Bilateral primary angiosarcoma of the breast: a case report.

BACKGROUND: Primary angiosarcoma of the breast is very rare, accounting for 0.05% of all malignant breast tumors. It has very high malignant potential and poor prognosis, though due to the rarity of the disease, there is no established treatment. We report this case along with a literature review. CASE PRESENTATION: We report the case of a 30-year-old Asian woman who was diagnosed with bilateral primary angiosarcoma of the breast while breastfeeding. After surgery, she underwent radiation therapy, chemotherapy, and hepatic arterial infusion chemotherapy for local recurrence of liver metastases, but these were ineffective, and she required several arterial embolization procedures for intratumoral bleeding and rupture of liver metastases. CONCLUSIONS: Angiosarcoma has a poor prognosis due to a high rate of local recurrence and distant metastasis. Although there is no established evidence for radiotherapy or chemotherapy, multimodality treatment may be necessary because of the high malignancy and rapid progression of the disease.

[A Case of Postoperative Recurrence of Bilateral Breast Cancer in Which Stable Disease Condition Was Achieved by Olaparib].

The patient is a 51-year-old female with comorbidity of schizophrenia. At the age of 41, she underwent surgery for bilateral breast cancer. Both sides were of the Luminal type, with Stage ⅢC on the right and Stage 0 on the left. She started to receive adjuvant chemotherapy but it was interrupted according to her wish. Approximately 3 years ago, she developed carcinomatous pleuritis, multiple liver metastases, and bone metastases. Despite receiving chemotherapy, her condition worsened. A BRACAnalysis revealed pathogenic variants in BRCA2. Upon initiating treatment with olaparib, both her liver metastases and carcinomatous pleuritis have shown reductions, and her tumor markers have also started to decline. Approximately 5 months after treatment with olaparib, it has been possible to continue without any side effects. Olaparib has shown good results in patients with germline BRCA1/2 mutation-positive HER2-negative advanced/recurrent breast cancer who have a history of receiving anthracycline and taxane-based therapies. It was considered that even in recurrent breast cancer, the presence or absence of BRCA1/2 mutations should be actively sought even in advanced cases, and the administration of olaparib should be considered.

[A Case of Resection of Right Axillary Accessory Breast Cancer with Skin Invasion].

A 56-year-old female was referred to our hospital for further examination and treatment because of her increasing right axillary mass for 1 year. Based on histological examination diagnosing the right axillary mass as carcinoma and radiological examination showing no evidence of distal metastasis, we decided to perform a radical resection. The patient underwent right axillary mass resection, axillary lymph node dissection, and latissimus dorsi musculocutaneous flap reconstruction. Right-sided breast cancer was diagnosed based on histopathological examination. The diagnosis was similar to that of breast cancer. The patient underwent adjunctive chemotherapy and is currently undergoing endocrine therapy. The incidence of accessory breast cancer is 0.2-0.6% among all breast cancers and is relatively rare. Postoperative adjuvant pharmacotherapy has no consensus. However, endocrine therapy, chemotherapy, and molecular target therapy are performed in cases of conventional breast cancer. Herein, we describe a case of right axillary accessory breast cancer with skin invasion successfully treated with radical resection.

Does residual ultrasound transmission gel affect the diagnostic ability of mammography?

This study aimed to assess whether residual ultrasound transmission gel (USTG) caused artifacts in mammography using a model 156 mammographic accreditation phantom and step phantom. Moreover, pig tissues with structures similar to those of the breast were imaged to assess whether USTG on the tissue appeared as a shadow on the mammogram, and how these shadows may be interpreted in clinical practice. The results showed that the visualization scores obtained for phantom mammograms decreased significantly for the fiber and mass samples after the application of USTG. Moreover, USTG on the tissues affected the visual evaluation of mammograms, leading to misinterpretation of mammographic findings.

Predicting axillary lymph node metastasis in breast cancer using the similarity of quantitative dual-energy CT parameters between the primary lesion and axillary lymph node.

PURPOSE: To evaluate the similarity of quantitative dual-energy computed tomography (DECT) parameters between the primary breast cancer lesion and axillary lymph node (LN) for predicting LN metastasis. MATERIALS AND METHODS: This retrospective study included patients with breast cancer who underwent contrast-enhanced DECT between July 2019 and April 2021. Relationships between LN metastasis and simple DECT parameters, similarity of DECT parameters, and pathological and morphological features were analyzed. ROC curve analysis was used to evaluate diagnostic ability. RESULTS: Overall, 137 LNs (39 metastases and 98 non-metastases) were evaluated. Significant differences were observed in some pathological (nuclear grade, estrogen receptor status, and Ki67 index) and morphological characteristics (shortest and longest diameters of the LN, longest-to-shortest diameter ratio, and hilum), most simple DECT parameters, and all DECT similarity parameters between the LN metastasis and non-metastasis groups (all, P < 0.001-0.004). The shortest diameter of the LN (odds ratio 2.22; 95% confidence interval 1.47, 3.35; P < 0.001) and the similarity parameter of 40-keV attenuation (odds ratio, 2.00; 95% confidence interval 1.13, 3.53; P = 0.017) were independently associated with LN metastasis compared to simple DECT parameters of 40-keV attenuation (odds ratio 1.01; 95% confidence interval 0.99, 1.03; P =0.35). The AUC value of the similarity parameters for predicting metastatic LN was 0.78-0.81, even in cohorts with small LNs (shortest diameter < 5 mm) (AUC value 0.73-0.78). CONCLUSION: The similarity of the delayed-phase DECT parameters could be a more useful tool for predicting LN metastasis than simple DECT parameters in breast cancer, regardless of LN size.

Sigmoid model analysis of breast dynamic contrast-enhanced MRI: Distinguishing between benign and malignant breast masses and breast cancer subtype prediction.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE-MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype. A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1-min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann-Whitney U-test was used for the statistical analysis. The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A-like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05). The sigmoid model analysis of breast DCE-MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A-like breast cancer.

Prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer using radiomics of pretreatment dynamic contrast-enhanced MRI.

PURPOSE: To investigate if the pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based radiomics machine learning predicts the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Seventy-eight breast cancer patients who underwent DCE-MRI before NAC and confirmed as pCR or non-pCR were enrolled. Early enhancement mapping images of pretreatment DCE-MRI were created using subtraction formula as follows: Early enhancement mapping = (Signal 1 min - Signal pre)/Signal pre. Images of the whole tumors were manually segmented and radiomics features extracted. Five prediction models were built using five scenarios that included clinical information, subjective radiological findings, first order texture features, second order texture features, and their combinations. In texture analysis workflow, the corresponding variables were identified by mutual information for feature selection and random forest was used for model prediction. In five models, the area under the receiver operating characteristic curves (AUC) to predict the pCR and several metrics for model evaluation were analyzed. RESULTS: The best diagnostic performance based on F-score was achieved when both first and second order texture features with clinical information and subjective radiological findings were used (AUC = 0.77). The second best diagnostic performance was achieved with an AUC of 0.76 for first order texture features followed by an AUC of 0.76 for first and second order texture features. CONCLUSIONS: Pretreatment DCE-MRI can improve the prediction of pCR in breast cancer patients when all texture features with clinical information and subjective radiological findings are input to build the prediction model.

[The Influence on Image Reconstruction Methods on Digital Breast Tomosynthesis Guided Vacuum-assisted Biopsy for Clustered Microcalcifications].

In this study, we verified the targeting time and coordinates of stereotactic vacuum-assisted biopsy (STVAB) and digital breast tomosynthesis-guided vacuum-assisted biopsy (DBTVAB). We used 23 fabricated phantom samples that consisted of small round, amorphous, and pleomorphic clustered microcalcifications, and two types of image reconstruction methods: filtered back projection (FBP) and iterative super-resolution reconstruction (ISR). Regarding targeting time, DBTVAB tended to be shorter than STVAB in the two image reconstruction methods and the targeting time was significantly shorter for the amorphous and pleomorphic calcifications using DBTVAB with FBP compared to that using STVAB (p=0.022 for amorphous, p=0.041 for pleomorphic). The targeting time for small round calcifications was longer using DBTVAB with ISR compared to that using STVAB (p=0.013). For targeting coordinates, using DBTVAB with FBP showed a significant difference only for pleomorphic calcifications but using DBTVAB with ISR showed no significance. The findings of this study suggest that FBP is more suitable than ISR to be used as an image reconstruction method, and DBTVAB can shorten the targeting time compared to STVAB.

Neural EGFL like 2 expressed in myoepithelial cells and suppressed breast cancer cell migration.

Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma. In this study, we detected expression of neural EGFL like (NELL) 2 and one of its receptors, roundabout guidance receptor (ROBO) 3, in myoepithelial and luminal epithelial cells (respectively) in normal breast tissue. NELL2 also was expressed in myoepithelial cells surrounding the non-cancerous intraductal proliferative lesions and DCIS. However, the expression level and proportion of NELL2-positive cells in DCIS were lower than those in normal and non-cancerous intraductal proliferative lesions. ROBO3 expression was decreased in invasive ductal carcinoma compared to that in normal and non-cancerous intraductal proliferative lesions. An evaluation of NELL2's function in breast cancer cell lines demonstrated that full-length NELL2 suppressed cell adhesion and migration in vitro. In contrast, the N-terminal domain of NELL2 increased cell adhesion in the early phase and migration in vitro in some breast cancer cells. These results suggested that full-length NELL2 protein, when expressed in myoepithelial cells, might serve as an inhibitor of breast cancer cell migration.

Triexponential Diffusion Analysis of Diffusion-weighted Imaging for Breast Ductal Carcinoma in Situ and Invasive Ductal Carcinoma.

PURPOSE: To obtain detailed information in breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) using triexponential diffusion analysis. METHODS: Diffusion-weighted images (DWI) of the breast were obtained using single-shot diffusion echo-planar imaging with 15 b-values. Mean signal intensities at each b-value were measured in the DCIS and IDC lesions and fitted with the triexponential function based on a two-step approach: slow-restricted diffusion coefficient (Ds) was initially determined using a monoexponential function with b-values > 800 s/mm2. The diffusion coefficient of free water at 37°C was assigned to the fast-free diffusion coefficient (Df). Finally, the perfusion-related diffusion coefficient (Dp) was derived using all the b-values. Furthermore, biexponential analysis was performed to obtain the perfusion-related diffusion coefficient (D*) and the perfusion-independent diffusion coefficient (D). Monoexponential analysis was performed to obtain the apparent diffusion coefficient (ADC). The sensitivity and specificity of the aforementioned diffusion coefficients for distinguishing between DCIS and IDC were evaluated using the pathological results. RESULTS: The Ds, D, and ADC of DCIS were significantly higher than those of IDC (P < 0.01 for all). There was no significant correlation between Dp and Ds, but there was a weak correlation between D* and D. The combination of Dp and Ds showed higher sensitivity and specificity (85.9% and 71.4%, respectively), compared to the combination of D* and D (81.5% and 33.3%, respectively). CONCLUSION: Triexponential analysis can provide detailed diffusion information for breast tumors that can be used to differentiate between DCIS and IDC.

Can digital breast tomosynthesis improve identification of malignant calcifications?

Digital breast tomosynthesis (DBT) is an emerging imaging tool for both the screening and diagnosis of breast cancers. However, the use of DBT in diagnosis of calcifications remains ambiguous. In this study, we investigated DBT findings that might help differentiate between benign and malignant calcifications. We enrolled 256 subjects and evaluated 303 breasts with grouped or segmental calcifications. All imaging examinations were performed using two-directional full-field digital mammography (FFDM) and DBT. We divided subjects into two groups, namely, "dense" and "fatty," based on the quantity of breast tissue and evaluated whether the growth of cancer causes increased the density overlapping with calcifications. Increased overlapping density was significantly associated with malignant calcifications (p < 0.001), and the identification of increased density was more accurate using DBT than using FFDM. Furthermore, we used DBT to evaluate whether segmental calcifications were continuous or discontinuous. Significantly more malignant than benign calcifications were associated with a continuous distribution (p = 0.035). Increased density overlapping with grouped calcifications was significantly associated with invasive cancers (p = 0.017). The findings of this study suggest that DBT improves the ability to differentiate between benign and malignant calcifications.

The relation between anti-TGBFR1 immunohistochemical reaction and low Ki67, small tumor size and high estrogen receptor expression in invasive breast cancer.

Most breast cancers are derived from the luminal epithelium, which composes the inside of the breast ductal structure. Ductal carcinoma in situ (DCIS) leads to invasive ductal carcinoma, but noncancerous intraductal proliferative lesions are also a risk factor for ductal carcinoma. The transforming growth factor beta (TGFB) signaling pathway behaves as a tumor suppressor in the early stage of cancer, and conversely as a tumor growth factor in invasive stages in several cancers. In this study, we performed immunohistochemistry with an antibody that detects the cytoplasmic region of TGFB receptor 1 (TGFBR1) and elucidated TGFBR1 protein expression in luminal epithelial cells of noncancerous breast ducts and in several cases of DCIS and invasive carcinoma. TGFBR1 expression was higher in noncancerous breast tissue than in cancerous tissue, and a difference in expression was also seen among histological subtypes. Comparing the expression level of TGFBR1 in cancer cells and clinico-pathological parameters, cases expressing low TGFBR1 tended to show low estrogen receptor expression, large tumor size (≥10 mm), and a high Ki67 labeling index. These data suggested that TGFBR1 protein expression may be related to the suppression of breast cancer cell growth.

[A Case of Thrombotic Microangiopathy Arising from Breast Cancer Treated with Chemotherapy].

The present study reports the case of a 49-year-old woman who was diagnosed with cancer of the left breast at the age of 43 years.Following chemotherapy, the patient had undergone partial mastectomy and axillary lymphadenectomy.Postoperatively, she underwent radiotherapy and hormone therapy.Five years and 4 months after the operation, the patient developed pain in the cervical vertebrae and was diagnosed with spinal metastasis.During the period, she began experiencing fatigue and hematological investigations indicated anemia, as well as thrombocytopenia, jaundice, and schistocytes.The patient was referred to our facility for further examination and treatment.On investigation, she was diagnosed with cancer-related thrombotic microangiopathy(TMA).The patient was advised to undergo chemotherapy due to which symptoms of TMA were relieved.She continued to receive chemotherapy for the following 3 years and 2 months until her death.

[A Case of Histiocytoid Breast Carcinoma Accompanied by Multiple Axillary Lymph Node Metastases].

According to previous reports in our country, histiocytoid breast carcinoma is a very rare case of its tissue type, accounting for only 0.3% of all breast cancer cases. We have neither established a diagnostic standard nor a general idea for these tumors. Previously, its inherited pathology was assumed to be a sub-form of invasive lobular carcinoma. However, some researchers indicate the presence of components that are assumed to originate from milk ducts or differentiation in the apocrine gland. In this way, origins of pathologies for these tumors seem to be complex. Previous reports suggest cases of relatively long survival times without spreading to distant sites. Recently, we encountered one case of histiocytoid breast carcinoma accompanied by multiple axillary lymph node metastases.

Amplicons in breast cancers analyzed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

Gene amplification is a common event in breast cancer, and identifies actual and potential targets of molecular therapy. The aim of the present study was to determine the amplification status of 22 genes that are reportedly frequently amplified in breast cancers. An archive of 322 formalin-fixed and paraffin-embedded invasive breast cancer tissues were screened by multiple ligation-dependent probe amplification (MLPA) and a total of 906 gene loci judged as 'gain' or 'amplified' was further confirmed to have been amplified based on fluorescence in situ hybridization (FISH). The results showed that 109 of 322 tumors (34%) displayed gene amplification of at least one of the 22 genes. The frequencies of the amplification of four regions containing known driver oncogenes were as follows: 8p11 (ZNF703, FGFR1, ADAM9, IKBKB), 8q24 (MYC), 11q13 (CCND1, C11ORF30), and 17q11-21 (CPD, MED1, ERBB2, CDC6, TOP2A, MAPT) exhibited amplification in 9.6%, 9.6%, 12.4%, and 12.1% of the tumors, respectively. In addition to homogeneously staining region- or double-minute chromosome-type amplifications, a centromere-associated-type amplification was found in nine tumors. Co-localization of the amplicon on 8p11 and the amplicon on 11q13 in single cells was found in 10 tumors, and in six of those tumors the two amplicons constituted single amplification units. Similarly, an amplicon consisting of ERBB2 and its flanking genes on 17q12-21 co-localized with an amplicon on 8p11 in 10 tumors and with the amplicon on 11q13 in five tumors. Thus, precise and feasible analysis of gene amplification status can be obtained using a combination of MLPA and FISH.

Changes in content of triterpenoids and polysaccharides in Ganoderma lingzhi at different growth stages.

Ganoderma lingzhi is a traditional medicinal mushroom, and its extract contains many bioactive compounds. Triterpenoids and polysaccharides are the primary bioactive components that contribute to its medicinal properties. In this study, we quantified 18 triterpenoids, total triterpenoid content and total polysaccharide content in the ethanol and water extracts of G. lingzhi at different growth stages. Triterpenoids were quantified by liquid chromatograph-tandem mass spectrometry in the multiple-reaction-monitoring mode. Total triterpenoid and total polysaccharide content were determined by colorimetric analysis. The results indicated that the fruit bodies at an early growth stage had a higher content of ganoderic acid A, C2, I and LM2, as well as of ganoderenic acid C and D, than those at a later growth stage. In contrast, ganoderic acid K, TN and T-Q contents were higher in mature fruit bodies (maturation stage). The highest total triterpenoid and total polysaccharide contents were found in fruit bodies before maturity (stipe elongation stage or early stage of pileus formation). Our results provide information which will contribute to the establishment of an efficient cultivation system for G. lingzhi with a higher content of triterpenoids.

Differentiation between phyllodes tumours and fibroadenomas using intravoxel incoherent motion magnetic resonance imaging: comparison with conventional diffusion-weighted imaging.

OBJECTIVE: To investigate whether the parameters derived from intravoxel incoherent motion (IVIM) MRI could differentiate phyllodes tumours (PTs) from fibroadenomas (FAs) by comparing the apparent diffusion coefficient (ADC) values. METHODS: This retrospective study included 7 FAs, 10 benign PTs (BPTs), 4 borderline PTs, and one malignant PT. Biexponential analyses of IVIM were performed using a 3 T MRI scanner. Quantitative IVIM parameters [pure diffusion coefficient (D), perfusion-related diffusion coefficient (D*), and fraction (f)] were calculated. The ADC was also calculated using monoexponential fitting. RESULTS: The D and ADC values showed an increasing tendency in the order of FA, BPT, and borderline or malignant PT (BMPT). No significant difference was found in the D value among the three groups. The ADC value of the BMPT group was significantly higher than that of the FA group (p = 0.048). The D* value showed an increasing tendency in the order of BMPT, BPT, and FA, and the D* value of the BMPT group was significantly lower than that of the FA group (p = 0.048). CONCLUSION: The D* derived from IVIM and the ADC were helpful for differentiating between FA and BMPT. Advances in knowledge: IVIM MRI examination showed that the perfusion-related diffusion coefficient is lower in borderline and malignant PTs than in FAs and the opposite is true for the ADC.

Influence of the menstrual cycle on compression-induced pain during mammography: correlation with the thickness and volume of the mammary gland.

In mammography, breast compression is necessary and an important factor influencing image quality. The purpose of this study was to determine the influence of the menstrual cycle on compression-induced pain during mammography and to evaluate the association between the thickness and volume of the mammary gland and pain. We examined basal body temperature and categorized the menstrual cycle into five phases. We executed breast compression in the craniocaudal view using a customized compression plate, to which we introduced an opening. We measured the thickness of the mammary gland under compression using echography. Immediately after releasing the compression, we evaluated pain using the visual analogue scale. We performed magnetic resonance imaging (MRI) on the same day and measured the volume of the mammary gland. The thickness of the mammary gland, pain, and the volume of the mammary gland were minimal in the late follicular phase and maximal in the late luteal and early follicular phases. It was shown that the changes in the thickness and volume of the mammary gland during the menstrual cycle accounted for the changes in compression-induced pain. On MRI examination of each breast quadrant, the same changes were observed in areas A and C. In area A, it was shown that both the anatomical characteristics and the increase in volume of the mammary gland were associated with pain. We concluded that the late follicular phase constitutes the optimal timing for mammography.

Differentiation Between Luminal-A and Luminal-B Breast Cancer Using Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: The study aimed to investigate whether intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) can differentiate luminal-B from luminal-A breast cancer MATERIALS AND METHODS: Biexponential analyses of IVIM and DCE MRI were performed using a 3.0-T MRI scanner, involving 134 patients with 137 pathologically confirmed luminal-type invasive breast cancers. Luminal-type breast cancer was categorized as luminal-B breast cancer (LBBC, Ki-67 ≧ 14%) or luminal-A breast cancer (LABC, Ki-67 < 14%). Quantitative parameters from IVIM (pure diffusion coefficient [D], perfusion-related diffusion coefficient [D*], and fraction [f]) and DCE MRI (initial percentage of enhancement and signal enhancement ratio [SER]) were calculated. The apparent diffusion coefficient (ADC) was also calculated using monoexponential fitting. We correlated these data with the Ki-67 status. RESULTS: The D and ADC values of LBBC were significantly lower than those of LABC (P = 0.028, P = 0.037). The SER of LBBC was significantly higher than that of LABC (P = 0.004). A univariate analysis showed that a significantly lower D (<0.847 x 10-3 mm2/s), lower ADC (<0.960 × 10-3 mm2/s), and higher SER (>1.071) values were associated with LBBC (all P values <0.01), compared to LABC. In a multivariate analysis, a higher SER (>1.071; odds ratio: 3.0099, 95% confidence interval: 1.4246-6.3593; P = 0.003) value and a lower D (<0.847 × 10-3 mm2/s; odds ratio: 2.6878, 95% confidence interval: 1.0445-6.9162; P = 0.040) value were significantly associated with LBBC, compared to LABC. CONCLUSION: The SER derived from DCE MRI and the D derived from IVIM are associated independently with the Ki-67 status in patients with luminal-type breast cancer.

[Phantom Study on Dose Reduction Using Iterative Reconstruction in Low-dose Computed Tomography for Lung Cancer Screening].

We investigated dose reduction ability of an iterative reconstruction technology for low-dose computed tomography (CT) for lung cancer screening. The Sinogram Affirmed Iterative Reconstruction (SAFIRE) provided in a multi slice CT system, Somatom Definition Flash (Siemens Healthcare) was used. An anthropomorphic chest phantom (N-1, Kyoto Kagaku) was scanned at volume CT dose index (CTDIvol) of 0.50-11.86 mGy with 120 kV. For noise (standard deviation) and contrast-to-noise ratio (CNR) measurements, CTP486 and CTP515 modules in the Catphan (The Phantom Laboratory) were scanned. Radiological technologists were participated in the perceptual comparison. SAFIRE reduced the SD values by approximately 50% compared with filter back projection (FBP). The estimated dose reduction rates by SAFIRE determined from the perceptual comparison was approximately 23%, while 75% dose reduction rate was expected from the SD value reduction of 50%.