The Japan Society of Ultrasonics in Medicine guidelines on non-mass abnormalities of the breast.

It is possible to appropriately diagnose non-mass abnormalities by elucidating ultrasound non-mass abnormality findings and sharing the concept. If non-mass abnormalities can be diagnosed early, the number of curable cases could increase, leading to fewer breast cancer deaths. The Japan Society of Ultrasonics in Medicine (JSUM) Terminology/Diagnostic Criteria Committee has classified non-mass abnormalities into five subtypes: hypoechoic area in the mammary gland, abnormalities of the ducts, architectural distortion, multiple small cysts, and echogenic foci without a hypoechoic area. We herein define the findings for each of these subtypes and present a summary of the JSUM guidelines on non-mass abnormalities of the breast generated based on those findings.

B-mode ultrasound diagnostic flowchart for solid breast masses: JABTS BC-01 study.

PURPOSE: Breast ultrasound has been widely used as an essential examination for diagnosing breast cancer. However, standardized diagnostic criteria are as yet lacking. This study aimed to develop a simple diagnostic flowchart for beginners learning breast ultrasonography. The diagnostic flowchart was developed based on the recall criteria widely used in Japan. METHODS: We conducted a multicenter study to examine recall criteria usefulness in the diagnostic phase of breast disease. Women with ultrasound-visible breast masses who underwent B-mode breast ultrasound examination were recruited from 22 hospitals in Japan between September 2009 and January 2010. B-mode images were evaluated by members of the centralized image interpretation committee. We developed the new diagnostic flowchart based on the results. The usefulness of the diagnostic flowchart was assessed by employing datasets from the current study and another study which we conducted (BC-04 study). RESULTS: We evaluated 1045 solid masses (malignant: 495, benign: 550). Multivariate analysis showed that shape, margin, echogenic halo, interruption of the mammary gland interface, and depth width ratio were significant findings for distinguishing between benign and malignant masses. We modified the recall criteria and developed our novel diagnostic flowchart using these findings. The sensitivity and specificity of the new flowchart (current study: 0.97, 0.45; BC-04 study dataset: 0.95, 0.45) were similar to those of experts (current study: 0.96, 0.54; BC-04 study dataset: 0.98, 0.38). CONCLUSION: We developed a simple diagnostic flowchart for breast ultrasound. This flowchart is anticipated to be applicable to educating beginners learning breast ultrasound.

Overall assessment system of combined mammography and ultrasound for breast cancer screening in Japan.

Mammography is the only screening method with evidence in support of reduced breast cancer mortality, but yields poor accuracy outcomes in women with dense breast tissue. The Japan Strategic Anti-cancer Randomized Trial (J-START) was conducted as part of the measures implemented to deal with women with dense breast tissue. Although the sensitivity was increased, the specificity was significantly lower in the intervention group because further examination was required in all positive cases classified by either mammography or ultrasound in the J-START. To address the issue, an overall assessment system of combined mammography and adjunctive ultrasound for breast cancer screening has been developed in Japan. The basic concept is based on a comprehensive assessment that includes a mammography assessment followed by an adjunctive assessment for ultrasound similar to the clinical setting. Currently, mammography alone is recommended for population-based breast cancer screening in Japan, but additional ultrasonography is extensively available for women, especially for women with dense breasts with shared decision-making for personalized breast cancer screening. The overall assessment system is recommended for use in Japan when breast cancer screening is conducted using both mammography and ultrasonography. In this article, we summarize the advantages of the overall assessment and the simultaneous mammography/ultrasound method, the basic approach used in Japan to assign the overall assessment category for breast cancer screening, and we outline the future directions of adjunctive screening ultrasound.

Investigation of the significance of population-based breast cancer screening among women aged under 40 years.

BACKGROUND: Owing to low incidence rates, population-based breast cancer screening is not recommended by many municipalities in Japan for women aged < 40 years. To evaluate the usefulness of screening in women aged < 40 years, we investigated the results of population-based breast cancer screening among young women performed in the Ibaraki Prefecture. METHODS: Data regarding histological characteristics, recall rates, cancer detection rates, positive predictive values, tumor categories, and status of lymph node metastases were obtained from population-based screening data from Ibaraki Health Service Association Institute. The "number needing to be screened" (NNS) was determined; using Pearson's chi-squared test, these data were compared between women aged < 40 years and > 40 years. RESULTS: The data of 428,560 women were evaluated. Cancer detection rates were significantly lower and the NNS and proportion of women with tumor category T2 or higher was significantly increased in women aged < 40 years than in those aged > 40 years (0.06% vs. 0.21%, 1505 vs. 281-439, and 28.9% vs. 6.3%, respectively; all, p < 0.05). The proportion of early-stage cancers was lower in women aged < 40 years than in those > 40 years, but this was not significant. CONCLUSIONS: These results suggest that population-based breast cancer screening should not be recommended for women aged < 40 years. To reduce the breast cancer-related mortality rate in young women and ensure efficient use of limited medical resources in Japan, a more efficient surveillance system, based on genetic propensity and family history, needs to be established.

Multicenter Prospective Study of Color Doppler Ultrasound for Breast Masses: Utility of Our Color Doppler Method.

The use of color Doppler ultrasound (CD) for distinguishing between benign and malignant breast lesions remains controversial. This study (JABTS BC-04 study) was aimed at confirming the usefulness of our CD diagnostic criteria. We evaluated ultrasound images of 1408 solid breast masses from 16 institutions in Japan (malignant: 839, benign: 569). Multivariate analysis indicated that vascularity (amount of blood flow), vascular flow pattern ("surrounding marginal flow" or "penetrating flow") and the incident angle of penetrating flow were significant findings for distinguishing between benign and malignant lesions. However, the sensitivity and specificity of B-mode alone did not improve significantly with CD addition (97.6% → 97.9%, 38.3% → 41.5%, respectively). We explored the causes of these negative results and found that age should have been considered when evaluating vascularity. Simulation experiments suggested that specificity is significantly improved when age is taken into consideration (38.3% → 46.0%, p < 0.001) and we thereby improved our diagnostic criteria.

Ultrasound Image Classification of Ductal Carcinoma In Situ (DCIS) of the Breast: Analysis of 705 DCIS Lesions.

The Japan Association of Breast and Thyroid Sonology (JABTS) proposed, in 2003, a conceptual classification system for non-mass abnormalities to be applied in addition to the conventional concept of masses, to facilitate detecting ductal carcinoma in situ (DCIS) lesions. The aim of this study was to confirm the utility of this system and to clarify the distribution of these findings in DCIS lesions. Data on 705 surgically treated DCIS lesions from 16 institutions in Japan were retrospectively reviewed. All 705 DCIS lesions could be classified according to the JABTS classification system. The most frequent findings were hypo-echoic areas in the mammary gland (48.6%), followed by solid masses (28.0%) and duct abnormalities (10.2%) or mixed masses (8.1%). Distortion (1.3%), clustered microcysts (1.4%) and echogenic foci without a hypo-echoic area (2.5%) were uncommon. These results suggest that the concept of non-mass abnormalities is useful in detecting DCIS lesions.

Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial.

BACKGROUND: Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography. METHODS: Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757. FINDINGS: Of 72,998 women enrolled, 36,859 were assigned to the intervention group and 36,139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2-95·0 vs 77·0%, 70·3-83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3-88·0 vs 91·4%, 91·1-91·7; p<0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034). INTERPRETATION: Adjunctive ultrasonography increases sensitivity and detection rate of early cancers. FUNDING: Ministry of Health, Labour and Welfare of Japan.

The essence of the Japan Radiological Society/Japanese College of Radiology Imaging Guideline.

Diagnostic imaging is undoubtedly important in modern medicine, and final clinical decisions are often made based on it. Fortunately, Japan has the highest numbers of diagnostic imaging instruments, such as CT and MRI devices, and boasts easy access to them as well as a high level of diagnostic accuracy. In consequence, a very large number of imaging examinations are performed, but diagnostic instruments are installed in so many medical facilities that expert management of these examinations tends to be insufficient. Particularly, in order to avoid risks, clinicians have recently become indifferent to indications of imaging modalities and tend to rely on CT or MRI resulting in increasing the number of imaging examinations in Japan. This is a serious problem from the viewpoints of avoidance of unnecessary exposure and medical economy. Under these circumstances, the Japan Radiological Society and Japanese College of Radiology jointly initiated the preparation of new guidelines for diagnostic imaging. However, the field of diagnostic imaging is extremely wide, and it is impossible to cover all diseases. Therefore, in drafting the guidelines, we selected important diseases and focused on "showing evidence and suggestions in the form of clinical questions (CQs)" concerning clinically encountered questions and "describing routine imaging techniques presently considered to be standards to guarantee the quality of imaging examinations". In so doing, we adhered to the basic principles of assuming the readers to be "radiologists specializing in diagnostic imaging", "simultaneously respecting the global standards and attending to the situation in Japan", and "making the guidelines consistent with those of other scientific societies related to imaging". As a result, the guidelines became the largest ever, consisting of 152 CQs, nine areas of imaging techniques, and seven reviews, but no other guidelines in the world summarize problems concerning diagnostic imaging in the form of CQs. In this sense, the guidelines are considered to reflect the abilities of diagnostic radiologists in Japan. The contents of the guidelines are essential knowledge for radiologists, but we believe that they are also of use to general clinicians and clinical radiological technicians. While the number and contents of CQs are still insufficient, and while chapters such as those on imaging in children and emergency imaging need to be supplemented, the guidelines will be serially improved through future revisions. Lastly, we would like to extend our sincere thanks to the 153 members of the drafting committee who authored the guidelines, 12 committee chairpersons who coordinated their efforts, six members of the secretariat, and affiliates of related scientific societies who performed external evaluation.

A preliminary prospective study to compare the diagnostic performance of assist strain ratio versus manual strain ratio.

OBJECTIVES: The objectives of this study were to demonstrate the non-inferiority of assist strain ratio (ASR)-a newly developed application tool-to manual strain ratio (MSR)-a currently available standard diagnostic tool-and to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MSR and ASR. METHODS: Ninety-eight mass lesions in the mammary gland (30 malignant and 68 benign) were included in the study. Skilled physicians performed the elastography scanning by applying minimal vibration. MSRs were obtained and compared with ASRs calculated from the same elastography image to test the correlation between the two groups of data. RESULTS: Diagnostic performance of MSR at a cut-off of 5.0 showed a sensitivity of 84.4 %, a specificity of 80.4 %, an accuracy of 81.6 %, a PPV of 65.5 %, and an NPV of 92.1 %. Diagnostic performance of ASR at a cut-off of 5.0 showed a sensitivity of 74.4 %, a specificity of 84.3 %, an accuracy of 81.3 %, a PPV of 67.7 %, and an NPV of 88.2 %. The areas under the curve (AUCs) for MSR and ASR were found to be 0.885 and 0.875, respectively. CONCLUSION: ASR demonstrated excellent diagnostic potential and was highly correlated with MSR performed by skilled physicians (r = 0.69, p < 0.05).

Spontaneous regression of breast angiosarcoma after conservative treatment with radiotherapy: a case report and review of the literature.

Angiosarcoma of the breast is a rare disease, and approximately 1 % of all affected patients are treated with breast-conserving therapy (BCT) and radiotherapy (RT) for primary breast cancer. The prognosis for this tumor is quite dismal, with high rates of recurrence and poor overall survival. This report presents the case of a 73-year-old female who underwent BCT followed by RT for left breast carcinoma 18 years previously. The patient visited the hospital with a complaint of a new mass in the left breast. The lesion initially decreased in size; however, it subsequently began to rapidly enlarge. A core needle biopsy of the mass was performed under ultrasonography, with a diagnosis of a spindle cell sarcoma, most conceivably an angiosarcoma, originating from the left breast, suspected to be induced by RT. The tumor was resected with the surrounding skin, and immunohistochemically diagnosed as angiosarcoma of the left breast, without evidence of breast cancer in any lesion, suggesting that RT induced the tumor formation. We herein report this rare case and the ultrasound imaging findings.

Malignant lymphoma of the breast in a male patient: ultrasound imaging features.

Non-Hodgkin lymphoma (NHL) of the breast is a rare disease. Herein, we report a rare case of secondary involvement of the breast by NHL in a male patient and the ultrasound imaging findings. A 70-year-old man noticed an induration of the subareolar region of the right breast. He had been diagnosed as having mantle cell lymphoma 5 years before and treated with several series of chemoradiotherapy. On supine examination, palpation revealed bilateral breast enlargement, but detection of a lump was difficult. Ultrasonography showed a hypoechoic non-mass image-forming lesion in the subareolar region of the right breast. The final pathological diagnosis was recurrence of mantle cell lymphoma in the right breast. The diagnosis of malignant lymphoma of the breast by imaging modalities is difficult because there are no specific features. Breast lymphoma should be included with gynecomastia and breast cancer in the differential diagnosis of male patients with breast enlargement.

A randomized controlled trial to verify the efficacy of the use of ultrasonography in breast cancer screening aged 40-49 (J-START): 76 196 women registered.

OBJECTIVE: The objective of the Japan Strategic Anti-cancer Randomized Trial was to verify the efficacy of the use of ultrasonography in breast cancer screening among women aged 40-49 years. The purpose of this paper was to report the design and recruitment result of this study. METHODS: In this study of women in their 40s, the participants were divided into two groups, one of which (the intervention group) was subjected to mammography and ultrasonography (using a standardized ultrasonography examination), while the other (the control group) was examined with mammography, in a randomized controlled trial, with the objective of verifying the accuracy and efficacy of examinations by comparing the two groups. RESULTS: The cumulative total number of participants registered in the study was 76 196 (38 313 in the intervention group and 37 883 in the control group). 71.0% of participants registered to the study were under individual randomized controlled trial, 25.0% were under cluster randomized controlled trial and 3.9% were under non-randomized controlled group. The study was designed so that participants registered at their first examination underwent examinations by the same method for the subsequent two years. 74.1% of participants scheduled for a second examination had undertaken it, while information regarding the presence of interval cancer had been obtained from a further 20.6% using a questionnaire. At July 2013, the status of 5.3% of all participants was unclear. CONCLUSIONS: It was the first large-scale randomized controlled trial carried out in Japan. The scheduled second examinations were completed at the end of fiscal 2012. Once the proportion of participants whose status is unclear has fallen to ≤5%, the authors plan to collate the data relating to the primary end points, and publish the results.

Sonographic and pathologic image analysis of pure mucinous carcinoma of the breast.

The aims of this study were to elucidate sonographic and histologic features of pure mucinous carcinoma (P-MC) of the breast using quantitative analysis and to evaluate the relationship between quantitative analysis and visual qualitative assessment. Eleven P-MCs (nine patients) were evaluated qualitatively and quantitatively. Three experts assessed these sonographic images using the Breast Imaging Reporting and Data System (BI-RADS) lexicon. For assessment of internal echoes and posterior echoes, quantitative measures were determined using ImageJ software. Histologic thin sections were stained for classification into separate parts of the tumor (stroma, mucin and cancer cells) and were digitized. Internal echoes were isoechoic in 7 of 11 (63.6%) tumors and hypoechoic in 4 of 11 (36.4%); all P-MCs were "enhanced" in qualitative evaluation. As internal echoes increased, the proportion of stroma increased and that of mucin decreased. The high level of internal echoes is correlated with reflection and back-scattering, which are caused mainly by the interface between mucin and stroma.

Effect of adding screening ultrasonography to screening mammography on patient recall and cancer detection rates: a retrospective study in Japan.

PURPOSE: To determine whether adding screening ultrasonography to screening mammography can reduce patient recall rates and increase cancer detection rates. MATERIALS AND METHODS: We analyzed the results of mammography and ultrasonography breast screenings performed at the Total Health Evaluation Center Tsukuba, Japan, between April 2011 and March 2012. We also reviewed the modalities and results of diagnostic examinations from women with mammographic abnormalities who visited the Tsukuba Medical Center Hospital for further testing. RESULTS: Of 11,753 women screened, cancer was diagnosed in 10 (0.22%) of the 4529 participants who underwent mammography alone, 23 (0.37%) of the 6250 participants who underwent ultrasonography alone, and 5 (0.51%) of the 974 participants who underwent mammography and ultrasonography. The recall rate due to mammographic abnormalities was 4.9% for women screened only with mammography and 2.6% for those screened with both modalities. The cancer detection rate was 0.22% for women screened only with mammography (positive predictive value, 4.5%) and 0.31% for those screened with both modalities (positive predictive value, 12.0%). Of the 211 lesions presenting as mammographic abnormalities investigated further, diagnostic ultrasonography found no abnormalities in 63 (29.9%) and benign findings in 69 (33.7%). The rest 36.4% needed mammography, cytological or histological examinations or follow-up in addition to diagnostic ultrasonography. CONCLUSIONS: It is possible to reduce the recall rate in screening mammography by combining mammography and ultrasonography for breast screening.

Harms of screening mammography for breast cancer in Japanese women.

BACKGROUND: The US Preventative Services Task Force assesses the efficacy of breast cancer screening by the sum of its benefits and harms, and recommends against routine screening mammography because of its relatively great harms for women aged 40-49 years. Assessment of the efficacy of screening mammography should take into consideration not only its benefits but also its harms, but data regarding those harms are lacking for Japanese women. METHODS: In 2008 we collected screening mammography data from 144,848 participants from five Japanese prefectures by age bracket to assess the harms [false-positive results, performance of unnecessary additional imaging, fine-needle aspiration cytology (FNA), and biopsy and its procedures]. RESULTS: The rate of cancer detected in women aged 40-49 years was 0.28%. The false-positive rate (9.6%) and rates of additional imaging by mammography (5.8%) and ultrasound (7.3%) were higher in women aged 40-49 years than in the other age brackets. The rates of FNA (1.6%) and biopsy (0.7%) were also highest in women aged 40-49 years. However, they seemed to be lower than the rates reported by the Breast Cancer Surveillance Consortium (BCSC) and other studies in the US. CONCLUSIONS: The results, although preliminary, indicate the possibility that the harms of screening mammography for Japanese women are less than those for American women.

Evaluation of liver function after proton beam therapy for hepatocellular carcinoma.

PURPOSE: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. METHODS AND MATERIALS: The subjects were 259 patients treated with PBT at the University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effect of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. RESULTS: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of ≥2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. CONCLUSION: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.

Investigation of the geometric accuracy of proton beam irradiation in the liver.

PURPOSE: To investigate the geometric accuracy of proton beam irradiation to the liver by measuring the change in Hounsfield units (HUs) after irradiation. METHODS AND MATERIALS: We examined 21 patients with liver tumors who were treated with respiratory-gated proton beam therapy (PBT). The radiation dose was 66 GyE in 12 patients and 72.6 GyE in 9 patients. Image registration and reslicing of the computed tomography (CT) results obtained within 1 month before and 3 months after PBT was performed, referring to the planning CT image. The resliced CT images obtained after PBT were subtracted from the images obtained before PBT. We investigated whether the area of the large HU change was consistent with the high-dose distribution area using the location of the largest change in HU around the tumor (peak) on the subtracted CT image and the 90% dose distribution area of the planning CT image. RESULTS: The number of patients (n = 20) whose left-right peaks were within the 90% dose distribution area was significantly larger than the number of patients whose anterior-posterior peaks and superior-inferior peaks were within the 90% dose distribution area (n = 14, n = 13, p = 0.034, and p = 0.02, respectively). Twelve patients exhibited a peak within the 90% dose distribution area in all directions. Nine of the 11 patients with smaller 90% confidence intervals of the percent normalization of the beam cycle (BC; 90% BC) showed a peak within the 90% dose distribution area in six directions, and this percentage was higher than that among the patients with larger 90% BC (3/10, p = 0.03). CONCLUSION: The geometric accuracy of proton beam irradiation to the liver was higher in the left-right direction than in the other directions. Patients with an irregular respiratory rhythm have a greater risk of a reduced geometric accuracy of PBT in the liver.

Educational program and testing using images for the standardization of breast cancer screening by ultrasonography.

BACKGROUND: To improve the quality of breast cancer screening by ultrasonography, both effective training and evaluation of the performance of the examiners of breast ultrasound are essential. METHODS: The Educational Committee of the Japan Association of Breast and Thyroid Sonology, an NPO, has established 2-day training programs on breast ultrasonography with tests at the end of the programs. The tests are performed using images to evaluate the ability of observers to detect and evaluate lesions on ultrasound. Ability to detect lesions was examined by using videos, and ability to evaluate lesions was examined by using still images. The results of tests taken by 422 physicians and 415 technologists were analyzed. RESULTS: In a comparison between physicians and technologists, the video specificity, the still image sensitivity, and the percentage of category agreement did not show any significant differences. The video sensitivity, the still image specificity, and the percentage of disease name agreement were significantly higher in technologists. Observers who had experienced <100 cases showed significantly poorer results in all subjects except for the video specificity in physicians and the still image specificity in technologists. CONCLUSIONS: Ultrasound technologists perform as well as physicians in recognizing and interpreting cancers on breast ultrasound, which supports their role in performing the initial screening examination.

Proton beam therapy for hepatocellular carcinoma: a comparison of three treatment protocols.

BACKGROUND: Our previous results for treatment of hepatocellular carcinoma (HCC) with proton beam therapy revealed excellent local control with low toxicity. Three protocols were used to avoid late complications such as gastrointestinal ulceration and bile duct stenosis. In this study, we examined the efficacy of these protocols. METHODS AND MATERIALS: The subjects were 266 patients (273 HCCs) treated by proton beam therapy at the University of Tsukuba between January 2001 and December 2007. Three treatment protocols (A, 66 GyE in 10 fractions; B, 72.6 GyE in 22 fractions; and C, 77 GyE in 35 fractions) were used, depending on the tumor location. RESULTS: Of the 266 patients, 104, 95, and 60 patients were treated with protocols A, B, and C, respectively. Seven patients with double lesions underwent two different protocols. The overall survival rates after 1, 3 and 5 years were 87%, 61%, and 48%, respectively (median survival, 4.2 years). Multivariate analysis showed that better liver function, small clinical target volume, and no prior treatment (outside the irradiated field) were associated with good survival. The local control rates after 1, 3, and 5 years were 98%, 87%, and 81%, respectively. Multivariate analysis did not identify any factors associated with good local control. CONCLUSIONS: This study showed that proton beam therapy achieved good local control for HCC using each of three treatment protocols. This suggests that selection of treatment schedules based on tumor location may be used to reduce the risk of late toxicity and maintain good treatment efficacy.