resulting depth dose curves were normalized to their 100% dose at the reference depth of 3 cm. We obtained the skin doses with the extrapolation chamber and with TOPAS. For the experimental approach this resulted in 79.7 ± 0.3%, 86.0 ± 0.6%, and 87.1 ± 0.1% for the proton energies 100, 150, and 226.7 MeV, respectively. The results for TOPAS were 80.1 ± 0.2% (100 MeV), 87.1 ± 0.5% (150 MeV), and 86.9 ± 0.4% (226.7 MeV), respectively. Based on the experimental results of the skin dose, we provided a clinically relevant surface extrapolation factor for the common measurement methods. This allows the result of the first measurement depth of a detector to be scaled to the dose at the skin depth. Most practical would be the use of the surface extrapolation factor for the PPC05 chamber, due to its direct reading, the wide availability in clinics and the low uncertainties. The calculated factors were 0.986 ± 0.004 for 100 MeV, 0.961 ± 0.008 for 150 MeV, and 0.963 ± 0.003 for 226.7 MeV. Conclusions In this study, dissimilar experimental approaches were evaluated with respect to measurements at depths close to the surface. The experimental depth dose curves are in good agreement with the simulation with TOPAS Monte Carlo. To the author's...

Objective: Side effects of radiation therapy may include skin damage. The surface dose is of great interest and contains the buildup effect. In particular, the proton therapy community requires further experimental data to quantify doses in the surface region. This specification includes the skin dose, which is defined according to ICRU Report No. 39 at 70 μm water equivalent depth. The aim of this study is to gather more knowledge of the skin dose by varying key parameters defined by the patient treatment plan. This consists of clinical aspects such as the influence of the air gap, the application of a range shifter (RS), or the proton delivery technique. Material/methods: Skin doses were determined with a PTW 23391 extrapolation chamber with three thin Kapton ® entrance windows operated as a conventional ionization chamber. The impact on the skin dose for quasi-monoenergetic pencil beam scanning (PBS) proton beams was evaluated for clinical air gaps between 3.5 and 51.1 cm. The differences in skin dose were assessed by irradiating equivalent fields with an RS of 51 mm water equivalent thickness (RS51) and without. Furthermore, the delivery techniques PBS, uniform scanning (US), and double scattering (DS) were compared by defining a spread-out Bragg peak (SOBP). TOPAS (V.3.1.2) was used to model an IBA nozzle with PBS and to score dose to water at the surface of a water phantom. Results: For the monoenergetic fields without the application of the RS the skin dose was constant down to an air gap of 6.2 cm. A lower air gap of 3.5 cm showed a variation in skin dose by up to 2.4% compared to the results obtained with larger air gaps. With the inserted RS51 an increase in the skin dose was found for air gaps smaller than 11.3 cm. Experimentally, a dose difference of 1.4% was recorded for an air gap of 6.2 cm by inserting an RS and none. With the Monte Carlo calculations the largest dose increase was observed at the air gap of 3.5 cm with 1.7% and 4.0% relative to the skin dose results without the RS and to the largest evaluated air gap of 51.1 cm, respectively. The SOBP comparison of the beam modalities at the measuring plane at the isocenter revealed higher skin doses without RS (including RS) by up to +1.9% (+1.5%) for DS and +1.3% (+1.1%) for US compared to PBS. For all three techniques an approx. 2% rise in skin dose was observed for the largest evaluated air gap of 37.7 cm to an air gap of 6.2 cm when using an RS51. Conclusion: The study investigated aspects of skin dose of a water equivalent phantom by varying key parameters of a proton treatment plan. Parameters like the RS, the air gap, and the delivery modality have an impact on the order of 4.0% for the skin dose at the depth of 70 μm. The increases 831

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