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

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.

Objective To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. Methods 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. Results 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 Conclusions 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.

Objective 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. Methods 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). Results 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 Conclusion 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.

We retrospectively assessed whether magnetic resonance imaging (MRI) radiomics combined with clinical parameters can improve the predictability of out-of-field recurrence (OFR) of cervical cancer after chemoradiotherapy. The data set was collected from 204 patients with stage IIB (FIGO: International Federation of Gynecology and Obstetrics 2008) cervical cancer who underwent chemoradiotherapy at 14 Japanese institutes. Of these, 180 patients were finally included for analysis. OFR-free survival was calculated using the Kaplan–Meier method, and the statistical significance of clinicopathological parameters for the OFR-free survival was evaluated using the log-rank test and Cox proportional-hazards model. Prediction of OFR from the analysis of diffusion-weighted images (DWI) and T2-weighted images of pretreatment MRI was done using the least absolute shrinkage and selection operator (LASSO) model for engineering image feature extraction. The accuracy of prediction was evaluated by 5-fold cross-validation of the receiver operating characteristic (ROC) analysis. Para-aortic lymph node metastasis (p = 0.003) was a significant prognostic factor in univariate and multivariate analyses. ROC analysis showed an area under the curve (AUC) of 0.709 in predicting OFR using the pretreatment status of para-aortic lymph node metastasis, 0.667 using the LASSO model for DWIs and 0.602 using T2 weighted images. The AUC improved to 0.734 upon combining the pretreatment status of para-aortic lymph node metastasis with that from the LASSO model for DWIs. Combining MRI radiomics with clinical parameters improved the accuracy of predicting OFR after chemoradiotherapy for locally advanced cervical cancer.

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

Purpose 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 192 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. Methods 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. Results A dose calibration curve was obtained in the range of 0.1 Gy to 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 dosimetry 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. Conclusions 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.

Purpose: Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models. Methods: Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium. Results: TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI. Conclusion: Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.

Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models.

Purpose The purpose of this study was to assess the quality of treatment planning using the PlanIQTM software and to investigate whether it is possible to improve the quality of treatment planning using the “Feasibility dose‐volume histogram (DVH)TM” implemented in the PlanIQTM software. Methods Using the PlanIQTM 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 DVHTM implemented in the PlanIQTM software and modified the treatment planning system based on the target dose and OAR constraints. Results Analysis of the learning curve of the treatment plans quality using PlanIQTM 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. Conclusions The PlanIQTM 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.

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

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.

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\le$\end{document}75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed.

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 [A total of 40 patients with tongue SCC who underwentSix 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 fromThe

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.

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.

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.

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/mOur findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

Introduction Software that evaluates the quality of treatment plans (PlanIQTM) 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 PlanIQTM assessment tool (Feasibility DVHTM) 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. Materials & Methods 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 DVHTM. The quality of each treatment plan was evaluated based on a scoring system implemented in PlanIQTM. Results Of 5 patients included, 4 received improved treatment plans when Feasibility DVHTM was used. Moreover, 4 of 5 treatment planners showed improvement in treatment planning using Feasibility DVHTM. Conclusions The findings suggest that using the Feasibility DVHTM 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.

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.

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.

Methods to evaluate the positional reproducibility of breath-hold irradiation mostly require manual operation. The purpose of this study is to propose a method to determine the reproducibility of breath-hold irradiation of lung tumors between fractions using non-artificial methods. This study included 13 patients who underwent terminal exhaled breath-hold irradiation for primary and metastatic lung cancer. All subjects received a prescribed dose of 60 Gy/8 fractions. The contours of the gross tumor volume (GTV) were extracted by threshold processing using treatment-planning computed tomography (CT) and cone-beam CT (CBCT), which was done just before the beginning of the treatment. The method proposed in this study evaluates the dice similarity coefficient (DSC) and Hausdorff distance (HD) by comparing two volumes, the GTVCTS (GTV obtained from treatment-planning CT) and GTVCBCT (GTV obtained from CBCT). The reference contours for DSC and HD are represented by GTVCTS. The results demonstrated good visual agreement for cases with a DSC of ~0.7. However, apparent misalignment occurred when the DSC was 2 mm in 3 out of 13 cases, and when the DSC was ~0.7, the HD was ~1 mm. In addition, cases with greater HD also demonstrated more significant variability. It was found that the DSC and HD evaluation methods for the positional reproducibility of breath-hold irradiation proposed in this study are straightforward and can be performed without the involvement of humans. Our study is of extreme significance in the field of radiation studies.

Background/Aim 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. Materials and Methods 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. Result 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. Conclusions The VMAT treatment planning with the least effect on dose distribution caused by rectal gas was shown to be a full arc.

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.

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.

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.

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.

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.

Background: We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. Materials and Methods: 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. Results: In cases with prostate volume more than 30 cm3, 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. Conclusion: Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.

Background/Aim 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. Materials and methods 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. Result 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. Conclusion 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.

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

Background and purpose: 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. Materials and methods: Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45 Gy in 25 fractions. S-1 (80 mg/m2/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 60 mg/m2 (level 1). Surgery was performed 6–10 weeks after the chemoradiotherapy. Results: 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 80 mg/m2 (level 2), but developed in 3 of the 6 patients who received irinotecan at 90 mg/m2 (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%. Conclusions: Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60 mg/m2.

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.

Introduction: 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. Patients and Methods: 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. Results: 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) Conclusions: 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.

Background 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. Objective 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. Methods The guideline was created according to the basic principles in creating the guidelines of JSGO. Results 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. Conclusion 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. Electronic supplementary material The online version of this article (doi:10.1007/s10147-017-1193-z) contains supplementary material, which is available to authorized users.