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Purpose A relative biological effectiveness (RBE) of 1.1 is commonly used in clinical proton therapy, irrespective of tissue type and depth. This in vitro study was conducted to quantify the RBE of scanned protons as a function of the dose-averaged linear energy transfer (LETd ) and the sensitivity factor (α/s)X . Additionally, three phenomenological models (McNamara, Rorvik, and Jones) and one mechanistic model (repair-misrepair-fixation, RMF) were applied to the experimentally derived data. Methods Four human cell lines (FaDu, HaCat, Du145, SKMel) with differential (α/s)X ratios were irradiated in a custom-designed irradiation setup with doses between 0 and 6 Gy at proximal, central, and distal positions of a 80 mm spread-out Bragg peak (SOBP) centered at 80 mm (setup A: proton energies 66.5-135.6 MeV) and 155 mm (setup B: proton energies 127.2-185.9 MeV) depth, respectively. LETd values at the respective cell positions were derived from Monte Carlo simulations performed with the treatment planning system (TPS, RayStation). Dosimetric measurements were conducted to verify dose homogeneity and dose delivery accuracy. RBE values were derived for doses that resulted in 90 % (RBE90 ) and 10 % (RBE10 ) of cell survival, and survival after a 0.5 Gy dose (RBE0.5Gy ), 2 Gy dose (RBE2Gy ), and 6 Gy dose (RBE6Gy ). Results LETd values at sample positions were 1.9, 2.1, 2.5, 2.8, 4.1, and 4.5 keV/µm. For the cell lines with high (α/s)X ratios (FaDu, HaCat), the LETd did not impact on the RBE. For low (α/s)X cell lines (Du145, SKMel), LQ-derived survival curves indicated a clear correlation of LETd and RBE. RBE90 values up to 2.9 and RBE10 values between 1.4 and 1.8 were obtained. Model-derived RBE predictions slightly overestimated the RBE for the high (α/s)X cell lines, although all models except the Jones model provided RBE values within the experimental uncertainty. For low (α/s)X cell lines, no agreement was found between experiments and model predictions, that is, all models underestimated the measured RBE. Conclusions The sensitivity parameter (α/s)X was observed to be a major influencing factor for the RBE of protons and its sensitivity toward LETd changes. RBE prediction models are applicable for high (α/s)X cell lines but do not estimate RBE values with sufficient accuracy in low (α/s)X cell lines.

Background/aim Two-thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced (LA) stages and have a poor survival rate. The aim of this study was to investigate the roles of the long non-coding RNAs MALAT1 on radiation and cisplatin sensitivity of HNSCC cells. Materials and methods Clonogenic, cell viability, and apoptosis assays were performed in cells following MALAT1 knockdown using CRISPR/Cas9 system. Results MALAT1 was overexpressed in HNSCC cell lines as compared to a non-tumorigenic cell line. The number of colonies formed after radiation was significantly reduced in MALAT1 knockdown cells. The IC50 value of cisplatin in MALAT1 knockdown cells was lower than that of the control cells. MALAT1 knockdown resulted in cell cycle arrest at G2/M phase, DNA damage and apoptotic cell death. Conclusion MALAT1 knockdown enhanced the sensitivity of HNSCC cells to radiation and cisplatin partly through the induction of G2/M cell cycle arrest resulting in DNA damage and apoptosis.

Purpose In-vitro radiobiological studies are essential for modelling the relative biological effectiveness (RBE) in proton therapy. The purpose of this study was to experimentally determine the RBE values in proton beams along the beam path for human prostate carcinoma cells (Du-145). RBE-dose and RBE-LETd (dose-averaged linear energy transfer) dependencies were investigated and three phenomenological RBE models, i.e. McNamara, Rorvik and Wilkens were benchmarked for this cell line. Methods Cells were placed at multiple positions along the beam path, employing an in-house developed solid phantom. The experimental setup reflected the clinical prostate treatment scenario in terms of field size, depth, and required proton energies (127.2–180.1 MeV) and the physical doses from 0.5 to 6 Gy were delivered. The reference irradiation was performed with 200 kV X-ray beams. Respective (α/β) values were determined using the linear quadratic model and LETd was derived from the treatment planning system at the exact location of cells. Results and Conclusion Independent of the cell survival level, all experimental RBE values were consistently higher in the target than the generic clinical RBE value of 1.1; with the lowest RBE value of 1.28 obtained at the beginning of the SOBP. A systematic RBE decrease with increasing dose was observed for the investigated dose range. The RBE values from all three applied models were considerably smaller than the experimental values. A clear increase of experimental RBE values with LETd parameter suggests that proton LET must be taken into consideration for this low (α/β) tissue.

Purpose: This study is to evaluate the difference between two QA IMRT techniques(single‐gantry‐angle composite and patient‐gantry angle) of patient delivery plan. Methods: 7 Head‐and‐Neck(H&N) and 4 BrainIMRT patient plan generated by Varian‐Eclipse treatment planning system are used in this study. Each patient plan was measured using MapCheck diode array(MapCheck2, SunNuclear) with 1527 diode detector. MapCheck array is mounted on the isocentric mounting fixture (IMF) attached to the gantry used for measuring dose. All measurement of two QA IMRT technique with single‐gantry‐angle composite at 0 degree gantry position and patient gantry angle were compared to the TPS dose plane using gamma evaluation. Gamma criteria are set to 3% dose difference and 3 mm distance to agreement(DTA) and 10% threshold criteria for dose comparison. Difference between two QA techniques was evaluated by using the percentage of passing point between measurement and TPS dose plan. Results: The percentage of passing point are different between two QA IMRT technique in the same patient plan. The difference of both relative and absolute pass rate range between 0 to 3% for Head and neck plan and 0– 1.5% for brain plan respectively. Almost all the relative pass rate and absolute pass rate of single‐gantry‐angle composite are higher than patient‐ gantry angle technique in the same plan. The different result of pass rate between two techniques due to the effect of gantry machine and MLC moving in gravity. Other issues might relate to set‐up uncertainty of measurement. The dominant gantry angle dependence is larger in complex H&N IMRT plan with large high dose gradient and smaller in brainIMRT plan. Conclusions: Because of gantry angle dependence, in complex IMRT patient plan should be verified by using patient gantry angle technique in order to achieve the QA result with real situation of patient IMRTtreatment.

Purpose: To commissioningRadCalc program for secondary point dose check in conventional 2D and 3DCRT calculation techniques. Methods: Test plans for 6 MV and 10 MV photon beams with conventional and 3DCRT planwere created inRadCalc program.Field was varied with a range of field sizes and modifier techniques referred to IAEA‐TECDOC‐1583 with central axis and off central axis calculation points. The measured dose for each field was then compared to the calculated dose (RadCalc program and Eclipse treatment planning system). Results: In conventional field validation,RadCalc shows good agreement with measured doses.For open and almost all wedge fields, RadCalccalculationagree with dose measurement within +/−1%. Differences of over 1% were found in maximum wedge fields and some half fields. However, the dose difference between calculation and measurementwas within +/−2% in all tests. In 3DCRT plan validation, the central axis point dose between calculation and measurement in all tests are agree within the IAEA‐TECDOC‐1583 criteria. When measured/ calculated dose points were in non‐tissue equivalent such as lung and bone which were off central axis situation, dose difference is more than +/−10%. Unfortunately if measured/ calculated dose points areoutside the field (scatter dose), the result cannot be validated. Part of this large difference between two calculated and measured can be the volume effect of the chamber.In comparison between dose calculated by RadCalc and Eclipse, overall results show dose difference within +/−5%. Conclusions: RadCalc program can be used as a point dose calculation check in conventional 2D and 3DCRT techniques.