小久保 雅樹

BACKGROUND: Postoperative regional nodal irradiation (RNI) is a standard treatment for breast cancer at high risk of regional recurrence; however, the necessity of including the internal mammary node (IMN) region in the radiation field remains unclear. This study aimed to evaluate treatment outcomes in a large cohort of patients who received postoperative radiotherapy with RNI excluding the IMN region. METHODS: This study included patients with breast cancer who underwent surgery followed by RNI without IMN irradiation between 2007 and 2018. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), breast cancer-specific mortality (BCM), distant metastasis-free survival (DMFS), recurrence patterns, and treatment-related adverse events. RESULTS: In total, 799 patients were included. The 5-year DFS, OS, BCM, and DMFS rates were 75.9, 88.3, 9.7, and 77.1%, respectively. Worse outcomes were associated with a higher number of positive lymph nodes and estrogen receptor (ER)-negative disease. Medial/central tumor location and younger age were each significantly associated with poorer outcomes, being associated with worse DFS and DMFS. Bone was the most common recurrence site. ER-negative disease, a higher number of positive lymph nodes, medial/central location, and younger age were significant risk factors for recurrence, particularly distant metastasis. IMN recurrence was rare. CONCLUSIONS: In this cohort, medial/central tumor location, ER-negative disease, and extensive nodal involvement were associated with poorer outcomes, suggesting that these factors may identify patients who can benefit from IMN irradiation. These findings may serve as important reference data when determining the indication for IMN irradiation on an individual patient basis.

This survey examined the real-world practice of radiotherapy for small-cell lung cancer (SCLC) in Japan, focusing on treatment strategies for limited-disease SCLC (LD-SCLC) and extensive-disease SCLC (ED-SCLC). This study aimed to identify inter-institutional differences, optimize treatment strategies and explore opportunities for standardization. A questionnaire was distributed to members of the Japanese Radiation Oncology Study Group, and responses were collected from 15 December 2023 to 14 March 2024. Responses to 11 questions specifically related to SCLC treatment strategies were analyzed. Among the 112 institutions, 38.3% did not set an upper age limit for concurrent chemoradiotherapy in LD-SCLC, whereas 31.3% set the limit at 80 years. The most commonly used chemotherapy regimen was cisplatin plus etoposide (79.5%), and the predominant radiotherapy fractionation schedule was twice-daily 45 Gy in 30 fractions (97.3%). Elective nodal irradiation (ENI) was ommited in 30.4% of institutions, while 17.9% reported performing ENI in all cases. Intensity-modulated radiation therapy (IMRT) was introduced in 71.4% of institutions, with D50% as the most frequently used dose-prescription method (47.5%). After achieving complete response, 16.1% of institutions routinely perform prophylactic cranial irradiation (PCI) in all patients. Hippocampus-sparing PCI was not widely used at the time of the survey (13.3%). In conclusion, this Japanese nationwide survey highlighted the SCLC treatment patterns and differences compared with non-small lung cancer (NSCLC). ENI omissions and IMRT have become increasingly adopted for SCLC, whereas clinical target volume margin definitions show some variation compared with NSCLC. Regular surveys are essential to monitor the evolution of treatment strategies.

This survey was conducted to examine the real-world practice of definitive chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC) in Japan, aiming to standardize treatment, reduce inter-institutional disparities and identify areas for future research. A questionnaire was sent to members of the Japanese Radiation Oncology Study Group through a mailing list, with responses collected between December 15, 2023, and March 14, 2024. Responses from 112 institutions revealed that 81.2% either did not set general upper age limits or established limits at 80 years or older for definitive CRT in LA-NSCLC. The most common absolute contraindications were active interstitial pneumonia (60.7%) and contralateral hilar lymph node metastasis (42.0%). Relative contraindications involved dose-volume indices of the normal lung (70.5%). The most commonly adopted dose-volume indices were lung V20Gy < 30%, lung V5Gy < 60% and mean lung dose <20 Gy, while no definite indices were established for heart V50Gy and mean heart dose in half of the institutions. Additionally, 88.4% of institutions reported using IMRT for LA-NSCLC. Involved-field radiotherapy (IFRT) was adopted regardless of institutional size, and institutions with higher IMRT usage for LA-NSCLC also had higher IFRT adoption rates. In conclusion, this nationwide survey revealed the expanded use of definitive CRT and a growing emphasis on reducing lung dose to mitigate pulmonary toxicities, facilitated by advancements in IMRT and IFRT. Regularly conducting these surveys is essential to monitor evolving treatment strategies.

Fungating lesions in advanced breast cancer often affect the quality of life. Fractionated radiation therapy is the preferred treatment over single-fraction radiation therapy because of the relatively favorable prognosis for breast cancer. Therefore, limited literature is available regarding the effectiveness of short-course radiation therapy, especially 8-Gy single-fraction radiation therapy. Herein, we describe the case of an 85-year-old patient diagnosed with locally advanced breast cancer for several years who underwent two sessions of 8-Gy single-fraction radiation therapy performed approximately one year apart. This therapy resulted in prolonged control of bleeding without severe side effects. The patient experienced bleeding from a fungating lesion and was referred to the Department of Radiation Oncology for palliative therapy to relieve the bleeding. Owing to limited support from her family and nursing care workers, she faced transportation challenges making frequent hospital visits infeasible, so 8-Gy single-fraction radiation therapy was performed. Radiation therapy was well tolerated, and hemostasis was achieved. Eleven months later, tumor regrowth and recurrent bleeding occurred, which necessitated another 8-Gy therapy. Re-irradiation was tolerated with only mild dermatitis noted, and the symptoms were relieved. Twelve months after re-irradiation, the breast cancer remained controlled, with no further bleeding. These findings indicate that 8-Gy single-fraction radiation therapy effectively controls bleeding from fungating breast cancer, and hemostasis may last longer than previously reported. Moreover, this method may be a valuable way to provide symptomatic relief, especially for elderly patients needing nursing care, even when their prognosis is relatively good.

PURPOSE: This multi-institutional prospective cohort trial aimed to demonstrate the changes in physician-evaluated dysphagia and patient-reported outcomes (PROs) after palliative external beam radiotherapy (EBRT) in patients with incurable esophageal cancer presenting with dysphagia. MATERIALS AND METHODS: We evaluated the rates of freedom from physician-evaluated dysphagia progression and improvement along with longitudinal changes in PROs (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life-Core 30 Questionnaire [QLQ-C30] and OES-18) after palliative EBRT. Multivariate analysis was used to identify the factors associated with freedom from physician-evaluated dysphagia progression at week 13. RESULTS: A total of 519 patients with esophageal cancer were screened; the full analysis set comprised 93 patients with a baseline median dysphagia score of 2 (IQR, 1-3) whose possible range was 1-4. Squamous cell carcinoma accounted for 94% of the full analysis set. The median prescribed dose of palliative EBRT was 40 Gy (IQR, 37.5-50). The rates of freedom from physician-evaluated dysphagia progression and improvement at 13 weeks were 76% (95% CI, 66 to 85) and 50% (95% CI, 39 to 60), respectively. Multivariate analysis suggested that high-dose palliative EBRT was more effective in preventing deterioration of physician-evaluated dysphagia than the low-dose one. Role functioning, fatigue, dyspnea, and appetite were worsened at week 4 but recovered at week 13. Patient-reported dysphagia, as represented in EORTC OES-18, demonstrated clinically significant improvement from weeks 13 through 52, relieving dysphagia-associated symptoms and enhancing global health. CONCLUSION: Palliative EBRT could relieve physician-evaluated and patient-reported dysphagia and dysphagia-associated symptoms and enhance global health in patients with incurable esophageal cancer, especially for squamous cell carcinoma despite transient dysfunction and aggravations of symptoms attributable to acute toxicity from palliative EBRT.

BACKGROUND: Despite advancements in liver tumor treatments, a persistent need remains for minimally invasive therapies with high efficacy and long-term outcomes. In a previous multicenter phase II study, the safety and efficacy of dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors were evaluated using a gimbal-mounted system. Herein, we report the updated long-term results of this technique. METHODS: This observational study examined patients with a single liver tumor, respiratory movement of at least 10 mm, performance status of 0-2, and Child-Pugh score of < 9. Patients who agreed to participate in the trial underwent dynamic tumor-tracking stereotactic body radiotherapy (prescribed dose, 40 Gy in five fractions for the planning target volume [D95]; 70% of the maximum dose). The primary endpoint was the 4-year overall survival rate. Secondary endpoints included 4-year local control and progression-free survival rates and the incidence of adverse events. RESULTS: Between September 2015 and March 2019, 48 patients (median age, 74 years; median tumor diameter, 17.5 mm) underwent dynamic tumor-tracking stereotactic body radiotherapy. All lesions were successfully treated (hepatocellular carcinoma, 39 patients; liver metastases, 9 patients). The median observation period was 46 months, and the 4-year overall survival, local control, and progression-free survival rates were 67.4%, 97.9%, and 29.1%, respectively. Eight patients had grade 3 hepatobiliary enzyme elevation, hematologic toxicity, or hyponatremia; none had grade ≥ 4 adverse events. CONCLUSION: These findings demonstrate the long-term safety and efficacy of dynamic tumor-tracking stereotactic body radiotherapy for liver tumors, with an excellent local control rate.

INTRODUCTION: Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)-adapted CRT in the immunotherapy era. METHODS: In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT. RESULTS: Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%-95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9-not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%). CONCLUSIONS: High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis. TRIAL REGISTRATION: University Hospital Medical Information Network database ID: UMIN000038366.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment approach for spinal metastases. However, local recurrence may occur. This prospective phase 2 trial evaluated whether SBRT with dose escalation in the gross tumor volume through simultaneous integrated boost (SIB-SBRT) can improve local control (LC) without increasing adverse events (AEs). METHODS AND MATERIALS: Eligible patients aged ≥ 20 years with spinal metastases and a life expectancy of > 1 year received SIB-SBRT in 5 fractions over 1 week. The prescribed dose was 30 Gy to the planning target volume for evaluation and an escalated dose of 40 to 45 Gy to the gross tumor volume through SIB. Neurologic examinations and magnetic resonance imaging were performed at 3-, 6-, and 12-month follow-up and every 6 months thereafter. The primary endpoint was the 1-year LC rate. The secondary endpoints included overall survival and AEs, such as vertebral compression fractures (VCFs). RESULTS: A total of 25 patients with 28 vertebral segments from September 2020 to March 2023 were enrolled in this study. The median follow-up was 26.2 months, and 24 segments in 21 patients were followed up for >1 year. The 1- and 2-year LC rates were 100.0% and 95.0%, respectively. Local recurrence developed in only 1 patient at 18 months. The 1- and 2-year overall survival rates were 92.0% and 72.8%, respectively. Six patients developed VCFs (3 cases each of grades 1 and 2), with 1- and 2-year cumulative incidence rates of 3.6% and 15.6%, respectively. No radiation myelopathy or other grade ≥ 2 AEs occurred, except for 1 case of grade 2 pain. CONCLUSIONS: Dose-escalated SIB-SBRT for spinal metastases demonstrates excellent LC with acceptable toxicity, supporting the need for a larger comparative trial.

The purpose of this study was to investigate the utilization and implementation of stereotactic body radiotherapy (SBRT) and intensity-modulated radiotherapy (IMRT) in Japan up to 2023. The survey was conducted by the Japanese Society for Radiation Oncology High-Precision External Beam Radiotherapy Group Subcommittee from December 2023 to February 2024. The study targeted patients treated with IMRT or SBRT between January 2021 and December 2022. A comprehensive web-based questionnaire was distributed to 880 facilities, with separate sections for radiation oncologists and medical physicists/radiotherapy technologists. A total of 360 facilities responded (response rate: 40.9%) for the section of radiation oncologists, and 405 facilities responded (response rate: 46.0%) for medical physicists/radiotherapy technologists, providing data on the implementation status, techniques, workload and challenges associated with IMRT and SBRT. Based on the responses in the section of radiation oncologists, IMRT was used in 68.6% of responding institutes, and SBRT in 87.8%. VMAT emerged as the most common IMRT technique (78.3%). The survey highlighted a high demand for medical physicists to perform IMRT (86.9%). Based on the responses in the section of medical physicists/radiotherapy technologists, 84.6% of the facilities that have not performed IMRT reported that the main reason was a lack of radiation oncologists. Furthermore, the survey also noted significant variations in prescribed doses and margin sizes across facilities, indicating the need for further standardization. High-precision radiation techniques such as IMRT and SBRT are getting popular, however, the facility requirements which mandate the presence of at least two radiation oncologists prevents IMRT from becoming more widespread in Japan.

Postoperative chemoradiotherapy (POCRT) is the standard treatment for patients with head and neck squamous cell carcinoma (HNSCC) with high-risk features (positive microscopic margins and/or extranodal extensions). We hypothesized that dose escalation using hyperfractionation in intensity-modulated radiotherapy (HF-IMRT) improves POCRT outcomes; however, no prospective trial has assessed the feasibility of POCRT in HF. Therefore, we evaluated the feasibility of POCRT using HF-IMRT. HNSCC patients with positive microscopic margins and/or extranodal extension following surgery were included. HF-IMRT (73.6 Gy in 64 fractions twice daily) was administered along with cisplatin at 40 mg/m2 once a week for seven cycles during radiotherapy. The primary endpoint was the proportion of patients who completed treatment, which included the planned radiotherapy and the administration of ≥200 mg/m2 of cisplatin. Feasibility was defined as the proportion of patients who completed treatment >60% using a one-sided binomial test. Ten patients were registered between October 2021 and April 2023. One patient was excluded because of tumor recurrence before POCRT. The median follow-up time was 18.2 months, and the proportion of patients who completed treatment was 88.9%. The median total dose of cisplatin was 240 mg/m2. The percentage of patients with grade 3 acute non-hematological adverse events was 77.8%. No patient experienced grade 4 or higher acute adverse events or grade 3 or higher late adverse events. POCRT using HF-IMRT is feasible for achieving adequate cisplatin doses and safe radiotherapy in patients with HNSCC.

PURPOSE: To report final results of a prospective study of stereotactic body radiation therapy (SBRT) in patients with previously untreated solitary primary hepatocellular carcinoma (HCC). METHODS AND MATERIALS: This prospective, single-arm, multicenter phase 2 trial recruited patients with HCC who were unsuitable for, or refused, surgery and radiofrequency ablation, with 3-year overall survival rates as the primary endpoint and survival outcomes and adverse events as secondary endpoints. The prescribed SBRT dose was 40 Gy in 5 fractions. The final data were analyzed in November 2022. RESULTS: Between 2014 and 2018, 36 patients (median age, 73.5 years) were registered; enrollment was closed before full recruitment due to slow accrual. Overall, 34 patients were analyzed for efficacy evaluation after excluding 2 patients. The median tumor size was 2.3 cm. The median follow-up times for all patients and for survivors were 49 and 56 months, respectively. The 3-year overall survival rate was 82% (95% confidence interval, 65%-92%). The 3-year local control rate was 93% (95% confidence interval, 76%-98%). Grade 3 or higher SBRT-related nonlaboratory toxicities were observed in 4 patients (11%). No grade 5 adverse events were observed. CONCLUSIONS: Final results of this phase 2 trial suggest the efficacy and safety of SBRT for newly diagnosed early-stage HCC that is unfit for other local therapies. Although this study was underpowered by the small number of registrations, the excellent results indicate that SBRT may be an alternative option for the management of early-stage HCC.

BACKGROUND: For delivering high radiation doses to pancreatic tumors, organ motion management is indispensable; however, studies on this are limited. We aimed to evaluate the efficacy and safety of dynamic tumor tracking (DTT) moderately hypofractionated intensity-modulated radiotherapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: Patients with histological confirmation for LAPC were included. A linac system, which was mounted with a gimbal function, was used for DTT-IMRT. The prescribed dose was 48 Gy in 15 fractions. The primary endpoint was the 1-year rate of freedom from locoregional progression (FFLP). RESULTS: DTT-IMRT was successfully administered in 25 patients enrolled from four institutions. The median range of respiratory motion during DTT-IMRT was 9.8 mm (range: 3.5-27.3 mm), and the median tracking accuracy was 2.6 mm (range: 0.7-5.2 mm). With a median follow-up period of 13.9 months, the 1-year FFLP rate was 75.3% (lower limit of one-sided 80% confidence interval [CI]: 60.2%), which satisfied the predetermined primary endpoint. One-year locoregional progression-free survival, progression-free survival, and overall survival were 56.0% (95% CI: 34.8%-72.7%), 44.0% (95% CI: 24.5%-61.9%), and 60.0% (95% CI: 38.4%-76.1%), respectively. Regarding nonhematologic toxicities, grade 3 acute gastrointestinal (GI) toxicity was observed in two patients (8%), and two patients (8%) each experienced grade 3 late GI and non-GI toxicities. No grade 4 or 5 nonhematologic toxicities were observed. CONCLUSIONS: DTT moderately hypofractionated IMRT shows preferable locoregional control without significant toxicity in patients with LAPC. TRIAL REGISTRATION: UMIN000017521.

INTRODUCTION: Primary vaginal carcinosarcoma is extremely rare, with only 12 cases reported to date. A consensus has not been reached on the best treatment approach as most patients undergo surgery; however, the disease is highly refractory. CASE PRESENTATION: We present the case of a 34-year-old woman diagnosed with vaginal carcinosarcoma after experiencing vaginal pain and bleeding. She opted for organ preservation and underwent definitive chemoradiotherapy (dCRT) using interstitial brachytherapy, receiving an initial concurrent chemoradiotherapy dose of 50 Gy in 25 fractions with weekly cisplatin. This treatment was followed by brachytherapy, in which 22.5 Gy was delivered in three fractions. To prevent vaginal stenosis, the patient was advised to undergo regular vaginal irrigation and to engage in sexual activity. At 25 months after treatment, the patient remained disease-free. The patient reported minimal impact on sexual activity, and her quality of life (QoL) was well maintained. CONCLUSION: To our knowledge, this is the first reported case of early-stage vaginal carcinosarcoma treated with dCRT. This suggests a promising treatment option for preserving organs. The prevention of vaginal stenosis following dCRT, in addition to organ conservation, is essential for preserving sexual function and QoL.

BACKGROUND AND PURPOSE: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT). MATERIALS AND METHODS: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test. RESULTS: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116). CONCLUSION: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM.

Space-making particle therapy, which consists of surgical placement of a spacer followed by particle therapy, has become a solution to the problem of normal organs being exposed to a high radiation dose. A bioabsorbable spacer is particularly suitable for this purpose, but is not widely used. Surgical placement of a spacer is performed mostly to protect the digestive tract, but can also be used to protect the kidneys. Therefore, we have been interested in the use of space-making particle therapy to preserve renal function. A 14 month-old boy with intermediate-risk retroperitoneal rhabdomyosarcoma underwent surgery with placement of a bioabsorbable spacer following neoadjuvant chemotherapy and then received proton beam therapy of 41.4 Gy (relative biological effectiveness) in 23 fractions. In the 41 months since PBT, he has survived without local recurrence or signs of renal impairment. This report describes the first-ever case of surgical placement of a bioabsorbable spacer with the aim of preserving renal function during proton beam therapy. Space-making particle therapy is an innovative solution for peritoneal tumors adjacent to the kidneys.

BACKGROUND: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. METHODS: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. RESULTS: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. CONCLUSIONS: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

BACKGROUND/AIM: Radiotherapy (RT) outcomes are generally reported based on stage, patient background, and concomitant chemotherapy. This study aimed to investigate the effects of the prescribed dose to gross tumor volume (GTV) and the calculation algorithm on local control in definitive RT for head and neck (H&N) cancers using follow-up images after RT. PATIENTS AND METHODS: This study included 154 patients with H&N cancers treated by Volumetric Modulated Arc Therapy at the Kobe City Medical Center General Hospital. Patients were classified into those receiving definitive RT (70 Gy of irradiation) and those not receiving it. Follow-up images were used to categorize the patients into the responders and non-responders groups. In the non-responders group, follow-up images were imported into the treatment planning system, and the contours of the residual or recurrent areas (local failure) were extracted and fused with computed tomography-simulated images for treatment planning. Dose evaluation parameters included maximum dose, dose administered to 1% of the volume, dose administered to 50% of the volume, dose administered to 99% of the volume (D99%), and minimum dose (Dmin) administered to the GTV. The doses to the GTV were compared between responders and non-responders. RESULTS: D99% exhibited significant differences between local failure and responders and between local failure and non-responders. Dmin showed significant differences between responders and non-responders and between responders and local failure. CONCLUSION: This study emphasizes the importance of verifying dose distribution in all slices of treatment planning, highlighting the need for precise assessment of the dose to the GTV in head and neck cancers.

BACKGROUND AND PURPOSE: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. MATERIALS AND METHODS: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. RESULTS: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. CONCLUSION: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

PURPOSE: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women. METHOD: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years. DISCUSSION: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI. REGISTRATION NUMBER AND DATE: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.

BACKGROUND: The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan. METHOD: Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility. RESULTS: Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63-78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events. CONCLUSION: Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.

Bowen's disease (BD) is a form of intraepidermal squamous cell carcinoma (SCC), and it occasionally occurs on the perianal site. BD is often treated with surgical excision; however, sometimes surgical excision for perianal BD cannot preserve anal function. We report the case of a 72-year-old man presenting with perianal pain and BD. He was treated with Radiotherapy (RT) and preserved his normal anal sphincter function without any recurrence or late adverse event. Moreover, we observed the unique skin reaction called 'tumoritis', which is characterized by mucosal inflammation. Tumoritis indicates the true extent of the tumor and evaluating the tumor or lesion size based on the extent of tumoritis when performing RT is important.

OBJECTIVE: Durvalumab was safe and effective in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT) in a phase 3 trial (PACIFIC trial). Although a history of radiation pneumonitis (RP) has been reported to increase the risk of exacerbation of pneumonitis associated with programmed death-1 axis inhibitors, the detailed clinical results of durvalumab treatment in patients with baseline grade 1 RP were not reported in the PACIFIC trial. Therefore, we aimed to evaluate the safety and effectiveness of durvalumab therapy in these patients. MATERIALS AND METHODS: This was a multicenter prospective cohort study involving 35 patients. Patients were eligible if they met the following criteria: inoperable stage III NSCLC, administration of durvalumab within 42 days after CCRT using platinum-based chemotherapy, no disease progression after CCRT, Eastern Cooperative Oncology Group performance status of 0-1, and presence of grade 1 RP at baseline. We assessed the effectiveness and safety of durvalumab with a minimum 1-year follow-up period for all patients. RESULTS: Thirty-five patients were enrolled in our study from February 2019 to December 2019. The median progression-free survival was 11.4 months (95 % confidence interval, 7.1 months-not reached), and the median overall survival was not reached. Eleven (31 %) patients had grade ≥2 pneumonitis/RP, 10 (28 %) developed grade 2 pneumonitis/RP, and 1 (3 %) developed grade 5 pneumonitis/RP. Five (14 %) patients experienced treatment-related grade ≥3 adverse events. CONCLUSION: Durvalumab might be safe and effective in patients with stage III NSCLC with baseline grade 1 RP following chemoradiotherapy.

BACKGROUND AND PURPOSE: This study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors. MATERIALS AND METHODS: Patients with cStage I primary lung cancer or metastatic lung cancer with an expected range of respiratory motion of ≥10 mm were eligible for the study. The prescribed dose was 50 Gy in four fractions. A gimbal-mounted linac was used for DTT-SBRT delivery. The primary endpoint was local control at 2 years. RESULTS: Forty-eight patients from four institutions were enrolled in this study. Forty-two patients had primary non-small-cell lung cancer, and six had metastatic lung tumors. DTT-SBRT was delivered for 47 lesions in 47 patients with a median treatment time of 28 min per fraction. The median respiratory motion during the treatment was 13.7 mm (range: 4.5-28.1 mm). The motion-encompassing method was applied for the one remaining patient due to the poor correlation between the abdominal wall and tumor movement. The median follow-up period was 32.3 months, and the local control at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval [CI]: 90.3%). The overall survival and progression-free survival at 2 years were 79.2% (95% CI: 64.7%-88.2%) and 75.0% (95% CI: 60.2%-85.0%), respectively. Grade 3 toxicity was observed in one patient (2.1%) with radiation pneumonitis. Grade 4 or 5 toxicity was not observed. CONCLUSION: DTT-SBRT achieved excellent local control with low incidences of severe toxicities in lung tumors with respiratory motion.

BACKGROUND: In infrared reflective (IR) marker-based hybrid real-time tumor tracking (RTTT), the internal target position is predicted with the positions of IR markers attached on the patient's body surface using a prediction model. In this work, we developed two artificial intelligence (AI)-driven prediction models to improve RTTT radiotherapy, namely, a convolutional neural network (CNN) and an adaptive neuro-fuzzy inference system (ANFIS) model. The models aim to improve the accuracy in predicting three-dimensional tumor motion. METHODS: From patients whose respiration-induced motion of the tumor, indicated by the fiducial markers, exceeded 8 mm, 1079 logfiles of IR marker-based hybrid RTTT (IR Tracking) with the gimbal-head radiotherapy system were acquired and randomly divided into two datasets. All the included patients were breathing freely with more than four external IR markers. The historical dataset for the CNN model contained 1003 logfiles, while the remaining 76 logfiles complemented the evaluation dataset. The logfiles recorded the external IR marker positions at a frequency of 60 Hz and fiducial markers as surrogates for the detected target positions every 80-640 ms for 20-40 s. For each logfile in the evaluation dataset, the prediction models were trained based on the data in the first three quarters of the recording period. In the last quarter, the performance of the patient-specific prediction models was tested and evaluated. The overall performance of the AI-driven prediction models was ranked by the percentage of predicted target position within 2 mm of the detected target position. Moreover, the performance of the AI-driven models was compared to a regression prediction model currently implemented in gimbal-head radiotherapy systems. RESULTS: The percentage of the predicted target position within 2 mm of the detected target position was 95.1%, 92.6% and 85.6% for the CNN, ANFIS, and regression model, respectively. In the evaluation dataset, the CNN, ANFIS, and regression model performed best in 43, 28 and 5 logfiles, respectively. CONCLUSIONS: The proposed AI-driven prediction models outperformed the regression prediction model, and the overall performance of the CNN model was slightly better than that of the ANFIS model on the evaluation dataset.

OBJECTIVES: The incidence of real-world pneumonitis and durvalumab rechallenge during chemoradiotherapy and durvalumab consolidation for non-small cell lung cancer is unknown. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 302 consecutive patients diagnosed with non-small cell lung cancer who started chemoradiotherapy between May 2018 and May 2019. RESULTS: Median age was 70 (range: 40-87) years. Volume of lung parenchyma that received 20 Gy (V20) exceeded 35% in 2% and mean lung dose exceeded 20 Gy in 1% of patients. Durvalumab consolidation was delivered to 225 patients (75%). Overall, 83% (n = 251), 34% (n = 103), 7% (n = 21), and 1% (n = 4) of the patients developed any grade of pneumonitis, symptomatic pneumonitis, ≥grade 3 pneumonitis, and fatal (grade 5) pneumonitis, respectively. Corticosteroids were administered to 25% of the patients to treat pneumonitis. Multivariate analysis identified the predictive factors for the development of symptomatic pneumonitis: V20 Gy or more ≥ 25% (odds ratio [OR]: 2.37, P = 0.008) and mean lung dose (MLD) ≥ 10 Gy (OR: 1.93, P < 0.0047). Of the 52 patients who received corticosteroids for pneumonitis after durvalumab initiation, 21 were rechallenged with durvalumab. Overall, 81% of patients met the PACIFIC study's rechallenge criteria and did not experience a severe pneumonitis relapse. CONCLUSION: High V20 and MLD were independent risk factors of symptomatic pneumonitis. More than 80% of the patients who were rechallenged with durvalumab after pneumonitis met the PACIFIC study's rechallenge criteria. Consequently, severe relapse did not occur. Cooperation between radiation and medical oncologists is important for safe chemoradiotherapy and the safe completion of durvalumab consolidation therapy.

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray's test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3-4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher's exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC.

Introduction/Background Durvalumab demonstrated a good efficacy and safety in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT) in the PACIFIC trial. Although a history of radiation pneumonitis (RP) has been reported to increase the risk of pneumonitis associated with programmed death-1 inhibitors, the safety and efficacy of durvalumab in patients with baseline Grade 1 RP have not been assessed. Therefore, we carried out a multicenter prospective cohort study to evaluate the efficacy and safety of durvalumab in these patients. Patients and Methods This was a multicenter prospective cohort study of 35 patients with Grade 1 RP after CCRT and before durvalumab initiation. This study was a first prespecified analysis for the first 20 patients with the primary objective of assessing the short-term safety; it was assessed 3 months after durvalumab initiation. Results Twenty patients were enrolled in this study between March 1, 2019, and September 3, 2019. Three patients (15%) experienced drug-related Grade ≥3 adverse events, while three patients (15%) had Grade ≥2 pneumonitis/RP within 3 months after durvalumab initiation. Three months after durvalumab initiation, all the patients were alive and four patients (20%) experienced disease progression. Conclusion Durvalumab can be a feasible treatment option for patients with stage III NSCLC with baseline Grade 1 RP following CCRT.(Trial registration number: UMIN000036061. The registration period was between March 2019 and December 2019.).

AIM: To prospectively evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for patients with previously untreated solitary primary hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria included the following: (1) primary solitary HCC; (2) no prior treatment for HCC; (3) Child-Turcotte-Pugh score of seven or less; and (4) unsuitability for or refusal of surgery and radiofrequency ablation (RFA). The prescribed dose of SBRT was 40 Gy in five fractions. The primary endpoint was 3-year overall survival (OS); the secondary endpoints included local progression-free survival (LPFS), local control (LC), and adverse events. The accrual target was 60 patients, expecting a 3-year OS of 70% with a 50% threshold. RESULTS: Between 2014 and 2018, 36 patients were enrolled; enrollment was closed early because of slow accrual. The median tumor size was 2.3 cm. The median follow-up at the time of evaluation was 20.8 months. The 3-year OS was 78% (95% confidence interval [CI]: 53%-90%). The 3-year LPFS and LC proportion were 73% (95% CI: 48%-87%) and 90% (95% CI: 65%-97%), respectively. Grade 3 or higher SBRT-related toxicities were observed in four patients (11%), and grade five toxicities were not observed. CONCLUSIONS: This study showed acceptably low incidence of SBRT-related toxicities. LC and OS after SBRT were comparable for previously untreated solitary HCC for patients unfit for resection and RFA. Although a definitive conclusion cannot be drawn by this study, the promising results indicate that SBRT may be an alternative option in the management of early HCC.

PURPOSE: To predict radiation pneumonitis (RP) grade 2 or worse after lung stereotactic body radiation therapy (SBRT) using dose-based radiomic (dosiomic) features. METHODS: This multi-institutional study included 247 early-stage nonsmall cell lung cancer patients who underwent SBRT with a prescribed dose of 48-70 Gy at an isocenter between June 2009 and March 2016. Ten dose-volume indices (DVIs) were used, including the mean lung dose, internal target volume size, and percentage of entire lung excluding the internal target volume receiving greater than x Gy (x = 5, 10, 15, 20, 25, 30, 35, and 40). A total of 6,808 dose-segmented dosiomic features, such as shape, first order, and texture features, were extracted from the dose distribution. Patients were randomly partitioned into two groups: model training (70%) and test datasets (30%) over 100 times. Dosiomic features were converted to z-scores (standardized values) with a mean of zero and a standard deviation (SD) of one to put different variables on the same scale. The feature dimension was reduced using the following methods: interfeature correlation based on Spearman's correlation coefficients and feature importance based on a light gradient boosting machine (LightGBM) feature selection function. Three different models were developed using LightGBM as follows: (a) a model with ten DVIs (DVI model), (b) a model with the selected dosiomic features (dosiomic model), and (c) a model with ten DVIs and selected dosiomic features (hybrid model). Suitable hyperparameters were determined by searching the largest average area under the curve (AUC) value in the receiver operating characteristic curve (ROC-AUC) via stratified fivefold cross-validation. Each of the final three models with the closest the ROC-AUC value to the average ROC-AUC value was applied to the test datasets. The classification performance was evaluated by calculating the ROC-AUC, AUC in the precision-recall curve (PR-AUC), accuracy, precision, recall, and f1-score. The entire process was repeated 100 times with randomization, and 100 individual models were developed for each of the three models. Then the mean value and SD for the 100 random iterations were calculated for each performance metric. RESULTS: Thirty-seven (15.0%) patients developed RP after SBRT. The ROC-AUC and PR-AUC values in the DVI, dosiomic, and hybrid models were 0.660 ± 0.054 and 0.272 ± 0.052, 0.837 ± 0.054 and 0.510 ± 0.115, and 0.846 ± 0.049 and 0.531 ± 0.116, respectively. For each performance metric, the dosiomic and hybrid models outperformed the DVI models (P < 0.05). Texture-based dosiomic feature was confirmed as an effective indicator for predicting RP. CONCLUSIONS: Our dose-segmented dosiomic approach improved the prediction of the incidence of RP after SBRT.

PURPOSE: To predict local recurrence (LR) and distant metastasis (DM) in early stage non-small cell lung cancer (NSCLC) patients after stereotactic body radiotherapy (SBRT) in multiple institutions using breath-hold computed tomography (CT)-based radiomic features with random survival forest. METHODS: A total of 573 primary early stage NSCLC patients who underwent SBRT between January 2006 and March 2016 and met the eligibility criteria were included in this study. Patients were divided into two datasets: training (464 patients in 10 institutions) and test (109 patients in one institution) datasets. A total of 944 radiomic features were extracted from manually segmented gross tumor volumes (GTVs). Feature selection was performed by analyzing inter-segmentation reproducibility, GTV correlation, and inter-feature redundancy. Nine clinical factors, including histology and GTV size, were also used. Three prognostic models (clinical, radiomic, and combined) for LR and DM were constructed using random survival forest (RSF) to deal with total death as a competing risk in the training dataset. Robust models with optimal hyper-parameters were determined using fivefold cross-validation. The patients were dichotomized into two groups based on the median value of the patient-specific risk scores (high- and low-risk score groups). Gray's test was used to evaluate the statistical significance between the two risk score groups. The prognostic power was evaluated by the concordance index with the 95% confidence intervals (CI) via bootstrapping (2000 iterations). RESULTS: The concordance indices at 3 yr of clinical, radiomic, and combined models for LR were 0.57 [CI: 0.39-0.75], 0.55 [CI: 0.38-0.73], and 0.61 [CI: 0.43-0.78], respectively, whereas those for DM were 0.59 [CI: 0.54-0.79], 0.67 [CI: 0.54-0.79], and 0.68 [CI: 0.55-0.81], respectively, in the test dataset. The combined DM model significantly discriminated its cumulative incidence between high- and low-risk score groups (P < 0.05). The variable importance of RSF in the combined model for DM indicated that two radiomic features were more important than other clinical factors. The feature maps generated on the basis of the most important radiomic feature had visual difference between high- and low-risk score groups. CONCLUSIONS: The radiomics approach with RSF for competing risks using breath-hold CT-based radiomic features might predict DM in early stage NSCLC patients who underwent SBRT although that may not have potential to predict LR.

Urinary retention and hematuria owing to radiation-induced mucositis are occasional late adverse events in patients with prostate cancer. Moreover, radiation-induced secondary malignancies are late adverse events, although they are extremely rare. Herein, we describe a case of radiation-induced secondary malignancy of the prostate that was initially difficult to distinguish from radiation mucositis. A 74-year-old man with prostate cancer underwent brachytherapy and external beam radiotherapy 9 years ago. Twenty-eight months after irradiation, he presented with urinary retention and hematuria owing to radiation mucositis and underwent transurethral resection of the prostate. At 89 months after irradiation, the patient again showed urinary retention and hematuria. The cause of urinary retention and hematuria could not be identified on cystoscopy. Despite receiving medications, the patient's symptoms did not improve. Therefore, transurethral fulguration was performed, and prostate biopsy revealed spindle cell sarcoma. A diagnosis of radiation-induced undifferentiated pleomorphic/spindle cell sarcoma was made, and the patient underwent total cystectomy and construction of the ileal conduit. Two weeks after the surgery, computed tomography revealed peritoneal dissemination. The patient died 5 weeks after the surgery. The case findings indicate that clinicians should consider the possibility of radiation-induced secondary malignancy; moreover, thorough pathological examination of the prostate with CT and MRI is important to distinguish RISM from radiation mucositis even if no tumors are found on cystoscopy.

PURPOSE: Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible after CRT in the real world. No study has been conducted on the patients who were ineligible for the PACIFIC trial, and hence, we conducted a retrospective study on them. METHODS: We identified 82 patients with stage III NSCLC who received definitive platinum-based concurrent CRT and had World Health Organization performance status of 0-1. We investigated the proportion, clinical characteristics, and prognoses of patients who became ineligible for the PACIFIC trial after CRT. RESULTS: After CRT, 19 of 82 patients (23%) became ineligible for the PACIFIC trial. Comparison between eligible and ineligible patients revealed that old age (p = 0.042), male gender (p = 0.031), and radiation therapy with V20 ≥ 35% (p = 0.032) were associated with ineligibility after CRT. Moreover, ineligible patients showed shorter PFS (6.6 vs. 15.7 months, hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.16-5.89, p = 0.016) and shorter OS (18.6 vs. 44.3 months, HR 3.03, 95% CI 1.29-7.10, p = 0.007) than eligible patients. CONCLUSIONS: Our study revealed the clinical characteristics and prognoses of patients who became ineligible for the PACIFIC trial after CRT. Physicians should be careful while prescribing CRT for patients with characteristics such as old age, male gender, and radiation therapy with V20 ≥ 35%.

PURPOSE: A dose escalation study to determine the recommended dose with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (JCOG0702) was conducted. The purpose of this paper is to report the survival and the late toxicities of JCOG0702. MATERIALS AND METHODS: The continual reassessment method was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose. The starting dose was 40 Gy in four fractions at D95 of PTV. RESULTS: Twenty-eight patients were enrolled. Ten patients were treated with 40 Gy at D95 of PTV, four patients with 45 Gy, eight patients with 50 Gy, one patient with 55 Gy and five patients with 60 Gy. Ten patients were alive at the last follow-up. Overall survival (OS) for all patients was 67.9% (95% CI 47.3-81.8%) at 3 years and 40.8% (95% CI 22.4-58.5%) at 5 years. No Grade 3 or higher toxicity was observed after 181 days from the beginning of the SBRT. Compared to the toxicities up to 180 days, chest wall related toxicities were more frequent after 181 days. CONCLUSIONS: The 5-year OS of 40.8% indicates the possibility that SBRT for peripheral T2N0M0 non-small cell lung cancer is superior to conventional radiotherapy. The effect of the SBRT dose escalation on OS is unclear and further studies are warranted.

UNLABELLED: Recently, with the spread of laser ablation therapy, it has been called into question whether flush ligation of the great saphenous vein (GSV) reduces varicose vein recurrence after surgery. Because we thought such recurrence was caused by a narrow branch resection area, we developed a new method of flush ligation (the avulsion technique method). MATERIALS AND METHODS: A total of 214 limbs in 180 patients whose GSV had become varicose were studied. In our procedure, we dissect the GSV, lift its proximal stump, and expose the tributaries. We pull out the distal side of the tributaries without ligature as far as possible. We evaluate the area of subcutaneous ecchymosis within a 15-cm radius of the inguinal incision visually on the third post-operative day. RESULTS: We were able to pull out over 10 cm per branch by this method. The area of subcutaneous ecchymosis was mostly less than 10%. No hematoma or pain was observed after the operation. CONCLUSION: This method was safe, with subcutaneous ecchymosis occurring only rarely. We expect this method to reduce saphenofemoral junction recurrence after the operation. (This is a translation of Jpn J Phlebol 2017; 28: 11-16.).

OBJECTIVES: Even with advanced image guidance, biopsies occasionally fail to diagnose small lung lesions, which are highly suggestive of primary lung cancer by radiological examination. The aim of this study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) to treat small lung lesions clinically diagnosed as primary lung cancer. MATERIALS AND METHODS: This is a prospective, multi-institutional observation study. Strict inclusion and exclusion criteria were determined in a nation-wide consensus meeting and used to include patients who were clinically diagnosed with primary lung cancer using precise imaging modalities, for whom further surgical intervention was not feasible, who refused watchful waiting, and who were highly tolerable of SBRT with informed consent. SBRT was performed with 48 Gy in 4 fractions at the tumor isocenter. RESULTS: From August 2009 to August 2014, 62 patients from 11 institutions were enrolled. Their median age was 80 years. The tumors ranged in size from 9 to 30 mm in diameter (median, 18 mm). The median follow-up interval was 55 months. The 3-year overall survival rate was 83.3% (95% confidence interval (CI) 71.1-90.7%) for all the patients and 94.7% (95% CI 68.1-99.2%) for the patients younger than 75 years. Local failure, regional lymph node metastases and distant metastases occurred in 4 (6.4%), 3 (4.8%) and 11 (17.7%) patients, respectively. Grades 3 and 4 toxicities were observed in 8 (12.9%) patients and 1 (1.6%) patient, respectively. No grade 5 toxicities were observed. CONCLUSIONS: SBRT is safe and effective for patients with small lung lesions clinically diagnosed as primary lung cancer that satisfied the proposed strict indication criteria as previously reported. A prospective interventional study is required to ascertain if SBRT is an alternative strategy for these patients.

The purpose of this study was to examine the characteristics and treatment plans of patients who experienced fatal radiation pneumonitis after stereotactic body radiation therapy for primary or oligometastatic lung cancer. Records of 1789 patients treated with stereotactic body radiation therapy for primary or oligometastatic lung cancer were retrospectively reviewed to identify those who developed fatal radiation pneumonitis. Twenty-three (1.3%; 18 men and 5 women) patients developed fatal radiation pneumonitis after stereotactic body radiation therapy for lung cancer; their median age was 74 years. The mean Krebs von den Lungen-6 level and percent vital capacity were 1320 U/mL and 82%, respectively. Prestereotactic body radiation therapy computed tomography revealed pulmonary interstitial change in 14 (73.7%) of 19 patients in whom computed tomography data could be reviewed. Seven (30.4%) of 23 patients had regularly used steroids. The median time duration between stereotactic body radiation therapy commencement and pneumonia symptom appearance was 75 (range: 14-204) days. Median survival time following pneumonia symptom appearance was 53 (range: 4-802) days. The 6- and 12-month overall survival rates were 34.8% and 13.0%, respectively. The 6-month overall survival rates in patients with and without heart disease were 50.0%, 16.7%, and 46.7% for heart disease existence, respectively. There were 4 patients in whom fatal radiation pneumonitis occurred within 2 months after stereotactic body radiation therapy and who died within 1 month. Three of them had no pulmonary interstitial change before stereotactic body radiation therapy, but had heart disease. In summary, the survival time in this case series was generally short but varied widely. More than half of the patients had pulmonary interstitial change before stereotactic body radiation therapy, although immediately progressive fatal radiation pneumonitis was also observed in patients without pulmonary interstitial change. True risk factors for fatal radiation pneumonitis should be examined in a prospective study with a larger cohort.

Stereotactic body radiotherapy is an alternative treatment option for small-sized, primary lung cancers and pulmonary metastatic diseases. In the case of local relapse after stereotactic body radiotherapy, salvage pulmonary resection is considered cautiously. However, no study has described the difficulty of the salvage operations. This study aimed to assess the difficulty associated with salvage operative procedures. Eight patients who developed local relapse after stereotactic body radiotherapy and had undergone salvage pulmonary operations were enrolled in this study (stereotactic body radiotherapy group). Additionally, 439 patients who underwent video-assisted thoracoscopic lobectomy without previous stereotactic body radiotherapy were enrolled as the standard operative control group (non-stereotactic body radiotherapy group). In the stereotactic body radiotherapy group, 1 of the 8 patients had undergone lobectomy with composite resection of the third and fourth ribs. Of the 8 patients, 6 had undergone video-assisted thoracoscopic lobectomy and 1 had been inoperable because of rapid tumor progression. The operation time and the incision length of the utility port were apt to be longer in the stereotactic body radiotherapy group than in the non-stereotactic body radiotherapy group. On the contrary, the duration of drain placement and the length of hospital stay after the operation were not different. Thus, the salvage pulmonary operations were performed in the usual video-assisted thoracoscopic lobectomy approach, but slightly complicated than the standard video-assisted thoracoscopic lobectomy. Although to decide the indication of salvage operation might be difficult, it could be a feasible treatment option in local relapse after stereotactic body radiotherapy.

BACKGROUND: To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). METHODS: Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. RESULTS: Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. CONCLUSIONS: The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. A total of 45 patients with LA-NSCLC were included, among which there were sufficient pre- and post-CCRT specimens in 35 patients. Overall, the percentage of tumor cells with PD-L1 expression significantly decreased between pre- and post-CCRT specimens (P = 0.024). Sixteen, 15, and 4 patients had decreased, unchanged, or increased PD-L1 expression after CCRT, respectively. Median OS of patients with decreased, unchanged, or increased PD-L1 expression was 85.1, 92.8, and 14.6 months, respectively (P < 0.001). In conclusion, the percentage of PD-L1-positive tumor cells significantly decreased after CCRT. Alteration of PD-L1 expression after neoadjuvant CCRT was associated with prognosis in patients with LA-NSCLC. These data should be considered when developing the optimal approach of integrating PD-1 axis inhibitors with CCRT.

PURPOSE: When treating large metastatic brain tumors with stereotactic radiotherapy (SRT), high dose conformity to target is difficult to achieve. Employing a modified planning target volume (mPTV) instead of the original PTV may be one way to improve the dose distribution in linear accelerator-based SRT using a dynamic conformal technique. In this study, we quantitatively analyzed the impact of a mPTV on dose distribution. MATERIALS AND METHODS: Twenty-four tumors with a maximum diameter of >2 cm were collected. For each tumor, two plans were created: one used a mPTV and the other did not. The mPTV was produced by shrinking or enlarging the original PTV according to the dose distribution in the original plan. The dose conformity was evaluated and compared between the plans using a two-sided paired t test. RESULTS: The conformity index defined by the Radiation Therapy Oncology Group was 1.34 ± 0.10 and 1.41 ± 0.13, and Paddick's conformity index was 0.75 ± 0.05 and 0.71 ± 0.06, for the plans with and without a mPTV, respectively. All of these improvements were statistically significant (P < 0.05). CONCLUSION: The use of a mPTV can improve target conformity when planning SRT for large metastatic brain tumors.

PURPOSE: To develop a four-dimensional (4D) dose calculation system for real-time tumor tracking (RTTT) irradiation by the Vero4DRT. METHODS: First, a 6-MV photon beam delivered by the Vero4DRT was simulated using EGSnrc. A moving phantom position was directly measured by a laser displacement gauge. The pan and tilt angles, monitor units, and the indexing time indicating the phantom position were also extracted from a log file. Next, phase space data at any angle were created from both the log file and particle data under the dynamic multileaf collimator. Irradiation both with and without RTTT, with the phantom moving, were simulated using several treatment field sizes. Each was compared with the corresponding measurement using films. Finally, dose calculation for each computed tomography dataset of 10 respiratory phases with the X-ray head rotated was performed to simulate the RTTT irradiation (4D plan) for lung, liver, and pancreatic cancer patients. Dose-volume histograms of the 4D plan were compared with those calculated on the single reference respiratory phase without the gimbal rotation [three-dimensional (3D) plan]. RESULTS: Differences between the simulated and measured doses were less than 3% for RTTT irradiation in most areas, except the high-dose gradient. For clinical cases, the target coverage in 4D plans was almost identical to that of the 3D plans. However, the doses to organs at risk in the 4D plans varied at intermediate- and low-dose levels. CONCLUSIONS: Our proposed system has acceptable accuracy for RTTT irradiation in the Vero4DRT and is capable of simulating clinical RTTT plans.

PURPOSE: A dose escalation study to determine the recommended dose (RD) with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (NSCLC) was conducted. The results of the group with PTV⩾100cc are reported in this paper. MATERIALS AND METHODS: The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was Grade 3 or higher radiation pneumonitis (RP), and Grade 2 or higher RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D95 of the PTV. RESULTS: Thirteen patients were accrued. More patients should have been enrolled but we decided not to prolong the study period. No patients experienced Grade 3 RP. Two patients experienced Grade 2 RP at 50Gy in 4 fractions. The predicted MTD was 50.2Gy. The posterior probability of the Grade 2 RP frequency over 40% was 5.3% for the dose level of 50Gy. The RD was determined to be 50Gy. CONCLUSIONS: The RD was determined to be 50Gy in 4 fractions in this population.

PURPOSE: We investigated the prevalence of hypothyroidism (HT) in patients with breast cancer who received radiation therapy to the supraclavicular (SC) field to evaluate the effect of radiation on thyroid. METHODS: Between April 2007 and May 2016, consecutive patients with invasive breast cancer who received SC radiation were recruited. Thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured between April and August 2016. On the basis of the radiation-planning CT images, thyroid volume was calculated and dose-volume parameters were estimated. The endpoints were the prevalence of HT as determined by high levels of TSH and low levels of fT4 in serum, and the prevalence of subclinical HT, determined by high-serum TSH and normal fT4. RESULTS: Among the 68 consecutive patients, 26 were excluded from evaluation (10 patients died, 6 had a history of previous thyroid disease and 10 were lost to follow-up). One (2.4%) and six (14.3%) of these patients had HT and subclinical HT, respectively, with a mean TSH level of 8.27 µU/mL. By univariate analysis, a predictive factor of HT and subclinical HT was a thyroid volume <8 cm3 (OR 6.44, 95% CI 1.14 to 36.6; p=0.043). Multivariate analysis also showed an association between thyroid volume <8 cm3 and HT or subclinical HT (OR 18.48, 95% CI 1.48 to 230.86; p=0.024). CONCLUSIONS: The prevalence of HT in patients with breast cancer studied was relatively low. Although thyroid volume appeared to be a predictive marker of HT in this cohort, further prospective evaluation is needed.

PURPOSE: The purposes of this study were two-fold: first, to develop a four-axis moving phantom for patient-specific quality assurance (QA) in surrogate signal-based dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT), and second, to evaluate the accuracy of the moving phantom and perform patient-specific dosimetric QA of the surrogate signal-based DTT-IMRT. METHODS: The four-axis moving phantom comprised three orthogonal linear actuators for target motion and a fourth one for surrogate motion. The positional accuracy was verified using four laser displacement gauges under static conditions (±40 mm displacements along each axis) and moving conditions [eight regular sinusoidal and fourth-power-of-sinusoidal patterns with peak-to-peak motion ranges (H) of 10-80 mm and a breathing period (T) of 4 s, and three irregular respiratory patterns with H of 1.4-2.5 mm in the left-right, 7.7-11.6 mm in the superior-inferior, and 3.1-4.2 mm in the anterior-posterior directions for the target motion, and 4.8-14.5 mm in the anterior-posterior direction for the surrogate motion, and T of 3.9-4.9 s]. Furthermore, perpendicularity, defined as the vector angle between any two axes, was measured using an optical measurement system. The reproducibility of the uncertainties in DTT-IMRT was then evaluated. Respiratory motions from 20 patients acquired in advance were reproduced and compared three-dimensionally with the originals. Furthermore, patient-specific dosimetric QAs of DTT-IMRT were performed for ten pancreatic cancer patients. The doses delivered to Gafchromic films under tracking and moving conditions were compared with those delivered under static conditions without dose normalization. RESULTS: Positional errors of the moving phantom under static and moving conditions were within 0.05 mm. The perpendicularity of the moving phantom was within 0.2° of 90°. The differences in prediction errors between the original and reproduced respiratory motions were -0.1 ± 0.1 mm for the lateral direction, -0.1 ± 0.2 mm for the superior-inferior direction, and -0.1 ± 0.1 mm for the anterior-posterior direction. The dosimetric accuracy showed significant improvements, of 92.9% ± 4.0% with tracking versus 69.8% ± 7.4% without tracking, in the passing rates of γ with the criterion of 3%/1 mm (p < 0.001). Although the dosimetric accuracy of IMRT without tracking showed a significant negative correlation with the 3D motion range of the target (r = - 0.59, p < 0.05), there was no significant correlation for DTT-IMRT (r = 0.03, p = 0.464). CONCLUSIONS: The developed four-axis moving phantom had sufficient accuracy to reproduce patient respiratory motions, allowing patient-specific QA of the surrogate signal-based DTT-IMRT under realistic conditions. Although IMRT without tracking decreased the dosimetric accuracy as the target motion increased, the DTT-IMRT achieved high dosimetric accuracy.

Management of metastatic malignant melanoma is challenging. Although several new systemic therapies for metastatic malignant melanoma have recently been developed, some patients still also require radiation therapy (RT) for palliative care. However, the safety and efficacy of combining use of novel drugs with RT remain unclear. Here, we report treating a patient with rapidly growing malignant melanoma with a programmed cell death protein 1 (PD-1) inhibitor and a BRAF inhibitor together with 60 Gy of hypofractionated RT without severe adverse effects. The tumor within the radiation field exhibited a more marked response than that outside it. A combination of RT with an anti-PD-1 antibody or a BRAF inhibitor may, therefore, be a useful and tolerable approach to treating metastatic BRAF-mutant melanoma.

PURPOSE: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). METHODS: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (Pt), and those markers with a 3D |TMDn| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (Pe) was calculated from a localization point consisting of one to three markers except Pt. Respiratory motion for Pt and Pe was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between Pt and Pe during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. RESULTS: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker's motion near the lung tumor. MRA showed that |aRM| in the left-right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left-right direction. The TLE calculated from the MRA ((MRA)TLE) increased as |TMD| and |aRM| increased and adversely decreased with each increment of n. The median 3D (MRA)TLE was 2.0 mm (range, 0.6-4.3 mm) for n = 1, 1.8 mm (range, 0.4-4.0 mm) for n = 2, and 1.6 mm (range, 0.3-3.7 mm) for n = 3. Although statistical significance between n = 1 and n = 3 was observed in all directions, the absolute average difference and the standard deviation of the (MRA)TLE between n = 1 and n = 3 were 0.5 and 0.2 mm, respectively. CONCLUSIONS: A large |TMD| and |aRM| increased the differences in TLE between each n; however, the difference in 3D (MRA)TLEs was, at most, 0.6 mm. Thus, the authors conclude that it is acceptable to continue fiducial marker-based radiotherapy as long as |TMD| is maintained at ≤58.7 mm for a 3D |aRM|  ≥  10 mm.

(Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA ≥20 ng/ml or clinical T stage ≥T3a, Gleason score ≥8) were treated with NeoADT and EBRT. EBRT consisted of three-dimensional conformal or intensity modulated radiotherapy with or without whole-pelvic radiation. Biochemical failure was defined according to the Phoenix definition. Biochemical progression-free survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method, and prognostic factors for bPFS were analyzed by using the Cox proportional hazard model. (Result) The median age and initial prostate-specific antigen (PSA) level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level ≥20 ng/ml, 51 patients had clinical stage ≥T3a, 27 patients had Gleason score ≥8. The number of risk factors patients possessed was 1 (RiskN-1) in 31 patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole-pelvic radiation was administered in 7 patients. After median follow-up of 4.8 years, biochemical and clinical failure occurred in 23 and 2 patients, respectively. No patients died of cancer. Five-year/8-year bPFS and OS were 63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51-498.05, p<0.01) and pre-EBRT PSA (continuous, hazard ratio 1.31, 95%CI 1.01-1.71, p<0.05) were the significant predictors of bPFS. Five-year/8-year bPFS in RiskN-1 group and RiskN-2 or -3 group were 89%/79% and 47%/39%, respectively. Grade 3/4 adverse events (CTCAE ver4.0-JCOG) occurred in 2 patients. (Conclusion) Median dose of 74 Gy EBRT with intermediate-term NeoADT was safe and beneficial for high-risk prostate cancer. The number of risk factors and pre-EBRT PSA level were the independent prognostic factors for biochemical progression-free survival.

We investigated whether non-contrast three-dimensional computed tomography-venography (3DCTV) using 128-row multidetector computed tomography (MDCT) could be the first-choice diagnostic imaging modality for the treatment of varicose veins. Its utility was assessed in terms of estimation of the venous function, ability to visualize incompetent perforators, association with deep venous diseases, and determination of surgical procedures in 1348 patients with 2696 limbs who underwent non-contrast 3DCTV between September 2009 and August 2013. A positive correlation was observed between the diameter of the great saphenous vein and the venous filling index (r = 0.539). The detection rate of incompetent perforators was 86.7%. In deep venous incompetence and deep venous thrombosis, a characteristic finding showing a wide net-like spread of varicose veins from a branch not communicating with the saphenous vein was observed. Non-contrast 3DCTV facilitated an objective understanding of the overall three-dimensional images of varices and was useful for determining surgical strategies. Although the concomitant use of duplex scan is necessary for assessment depending on the situation, it appears that non-contrast 3DCTV could be the first-choice diagnostic imaging modality. (This article is a translation of Jpn J Phlebol 2014; 25: 332-9.).