Eriko Tohno

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.

Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to the Porta Hepatis

PURPOSE To evaluate the efficacy and safety of proton beam therapy (PBT) for patients with hepatocellular carcinoma (HCC) located adjacent to the porta hepatis. METHODS AND MATERIALS Subjects of the study were 53 patients with HCC located within 2 cm of the main portal vein. All patients had tumor confined to the radiation field with no evidence of metastatic disease. All patients had hepatic function levels of a Child-Pugh score of 10 or less, Eastern Cooperative Oncology Group performance status of 2 or less, and no uncontrolled ascites. Patients underwent PBT of 72.6 GyE in 22 fractions from Sept 2001 to Dec 2004. RESULTS After 3 years, the actuarial survival rate was 45.1% and local control rate was 86.0%. Prognostic factors for survival included Child-Pugh score, number of tumors, and alpha-fetoprotein levels. No late treatment-related toxicity of Grade 2 or higher was observed. CONCLUSIONS The PBT delivering 72.6 GyE in 22 fractions appears to be effective and safe for HCC adjacent to the porta hepatis.

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.

Ultrasound screening of breast cancer.

Ultrasound (US) screening of breast cancer was surveyed with the results of breast screening combined with mammography (MMG), US and clinical breast examination (CBE) at Ibaraki Health Service Association. Breast cancer is common among women in their late 40s in Japan, who tend to have small and dense breasts. Our results showed that US works as well as MMG in detecting breast cancers in women in their 40s, and both modalities are compensatory. There are many reports that the combination of MMG and US is a suitable method for breast screening in Japan. A large-scale randomized control trial is now ongoing to investigate whether breast screening by both MMG and US is useful to decrease breast cancer mortality.

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.

Current improvements in breast ultrasound, with a special focus on elastography

Current improvements in the area of breast ultrasound are described. Digital beam formers contributed to improving both contrast and special resolution of B-mode images and enabled other techniques. Four-dimensinal images and CAD are still in progress. Elastography may reduce false-positives and unnecessary interventional procedures, especially in nonsymptomatic patients.

A CAD system for the 3D location of lesions in mammograms

A CAD system for estimating the 3D (three-dimensional) positions of lesions found in two mammographic views is described. The system is an extension of our previous method [Comput. Vis. Image Understand. 83 (2001) 38] which finds corresponding 2D positions in different mammographic views. The method calculates curved epipolar lines by developing a simulation of breast deformation into stereo camera geometry. Using such curved epipolar lines, not only can we determine point correspondences, but can estimate the 3D location of a lesion. In this paper, we first explain the underlying principles and system organisation. The correctness of the 3D positions calculated by the system is examined using a set of breast lesions, which appear both in mammograms and in MRI data. The experimental results demonstrate the clinical promise of the CAD system.

Fat suppression strategies in enhanced MR imaging of the breast: Comparison of SPIR and water excitation sequences

To compare two fat suppression techniques of spectrally‐selective inversion pulse (spectral presaturation with inversion recovery—SPIR) and spectral‐spatial excitation pulse of water excitation (WE) for contrast‐enhanced MR imaging of the breast.

Proton irradiation in a single fraction for hepatocellular carcinoma patients with uncontrollable ascites. Technical considerations and results.

Purpose:To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma (HCC) patients with uncontrollable ascites.Patients and Methods:Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water-equivalent thickness.Results:All irradiated tumors showed objective responses, and were controlled during the follow-up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy-related toxicity of grade 3 or more was observed.Conclusion:Proton beams were successfully adjusted immediately before irradiation. Single-dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.Ziel:Vorstellung technischer Überlegungen und der Ergebnisse von Protonenbestrahlungen in einer einzigen Fraktion bei Patienten mit Leberzellkarzinom (HCC [„hepatocellular carcinoma“]) und unkontrollierbarem Aszites.Patienten und Methodik:Drei HCC-Patienten mit unkontrollierbarem Aszites erhielten eine Protonenbestrahlung von 24 Gy als Einzelfraktion. Bei den Lebertumoren handelte es sich in zwei Fällen um solitäre Tumoren und in einem Fall um multiple Tumoren, deren maximaler Durchmesser jeweils 30, 30 und 33 mm betrug. Bei keinem der Patienten lagen Lymphknoten- oder Fernmetastasen vor. Das Zentrum des Bestrahlungsbereichs wurde anhand der unmittelbar vor der Bestrahlung erhobenen CT-Daten festgelegt, und der Strahlbereich wurde entsprechend eingestellt, um Änderungen im Aszitesvolumen auszugleichen. Die Einstellung des Strahlbereichs lag innerhalb einer wasseräquivalenten Schichtdicke von 6 mm.Ergebnisse:Bei allen bestrahlen Tumoren wurde eine objektive Veränderung registriert und während der Beobachtungszeit kontrolliert. Zwei der drei Patienten waren jeweils 13 und 30 Monate nach der Behandlung ohne Anzeichen der Krankheit am Leben. Der andere Patient verstarb 6 Monate nach der Behandlung an einer Ruptur ösophagealer Varizen. Therapiebezogene Toxizität eines Schweregrades von 3 oder höher wurde nicht beobachtet.Schlussfolgerung:Protonenstrahlen wurden unmittelbar vor der Bestrahlung erfolgreich eingestellt. Die Bestrahlung als Einzeldosis mit einem genau eingestellten Protonenstrahl scheint für HCC-Patienten mit unkontrollierbarem Aszites tolerierbar zu sein.

Proton Irradiation in a Single Fraction for Hepatocellular Carcinoma Patients with Uncontrollable Ascites

Purpose:To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma (HCC) patients with uncontrollable ascites.Patients and Methods:Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water-equivalent thickness.Results:All irradiated tumors showed objective responses, and were controlled during the follow-up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy-related toxicity of grade 3 or more was observed.Conclusion:Proton beams were successfully adjusted immediately before irradiation. Single-dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.Ziel:Vorstellung technischer Überlegungen und der Ergebnisse von Protonenbestrahlungen in einer einzigen Fraktion bei Patienten mit Leberzellkarzinom (HCC [„hepatocellular carcinoma“]) und unkontrollierbarem Aszites.Patienten und Methodik:Drei HCC-Patienten mit unkontrollierbarem Aszites erhielten eine Protonenbestrahlung von 24 Gy als Einzelfraktion. Bei den Lebertumoren handelte es sich in zwei Fällen um solitäre Tumoren und in einem Fall um multiple Tumoren, deren maximaler Durchmesser jeweils 30, 30 und 33 mm betrug. Bei keinem der Patienten lagen Lymphknoten- oder Fernmetastasen vor. Das Zentrum des Bestrahlungsbereichs wurde anhand der unmittelbar vor der Bestrahlung erhobenen CT-Daten festgelegt, und der Strahlbereich wurde entsprechend eingestellt, um Änderungen im Aszitesvolumen auszugleichen. Die Einstellung des Strahlbereichs lag innerhalb einer wasseräquivalenten Schichtdicke von 6 mm.Ergebnisse:Bei allen bestrahlen Tumoren wurde eine objektive Veränderung registriert und während der Beobachtungszeit kontrolliert. Zwei der drei Patienten waren jeweils 13 und 30 Monate nach der Behandlung ohne Anzeichen der Krankheit am Leben. Der andere Patient verstarb 6 Monate nach der Behandlung an einer Ruptur ösophagealer Varizen. Therapiebezogene Toxizität eines Schweregrades von 3 oder höher wurde nicht beobachtet.Schlussfolgerung:Protonenstrahlen wurden unmittelbar vor der Bestrahlung erfolgreich eingestellt. Die Bestrahlung als Einzeldosis mit einem genau eingestellten Protonenstrahl scheint für HCC-Patienten mit unkontrollierbarem Aszites tolerierbar zu sein.