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Background Axillary dissection is routinely conducted for all patients with sentinel node (SN)-positive breast cancer. Metastasis to non SNs is not often found after axillary dissection in patients with SN-positive breast cancer. Thus, we investigated clinicopathological features, including immune cells in peripheral blood, in order to identify factors related to metastasis to non-SNs. Patients and methods We retrospectively investigated 184 patients with SN-positive disease, treated at our institution during the 2013 through 2018 period. All clinicopathological data were obtained before and during surgery. Results Metastasis to non SNs was observed in 64 cases (35%). The platelet-to-lymphocyte ratio (PLR) and the number of SN metastases were independent of metastasis to non SNs (p=0.023 and p=0.017, respectively). Patients with metastasis to non SNs had significantly lower PLR and more SN metastases. High lymphocyte number and low platelet number resulted in a low PLR. Conclusion PLR might be a marker of metastasis to non SNs.

In 2016, the American Association of Physicists in Medicine (AAPM) has published a report of task group (TG) 100 with a completely new concept, entitled "application of risk analysis methods to radiation therapy quality management." TG-100 proposed implementation of risk analysis in radiotherapy to prevent harmful radiotherapy accidents. In addition, it enables us to conduct efficient and effective quality management in not only advanced radiotherapy such as intensity-modulated radiotherapy and image-guided radiotherapy but also new technology in radiotherapy. It should be noted that treatment process in modern radiotherapy is absolutely more complex and it needs skillful staff and adequate resources. TG-100 methodology could identify weakness in radiotherapy procedure through assessment of failure modes that could occur in overall treatment processes. All staff in radiotherapy have to explore quality management in radiotherapy safety.

Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US residents with Japanese origin (USJ), and US residents with other origins (USO). Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan–Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status. We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval [CI] 0.45–0.47 for Japanese and 0.66 [95% CI 0.59–0.74] for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 [95% CI 0.51–0.55] for Japanese and 0.53 [95% CI 0.52–0.74] for USJ). In stage I–III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.

The Japanese Breast Cancer Society (JBCS) registry began data collection in 1975, and it was integrated into National Clinical Database in 2012. As of 2016, the JBCS registry contains records of 656,896 breast cancer patients from more than 1400 hospitals throughout Japan. In the 2016 registration, the number of institutes involved was 1422, and the total number of patients was 95,870. We herein present the summary of the annual data of the JBCS registry collected in 2016. We analyzed the demographic and clinicopathologic characteristics of registered breast cancer patients from various angles. Especially, we examined the registrations on family history, menstruation, onset age, body mass index according to age, nodal status based on tumor size and subtype, and proportion based on ER, PgR, and HER2 status. This report based on the JBCS registry would support clinical management for breast cancer patients and clinical study in the near future.

We developed an efficient postal audit system to independently assess the delivered dose using radiophotoluminescent glass dosimeters (RPLDs) and the positional differences of fields using EBT3 film at the axial plane for intensity-modulated radiotherapy (IMRT). The audit phantom had a C-shaped target structure as a planning target volume (PTV) with four measurement points for the RPLDs and a cylindrical structure as the organ at risk (OAR) for one measurement point. The phantoms were sent to 24 institutions. Point dose measurements with a 0.6 cm3 PTW farmer chamber were also performed to justify glass dosimetry in IMRT. The measured dose with the RPLDs was compared to the calculated dose in the institution’s treatment planning system (TPS). The mean ± 1.96σ of the ratio of the measured dose with the RPLDs to the farmer chamber was 0.997 ± 0.024 with no significant difference (p = .175). The investigations demonstrated that glass dosimetry was reliable with a high measurement accuracy comparable to the chamber. The mean ± 1.96σ for the dose differences with a reference of the TPS dose for the PTV and the OAR was 0.1 ± 2.5% and −2.1 ± 17.8%, respectively. The mean ± 1.96σ for the right-left and the anterior–posterior direction was −0.9 ± 2.8 and 0.5 ± 1.4 mm, respectively. This study is the first report to justify glass dosimetry for implementation in IMRT audit in Japan. We demonstrate that our postal audit system has high accuracy with a high-level criterion of 3%/3 mm.

The multi-foil method is commonly used to determine upon an energy spectrum of neutrons in boron neutron capture therapy. The method requires to measure the radioactivation of the foils. This study develops a simple modeling procedure of a high-purity Ge detector, which is used to measure the radioactivation, in order to calculate the detection efficiency with GEANT4. By changing four parameters from their manufacturing specifications of the detector, the simulated detection efficiency is able to reproduce the actual detection efficiency.

This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system.

Several clinical studies have examined circulating tumour cells (CTCs). However, the application of CTCs as a predictive/prognostic marker for breast cancer patients has yet to be established, particularly the selection of suitable markers for detecting CTCs. We recently investigated CTCs, including mesenchymal status, from metastatic breast cancer patients who had received eribulin-based treatment. We found that assessment of both mesenchymal and epithelial CTCs might be important for predicting eribulin responsiveness. In the current study, we followed up the outcomes of these patients after eribulin treatment and investigated the possibility of CTC analysis results serving as prognostic markers for this patient population. Twenty-one patients were enrolled and peripheral blood samples were collected before eribulin-based treatments. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Overall survival (OS) was assessed in relation to the number of CTCs and clinicopathological factors. During the observation period, 13 patients (62%) died due to breast cancer and the median OS was 18 months. Patients with high-grade tumours and a high total number of CTCs showed significantly shorter OS than those with low-grade tumours and smaller CTC burdens (p = 0.026 and 0.037, respectively). Patients who received eribulin as the first chemotherapy for metastatic disease showed longer OS (p = 0.006). Our data suggest that determining numbers of both mesenchymal and epithelial CTCs might predict survival for patients receiving eribulin.

The role of postmastectomy radiotherapy (PMRT) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is controversial. We aimed to evaluate the effectiveness of radiotherapy in patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry. We enrolled patients who received NAC and mastectomy for cT1–4 cN0–2 M0 breast cancer. We evaluated the association between radiotherapy and outcomes, locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) based on ypN status by multivariable analysis. Of the 145,530 patients, we identified 3226 who met the inclusion criteria. Among ypN1 patients, no differences were found in LRR, DDFS, or OS between groups with and without radiotherapy (p = 0.72, p = 0.29, and p = 0.36, respectively). Radiotherapy was associated with improved LRR-free survival (p

The aim of the study was to evaluate inter-fractional dosimetric variations for high-dose rate breast brachytherapy using a strut-adjusted volume implant (SAVI). For the nine patients included, dosimetric constraints for treatment were as follows: for the planning target volume for evaluation (PTV_Eval), the volume receiving 90, 150 and 200% of the prescribed dose (V90%,150%,200%) should be >90%, ≤50 cm3 and ≤20 cm3, respectively; the dose covering 1 cm3 (D1cc) of the organs at risk should be ≤110% of the prescribed dose; and the air volume should be ≤10% of PTV_Eval. Differences in V90%,150%,200%, D1cc and air volume (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\Delta V$\end{document} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\Delta D$\end{document}) as inter-fractional dosimetric variations and SAVI displacements were measured with pretreatment and planning computed tomography (CT) images. Inter-fractional dosimetric variations were analyzed for correlations with the SAVI displacements. The patients were divided into two groups based on the distance of the SAVI from the surface skin to assess the relationship between the insertion position of the SAVI and dosimetric parameters. The median ΔV90%,150%,200% for the PTV_Eval in all patients was −0.3%, 0.2 cm3 and 0.2 cm3, respectively. The median (range) ΔD1cc for the chest wall and surface skin was −0.8% (−18.9 to 9.4%) and 0.3% (−7.6 to 5.3%), respectively. SAVI displacement did not correlate with inter-fractional dosimetric variations. In conclusion, the dose constraints were satisfied in most cases. However, there were inter-fractional dosimetric changes due to SAVI displacement.

In our institution, we installed MRI-guided radiotherapy system (MRIdian, ViewRay Inc.), allowing to perform on-line adaptive radiotherapy (ART). The MRIdian has three

Background/Aim: The rate of obesity, an independent risk factor for breast cancer in post-menopausal women, is quite low in Japan, indicating breast cancer in lean women to be more common in the Japanese than in Westerners. However, biological characteristics of such breast cancers have not been adequately investigated. Patients and Methods: We retrospectively investigated clinicopathological breast cancer features of 566 postmenopausal Japanese women, who underwent curative surgery, in relation to patient physique based on the body mass index. Results: There were no differences in several factors examined such as tumour size according to patient physique. On the other hand, mean values of the Ki67 labelling index were significantly higher in lean compared to obese patients (p=0.027). Likewise, HER2-positive tumours were more often observed in lean patients (p=0.051). Conclusion: Lean postmenopausal women had more aggressive tumours, apparently contradicting the widely held view for breast cancer in obese women.

Introduction Previous studies have shown that simultaneous treatment with sorafenib, a vascular endothelial growth factor receptor tyrosine-kinase inhibitor (VEGFR-TKI), and radiation therapy (RT) can cause gastrointestinal hemorrhage (GH) as an adverse event. However, it is known that sorafenib monotherapy can cause GH. Thus it is essential to know the association between the radiation field and the bleeding site. Case presentation We report a case of bleeding ulcers on the ascending colon in a patient undergoing simultaneous RT and sorafenib administration. Two clips were placed at the proximal and distal ends of the ulcer lesions and the relevance to the radiation field was evaluated using computed tomography images. We observed that the sites of the bleeding ulcers corresponded with radiation dose distribution. In addition, we report on intramuscular bleeding corresponding with radiation dose distribution, which has not been previously reported on. Conclusions The administration of sorafenib during RT can lead to intestinal and intramuscular bleeding. Therefore, the risk of bleeding from organs exposed to RT must be taken into account when RT and VEGFR-TKI administration occurs simultaneously or in succession.

An accelerator-based boron neutron capture therapy (BNCT) system with a solid-state Li target is reported to have degradation of the Li target. The degradation reduces the Li thickness, which may change spectra of the generated neutrons corresponding to the Li thickness. This study aims to examine the relationship between the Li thickness and the generated neutrons and to investigate the effects of the Li thickness on the absorbed dose in BNCT.The neutron energy spectra were calculated via Monte Carlo simulation for Li thicknesses ranging from 20 to 150 μm. Using the system, the saturated radioactivity of gold induced by reactions betweenThe measurement and simulation indicated a reduction in the number of neutrons due to the degradation of the Li target. However, the absorbed doses were comparable for each Li thickness when the requisite number of neutrons for BNCT was delivered. Additionally, the saturated radioactivity ofNo notable effect to the absorbed dose was observed when required neutron fluence was delivered in the BNCT even if the degradation of the Li was observed.

Advanced radiotherapy such as intensity-modulated radiotherapy offers many advantages of high accuracy and efficiency of radiotherapy. To date, many technical guidelines with description of quality assurance and quality control have been reported. However, some reports indicated that human factor and environment is major cause of radiotherapy incidents. If radiotherapy systems depend on automation and computer system, individual risk management is degraded and ability of preventing radiotherapy incidents weaken. Recently, the American Association of Physicists in Medicine (AAPM) task group-100 was reported and it has a new concept guideline, which proposed the comprehensive risk management and education of non-technical skills for overall radiotherapy processes. The TG-100 recommends implementation of process map, reporting system, risk assessment such as failure mode and effects analysis (FMEA) and fault tree analysis (FTA) especially for advanced radiotherapy. In this paper, we described effective and efficient procedures to improve the treatment processes and education of non-technical skills using the such management tools proposed by the TG-100 guide-lines.

Objective: This study aimed to assess the dosimetric effect of intestinal gas of stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) on target and critical organs for pancreatic cancer without online electron density correction (EDC). Methods: Thirty pancreatic cancer patients who underwent online SMART were selected for this study. The treatment time of each stage and the total treatment time were recorded and analyzed. The concerned dose-volume parameters of target and organs-at-risk (OAR) were compared with and without an intestinal gas EDC using the Wilcoxon-signed rank test. Analysis items with p value < 0.05 were considered statistically significant. The relationships between dosimetric differences and intestinal gas volume variations were investigated using the Spearman test. Results: The average treatment time was 82 min, and the average EDC time was 8 min, which accounted for 10% of the overall treatment time. There were no significant differences in CTV (GTV), PTV, bowel, stomach, duodenum, and skin (p > 0.05) with respect to dose volume parameters. For the Dmax of gastrointestinal organs (p = 0.03), the mean dose of the liver (p = 0.002) and kidneys (p = 0.03 and p = 0.04 for the left and right kidneys, respectively), there may be a risk of slight overestimation compared with EDC, and for the Dmax of the spinal cord (p = 0.02), there may be a risk of slight underestimation compared with EDC. A weak correlation for D95 in the PTV and D0.5 cc in the duodenum was observed. Conclusion: For patients with similar inter-fractional intestinal gas distribution, EDC had little dosimetric effects on the D0.5 cc of all GI organs and dose volume parameters of target in most plans. Advances in knowledge: By omitting the EDC of intestinal gas, the online SMART treatment time can be shortened.

The rate of breast cancer screening for women of all ages in Japan is increasing. However, little is known about the biological differences between screen- and self-detected tumors. We used data from the Japanese Breast Cancer Registry (JBCR), a nationwide registry of newly diagnosed breast cancer cases in Japan, to investigate patients diagnosed between January 1, 2004 and December 31, 2011. We compared the clinicopathological features of tumors and assessed yearly trends regarding the proportion of screen-detected cases during the study period. We found that 31.8 % (65,358/205,544) of cancers were detected by screening. Asymptomatic tumors detected by screening (asymptomatic) were more likely to have favorable prognostic features than those that were self-detected (ductal carcinoma in situ [DCIS]: 19.8 versus 4.1 %, node-negative: 77.0 versus 61.6 %, and estrogen receptor-positive [ER+]: 82.0 versus 72.9 %, respectively). All these findings were statistically significant (p

Background We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. Patients and methods Records of more than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. Results pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. Conclusion We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.

Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed‐up for a median period of 6.7 years entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m2) categories

Rationale Gynecological high-dose-rate (HDR) brachytherapy has progressed for years, but it remains difficult for bulky tumors to be controlled locally. Dose limitations to organs at risk (OARs) are invariably obstacles in increasing the prescription dose. Additionally, it is controversial that the excessive hyperdose sleeve, the volume receiving a dose equal to or greater than twice the reference dose, should be eliminated in gynecological HDR brachytherapy. On the other hand, the technique of simultaneous integrated protection was reported for large hepatocellular carcinoma treatment, and similarly, internal high-dose brachytherapy could be used for treating bulky cervical carcinoma. Patient concerns A 54-year-old female had irregular genital bleeding and lost 13 kg in one year. Diagnosis She was diagnosed with T3bN1M0 cervical cancer in another hospital. The transverse diameter of the primary tumor was 10.5 cm. Interventions The whole pelvis and para-aortic lymph node were irradiated with a total of 50 Gy in 25 fractions, but the size of the tumor showed only a slight decrease to 8.9 cm. After external beam radiotherapy, first-time high-dose-rate interstitial brachytherapy (HDR-ISBT) was administered without "intentional internal high-dose (IIHD) policy," the technique of high-dose administration to only the inside of the tumor. Considering the rectum dose limitation, in the additional 2 times of brachytherapy, "IIHD policy" HDR-ISBT was applied. In the second and third HDR-ISBT, the percentage of the volume exposed to 200% of the prescribed dose for high-risk clinical target volume increased by 241% and 204% compared with the first HDR-ISBT, while the doses to OARs were not significantly higher than those of the first-time HDR-ISBT. Outcomes Complete response was obtained, and no recurrence findings and side effects caused by HDR-ISBT have been detected for 2 years and 9 months. Lessons To our knowledge, this is the first report of IIHD HDR-ISBT for bulky cervical cancer. This technique can be the solution for treating bulky cervical cancer.

Background Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy. Methods Twenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs. Results Numbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively). Conclusions Our data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM). Electronic supplementary material The online version of this article (10.1186/s12967-018-1663-8) contains supplementary material, which is available to authorized users.

An accelerator-based boron neutron capture therapy (BNCT) system that employs a solid-state Li target can achieve sufficient neutron flux derived from the 7Li(p,n) reaction. However, neutron production is complicated by the large thermal load expected on the target. The relationship between neutron production and thermal load was examined under various conditions. A target structure for neutron production consists of a Li target and a target basement. Four proton beam profiles were examined to vary the local thermal load on the target structure while maintaining a constant total thermal load. The efficiency of neutron production was evaluated with respect to the total number of protons delivered to the target structure. The target structure was also evaluated by observing its surface after certain numbers of protons were delivered. The yield of the sputtering effect was calculated via a Monte Carlo simulation to investigate whether it caused complications in neutron production. The efficiency of neutron production and the amount of damage done depended on the proton profile. A more focused proton profile resulted in greater damage. The efficiency decreased as the total number of protons delivered to the target structure increased, and the rate of decrease depended on the proton profile. The sputtering effect was not sufficiently large to be a main factor in the reduction in neutron production. The proton beam profile on the target structure was found to be important to the stable operation of the system with a solid-state Li target. The main factor in the rate of reduction in neutron production was found to be the local thermal load induced by proton irradiation of the target.

Artificial ascites has been reported as an effective technique to reduce the risk of thermal injury in radiofrequency ablation of liver tumors by increasing the distance of collateral organs located next to the ablated sites. In this case report we share our experience with artificial ascites in an attempt to reduce the toxicity of collateral adjacent organs in the setting of re-irradiation for recurrent cervical cancer. A 52-year-old female who developed local recurrence after definitive radiation therapy was treated with interstitial re-irradiation by means of image-guided, (single-implant/multi fraction) high-dose-rate brachytherapy. Because the sigmoid colon was in close proximity to the recurrent tumor lesion, artificial ascites was generated before each treatment fraction by percutaneous injection of a defined amount of saline solution through the abdominal wall to create additional space between the two volumes. Artificial ascites showed a dosimetric improvement by reducing the sigmoid colon D0.1cc per fraction from 286 cGy before to 189 cGy after saline injection. No severe complication was associated with the injection procedure.

Our purpose was to establish the commissioning procedure of Monte Carlo modeling on a magnetic resonance imaging–guided radiotherapy system (MRIdian, Viewray Inc.) under a magnetic field of 0.345 T through experimental measurements. To do this, we sought (i) to assess the depth–dose and lateral profiles generated by the Geant4 using either EBT3 film or the BJR-25 data; (ii) to assess the calculation accuracy under a magnetic field of 0.345 T. The radius of the electron trajectory caused by the electron return effect (ERE) in a vacuum was obtained both by the Geant4 and the theoretical methods. The surface dose on the phantom was calculated and compared with that obtained from the film measurements. The dose distribution in a phantom having two air gaps was calculated and measured with EBT 3 film. (i) The difference of depth–dose profile generated by the Geant4 from the BJR-25 data was 0.0 ± 0.8% and 0.3 ± 1.5% for field sizes of 4.5 and 27.3 cm2, respectively. Lateral dose profiles generated by Geant4 agreed well with those generated from the EBT3 film data. (ii) The radius of the electron trajectory generated by Geant4 agreed well with the theoretical values. A maximum of ~50% reduction of the surface dose under a magnetic field of 0.345 T was observed due to elimination of the electron contamination caused by the magnetic field, as determined by both the film measurements and the Geant4. Changes in the dose distributions in the air gaps caused by the ERE were observed on the Geant4 and in the film measurements. Gamma analysis (3%/3 mm) showed a pass rate of 95.1%. Commissioning procedures for the MRI-guided radiotherapy system on the Geant4 were established, and we concluded that the Geant4 had provided high calculation accuracy under a magnetic field of 0.345 T.

Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy for 2-3 years is the treatment of choice for hormone-receptor-positive breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may reduce the risk of breast cancer recurrence. Methods: We conducted a prospective randomized multi-center open-label phase III trial to assess the effect of the extended use of anastrozole for an additional 5 years. Postmenopausal patients with stageI-III, hormone-receptor-positive breast cancer, disease-free after 5 years of either anastrozole alone or tamoxifen 2-3 years followed by anastrozole 3-2 years were randomized to continual group with anastrozole for an additional 5 years or stop group without an additional anastrozole. Our primary end point was disease-free survival. Results: We enrolled 1697 women. After a median follow up of 4.9 years, there were 149 events involving disease recurrence or the occurrence of contralateral breast cancer (51 in continual group and 98 in stop group) and 7 deaths (3 in continual group and 4 in stop group). The 5-year disease-free survival rate was 91.9% (95% confidence interval [CI], 89.4 to 93.8) in continual group and 84.4% (95% CI: 80.0 to 88.0) in stop group (hazard ratio for disease-free survival,0.548 ;P=0.0004. by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, institution, and choice of anastrozole or tamoxifen). The rate of 5-year overall survival was 99.5% in continual group and 99.6% in stop group. (hazard ratio,1.389 ;P=0.665). The rate of 5-year distant disease-free survival was 97.2% in continual group and 94.3% in stop group (hazard ratio,0.514 ;P=0.0077). Bone-related adverse events were observed more frequently among patients in continual group than among patients in stop group, including a higher incidence of bone pain, stiff joints, bone fractures, and new-onset osteoporosis. Conclusion: The extension of treatment with an adjuvant aromatase inhibitor (anastrozole) to 10 years resulted in significantly higher rates of disease-free survival and distant disease-free survival than those with no additional anastrozole, but the rate of overall survival was not different between two groups. Our study shows that it is safe and beneficial for postmenopausal patients with hormone-receptor-positive breast cancer to take an anastrozole as adjuvant therapy for an additional 5 years after initial treatment. (UMIN:000000818) Citation Format: Ohtani S, Iijima K, Higaki K, Sato Y, Hozumi Y, Hasegawa Y, Takei H, Tanaka M, Yagata H, Masuoka H, Tanabe M, Egawa C, Komoike Y, Saji S, Nakamura T, Yanagita Y, Ohtsu H, Mukai H, Iwase T. A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-04.

A population-based cancer registry has been used for the planning and evaluation of cancer control activities based on administration and the care of individual cancer patients by those in the medical profession. The Japanese Breast Cancer Society (JBCS) registry was started in 1975. In 2004, the registry system was moved to a new system using web registration with the cooperation of the Non-Profit Organization Japan Clinical Research Support Unit and Public Health Research Foundation (Tokyo, Japan). Comprehensive individual patient data were recorded according to the Unio Internationalis Contra Cancrum (UICC) TNM classification [1] and the World Health Organization histological classification [2]. The details are described elsewhere [3]. Annual reports on this registry have since been published in Japanese and publicized through the JBCS web site to active members of the JBCS [4]. We herein report the results of a 5-year prognostic analysis of cases registered in 2005 (Figs. 1, 2, 3, 4, 5, 6, 7, 8 and 9; Supplementary Tables 1–9). The number of facilities involved in the 2005 registration was 354 and the total number of cases was 20,786. The estimated incidence of breast cancer was reported to be 50,695 cases in 2005 by the National Cancer Center [5]. Therefore, approximately Electronic supplementary material The online version of this article (doi:10.1007/s12282-015-0645-4) contains supplementary material, which is available to authorized users.

We classified ipsilateral breast tumor recurrences (IBTRs) based on strict pathological rules. Ninety-six women who were surgically treated for IBTR were included. IBTRs were classified according to their origins and were distinguished based on strict pathological rules: relationship between the IBTR and the primary lumpectomy scar, surgical margin status of the primary cancer, and the presence of in situ lesions of IBTR. The prognosis of these subgroups were compared to that of new primary tumors (NP) in the narrow sense (NPn) that occurred far from the scar. Distant-disease free survival of IBTR that occurred close to the scar with in situ lesions and a negative surgical margin of the primary cancer (NP occurred close to the scar, NPcs) was similar to that of NPn. In contrast, IBTR that occurred close to the scar without in situ lesions (true recurrence (TR) that arose from residual invasive carcinoma foci, TRinv) had significantly poorer prognosis than NPn. IBTR that occurred close to the scar with in situ lesions and a positive surgical margin of the primary cancer (TR arising from a residual in situ lesion, TRis) had more late recurrences than NPcs. Precise pathological examinations indicated four distinct IBTR subtypes with different characteristics.

Purpose To propose a geometrical margin for definition of the vaginal cuff PTV using only CT images of the full bladder (CTfull) in postoperative cervical cancer patients. Methods Twenty-nine operated cervical cancer patients underwent volumetric arc therapy with a bladder filling protocol. This study assessed bladder filling using a portable bladder scanner and cone-beam computed tomography (CBCT) during the entire treatment period. The measured bladder volumes with a BladderScan® were compared with the delineated volume on CBCT. Titanium clips in the vaginal cuff were analysed to assess geometrical uncertainty and the influence of rectal and bladder volume changes. Results BladderScan® showed good agreement with the delineated volume (R = 0.80). The volume changes in the bladder have a greater influence on the clip displacements than in the rectum. The 95th percentile of uncertainty of the clips in reference to CTfull in the right-left (RL), the superoinferior (SI), and the anteroposterior (AP) was 0.32, 0.65, and 1.15 cm, respectively. From this result and intra-fractional movements of the vaginal cuff reported by Haripotepornkul, a new geometrical margin was proposed for definition of the vaginal cuff planning target volume (PTV): 0.5, 0.9, and 1.4 cm in the RL, SI, and AP directions, respectively. Conclusions A new geometrical margin was proposed for definition of the vaginal cuff PTV based on CTfull, which will be needless of empty bladder at the planning CT scan. This method allows patients to reduce the burden and efficient routine CT scans can be improved.

Purpose : The aim of this study is to describe a phantom designed for independent examination of a source position in brachytherapy that is suitable for inclusion in an external auditing program. Material and methods : We developed a phantom that has a special design and a simple mechanism, capable of firmly fixing a radiochromic film and tandem-ovoid applicators to assess discrepancies in source positions between the measurements and treatment planning system (TPS). Three tests were conducted: 1) reproducibility of the source positions (n = 5); 2) source movements inside the applicator tube; 3) changing source position by changing curvature of the transfer tubes. In addition, as a trial study, the phantom was mailed to 12 institutions, and 23 trial data sets were examined. The source displacement ΔX and ΔY (reference = TPS) were expressed according to the coordinates, in which the positive direction on the X-axis corresponds to the external side of the applicator perpendicular to source transfer direction Y-axis. Results : Test 1: The 1σ fell within 1 mm irrespective of the dwell positions. Test 2: ΔX were greater around the tip of the applicator owing to the source cable. Test 3: All of the source position changes fell within 1 mm. For postal audit, the mean and 1.96σ in ΔX were 0.8 and 0.8 mm, respectively. Almost all data were located within a positive region along the X-axis due to the source cable. The mean and 1.96σ in ΔY were 0.3 and 1.6 mm, respectively. The variance in ΔY was greater than that in ΔX, and large uncertainties exist in the determination of the first dwell position. The 95% confidence limit was 2.1 mm. Conclusions : In HDR brachytherapy, an effectiveness of independent source position assessment could be demonstrated. The 95% confidence limit was 2.1 mm for a tandem-ovoids applicator.

The TNM classification of the Unio Internationalis Contra Cancrum was revised for the seventh edition. The major change concerning breast cancer is a change in the stages for patients with T0 or T1N1miM0. In the present study, the seventh edition of the TNM classification was validated in breast cancer.The stages of 416 breast cancer patients, treated at our hospital in 1996, were classified according to the TNM classification, sixth and seventh editions, and their prognoses were compared.Case distribution using the sixth edition was stage 0, 56 cases (13.5 %); stage I, 158 cases (38.0 %); stage II, 130 [A, 102; B, 28] cases (31.2 [A, 24.5; B, 6.7] %); and stage III, 72 [A, 31; B, 8; C, 33] cases (17.3 [A, 7.5; B, 1.9; C, 7.9] %). According to the seventh edition, the stages for 20 patients, accounting for 19.6 % of IIA cases according to the sixth edition, decreased from IIA to IB. The 10-year overall survivals were stage 0, 91.1 %; stage I, 88.6 %; stage II, 80.8 %; and stage III, 63.9 % according to the sixth edition; and stage 0, 91.1 %; stage I, 88.8 %; stage II, 79.1 %; and stage III, 63.9 % according to the seventh edition. Although no significant differences were seen among the survival rates for stages 0 to II according to the sixth edition, there was a significant difference between stage I and II according to the seventh edition (p = 0.026).The latest revision of the TNM classification is appropriate for breast cancer from the perspective of prognosis.

Background The definition of complete resection of ductal carcinoma in situ (DCIS) is difficult to standardize because of the high variety of surgical breast conserving procedures, specimen handling, and pathological examinations. Using strictly controlled criteria in a single institute, the present study aimed to determine the ipsilateral breast cancer rate when radiotherapy is omitted following complete resection of DCIS. Methods We retrospectively examined 363 consecutive DCIS patients who underwent breast-conserving surgery, and of these, 125 (34.4%) had complete resection according to the criteria. We finally included 103 patients who omitted radiotherapy. Ipsilateral and contralateral breast cancer events were assessed. Results The median follow-up period was 118 months. The incidences of ipsilateral and contralateral breast cancer and ipsilateral invasive breast cancer at 10 years were 10.8%, 9.1%, and 3.6%, respectively. No patient died of breast cancer. Conclusion If complete resection of DCIS can be ensured, the annual incidence of ipsilateral breast cancer, even without irradiation, can be limited to approximately 1%, which equals the incidence of contralateral breast cancer.

The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status.Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status.Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p0.001 vs. p = 0.295).Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

The purpose of this study was to determine the incidence of amenorrhea among breast cancer patients aged 40 years and younger following adjuvant chemotherapy.A follow-up questionnaire survey was conducted with premenopausal women with breast cancer who were treated with adjuvant anthracycline and taxane-based chemotherapy.In total, 66 women were retrospectively reviewed. Forty-nine patients were treated with a regimen containing anthracycline followed by taxane and 17 patients with anthracycline alone. Fifty-eight patients (87.9%) experienced amenorrhea during chemotherapy; 14 patients (21.2%) had persistent amenorrhea after chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients older than 36 than in younger patients (97.9 vs. 63.2%, 27.7 vs. 5.3%). Additional taxane resulted in a higher incidence of amenorrhea compared with anthracycline-containing regimen alone (93.9 vs. 70.6%). Multivariate analysis showed that age (≥36 years) was independently associated with the incidences of amenorrhea during chemotherapy (p = 0.007).Age was the strongest predictor of the incidence of amenorrhea during chemotherapy. It is unclear whether additional taxane may contribute to amenorrhea. This information could be useful in deciding whether to use adjuvant chemotherapy.

Purpose: To investigate the relationship between the tumor size of breast cancer by palpation and the sensitivity of mammography (MMG) and ultrasonography (US), and which modality can detect nonpalpable breast cancer in women aged 30 to 39 years. Methods: We retrospectively evaluated the tumor size by palpation, breast density, and the sensitivity of MMG and US in 165 patients aged 30 to 39 years. Palpation, US, and MMG were performed with prior knowledge of the results of other modalities. The tumor size on palpation were classified into Tnp; nonpalpable, T1p; 2 cm or less, T2p; more than 2 cm, but not more than 5 cm, and T3p; more than 5 cm. Results: Of 165 patients, 147 patients (89%) showed mammographically dense breasts. Of 165 cancers, 14 (8%) were Tnp, 40 (24%) were T1p, 82 (50%) were T2p, and 29 (18%) were T3p. The sensitivity of MMG was 57% (8 of 14) for Tnp, 78% (31 of 40) for T1p, 90% (74 of 82) for T2p, and 97% (28 of 29) for T3p. The sensitivity of US was 43% (6 of 14) for Tnp and 100% for palpable cancers. Of 14 nonpalpable cancers, 4 (29%), 4 (29%), and 2 (14%) could be detected by only MMG, bloody nipple discharge, and US. Conclusions: The sensitivity of MMG depends on the tumor size on palpation in this age range. MMG fails to detect relatively large palpable cancers. On the other hand, US can detect all palpable cancers. However, the sensitivity of US declines for nonpalpable cancers. For the detection of nonpalpable cancers, MMG, US, and nipple discharge are complementary modalities.

To confirm which modality, ultrasonography (US) or mammography (MMG), is useful to detect breast cancer in women aged 30 to 39 years, and to compare the sensitivity and findings of these two modalities for invasive carcinoma and ductal carcinomain situ (DCIS) in the diagnostic setting. We retrospectively evaluated the sensitivity and findings of these two modalities in 165 patients aged 30 to 39 years, who underwent surgery at the Cancer Institute Hospital between 2001 and 2003. US or MMG were performed after obtaining information on the other modalities previously used and physical examination. The abnormal findings of US were defined as mass lesions and focal hypoechoic areas due to breast cancer. The abnormal findings of MMG were defined as category 3 to 5 (Japanese Mammography Guidelines) masses, calcifications, and other findings due to cancer. Of 165 patients, 147 patients (89%) mammographicaly showed dense breasts. Histologically, 146 (88%) were invasive carcinomas and 19 (12%) were DCIS. In all carcinomas, the sensitivity of US (95%) was higher than that of MMG (85%). The sensitivity of US for invasive carcinoma (99%) was higher than that of MMG (85%). On the other hand, the sensitivity of MMG for DCIS (89%) was much higher than that of US (68%). US is more sensitive to detect breast cancers than MMG in this age range, especially for invasive carcinoma. On the other hand, MMG is useful for detecting DCIS, especially when it manifests with microcalcifications.

Purpose There is a significant difference in the mean tumor size between very young breast cancer patients and their elder counterparts. A simple comparison may show obvious prognostic differences. We investigated the prognostic impact of age by reducing the influence of the tumor size, which is thought to be a confounding factor. Patients and methods We investigated 1,880 consecutive pT1-4N0-3M0 breast cancer patients treated at less than 45 years of age between 1986 and 2002 and conducted a case–control study of breast cancer subjects less than 30 years of age. Each patient (Younger than 30) was matched with a corresponding control subject (Elder counterpart) based on an age 15 years above the patient’s age, a similar tumor size and a status of being within 1 year after surgery. In addition, we assessed 47 patients with pregnancy-associated breast cancer (PABC). The levels of hormone receptors were measured using an enzyme immunoassay (EIA), and receptor-positive cases were divided into “weakly” and “strongly” positive groups based on the median value. Years from the last childbirth (YFLC) was categorized as “recent” and “past” at the time point of 8 years. Results There were fewer past YFLC cases, more partial mastectomy cases, a higher rate of scirrhous carcinoma or solid-tubular carcinoma in the Younger than 30 group than in the Elder counterpart group. The rates of a PgR-negative status in the Younger than 30 and Elder counterpart groups were 45.1 and 29.9%, respectively, As for the relationship between the PgR-negative rate and YFLC, the rates of a PgR-negative status in the past YFLC, nulliparous, recent YFLC and PABC groups were 31.9, 37.7, 44.4 and 65.7%, respectively. On the other hand, the rates of strongly positive cases were 42.6, 30.2, 22.2 and 8.6%, respectively. The 10-year recurrence-free survival rates in the Younger than 30, Elder counterpart and PABC groups were 61.7, 65.6 and 54.1%, respectively. The differences between the groups were not significant. In a multivariate analysis, independent prognostic facers included the number of lymph node metastases (4–9, HR:3.388, 95% CI 1.363–8.425, p = 0.0086, over 10, HR: 6.714, 2.033–22.177, p = 0.0018), solid-tubular carcinoma (HR 3.348, 1.352–8.292, p = 0.0090), scirrhous carcinoma (HR 2.294, 1.013–5.197, p = 0.0465) and past YFLC (HR 0.422, 0.186–0.956, p = 0.0387). An age younger than 30 was not found to be an independent prognostic factor. Conclusions The prognosis of the very young women was the same as their elder counterparts with a matched tumor size, and age was not identified to be an independent prognostic factor according to the multivariate analysis. Recent childbirth probably influences the prognosis of patients younger than 30 years of age with breast cancer by lowering hormonal sensitivity.

Background & Aims: The purpose of this study was to investigate the influence of pregnancy on breast\ncancer prognosis by analyzing clinical and pathological features of young patients with breast cancer in\nrelation to last birth. Method: A total of 622 young breast cancer patients under 35 years of age\nundergoing surgical treatment between 1960 and 1990 at Cancer Institute Hospital were included in this\nstudy. The patients were classified into four groups; group A patients who were diagnosed during\npregnancy or within one year after delivery, group B patients who were diagnosed from one to three years\nafter delivery, group C patients who were diagnosed three years or more after delivery, and group D\npatients who were nulliparous. All four groups were examined from the viewpoint of clinical and\npathological findings with regard to age, disease duration, first childbirth, clinical stage, histopathological\ntype, lymph node metastasis, and survival. Furthermore, nuclear grade and immunohistochemical\nstaining of both estrogen receptor (ER) and factor-VIII were examined in early-stage breast\ncancer patients. Result: The incidence of early-stage(0, I and II) breast cancer was significantly(p＜\n0.05) lower in group A (69％) than in groups C (88％) and D (85％). The incidence of nodal involvement\ndecreased from group A (61％), B (59％), C (51％) to D (43％) in that order. The incidence of\nnodal involvement in group D was significantly (p＜0.05) lower than that in groups A and B. The\npositive rate of estrogen receptor increased from group A (50％), B (56％) to C (72％) in that order. \nDisease-free survival was significantly (p＜0.05) more favorable in group D than in groups A and C. \nThe similar result was obtained in patients with clinically early-stage breast cancer. Conclusion:\nPatients who developed breast cancer during pregnancy or within less than one year postpartum have a\npoor prognosis among patients under 35 years old. Patients having no childbirth history generally have\na high risk factor of developing breast cancer, however, breast cancer patients without childbirth history\nunder 35 years old result in a favourable prognosis.

A 45-year-old woman underwent a modified radical mastectomy for right breast cancer in July 1996. As lymph node metastases were quite advanced, chemotherapy was started with anthracyclines. Four years after surgery, cough and dyspnea appeared. Chest radiograph and CT showed reticular shadows bilaterally and slight pleural effusion, suggesting lymphangitic lung metastasis of breast cancer. Biweekly intravenous docetaxel (TXT,45 mg/m2) was initiated. Four courses of TXT ameliorated her complaints and radiographic findings. A total of 30 continuous courses of TXT suppressed disease exacerbation for 18 months until new lesions manifested in January 2002. The main side effects were grade 2 leukopenia and alopecia. This case report describes a patient with long-term suppression of lymphangitic lung metastasis of breast cancer using biweekly TXT without severe side effects or worsening quality of life.

A 78-year-old man consulted our hospital after experiencing nipple discharge although there was no pain or itching. A firm tumor with irregular surface was palpable at the right nipple. No swelling of axillary lymph nodes was noted. The levels of tumor markers, carcino-embrionic antigen and carbohydrate antigen 15-3, were within a normal range. Mammograms showed a tumor shadow with spicula and microcalcification. Computed tomography (CT) of the right breast indicated no invasion of the tumor into the right major pectoralis muscle. Chest and abdominal CT and systemic bone X-ray showed no evidence of distant metastasis. Diagnosis following biopsy was ductal carcinoma of the breast. A simple mastectomy was performed in November 1997. The cut-section was composed of a white-color solid mass. The values of estrogen and progesterone receptors were 110 fmol/mg and 270 fmol/mg, respectively. As an adjuvant therapy, tamoxifen at a dose of 20 mg/day was administered for 2 years and 10 months after the operation. There have been no recurrence or metastasis of breast cancer for 5 years after the operation. (Kitakanto Med J 2003 ; 53 : 299302)