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Aim: To develop a model using radiomics features extracted from magnetic resonance imaging (MRI) images of Gamma Knife radiosurgery (GKRS) to predict the BRAF mutation in patients with melanoma brain metastases (MBM)., Materials and Methods: Data of 220 tumours were classified into two groups. One was a group whose BRAF mutation was identified, and the other group whose BRAF mutation was not identified. We extracted 1,962 radiomics features from gadolinium contrast-enhanced T1-weighted MRI treatment-planning images. Synthetic Minority Over-sampling TEchnique (SMOTE) was performed to address the unbalanced data-related issues. A single-layer neural network (NN) was used to build predictive models with radiomics features. The sensitivity, specificity, accuracy, and the area under the curve (AUC) were evaluated to assess the model performance., Results: The prediction performance for the final evaluation without the SMOTE had an accuracy of 77.14%, a specificity of 82.44%, a sensitivity of 81.85%, and an AUC of 0.79. The application of SMOTE improved the prediction model to an accuracy of 83.1%, a specificity of 87.07%, a sensitivity of 78.82%, and an AUC of 0.82., Conclusion: The current study showed the feasibility of generating a highly accurate NN model for the BRAF mutation prediction. The prediction performance improved with SMOTE. The model assists physicians to obtain more accurate expectations of the treatment outcome without a genetic test., (Copyright © 2023. Published by Elsevier Ltd.)

This study aimed to expand the biological conversion factor (BCF) model, which converts the physical dosimetric margin (PDM) to the biological dosimetric margin (BDM) for point prescription with 3-dimensional conformal radiation therapy (3DCRT) and the marginal prescription method with volumetric-modulated arc radiotherapy (VMAT). The VMAT of the marginal prescription and the 3DCRT of the point prescription with lung stereotactic body radiation therapy (SBRT) by using RayStation were planned. The biological equivalent dose (BED) for a dose per fraction (DPF) of 3-20 Gy was calculated from these plans. The dose was perturbed with the calculation using a 1-mm step isocenter shift. The dose covering 95% of the target was greater than or equal to 90% of the prescribed physical dose, and the BED were defined as the PDM and BDM, respectively. The BCF was created as a function of the DPF. The PDM and BDM for all DPFs were larger with the point prescription method than with the marginal prescription method. The marginal prescription method with a 60% isodose line had a larger PDM and BDM. The BCF with the point prescription was smaller than that with the marginal prescription in the left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) directions. In the marginal prescription method, the 60% isodose line had a higher BCF. In conclusion, the improved BCF method could be converted to BDM for point prescription with 3DCRT and marginal prescription method with VMAT, which is required for stereotactic radiation therapy in radiobiology-based treatment planning., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

We investigated the effects of indirect apoptotic cell death due to vascular damage on tumor response to a single large dose with an improved two-dimensional cellular automata model. The tumor growth was simulated by considering the oxygen and nutrients supplied to the tumor through the blood vessels. The cell damage processes were modeled by taking account of the direct cell death and the indirect death due to the radiation-induced vascular damages. The radiation increased the permeation of oxygen and nutrients through the blood vessel or caused the breakdown of the vasculature. The amount of oxygen in cancer cells affected the response of cancer cells to radiation and the tumor growth rate after irradiation. The lack of oxygen led to the apoptotic death of cancer cells. We calculated the tumor control probability (TCP) at different radiation doses, the probability of apoptotic death, the threshold of the oxygen level for indirect apoptotic death, the average oxygen level in cancer cells and the vessel survival probability after radiation damage. Due to the vessel damage, indirect cell death led to a 4% increase in TCP for the dose ranging from 15 Gy to 20 Gy. TCP increased with increasing the probability of apoptotic death and the threshold of the oxygen level for indirect apoptotic death due to increased apoptotic death. The variation of TCP as a function of the average oxygen level exhibited the minimum at the average oxygen level of 2.7%. The apoptosis increased as the average oxygen level decreased, leading to an increasing TCP. On the other hand, the direct radiation damage increased, and the apoptosis decreased for higher average oxygen level, resulting in a higher TCP. We showed by modeling the radiation damage of blood vessels in a 2D CA simulation that the indirect apoptotic death of cancer cells, caused by the reduction of the oxygen level due to vascular damage after high dose irradiation, increased TCP., (© 2021 IOP Publishing Ltd.)

Purpose: To develop a dosimetric internal target volume (ITV) margin (DIM) for respiratory motion in lung stereotactic body radiotherapy (SBRT) and to evaluate DIM with a nonuniform volume prescription (NVP) and the point prescription (PP)., Methods: Volumetric modulated arc therapy (VMAT) treatment plans with PP and NVP were created on a heterogeneous programmable respiratory motion phantom, with a tumor (30-mm diameter) inside a cylindrical lung insert. The tumor was defined as the gross tumor volume (GTV), equal to the clinical target volume (CTV). Five-millimeter and 0-mm margins were used for the ITV and setup margins, respectively. The phantom was moved in cranio-caudal direction with a biquadratic sinusoidal waveform with a 4-s cycle and an amplitude of ±5-10 mm. The interplay effect was evaluated by measuring the dose profile with a film in the sagittal plane for different respiratory periods and different initial respiratory phases. DIM was based on the respiratory motion amplitude that satisfied 100% and 95% coverage of the prescribed dose by the minimum dose of the CTV. Moreover, the absolute dose was measured with and without respiratory motion for NVP by a pinpoint chamber., Results: The dose difference in the tumor region due to the interplay effect was within 1.0%. The gamma passing rate was over 95.1% for different respiratory periods and 98.6% for different initial respiratory phases. DIM with PP was almost equivalent to the margin of the respiratory motion. However, DIM with NVP was 2.0 and 1.8 times larger than the margin of the respiratory motion for the 100% and 95% coverage of the prescribed doses, respectively., Conclusion: The interplay effects experienced between the MLC sequence and tumor motion were negligible for NVP. The DIM analysis revealed that the margin to compensate the respiratory tumor motion could be reduced by more than 44-50% for NVP in SBRT., (© 2021 American Association of Physicists in Medicine.)

The current study aims to determine the optimal irradiation interval of fractionated stereotactic radiosurgery (SRS) by using an improved cellular automata (CA) model. The tumor growth process was simulated by considering the amount of oxygen and the density of blood vessels, which supplied oxygen and nutrient required for cell growth. Cancer cells died by the mitotic death process due to radiation, which was quantified by the LQ-model, or the apoptosis due to the lack of nutrients. The radiation caused increased permeation of plasma protein through the blood vessel or the breakdown of the vasculature. Consequently, these changes lead to a change in radiation sensitivity of cancer cells and tumor growth rate after irradiation. The optimal model parameters were determined with experimental data of the rat tumor volume. The tumor control probability (TCP) was defined as the ratio of the number of histories in which all cancer cells died after the irradiation to the total number of the histories per simulation. The optimal irradiation interval was defined as the irradiation interval that TCP was the maximum. For one fractionation treatment, the ratio of hypoxic cells to the total number of cancer cells kept decreasing until day 16th after irradiation; whereas the number of surviving cancer cells begun increasing immediately after irradiation. This intricate relationship between the hypoxia (or reoxygenation) and the number of cancer cells lead to an optimal irradiation interval for the second irradiation. The optimal irradiation interval for two-fraction SRS was six days. The optimum intervals for the first-second irradiations and the second-third irradiations were five and two days, respectively, for three fraction SRS. For 4 and 5-fraction treatments, the optimum first-interval was five days, which was similar to three fraction treatment. The remaining intervals should be one day. We showed that the improved CA model could be used to optimize the irradiation interval by explicitly including the reoxygenation after irradiation in the model.

Purpose: To develop a novel biological dosimetric margin (BDM) and to create a biological conversion factor (BCF) that compensates for the difference between physical dosimetric margin (PDM) and BDM, which provides a novel scheme of a direct estimation of the BDM from the physical dose (PD) distribution., Methods: The offset to isocenter was applied in 1-mm steps along left-right (LR), anterior-posterior (AP), and cranio-caudal (CC) directions for 10 treatment plans of lung stereotactic body radiation therapy (SBRT) with a prescribed dose of 48 Gy. These plans were recalculated to biological equivalent dose (BED) by the linear-quadratic model for the dose per fraction (DPF) of d = 3-20 Gy/fr and α / β = 3 - 10 . BDM and PDM were defined so that the region that satisfied that the dose covering 95% (or 98%) of the clinical target volume was greater than or equal to the 90% of the prescribed PD and BED, respectively. An empirical formula of the BCF was created as a function of the DPF., Results: There was no significant difference between LR and AP directions for neither the PDM nor BDM. On the other hand, BDM and PDM in the CC direction were significantly larger than in the other directions. BCFs of D 95% and D 98% were derived for the transverse (LR and AP) and longitudinal (CC) directions., Conclusions: A novel scheme to directly estimate the BDM using the BCF was developed. This technique is expected to enable the BED-based SBRT treatment planning using PD-based treatment planning systems., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To quantify the patient-specific imaging dose for real-time tumour monitoring in the lung during respiratory-gated stereotactic body radiotherapy (SBRT) in clinical cases using SyncTraX., Methods and Materials: Ten patients who underwent respiratory-gated SBRT with SyncTraX were enrolled in this study. The imaging procedure for real-time tumour monitoring using SyncTraX was simulated using Monte Carlo. We evaluated the dosimetric effect of a real-time tumour monitoring in a critical organ at risk (OAR) and the planning target volume (PTV) over the course of treatment. The relationship between skin dose and gating efficiency was also investigated., Results: For all patients, the mean D50 to the PTV, ipsilateral lung, liver, heart, spinal cord and skin was 118.3 (21.5-175.9), 31.9 (9.5-75.4), 15.4 (1.1-31.6), 10.1 (1.3-18.1), 25.0 (1.6-101.8), and 3.6 (0.9-7.1) mGy, respectively. The mean D2 was 352.0 (26.5-935.8), 146.4 (27.3-226.7), 90.7 (3.6-255.0), 42.2 (4.8-82.7), 88.0 (15.4-248.5), and 273.5 (98.3-611.6) mGy, respectively. The D2 of the skin dose was found to increase as the gating efficiency decreased., Conclusions: The additional dose to the PTV was at most 1.9% of the prescribed dose over the course of treatment for real-time tumour monitoring. For OARs, we could confirm the high dose region, which may not be susceptible to radiation toxicity. However, to reduce the skin dose from SyncTraX, it is necessary to increase the gating efficiency.

Purpose: Lipiodol, which was used in transcatheter arterial chemoembolization before liver stereotactic body radiation therapy (SBRT), remains in SBRT. Previous we reported the dose enhancement in Lipiodol using 10 MV (10×) FFF beam. In this study, we compared the dose enhancement in Lipiodol and evaluated the probability of electron generation (PEG) for the dose enhancement using flattening filter (FF) and flattening filter free (FFF) beams., Methods: FF and FFF for 6 MV (6×) and 10× beams were delivered by TrueBeam. The dose enhancement factor (DEF), energy spectrum, and PEG was calculated using Monte Carlo (MC) code BEAMnrc and heavy ion transport code system (PHITS)., Results: DEFs for FF and FFF 6× beams were 7.0% and 17.0% at the center of Lipiodol (depth, 6.5 cm). DEFs for FF and FFF 10× beams were 8.2% and 10.5% at the center of Lipiodol. Spectral analysis revealed that the FFF beams contained more low-energy (0-0.3 MeV) electrons than the FF beams, and the FF beams contained more high-energy (>0.3 MeV) electrons than the FFF beams in Lipiodol. The difference between FFF and FF beam DEFs was larger for 6× than for 10×. This occurred because the 10× beams contained more high-energy electrons. The PEGs for photoelectric absorption and Compton scattering for the FFF beams were higher than those for the FF beams. The PEG for the photoelectric absorption was higher than that for Compton scattering., Conclusions: FFF beam contained more low-energy photons and it contributed to the dose enhancement. Energy spectra and PEGs are useful for analyzing the mechanisms of dose enhancement., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: In this study, we demonstrate the feasibility of using split-arcs in volumetric modulated arc therapy (VMAT), tailored for expiratory breath-hold in stereotactic body radiation therapy (SBRT) for liver tumors. We compare it with three-dimensional conformal radiation therapy (3D-CRT) and continuous-VMAT, for ten randomly selected hepatocellular carcinoma cases., Methods: Four coplanar and four non-coplanar beams were used for the 3D-CRT plans. A pair of partial arcs, chosen using a back-and-forth rotating motion, were used for the continuous-VMAT plans. Split-VMAT plans were created using the same arc range as the continuous-VMAT plans, but were split into smaller arcs (<90°), to simulate an expiratory breath hold of <15s. The dose distribution, treatment delivery efficiency, and patient specific quality assurance of the split-VMAT, were verified to ensure that the outcomes were equal, or better than, those for 3D-CRT and continuous-VMAT. The prescription was 48Gy/4 fractions, to 95% of the PTV, using 10MV FFF X-ray beams., Results: The mean dose of the liver-GTV was lower in the split-VMAT compared with that of 3D-CRT. Split-VMAT was more conformal compared with 3D-CRT. The total treatment time for split-VMAT was shorter than that of 3D-CRT. Similar dosimetric indices were observed for split-VMAT and continuous-VMAT. All VMAT plans passed the gamma acceptance test., Conclusions: Split-VMAT designed to accommodate an expiratory breath-hold period of 15s is a feasible and efficient use of liver SBRT, because it does not compromise the quality of the plan, when compared with 3D-CRT or continuous-VMAT., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) combining trans-arterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study is aimed to estimate the dose enhancement in Lipiodol's proximity and to evaluate the dose calculation accuracy of the Acuros XB (AXB) algorithm and anisotropic analytical algorithm (AAA) in the Eclipse treatment planning system (TPS) (ver. 11, Varian Medical Systems, Palo Alto, USA), compared with that of the Monte Carlo (MC) calculation (using BEAMnrc/DOSXYZnrc code) for a virtual phantom and a treatment plan for liver SBRT after TACE., Methods: The MC calculation accuracy was validated by comparing its results with the percent depth dose (PDD) and the off-axis ratio (OAR) measured using a water-equivalent phantom containing Lipiodol. The dose difference in Lipiodol's proximity and the inhomogeneity correction accuracies of the AAA, AXB algorithm, and MC calculation were evaluated by calculating the PDDs and OARs for the virtual phantom with Lipiodol and the lateral profile for the clinical plan data., Results: The measured data and the MC results agreed within 3%. The average dose in the Lipiodol uptake region was higher by 8.1% for the virtual phantom and 6.0% for the clinical case compared to that in regions without Lipiodol uptake. For the virtual phantom, compared with the MC calculation, the AAA and the AXB algorithm underestimated the doses immediately upstream of the Lipiodol region by 5.0% and 4.2%, in the Lipiodol region by 7.4% and 9.8%, and downstream of the Lipiodol region by 5.5% and 3.9% respectively. These discrepancy between the AXB and MC calculations were due to the incorrect assignment of Lipiodol material properties. Namely, the bone material was assigned automatically by the AXB algorithm as the materials for the AXB algorithm do not contain iodine, which is the main constituent of Lipiodol., Conclusions: The MC calculation indicated a larger and more accurate dose increase in Lipiodol compared with the TPS algorithms. The observed dose enhancement in the tumor area could be clinically significant., (© 2016 American Association of Physicists in Medicine.)

A new randomized Phase III trial, the Japan Clinical Oncology Group (JCOG) 1408, which compares two dose fractionations (JCOG 0403 and JCOG 0702) for medically inoperable Stage IA NSCLC or small lung lesions clinically diagnosed as primary lung cancer, involves the introduction of a prescribed dose to the D 95% of the planning target volume (PTV) using a superposition/convolution algorithm. Therefore, we must determine the prescribed dose in the D 95% prescribing method to begin JCOG1408. JCOG 0702 uses density correction and the D 95% prescribing method. However, JCOG 0403 uses no density correction and isocenter- prescribing method. The purpose of this study was to evaluate the prescribed dose to the D 95% of the PTV equivalent to a dose of 48 Gy to the isocenter (JCOG 0403) using a superposition algorithm. The peripheral isodose line, which has the highest conformity index, and the D 95% of the PTV were analyzed by considering the weighting factor, i.e. the inverse of the difference between the doses obtained using the superposition and Clarkson algorithms. The average dose at the isodose line of the highest conformity index and the D 95% of the PTV were 41.5 ± 0.3 and 42.0 ± 0.3 Gy, respectively. The D 95% of the PTV had a small correlation with the target volume (r 2  = 0.0022) and with the distance between the scatterer and tumor volumes (r 2  = 0.19). Thus, the prescribed dose of 48 Gy using the Clarkson algorithm (JCOG0403) was found to be equivalent to the prescribed dose of 42 Gy to the D 95% of the PTV using the superposition algorithm., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: Image-guided radiotherapy (IGRT) based on bone matching can produce large target-positioning errors because of expiration breath-hold reproducibility during stereotactic body radiation therapy (SBRT) for liver tumors. Therefore, the feasibility of diaphragm-based 3D image matching between planning computed tomography (CT) and pretreatment cone-beam CT was investigated., Methods: In 59 liver SBRT cases, Lipiodol uptake after transarterial chemoembolization was defined as a tumor marker. Further, the relative isocenter coordinate that was obtained by Lipiodol matching was defined as the reference coordinate. The distance between the relative isocenter coordinate and reference coordinate, which was obtained from diaphragm matching and bone matching techniques, was defined as the target positioning error. Furthermore, the target positioning error between liver matching and Lipiodol matching was evaluated., Results: The positioning errors in all directions by the diaphragm matching were significantly smaller than those obtained by using by the bone matching technique (p < 0.05). Further, the positioning errors in the A-P and C-C directions that were obtained by using liver matching were significantly smaller than those obtained by using bone matching (p < 0.05). The estimated PTV margins calculated by the formula proposed by van Herk for diaphragm matching, liver matching, and bone matching were 5.0 mm, 5.0 mm, and 11.6 mm in the C-C direction; 3.6 mm, 2.4 mm, and 6.9 mm in the A-P direction; and 2.6 mm, 4.1 mm, and 4.6 mm in the L-R direction, respectively., Conclusions: Diaphragm matching-based IGRT may be an alternative image matching technique for determining liver tumor positions in patients., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Liver image guided radiation therapy (IGRT) based on bone matching risks generating serious target positioning errors for reasons of lack of reproducibility of expiration breath hold. We therefore investigated the feasibility of 3D image matching between planning CT images and pretreatment cone-beam computed tomography (CBCT) images based on diaphragm surface matching., Method: 27 liver stereotactic body radiotherapy (SBRT) cases in whom trancecatheter arterial chemoembolization (TACE) had been performed in advance of radiotherapy were manually image-matched based on contrast, Lipiodol used in the TACE as the marker of the tumor, and the relative coordinates of the isocenter obtained by contrast matching, defined as the reference coordinate. The target positioning difference between diaphragm matching and bone matching were evaluated by using relative coordinates of the isocenter from the reference obtained for each matching technique., Results: The target positioning error using diaphragm matching and bone matching was 1.31±0.83 and 3.10±2.80 mm in the cranial-caudal (C-C) direction, 1.04±0.95 and 1.62±1.02 mm in the anterior-posterior (A-P) direction, and 0.93±1.19 and 1.12±0.94 mm in the left-right (L-R) direction, respectively. The positioning error due to diaphragm matching was significantly smaller than for bone matching in the C-C direction (p<0.05)., Conclusion: IGRT based on diaphragm matching has potential as an alternative image matching technique for the positioning of liver patients.