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We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

This study investigates the dosimetric effects of different gantry rotation angles used in volumetric modulated arc therapy (VMAT) for early glottic carcinoma. VMAT treatment plans using full-arc, half-arc, and partial-arc gantry rotation angles were generated from 22 computed tomography datasets of early-stage (T1-2N0) glottic laryngeal cancer. Dosimetric parameters associated with the planning target volume (PTV) and organs at risk (OARs), specifically the carotid arteries and thyroid, were compared. To assess the robustness of the VMAT plans, dose variations were analyzed by introducing positional shifts of 1, 3, and 5 mm from the isocenter of each plan along the superior-inferior, left-right, and anterior-posterior axes. Furthermore, we examined the size of the PTV, the air cavity volume within the PTV, and the variability of the beam path length through the gantry angles to investigate their correlations with PTV dose variations in the presence of positioning errors. Compared to full-arc and half-arc plans, the dosimetric parameters of partial-arc plans were found to be higher in PTV (D2%, D5%, D50%, and D mean ) and lower in OARs, while their dose variations of OAR parameters were greater for positioning errors. In addition, a correlation was observed between PTV size and PTV dose variations. Air cavity volume and depth variability were also correlated with some PTV parameters, depending on the arc plan. The results presented in this study suggest that the partial-arc gantry angles can allow higher PTV doses while minimizing OAR doses in VMAT treatment planning for early glottic cancer. However, the small delivery angles may lead to greater dose variations in the OARs when positioning errors occur., 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 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer., Materials and Methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival., Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival., Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy., 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., (© 2023 The Authors.)

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial., Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%., Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met., Conclusion: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses., Competing Interests: Dr. Itami reports personal fees from HekaBio, grants and personal fees from Itochu, grants from Elekta, personal fees from AlphaTAU, personal fees from ViewRay, personal fees from Palette Science, outside the submitted work., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis., Methods: We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group., Results: Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group., Conclusions: Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background and Purpose: To determine the optimal primary tumor dose for cervical cancer treatment using computed tomography (CT)-based image-guided brachytherapy (IGBT)., Materials and Methods: We retrospectively reviewed 171 patients with cervical cancer who underwent both external beam radiation therapy (EBRT) and IGBT between May 2015 and December 2019. Majority of EBRT plan included central shielding technique. CT-based IGBT was performed weekly a median of three times. Magnetic resonance imaging preceded the first and third session of IGBT for target delineation., Results: The median age of the patients was 64 years (range: 30-91 years). The median follow-up time for living patients was 43 months (range: 6-76 months). The 3-year local control rates according to the International Federation of Gynecology and Obstetrics (FIGO, 2008) stages were 89%, 100%, 92%, 89%, 78%, and 100% for stages IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. The median EBRT dose to the central pelvis and parametrium/pelvic wall was 41.4 Gy and 50.4 Gy, respectively. Patients who received a cumulative 2 Gy equivalent dose (EQD2) (α/β = 10 Gy) of high-risk clinical target volume (HR CTV) D90% ≥ 75 Gy achieved a long-term local control rate of 93%, compared with 80% in those who received <75 Gy (p = 0.02)., Conclusion: This is one of the largest CT-based IGBT series examining the treatment of cervical cancer based on the tumor dose-volume relationship. An HR CTV D90% ≥75 Gy was significantly associated with favorable local control in this study., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer., Methods: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%., Results: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036)., Conclusion: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: There are limited reports on outcomes of three-dimensional image-guided brachytherapy (3D-IGBT) for cervical adenocarcinoma in Asia. In a multi-institutional retrospective study, we assessed the clinical outcomes of three-dimensional image-guided brachytherapy for cervical adenocarcinoma or adenosquamous carcinoma (CA/CAC) in Asian countries., Material and Methods: Patients who had undergone definitive radiation therapy/concurrent chemoradiotherapy for untreated cervical cancer between 2000 and 2016 were registered. Those who had undergone 3D-IGBT for histologically proven CA/CAC were included. Data on patients' characteristics and treatment were collected, including tumor reduction rate (defined as a percentage of reduction in tumor size before brachytherapy compared with that at diagnosis) and high-risk clinical target volume D 90 . Overall survival (OS), local control (LC), and progression-free survival (PFS) rates were calculated using Kaplan-Meier method. Late toxicities were assessed using common terminology criteria for adverse events version 4.0., Results: Anonymized data of 498 patients were collected. Of the 498 patients, 36 patients met inclusion criteria. The median follow-up period was 39 months. The 3-year OS, LC, and PFS rates were 68.4%, 68.5%, and 44.4%, respectively. After treatment, five patients had tumor re-growth without complete disappearance of the tumor. Two patients developed grade 3 vaginal toxicity or grade 4 rectal toxicity; none developed other severe late toxicities. A tumor reduction rate of > 26.3% was the only significant factor in multivariate analyses, and was associated with significantly better OS ( p = 0.018), LC ( p = 0.022), and PFS ( p = 0.013). There were no significant trends in local control or dose to high-risk clinical target volume D 90 ., Conclusions: LC rate of CA/CAC was insufficient despite 3D-IGBT. Meanwhile, tumor reduction rate was associated with LC, OS, and PFS rates. Therefore, CA/CAC may require a different treatment strategy than that applied in cervical squamous cell carcinoma., Competing Interests: Dr Okonogi reports grants and other (investigational drug supply) from AstraZeneca clinical trial, outside the submitted work. Dr Igaki reports grants and personal fees from HekaBio, grants from CICS, grants from Elekta KK, personal fees from AstraZeneca, personal fees from Itochu, personal fees from HIMEDIC, and personal fees from Varian, outside the submitted work. Dr Itami reports grants from Elekta KK, grants and personal fees from Itochu, personal fees from ViewRay, personal fees from Palette Science, personal fees from Alpha-TAU, and personal fees from HekaBio, outside the submitted work. This study received no financial support from any company; thus, there are no conflicts of interests to declare., (Copyright © 2022 Termedia.)

This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1-139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding., Methods: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment., Results: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/β = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively., Conclusions: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding., (© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

High-dose-rate brachytherapy by remote afterloading is now performed under three-dimensional image guidance by CT or MRI. Three-dimensional image-guided brachytherapy in cervical cancer disclosed that the traditional intracavitary brachytherapy by Manchester method cannot deliver an adequate dose to the large tumor with resulting local recurrence. To improve the local control rate, combined interstitial and intracavitary (hybrid) brachytherapy can increase the dose to the large parametrial involvement without increasing the dose to the rectum and bladder. Whether hybrid brachytherapy can be performed safely on a multi-institutional basis remains to be studied. From 2015, phase I/II study of hybrid brachytherapy was launched in Japan, and it was revealed that hybrid brachytherapy can be performed safely and with a high quality of radiation dose distribution in a multi-institutional study. In Japan, the number of patients undergoing hybrid brachytherapy in cervical cancer is rapidly rising. Education and clinical trial are very important to establish hybrid brachytherapy in the management of cervical cancer., Competing Interests: The authors report research grant from Elekta and ITOCHU and consultation honoraria from HekaBio, Alpha-TAU, and Palette Science., (Copyright © 2022 Itami, Murakami, Watanabe, Sekii, Kasamatsu, Kato, Hirowatari, Ikushima, Ando, Ohno, Okamoto, Okuma and Igaki.)

Objective: The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity., Methods: From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTV HR D 90 were compared., Results: Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTV HR D 90 50-60 Gy, 60-70 Gy, 70-80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D 2cc and incidence of late adverse events decreased as CTV HR D 90 decreased., Conclusions: The low-risk patients achieved favorable local control with CTV HR D 90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups' backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer., Methods: Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer., Results: Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival., Conclusions: Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Some studies have demonstrated that concurrent chemo-radiotherapy is an effective salvage treatment for isolated para-aortic lymph node (PALN) recurrence. However, no studies have compared multi-treatment modalities, such as radiation therapy (RT), concurrent chemoradiotherapy (CCRT), surgery, chemotherapy, and best supportive care (BSC), across a sufficient number of patients with PALN recurrence. We thus aimed to evaluate the clinical outcomes of multi-treatment modalities for isolated PALN recurrence in uterine cervical cancer., Methods: Records of 50 patients who were first diagnosed with isolated PALN recurrence after definitive cervical cancer treatment from 2002 to 2016 at our institution were reviewed retrospectively. The initial definitive cervical cancer therapies included RT alone, CCRT, or surgery with or without post-operative RT. The median follow-up time was 33 months. The median age at recurrence diagnosis was 57 years (range, 26-84 years). The median duration between the end of initial treatment and recurrence was 10 months (range, 1-91 months). The median maximum metastatic lesion size was 17 mm (range, 8-60 mm). Twenty-four patients had one or two PALN metastases, while 26 had 3 or more. Eighteen patients were treated for recurrence with RT alone, seven with CCRT, three with surgery, 17 with chemotherapy, and five with BSC. Potential prognostic factors included histopathology, initial FIGO stage, initial treatment, age at recurrence, tumor markers (serum SCC-Ag and CEA) at recurrence, time to recurrence, maximum size of the metastatic lesion, number of metastases, and the recurrence treatment method., Results: The 3-year overall survival (OS) rates of all patients were 47.0%. The 3-year OS rate of patients who underwent CCRT for recurrence was 85.7%; surgery, 66.7%; chemotherapy, 48.8%; RT, 41.3%; and BSC, 0% (p = 0.014). Univariate analysis revealed that only the recurrence treatment method was significantly associated with OS. The 3-year local control rate (LCR) and progression free survival (PFS) rate for CCRT were 100 and 71.4%; for surgery, 100 and 66.7%; for chemotherapy, 33.6 and 13.7%; and for RT, 55.5 and 14.1%, respectively (LCR: p = 0.028, PFS: p = 0.059). The number of metastatic lesions, SCC-Ag levels and recurrence treatment method were significantly associated with LCR. Age at recurrence, SCC-Ag levels, and number of metastatic lesions were significantly associated with PFS., Conclusions: Although our patient cohort size was small, our results suggest that CCRT may be effective in preventing local disease recurrence in the PALN and may improve OS.

Our observational study aimed to verify the safety of our original titanium fiducial markers in gynecological cancer by using a simple insertion method. We prospectively evaluated the safety in patients with gynecological cancer who had undergone our insertion procedure of the titanium markers. The decision to implant a titanium marker was at the discretion of each radiation oncologist. The fiducial markers were manufactured by severing ligating clips for surgery into 3-6 mm pieces and were sterilized thereafter. We inserted an 18-gauge injection needle containing the marker before the marker was extruded by a 22-gauge Cattelan needle or shape memory alloy wire into the tumor or tissues close to the tumor. Severe complications within 3 months after implantation were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0. Between August 2016 and December 2018, we enrolled 46 patients. Of 46, 44 underwent implantation. The median age was 58.5 years. The most common primary site was the cervix. Two patients experienced detachment of the markers after implantation. No Grade 3 or higher level of complications was observed. Our simple insertion technique for original titanium fiducial markers was well-tolerated., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: The selection of radiation therapy dose fractionation schedules for bone metastases is often based on the estimation of life expectancy. Therefore, accurate prognosis prediction is an important issue. It is reported that the Katagiri scoring system can be used to predict the survival of patients with bone metastases. We aimed to assess prognostic factors and validate the Katagiri scoring system in patients who were treated with radiation therapy for bone metastases., Materials/methods: We retrospectively reviewed data of all patients who were treated with radiation therapy for bone metastases between 2004 and 2013. Age, sex, Karnofsky performance status (KPS), Eastern Cooperative Oncology Group performance status (ECOG PS), primary site (lesions and characteristics), visceral metastases, laboratory data, previous chemotherapy, and multiple bone metastases were analyzed for associations with overall survival (OS). Katagiri scores were calculated for each patient and were used to compare OS., Results: Out of the 616 patients included in this analysis, 574 had died and 42 remained alive. The median follow-up time for survivors was 42 months. Univariate analysis revealed that age (P = 0.604) and multiple bone metastases (P = 0.691) were not significantly associated with OS. Multivariate analysis revealed that sex, ECOG PS, KPS, primary characteristics, visceral metastases, laboratory data, and previous chemotherapy were significantly associated with OS. The survival rates at 3, 6, 12, and 24 months, categorized by Katagiri score, were as follows: score 0-3, 94.4, 77.8, and 61.1%, respectively; score 4-6, 67.7, 48.7, and 31.2%, respectively; and score 7-10, 39.1, 22.1, and 9.0%, respectively (P < 0.001)., Conclusion: Sex, ECOG PS, KPS, primary characteristics, visceral metastases, laboratory data, and previous chemotherapy were significant predictors of survival in patients with bone metastases. The Katagiri scoring system was significantly correlated with OS and can help us select the optimal dose-fractionation.

Purpose: In this paper, we report cases of two patients with vaginal tumor who underwent interstitial brachytherapy (ISBT), using three-dimensional (3D)-printed personalized templates designed inversely from computed tomography (CT) or magnetic resonance (MR) images., Material and Methods: Patient 1 presenting with vaginal vault recurrence was planned to receive whole pelvis external beam radiotherapy (EBRT) followed by ISBT. The tumor invaded the paracolpium; thus, we planned to administer ISBT to include the tumor and vaginal membrane. A template was designed with holes for plastic needle applicator insertion considering the appropriate direction based on pre-treatment medical images. Patient 2 presenting with vaginal cancer was scheduled to receive EBRT and ISBT because of a paracolpium invasion. Before ISBT, MR imaging was performed with vaginal cylinder inserted in the patient's vagina. By measuring the length of the tumor manually and projecting the tumor orthogonally to a plane parallel to the bottom surface of the cylinder applicator, a template was designed. Computer-aided design software was used for planning both templates. Polycarbonate/acrylonitrile-butadiene-styrene resin was selected as material of the templates., Results: Patient 1 received 4-fraction ISBT one week apart. A mean of 10 applicators were inserted through the holes of the template in an average of 9 minutes (range, 5-15 minutes). All applicators were inserted toward the planned directions. Median minimum dose covering 90% (D 90% ) of the clinical target volume (CTV) was 634 cGy. Patient 2 underwent three-fraction irradiation twice daily at 6-hour interval. All applicators were inserted through the inside of the template. The median D 90% of the CTV was 703 cGy. No grade 3 or higher toxicity were found in both series., Conclusions: 3D-printed templates designed using medical images are useful, especially for ISBT of vaginal tumors. Further verification of clinical indications, design of templates, and manufacturing process are needed., Competing Interests: Authors report no conflict of interest.

Aim: To investigate the intrafraction movement of the esophagus using fiducial markers., Background: Studies on intrafraction esophageal motion using the fiducial markers are scarce., Materials and Methods: We retrospectively analyzed patients with clinical T1N0 esophageal cancer who had received fiducial markers at our hospital between July 2007 and December 2013. Real-Time Position Management System to track the patient's respiration was used, and each patient underwent three-dimensional computed tomography of the resting expiratory and inspiratory level. We used the center of the marker to calculate the distance between the expiratory and inspiratory breath-holds, which were measured with the radiotherapy treatment planning system in three directions: left-right (LR), superior-inferior (SI), and anterior-posterior (AP). The movements at each site were compared with the Kruskal-Wallis analysis and Wilcoxon rank sum test with a Bonferroni correction., Results: A total of 101 patients with 201 fiducial markers were included. The upper, middle and lower thoracic positions had 40, 77, and 84 markers, respectively. The mean absolute magnitudes of the shifts (standard deviation) were 0.18 (0.19) cm, 0.68 (0.46) cm, and 0.24 (0.24) cm in the LR, SI, and AP directions, respectively. From the cumulative frequency distribution, we assumed that 0.35 cm LR, 0.8 cm SI, and 0.3 cm AP in the upper; 0.5 cm LR, 1.55 cm SI, and 0.55 cm AP in the middle; and 0.75 cm LR, 1.9 cm SI, and 0.95 cm AP in the lower thoracic esophagus covered 95% of the cases., Conclusions: The internal margin based on the site of esophagus was estimated.

Objective: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy., Methods: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated., Results: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival., Conclusions: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Purpose: This study was designed to retrospectively analyze outcomes of high-dose-rate (HDR) brachytherapy, with or without external beam radiotherapy (EBRT), in patients with vaginal recurrence of endometrial carcinoma, and to identify factors prognostic of patient outcomes., Material and Methods: The medical records of all patients who underwent HDR brachytherapy for initial recurrence in the vagina of endometrial cancer after definitive surgery between 1992 and 2014 were retrospectively reviewed. All patients underwent either intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT) with or without EBRT. Late toxicity was graded using the EORTC (LENT/SOMA) scale, revised in 1995., Results: Thirty-seven patients were identified. The median follow-up time was 48 months (range: 6-225 months). Of these 37 patients, 23 underwent ICBT, 14 underwent ISBT, and 26 underwent EBRT. Tumor size at first examination of initial relapse was significantly larger in the ISBT than in the ICBT group. The 4-year respective overall survival (OS), local control (LC), and progression-free survival (PFS) rates in the entire cohort were 81.0%, 77.9%, and 56.8%, respectively. The interval between diagnosis of first recurrence and radiotherapy (< 3 months, ≥ 3 months) was a significant predictor of LC and PFS. OS and LC rates did not differ significantly in the ICBT and ISBT groups. Two patients experienced grade 2 rectal bleeding, and four experienced grade 2 hematuria. No grade 3 or higher late complications were observed., Conclusions: Salvage HDR brachytherapy is an optimal for treating vaginal recurrence of endometrial carcinoma with acceptable morbidity. Early radiotherapy, including brachytherapy, should be considered for women who experience vaginal recurrence of endometrial cancer., Competing Interests: Authors report no conflict of interest.

Background: This prospective study aimed to compare dose volume histograms (DVH) of the breasts and organs at risk (OARs) of whole breast radiotherapy in the supine and prone positions, and frequency and severity of acute and late toxicities were analyzed., Methods: Early-stage breast cancer patients with large breasts (Japanese bra size C or larger, or the widest measurements of the bust ≥ 95 cm) undergoing partial mastectomy participated in this study. CT-based treatment plans were made in each position, and various dosimetric parameters for the breast and OARs were calculated to compare the supine and prone radiotherapy plans. The actual treatment was delivered in the position regarded as better., Results: From 2009 to 2010, 22 patients were prospectively accrued. Median follow-up period was 58 months. The homogeneity index and lung doses were significantly lower in the prone position (P = 0.008, P < 0.0001 and P < 0.0001, respectively). Cardiac dose showed no significant differences between two positions. By comparing two plans, the prone position was chosen in 77 % of the patients. In the prone position, ≥ grade 2 acute dermatitis were seen in 47 % of patients treated, whereas 20 % of the patients treated in the supine position had grade 2 and no cases of grade 3, although without a statistical significance of the rates of ≥ grade 2 acute dermatitis between the two positions (P = 0.28). The actual dose measurement using a breast phantom revealed significantly higher surface dose of the breast treated in the prone position than that in the supine position., Conclusions: Breast irradiation in the prone position improves PTV homogeneity and lowers doses to the OARs in the Japanese large-breast patients. However meticulous positioning of the breast in the prone board avoiding the bolus effect is necessary to prevent acute dermatitis.

Purpose: The kidney is a dose-limiting organ for upper abdominal radiotherapy. In this study, radiation-induced kidney injury represented by changes of creatinine clearance (Ccr) and renal parenchymal volume measured by computed tomography (CT) were evaluated by analysing dose-volume histograms (DVHs) in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL) treated with chemoradiotherapy., Materials and Methods: Thirty-eight PGDLBCL patients (seventy-six kidneys) treated with chemoradiotherapy were included in this study. At least 4 years of follow-up was required for eligibility. Patients underwent (immuno-) chemotherapy followed by radiotherapy with approximately 40Gy to the whole stomach and perigastric lymph nodes. Ccr and CT were obtained at least annually. Changes of Ccr and renal parenchymal volume before and 4years after radiotherapy were compared using DVH parameters., Results: Mean Ccr decreased significantly from 82.7mL/min (range, 39-124mL/min) before radiotherapy to 70.4mL/min (range, 35-109mL/min) (p=0.01) 4years after radiotherapy. Mean reduction of bilateral renal parenchymal volume was 12% (range, -5-37%) in the same time period. Ccr and renal parenchymal volume tended to lower over time more than 4years after radiotherapy. Concerning DVH analysis, V20Gy⩾26.6% and D30%⩾19Gy had a significant risk of bilateral renal atrophy of ⩾14% and reduction of the Ccr⩾20mL/min., Conclusion: This study revealed that there was a definite relationship between DVH, renal atrophy and Ccr reduction. V20Gy<26.6% and D30%<19Gy appeared to be safe dose constraints for a Ccr reduction of <20mL/min 4years after radiotherapy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this study was to report the clinical results of salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with cervical cancer with pelvic recurrence after hysterectomy., Patients and Methods: When there was no indication for total pelvic extenteration (TPE) and the tumor depth was more than 5 mm of invasion in the paracolpium, salvage HDR-ISBT was applied., Results: A total of 26 patients were included in this study. The median number of fractions and dose per fraction of HDR-ISBT were 5 (range=3-20 fractions) and 6 Gy (range=2.5-6 Gy), respectively. Three-year local control, progression-free survival, and overall survival were 51.1%, 34.4% and 57.1%, respectively. Combination of external-beam radiation therapy, clinical target volume D90 greater than 65 Gy, and dose per fraction greater than 5 Gy were associated with favorable local control., Conclusion: For patients with recurrent cervical cancer post hysterectomy who are not candidates for TPE, salvage HDR-ISBT is a possible curative treatment modality., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The radiation field for patients with postoperative head and neck squamous cell carcinoma is narrower in our institution than in Western countries to reduce late radiation related toxicities. This strategy is at a risk of loco-regional or distant metastasis. However, because patients are more closely checked than in Western countries by every 1 to 2 months intervals and it is supposed that regional recurrences are identified and salvage surgeries are performed more quickly. Therefore, it is considered that patient survival would not be compromised with this strategy. The aim of this study was to investigate the feasibility of this strategy retrospectively., Methods: Patients who underwent neck dissection with close or positive margin, extra-capsular spread (ECS), multiple regional lymph node metastasis, pT4, with or without primary tumor resection were treated with postoperative radiation therapy. The volume of radiation field, especially the coverage of prophylactic regional lymph node area, was discussed among head and neck surgeons and radiation oncologists taking into account the clinical factors including patient's age, performance status, number of positive lymph nodes, size of metastatic lymph nodes, extension of primary tumor beyond the midline, and existence of ECS., Results: Seventy-two patients were identified who were treated with postoperative radiation therapy for head and neck squamous cell carcinoma between November 2005 and December 2014. There were 20 patients with oropharynx, 19 with hypopharynx, 7 with larynx, 23 with oral cavity, and 3 with other sites. Thirty eight patients had their neck irradiated bilaterally and 34 unilaterally. Median follow-up period for patients without relapse was 20.7 months (5.1-100.7). Thirty two patients had disease relapse after treatment including 22 loco-regional recurrence and 14 distant metastases. Among 22 loco-regional recurrence, seven patients underwent salvage surgery and one of them was no relapse at the time of the analysis. Among patients without bilateral neck lymph node metastasis who were treated with unilateral neck irradiation, patients with oral cavity or recurrent disease had significantly lower DFS compared with those without (2-y DFS 41.7 % vs 88.2 %, p = 0.017)., Conclusions: In patients without bilateral neck lymph node involvement, the postoperative unilateral neck irradiation is a reasonable treatment strategy for patients with the exception of oral cavity or recurrent disease.

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy)., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: The endobronchial brachytherapy (EBBT) is an established treatment method for tumors of the tracheobronchial system, however, little is known about the tolerance dose for organ at risk (OAR) in EBBT. The purpose of this study is to analyze patients with superficial bronchial carcinoma treated with definitive EBBT, and to investigate a relationship between late complications and dose for OAR., Material and Methods: Endobronchial brachytherapy was performed 6 Gy per fraction for three to four fractions with or without external beam radiation therapy (EBRT). For the purpose of dosimetric analysis, the wall of the lower respiratory tract (LRT: trachea, main bronchus, and lobar bronchiole), trachea, and main bronchus (TMB) was extracted. D0.5cc, D1cc, and D2cc of LRT and TMB were calculated in each EBBT session and added together. V100, V150, and V200 of LRT were also calculated., Results: Between March 2008 and April 2014, EBBT was performed in 14 patients for curative intent. The 2-year overall survival (OS), progression-free survival (PFS), and local recurrence free survival (LRFS) was 82.1%, 77.9%, and 91.7%, respectively. There was one patient with grade 5, one grade 4, and three grade 3 obstruction of trachea or bronchus. The mean EQD2 of LRT D2cc, TMB D2cc, D1cc, and D0.5cc of patients with or without late severe respiratory complications was significantly different between two groups (p = 0.018, 0.008, 0.009, and 0.013, respectively). The 2-year incidence rates of late severe complications in patients with TMB D2cc ≤ 85 Gy in EQD2 and > 85 Gy were 0% and 83.3%, respectively with a statistically significance (p = 0.014)., Conclusions: It was discovered that TMB D2cc > 85 Gy in EQD2 is a strong risk factor for severe late respiratory complication after EBBT.