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Background: Predicting models of the gamma passing rate (GPR) have been studied to substitute the measurement‐based gamma analysis. Since these studies used data from different radiotherapy systems comprising TPS, linear accelerator, and detector array, it has been difficult to compare the performances of the predicting models among institutions with different radiotherapy systems. Purpose: We aimed to develop unbiased scoring methods to evaluate the performance of the models predicting the GPR, by introducing both best and worst limits for the performance of the GPR prediction. Methods: Two hundred head‐and‐neck VMAT plans were used to develop a framework. The GPRs were measured using the ArcCHECK device. The predicted GPR [p] was generated using a deep learning‐based model [pDL]. The predicting model was evaluated using four metrics: standard deviation (SD) [σ], Pearson's correlation coefficient (CC) [r], mean squared error (MSE) [s], and mean absolute error (MAE) [a]. The best limit [σm${\sigma _m}$, rm${r_m}$, sm${s_m}$, and am${a_m}$] was estimated by measuring the SD of measured GPR [m] by shifting the device along the longitudinal direction to measure different sampling points. Mimicked best and worst p's [pbest and pworst] were generated from pDL. The worst limit was defined such that m and p have no correlation [CC ∼ 0]. The worst limit [σMix, rMix, sMix, and aMix] was generated using the event‐mixing (EM) technique originally introduced in high‐energy physics experiments. The range of σ, r, s, and a was defined to be [σm,σMix]$[ {{\sigma _m},{\sigma _{{\mathrm{Mix}}}}} ]$, [0,rm]$[ {0,{r_m}} ]$, [sm,sMix]$[ {{s_m},{s_{{\mathrm{Mix}}}}} ]$, and [am,aMix]$[ {{a_m},{a_{{\mathrm{Mix}}}}} ]$. The achievement score (AS) independently based on σ, r, s, and a were calculated for pDL, pbest and pworst. The probability that p fails the gamma analysis (alert frequency; AF) was estimated as a function of σd${\sigma _d}$ values within the [σm${\sigma _m}$, σMix] range for the 3%/2 mm data with a 95% criterion. Results: SDs of the best limit were well reproduced by σm=0.531100−m${\sigma _m} = \;0.531\sqrt {100 - m} $. The EM technique successfully generated the (m,p)$({m,p})$ pairs with no correlation. The AS using four metrics showed good agreement. This agreement indicates successful definitions of both best and worst limits, consistent definitions of the AS, and successful generations of mixed events. The AF for the DL‐based model with the 3%/2 mm tolerance was 31.5% and 63.0% with CL's 99% and 99.9%, respectively. Conclusion: We developed the AS to evaluate the predicting model of the GPR in an unbiased manner by excluding the effects of the precision of the radiotherapy system and the spreading of the GPR. The best and worst limits of the GPR prediction were successfully generated using the measured precision of the GPR and the EM technique, respectively. The AS and σp${\sigma _p}$ are expected to enable objective evaluation of the predicting model and setting exact achievement goal of precision for the predicted GPR. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the impact of the coronavirus disease 2019 (COVID‐19) pandemic on radiotherapy delivery in Japan using a high‐quality Japanese national database based on universal health coverage. Methods: We performed a retrospective observational study using National Database of Health Insurance Claims and Specific Health Checkups of Japan open data focused on radiotherapy between fiscal year (FY) 2019 and FY2020 and the number of COVID‐19 cases from the Ministry of Health, Labour, and Welfare. We statistically analyzed the relationship between the number of COVID‐19 cases and the number of radiotherapy deliveries in Japan as a whole and by prefecture. Results: The total number of external beam radiotherapy (EBRT) fractions was 4,472,140 in FY2019 and 4,227,673 in FY2020 (−5.8%). EBRT courses were 250,395 in FY2019 and 240,329 in FY2020 (−4.0%), stereotactic radiotherapy courses were 27,619 in FY2019 and 31,786 in FY2020 (+15.1%), and single‐fraction palliative radiotherapy courses were 4124 in FY2019 and 5255 in FY2020 (+21.5%). The total number of breast and prostate hypofractionated radiotherapy (HFRT) fractions was 155,773 and 48,188 in FY2019, and 200,256 and 84,230 in FY2020 (+28.6% and +74.8%), respectively. In the Pearson correlation analysis, EBRT fractions were lower, and breast HFRT fractions were higher in prefectures with more COVID‐19 cases. Conclusions: Overall, radiotherapy delivery in Japan was relatively stable after the pandemic, with an increase in HFRT. Also, EBRT fractions decreased, and breast HFRT were more likely to be used in prefectures with more COVID‐19 cases. [ABSTRACT FROM AUTHOR]

Aim: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. Methods: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child–Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence‐free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. Results: Seventy‐three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50–89 years), and the median tumor size was 23 mm (range: 6–50 mm). The median radiation dose was 40 Gy (range: 35–60 Gy) in five fractions (range: 4–8). The median follow‐up period was 45 months (range: 0–103 months). The 3‐year overall survival, recurrence‐free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%–81%), 57.9% (95% CI: 45.2%–70.5%), and 20.0% (95% CI: 11.2%–30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. Conclusion: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the impact of scanning orientation and lateral response artifact (LRA) effects on the dose‐response of EBT4 films and compare it with that of EBT3 films. Dose‐response curves for EBT3 and EBT4 films in red‐green‐blue (RGB) color channels in portrait orientation were created for unexposed films and for films exposed to doses ranging from 0 to 1 000 cGy. Portrait and landscape orientations of the EBT3 and EBT4 films were scanned to investigate the scanning orientation effect in the red channel. EBT3 and EBT4 films were irradiated to assess the LRA in the red channel using a field size of 15 × 15 cm2 and delivered doses of 200, 400, and 600 cGy. Films were scanned at the edge of the scanner bed, and the measured doses were compared with the treatment planning system (TPS) calculated doses at a position 100 mm lateral to the scanner center. At a dose of 200 cGy, the differences in optical density (OD) in the red, green, and blue color channels between EBT3 and EBT4 films were 0.035 (24.8%), 0.042 (49.7%), and 0.022 (64.4%), respectively. The EBT4 film slightly improved the scanning orientation compared to the EBT3 film. The OD difference in the different scanning orientations for the EBT3 and EBT4 films was 0.015 (6.8%) and 0.007 (3.9%), respectively, at a dose of 200 cGy. This is equivalent to a 20 or 10 cGy variation at a dose of 200 cGy. Compared with the TPS calculation, the measurement doses for EBT3 and EBT4 films irradiated at 200 cGy were approximately 16% and 13% higher, respectively, at the 100 mm off‐centered position. The EBT4 film showed an improvement concerning the impact of LRA compared with the EBT3 film. This study demonstrated that the response of EBT4 film to a dose in the blue channel was less sensitive and showed an improvement in the scanning orientation and LRA effects. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effect of different air computed tomography (CT) numbers of the image value density table (IVDT) on the retrospective dose calculation of head‐and‐neck (HN) radiotherapy using TomoTherapy megavoltage CT (MVCT) images. The CT numbers of the inside and outside air and each tissue‐equivalent plug of the "Cheese" phantom were obtained from TomoTherapy MVCT. Two IVDTs with different air CT numbers were created and applied to MVCT images of the HN anthropomorphic phantom and recalculated by Planned Adaptive to verify dose distribution. We defined the recalculation dose with MVCT images using both inside and outside air of the IVDT as IVDTMVCTinair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDTMVCToutair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$, respectively. Treatment planning doses calculated on kVCT images were compared with those calculated on MVCT images using two different IVDT tables, namely, IVDTMVCTinair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDTMVCToutair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$. The difference between average MVCT numbers ±1 standard deviation on inside and outside air of the calibration phantom was 65 ± 36 HU. This difference in MVCT number of air exceeded the recommendation lung tolerance for dose calculation error of 2%. The dose differences between the planning target volume (PTV): D98%, D50%, D2% and the organ at risk (OAR): Dmax, Dmean recalculated by IVDTMVCTinair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDTMVCToutair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ using MVCT images were a maximum of 0.7% and 1.2%, respectively. Recalculated doses to the PTV and OAR with MVCT showed that IVDTMVCToutair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was 0.5%–0.7% closer to the kVCT treatment planning dose than IVDTMVCTinair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$. This study showed that IVDTMVCToutair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was more accurate than IVDTMVCTinair${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ in recalculating the dose HN cases of MVCT using TomoTherapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to propose optimal robust planning by comparing the robustness with setup error with the robustness of a conventional planning target volume (PTV)‐based plan and to compare the robust plan to the PTV‐based plan for the target and organ at risk (OAR). Data from 13 patients with intermediate‐to‐high‐risk localized prostate cancer who did not have T3b disease were analyzed. The dose distribution under multiple setup error scenarios was assessed using a conventional PTV‐based plan. The clinical target volume (CTV) and OAR dose in moving coordinates were used for the dose constraint with the robust plan. The hybrid robust plan added the dose constraint of the PTV‐rectum to the static coordinate system. When the isocenter was shifted by 10 mm in the superior–inferior direction and 8 mm in the right‐left and anterior directions, the doses to the CTV, bladder, and rectum of the PTV‐based plan, robust plan, and hybrid robust plan were compared. For the CTV D99% in the PTV‐based plan and hybrid robust plan, over 95% of the prescribed dose was secured in all directions, except in the inferior direction. There was no significant difference between the PTV‐based plan and the hybrid robust plan for rectum V70Gy, V60Gy, and V40Gy. This study proposed an optimization method for patients with prostate cancer. When the setup error occurred within the PTV margin, the dose robustness of the CTV for the hybrid robust plan was higher than that of the PTV‐based plan, while maintaining the equivalent OAR dose. [ABSTRACT FROM AUTHOR]

Purpose: Adaptive radiotherapy requires auto‐segmentation in patients with head and neck (HN) cancer. In the current study, we propose an auto‐segmentation model using a generative adversarial network (GAN) on magnetic resonance (MR) images of HN cancer for MR‐guided radiotherapy (MRgRT). Material and methods: In the current study, we used a dataset from the American Association of Physicists in Medicine MRI Auto‐Contouring (RT‐MAC) Grand Challenge 2019. Specifically, eight structures in the MR images of HN region, namely submandibular glands, lymph node level II and level III, and parotid glands, were segmented with the deep learning models using a GAN and a fully convolutional network with a U‐net. These images were compared with the clinically used atlas‐based segmentation. Results: The mean Dice similarity coefficient (DSC) of the U‐net and GAN models was significantly higher than that of the atlas‐based method for all the structures (p < 0.05). Specifically, the maximum Hausdorff distance (HD) was significantly lower than that in the atlas method (p < 0.05). Comparing the 2.5D and 3D U‐nets, the 3D U‐net was superior in segmenting the organs at risk (OAR) for HN patients. The DSC was highest for 0.75–0.85, and the HD was lowest within 5.4 mm of the 2.5D GAN model in all the OARs. Conclusions: In the current study, we investigated the auto‐segmentation of the OAR for HN patients using U‐net and GAN models on MR images. Our proposed model is potentially valuable for improving the efficiency of HN RT treatment planning. [ABSTRACT FROM AUTHOR]

Thermoplastic masks, used along with surgical masks, enable immobilization methods to reduce the risk of infection in patients undergoing intracranial stereotactic radiosurgery and stereotactic radiotherapy (SRS/SRT) during the COVID‐19 crisis. The purpose of this study was to investigate the feasibility of thermoplastic mask immobilization with a surgical mask using an ExacTrac system. Twelve patients each with brain metastases were immobilized using a thermoplastic mask and a surgical mask and only a thermoplastic mask. Two x‐ray images were acquired to correct (XC) and verify (XV) the patient's position at a couch angle of 0°. Subsequently, the XC and XV images were acquired at each planned couch angle for non‐coplanar beams. When the position errors were detected after couch rotation for non‐coplanar beams, the errors were corrected at each planned couch angle until a clinically acceptable tolerance was attained. The position errors in the translational and rotational directions (vertical, lateral, longitudinal, pitch, roll, and yaw) were retrospectively investigated using data from the ExacTrac system database. A standard deviation of XC translational and rotational position errors with and without a surgical mask in the lateral (1.52 vs 2.07 mm), longitudinal (1.59 vs 1.87 mm), vertical (1.00 vs 1.73 mm), pitch (0.99 vs 0.79°), roll (1.24 vs 0.68°), and yaw (1.58 vs 0.90°) directions were observed at a couch angle of 0°. Most of patient positioning errors were less than 1.0 mm or 1.0° after the couch was rotated to the planned angle for non‐coplanar beams. The overall absolute values of the translational and rotational XV position errors with and without the surgical mask were less than 0.5 mm and 0.5°, respectively. This study showed that a thermoplastic mask with a surgical mask is a feasible immobilization technique for brain SRS/SRT patients using the ExacTrac system. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To synthesize a dual‐energy computed tomography (DECT) image from an equivalent kilovoltage computed tomography (kV‐CT) image using a deep convolutional adversarial network. Methods: A total of 18,084 images of 28 patients are categorized into training and test datasets. Monoenergetic CT images at 40, 70, and 140 keV and equivalent kV‐CT images at 120 kVp are reconstructed via DECT and are defined as the reference images. An image prediction framework is created to generate monoenergetic computed tomography (CT) images from kV‐CT images. The accuracy of the images generated by the CNN model is determined by evaluating the mean absolute error (MAE), mean square error (MSE), relative root mean square error (RMSE), peak signal‐to‐noise ratio (PSNR), structural similarity index (SSIM), and mutual information between the synthesized and reference monochromatic CT images. Moreover, the pixel values between the synthetic and reference images are measured and compared using a manually drawn region of interest (ROI). Results: The difference in the monoenergetic CT numbers of the ROIs between the synthetic and reference monoenergetic CT images is within the standard deviation values. The MAE, MSE, RMSE, and SSIM are the smallest for the image conversion of 120 kVp to 140 keV. The PSNR is the smallest and the MI is the largest for the synthetic 70 keV image. Conclusions: The proposed model can act as a suitable alternative to the existing methods for the reconstruction of monoenergetic CT images in DECT from single‐energy CT images. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of interruption in radiotherapy due to machine failure in patients and medical institutions using machine failure risk analysis (MFRA). Material and methods: The risk of machine failure during treatment is assigned to three scores (biological effect, B; occurrence, O; and cost of labor and repair parts, C) for each type of machine failure. The biological patient risk (BPR) and the economic institution risk (EIR) are calculated as the product of B and O (B×O) and C and O (C×O), respectively. The MFRA is performed in two linear accelerators (linacs). Result: The multileaf collimator (MLC) fault has the highest BPR and second highest EIR. In particular, TrueBeam has a higher BPR and EIR for MLC failures. The total EIR in TrueBeam was significantly higher than that in Clinac iX. The minor interlock had the second highest BPR, whereas a smaller EIR. Meanwhile, the EIR for the LaserGuard fault was the highest, and that for the monitor chamber fault was the second highest. These machine failures occurred in TrueBeam. The BPR and EIR should be evaluated for each linac. Further, the sensitivity of the BPR, it decreased with higher T1/2 and α/β values. No relative difference is observed in the BPR for each machine failure when T1/2 and α/β were varied. Conclusion: The risk faced by patients and institutions in machine failure may be reduced using MFRA. Advances in knowledge: For clinical radiotherapy, interruption can occur from unscheduled downtime with machine failures. Interruption causes sublethal damage repair. The current study evaluated the effect of interruption in radiotherapy owing to machine failure on patients and medical institutions using a new method, that is, machine failure risk analysis. [ABSTRACT FROM AUTHOR]

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 D95% and D98% 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. [ABSTRACT FROM AUTHOR]

Purpose: In photon radiation therapy, computed tomography (CT) numbers are converted into values for mass density (MD) or relative electron density to water (RED). CT‐MD or CT‐RED calibration tables are relevant for human body dose calculation in an inhomogeneous medium. CT‐MD or CT‐RED calibration tables are influenced by patient imaging (CT scanner manufacturer, scanning parameters, and patient size), the calibration process (tissue‐equivalent phantom manufacturer, and selection of tissue‐equivalent material), differences between tissue‐equivalent materials and standard tissues, and the dose calculation algorithm applied; however, a CT number calibration audit has not been established. The purposes of this study were to develop a postal audit phantom, and to establish a CT number calibration audit process. Methods: A conventional stoichiometric calibration conducts a least square fit of the relationships between the MD, material weight, and measured CT number, using two parameters. In this study, a new stoichiometric CT number calibration scheme has been empirically established, using three parameters to harmonize the calculated CT number with the measured CT number for air and lung tissue. In addition, the suitable material set and the minimal number of materials required for stoichiometric CT number calibration were determined. The MDs and elemental weights from the International Commission on Radiological Protection Publication 110 were used as standard tissue data, to generate the CT‐MD and CT‐RED calibration tables. A small‐sized, CT number calibration phantom was developed for a postal audit, and stoichiometric CT number calibration with the phantom was compared to the CT number calibration tables registered in the radiotherapy treatment planning systems (RTPSs) associated with five radiotherapy institutions. Results: When a least square fit was performed for the stoichiometric CT number calibration with the three parameters, the calculated CT number showed better agreement with the measured CT number. We established stoichiometric CT number calibration using only two materials because the accuracy of the process was determined not by the number of used materials but by the number of elements contained. The stoichiometric CT number calibration was comparable to the tissue‐substitute calibration, with a dose difference less than 1%. An outline of the CT number calibration audit was demonstrated through a multi‐institutional study. Conclusions: We established a new stoichiometric CT number calibration method for validating the CT number calibration tables registered in RTPSs. We also developed a CT number calibration phantom for a postal audit, which was verified by the performances of multiple CT scanners located at several institutions. The new stoichiometric CT number calibration has the advantages of being performed using only two materials, and decreasing the difference between the calculated and measured CT numbers for air and lung tissue. In the future, a postal CT number calibration audit might be achievable using a smaller phantom. [ABSTRACT FROM AUTHOR]

Purpose: We aim to develop a method to predict the gamma passing rate (GPR) of a three‐dimensional (3D) dose distribution measured by the Delta4 detector system using the dose uncertainty potential (DUP) accumulation model. Methods: Sixty head‐and‐neck intensity‐modulated radiation therapy (IMRT) treatment plans were created in the XiO treatment planning system. All plans were created using nine step‐and‐shoot beams of the ONCOR linear accelerator. Verification plans were created and measured by the Delta4 system. The planar DUP (pDUP) manifesting on a field edge was generated from the segmental aperture shape with a Gaussian folding on the beam's‐eye view. The DUP at each voxel (u) was calculated by projecting the pDUP on the Delta4 phantom with its attenuation considered. The learning model (LM), an average GPR as a function of the DUP, was approximated by an exponential function aGPRu=e-qu to compensate for the low statistics of the learning data due to a finite number of the detectors. The coefficient q was optimized to ensure that the difference between the measured and predicted GPRs (dGPR) was minimized. The standard deviation (SD) of the dGPR was evaluated for the optimized LM. Results: It was confirmed that the coefficient q was larger for tighter tolerance. This result corresponds to the expectation that the attenuation of the aGPRu will be large for tighter tolerance. The pGPR and mGPR were observed to be proportional for all tolerances investigated. The SD of dGPR was 2.3, 4.1, and 6.7% for tolerances of 3%/3 mm, 3%/2 mm, 2%/2 mm, respectively. Conclusion: The DUP‐based predicting method of the GPR was extended to 3D by introducing DUP attenuation and an optimized analytical LM to compensate for the low statistics of the learning data due to a finite number of detector elements. The precision of the predicted GPR is expected to be improved by improving the LM and by involving other metrics. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the effect against active cystic components has not been documented yet. Materials and Methods: Between 2008 and 2018, 139 patients with primary or metastatic brain tumors were treated with bevacizumab (BEV) in our institution. The images and symptoms before and after administration of BEV were examined, and changes in size of cysts were evaluated as follows: CR (complete disappearance), PR (reduction by ≥50%), MR (reduction by ≥25%), SD (size change <25%), PD (increase by ≥25%). The effect of BEV on tumor itself was determined according to Response Assessment in Neuro‐Oncology criteria. Results: Of the 139 patients, 21 (15.1%) had cystic components. The best responses of cysts to BEV treatment were as follows: CR 6, PR 7, MR 4, SD 4. The group of patients with progressively increasing cysts prior to BEV treatment had significant cyst size reduction compared to stable cyst size groups, at initial imaging after BEV (mean 62.6% vs 22.5%, P = .0055) and at best response timing (mean 76.3% vs 32.8%, P = .0050). Patients with cysts showed significant improvement in symptoms after the treatment with BEV compared to patients without cysts (P = .0033). However, response rate was not different between patients with or without cysts. Overall survival after starting BEV was not different between glioblastoma patients with or without cysts. Conclusion: Bevacizumab is effective against progressively increasing cysts. Although cysts reduction effect and tumor response and/or overall survival are independent, BEV may be effective in patients who are symptomatic due to cyst enlargement. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study was to evaluate the backscatter dose and energy spectrum from the Lipiodol with flattening filter (FF) and flattening filter‐free (FFF) beams. Moreover, the backscatter range, that was defined as the backscatter distance (BD) are revealed. Methods: 6 MVX FF and FFF beams were delivered by TrueBeam. Two dose calculation methods with Monte Carlo calculation were used with a virtual phantom in which the Lipiodol (3 × 3 × 3 cm3) was located at a depth of 5.0 cm in a water‐equivalent phantom (20 × 20 × 20 cm3). The first dose calculation was an analysis of the dose and energy spectrum with the complete scattering of photons and electrons, and the other was a specified dose analysis only with scattering from a specified region. The specified dose analysis was divided into a scattering of primary photons and a scattering of electrons. Results: The lower‐energy photons contributed to the backscatter, while the high‐energy photons contributed the difference of the backscatter dose between the FF and FFF beams. Although the difference in the dose from the scattered electrons between the FF and FFF beams was within 1%, the difference of the dose from the scattered photons between the FF and FFF beams was 5.4% at a depth of 4.98 cm. Conclusions: The backscatter range from the Lipiodol was within 3 mm and depended on the Compton scatter from the primary photons. The backscatter dose from the Lipiodol can be useful in clinical applications in cases where the backscatter region is located within a tumor. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) data are required to calculate the dose distribution in a patient's body. Generally, there are two CT number calibration methods for commercial radiotherapy treatment planning system (RTPS), namely CT number‐relative electron density calibration (CT‐RED calibration) and CT number‐mass density calibration (CT‐MD calibration). In a previous study, the tolerance levels of CT‐RED calibration were established for each tissue type. The tolerance levels were established when the relative dose error to local dose reached 2%. However, the tolerance levels of CT‐MD calibration are not established yet. We established the tolerance levels of CT‐MD calibration based on the tolerance levels of CT‐RED calibration. In order to convert mass density (MD) to relative electron density (RED), the conversion factors were determined with adult reference computational phantom data available in the International Commission on Radiological Protection publication 110 (ICRP‐110). In order to validate the practicability of the conversion factor, the relative dose error and the dose linearity were validated with multiple RTPSes and dose calculation algorithms for two groups, namely, CT‐RED calibration and CT‐MD calibration. The tolerance levels of CT‐MD calibration were determined from the tolerance levels of CT‐RED calibration with conversion factors. The converted RED from MD was compared with actual RED calculated from ICRP‐110. The conversion error was within ±0.01 for most standard organs. It was assumed that the conversion error was sufficiently small. The relative dose error difference for two groups was less than 0.3% for each tissue type. Therefore, the tolerance levels for CT‐MD calibration were determined from the tolerance levels of CT‐RED calibration with the conversion factors. The MD tolerance levels for lung, adipose/muscle, and cartilage/spongy‐bone corresponded to ±0.044, ±0.022, and ±0.045 g/cm3, respectively. The tolerance levels were useful in terms of approving the CT‐MD calibration table for clinical use. [ABSTRACT FROM AUTHOR]

Purpose: A patient's respiratory monitoring is one of the key techniques in radiotherapy for a moving target. Generally, such monitoring systems are permanently set to a fixed geometry during the installation. This study aims to enable a temporary setup of such a monitoring system by developing a fast method to automatically calibrate the geometrical position by a quick measurement of calibration markers. Methods: One calibration marker was placed on the isocenter and the other six markers were placed at positions 5‐cm apart from the isocenter to the left, right, anterior, posterior, superior, and inferior directions. A near‐infrared (NIR) camera (NIC) [Kinect v2 (Microsoft Corp.)] was arbitrarily set with ten different angles around the calibration phantom with a fixed tilting‐down angle at approximately 45° in a linear accelerator treatment vault. The three‐dimensional (3D) coordinates in the camera (Cam) coordinate system (CS; x and y are the horizontal and vertical coordinates of the image, respectively, and z is a coordinate along the NIR time‐of‐flight) were taken for 1 min with 30 frames per second. The data corresponding to the measurement times of 1, 3, 10, 30, and 60 s were created to mimic various measurement times. These data were used to calculate the initial matrix elements, which included six parameters of the pitching, yawing, and rolling angles; horizontal two‐dimensional translation in the treatment room; and the source‐to‐axis distance of NIC, for a conversion from the Cam CS to the treatment room CS for which the origin was defined at the isocenter (Iso coordinate). The six parameters were then optimized to minimize the displacements of the calculated marker coordinates from the actual positions in the Iso CS. The 3D positional accuracy and angular accuracy of the conversion were evaluated. The random error of the Iso coordinates was analyzed through a relation with the angle of each measurement setup. Results: Three angles of NIC and relative translation vectors were successfully calculated from the measurement data of the calibration markers. The achieved spatial and angular accuracies were 0.02 mm and 1.6°, respectively, after the optimization. Among the mimicked measurement times investigated in this study, both spatial and angular accuracies had no dependence on the measurement time. The average random error of a static marker was 0.46 mm after the optimization. Conclusion: We developed an automatic method to calibrate the 3D patient surface monitoring system. The procedure developed in this study enabled a quick calibration of NIC, which can be easily repeated multiple times for a frequent and quick setup of the monitoring system. [ABSTRACT FROM AUTHOR]

Purpose: Intensity‐modulated radiation therapy (IMRT) utilizes many small fields for producing a uniform dose distribution. Therefore, there are many field junctions in the target region, and resulting dose uncertainties are accumulated. However, such accumulation of the dose uncertainty has not been implemented in the current practice of IMRT dose verification. The purpose of this study is to develop a method to predict the gamma passing rate (GPR) using a dose uncertainty accumulation model. Methods: Thirty‐three intensity‐modulated (IM) beams for head‐and‐neck cases with step‐and‐shoot techniques were used in this study. The treatment plan was created using the XiO treatment planning system (TPS). The IM beam was produced by the ONCOR Impression Plus linear accelerator. MapCHECK was used to measure the dose distribution. The distribution of a dose uncertainty potential (DUP) was generated by in‐house software that accumulated field shapes weighted by a segmental monitor unit, followed by Gaussian folding. The width of the Gaussian was determined from the width of the lateral penumbra. The dose difference between the calculated and measured doses was compared with the estimated DUP at each point. The GPR of each beam was predicted for 2%/2‐mm, 3%/2‐mm, and 3%/3‐mm tolerances by its own DUP histogram and a GPR‐vs‐DUP correlation of other beams using the leave‐one‐out cross‐validation method. The predicted GPR was compared with the measured GPR to evaluate the performance of this prediction method. The criteria for the predicted GPR corresponding to a measured GPR ≥ 90% were estimated to examine the feasibility of estimating the measured GPR by this GPR prediction method. Results: The DUP was confirmed to have proportionality to the standard deviation (SD) of the dose difference. The SDs of the difference between the measured and predicted GPRs were 3.1, 1.7, and 1.4% for 2%/2‐mm, 3%/2‐mm, and 3%/3‐mm tolerances, respectively. The criteria of the predicted GPR corresponding to the measured GPR ≥ 90% were 94.1 and 95.0% with confidence levels of 99 and 99.9%, respectively. Conclusion: In this study, we confirmed the good proportionality between the dose difference and the estimated DUP. The results showed a feasibility to predict the dose difference from DUP as estimated by a DUP accumulation model. The predicted GPR developed in this study showed good accuracy for planar dose distributions of head and neck IMRT. The prediction method developed in this study is considered to be feasible as a substitute for the current practice of measurement‐based verification of the dose distribution with gamma analysis. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the long‐term outcome of stereotactic body radiotherapy in patients with small hepatocellular carcinoma who were ineligible for resection or ablation therapies. Methods: A total of 65 patients with 74 hepatocellular carcinomas (median tumor size 16 mm) were enrolled in the present study. They were treated with the prescribed dose of 48 Gy in four fractions at the isocenter. We extended the observation period and analyzed long‐term outcomes, including overall survival, progression‐free survival, local control, and various prognostic factors, in these patients. Results: The median follow‐up period was 41 months for all patients and 62 months for surviving patients. The 3‐ and 5‐year overall survival rates were 56.3% (95% confidence interval, 44.1–68.5%) and 41.4% (95% confidence interval, 28.7–54.1%), respectively. The 3‐ and 5‐year progression‐free survival rates were 25.4% (95% confidence interval, 14.0–36.8%) and 10.6% (95% confidence interval, 1.5–19.8%), respectively. The 3‐ and 5‐year local control rates were both 100% (95% confidence interval 100%). Liver toxicities exceeding grade 3 were observed in 15 patients (23.1%). The proportion of patients who had grade ≥3 toxicities did not increase. Adverse effects (grade ≤2) presented as significant prognostic factors of overall survival, while TNM stage (T1N0M0) was a significant prognostic factor of progression‐free survival after multivariate analysis. Conclusions: Stereotactic body radiotherapy was effective for patients with small hepatocellular carcinomas who were ineligible for resection or ablation therapies. The incidence of grade ≥3 adverse effects did not increase, even after longer follow‐up times. [ABSTRACT FROM AUTHOR]

Purpose: High accuracy of the beam‐irradiated position is required for high‐precision radiation therapy such as stereotactic body radiation therapy (SBRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT). Users generally perform the verification of the mechanical and radiation isocenters using the star shot test and the Winston Lutz test that allow evaluation of the displacement at the isocenter. However, these methods are unable to evaluate directly and quantitatively the sagging angle that is caused by the weight of the gantry itself along the gantry rotation axis. In addition, the verification of the central axis of the irradiated beam that is not dependent at the isocenter is needed for the mechanical quality assurance of a nonisocentric irradiation technique. In this study, we have developed a prototype system for the verification of three‐dimensional (3D) beam alignment and we have verified the system concept for 3D isocentricity. Our system allows detection of the central axis in 3D coordinates and evaluation of the irradiated oblique angle to the gantry rotation axis, i.e., the sagging angle. Materials & Methods: In order to measure the central axis of the irradiated beam in 3D coordinates, we constructed the prototype verification system consisting of a column‐shaped plastic scintillator (CoPS), a truncated cone‐shaped mirror (TCsM), and a cooled charged‐coupled device (CCD) camera. This verification system was irradiated with 6‐MV photon beams and the scintillation light was measured using the CCD camera. The central axis on the axial plane (two‐dimensional (2D) central axis) was acquired from the integration of the scintillation light along the major axis of the CoPS, and the central axis in 3D coordinates (3D central axis) was acquired from two curve‐shaped profiles which were reflected by the TCsM. We verified the calculation accuracy of the gantry rotation axis, θz. Additionally, we calculated the 3D central axis and the sagging angle at each gantry angle. Results: We acquired the measurement images composed of the 2D central axis and the two curve‐shaped profiles. The relationship between the irradiated and measured angles with respect to the gantry rotation axis had good linearity. The mean and standard deviation of the difference between the irradiated and measured angles were 0.012 and 0.078 degrees, respectively. The size of the 2D and 3D radiation isocenters were 0.470 and 0.652 mm on the axial plane and in 3D coordinates, respectively. The sagging angles were −0.31, 0.39, and 0.38 degrees at the gantry angles of 0, 180, and 180E degrees, respectively. Conclusion: We developed a novel verification system, designated as the “kompeito shot test system,” to verify the 3D beam alignment. This system concept works for both verification of the 3D isocentricity and the direct evaluation of the sagging angle. Next, we want to improve the aspects of this system, such as the shape and the type of scintillator, to increase the system accuracy and nonisocentric beam alignment performance. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Dual‐source cone‐beam computed tomography (DCBCT) is currently available in the Vero4DRT image‐guided radiotherapy system. We evaluated the image quality and absorbed dose for DCBCT and compared the values with those for single‐source CBCT (SCBCT). Methods: Image uniformity, Hounsfield unit (HU) linearity, image contrast, and spatial resolution were evaluated using a Catphan phantom. The rotation angle for acquiring SCBCT and DCBCT images is 215° and 115°, respectively. The image uniformity was calculated using measurements obtained at the center and four peripheral positions. The HUs of seven materials inserted into the phantom were measured to evaluate HU linearity and image contrast. The Catphan phantom was scanned with a conventional CT scanner to measure the reference HU for each material. The spatial resolution was calculated using high‐resolution pattern modules. Image quality was analyzed using ImageJ software ver. 1.49. The absorbed dose was measured using a 0.6‐cm3 ionization chamber with a 16‐cm‐diameter cylindrical phantom, at the center and four peripheral positions of the phantom, and calculated using weighted cone‐beam CT dose index (CBCTDIw). Results: Compared with that of SCBCT, the image uniformity of DCBCT was slightly reduced. A strong linear correlation existed between the measured HU for DCBCT and the reference HU, although the linear regression slope was different from that of the reference HU. DCBCT had poorer image contrast than did SCBCT, particularly with a high‐contrast material. There was no significant difference between the spatial resolutions of SCBCT and DCBCT. The absorbed dose for DCBCT was higher than that for SCBCT, because in DCBCT, the two x‐ray projections overlap between 45° and 70°. Conclusions: We found that the image quality was poorer and the absorbed dose was higher for DCBCT than for SCBCT in the Vero4DRT. [ABSTRACT FROM AUTHOR]

Background: Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy.Methods: We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative-intent esophagectomy.Results: Thirty-four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30-4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12-4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68-8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51-5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09-4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79-8.48; p = 0.001) were also independent covariates for OS.Conclusions: Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma (HCC) in elderly patients. Methods: From 2008 to 2015, 117 patients with HCC (≤3 nodules, ≤30 mm in diameter, Child–Pugh score ≤7, and no vascular or extracellular metastasis) were treated with SBRT at our hospital. We evaluated overall survival (OS), disease‐free survival (DFS), local control, and adverse events. Patients were stratified according to age 75 years and older (elderly group, n = 54) and age younger than 75 years (young group, n = 63). Results: The median OS in the elderly group was not significantly different from that in the young group (52 months vs. not reached, P = 0.27). The 1‐, 2‐, and 3‐year OS rates were 96.2%, 77.6%, and 63.9%, respectively, in the elderly group, and 96.8%, 84.8%, and 67.7%, respectively, in the young group. The median DFS in the elderly group was significantly shorter than that in the young group (13 vs. 25 months, respectively; P = 0.03). The 1‐, 2‐, and 3‐year DFS rates were 50.6%, 30.4%, and 26.6%, respectively, in the elderly group and 66.5%, 50.7%, and 45.3%, respectively, in the young group. The 3‐year local tumor control rate in the elderly group was 98.1%, and that in the young group was 98.4% (P = 0.83). There was no difference between groups in the incidence of any adverse events. Conclusions: Stereotactic body radiotherapy can be effective and safe for the treatment of HCC in elderly patients. [ABSTRACT FROM AUTHOR]

Abstract: The accuracy of computed tomography number to electron density (CT‐ED) calibration is a key component for dose calculations in an inhomogeneous medium. In a previous work, it was shown that the tolerance levels of CT‐ED calibration became stricter with an increase in tissue thickness and decrease in the effective energy of a photon beam. For the last decade, a low effective energy photon beam (e.g., flattening‐filter‐free (FFF)) has been used in clinical sites. However, its tolerance level has not been established yet. We established a relative electron density (ED) tolerance level for each tissue type with an FFF beam. The tolerance levels were calculated using the tissue maximum ratio (TMR) and each corresponding maximum tissue thickness. To determine the relative ED tolerance level, TMR data from a Varian accelerator and the adult reference computational phantom data in the International Commission on Radiological Protection publication 110 (ICRP‐110 phantom) were used in this study. The 52 tissue components of the ICRP‐110 phantom were classified by mass density as five tissues groups including lung, adipose/muscle, cartilage/spongy‐bone, cortical bone, and tooth tissue. In addition, the relative ED tolerance level of each tissue group was calculated when the relative dose error to local dose reached 2%. The relative ED tolerances of a 6 MVFFF beam for lung, adipose/muscle, and cartilage/spongy‐bone were ±0.044, ±0.022, and ±0.044, respectively. The thicknesses of the cortical bone and tooth groups were too small to define the tolerance levels. Because the tolerance levels of CT‐ED calibration are stricter with a decrease in the effective energy of the photon beam, the tolerance levels are determined by the lowest effective energy in useable beams for radiotherapy treatment planning systems. [ABSTRACT FROM AUTHOR]

This study investigated position dependence in planning target volume ( PTV)-based and robust optimization plans using full-arc and partial-arc volumetric modulated arc therapy ( VMAT). The gantry angles at the periphery, intermediate, and center CTV positions were 181°-180° (full-arc VMAT) and 181°-360° (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm margin expansion of the CTV to a PTV volume, on which the dose constraints were applied. The robust optimization plan consisted of a directly optimized dose to the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was normalized to the CTV D99% (the minimum relative dose that covers 99% of the volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right-left (R-L) directions from the original position to the maximum-uncertainties setup of 5 mm in the original plan, yielding recalculated dose distributions. It was found that for the intermediate and center positions, the uncertainties in the D99% doses to the CTV for all directions did not significantly differ when comparing the PTV-based and robust optimization plans ( P > 0.05). For the periphery position, uncertainties in the D99% doses to the CTV in the R-L direction for the robust optimization plan were found to be lower than those in the PTV-based optimization plan ( P < 0.05). Our study demonstrated that a robust optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV position. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim To evaluate the response, survival and safety on 3-D conformal radiotherapy (3D- CRT) for major portal vein tumor thrombosis ( PVTT) combined with hepatic arterial infusion chemotherapy ( HAIC) for advanced hepatocellular carcinoma ( HCC). Methods In this retrospective study, 83 advanced HCC patients treated with HAIC who met the following criteria were enrolled: (i) PVTT of the main trunk or first branch of the portal vein; (ii) no extrahepatic metastasis; (iii) Child- Pugh score of 5-7; (iv) performance status of 0 or 1; and (v) no history of sorafenib treatment. The response, overall survival ( OS), time to treatment failure ( TTF), post-progression survival ( PPS) and safety were compared between HAIC combined with 3D- CRT for PVTT ( RT group, n = 41) and HAIC alone (non- RT group, n = 42). Results The objective response of PVTT was significantly higher in the RT group (56.1%) than in the non- RT group (33.3%), while that of intrahepatic tumor and OS were not significantly different between groups. Median OS, TTF and PPS were significantly longer in the RT group than in the non- RT group (8.6 and 5.0 months, 5.0 and 2.7 months, and 5.3 and 1.5 months, respectively) among intrahepatic tumor non-responders to HAIC, whereas those were not significantly different between groups among intrahepatic tumor responders to HAIC. By multivariate analysis, the combination of 3D- CRT with HAIC was an independent contributing factor for OS (hazard ratio, 3.2; 95% confidence interval, 1.692-6.021; P < 0.001) among intrahepatic HCC non-responders to HAIC. Conclusion 3D- CRT for PVTT combined with HAIC could provide survival benefit to non-responder to HAIC. [ABSTRACT FROM AUTHOR]

Aim To evaluate the efficacy and safety of stereotactic body radiotherapy ( SBRT) in patients with small hepatocellular carcinoma ( HCC) who were ineligible for resection or ablation therapies. Methods Overall, 65 patients with 74 HCC (median tumor size, 16 mm) were enrolled. They were treated at the prescribed dose of 48 Gy in four fractions at the isocenter. Child- Turcotte- Pugh ( CTP) scoring was used to classify 56 and nine patients into classes A and B, respectively. Local progression was defined as irradiated tumor growth on a dynamic computed tomography follow up. The median follow-up period was 26 months. Tumor responses were assessed according to the modified Response Evaluation Criteria in Solid Tumors. Treatment-related toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. Results The 2-year overall survival, progression-free survival and local control rates were 76.0% (95% confidence interval [ CI], 65.4-86.7%), 40.0% (95% CI, 27.6-52.3%) and 100% (95% CI, 100%), respectively. At 6-12 months after SBRT, grade 3 or higher toxicities was observed in 15 (23.1%) patients. The incidence of grade 3 or higher toxicities was higher in CTP class B than in class A ( P = 0.0127). Conclusion SBRT was effective and relatively safe for patients with small HCC who were ineligible for resection or ablation therapies. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate portal vein and bile duct toxicity after stereotactic body radiation therapy ( SBRT) for hepatocellular carcinoma ( HCC). We retrospectively reviewed 63 patients who were administrated SBRT once for HCC. The prescribed doses were from 48 Gy in four fractions to 60 Gy in eight fractions. Portal vein thrombosis and bile duct stenosis were evaluated. The dose received by 2% of the volume ( D2) of the portal vein and bile duct was calculated. Portal vein thrombosis was observed in three patients (4.8%). Common points of these patients were Child- Pugh class B and D2 of the portal vein 40 Gy or more ( BED3 ≥200 Gy). Bile duct stenosis was observed in one patient (1.6%). The patient had a history of cholangiocarcinoma and left hepatic lobectomy. Portal vein thrombosis may be necessary to be considered when SBRT for HCC is administrated to patients in higher Child- Pugh class with higher D2 of the portal vein. [ABSTRACT FROM AUTHOR]

Aim To evaluate the dynamic computed tomography ( CT) appearance of tumor response after stereotactic body radiation therapy ( SBRT) for hepatocellular carcinoma ( HCC) and reconsider response evaluation criteria for SBRT that determine treatment outcomes. Methods Fifty-nine patients with 67 tumors were included in the study. Of these, 56 patients with 63 tumors underwent transarterial chemoembolization using lipiodol prior to SBRT that was performed using a 3- D conformal method (median, 48 Gy/four fractions). Dynamic CT scans were performed in four phases, and tumor response was evaluated by comparing tumor appearance on CT prior SBRT and at least 6 months after SBRT. The median follow-up time was 12 months. Results The dynamic CT appearance of tumor response was classified into the following: type 1, continuous lipiodol accumulation without early arterial enhancement (26 lesions, 38.8%); type 2, residual early arterial enhancement within 3 months after SBRT (17 lesions, 25.3%); type 3, residual early arterial enhancement more than 3 months after SBRT (19 lesions, 28.4%); and type 4, shrinking low-density area without early arterial enhancement (five lesions, 7.5%). Only two tumors with residual early arterial enhancement did not demonstrate remission more than 6 months after SBRT. Conclusion The dynamic CT appearance after SBRT for HCC was classified into four types. Residual early arterial enhancement disappeared within 6 months in most type 3 cases; therefore, early assessment within 3 months may result in a misleading response evaluation. [ABSTRACT FROM AUTHOR]

Abstact Background and Aims To compare the tumor control and safety of stereotactic body radiation therapy ( SBRT) combined with transcatheter arterial chemoembolization ( TACE) for small, solitary, and hypervascular hepatocellular carcinoma ( HCC) with TACE alone. Methods Three hundred and sixty-five HCC patients who had solitary, ≤ 3 cm, and hypervascular nodule were treated with TACE. Among them, 30 patients followed by SBRT ( SBRT group) and 38 patients without additional therapy and previous HCC treatment (control group) were enrolled in this retrospective cohort study. Local tumor progression, complication, and disease-free survival were compared between these groups. Results There was no difference in clinical background between these groups. Complete response to therapy was noted in 29 (96.3%) patients of the SBRT group, and in only one (3.3%) patient of the TACE group ( P < 0.001). None of the patients developed acute hematologic toxicity of more than Common Terminology Criteria for Adverse Events Grade 3 during and after the treatment. Furthermore, none of the SBRT group developed radiation-induced liver damage. Disease-free survival of the 12 patients without previous HCC treatments in SBRT group was significantly superior to that in control group (15.7 months vs 4.2 months; P = 0.029). Conclusion The results indicated that SBRT combined with TACE is a safe and effective modality for locoregional treatment of small solitary primary HCC, and could be potentially a suitable option. [ABSTRACT FROM AUTHOR]

Aim: We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and systemic interferon (IFN)-α (HAIC-5-FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3). Methods: Thirty-three patients with HCC/Vv2/3 underwent HAIC with 5-FU (500 mg/body weight/day, into hepatic artery on days 1-5 on the first and second weeks) and IFN-α (recombinant IFN-α-2b 3 000 000 U or natural IFN-α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three-dimensional conformal radiotherapy (3D-CRT) was used in combination with HAIC-5-FU/IFN in 14 of 33 patients to reduce VTT. Result: The median survival time (MST) was 7.9 months, and 1- and 2-year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC-5-FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT ( P = 0.0006), size of largest tumor ( P = 0.013) and intrahepatic response CR/PR ( P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate ( P = 0.016) and hepatitis C virus Ab ( P = 0.010). Reduction of VTT correlated significantly with radiotherapy ( P = 0.021) and platelet count ( P = 0.015). Radiotherapy-related reduction in VTT significantly improved survival of 16 patients with Vv3 and non-CR/PR response of HAIC-5-FU/IFN ( P = 0.028). Conclusion: As for advanced HCC with VTT of Vv2/3, HAIC-5-FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC-5-FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis. [ABSTRACT FROM AUTHOR]

Aim: To analyze the clinical outcome of esophageal varices (EV) after hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombus (Vp3/4). Methods: The study subjects were 45 consecutive patients who received HAIC for HCC with Vp3/4 between January 2005 and December 2009. HAIC comprised the combination therapy of intra-arterial 5-FU with interferon-α (5-FU/IFN) in 23 patients and low-dose cisplatin plus 5-FU (FP) in 22. Radiotherapy (RT) was also provided in 19 patients for portal vein tumor thrombosis. Aggravation rate for EV and overall survival rate were analyzed. Results: The aggravation rates for EV were 47% and 64% at 12 and 24 months, respectively. The survival rates were 47% and 33% at 12 and 24 months, respectively. The response rates to 5-FU/IFN and FP were 35% and 41%, while the disease control rates in these two groups were 57% and 50%, respectively. There were no significant differences in the objective response and disease control between 5-FU/IFN and FP. Multivariate analysis identified size of EV (F2/F3) ( HR = 7.554, P = 0.006) and HCC disease control ( HR = 5.948, P = 0.015) as significant and independent determinants of aggravation of EV, and HCC disease control ( HR = 12.233, P < 0.001), metastasis from HCC ( HR = 11.469, P = 0.001), ascites ( HR = 8.825, P = 0.003) and low serum albumin ( HR = 4.953, P = 0.026) as determinants of overall survival. RT for portal vein tumor thrombosis tended to reduce the aggravation rate for EV in patients with these risk factors. Conclusions: Hepatocellular carcinoma disease control was the most significant and independent factor for aggravation of EV and overall survival in HCC patients with major portal vein tumor thrombosis treated with HAIC. [ABSTRACT FROM AUTHOR]

Since stereotactic body radiotherapy (SBRT) was started for patients with lung tumor in 1998 in our institution, x-ray fluoroscopic examination and slow computed tomography (CT) scan with a rotation time of 4 s have been routinely applied to determine target volumes. When lung tumor motion observed with x-ray fluoroscopy is larger than 8 mm, diaphragm control (DC) is used to reduce tumor motion during respiration. After the installation of a four-dimensional (4D) CT scanner in 2006, 4D CT images have been supplementarily acquired to determine target volumes. It was found that target volumes based on slow CT images were substantially different from those on 4D CT images, even for patients with lung tumor motion no larger than 8 mm. Although slow CT scan might be expected to fare well for lung tumors with motion range of 8 mm or less, the potential limitations of slow CT scan are unknown. The purpose of this study was to evaluate the geometrical differences in target volumes between slow CT and 4D CT imaging for lung tumors with motion range no larger than 8 mm in the upper and middle lobe. Of the patients who underwent SBRT between October 2006 and April 2008, 32 patients who had lung tumor with motion range no larger than 8 mm and did not need to use DC were enrolled in this study. Slow CT and 4D CT images were acquired under free breathing for each patient. Target volumes were manually delineated on slow CT images (TVslow CT). Gross tumor volumes were also delineated on each of the 4D CT volumes and their union (TV4D CT) was constructed. Volumetric and statistical analyses were performed for each patient. The mean±standard deviation (S.D.) of TVslow CT/TV4D CT was 0.75±0.17 (range, 0.38–1.10). The difference between sizes of TVslow CT and TV4D CT was not statistically significant (P=0.096). A mean of 8% volume of TVslow CT was not encompassed in TV4D CT (mean±S.D.=0.92±0.07). The patients were separated into two groups to test whether the quality of target delineation on slow CT scans depends on respiratory periods below or above the CT rotation time of 4 s. No significant difference was observed between these groups (P=0.229). Even lung tumors with motion range no larger than 8 mm might not be accurately depicted on slow CT images. When only a single slow CT scan was used for lung tumors with motion range of 8 mm or less, 95% confidence values for additional margins for TVslow CT to encompass TV4D CT were 4.0, 5.4, 4.9, 5.1, 1.8, and 1.7 mm for lateral, medial, ventral, dorsal, cranial, and caudal directions, respectively. [ABSTRACT FROM AUTHOR]

Abstract Background Retinoic acid, a metabolic product of retinol, is essential for craniofacial morphogenesis. Transthyretin (TTR) is a plasma protein delivering retinol to tissues. We produced several transgenic mouse lines using the human mutant TTR (hTTR Met30 ) gene to establish a mouse model of familial amyloidotic polyneuropathy. One of the lines showed an autosomal dominant inheritance of n aso-max illary deformity termed Nax . Results: The Nax malformation was characterized by a hypoplastic developmental defect of the frontonasal region. Homozygous mice with higher transgene expressions showed more severe phenotypes, but a subline, in which the copy number and expression of the transgene was reduced, showed a normal phenotype, indicating that the hTTR Met30 expression caused the malformation. Nax mice began to express the hTTR Met30 gene in the nasal placode from embryonic day 10.5 (E10.5), which was 2 days earlier than in the other transgenic lines with a normal phenotype. Excessive cell death was observed in the nasal placode of the E10.5 Nax embryos. In addition, the forced expression of hTTR Met30 in the nasal placode of transgenic mice resulted in similar phenotypes. Conclusion: The expression of the hTTR Met30 gene in the nasal placode at E10.5 induced apoptotic cell death, leading to hypoplastic deformity in the frontonasal region. [ABSTRACT FROM AUTHOR]