Search

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.

Objective The purpose of this study was to develop a model using dose volume histogram (DVH) and dosiomic features to predict the risk of radiation pneumonitis (RP) in the treatment of esophageal cancer with radiation therapy and to compare the performance of DVH and dosiomic features after adjustment for the effect of fractionation by correcting the dose to the equivalent dose in 2 Gy (EQD2). Materials and methods DVH features and dosiomic features were extracted from the 3D dose distribution of 101 esophageal cancer patients. The features were extracted with and without correction to EQD2. A predictive model was trained to predict RP grade ≥ 1 by logistic regression with L1 norm regularization. The models were then evaluated by the areas under the receiver operating characteristic curves (AUCs). Result The AUCs of both DVH-based models with and without correction of the dose to EQD2 were 0.66 and 0.66, respectively. Both dosiomic-based models with correction of the dose to EQD2 (AUC = 0.70) and without correction of the dose to EQD2 (AUC = 0.71) showed significant improvement in performance when compared to both DVH-based models. There were no significant differences in the performance of the model by correcting the dose to EQD2. Conclusion Dosiomic features can improve the performance of the predictive model for RP compared with that obtained with the DVH-based model.

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

Modern radiotherapy (RT) uses altered fractionation, long beam-on time and image-guided procedure. This study aimed to compare secondary cancer risk (SCR) associated with primary field, scatter/leakage radiations and image-guided procedure in prostate treatment using intensity-modulated RT (IMRT), CyberKnife stereotactic body RT (CK-SBRT) in relative to 3-dimensional conformal RT (3D-CRT). Prostate plans were generated for 3D-CRT, IMRT (39 fractions of 2 Gy), and CK-SBRT (five fractions of 7.25 Gy). Excess absolute risk (EAR) was calculated for organs in the primary field using Schneider’s mechanistic model and concept of organ equivalent dose (OED) to account for dose inhomogeneity. Doses from image-guided procedure and scatter/leakage radiations were determined by phantom measurements. The results showed that hypofractionation relative to conventional fractionation yielded lower SCR for organs in primary field (p ≤ 0.0001). SCR was further modulated by dose-volume distribution. For organs near the field edge, like the rectum and pelvic bone, CK-SBRT plan rendered better risk profiles than IMRT and 3D-CRT because of the absence of volume peak in high dose region (relative risk [RR]: 0.65, 0.22, respectively, p ≤ 0.0004). CK-SBRT and IMRT generated more scatter/leakage and imaging doses than 3D-CRT (p ≤ 0.0002). But primary field was the major contributor to SCR. EAR estimates (risk contributions, primary field: scatter/leakage radiations: imaging procedure) were 7.1 excess cases per 104 person–year (PY; 3.64:2.25:1) for CK-SBRT, 9.93 (7.32:2.33:1) for IMRT and 8.24 (15.99:2.35:1) for 3D-CRT (p ≤ 0.0002). We conclude that modern RT added more but small SCR from scatter/leakage and imaging doses. The primary field is a major contributor of risk which can be mitigated by the use of hypofractionation.

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.

Recently, a new type of radiochromic film, the EBT-XD film, has been introduced for high dose radiotherapy. The EBT-XD film contains the same structure as the EBT3 film but has a slightly different composition and a thinner active layer. This study benchmarks the EBT-XD against EBT3 film for 6 MV and 10 MV photon beams, as well as for 97.4 MeV and 148.2 MeV proton beams and 15-100 kV x-rays. Dosimetric and film reading characteristics, such as post irradiation darkening, film orientation effect, lateral response artifact (LRA), film sensitivity, energy and beam quality dependency were investigated. Furthermore, quenching effects in the Bragg peak were investigated for a single proton beam energy for both film types, in addition measurements were performed in a spread-out Bragg peak. EBT-XD films showed the same characteristic on film darkening as EBT3. The effects between portrait and landscape orientation were reduced by 3.1% (in pixel value) for EBT-XD compared to EBT3 at a dose of 2000 cGy. The LRA is reduced for EBT-XD films for all investigated dose ranges. The sensitivity of EBT-XD films is superior to EBT3 for doses higher than 500 cGy. In addition, EBT-XD showed a similar dosimetric response for photon and proton irradiation with low energy and beam quality dependency. A quenching effect of 10% was found for both film types. The slight decrease in the thickness of the active layer and different composition configuration of EBT-XD resulted in a reduced film orientation effect and LRA, as well as a sensitivity increase in high-dose regions for both photon and proton beams. Overall, the EBT-XD film improved regarding film reading characteristics and showed advantages in the high-dose region for photon and proton beams.

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.

To determine the chest wall movement of each patient during deep inspiratory breath hold (DIBH) and expiratory breath hold (EBH) in postoperative breast cancer patients. Postoperative breast cancer patients who underwent CT simulation for 3D radiotherapy treatment planning during December 2012 to November 2013 were included. Before scanning the radio-opaque wire was placed on the surface for breast and chest wall visualization on CT images, then the patient underwent three phases of CT scanning (free breathing, DIBH, and EBH, respectively). The distances of chest wall motion at five reference points were calculated using the treatment planning system. 38 breast cancer patients who underwent surgery were included. Median age was 48.5 (28-85) years. Median BMI was 23.4 (16.6-38.3) kg/m(2). Median lung volume was 3160.5 (1830.8-4754.0) cm(3). Median Haller index was 2.43 (1.92-3.56). Median chest wall movement was wider in anteroposterior (A-P, 4.2-5.4 mm) than superoinferior (S-I, 2.5-2.6 mm) and mediolateral (M-L, 0.6-1.1 mm) dimension in all five measured points. There was no significant effect of the type of surgery, BMI, lung volume, and the Haller index on the distances of chest wall movement. Additional margins of 7, 5, and 2 mm to the A-P, S-I, and M-L dimension should adequately cover the extreme chest wall movement in 95 % of the patients. This study showed that the maximal movement of the chest wall during DIBH and EBH was greatest in the A-P axis followed by the S-I axis, while the M-L axis was minimally affected by respiration.