Review of Multimodal Imaging in Cardiac Sarcoidosis

The Journal of Medical Investigation : JMI


Linear accelerator selection: Impact on feasibility dosevolume histograms and practicality in dose reduction for organs at risk during prostate volumetric-modulated arc therapy

Reports of Practical Oncology and Radiotherapy


Comparative evaluation of two dose-volume histogram prediction tools for treatment planning: treatment planning quality and dose verification accuracy

This study aims to compare treatment plans created using RapidPlan and PlanIQ for twelve patients with prostate cancer, focusing on dose uniformity, dose reduction to organs at risk (OARs), plan complexity, and dose verification accuracy. The goal is to identify the tool that demonstrates superior performance in achieving uniform target dose distribution and reducing OAR dose, while ensuring accurate dose verification. Dose uniformity in the planning target volume, excluding the rectum, and dose reduction in the OARs (the rectum and bladder) were assessed. The validation included point-dose measurements with an ionization chamber dosimeter and gamma analysis of dose distributions. Monitor units were calculated to evaluate plan complexity. PlanIQ provided superior dose uniformity, with improvements in the dose homogeneity index compared with RapidPlan. RapidPlan was more effective in reducing OAR doses, particularly in the rectum, with significant reductions at various dose levels. Dose verification showed no significant differences between the two tools. However, PlanIQ showed a smaller mean difference between the calculated and measured doses and a slightly better dose distribution match with less variability than RapidPlan. RapidPlan was more effective at reducing OAR doses, whereas PlanIQ achieved better dose uniformity and lower plan complexity. Both tools performed similarly in terms of dose verification accuracy, with PlanIQ showing a slight advantage in dose-distribution matching. The choice of planning tool depends on the primary treatment goal, whether it is to reduce the OAR doses or improve the target dose uniformity.

Technical Innovations & Patient Support in Radiation Oncology


Current status of the working environment of brachytherapy in Japan: A nationwide survey-based analysis focusing on radiotherapy technologists and medical physicists

Brachytherapy (BT), especially in high dose rate (HDR), has become increasingly complex owing to the use of image-guided techniques and the introduction of advanced applicators. Consequently, radiotherapy technologists and medical physicists (RTMPs) require substantial training to enhance their knowledge and technical skills in image-guided brachytherapy. However, the current status of the RTMP workload, individual abilities and quality control (QC) of BT units in Japan remains unclear. To address this issue, we conducted a questionnaire survey from June to August 2022 in all 837 radiation treatment facilities in Japan involving RTMPs. This survey focused on gynecological cancers treated with HDR-BT (GY-HDR) and permanent prostate implantation using low-dose-rate BT (PR-LDR). The responses revealed that the average working time in the overall process for HDR varied: 120 min for intracavitary BT and 180 min for intracavitary BT combined with interstitial BT. The QC implementation rate, in accordance with domestic guidelines, was 65% for GY-HDR and 44% for PR-LDR, which was lower than the 69% observed for external beam radiation therapy (EBRT). Additionally, the implementation rate during regular working hours was low. Even among RTMP working in facilities performing BT, the proportion of those able to perform QC for BT units was ~30% for GY-HDR and <20% for PR-LDR, significantly lower than the 80% achieved for EBRT. This study highlights the vulnerabilities of Japan's BT unit QC implementation structure. Addressing these issues requires appropriate training of the RTMP staff to safely perform BT tasks and improvements in practical education and training systems.


Ventilation/Perfusion Mismatch in Pulmonary Vein Stenosis Secondary to Atrial Fibrillation Ablation

We present two patients with a history of paroxysmal atrial fibrillation who developed pulmonary vein stenosis (PVS) following atrial fibrillation (AF) ablation. Case 1 involved a female patient in her 50s who was asymptomatic for pulmonary symptoms but was found to have a high degree of left superior PVS 15 months after AF ablation. This was demonstrated using contrast-enhanced computed tomography (CE-CT) and supported by findings of perfusion defects on ventilation-perfusion (V/Q) scan. Case 2 was a male patient in his 60s who developed progressive left superior PVS nine months after AF ablation, evidenced by serial CE-CT and V/Q scans. PVS is a rare but well-known complication of pulmonary vein ablation for the treatment of AF that can lead to severe complications if left untreated. V/Q scans effectively assess the functional significance of PVS by detecting abnormal blood flow segments. Although a V/Q mismatch characterized by reduced perfusion defects is more commonly used in evaluating pulmonary embolism, PVS should not be disregarded as a differential diagnosis. Few studies emphasize the utility of V/Q scans in managing PVS and highlight V/Q mismatch as a notable finding. This case report aimed to highlight their significance.

Asia Oceania Journal of Nuclear Medicine & Biology


子宮頸癌IGBTにおける子宮体部・腟側に対する線量評価に関するアンケート調査

子宮頸癌IGBTにおける子宮体部・腟側に対する線量評価に関するアンケート調査

日本放射線科専門医会・医会学術雑誌


Comparative analysis of two dose-volume histogram prediction tools for treatment planning in volumetric-modulated arc therapy: A multi-planner study

The increase in high-precision radiation therapy, particularly volumetric-modulated arc therapy (VMAT), has increased patient numbers and expanded treatment sites. However, a significant challenge in VMAT treatment planning is the inconsistent plan quality among different planners and facilities. This study explored the use of dose-volume histogram (DVH) prediction tools to address these disparities, specifically focusing on RapidPlan (Varian Medical Systems) and PlanIQ (Sun Nuclear). RapidPlan predicts achievable DVHs and automatically generates optimization objectives. While it has demonstrated organ-at-risk (OAR) dose reduction benefits, the quality of the plan used to build its model significantly affects its predictions. On the other hand, PlanIQ offers ease of use and does not require prior model-building. Five planners participated in this study, each creating two treatment plans: one referencing RapidPlan and the other using PlanIQ. The planners had the freedom to adjust parameters while referencing the DVH predictions. The plans were evaluated using "Plan Quality Metric" (PQM) scores to assess the planning target volume excluding the rectum and OARs. The results revealed that RapidPlan-referenced plans often outperformed PlanIQ-based plans, with less interplanner variability. PlanIQ played a pivotal role in the construction of the RapidPlan model. This study is the first to compare plans generated by multiple planners using both tools. This study provides insights into optimizing treatment planning by considering the characteristics of both RapidPlan and PlanIQ.


Knowledge-based model building for treatment planning for prostate cancer using commercial treatment planning quality assurance software tools

This study devised a method to efficiently launch the RapidPlan model for volumetric-modulated arc therapy for prostate cancer in small- and medium-sized facilities using high-quality treatment plans with the PlanIQ software as a reference. Treatment plans were generated for 30 patients with prostate cancer to construct the RapidPlan model using PlanIQ as a reference. In the context of PlanIQ-referenced treatment planning, treatment plans were developed, such that the feasibility dose-volume histogram of each organ-at-risk fell within F ≤ 0.1. For validation of the RapidPlan model, treatment plans were formulated for 20 patients using both RapidPlan and PlanIQ, and the differences were evaluated. The results of RapidPlan model validity assessment revealed that the RapidPlan-produced treatment plans exhibited higher quality in 11 of 20 patients. No significant differences were found between the treatment plans. In conclusion, high-quality treatment plans formulated using PlanIQ as reference facilitated efficient implementation of RapidPlan modeling.


Patterns of care for brachytherapy in Japan

This study aimed to assess the current state of brachytherapy (BT) resources, practices and resident education in Japan. A nationwide survey was undertaken encompassing 177 establishments facilitating BT in 2022. Questionnaires were disseminated to each BT center, and feedback through online channels or postal correspondence was obtained. The questionnaire response rate was 90% (159/177), and every prefecture had a response in at least one center. The number of centers in each prefecture ranged from 0.6 to 3.6 (median: 1.3) per million population. The annual number of patients in each center ranged from 0 to 272 (median: 31). While most prefectures provided intracavitary (IC) BT for gynecological cancers and interstitial (IS) BT for prostate cancer, only one-third of the prefectures provided IS BT for cancer sites other than the prostate. The institutional image-guided BT implementation rate was 71%. IC and IS BT was performed for 15.4% of IC BT cases of gynecological cancer. Only 47% of the BT training centers answered that they could provide adequate training in BT for residents. The most common reason for this finding was the insufficient number of patients in each center. The results show that, although BT has achieved uniformity in terms of facility penetration, new technologies are not yet widespread enough. Furthermore, IS BT, which requires advanced skills, is limited to a few BT centers, and considerable number of BT training centers do not have sufficient caseloads to provide the necessary experience for their residents.


Differences between professionals in planning treatment for patients with stage III lung cancer using treatment-planning QA software

The quality of treatment planning for stage III non-small cell lung cancer varies within and between facilities due to the different professions involved in planning. Dose estimation parameters were calculated using a feasibility dose-volume histogram (FDVH) implemented in the treatment planning quality assurance software PlanIQ. This study aimed to evaluate differences in treatment planning between occupations using manual FDVH-referenced treatment planning to identify their characteristics. The study included ten patients with stage III non-small cell lung cancer, and volumetric-modulated arc therapy was used as the treatment planning technique. Fifteen planners, comprising five radiation oncologists, five medical physicists, and five radiological technologists, developed treatment strategies after referring to the FDVH. Medical physicists had a higher mean dose at D98% of the planning target volume (PTV) and a lower mean dose at D2% of the PTV than those in other occupations. Medical physicists had the lowest irradiation lung volumes (V5 Gy and V13 Gy) compared to other professions, and radiation oncologists had the lowest V20 Gy and mean lung dose. Radiological technologists had the highest irradiation volumes for dose constraints at all indexes on the normal lung volume. The quality of the treatment plans developed in this study differed between occupations due to their background expertise, even when an FDVH was used as a reference. Therefore, discussing and sharing knowledge and treatment planning techniques among professionals is essential to determine the optimal treatment plan for each facility and patient.

Reports of Practical Oncology and Radiotherapy


Effect of Positive Biopsy Core Rate on Low-dose-rate Brachytherapy Outcomes in Intermediate-risk Prostate Cancer.

Positive core ratios observed on prostate biopsy correlated with higher recurrence rates after LDR-BT. This indicates that the proportion of positive cores in the biopsy may be an important factor in predicting the likelihood of recurrence, especially for patients with GG3 PCa.


Current status and issues with the dosimetric assay of iodine-125 seed sources at medical facilities in Japan: a questionnaire-based survey

In conducting dosimetric assays of seed sources containing iodine-125 (125I), several major guidelines require the medical physicist to verify the source strength before patient treatment. Japanese guidelines do not mandate dosimetric assays at medical facilities, but since 2017, three incidents have occurred in Japan wherein seeds with incorrect strengths were delivered to medical facilities. Therefore, this study aimed to survey the current situation and any barriers to conducting the dosimetric assay of iodine-125 seeds at medical facilities in Japan. We conducted a questionnaire-based survey from December 2020 to April 2021, to examine whether seed assay and verification of the number of seeds delivered were being performed. We found that only 9 facilities (16%) performed seed assay and 28 (52%) verified the number of seeds. None of the facilities used an assay method that ensured traceability. The reasons for not performing an assay were divided into two categories: lack of resources and legal issues. Lack of resources included lack of instruments, lack of knowledge of assay methods, shorthand, or all of the above, whereas legal issues included the inability to resterilize iodine-125 seeds distributed in Japan and/or purchase seeds dedicated to the assay. Dosimetric assays, including simple methods, are effective in detecting calibration date errors and non-radioactive seeds. The study findings suggest that familiarization of medical personnel with these assay methods and investigation of the associated costs of labor and equipment should be recommended, as these measures will lead to medical reimbursement for quality assurance.


Early Prediction of Radiotherapeutic Effecacy in a Mouse Model of Non-Small Cell Lung Carcinoma Using 18F-FLT and 18F-FDG PET/CT

This study investigated the usefulness of [18F]-3'-deoxy-3'-fluorothymidine (18F-FLT) and [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for predicting the therapeutic efficacy of non-small cell lung cancer (NSCLC) irradiation at an early stage after radiation treatment. Mice were xenografted with the human lung adenocarcinoma line A549 or large cell lung cancer line FT821. Tumour uptake of 18F-FLT and 18F-FDG was imaged using PET/CT before and 1 week after irradiation. In A549 tumours, 18F-FLT uptake was significantly decreased, and 18F-FDG uptake was unchanged post-irradiation compared with pre-irradiation. In FT821 tumours, uptake of both 18F-FLT and 18F-FDG uptake was substantially decreased post-irradiation compared with pre-irradiation. In both xenografts, tumour volumes in the irradiated groups were significantly decreased compared with those in the control group. 18F-FLT is expected to contribute to individual NSCLC therapy because it accurately evaluates the decrease in tumour activity that cannot be captured by 18F-FDG. 18F-FDG may be useful for evaluating surviving cells without being affected by the inflammatory reaction at an extremely early stage, approximately 1 week after irradiation. Combined use of 18F-FLT and 18F-FDG PET/CT imaging may increase the accurate prediction of radiotherapy efficacy, which may lead to improved patient outcomes and minimally invasive personalised therapy. J. Med. Invest. 70 : 361-368, August, 2023.

The Journal of Medical Investigation : JMI


Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range

To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.


Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer

Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001). It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.


Prostate-specific Antigen Levels Following Brachytherapy Impact Late Biochemical Recurrence in Japanese Patients With Localized Prostate Cancer.

PSA levels at 5 years post-treatment were associated with long-term recurrence of localized prostate cancer, which can help alleviate patient anxiety concerning prostate cancer recurrence if PSA levels remain low at 5 years after LDR-BT.


Predicting the complexity of head-and-neck volumetric-modulated arc therapy planning using a radiation therapy planning quality assurance software

The more complex the treatment plan, the higher the possibility of errors in dose verification. Recently, a treatment planning quality assurance (QA) software (PlanIQ) with a function to objectively evaluate the quality of volumetric-modulated arc therapy (VMAT) treatment plans by scoring and calculating the ideal dose-volume histogram has been marketed. This study aimed to assess the association between the scores of ideal treatment plans identified using PlanIQ and the results of dose verification and to investigate whether the results of dose verification can be predicted based on the complexity of treatment plans. Dose verification was performed using an ionization chamber dosimeter, a radiochromic film, and a three-dimensional dose verification system, Delta4 PT. Correlations between the ideal treatment plan scores obtained by PlanIQ and the results of the absolute dose verification and dose distribution verification were obtained, and it was examined whether dose verifications could be predicted from the complexity of the treatment plans. Even when the score from the ideal treatment plan was high, the results of absolute dose verification and dose distribution verification were sometimes poor. However, even when the score from the ideal treatment plan was low, the absolute volume verification and dose distribution verification sometimes yielded good results. Treatment plan complexity can be determined in advance from the ideal treatment plan score calculated by PlanIQ. However, it is difficult to predict the results of dose verification using an ideal treatment plan.


診療用放射線照射装置使用室(RALS室)に併設された診療用CTエックス線撮影装置の単独使用に関するアンケート報告


Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial

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. 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%. 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). The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.


Japanese Society for Radiation Oncology Consensus Guidelines of combined intracavitary and interstitial brachytherapy for gynecological cancers.

It has been postulated that the combination of intracavitary and interstitial brachytherapy (IC/IS) is effective and safe for large and irregularly shaped uterine cervical cancer patients. However, due to its invasiveness compared to conventional intracavitary brachytherapy (ICBT), it has to be said that the implementation speed of IC/IS is slow. Until now, there have been no guidelines for required equipment, human resources, and procedural guide focusing solely on IC/IS. The purpose of this guideline is to provide radiation oncologists and medical physicists who wish to start IC/IS with practical and comprehensive guidance for a safe IC/IS introduction and to help accelerate the spread of the utilization of IC/IS nationwide. This is the English translation of the Japanese IC/IS Guidelines, and it was created in an effort to share the Japanese approach to the management of locally advanced uterine cervical cancer worldwide.


Radiomics analysis of [18F]-fluoro-2-deoxyglucose positron emission tomography for the prediction of cervical lymph node metastasis in tongue squamous cell carcinoma

This study aimed to create a predictive model for cervical lymph node metastasis (CLNM) in patients with tongue squamous cell carcinoma (SCC) based on radiomics features detected by [F]-fluoro-2-deoxyglucose (F-FDG) positron emission tomography (PET). A total of 40 patients with tongue SCC who underwent F-FDG PET imaging during their first medical examination were enrolled. During the follow-up period (mean 28 months), 20 patients had CLNM, including six with late CLNM, whereas the remaining 20 patients did not have CLNM. Radiomics features were extracted from F-FDG PET images of all patients irrespective of metal artifact, and clinicopathological factors were obtained from the medical records. Late CLNM was defined as the CLNM that occurred after major treatment. The least absolute shrinkage and selection operator (LASSO) model was used for radiomics feature selection and sequential data fitting. The receiver operating characteristic curve analysis was used to assess the predictive performance of the F-FDG PET-based model and clinicopathological factors model (CFM) for CLNM. Six radiomics features were selected from LASSO analysis. The average values of the area under the curve (AUC), accuracy, sensitivity, and specificity of radiomics analysis for predicting CLNM from F-FDG PET images were 0.79, 0.68, 0.65, and 0.70, respectively. In contrast, those of the CFM were 0.54, 0.60, 0.60, and 0.60, respectively. The F-FDG PET-based model showed significantly higher AUC than that of the CFM. The F-FDG PET-based model has better potential for diagnosing CLNM and predicting late CLNM in patients with tongue SCC than the CFM.


Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy

Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. The patients' median age was 60 (range 33-80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m) before treatment had a poor prognosis (p = 0.016 and p < 0.001). Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

International Journal of Clinical Oncology


Differences in image density adjustment parameters on the image matching accuracy of a floor-mounted kV X-ray image-guided radiation therapy system

This study aimed to investigate the effect of two different image density adjustment parameters on the results of image matching at six degrees of freedom using radiographic images generated by the ExacTrac X-ray system in brain stereotactic radiosurgery (SRS). This study comprised 32 patients who underwent brain SRS at our hospital from January 2020 to December 2020. In this study, (1) the default parameter (an image density parameter between "tissue" and "bone") was an image density parameter for digitally reconstructed radiograph (DRR) generation used at many facilities, and (2) the bone parameter was the steepest contrast parameter used at our hospital. Of the 32 patients, 24 (75%) had a couch angle of 0.5 mm or more in the translational direction or 0.5° or more in the rotational direction, and 10 (31%) had a couch angle of 1.0 mm or more in the translational direction or 1.0° or more in the rotational direction. Among the 131 cases of all couch angles, 46 (35%) cases had a translational direction of 0.5 mm or more or a rotational direction of 0.5° or more, and 15 (11%) had a translational direction of 1.0 mm or more or a rotational direction of 1.0° or more. The results of this study indicate the usefulness of using appropriate DRR parameters for each case, rather than using the default settings. The use of appropriate DRR parameters can lead to accurate position matching results, leading to fewer image-guided radiation therapy shots and a lower imaging dose.

Journal of Applied Clinical Medical Physics


Combined Interstitial and Intracavitary High-Dose Rate Brachytherapy of Cervical Cancer

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.


Prediction of out-of-field recurrence after chemoradiotherapy for cervical cancer using a combination model of clinical parameters and magnetic resonance imaging radiomics: a multi-institutional study of the Japanese Radiation Oncology Study Group


Clinical value of serum biomarkers, squamous cell carcinoma antigen and apolipoprotein C-II in follow-up of patients with locally advanced cervical squamous cell carcinoma treated with radiation: A multicenter prospective cohort study

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.


Impact of treatment planning quality assurance software on volumetric-modulated arc therapy plans for prostate cancer patients

Software that evaluates the quality of treatment plans (PlanIQ) has become commercially available in recent years. It includes a feasibility assessment tool that provides the ideal dose volume histogram (DVH) for each organ at risk, based on the ideal dose falloff from the prescribed dose at the target boundary. It is important to investigate whether the PlanIQ assessment tool (Feasibility DVH) can assist treatment planners who have limited to no experience in treatment planning. Therefore, the present study aimed to evaluate this tool's usefulness for improving the quality of treatment plans. This study included 5 patients with prostate cancer. The treatment planners were 2 graduate students, 2 undergraduate students, and one clinical planner. All students were radiological technology and medical physics students with no clinical experience. Two different volumetric-modulated arc therapy (VMAT) plans were developed before and after Feasibility DVH. The quality of each treatment plan was evaluated based on a scoring system implemented in PlanIQ. Of 5 patients included, 4 received improved treatment plans when Feasibility DVH was used. Moreover, 4 of 5 treatment planners showed improvement in treatment planning using Feasibility DVH. The findings suggest that using the Feasibility DVH tool may improve treatment plans for different planners and patients. However, planners at any level of experience should be trained to check the dose distribution in addition to checking the DVH, which depends on the adequacy of the contours.


Automatic Contour Segmentation of Cervical Cancer using Artificial Intelligence

In cervical cancer treatment, radiation therapy is selected based on the degree of tumor progression, and radiation oncologists are required to delineate tumor contours. To reduce the burden on radiation oncologists, an automatic segmentation of the tumor contours would prove useful. To the best of our knowledge, automatic tumor contour segmentation has rarely been applied to cervical cancer treatment. In this study, diffusion-weighted images (DWI) of 98 patients with cervical cancer were acquired. We trained an automatic tumor contour segmentation model using 2D U-Net and 3D U-Net to investigate the possibility of applying such a model to clinical practice. A total of 98 cases were employed for the training, and they were then predicted by swapping the training and test images. To predict tumor contours, six prediction images were obtained after six training sessions for one case. The six images were then summed and binarized to output a final image through automatic contour segmentation. For the evaluation, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) was applied to analyze the difference between tumor contour delineation by radiation oncologists and the output image. The DSC ranged from 0.13 to 0.93 (median 0.83, mean 0.77). The cases with DSC <0.65 included tumors with a maximum diameter < 40 mm and heterogeneous intracavitary concentration due to necrosis. The HD ranged from 2.7 to 9.6 mm (median 4.7 mm). Thus, the study confirmed that the tumor contours of cervical cancer can be automatically segmented with high accuracy.


Dose Assessment on the Mean Absorbed Estimates Derived from the Simple Approach Method Applying Marinelli-Quimby's Formula for Ambient Risk Organs to Thyroid Uptake in the Administered131 I Radiopharmaceutical of Graves' Disease Using PHITS and ICRP Reference Computational Voxel Phantom


Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice.

International Journal of Radiation Biology


Analysis of prostate intensity- and volumetric-modulated arc radiation therapy planning quality with PlanIQTM

The purpose of this study was to assess the quality of treatment planning using the PlanIQ software and to investigate whether it is possible to improve the quality of treatment planning using the "Feasibility dose-volume histogram (DVH) " implemented in the PlanIQ software. Using the PlanIQ software, we retrospectively analyzed the learning curve regarding the quality of the treatment plans for 148 patients of prostate intensity-modulated radiation therapy and volumetric-modulated radiation therapy performed at our institution over the past eight years. We also sought to examine the possibility of improving treatment planning quality by re-planning in 47 patients where the quality of the target dose and the dose limits for organs at risk (OARs) were inadequate. The re-planning treatment plans referred to the Feasibility DVH implemented in the PlanIQ software and modified the treatment planning system based on the target dose and OAR constraints. Analysis of the learning curve of the treatment plans quality using PlanIQ software retrospectively showed a trend of improvement in the treatment plan quality from year to year. The improvement in the treatment plans quality was more influenced by dose reduction in the OARs than by target coverage. In all cases where re-planning was performed, the improvement in the treatment plan's quality resulted in a better treatment plan than the one adopted for delivery to patients in the clinical plan. The PlanIQ provided insights into the quality of the treatment plans at our institution and identified problems and areas for improvement in the treatment plans, allowing for the development of appropriate treatment plans for specific patients.


A disposable OSL dosimeter for in-vivo measurement of rectum dose during brachytherapy

We aimed to develop a disposable rectum dosimeter and to demonstrate its ability to measure exposure dose to the rectum during brachytherapy for cervical cancer treatment using high-dose rate Ir. Our rectum dosimeter measures the dose with an optically stimulated luminescence (OSL) sheet which was furled to a catheter. The catheter we used is 6 mm in diameter; therefore, it is much less invasive than other rectum dosimeters. The rectum dosimeter developed in this study has the characteristics of being inexpensive and disposable. It is also an easy-to-use detector that can be individually sterilized, making it suitable for clinical use. To obtain a dose calibration curve, phantom experiments were performed. Irradiation was performed using a cubical acrylic phantom, and the response of the OSL dosimeter was calibrated with the calculation value predicted by the treatment planning system (TPS). Additionally, the dependence of catheter angle on the dosimeter position and repeatability were evaluated. We also measured the absorbed dose to the rectum of patients who were undergoing brachytherapy for cervical cancer (n = 64). The doses measured with our dosimeters were compared with the doses calculated by the TPS. In order to examine the causes of large differences between measured and planned doses, we classified the data into common and specific cases when performing this clinical study. For specific cases, the following three categories were considered: (a) patient movement, (b) gas in the vagina and/or rectum, and (c) artifacts in the X-ray image caused by applicators. A dose calibration curve was obtained in the range of 0.1 Gy-10.0 Gy. From the evaluation of the dependence of catheter angle on the dosimeter position and repeatability, we determined that our dosimeter can measure rectum dose with an accuracy of 3.1% (k = 1). In this clinical study, we succeeded in measuring actual doses using our rectum dosimeter. We found that the deviation of the measured dose from the planned dose was derived to be 12.7% (k = 1); this result shows that the clinical study included large elements of uncertainty. The discrepancies were found to be due to patient motion during treatment, applicator movement after planning images were taken, and artifacts in the planning images. We present the idea that a minimally invasive rectum dosimeter can be fabricated using an OSL sheet. Our clinical study demonstrates that a rectum dosimeter made from an OSL sheet has sufficient ability to evaluate rectum dose. Using this dosimeter, valuable information concerning organs at risk can be obtained during brachytherapy.


Effect of dental metal artifact conversion volume on dose distribution in head-and-neck volumetric-modulated arc therapy

Purpose: During treatment planning for head-and-neck volumetric-modulated arc therapy (VMAT), manual contouring of the metal artifact area of artificial teeth is done, and the area is replaced with water computed tomography (CT) values for dose calculation. This contouring of the metal artifact areas, which is performed manually, is subject to human variability. The purpose of this study is to evaluate and analyze the effect of inter-observer variation on dose distribution.Methods: The subjects were 25 cases of cancer of the oropharynx for which VMAT was performed. Six radiation oncologists (ROs) performed metal artifact contouring for all of the cases. Gross tumor volume, clinical target volume, planning target volume (PTV), and oral cavity were evaluated. The contouring of the six ROs was divided into two groups, small and large groups. A reference RO was determined for each group and the dose distribution was compared with those of the other radiation oncologists by gamma analysis (GA).As an additional experiment, we changed the contouring of each dental metal artifact area, creating enlarged contours (L), reduced contours (S), and undrawn contours (N) based on the contouring by the six ROs and compared these structure-sets.Results: The evaluation of inter-observer variation showed no significant difference between the large and small groups, and the GA pass rate was 100%. Similar results were obtained comparing structure-sets L and S, but in the comparison of structure-sets L and N, there were cases with pass rates below 70%.Conclusions: The results show that the artificial variability of manual artificial tooth metal artifact contouring has little effect on the dose distribution of VMAT. However, it should be noted that the dose distribution may change depending on the contouring method in cases where the overlap between PTV and metal artifact areas is large.

Journal of Applied Clinical Medical Physics


Determination of reproducibility of end-exhaled breath-holding in stereotactic body radiation therapy


The effect of rectal gas on dose distribution during prostate cancer treatment using full arc and partial arc Volumetric Modulated Arc Therapy (VMAT) treatment plans

In this study, we investigated the effect of rectal gas on the dose distribution of prostate cancer using a volumetric modulated arc therapy (VMAT) treatment planning. The first is the original structure set, clinical target volume (CTV), the rectum, and the bladder used clinically. The second is a structure set (simulated gas structure set) in which the overlapping part of the rectum and PTV is overwritten with Hounsfield Unit -950 as gas. Full arc and limited gantry rotation angle with VMAT were the two arcs. The VMAT of the full arc was 181°-179° in the clockwise (CW) direction and 179°-181° in the counterclockwise (CCW) direction. Three partial arcs with a limited gantry rotation angle were created: 200°-160 °CW and 160°-200 °CCW; 220°-140 °CW and 140°-220 °CCW; and finally, 240°-120 °CW and 120°-240 °CCW. The evaluation items were dose difference, distance to agreement, and gamma analysis. In the CTV, the full arc was the treatment planning technique with the least effect of rectal gas. In the rectum, when the gantry rotation angle range was short, the pass rate tended to reduce for all evaluation indices. The bladder showed no characteristic change between the treatment planning techniques in any of the evaluation indices. The VMAT treatment planning with the least effect on dose distribution caused by rectal gas was shown to be a full arc.

Reports of Practical Oncology and Radiotherapy


Impact of Changes in Body Contours on Radiation Therapy Dose Distribution After Uterine Cervical Cancer Surgery

Patients receiving postoperative irradiation for uterine cervical cancer might not be able to eat during radiation therapy because of the effects of concurrent chemo-radiotherapy; this may lead to changes in the patient's body shape during treatment. When performing image-guided radiotherapy, it is necessary to determine immediately whether treatment can be performed on the day or whether re-planning is required. The purpose of this study was to determine indicators for re-planning by examining the effects of changing body contours on radiation therapy dose. The original body contour was reduced by 1 cm in the front portion (structure-set 1). Based on the original dose distribution, the dose recalculation was performed with a structure set created using the body contour of structure-set 1. The difference between the original and recalculated dose distributions of structure-set 1 was evaluated through gamma analysis (GA). In the GA results for dose distribution obtained via recalculation with structure-set 1, a pass rate of 90% or more was obtained for a criterion of 2 mm/2% in all cases. The results suggest that dose re-planning is rarely required when the body shape is reduced by only 1 cm in the front.


Radiation protection in radiological imaging: a survey of imaging modalities used in Japanese institutions for verifying applicator placements in high-dose-rate brachytherapy


A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20-70 years old with Stages IB1-IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians' questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients' questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4-5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients' questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.


Simplification of Head and Neck Volumetric Modulated Arc Therapy Patient-specific Quality Assurance, Using a Delta4 PT

In many facilities, intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) use intensity-modulated beams, formed by a multi-leaf collimator (MLC). In IMRT and VMAT, MLC and linear accelerator errors (both geometric and dose), can significantly affect the doses administered to patients. Therefore, IMRT and VMAT treatment plans must include the use of patient-specific quality assurance (QA) before treatment to confirm dose accuracy. In this study, we compared and analyzed the results of dose verification using a multi-dimensional dose verification system Delta4 PT, an ionization chamber dosimeter, and gafchromic film, using data from 52 patients undergoing head and neck VMAT as the test material. Based on the results of the absolute dose verification for the ionization chamber dosimeter and Delta4 PT, taking an axial view, the upper limit of the 95% confidence interval was 3.13%, and the lower limit was -3.67%, indicating good agreement. These results mean that as long as absolute dose verification for the axial view does not deviate from this range, Delta4 PT can be used as an alternative to an ionization chamber dosimeter for absolute dose verification. When we then reviewed dose distribution verification, the pass rate for Delta4 PT was acceptable, and was less varied than that of gafchromic film. This results in that provided the pass rate result for Delta4 PT does not fall below 96%, it can be used as a substitute for gafchromic film in dose distribution verification. These results indicate that patient-specific QA could be simplified.


Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma.

The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC. Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy. DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI < 1, respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients. Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC.


Long-term stability of a three-dimensional dose verification system.

Recently, the number of patients undergoing intensity-modulated radiation therapy and volumetric modulated arc therapy has increased with the expansion of the adaptation site. However, it is necessary to improve the efficiency of time-consuming dose verification. Therefore, patient-specific quality assurance is expected to shift from dose verification using a conventional ionization chamber dosimeter and film to a three-dimensional dose verification system. However, caution is required when using a three-dimensional dose verification system, especially when it comes to the calibration of the detector. Calibration is performed regularly, but not all necessary verifications are done routinely. There are many uncertainties on how the sensitivity of the three-dimensional dose verification system changes over time. In this study, on the same day, when dose verification using a three-dimensional system for one head and neck case was performed, dose verification using a conventional ionization chamber dosimeter and film was also performed once every two months, for 2 years. From the results of the absolute dose and dose distribution verification using the ionization chamber dosimeter and Gafchromic film, the output of the linear accelerator, mechanical accuracy and precision were secured. From the results of the three-dimensional dose verification system, when the distance to agreement was evaluated at 2 mm and 3 mm, and gamma analysis was performed at 2 mm/2% and 3 mm/3%, the passing rate was almost 100%, and a sensitivity change in 2 years was not observed.


Clinical outcomes and prognostic factors of definitive radiotherapy for esophageal cancer

Purpose To assess the treatment results of definitive radiotherapy for esophageal cancer at Tokushima University Hospital and clarify the prognostic factors. Methods Seventy consecutive patients with esophageal cancer who underwent definitive radiotherapy between May 2004 and March 2012 were included in the present study. Local control rate, overall survival rate, and radiation morbidity were examined and univariate and multivariate analyses were performed to investigate prognostic factors. Results The 5-yearoverall survival rates of stages I, II, III, and IVA were 81%, 71%, 0%, and 9%, respectively. Performance status, clinical stage, and neoadjuvant chemotherapy were significant prognostic factors. A past history of interstitial pneumonia was associated with severe radiation-induced lung injury. Conclusions Patients who underwent definitive chemoradiotherapy for esophageal cancer in stage I/II showed good prognosis. However, treatment results of the patients in stage III/IV were not satisfactory, and those who could not undergo surgery after neoadjuvant chemotherapy had the worst prognosis.J.Med.Invest.66:99-105, February, 2019.

The Journal of Medical Investigation : JMI


Clinical outcomes of hypofractionated image-guided multifocal irradiation using volumetric-modulated arc therapy for brain metastases.

Volumetric-modulated arc therapy (VMAT) can be used to design hypofractionated radiotherapy treatment plans for multiple brain metastases. The purpose of this study was to evaluate treatment outcomes of hypofractionated image-guided multifocal irradiation using VMAT (HFIGMI-VMAT) for brain metastases. From July 2012 to December 2016, 67 consecutive patients with 601 brain metastases were treated with HFIGMI-VMAT at our institution. The prescribed dose was 50 Gy to a 95% volume of the planning target volume in 10 fractions. Fifty-five of the 67 patients had non-small-cell lung cancer, and the remaining 12 had other types of cancer. The median number of brain metastases was five, and the median maximum diameter was 1.2 cm. The median duration of follow-up was 12.0 months (range, 1.9-44.8 months), and the median survival time 18.7 months. Four patients with six lesions had local recurrences. The local control rate in the 64 assessed patients was 98.4% and 95.3% at 6 and 12 months, respectively (three died before assessment). The local control rate for the 572 assessed lesions was 99.8% and 99.3% at 6 and 12 months, respectively. Thirty-nine patients developed distant brain metastases, the distant brain control rate being 59.7% and 40.5% at 6 and 12 months, respectively. Acute toxicities were generally mild (Grade 1-2). Three patients (4.5%) developed radiation necrosis requiring corticosteroid therapy. The HFIGMI-VMAT technique with flat dose delivery was well tolerated and achieved excellent local control. This technique is a promising treatment option for patients with multiple and large brain metastases.


Development of Novel Rectum Dosimeter using OSL sheet with the aim of Direct Dose Measurement of Organ Dose during Brachytherapy

Progress in Nuclear Science and Technology


Direct Radiation Dose Measurement of Rectum during High-Dose-Rate 192Ir Brachytherapy for Cervical Cancer Treatment


子宮頸癌患者に対する日本語版QOL調査票の開発

子宮頸癌患者に対する日本語版QOL調査票の開発

Japanese Journal of Gynecological Oncology


National survey of intracavitary brachytherapy for intact uterine cervical cancer in Japan

To review the current status of, and labor expended for (in terms of time required), intracavitary brachytherapy (ICBT) in definitive radiotherapy/chemoradiotherapy for cervical cancer patients, two national surveys were performed. The first survey was conducted between July and August 2016 and consisted of a questionnaire of 12 items regarding ICBT procedures for cervical cancer, which was sent to 173 centers installed with high-dose-rate remote after-loading brachytherapy systems. Between November and December 2016, another survey was performed in 79 centers to evaluate labor required for ICBT procedures in terms of time spent and number of staff involved. In the first survey, the response rate was 77% of the 173 centers. ICBT was performed for cervical cancer in 118 (89%) centers. Imaging modalities used after applicator insertion were X-ray alone in 46 (40%), computed tomography in 69 (60%) and magnetic resonance imaging in 5 (4%) centers. Three-dimensional (3D) planning was performed in 55 centers (48%). Fifty-five (70%) centers responded to the second survey regarding ICBT-mandated labor. The median cumulative duration of the entire ICBT procedure was 330 min (the sum of the times spent by each staff member) and was longer in the 3D image-guided brachytherapy (3D-IGBT) (405 min) than in the X-ray group (230 min). This trend was significant for the specific processes of image acquisition and treatment planning, especially for radiation oncologists. In definitive radiotherapy/chemoradiotherapy for cervical cancer patients, 3D-IGBT use has been gradually spreading in Japan. The present survey revealed that ICBT, especially 3D-IGBT, requires substantial labor and time from staff.


Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. The guideline was created according to the basic principles in creating the guidelines of JSGO. The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

International Journal of Clinical Oncology


Radiotherapy for vaginal cancer: a multi-institutional survey study of the Japanese Radiation Oncology Study Group

Our aim was to assess the patterns of practice and treatment outcomes of definitive radiotherapy (RT) for vaginal cancer in Japan. RT methods and outcomes of patients with vaginal cancer treated with definitive RT or chemoradiotherapy at 10 institutes of the Japanese Radiation Oncology Study Group between January 2000 and March 2010 were retrospectively evaluated. A total of 90 patients were enrolled in the study. The clinical stages were I, II, III, and IVA in 34, 36, 16, and 4 patients, respectively. Seventy patients were treated with three-dimensional conformal RT (3DCRT) and brachytherapy (BT), 12 with BT alone, and 8 with 3DCRT alone. Chemotherapy was administered to 29 patients. The 5-year overall survival and local control rates were 77 and 83% with a median follow-up period of 94 months for surviving or lost patients. The 5-year overall survival rates according to stage were 94, 71, 56, and 75% for stages I, II, III, and IVA, respectively. The 5-year local control rates according to stage were 94, 77, 74, and 75% for stages I, II, III, and IVA, respectively. Twenty-nine percent (6 of 21 patients) of local recurrences occurred between 5 and 10 years after RT. The 10-year local control rate of all patients was 71%. Significant prognostic factors for overall survival by univariate and multi-variate analyses were performance status, tumor size, and pelvic lymph node metastasis. Grade 3 late radiation morbidity of the rectum, pelvic bone, urinary bladder, and skin developed in 9% (8 of 90 patients). Good outcomes similar to those of cervical cancer can be achieved with definitive RT delivered by 3DCRT and/or BT for vaginal cancer. Long follow-up is necessary for a continuing risk of local recurrence after 5 years.


Predictive Factors for Prolonged Urination Disorder After Permanent 125I Brachytherapy for Localized Prostate Cancer

We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. Four hundred and four patients received prostate brachytherapy at our institution and were followed-up for at least 2 years. We evaluated the correlation of mean IPSS changes and clinical factors. Using multivariate analysis, we also evaluated clinical factors with potential to delay IPSS resolution. In cases with prostate volume more than 30 cm, radiation dose to 90% of prostate volume (D90) more than 160 Gy, and radiation dose to 30% of the urethral volume (UD30) more than 240 Gy, mean IPSS levels were significantly higher, even 30 months after treatment. On multivariate analysis, baseline IPSS more than 8 points and D90 more than 160 Gy were significant predictors for delayed IPSS resolution. Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.


Influence of multi-leaf collimator leaf transmission on head and neck intensity-modulated radiation therapy and volumetric-modulated arc therapy planning.

The aim of this study was to quantify the effect of multi-leaf collimators (MLCs) with different leaf widths on the planning of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). Toward this objective, dose transmission through a high-definition 120-leaf MLC (HD120MLC) and 120-leaf Millennium MLC (M120MLC) was investigated, using it with a test case and clinical case studies. In test case, studies with IMRT and VMAT plans, the difference in MLC leaf width had a limited effect on planning target volumes (PTVs). Organs at risk (OARs) were more affected by a reduction in dose transmission through the MLC than by a reduction in MLC leaf width. The results of the test case studies and clinical case studies were mostly similar. In the latter, the different MLCs had no effect on the PTV regardless of the treatment method; however, the HD120MLC plans achieved dose reductions to OARs similar to or larger than the dose reduction of the M120MLC plans. The similar results of the test case and clinical case studies showed that despite a limitation of the irradiation field size, the HD120MLC plans were superior.


Effectiveness of Newly Developed Water-Equivalent Mouthpiece during External Beam Radiotherapy for Oral Cancer


Recommendations for high-risk clinical target volume definition with comp@uted tomography for three-dimensional image-guided brachytherapy in cervical cancer patients.

Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial-caudal, lateral, or anterior-posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning.


A multicenter phase I study of preoperative chemoradiotherapy with S-1 and irinotecan for locally advanced lower rectal cancer (SAMRAI-1).

Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1. Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45Gy in 25 fractions. S-1 (80mg/m(2)/day) was administered on days 1-5, 8-12, 22-26, and 29-33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60mg/m(2) (level 1). Surgery was performed 6-10weeks after the chemoradiotherapy. Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80mg/m(2) (level 2), but developed in 3 of the 6 patients who received irinotecan at 90mg/m(2) (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%. Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60mg/m(2).


Primary Pulmonary Synovial Sarcoma Showing a Prolonged Survival with Multimodality Therapy

A 54-year-old man was referred to our hospital due to a mass shadow noted on a chest X-ray. Thoracoscopic lobectomy yielded a diagnosis of primary pulmonary synovial sarcoma according to the histology and SYT-SSX1 gene analyses. Five months after the thoracic surgery, he developed brain metastasis; therefore, we performed resection of the brain metastatic focus followed by radiotherapy. As a local recurrence in the thoracic cavity concurrently emerged, systemic chemotherapy was also administered. These observations indicated that a multidisciplinary approach may be useful against primary pulmonary synovial sarcoma, although there is presently no established therapeutic strategy due to its rarity and highly aggressive nature.


Dose impact of rectal gas on prostatic IMRT and VMAT

In this study, we compared the dose impact of the heterogeneity caused by rectal gas using two methods of treatment planning for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). In addition to the structure set used for the standard treatment plan, we created a structure set for evaluation for each patient. These sets were transferred to the same isocenter as the respective treatment plans for IMRT and VMAT that were to become the standard. Values were then recalculated. During the standard prostatic IMRT and VMAT treatment planning, all study participants met dose restrictions in place at our hospital. Dose restrictions were fulfilled in treatment plans for evaluation, excluding those with a clinical target volume (CTV) of V(100%) and planning target volume (PTV) of D95 when the rectum was excluded. However, in treatment plans for evaluation, IMRT was shown to have a higher concordance rate with standard treatment plans than VMAT. If rectal gas is present during either IMRT or VMAT, a dose decrease will occur in relation to CTV and PTV, suggesting that a plan does not eliminate adverse effects on organs at risk.


Clinical Significance of Neoadjuvant Combined Androgen Blockade for More Than Six Months in Patients with Localized Prostate Cancer Treated with Prostate Brachytherapy.

The aim of this study is to clarify the clinical significance of neoadjuvant combined androgen blockade (CAB) for ≥ 6 months in patients with localized prostate cancer. A total of 431 patients with localized prostate cancer who underwent prostate brachytherapy (BT) with or without neoadjuvant CAB for ≥ 6 months with mean follow-up time of 64.6 months (range 24-108 months) were evaluated retrospectively. Of those 431, 232 patients received BT in combination with neoadjuvant CAB for ≥ 6 months. Biochemical recurrence-free rates (BRFRs) in 364 patients with at least 3 years of follow-up were evaluated by log-rank test. BRFR in patients with low-, intermediate- and high-risk prostate cancer were 98.1, 94.2 and 89.1%, respectively. In patients with intermediate-risk prostate cancer only, neoadjuvant CAB was significantly associated with BRFR (p = 0.0468). Especially in patients with intermediate-risk prostate cancer with radiation dose received by 90% of the prostate (D90) < 180 Gy, neoadjuvant CAB exerted a favorable impact on BRFR (p = 0.0429). On multivariate analyses, neoadjuvant CAB and D90 were independent predictors of BRFR (p = 0.0061 and p < 0.0001, respectively). Neoadjuvant CAB for ≥ 6 months has a favorable impact on BRFR in patients with intermediate-risk prostate cancer, particularly in patients with relatively low radiation doses of D90.


A Phase I/II Study of Fixed-dose-rate Gemcitabine and S-1 with Concurrent Radiotherapy for Locally Advanced Pancreatic Cancer

This study was conducted to identify the maximum-tolerated dose (MTD) of fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and radical radiation for locally advanced pancreatic cancer (LAPC) and to provide efficacy and safety data. Patients with unrespectable pancreatic cancer confined to the pancreatic region were treated with FDR-gem (300-400 mg/m(2), 5 mg/m(2)/min) on days 1, 8, 22, and 29 and 60 mg/m(2) of S-1 orally on days 1-14, 22-35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28 fractions) was delivered concurrently. Twenty-five patients were enrolled; all were evaluable for toxicity assessment. In phase I, eight patients were treated in sequential cohorts of three to five patients per dose level. The MTD was reached at level 2, and dose-limiting toxicities were neutropenia and thrombocytopenia. The recommended doses were 300 mg/m(2) of gemcitabine and 60 mg/m(2) of S-1 daily. The overall response rate was 25% and disease control rate (partial response plus stable disease) was 92%. The progression-free survival was 11.0 months. The median overall survival and 1-year survival rates were 16.0 months and 73%, respectively. The combination of FDR-gem and S-1 with radiation is a feasible regimen that shows favorable antitumor activity with an acceptable safety profile in patients with LAPC.


Radiation therapy definitions and reporting guidelines for thymic malignancies


Comparing the performance of visual estimation and standard uptake value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography for detecting malignancy in pancreatic tumors other than invasive ductal carcinoma.

The utility of FDG PET/CT for the detection and evaluation of invasive ductal carcinoma has been widely reported, but a few studies have assessed the utility of FDG PET/CT to detect malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma. To compare the diagnostic performance of visual estimation with the semi-quantitative scores of FDG PET/CT for detecting malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma. Images of pathologically proven pancreatic lesions from 32 patients were retrospectively evaluated: 14 benign lesions, 7 borderline (low malignant) lesions, and 11 malignant lesions. The average scores from visual estimation by the two observers were compared to two semi-quantitative analyses of FDG uptake in the lesions, namely the maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean). Visual analysis value, SUVmax and SUVmean were 0.33 ± 0.21, 1.8 ± 0.7 and 1.5 ± 0.7 for the benign lesions, 0.70 ± 0.28, 5.0 ± 2.6 and 3.1±1.7 for the borderline lesions, and 0.73 ± 0.18, 4.7 ± 2.5 and 3.2 ± 1.6 for the malignant lesions, respectively. Receiver operating characteristic analysis revealed the areas under the curves for detecting non-benign (malignant or borderline) lesions through visual analysis, SUVmax, and SUVmean were 0.914, 0.954, and 0.875, respectively. For a variety of pancreatic lesions other than invasive ductal carcinoma, visual analysis and semi-quantitative analyses all showed strong diagnostic performance. However, semi-quantitative analysis with SUVmax proved to be the most effective method for detecting non-benign pancreatic lesions.

The Journal of Medical Investigation : JMI


Clinical evaluation of automatic contours for head and neck region using deformable image registration software

The purpose of this study was to clinically evaluate the automatic outline extraction properties using general-purpose deformable image registration (DIR) software for the head and neck region. To this end, we evaluated the following: (1) the difference between manual outline extraction carried out by a radiation therapy specialist and automatic outline extraction using the DIR software, and (2) the precision of the automatic outline extraction for the diachronic figure change and change in the organ shape. The manually-extracted outline and that extracted using the DIR software closely resembled each other at 0.70. Further, in the same case, the automatic outline extraction precision of the DIR software was greater at about 0.80. Our findings suggest DIR software to be useful for lessening the work involved in outline extraction.

Japanese Journal of Radiological Technology


A comparison of four commercial radiation treatment planning systems for prostate intensity modulated radiation therapy

At present, every manufacturer of intensity modulated radiation therapy (IMRT) equipment uses multi-leaf collimators (MLCs); however, each company's intensity modulation methods and dose calculation algorithms differ. This study used four typical radiation treatment planning systems (RTPSs) employed domestically for prostate IMRT plans to carry out 15 case studies by one planner based on the dose limits at this clinic. The results were used to compare the differences, if any, in RTPS treatment plans. With prostate IMRT plans, an overlap area exists between the PTV and the rectum. For this reason, while observing dose limits of 60-75 Gy (within the dose tolerated by the rectum), securing uniformity and concentration of dose is essential to create the most appropriate treatment plan for the PTV and other targets. Although each RTPS uses different planning methods, it was generally possible to observe this clinic's dose limits by adjusting the parameter values. When identical beam data is used, it is possible to create similar treatment plans.


Changes of tumor and normal structures of the neck during radiation therapy for head and neck cancer requires adaptive strategy.

The treatment period over which radiation therapy is administered extends over several weeks. Since tumor shrinkage in response to radiation therapy and weight loss due to radiation-induced mucositis may impact on the dose distribution in both target and organ at risk in patients with head and neck cancer, the anatomical changes of tumor and neck volumes during this period should be taken into consideration. We investigated the anatomical changes that occurred in the target and normal structure of the neck during radiation therapy for pharyngeal cancer, and evaluated the necessity of an adaptive strategy. Ten patients with pharyngeal cancer who underwent radical chemoradiation therapy using 3-dimensional conformal radiation therapy RT (66-70 Gy in 33-35 fractions) between April 2009 and September 2010 were enrolled in the study. Patients underwent CT scans every week during their course of treatment. We analyzed the CT data in the radiation treatment planning system and measured changes of tumor, organ at risk, and neck volume. Gross tumor volume (GTV) was rapidly reduced by 28% of the original volume on average in the first 3 weeks. The right and left submandibular glands volume decreased to 70% and 63% of their initial volumes on average, respectively. The volume of the neck in the radiation fields decreased to 89% of its initial volume on average by the sixth week mainly caused by body weight loss due to acute radiation morbidity. Considerable anatomical change in the radiation filed that will affect dose distribution of the target and organ at risk was observed during radiation therapy for head and neck cancer.


The value of diagnostic imaging in neoadjuvant chemoradiation therapy for non-small cell lung cancer

非小細胞肺癌に対する術前導入化学放射線療法における画像診断の有用性


Shielding Effect of a Customized Intraoral Mold Including Lead Material in High-dose-rate 192-Ir Brachytherapy for Oral Cavity Cancer.

A high-dose-rate (HDR) 192-Ir brachytherapy using a customized intraoral mold is effective for superficial oral cavity cancer, and the surrounding normal tissue is kept away from the radioactive source with gauze pads and/or mouth piece for reducing the dose on the normal tissues. In the Tokushima university hospital, the mold has a lead shield which utilizes the space prepared with sufficient border-molding by a specific dental technique using modeling compound. In HDR 192-Ir brachytherapy using a lead shielded customized intraoral mold, there are no reports measuring the absorbed dose. The purpose of the present study is to measure the absorbed dose and discuss the optimum thickness of lead in HDR 192-Ir brachytherapy using a customized intraoral mold with lead shield using a 1 cm thickness mimic mold. The thickness of lead in the mold could be changed by varying the arrangement of 0.1 cm thickness sheet of the acrylic resin plate and lead. The measured doses at the lateral surface of the mold with thermo-luminescence dosimeter were reduced to 1.12, 0.79, 0.57, 0.41, 0.31, 0.24 and 0.19 Gy and the ratios to the prescription dose were reduced to 56, 40, 29, 21, 16, 12 and 10 percent as lead thickness increased from 0 to 0.6 cm in 0.1 cm increments, respectively. A 0.3 cm thickness lead was considered to be required for a 1 cm thickness mold, and it was necessary to thicken the lead as much as possible with the constraint of limited space in the oral cavity, especially at the fornix vestibule.


Reirradiation of paraaortic lymph node metastasis by brachytherapy with hyaluronate injection via paravertebral approach: With DVH comparison to IMRT.

PURPOSE/INTRODUCTION: To safely irradiate retroperitoneal targets as paraaortic lymph node by separating abdominal at-risk organs from the target during irradiation, we created a percutaneous paravertebral approach of high-dose-rate brachytherapy with hyaluronate gel injection (HGI). We report a case treated with this technique. We encountered a patient with symptomatic regrowth of paraaortic lymph node metastasis from prostatic cancer. He had previously received 58.4Gy of radiotherapy to the same region 12 months prior. Brachytherapy needles and a HGI needle were deployed via the paravertebral approach under local anesthesia at our outpatient clinic. A single dose of 22.5Gy (equivalent to 60.94Gy in 2Gy per fraction schedule calculated at α/β=10) was delivered to the target, with preservation of the surrounding small intestine by HGI with D(2cc) (minimum dose to the most irradiated volume of 2mL) of 5.05Gy. Therapeutic ratio was 3.64 times higher for this brachytherapy plan compared with an intensity-modulated radiation therapy plan. At followup at 1 year after brachytherapy, the symptoms had disappeared, tumor size had reduced with no fluorodeoxyglucose accumulation, and prostate-specific antigen level had decreased. We consider that high-dose-rate brachytherapy with the HGI procedure offers effective treatment even in this type of reirradiation situation.


Radiation therapy definitions and reporting guidelines for thymic malignancies.


中間リスク群，高リスク群前立腺癌に対するI-125密封小線源療法の治療成績

中間リスク群，高リスク群前立腺癌に対するI-125密封小線源療法の治療成績


Impact of multileaf collimator leaf positioning accuracy on intensity modulated radiation therapy.

マルチリーフコリメータの位置精度が強度変調放射線治療に及ぼす影響

In multileaf collimator (MLC)-based intensity modulated radiation therapy (IMRT), the dose is influenced by the uncertainty of MLC driving control. In this study, we examined the influence of MLC driving control accuracy on dose evaluation (gamma analysis) by evaluating 60-day MLC driving control accuracy (stationary positioning accuracy and positioning reproducibility) once a week as well as measuring IMRT dose distribution. The MLC positioning accuracy accompanied variation over time and tended to expand by 0.1 to 0.15 mm in one week and about 1 mm in 60 days. In terms of reproducibility, errors were within 0.2 mm for more than 95%. For prostate IMRT, when MLC stationary positioning accuracy was around 1 mm, no significant difference was observed in the pass rate in gamma analysis. Therefore, the results suggest that regular maintenance by setting a permissible value determined by the MLC positioning accuracy test can be an effective indicator in the future for maintaining the safety of IMRT.


強度変調放射線治療におけるradiographic filmと radiochromic filmの比較評価

Purpose: Radiographic film is generally used for inspection of dose distribution in intensity modulated radiation therapy (IMRT) at many institutions. However, the distribution of filmless systems can be expected to be used increasingly in the future. Therefore, we confirmed the utility of radiochromic film by comparing it with radiographic film that does not need an automatic processor. Result: Difference in does measured by radiographic film and radiochromic film tended to increase in the low does area, but it was limited in a range of 1.5%. Conclusion: When the dose distribution was verified in a highly accurate radiation therapy such as IMRT, the results suggested that radiochromic film can be useful in addition to radiographic film.


Daily Alignment Results of In-Room Computed Tomography-Guided Stereotactic Body Radiation Therapy for Lung Cancer

To determine the extent of interfractional setup errors and day-to-day organ motion errors by assessing daily bone alignment results and changes in soft tissue tumor position during hypofractionated, in-room computed tomography (CT)-guided stereotactic body radiation therapy (SBRT) of lung cancer. Daily alignment results during SBRT were analyzed for 117 tumors in 112 patients. Patients received 40-50 Gy of SBRT in four to five fractions using an integrated CT-LINAC system. The free-breathing CT scans acquired during treatment setup were retrospectively realigned to match with each of the bony references and the gross tumor volume (GTV) defined on the reference CT by rigid-body registration, and the daily deviations were calculated. The mean magnitude (± SD) three-dimensional shift from the initial skin marks to the final bone-aligned positions was 9.4 ± 5.7 mm. The mean daily GTV deviation from the bone position was 0.1 ± 3.8 mm in the anterior-posterior direction, -0.01 ± 4.2 mm in the superior-inferior direction, and 0.2 ± 2.5 mm in the lateral direction. A clinically noteworthy trend (net change >5 mm in any direction) in GTV position relative to the bone was observed in 23 cases (20%). Soft tissue target position can change significantly beyond the motion envelope defined in the original internal target volume in four-dimensional CT-based treatment planning for SBRT of lung cancer. Additional margin should be considered for adequate coverage of interfractional changes.

International Journal of Radiation Oncology*Biology*Physics


Predictive Value of 18F-Fluorodeoxyglucose Uptake by Positron Emission Tomography for Non-Small Cell Lung Cancer Patients Treated with Radical Radiotherapy

The purpose of this study is to assess predictive value of the positron emission tomography (PET) with 18F-fluoro-deoxyglucose (FDG) for recurrence and survival after radiotherapy (RT) for non-small cell lung cancer (NSCLC). One hundred forty-nine patients underwent pretreatment PET (n = 67) or PET/computed tomography (CT) (n = 82) and definitive RT for NSCLC. We evaluated the relationship between the maximum-pixel standardized uptake value (SUV(max)) and clinical tumor features. Univariate Cox proportional hazard analysis (UVA) was used to quantify the risk for local-regional recurrence, distant metastases, and death. Multivariate Cox proportional hazard analysis (MVA) was used to assess the potential independent effect of SUV(max). In the PET group, T1 tumors showed significantly lower SUV(max) than T2, T3, and T4 tumors; in the PET/CT group, T1 tumors showed significantly lower SUV(max) than T3 and T4 tumors. A high SUV(max )was a negative factor for local-regional control (LRC) (p < 0.001), distant metastasis-free survival (DMFS) (p = 0.02), and overall survival (OS) (p = 0.001) on UVA in the PET group. However, the significance decreased to 0.05 for LRC, 0.04 for DMFS, and 0.04 for OS by MVA when tumor size was included in the analysis. A high SUV(max) was not a negative factor for LRC, DMFS, or OS on UVA and MVA in the PET/CT group. In conclusion, assessment of predictive value of SUV(max) for NSCLC requires consideration of primary tumor size, and the evidence is not sufficient to suggest that FDG uptake in a primary NSCLC provides prognostic information.


Use of a diagnostic positron emission tomography-computed tomography system for planning radiotherapy positioning: distortion of the tabletop.

The aim of this study was to evaluate distortion of the tabletop in a diagnostic positron emission tomography-computed tomography (PET-CT) system to determine its suitability for planning radiotherapy positioning. Distortion of the tabletop was compared among PET-CT, lineac CT, and CT simulator systems. A phantom or angiography catheter was fixed to the tabletop and imaged after iron plate weight loading. The acquired images were analyzed using radiotherapy planning software. Distortion of the tabletop was measured based on the displayed coordinates. Sinking represented the greatest distortion of the tabletop in all systems. Using the same baseline, the maximum sinking were -0.4, -0.2, and +0.4 cm, respectively. The distortion of the tabletop in the PET-CT system was more similar to that in the lineac CT than in the CT simulator system. Distortion of the tabletop in a diagnostic PET-CT system may be within the acceptable range to allow its use for planning radiotherapy positioning.


Radiation therapy: state of the art and the future.

Technical innovation in radiation therapy (RT) such as stereotactic irradiation, intensity modulated RT, image-guided RT, and brachytherapy using remote controlled after-loading system have made it possible to deliver ideally distributed radiation dose to the target with great accuracy, while sparing the adjacent organs at risk. As a result, tumor control rate by RT improved markedly and became excellent alternative to surgery for asymptomatic or mildly symptomatic brain tumors, early stage lung cancer, and low-risk prostate cancer. In locally advanced stage of cancer, randomized controlled trials established the chemoradiation therapy as a standard treatment option for patients with head and neck cancer, lung cancer, esophageal cancer, and cervical cancer. RT is also a valuable treatment for palliation of local symptoms caused by cancer with consistently high response rates. Minimally invasive therapy has come to be emphasized its needs in the background of increased tendency of elderly patients with cancer, and advances in conformal dose delivery technique raise the RT at a more important position in cancer therapy. However, adequate number of RT profession is indispensable to utilize highly-sophisticated RT technology. Substantiality of an education system for radiation oncologist, RT technologist, and medical physicists is our current most important issue.

The Journal of Medical Investigation : JMI


High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique.

OBJECTIVE: The purpose of this study was to introduce a novel customized intraoral mold treatment for maxillary gingival carcinoma (UGC). STUDY DESIGN: Two patients with UGC were treated as salvage therapy using this technique. The mold was designed to keep normal soft tissues adjacent to the tumor away from the radioactive source as much as possible, and it was shielded by lead. The radiation dose on the buccal mucosa and tongue was measured at the inner and outer surfaces of the intraoral mold before starting high-dose-rate brachytherapy by the remote afterloading system, and was reduced to almost one tenth. RESULTS: The patient had no recurrence and no severe adverse effects on the normal soft tissue adjacent to the tumor until the end of the follow-up period. CONCLUSION: High-dose-rate brachytherapy using the novel customized intraoral mold might be a treatment option of not only salvage therapy, but definitive therapy of UGC.

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics


Risk factors for radiation pneumonitis caused by whole breast irradiation following breast-conserving surgery.

We evaluated risk factors of radiation pneumonitis (RP) after whole breast irradiation following breast-conserving surgery. Four hundred and seventy-two cases underwent whole breast irradiation with tangential field following breast-conserving surgery in our hospital, between January 2005 and April 2007. Of these cases, we performed statistical analyses for 423 breasts of 413 patients, using a pulmonary dose-volume histogram. Patient characteristics, treatment regimens and irradiation methods were included as variables in the analyses on risk factors of RP. As a result, 89 breasts of 84 cases (21%) were diagnosed with RP. The version 3.0 of the NCI Common Terminology Criteria for Adverse Events was used to evaluate the grade of pneumonitis: 77 cases (18.2%) were diagnosed as Grade 1 RP, 10 cases (2.3%) as Grade 2, and 2 cases (0.5%) as Grade 3. Multivariate analysis indicated that the significant risk factors for RP were central lung distance (CLD) (>1.8 cm) and the short axis length of the radiation field. The incidence of radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome significantly correlated only with CLD. The lung volume within the radiation field was shown to be a significant risk factor for RP and radiation-induced BOOP syndrome.


Effective bladder preservation strategy with low-dose radiation therapy and concurrent intraarterial chemotherapy for muscle-invasive bladder cancer.

PURPOSE: The aim of this study was to evaluate retrospectively the toxicity and response, bladder preservation, and survival of patients with muscle-invasive bladder cancer treated with multimodality therapy consisting of low-dose radiation therapy (RT) and concurrent intraarterial chemotherapy (IACT). METHODS AND MATERIALS:. Between November 1999 and July 2005, a total of 27 consecutive, previously untreated patients with muscle-invasive bladder cancer underwent transurethral bladder tumor resection followed by concurrent low-dose RT and IACT. Patients who achieved a complete response (CR) were followed up closely without further therapy, and patients who did not achieve a CR underwent further treatment. RESULTS: Complete response was achieved in 22 of 27 patients (81%). Of these 22 patients, 7 developed recurrences, and 3 died of their disease. In five patients who did not achieve CR, one died from bone metastases. The 3-year overall survival rate was 81%, with a median follow-up time of 27 months; and 22 of 27 patients (81%) with a preserved bladder were tumor-free at the last follow-up. Three patients (11%) developed grade 3 acute hematological toxicity. CONCLUSION: Multimodality therapy consisting of low-dose RT and concurrent IACT for muscle-invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation and minimal adverse effects.


Prognostic significance of HIF-2alpha expression on tumor infiltrating macrophages in patients with uterine cervical cancer undergoing radiotherapy.

Hypoxia-inducible factor (HIF)-2alpha, a basic helix-loop-helix (bHLH)-PAS protein, is the principal regulator of the hypoxic transcriptional response. An immunohistochemical study reported strong HIF-2alpha expression in the cytoplasm of tumor infiltrative macrophages (TIMs). Thus we assessed the expression of HIF-2alpha in human cervical cancer tissue before radiation therapy and its relationship to the clinical outcome. Seventy three patients with histologically proven primary advanced squamous cell carcinoma of the uterine cervix underwent radiotherapy in Tokushima University Hospital after biopsy specimens were taken. Among 73 specimens stained for HIF-2alpha, 53 (72.6%) exhibited HIF-2alpha immunoreactivity in the TIMs. In only 5 of 73 cases, HIF-2alpha immunoreactivity was observed in the nuclei of tumor cells. The HIF-2alpha positive cell count ratio in TIMs was associated with disease-free survival (DFS) with the worst DFS (p=0.024) being in cases in the group with a high positive cell count ratio. A high HIF-2alpha positive cell count ratio in TIMs increased the risk of local recurrence (p=0.0142). These findings might suggest that the ratio of the HIF-2alpha positive cell in TIMs may be a new predictive indicator for prognosis before radiation therapy for uterine cervical cancer.


Can Kampo Therapy prolong the life of cancer patients?

Our policy regarding the performance of radiotherapy to squamous cell carcinoma of the uterine cervix has not changed since 1969. We have already reported the treatment results which were as good as those from other institutions. Since 1978, Kampo therapy was first introduced in the treatment of cancer patients in dealing with problems such as the side effects of radiotherapy and chemotherapy and various types of general malaise. We analyzed our treatment results in order to re-evaluate the chemo-radiotherapy in combination with Kampo. Survival rates for 5, 10 and 15 years, respectively, were 90.9%, 71.6% and 71.6% for Stage IB, 78.9%, 61.8% and 41.8% for Stage II, 62.3%, 49.1% and 41.2% for Stage III and 53.1%, 36.5% and 16.7% for Stage IV. The Kampo significantly extended the survival of patients with uterine cervical cancer. We intend to perform further research with more patients to explore how this therapy contributes to the prolonging of patients survival.