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To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET}}^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE}{\mathrm{T}}^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40 Gy(RBE)/5 fractions: 'Plan A', using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and 'Plan B', using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Locoregional recurrence of non-small-cell lung cancer (NSCLC) after complete resection lacks standard treatment. Durvalumab after chemoradiotherapy (CRT) or CRT alone is often selected in daily clinical practice for patients with locoregional recurrence; however, the therapeutic efficacy of these treatments remains unclear, and we aimed to assess this. This retrospective observational study used data from patients with NSCLC diagnosed with locoregional recurrence after complete resection who subsequently underwent concurrent CRT followed by durvalumab (CRT-D group) or CRT alone (CRT group). We employed propensity score analysis with inverse probability treatment weighting (IPTW) to adjust for various confounders and evaluate efficacy in the CRT-D group. After IPTW adjustment, the CRT-D group contained 119 patients (64.7% male; 69.7% adenocarcinoma), and the CRT group contained 111 patients (60.5% male; 73.4% adenocarcinoma). Their mean ages were 66 and 65 years, respectively. The IPTW-adjusted median progression-free survival was 25.4 and 11.5 months for the CRT-D and CRT groups, respectively (hazard ratio, 0.44; 95% confidence interval, 0.30-0.64); the median overall survival was not reached in either group favoring CRT-D (hazard ratio, 0.49; 95% confidence interval, 0.24-0.99). Grade 3 or 4 adverse events were observed in 48.8% of patients during CRT, 10.7% after initiating durvalumab maintenance therapy in the CRT-D group, and 57.3% in the CRT group. Overall, the sequential approach of CRT followed by durvalumab is a promising treatment strategy for locoregional recurrence of NSCLC after complete resection., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: To report the patterns of care for brain metastases (BMs) in the Federation of Asian Organizations for Radiation Oncology (FARO)., Methods: Overall, 37 questions were prepared. The survey was conducted online using Google Forms, and the URL was distributed to members of the FARO research committee. Radiation oncologists associated with FARO responded to the questionnaire between May 2023 and June 2023, and their answers were analyzed., Results: Responses were received from 32 radiation oncologists in 13 countries participating in FARO. Twenty-six physicians (81.3%) were affiliated with academic centers, and 22 (68.8%) were able to perform stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (fSRT) for BMs at their institution. The most typically used prognostic index for BM was the recursive partitioning analysis classification (17 physicians, 53.1%). The maximum number of BMs indicated for SRT/SRS was ≤three (11 physicians, 34.4%), whereas eight (25.0%) physicians answered for 6-10 BMs. The maximum size of BMs considered for SRS/fSRT was ≤3 cm (14 physicians, 43.8%), whereas nine (28.1%) answered that SRS/fSRT was preferred if the maximum size was >4 cm. When whole-brain radiotherapy (RT) was indicated, hippocampal avoidance and memantine usage were limited to 50.0% and 25.0% of patients, respectively. The most typical RT modality after BM resection was SRS/fSRT alone, regardless of whether the margin was positive (19 physicians, 59.4%) or negative (13 physicians, 40.6%)., Conclusion: We report the survey results of the patterns of care for BMs in the FARO. This survey was conducted only among a limited number of FARO members. Since many respondents were affiliated with relatively large-scale academic centers, large-scale surveys, including community hospitals, are warranted for future initiatives.

Purpose: To demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy., Methods: Time-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms., Results: Except for outliers in the superior-inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more., Conclusions: Motion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Real-time tumor-tracking volumetric modulated arc therapy (RT-VMAT) enabling beam-gating based on continuous X-ray tracking of the three-dimensional position of internal markers is relevant for moving tumors. Dose-volume characteristics and treatment time were evaluated in ten consecutive patients who underwent liver stereotactic body radiation therapy with RT-VMAT. Target dose conformity and sparing of the stomach and the intestine were improved comparing RT-VMAT with RT-3D conformal radiotherapy. The mean treatment time for each fraction was less than 10 min. RT-VMAT could be effective, especially for targets located adjacent to organs at risk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: To investigate the clinical significance of adaptive radiotherapy (ART) in locally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT)., Materials and Methods: Eligible patients were treated with concurrent chemoradiotherapy using IMRT. Planning computed tomography in ART was performed during radiotherapy, and replanning was performed. Since ART was started in May 2011 (ART group), patients who were treated without ART up to April 2011 (non-ART group) were used as the historical control. The Kaplan-Meier method was used to calculate overall survival (OS), locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). LRFS for the primary tumor (LRFS&#95;P) and regional lymph node (LRFS&#95;LN) were also studied for more detailed analysis. Statistical significance was evaluated using the log-rank test for survival., Results: The ART group tended to have higher radiation doses. The median follow-up period was 127 months (range, 10 to 211 months) in the non-ART group and 61.5 months (range, 5 to 129 months) in the ART group. Compared to the non-ART group, the ART group showed significantly higher 5-year PFS (53.8% vs. 81.3%, p = 0.015) and LRFS (61.2% vs. 85.3%, p = 0.024), but not OS (80.7% vs. 80.8%, p = 0.941) and DMFS (84.6% vs. 92.7%, p = 0.255). Five-year LRFS&#95;P was higher in the ART group (61.3% vs. 90.6%, p = 0.005), but LRFS&#95;LN did not show a significant difference (91.9% vs. 96.2%, p = 0.541)., Conclusion: Although there were differences in the patient backgrounds between the two groups, this study suggests the potential effectiveness of ART in improving locoregional control, especially in the primary tumor.

Background: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan., Methods: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included., Results: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05)., Conclusion: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC)., Methods and Materials: Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated., Results: Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P < .001) and <5 versus ≥10 cm (P < .001); Child-Pugh score A/B versus C (P < .001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P < .008) and <1 versus >2 cm (P < .001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common., Conclusions: This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer., Methods and Materials: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE., Results: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%)., Conclusions: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies., (© 2024 The Author(s).)

The SyncTraX series enables real-time tumor-tracking radiotherapy through the real-time recognition of a fiducial marker using fluoroscopic images. In this system, the isocenter should be located within approximately 5-7.5 cm from the marker, depending on the version, owing to the limited field of view. If the marker is placed away from the tumor, the isocenter should be shifted toward the marker. This study aimed to investigate stereotactic body radiotherapy (SBRT) outcomes of primary liver tumors treated with SyncTraX in cases where the isocenter was shifted marginally or outside the planning target volume (PTV). Twelve patients with 13 liver tumors were included in the analysis. Their isocenter was shifted toward the marker and was placed marginally or outside the PTV. The prescribed doses were generally 40 Gy in four fractions or 48 Gy in eight fractions. The overall survival (OS) and local control (LC) rates were calculated using the Kaplan-Meier method. All patients completed the scheduled SBRT. The median distance between the fiducial marker and PTV centroid was 56.0 (interquartile range [IQR]: 52.7-66.7) mm. By shifting the isocenter toward the marker, the median distance between the marker and isocenter decreased to 34.0 (IQR: 33.4-39.7) mm. With a median follow-up period of 25.3 (range: 6.9-70.0) months, the 2-year OS and LC rates were 100.0% (95% confidence interval: 100-100). An isocenter shift makes SBRT with SyncTraX feasible in cases where the fiducial marker is distant from the tumor., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66 Gy in 33 fractions for T1 disease and 70 Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0 to 2.5 Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9 months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT., Methods: We analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors., Results: The median age of the 49 patients was 72 (range: 70-78) years. The median CDDP dose was 200 (40-280) mg/ m 2 , and 47 patients completed scheduled radiotherapy. Forty-eight patients (98.0%) had a performance status of ≥ 1 at the initial visit. The 3-year OS, PFS, and CSS were 80.9% (95% confidence interval [CI]: 64.8-90.7), 68.3% (95% CI 51.8-81.2), and 85.0% (95% CI 68.7-93.4), respectively. In the multivariate analysis, the cumulative CDDP dose (< 200 or ≥ 200 mg/m 2 ) was a significant factor for OS (hazard ratio: 0.29 [95% CI 0.08-0.97], p = 0.044). There was one case of early mortality. Grade 3 or higher late adverse events were observed in four patients (8.2%)., Conclusions: Weekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m 2 in older patients. Trial registration Retrospectively registered., (© 2023. The Author(s).)

Objectives: We aimed to investigate whether daily computed tomography (CT) images could predict the daily gastroduodenal, small intestine, and large intestine doses of stereotactic body radiation therapy (SBRT) for pancreatic cancer based on the shortest distance between the gross tumor volume (GTV) and gastrointestinal (GI) tract., Methods: Twelve patients with pancreatic cancer received SBRT of 40 Gy in five fractions. We recalculated the reference clinical SBRT plan (PLAN ref ) using daily CT images and calculated the shortest distance from the GTV to each GI tract. The maximum dose delivered to 0.5 cc (D 0.5cc ) was evaluated for each planning at-risk volume of the GI tract. Spearman's correlation test was used to determine the association between the daily change in the shortest distance (Δshortest distance) and the ratio of ΔD 0.5cc dose to D 0.5cc dose in PLAN ref (ΔD 0.5cc /PLAN ref ) for quantitative analysis., Results: The median shortest distance in PLAN ref was 0 mm in the gastroduodenum (interquartile range, 0-2.7), 16.7 mm in the small intestine (10.0-23.7), and 16.7 mm in the large intestine (8.3-28.1 mm). The D 0.5cc of PLAN ref in the gastroduodenum was >30 Gy in all patients, with 10 (83.3%) having the highest dose. A significant association was found between the Δshortest distance and ΔD 0.5cc / PLAN ref in the small or large intestine ( p < 0.001) but not in the gastroduodenum ( p = 0.404)., Conclusions: The gastroduodenum had a higher D 0.5cc and predicting the daily dose was difficult. Daily dose calculations of the GI tract are recommended for safe SBRT., Advances in Knowledge: This study aimed to predict the daily doses in SBRT for pancreatic cancer from the shortest distance between the GTV and the gastrointestinal tract.Daily changes in the shortest distance can predict the daily dose to the small or large intestines, but not to the gastroduodenum., (© 2023 The Authors. Published by the British Institute of Radiology.)

Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account., (© 2023. The Author(s).)

Background: The standard of care for sinonasal mucosal melanoma is surgery and postoperative radiotherapy (PORT). Our treatment strategy comprises endoscopic resection and PORT. We performed combined endoscopic and open resection or applied an external approach alone when sufficient resection was difficult to achieve endoscopically. The objective of this study was to evaluate the validity of our treatment strategy., Methods: We assessed 30 patients with sinonasal mucosal melanoma who underwent definitive therapy between January 2002 and April 2021, and conducted a retrospective analysis. The median follow-up period was 2.2 years. The primary endpoint was overall survival. The Kaplan-Meier method was used for the calculation of survival rates, the cumulative incidence of distant metastasis, and local recurrence., Results: Twenty-eight patients underwent surgery. The other two patients were treated by definitive proton beam therapy. Twenty-one of 28 (75%) patients underwent resection by endoscopic approach alone. Postoperative radiotherapy was performed for all 28 patients who underwent surgery. Twenty-one patients (70%) experienced recurrence during the observation period. Overall, distant metastasis was observed in 19 patients. Twelve patients died during the observation period, with 10 of the 12 patients (83%) dying of distant metastasis. The overall survival rate at 2 and 5 years was 70% and 46%, respectively. The cumulative incidence rate of distant metastasis at 2 years was 63%, while the 2-year cumulative incidence rate of local recurrence was 6.7%., Conclusion: The local disease was controlled by our treatment strategy. To improve treatment outcomes, control of the distant metastasis is needed., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT)., Methods: A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score., Results: A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1 year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04)., Conclusion: This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The local anesthetic (LA) systemic toxicity of trunk blocks is a major concern. Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has attracted attention; however, plasma LA level is unknown. We tested whether the peak plasma LA concentration following M-TAPA, using 25 mL of 0.25% levobupivacaine mixed with epinephrine on each side, would be below the toxic level (2.6 μg/mL). We recruited 10 patients undergoing abdominal surgery with planned M-TAPA between November 2021 and February 2022. In all patients, 25 mL of 0.25% levobupivacaine mixed with 1:200,000 epinephrine was administered on each side. Blood samples were obtained at 10, 20, 30, 45, 60, and 120 min after the block. The highest individual peak and the mean peak plasma LA concentrations were 1.03 and 0.73 μg/mL, respectively. We could not capture the peak in five patients; however, the highest concentrations in all patients were significantly lower than the toxic level. A negative correlation between the peak level and body weight was observed. Our results indicated that the plasma LA concentration following M-TAPA using total of 50 mL of 0.25% levobupivacaine with epinephrine remains below the toxic level. Further research is required due to the small sample size of this study.Trial registry number: UMIN000045406., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control., Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis., Results: The 59 patients (35 men, 24 women; median age: 71 years; range: 41-91 years) had PS of 0 ( n = 47), 1 ( n = 10), and 2 ( n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A ( n = 46), B ( n = 7), and unknown ( n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I ( n = 12), II ( n = 19), III ( n = 10), and IV ( n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher., Conclusion: PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69 years (range: 41-88 years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908 days (range: 76-1669 days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity., Purpose: We evaluated the effectiveness of computed tomography (CT)-image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image-guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated., Methods: A retrospective analysis was conducted using 570 sets of daily CT (dCT) images throughout whole treatment fractions for 38 HCC patients who underwent passive scattering proton therapy with either a 66 cobalt gray equivalent (GyE)/10 fractions (n = 19) or 76 GyE/20 fractions (n = 19) protocol. The actual daily delivered dose distributions were estimated by forward calculation using the dCT sets, their corresponding treatment plans, and the recorded daily couch correction information. We then evaluated the daily changes of the dose indices D 99% , V 30GyE , and D max for the tumor volumes, non-tumorous liver, and other OARs, that is, stomach, esophagus, duodenum, colon, respectively. Contours were created for all dCT sets. We validated the efficacy of the dCT-based tumor registrations (hereafter, "tumor registration") by comparing them with the bone registration and diaphragm registration as a simulation of the treatment based on the positioning using the conventional kV X-ray imaging. The dose distributions and the indices of three registrations were obtained by simulation using the same dCT sets., Results: In the 66 GyE/10 fractions, the daily D 99% value in both the tumor and diaphragm registrations agreed with the planned value with 3%-6% (SD), and the V 30GyE value for the liver agreed within ±3%; the indices in the bone registration showed greater deterioration. Nevertheless, tumor-dose deterioration occurred in all registration methods for two cases due to daily changes of body shape and respiratory condition. In the 76 GyE/20 fractions, in particular for such a treatment that the dose constraints for the OARs have to be cared in the original planning, the daily D 99% in the tumor registration was superior to that in the other registration (p < 0.001), indicating the effectiveness of the tumor registration. The dose constraints, set in the plan as the maximum dose for OARs (i.e., duodenum, stomach, colon, and esophagus) were maintained for 16 patients including seven treated with re-planning. For three patients, the daily D max increased gradually or changed randomly, resulting in an inter-fractional averaged D max higher than the constraints. The dose distribution would have been improved if re-planning had been conducted. The results of these retrospective analyses indicate the importance of daily dose monitoring followed by adaptive re-planning when needed., Conclusions: The tumor registration in proton treatment for HCC was effective to maintain the daily dose to the tumor and the dose constraints of OARs, particularly in the treatment where the maintenance for the dose constraints needs to be considered throughout the treatment. Nevertheless daily proton dose monitoring with daily CT imaging is important for more reliable and safer treatment., (© 2023 American Association of Physicists in Medicine.)

Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: In a previous study of hepatic toxicity, the following three factors were identified to predict the benefits of proton beam therapy (PBT) for hepatocellular carcinomas (HCCs) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (1 vs ≥2), the location of tumors (hepatic hilum or others), and the sum of the diameters of lesions. The aim of this study is to analyze the association between these three factors and hepatic toxicity., Methods: We retrospectively reviewed patients of CP-A treated with PBT or photon stereotactic body radiotherapy (X-ray radiotherapy, XRT) for HCC ≤5 cm. For normal liver dose, the V5, V10, V20 (volumes receiving 5, 10, and 20 Gy at least), and the mean dose was evaluated. The albumin-bilirubin (ALBI) and CP score changes from the baseline were evaluated at 3 and 6 months after treatment., Results: In 89 patients (XRT: 48, PBT: 41), those with two or three (2-3) predictive factors were higher normal liver doses than with zero or one (0-1) factor. In the PBT group, the ALBI score worsened more in patients with 2-3 factors than those with 0-1 factor, at 3 months (median: 0.26 vs 0.02, p = 0.032) and at 6 months (median: 0.35 vs 0.10, p = 0.009). The ALBI score change in the XRT group and CP score change in either modality were not significantly different in the number of predictive factors., Conclusion: The predictive factor numbers predicted the ALBI score change in PBT but not in XRT., Advances in Knowledge: This study suggest that the number of predictive factors previously identified (0-1 vs 2-3) were significantly associated with dosimetric parameters of the normal liver in both modalities. In the proton group, the number of predictive factors was associated with a worsening ALBI score at 3 and 6 months, but these associations were not found in the photon SBRT group.

Background: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed., Methods: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results., Results: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months)., Conclusions: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions., (© 2023. The Author(s).)

Introduction: Sequential boost intensity-modulated radiotherapy (SQB-IMRT) uses two different planning CTs (pCTs) and treatment plans. SQB-IMRT is a form of adaptive radiotherapy that allows for responses to changes in the shape of the tumour and organs at risk (OAR). On the other hand, dose accumulation with the two plans can be difficult to evaluate. The purpose of this study was to analyse patterns of loco-regional failure using deformable image registration (DIR) in hypopharyngeal cancer patients treated with SQB-IMRT., Methods: Between 2013 and 2019, 102 patients with hypopharyngeal cancer were treated with definitive SQB-IMRT at our institution. Dose accumulation with the 1st and 2nd plans was performed, and the dose to the loco-regional recurrent tumour volume was calculated using the DIR workflow. Failure was classified as follows: (i) in-field (≥95% of the recurrent tumour volume received 95% of the prescribed dose); (ii) marginal (20-95%); or (iii) out-of-field (<20%)., Results: After a median follow-up period of 25 months, loco-regional failure occurred in 34 patients. Dose-volume histogram analysis showed that all loco-regional failures occurred in the field within 95% of the prescribed dose, with no marginal or out-of-field recurrences observed., Conclusion: The dosimetric analysis using DIR showed that all loco-regional failures were within the high-dose region. More aggressive treatment may be required for gross tumours., (© 2022 Royal Australian and New Zealand College of Radiologists.)

Background: Online adaptation during intensity-modulated proton therapy (IMPT) can minimize the effect of inter-fractional anatomical changes, but remains challenging because of the complex workflow. One approach for fast and automated online IMPT adaptation is dose restoration, which restores the initial dose distribution on the updated anatomy. However, this method may fail in cases where tumor deformation or position changes occur., Purpose: To develop a fast and robust IMPT online adaptation method named "deformed dose restoration (DDR)" that can adjust for inter-fractional tumor deformation and position changes., Methods: The DDR method comprises two steps: (1) calculation of the deformed dose distribution, and (2) restoration of the deformed dose distribution. First, the deformable image registration (DIR) between the initial clinical target volume (CTV) and the new CTV were performed to calculate the vector field. To ensure robustness for setup and range uncertainty and the ability to restore the deformed dose distribution, an expanded CTV-based registration to maintain the dose gradient outside the CTV was developed. The deformed dose distribution was obtained by applying the vector field to the initial dose distribution. Then, the voxel-by-voxel dose difference optimization was performed to calculate beam parameters that restore the deformed dose distribution on the updated anatomy. The optimization function was the sum of total dose differences and dose differences of each field to restore the initial dose overlap of each field. This method only requires target contouring, which eliminates the need for organs at risk (OARs) contouring. Six clinical cases wherein the tumor deformation and/or position changed on repeated CTs were selected. DDR feasibility was evaluated by comparing the results with those from three other strategies, namely, not adapted (continuing the initial plan), adapted by previous dose restoration, and fully optimized., Results: In all cases, continuing the initial plan was largely distorted on the repeated CTs and the dose-volume histogram (DVH) metrics for the target were reduced due to the tumor deformation or position changes. On the other hand, DDR improved DVH metrics for the target to the same level as the initial dose distribution. Dose increase was seen for some OARs because tumor growth had reduced the relative distance between CTVs and OARs. Robustness evaluation for setup and range uncertainty (3 mm/3.5%) showed that deviation in DVH-bandwidth for CTV D 95% from the initial plan was 0.4% ± 0.5% (Mean ± S.D.) for DDR. The calculation time was 8.1 ± 6.4 min., Conclusions: An online adaptation algorithm was developed that improved the treatment quality for inter-fractional anatomical changes and retained robustness for intra-fractional setup and range uncertainty. The main advantage of this method is that it only requires target contouring alone and saves the time for OARs contouring. The fast and robust adaptation method for tumor deformation and position changes described here can reduce the need for offline adaptation and improve treatment efficiency., (© 2022 American Association of Physicists in Medicine.)

Background: The aim of this study is to quantify the short-term motion of the gastrointestinal tract (GI-tract) and its impact on dosimetric parameters in stereotactic body radiation therapy (SBRT) for pancreatic cancer., Methods: The analyzed patients were eleven pancreatic cancer patients treated with SBRT or proton beam therapy. To ensure a fair analysis, the simulation SBRT plan was generated on the planning CT in all patients with the dose prescription of 40 Gy in 5 fractions. The GI-tract motion (stomach, duodenum, small and large intestine) was evaluated using three CT images scanned at spontaneous expiration. After fiducial-based rigid image registration, the contours in each CT image were generated and transferred to the planning CT, then the organ motion was evaluated. Planning at risk volumes (PRV) of each GI-tract were generated by adding 5 mm margins, and the volume receiving at least 33 Gy (V 33 ) < 0.5 cm 3 was evaluated as the dose constraint., Results: The median interval between the first and last CT scans was 736 s (interquartile range, IQR:624-986). To compensate for the GI-tract motion based on the planning CT, the necessary median margin was 8.0 mm (IQR: 8.0-10.0) for the duodenum and 14.0 mm (12.0-16.0) for the small intestine. Compared to the planned V 33 with the worst case, the median V 33 in the PRV of the duodenum significantly increased from 0.20 cm 3 (IQR: 0.02-0.26) to 0.33 cm 3 (0.10-0.59) at Wilcoxon signed-rank test (p = 0.031)., Conclusion: The short-term motions of the GI-tract lead to high dose differences., Competing Interests: K.K. is an employee of the research institute of Hitachi, Ltd., currently working at Hokkaido University, under a secondary agreement. K.K. declares that this research has no relationship with Hitachi, Ltd. All other authors declare that they have no conflicts of interest., (© 2023 The Authors.)

Purpose: Studies in adults have reported that video laryngoscope is more useful than direct laryngoscope when training less experienced anesthesiologists. However, whether this is true for infants remains unclear. Therefore, this study aimed to evaluate whether the use of video laryngoscope would result in smaller differences in success rate according to anesthesiologists' expertise than those in direct laryngoscope., Methods: Medical records and video recordings from the operating room of patients aged < 1 year who underwent non-cardiac surgery between March 2019 and September 2021 were reviewed. Tracheal intubations between April 8, 2020, and June 20, 2021, were excluded due to the shortage of video laryngoscope blades during the COVID-19 pandemic. Rates of first-time tracheal intubation success were compared by years of anesthesia experience and initial intubation device., Results: In total, 125 of 175 tracheal intubations were analyzed (direct laryngoscope group, n = 72; video laryngoscope group, n = 53). The first-time tracheal intubation success rate increased with years of experience as an anesthesiologist in the direct laryngoscope group (odds ratio OR 1.70, 95% confidence interval CI 1.15, 2.49; P = 0.0070), but not the video laryngoscope group (OR 0.99, 95% CI 0.74, 1.35; P = 0.99)., Conclusion: The differences in success rate according to the anesthesiologists' years of experience were non-significant when using video laryngoscope in infants, compared to those in direct laryngoscope., (© 2022. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Background: The relative biological effectiveness (RBE) of proton is considered to be dependent on biological parameters and fractional dose. While hyperfractionated photon therapy was effective in the treatment of patients with head and neck cancers, its effect in intensity-modulated proton therapy (IMPT) under the variable RBE has not been investigated in detail., Purpose: To study the effect of variable RBE on hyperfractionated IMPT for the treatment of pharyngeal cancer. We investigated the biologically effective dose (BED) to determine the theoretical effective hyperfractionated schedule., Methods: The treatment plans of three pharyngeal cancer patients were used to define the ΔBED for the clinical target volume (CTV) and soft tissue (acute and late reaction) as the difference between the BED for the altered schedule with variable RBE and conventional schedule with constant RBE. The ΔBED with several combinations of parameters (treatment days, number of fractions, and prescribed dose) was comprehensively calculated. Of the candidate schedules, the one that commonly gave a higher ΔBED for CTV was selected as the resultant schedule. The BED volume histogram was used to compare the influence of variable RBE and fractionation., Results: In the conventional schedule, compared with the constant RBE, the variable RBE resulted in a mean 2.6 and 2.7 Gy reduction of BED mean for the CTV and soft tissue (acute reaction) of the three plans, respectively. Moreover, the BED mean for soft tissue (late reaction) increased by 7.4 Gy, indicating a potential risk of increased RBE. Comprehensive calculation of the ΔBED resulted in the hyperfractionated schedule of 80.52 Gy (RBE = 1.1)/66 fractions in 6.5 weeks. When variable RBE was used, compared with the conventional schedule, the hyperfractionated schedule increased the BED mean for CTV by 7.6 Gy; however, this was associated with a 7.8 Gy increase for soft tissue (acute reaction). The BED mean for soft tissue (late reaction) decreased by 2.4 Gy., Conclusion: The results indicated a potential effect of the variable RBE on IMPT for pharyngeal cancer but with the possibility that hyperfractionation could outweigh this effect. Although biological uncertainties require conservative use of the resultant schedule, hyperfractionation is expected to be an effective strategy in IMPT for pharyngeal cancer., (© 2022 American Association of Physicists in Medicine.)

Background: For small primary liver tumors, favorable outcomes have been reported with both of proton beam therapy (PBT) and X-ray therapy (XRT). However, no clear criteria have been proposed in the cases for which and when of PBT or XRT has to be used. The aim of this study is to investigate cases that would benefit from PBT based on the predicted rate of hepatic toxicity., Materials and Methods: Eligible patients were those who underwent PBT for primary liver tumors with a maximum diameter of ≤ 5 cm and Child-Pugh grade A (n = 40). To compare the PBT-plan, the treatment plan using volumetric modulated arc therapy was generated as the XRT-plan. The rate of predicted hepatic toxicity was estimated using five normal tissue complication probability (NTCP) models with three different endpoints. The differences in NTCP values (ΔNTCP) were calculated to determine the relative advantage of PBT. Factors predicting benefits of PBT were analyzed by logistic regression analysis., Results: From the dose-volume histogram comparisons, an advantage of PBT was found in sparing of the normal liver receiving low doses. The factors predicting the benefit of PBT differed depending on the selected NTCP model. From the five models, the total tumor diameter (sum of the target tumors), location (hepatic hilum vs other), and number of tumors (1 vs 2) were significant factors., Conclusions: From the radiation-related hepatic toxicity, factors were identified to predict benefits of PBT in primary liver tumors with Child-Pugh grade A, with the maximum tumor diameter of ≤ 5 cm., Competing Interests: K.K. is an employee of the research institute of Hitachi, Ltd., currently working for Hokkaido University under a secondment agreement. K.K. declares that this research has no relationship to Hitachi, Ltd. All other authors declare that they have no conflicts of interest to declare., (© 2022 The Author(s).)

Aim: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients., Methods: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/β ratio of 10 (BED 10 ), the median dose in BED 10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method., Results: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED 10 ≥100 Gy group than in the BED 10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point., Conclusion: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED 10 ≥100 Gy to the reference point., (© 2021 The Japan Society of Hepatology.)

Background: Aging and pre-existing cognitive impairment are considered to be independent risk factors for sepsis-associated encephalopathy. This study aimed to investigate the manner in which aging and pre-existing cognitive dysfunction modified neuroinflammation, synaptic plasticity, and basal synaptic transmission during the acute phase of sepsis using Senescence-Accelerated Mice Prone 8 (SAMP8) and Senescence-Accelerated Resistant Mice 1 (SAMR1)., Methods: We used 6-month-old SAMP8 and SAMR1. Sepsis was induced using cecal ligation and puncture (CLP). The animal's hippocampi and blood were collected for subsequent investigations 24 h after surgery., Results: Long-term potentiation (LTP) was impaired in the Shaffer-collateral (SC)-CA1 pathway of the hippocampus in SAMP8 without surgery compared to the age-matched SAMR1, which was reflective of cognitive dysfunction in SAMP8. CLP impaired the SC-CA1 LTP in SAMR1 compared to the sham-operated controls, but not in SAMP8. Moreover, CLP decreased the input-output curve and increased the paired-pulse ratio in SAMP8, suggesting the reduced probability of basal synaptic transmission due to sepsis. Immunohistochemical analysis revealed that CLP elevated IL-1β levels, especially in the hippocampi of SAMP8 with microglial activation. In vivo peripheral IL-1 receptor antagonist (IL-1ra) administration in the septic SAMP8 revealed that the neuroinflammation was not correlated with the peripheral elevation of IL-1β. Ex vivo IL-1ra administration to the hippocampus ameliorated LTP impairment in SAMR1 and the reduction in basal transmission in SAMP8 after sepsis., Conclusions: The mechanism of the modulation of synaptic transmission and synaptic plasticity by the acute stage of sepsis differed between SAMR1 and SAMP8. These changes were related to centrally derived IL-1 receptor-mediated signaling and were accompanied by microglial activation, especially in SAMP8., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hoshino, Uchinami, Uchida, Saito and Morimoto.)

Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating. Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed. Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver ( n =  4) or intrahepatic vessels ( n =  5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered. Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.