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研究者情報

マスター

アカウント（マスター）

  • 氏名

    木下　留美子(キノシタ　ルミコ), キノシタ　ルミコ

所属（マスター）

  • 北海道大学病院　放射線科

所属（マスター）

  • 北海道大学病院　放射線科

独自項目

syllabus

  • 2021, 基本医学研究, Master's Thesis Research in Medical Sciences, 修士課程, 医学院, 放射線生物学、放射線腫瘍学、放射線治療
  • 2021, 基本医学総論, Basic Principles of Medicine, 修士課程, 医学院, 放射線生物学、放射線腫瘍学、放射線治療
  • 2021, 臨床腫瘍学特論, 修士課程, 保健科学院
  • 2021, 医学総論, Principles of Medicine, 博士後期課程, 医学院, 放射線生物学、放射線腫瘍学、放射線治療
  • 2021, 基盤医学研究, Dissertation Research in Medical Sciences, 博士後期課程, 医学院, 放射線生物学、放射線腫瘍学、放射線治療
  • 2021, 臨床医学研究, Dissertation Research in Clinical Medicine, 博士後期課程, 医学院, 放射線生物学、放射線腫瘍学、放射線治療
  • 2021, 放射線医学, Radiation Medicine, 学士課程, 医学部, 放射線生物学、放射線腫瘍学、放射線治療
  • 2021, 放射線腫瘍学, Radiation Oncology, 学士課程, 医学部, 放射線腫瘍学

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プロフィール情報

学位

  • 博士（医学）（北海道大学）

プロフィール情報

  • 姓

    木下, キノシタ

  • 名

    留美子, ルミコ

  • ID各種

    201301035935334720

対象リソース

業績リスト

研究分野

  • ライフサイエンス / 放射線科学

経歴

  • 2012年 北海道大学 医学(系)研究科(研究院) その他

論文

  • Kentaro Nishioka, Takayuki Hashimoto, Takashi Mori, Yusuke Uchinami, Rumiko Kinoshita, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Yoichi M Ito, Seishin Takao, Masaya Tamura, Taeko Matsuura, Shinichi Shimizu, Hiroki Shirato, Hidefumi Aoyama
    Advances in radiation oncology 9 5 101464 - 101464 2024年05月 
    PURPOSE: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. METHODS AND MATERIALS: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE. RESULTS: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%). CONCLUSIONS: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.
  • Takaaki Yoshimura, Ryota Yamada, Rumiko Kinoshita, Taeko Matsuura, Takahiro Kanehira, Hiroshi Tamura, Kentaro Nishioka, Koichi Yasuda, Hiroshi Taguchi, Norio Katoh, Keiji Kobashi, Takayuki Hashimoto, Hidefumi Aoyama
    Journal of radiation research 2024年03月17日 
    This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.
  • Yusuke Uchinami, Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Noboru Nishikawa, Rumiko Kinoshita, Kentaro Nishioka, Norio Katoh, Takashi Mori, Manami Otsuka, Naoki Miyamoto, Ryusuke Suzuki, Keiji Kobashi, Yasushi Shimizu, Jun Taguchi, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Hidefumi Aoyama
    Radiation oncology journal 42 1 74 - 82 2024年03月 
    PURPOSE: To investigate the clinical significance of adaptive radiotherapy (ART) in locally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Eligible patients were treated with concurrent chemoradiotherapy using IMRT. Planning computed tomography in ART was performed during radiotherapy, and replanning was performed. Since ART was started in May 2011 (ART group), patients who were treated without ART up to April 2011 (non-ART group) were used as the historical control. The Kaplan-Meier method was used to calculate overall survival (OS), locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). LRFS for the primary tumor (LRFS_P) and regional lymph node (LRFS_LN) were also studied for more detailed analysis. Statistical significance was evaluated using the log-rank test for survival. RESULTS: The ART group tended to have higher radiation doses. The median follow-up period was 127 months (range, 10 to 211 months) in the non-ART group and 61.5 months (range, 5 to 129 months) in the ART group. Compared to the non-ART group, the ART group showed significantly higher 5-year PFS (53.8% vs. 81.3%, p = 0.015) and LRFS (61.2% vs. 85.3%, p = 0.024), but not OS (80.7% vs. 80.8%, p = 0.941) and DMFS (84.6% vs. 92.7%, p = 0.255). Five-year LRFS_P was higher in the ART group (61.3% vs. 90.6%, p = 0.005), but LRFS_LN did not show a significant difference (91.9% vs. 96.2%, p = 0.541). CONCLUSION: Although there were differences in the patient backgrounds between the two groups, this study suggests the potential effectiveness of ART in improving locoregional control, especially in the primary tumor.
  • 木下 留美子, 田口 大志, 高橋 周平, 宮崎 智彦, 森 崇, 西岡 健太郎, 橋本 孝之, 青山 英史
    北海道外科雑誌 68 2 163 - 164 北海道外科学会 2023年12月
  • Hajime Higaki, Kentaro Nishioka, Manami Otsuka, Noboru Nishikawa, Motoyasu Shido, Hideki Minatogawa, Yukiko Nishikawa, Rikiya Takashina, Takayuki Hashimoto, Norio Katoh, Hiroshi Taguchi, Rumiko Kinoshita, Koichi Yasuda, Takashi Mori, Yusuke Uchinami, Fuki Koizumi, Yoshihiro Fujita, Shuhei Takahashi, Takahiro Hattori, Noriaki Nishiyama, Hidefumi Aoyama
    Radiation oncology (London, England) 18 1 25 - 25 2023年02月07日 
    BACKGROUND: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. METHODS: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results. RESULTS: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months). CONCLUSIONS: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions.
  • 尿管癌への放射線治療後に転移による直腸狭窄を来した1例
    服部 敬寛, 西岡 健太郎, 橋本 孝之, 大塚 愛美, 木下 留美子, 青山 英史, 安部 崇重, 大澤 崇宏, 松本 隆児, 菊地 央, 篠原 信雄, 高桑 恵美
    Japanese Journal of Radiology 41 Suppl. 4 - 4 (公社)日本医学放射線学会 2023年02月
  • Rumiko Kinoshita, Takashi Mitamura, Fumi Kato, Takahiro Hattori, Hajime Higaki, Shuhei Takahashi, Yoshihiro Fujita, Manami Otsuka, Fuki Koizumi, Yusuke Uchinami, Takashi Mori, Kentaro Nishioka, Takayuki Hashimoto, Yoichi M Ito, Hidemichi Watari, Hidefumi Aoyama
    Journal of radiation research 64 2 463 - 470 2023年01月03日 
    Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.
  • 木下 留美子, 檜垣 朔, 藤田 祥博, 森 崇, 西岡 健太郎, 橋本 孝之, 青山 英史, 押野 智博, 高橋 将人, 加藤 扶美, 金平 孝博
    北海道外科雑誌 67 2 162 - 163 北海道外科学会 2022年12月
  • 【がん免疫療法の展望:免疫チェックポイント阻害薬の併用療法に中心に】免疫チェックポイント阻害薬の併用療法のエビデンス 免疫チェックポイント阻害薬と放射線治療
    安田 耕一, 志藤 元泰, 小泉 富基, 高橋 周平, 藤田 祥博, 大塚 愛美, 宮崎 智彦, 西川 昇, 打浪 雄介, 森 崇, 西岡 健太郎, 木下 留美子, 田口 大志, 加藤 徳雄, 橋本 孝之, 青山 英史
    腫瘍内科 30 1 23 - 28 (有)科学評論社 2022年07月
  • 北海道大学病院放射線治療科関連施設における子宮頸癌に対する根治放射線治療に関するアンケート結果について
    木下 留美子, 打浪 雄介, 高橋 周平, 小泉 富基, 森 崇, 西岡 健太郎, 田口 大志, 橋本 孝之, 高邑 明夫, 西岡 井子, 北原 利博, 土屋 和彦, 井上 哲也, 有本 卓郎, 出倉 康裕, 米坂 祥朗, 鈴木 恵士郎, 川島 和之, 小野寺 俊輔, 喜多村 圭, 長谷川 雅一, 鬼丸 力也, 富田 雅義, 池田 潤, 西山 典明, 青山 英史
    北海道放射線医学雑誌 2 13 - 18 (NPO)メディカルイメージラボ 2022年03月 [査読有り][通常論文]
     
    子宮頸癌に対する根治的放射線治療において子宮内から照射を行う腔内照射は必要不可欠な要素である。腔内照射の設備の維持・更新および子宮頸癌根治照射人数等について北海道大学病院放射線治療科関連病院にアンケートを行った。道内の施設の子宮頸癌根治照射人数は年間10人以下の施設が大半で、腔内照射設備を保有している施設の年間の腔内照射人数は5-9人が4施設、10人以上が2施設であった。腔内照射設備を保有している6施設の内4施設で設備の維持・更新が採算面で難しいという理由で腔内照射の休止を検討している事が明らかとなった。北海道内の子宮頸癌に対する根治照射を継続して行うためには、腔内照射設備を持つ施設への適切な紹介システムの構築と腔内照射が可能な施設の地域性を考慮した適切な集約化が必要と考えられた。(著者抄録)
  • 橋本 孝之, 森 崇, 西岡 健太郎, 打浪 雄介, 安田 耕一, 木下 留美子, 田口 大志, 加藤 徳雄, 清水 伸一, 青山 英史
    日本小児血液・がん学会雑誌 58 2 89 - 93 (一社)日本小児血液・がん学会 2021年08月 
    陽子線治療は通常のX線による放射線治療に比べて線量集中性に優れ,標的への線量を保ったまま周囲の正常組織線量を低減することで,小児がん患者の急性期並びに晩期有害事象の軽減が可能である.2016年4月からは20歳未満の限局性固形悪性腫瘍に対する根治的な陽子線照射が保険適応となり,各施設で小児がんの陽子線治療実施件数が増加傾向にある.局所領域再発に対する再照射は,腫瘍進行抑制・症状緩和と,時に治癒や長期の腫瘍制御による健康状態・QOLの維持をもたらす可能性がある.小児患者に対する再照射における重要臓器・器官の累積耐容線量や安全性は確立していないが,中枢神経腫瘍に対する陽子線再照射により,有害事象の発生を抑えた良好な治療成績が報告されている.今後,小児がん再発の治療選択肢における陽子線再照射の有用性については,前向き臨床試験での評価が必要と考える.(著者抄録)
  • 尿量の経日変化および前立腺体積が放射線治療時の前立腺の位置に与える影響(The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy)
    Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi
    日本医学放射線学会学術集会抄録集 80回 S193 - S194 2021年03月
  • The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy(和訳中)
    Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi
    日本医学放射線学会学術集会抄録集 80回 S193 - S194 2021年03月
  • Kentaro Nishioka, Kento Gotoh, Takayuki Hashimoto, Takashige Abe, Takahiro Osawa, Ryuji Matsumoto, Isao Yokota, Norio Katoh, Rumiko Kinoshita, Koichi Yasuda, Toshiaki Yakabe, Takaaki Yoshimura, Seishin Takao, Nobuo Shinohara, Hidefumi Aoyama, Shinichi Shimizu, Hiroki Shirato
    BJR|Open 3 1 2021年01月 [査読有り][通常論文]
     
    Objectives: The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer. Methods: A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV. Results: The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years. Conclusions: Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated. Advances in knowledge: Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.
  • T. Yoshimura, R. Yamada, R. Kinoshita, H. Tamura, T. Matsuura, S. Takao, M. Tamura, S. Tanaka, N. Nagae, K. Kobashi, H. Aoyama, S. Shimizu
    International Journal of Radiation Oncology*Biology*Physics 108 3 e494 - e494 2020年11月
  • K. Nishioka, Y. Nomura, T. Hashimoto, R. Kinoshita, N. Katoh, H. Taguchi, K. Yasuda, T. Mori, Y. Uchinami, M. Otsuka, T. Matsuura, S. Takao, R. Suzuki, S. Tanaka, T. Yoshimura, H. Aoyama, S. Shimizu
    International Journal of Radiation Oncology*Biology*Physics 108 3 e288 - e289 2020年11月
  • 画像誘導治療の今後について 画像誘導陽子線治療の将来展望
    田口 大志, 橋本 孝之, 加藤 徳雄, 木下 留美子, 安田 耕一, 西岡 健太郎, 森 崇, 打浪 雄介, 宮本 直樹, 高尾 聖心, 清水 伸一, 青山 英史
    日本癌治療学会学術集会抄録集 58回 SY14 - 3 2020年10月
  • Kato F, Kudo K, Yamashita H, Baba M, Shimizu A, Oyama-Manabe N, Kinoshita R, Li R, Shirato H
    Breast cancer (Tokyo, Japan) 26 5 628 - 636 2019年04月 [査読有り][通常論文]
     
    BACKGROUND: We investigated the usefulness of the minimum ADC value of primary breast lesions for predicting axillary lymph node (LN) status in luminal A-like breast cancers with clinically negative nodes in comparison with the mean ADC. METHODS: Forty-four luminal A-like breast cancers without axillary LN metastasis at preoperative clinical evaluation, surgically resected with sentinel LN biopsy, were retrospectively studied. Mean and minimum ADC values of each lesion were measured and statistically compared between LN positive (n = 12) and LN negative (n = 32) groups. An ROC curve was drawn to determine the best cutoff value to differentiate LN status. Correlations between mean and minimum ADC values and the number of metastatic axillary LNs were investigated. RESULTS: Mean and minimum ADC values of breast lesions with positive LN were significantly lower than those with negative LN (mean 839.9 ± 110.9 vs. 1022.2 ± 250.0 × 10- 6 mm2/s, p = 0.027, minimum 696.7 ± 128.0 vs. 925.0 ± 257.6 × 10- 6 mm2/s, p = 0.004). The sensitivity and NPV using the best cutoff value from ROC using both mean and minimum ADC were 100%. AUC of the minimum ADC (0.784) was higher than that of the mean ADC (0.719). Statistically significant negative correlations were observed between both mean and minimum ADCs and number of positive LNs, with stronger correlation to minimum ADC than mean ADC. CONCLUSIONS: The minimum ADC value of primary breast lesions predicts axillary LN metastasis in luminal A-like breast cancer with clinically negative nodes, with high sensitivity and high NPV.
  • Kanae Fukutsu, Satoru Kase, Kan Ishijima, Rumiko Kinoshita, Susumu Ishida
    Radiation Oncology 13 1 1045 - 1047 2018年05月16日 [査読有り][通常論文]
     
    Background: To examine the clinical features of radiation cataract in patients with ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Twenty-one patients with 26 eyes diagnosed with ocular adnexal MALT lymphoma (26 eyes), who were treated in Hokkaido University Hospital, were retrospectively reviewed based on medical records. Results: Out of the 21 patients, 16 patients (21 eyes) received radiation therapy (RT) with a total dose of 30 Gy. All cases eventually achieved complete remission. Eight of these patients (11 eyes: 52.3%) required cataract surgery after RT. The mean age at surgery was 56.8 (40-70) years. The mean latency between RT and the indication for surgery was 43.3 months. The percentage of females was significantly higher in patients who required surgery (P < 0.01), compared with those without surgery. The eyes of patients who received bolus technique on radiation treatment developed cataract more frequently (P < 0.05). In contrast, none of the patients without RT required cataract surgery. Conclusions: Patients with ocular adnexal MALT lymphoma who underwent surgery for radiation cataract were seen more often in relatively young, female patients, and surgery was required about 3 years after RT. A long-term observation may be needed for patients after RT for a tumor. A female sex and the bolus technique may be risk factors for radiation cataract.
  • Kentaro Nishioka, Anussara Prayongrat, Kota Ono, Shunsuke Onodera, Takayuki Hashimoto, Norio Katoh, Tetsuya Inoue, Rumiko Kinoshita, Koichi Yasuda, Takashi Mori, Rikiya Onimaru, Hiroki Shirato, Shinichi Shimizu
    Journal of Radiation Research 59 i63 - i71 2018年03月01日 [査読有り][通常論文]
     
    © The Author(s) 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.
  • Kentaro Nishioka, Shinichi Shimizu, Nobuo Shinohara, Yoichi M. Ito, Takashige Abe, Satoru Maruyama, Norio Katoh, Rumiko Kinoshita, Takayuki Hashimoto, Naoki Miyamoto, Rikiya Onimaru, Hiroki Shirato
    RADIATION ONCOLOGY 12 1 44  2017年03月 [査読有り][通常論文]
     
    Background: Current adaptive and dose escalating radiotherapy for muscle invasive bladder cancer requires knowledge of both inter-fractional and intra-fractional motion of the bladder wall involved. The purpose of this study is to characterize inter-and intra-fractional movement of the partial bladder wall using implanted fiducial markers and a real-time tumor-tracking radiotherapy system. Methods: Two hundred fifty one sessions with 29 patients were analysed. After maximal transurethral bladder tumor resection and 40 Gy of whole bladder irradiation, up to six gold markers were implanted transurethrally into the bladder wall around the tumor bed and used for positional registration. We compared the systematic and random uncertainty of positions between cranial vs. caudal, left vs. right, and anterior vs. posterior tumor groups. The variance in intrafractional movement and the percentage of sessions where 3 mm and 5 mm or more of intrafractional wall movement occurring at 2, 4, 6, 8, 10, and at more than 10 min until the end of a session were determined. Results: The cranial and anterior tumor group showed larger interfractional uncertainties in the position than the opposite side tumor group in the CC and AP directions respectively, but these differences did not reach significance. Among the intrafractional uncertainty of position, the cranial and anterior tumor group showed significantly larger systematic uncertainty of position than the groups on the opposite side in the CC direction. The variance of intrafractional movement increased over time; the percentage of sessions where intrafractional wall movement was larger than 3 mm within 2 min of the start of a radiation session or larger than 5 mm within 10 min was less than 5%, but this percentage was increasing further during the session, especially in the cranial and anterior tumor group. Conclusions: More attention for intrafractional uncertainty of position is required in the treatment of cranial and anterior bladder tumors especially in the CC direction. The optimal internal margins in each direction should be chosen or a precise intrafractional target localization system is required depending on the tumor location and treatment delivery time in the setting of partial bladder radiotherapy.
  • 出倉康裕, 森崇, 西川由記子, 木下留美子, 橋本孝之, 白土博樹, 西岡健太郎, 清水伸一, 細田充主, 山下啓子
    Japanese Journal of Radiology 35 Supplement 4 - 4 (公社)日本医学放射線学会 2017年02月25日 [査読無し][通常論文]
  • 後藤謙斗, 西岡健太郎, 松崎有華, 松浦妙子, 高尾聖心, 橋本孝之, 木下留美子, 西川由記子, 清水伸一, 白土博樹
    日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集 30th 55  2017年 [査読無し][通常論文]
  • Takaaki Yoshimura, Rumiko Kinoshita, Shunsuke Onodera, Chie Toramatsu, Ryusuke Suzuki, Yoichi M. Ito, Seishin Takao, Taeko Matsuura, Yuka Matsuzaki, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu
    PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS 32 9 1095 - 1102 2016年09月 [査読有り][通常論文]
     
    Purpose: This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade >= 3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). Methods and materials: The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. Results: The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 +/- 0.01 and 0.19 +/- 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 +/- 0.01 and 0.96 +/- 0.02, p = 0.3177, and HI = 1.24 +/- 0.11 and 1.27 +/- 0.05, p = 0.8473, respectively). Conclusion: The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
  • 安田耕一, 清水伸一, 橋本孝之, SUTHERLAND Ken, 白土博樹, 土屋和彦, 加藤徳雄, 鬼丸力也, 木下留美子, 井上哲也, 西岡健太郎, 西川由記子, 森崇, 原田慶一, 原田八重, 鈴木隆介, 寅松千枝, 松浦妙子, 高尾聖心, 宮本直樹, 伊藤陽一
    Japanese Journal of Radiology 34 Supplement 5 - 5 (公社)日本医学放射線学会 2016年02月25日 [査読無し][通常論文]
  • T. Yoshimura, R. Kinoshita, S. Onodera, C. Toramatsu, R. Suzuki, Y.M. Ito, S. Takao, T. Matsuura, Y. Matsuzaki, S. Shimizu, K. Umegaki, H. Shirato
    International Journal of Radiation Oncology*Biology*Physics 93 3 E254 - E254 2015年11月
  • S. Shimizu, N. Katoh, S. Takao, T. Matsuura, N. Miyamoto, T. Hashimoto, K. Nishioka, T. Yoshimura, Y. Matsuzaki, R. Kinoshita, Y. Nishikawa, R. Onimaru, K. Umegaki, H. Shirato
    International Journal of Radiation Oncology*Biology*Physics 93 3 S42 - S42 2015年11月
  • Shinichi Shimizu, Kentaro Nishioka, Ryusuke Suzuki, Nobuo Shinohara, Satoru Maruyama, Takashige Abe, Rumiko Kinoshita, Norio Katoh, Rikiya Onimaru, Hiroki Shirato
    RADIATION ONCOLOGY 9 118  2014年05月 [査読有り][通常論文]
     
    Background: We prospectively assessed the utility of intensity-modulated radiation therapy (IMRT) with urethral dose reduction and a small margin between the clinical target volume (CTV) and the planning target volume (PTV) for patients with localized prostate cancer. Methods: The study population was 110 patients in low- (14.5%), intermediate- (41.8%), and high-risk (43.6%) categories. Three gold fiducial markers were inserted into the prostate. A soft guide-wire was used to identify the urethra when computed tomography (CT) scan for treatment planning was performed. A dose constraint of V70 < 10% was applied to the urethral region. Margins between the CTV-PTV were set at 3 mm in all directions. Patients were treated with 70 Gy IMRT in 30 fractions (D95 of PTV) over 7.5 weeks. The patient couch was adjusted to keep the gold markers within 2.0 mm from their planned positions with the use of frequent on-line verification. Results: The median follow-up period was 31.3 (3.2 to 82.1) months. The biochemical relapse-free survival (bRFS) rates at 3 years were 100%, 93.8% and 89.5% for the low-, intermediate-, and high-risk patients, respectively. The incidences of acute adverse events (AEs) were 45.5% and 0.9% for grades 1 and 2, respectively. The late AEs were grade 1 cystitis in 10.0% of the patients, rectal bleeding in 7.3%, and urinary urgency in 6.4%. Only three patients (2.7%) developed grade 2 late AEs. Conclusions: On-line image guidance with precise correction of the table position during radiotherapy achieved one of the lowest AEs rates with a bRFS equal to the highest in the literature.
  • 安田耕一, 土屋和彦, 井上哲也, 西岡健太郎, 原田慶一, 西川由記子, 鬼丸力也, 清水伸一, 加藤徳雄, 木下留美子, 小野寺俊介, 白土博樹, 鈴木隆介, 藤田勝久, 辻真太郎, 山崎理衣
    Jpn J Radiol 32 Supplement 7 - 7 (公社)日本医学放射線学会 2014年02月25日 [査読無し][通常論文]
  • 西川由記子, 原田慶一, 西岡健太郎, 安田耕一, 井上哲也, 土屋和彦, 小野寺俊輔, 木下留美子, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹, 鈴木隆介, 石川正純
    Jpn J Radiol 32 Supplement 5 - 5 (公社)日本医学放射線学会 2014年02月25日 [査読無し][通常論文]
  • Nishioka K, Shimizu S, Shinohara N, Ito Y. M, Abe T, Maruyama S, Kinoshita R, Harada K, Nishikawa N, Miyamoto N, Onimaru R, Shirato H
    Jpn J Clin Oncol 44 1 28 - 35 2014年 [査読有り][通常論文]
  • Kazuhiko Tsuchiya, Rumiko Kinoshita, Shinichi Shimizu, Kentaro Nishioka, Keiichi Harada, Noboru Nishikawa, Ryusuke Suzuki, Hiroki Shirato
    Radiological Physics and Technology 7 1 67 - 72 2014年 [査読有り][通常論文]
     
    We sought to investigate whether intensity-modulated radiotherapy (IMRT) has a dosimetric advantage compared to the standard wedged tangential technique (SWT) for whole-breast radiotherapy (WBRT) in Asian women with relatively small breast volume. Computed tomography images of 25 Asian patients with early-stage breast cancer (right 15, left 10) used for WBRT planning were examined. After contouring the target volumes and bilateral lungs and, for left-side treatment, the heart, 4 plans were made for each patient: namely, SWT, tangential-field IMRT (T-IMRT), 3-field IMRT (3F-IMRT), and 4-field IMRT (4F-IMRT). The prescribed dose was 5000 cGy. The median planning target volume (PTV) for WBRT was 552.6 cc (range 288.8-1518.4 cc). Compared to SWT, (1) T-IMRT achieved significant improvement for dose homogeneity in the PTV (p < 0.001) and the dose received by 2 % (D2) of the PTV (p < 0.001). T-IMRT also reduced the bilateral lung mean dose (p < 0.001) and the ipsilateral lung volume which received more than 20 Gy (V20) (p = 0.01). (2) 3F-IMRT resulted in a significant increase in the mean dose to the ipsilateral lung (p < 0.001) and to the contralateral lung (p < 0.001). (3) 4F-IMRT also resulted in a significant increase in the mean dose to the ipsilateral lung (p < 0.001) and to the contralateral lung (p < 0.001). Tangential-field IMRT provided an improved dose distribution compared with SWT for WBRT in Asian women with a relatively small breast volume. © Japanese Society of Radiological Technology and Japan Society of Medical Physics 2013.
  • Kentaro Nishioka, Shinichi Shimizu, Nobuo Shinohara, Yoichi M. Ito, Takashige Abe, Satoru Maruyama, Rumiko Kinoshita, Keiichi Harada, Noboru Nishikawa, Naoki Miyamoto, Rikiya Onimaru, Hiroki Shirato
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 44 1 28 - 35 2014年01月 [査読有り][通常論文]
     
    The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than 2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65. Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients quality of life.
  • Rumiko Kinoshita, Jin-Min Nam, Yoichi M. Ito, Kanako C. Hatanaka, Ari Hashimoto, Haruka Handa, Yutaro Otsuka, Shigeru Hashimoto, Yasuhito Onodera, Mitsuchika Hosoda, Shunsuke Onodera, Shinichi Shimizu, Shinya Tanaka, Hiroki Shirato, Mishie Tanino, Hisataka Sabe
    PLOS ONE 8 10 e76791  2013年10月 [査読有り][通常論文]
     
    A major problem of current cancer research and therapy is prediction of tumor recurrence after initial treatment, rather than the simple biological characterization of the malignancy and proliferative properties of tumors. Breast conservation therapy (BCT) is a well-approved, standard treatment for patients with early stages of breast cancer, which consists of lumpectomy and whole-breast irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity' have been identified to be well correlated with local recurrence after BCT. An Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and employs AMAP1 as its effector, is crucial for invasion and metastasis of some breast cancer cells. This pathway activates beta 1 integrins and perturbs E-cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal transdifferentiation (EMT). We here show that expression of the Arf6 pathway components statistically correlates with rapid local recurrence after BCT. We retrospectively analyzed four hundred seventy-nine patients who received BCT in Hokkaido University Hospital, and found 20 patients had local recurrence. We then analyzed pathological samples of patients who experienced local recurrence by use of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled with immunostaining, and found that co-overexpression of GEP100 and AMAP1 correlates with rapidity of the local recurrence. Their margin-status, node-positivity, and estrogen receptor (ER)-or progesterone receptor (PgR)positivity did not correlated with the rapidity. This study is the first to show that expression of a certain set of proteins correlates with the rapidity of local recurrence. Our results are useful not only for prediction, but highlight the possibility of developing novel strategies to block local recurrence. We also discuss why mRNAs encoding these proteins have not been identified to correlate with local recurrence by previous conventional gene expression profiling analyses.
  • Jin-Min Nam, Kazi M. Ahmed, Sylvain Costes, Hui Zhang, Yasuhito Onodera, Adam B. Olshen, Kanako C. Hatanaka, Rumiko Kinoshita, Masayori Ishikawa, Hisataka Sabe, Hiroki Shirato, Catherine C. Park
    Breast Cancer Research 15 4 R60  2013年07月25日 [査読有り][通常論文]
     
    Introduction: Ductal carcinoma in situ (DCIS) is characterized by non-invasive cancerous cell growth within the breast ducts. Although radiotherapy is commonly used in the treatment of DCIS, the effect and molecular mechanism of ionizing radiation (IR) on DCIS are not well understood, and invasive recurrence following radiotherapy remains a significant clinical problem. This study investigated the effects of IR on a clinically relevant model of Akt-driven DCIS and identified possible molecular mechanisms underlying invasive progression in surviving cells.Methods: We measured the level of phosphorylated-Akt (p-Akt) in a cohort of human DCIS specimens by immunohistochemistry (IHC) and correlated it with recurrence risk. To model human DCIS, we used Akt overexpressing human mammary epithelial cells (MCF10A-Akt) which, in three-dimensional laminin-rich extracellular matrix (lrECM) and in vivo, form organotypic DCIS-like lesions with lumina expanded by pleiomorphic cells contained within an intact basement membrane. In a population of cells that survived significant IR doses in three-dimensional lrECM, a malignant phenotype emerged creating a model for invasive recurrence.Results: P-Akt was up-regulated in clinical DCIS specimens and was associated with recurrent disease. MCF10A-Akt cells that formed DCIS-like structures in three-dimensional lrECM showed significant apoptosis after IR, preferentially in the luminal compartment. Strikingly, when cells that survived IR were repropagated in three-dimensional lrECM, a malignant phenotype emerged, characterized by invasive activity, up-regulation of fibronectin, α5β1-integrin, matrix metalloproteinase-9 (MMP-9) and loss of E-cadherin. In addition, IR induced nuclear translocation and binding of nuclear factor-kappa B (NF-κB) to the β1-integrin promoter region, associated with up-regulation of α5β1-integrins. Inhibition of NF-κB or β1-integrin signaling abrogated emergence of the invasive activity.Conclusions: P-Akt is up-regulated in some human DCIS lesions and is possibly associated with recurrence. MCF10A-Akt cells form organotypic DCIS-like lesions in three-dimensional lrECM and in vivo, and are a plausible model for some forms of human DCIS. A population of Akt-driven DCIS-like spheroids that survive IR progresses to an invasive phenotype in three-dimensional lrECM mediated by β1-integrin and NF-κB signaling. © 2013 Nam et al. licensee BioMed Central Ltd.
  • Taeko Matsuura, Naoki Miyamoto, Shinichi Shimizu, Yusuke Fujii, Masumi Umezawa, Seishin Takao, Hideaki Nihongi, Chie Toramatsu, Kenneth Sutherland, Ryusuke Suzuki, Masayori Ishikawa, Rumiko Kinoshita, Kenichiro Maeda, Kikuo Umegaki, Hiroki Shirato
    MEDICAL PHYSICS 40 7 071729  2013年07月 [査読有り][通常論文]
     
    Purpose: In spot-scanning proton therapy, the interplay effect between tumor motion and beam delivery leads to deterioration of the dose distribution. To mitigate the impact of tumor motion, gating in combination with repainting is one of the most promising methods that have been proposed. This study focused on a synchrotron-based spot-scanning proton therapy system integrated with real-time tumor monitoring. The authors investigated the effectiveness of gating in terms of both the delivered dose distribution and irradiation time by conducting simulations with patients' motion data. The clinically acceptable range of adjustable irradiation control parameters was explored. Also, the relation between the dose error and the characteristics of tumor motion was investigated. Methods: A simulation study was performed using a water phantom. A gated proton beam was irradiated to a clinical target volume (CTV) of 5 x 5 x 5 cm(3), in synchronization with lung cancer patients' tumor trajectory data. With varying parameters of gate width, spot spacing, and delivered dose per spot at one time, both dose uniformity and irradiation time were calculated for 397 tumor trajectory data from 78 patients. In addition, the authors placed an energy absorber upstream of the phantom and varied the thickness to examine the effect of changing the size of the Bragg peak and the number of required energy layers. The parameters with which 95% of the tumor trajectory data fulfill our defined criteria were accepted. Next, correlation coefficients were calculated between the maximum dose error and the tumor motion characteristics that were extracted from the tumor trajectory data. Results: With the assumed CTV, the largest percentage of the data fulfilled the criteria when the gate width was +/- 2 mm. Larger spot spacing was preferred because it increased the number of paintings. With a prescribed dose of 2 Gy, it was difficult to fulfill the criteria for the target with a very small effective depth (the sum of an assumed energy absorber's thickness and the target depth in the phantom) because of the sharpness of the Bragg peak. However, even shallow targets could be successfully irradiated by employing an adequate number of paintings and by placing an energy absorber of sufficient thickness to make the effective target depth more than 12 cm. The authors also observed that motion in the beam direction was the main cause of dose distortion, followed by motion in the lateral plane perpendicular to the scan direction. Conclusions: The results suggested that by properly adjusting irradiation control parameters, gated proton spot-scanning beam therapy can be robust to target motion. This is an important first step toward establishing treatment plans in real patient geometry. (C) 2013 American Association of Physicists in Medicine.
  • Kentaro Nishioka, Shinichi Shimizu, Rumiko Kinoshita, Tetsuya Inoue, Shunsuke Onodera, Koichi Yasuda, Keiichi Harada, Yukiko Nishikawa, Rikiya Onimaru, Hiroki Shirato
    RADIATION ONCOLOGY 8 185  2013年07月 [査読有り][通常論文]
     
    Background: In-room cone-beam computerized tomography (CBCT) imaging is a promising method to reduce setup errors, especially in organs such as the bladder that often have large intrafractional variations due to organ movement. CBCT image quality is limited by low contrast and imaging artifacts, but few data have been reported about inter-observer variability of bladder boundary delineation on CBCT. The aim of this work was to analyze and evaluate the inter-observer contouring uncertainties of bladder boundary delineation on CBCT images in a prospective fashion. Methods: Five radiation oncologists contoured 10 bladders using the CBCT datasets of consecutive 10 patients (including 4 females) who were irradiated to the pelvic region. Prostates were also contoured in male patients. Patients who had had prostatectomy were excluded. The coefficient of variation (COV), conformity index (CIgen), and coordinates of center-of-mass (COM) of the bladder and prostate were calculated for each patient. Results: The mean COV for the bladder and prostate was 0.08 and 0.20, respectively. The mean CIgen of the bladder and prostate was 0.81 and 0.66, respectively. The root mean square (RMS) of the inter-observer standard deviation (s) of the COM displacement in the left-right (LR) and anterior-posterior (AP) direction was 0.79, 0.87 and 0.54 for the bladder and 0.63, 0.99 and 1.72 for the prostate. Regarding the mean COV and CIgen for the bladder, the differences between males and females were not significant. Conclusions: Inter-observer variability for bladder delineation on CBCT images was substantially small regardless of gender. We believe that our results support the applicability of CBCT in adaptive radiotherapy for bladder cancer.
  • Hideomi Yamashita, Yuzuru Niibe, Takafumi Toita, Tomoko Kazumoto, Tetsuo Nishimura, Takeshi Kodaira, Hidehiro Eto, Rumiko Kinoshita, Kayoko Tsujino, Hiroshi Onishi, Mitsuhiro Takemoto, Kazushige Hayakawa
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 43 5 547 - 552 2013年05月 [査読有り][通常論文]
     
    The current study was designed to evaluate the clinical outcomes of curative intent radiation therapy for young patients with invasive uterine cervical carcinoma in Japan.One hundred and eighteen patients aged 40 were registered in the multi-institutional study of the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) from 26 major institutions in Japan. The age range was 2439 years and the maximum tumor diameter was 2.09.2 cm. The International Federation of Gynecology and Obstetrics clinical stages were Ib, IIa, IIb, IIIa, IIIb and IVa in 17, 6, 40, 2, 50 and 3, respectively. Curative intent radiation therapy consisted of the combination of external beam radiation therapy and high-dose rate intra-cavitary brachytherapy. The total dose of external beam radiation therapy ranged between 44 and 68 Gy. Both the median and mode of total high-dose-rate intra-cavitary brachytherapy dose to point A were 24 Gy in four fractions. Ninety-six patients (58) received chemotherapy.The 5-year overall survival rate and local control rate of all patients were 61 and 65, respectively. The 5-year overall survival rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 88, 100, 75, 100, 37 and 0, respectively. The 5-year local control rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 82, 75, 75, 100, 51 and 0, respectively. Sixteen patients experienced grade 3 or greater late radiation morbidity.The 5-year overall survival rate of young patients with Stage IIIb was comparatively low at 37.
  • Chie Toramatsu, Norio Katoh, Shinichi Shimizu, Hideaki Nihongi, Taeko Matsuura, Seishin Takao, Naoki Miyamoto, Ryusuke Suzuki, Kenneth Sutherland, Rumiko Kinoshita, Rikiya Onimaru, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato
    RADIATION ONCOLOGY 8 48  2013年03月 [査読有り][通常論文]
     
    Background: We performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD). Methods: A number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm(3). Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model. Results: For IMRT the risk of RILD increased drastically between 6.3-7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT. Conclusions: Regarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm.
  • 西岡健太郎, 清水伸一, 安部崇重, 丸山覚, 鬼丸力也, 木下留美子, 小野寺俊輔, 原田慶一, 篠原信雄, 白土博樹
    日本医学放射線学会総会抄録集 72nd S397 - S397 (公社)日本医学放射線学会 2013年02月28日 [査読無し][通常論文]
  • 土屋和彦, 原田慶一, 西岡健太郎, 木下留美子, 清水伸一, 白土博樹
    Jpn J Radiol 31 Supplement 1 11  2013年02月25日 [査読無し][通常論文]
  • Jin-Min Nam, Kazi M. Ahmed, Sylvain Costes, Hui Zhang, Yasuhito Onodera, Adam B. Olshen, Kanako C. Hatanaka, Rumiko Kinoshita, Masayori Ishikawa, Hisataka Sabe, Hiroki Shirato, Catherine C. Park
    BREAST CANCER RESEARCH 15 4 2013年 [査読有り][通常論文]
     
    Introduction: Ductal carcinoma in situ (DCIS) is characterized by non-invasive cancerous cell growth within the breast ducts. Although radiotherapy is commonly used in the treatment of DCIS, the effect and molecular mechanism of ionizing radiation (IR) on DCIS are not well understood, and invasive recurrence following radiotherapy remains a significant clinical problem. This study investigated the effects of IR on a clinically relevant model of Akt-driven DCIS and identified possible molecular mechanisms underlying invasive progression in surviving cells. Methods: We measured the level of phosphorylated-Akt (p-Akt) in a cohort of human DCIS specimens by immunohistochemistry (IHC) and correlated it with recurrence risk. To model human DCIS, we used Akt overexpressing human mammary epithelial cells (MCF10A-Akt) which, in three-dimensional laminin-rich extracellular matrix (lrECM) and in vivo, form organotypic DCIS-like lesions with lumina expanded by pleiomorphic cells contained within an intact basement membrane. In a population of cells that survived significant IR doses in three-dimensional lrECM, a malignant phenotype emerged creating a model for invasive recurrence. Results: P-Akt was up-regulated in clinical DCIS specimens and was associated with recurrent disease. MCF10A-Akt cells that formed DCIS-like structures in three-dimensional lrECM showed significant apoptosis after IR, preferentially in the luminal compartment. Strikingly, when cells that survived IR were repropagated in three-dimensional lrECM, a malignant phenotype emerged, characterized by invasive activity, up-regulation of fibronectin, alpha 5 beta 1-integrin, matrix metalloproteinase-9 (MMP-9) and loss of E-cadherin. In addition, IR induced nuclear translocation and binding of nuclear factor-kappa B (NF-kappa B) to the beta 1-integrin promoter region, associated with up-regulation of alpha 5 beta 1-integrins. Inhibition of NF-kappa B or beta 1-integrin signaling abrogated emergence of the invasive activity. Conclusions: P-Akt is up-regulated in some human DCIS lesions and is possibly associated with recurrence. MCF10A-Akt cells form organotypic DCIS-like lesions in three-dimensional lrECM and in vivo, and are a plausible model for some forms of human DCIS. A population of Akt-driven DCIS-like spheroids that survive IR progresses to an invasive phenotype in three-dimensional lrECM mediated by beta 1-integrin and NF-kappa B signaling.
  • Nishioka K, Shimizu S, Onimaru R, Kinoshita R, Kato N, Harada K, Abe T, Maruyama S, Shinohara N, Shirato H
    International Journal of Radiation Oncology Biology Physics 87 2 S397  2013年 [査読有り][通常論文]
  • 高尾聖心, 松浦妙子, 寅松千枝, 二本木英明, 宮本直樹, 清水伸一, 木下留美子, 松田浩二, 木谷貴雄, 梅垣菊男, 白土博樹
    医学物理 Supplement 32 3 169 - 170 2012年09月13日 [査読無し][通常論文]
  • リンフォーマの画像診断と新規治療のプラクティス 皮膚悪性リンパ腫に対する放射線治療
    鬼丸 力也, 清水 伸一, 土屋 和彦, 加藤 徳雄, 木下 留美子, 井上 哲也, 小野寺 俊輔, 安田 耕一, 西岡 健太郎, 白土 博樹
    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 28回 82 - 82 日本皮膚悪性腫瘍学会 2012年06月 [査読無し][通常論文]
  • Takuro Ariga, Yuzuru Niibe, Takafumi Toita, Tomoko Kazumoto, Hidehiro Eto, Osamu Suzuki, Rumiko Kinoshita, Kayoko Tsujino, Mitsuhiro Takemoto, Takeshi Kodaira, Hideomi Yamashita, Kazushige Hayakawa
    JOURNAL OF CLINICAL ONCOLOGY 30 15 2012年05月 [査読有り][通常論文]
  • 二本木英明, 寅松千枝, 松浦妙子, 高尾聖心, 宮本直樹, 梅垣菊男, 清水伸一, 木下留美子, 白土博樹
    医学物理 Supplement 32 1 190  2012年04月01日 [査読無し][通常論文]
  • Hidemichi Watari, Rumiko Kinoshita, Yimin Han, Lei Wang, Masayoshi Hosaka, Hiroshi Taguchi, Kazuhiko Tsuchiya, Shinya Tanaka, Hiroki Shirato, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 22 3 465 - 470 2012年03月 [査読有り][通常論文]
     
    Objective: Overexpression of clusterin (CLU), an antiapoptotic molecule, has been reported to induce resistance to radiotherapy (RT) in a variety of cancer cell types. The aim of this study was to evaluate the significance of CLU expression to predict survival of patients with advanced-stage cervical cancer who received curative intended RT. Methods: Biopsy tissue specimens of advanced-stage cervical cancer before curative intended RT were obtained from 34 patients who were treated at Hokkaido University Hospital between 1998 and 2008 and whose complete medical records were available. The expression of CLU protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed using the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Results: Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of CLU protein in cervical cancer tissues before curative intended RT was not significantly related to any clinicopathological factors analyzed, including age, clinical stage, histologic type, and response to RT. Univariate analysis on prognostic factors showed that histologic type (P = 0.001), and CLU expression (P = 0.02) were related to survival. Multivariate analysis revealed that both histologic type (P = 0.002), and CLU expression (P = 0.02) were independent prognostic factors for overall survival. Conclusion: We conclude that CLU could be a new molecular marker to predict overall survival of patients with advanced-stage cervical cancer treated with curative intended RT.
  • 原田慶一, 木下留美子, 加藤徳雄, 西岡健太郎, 清水伸一, 鬼丸力也, 白土博樹
    日本医学放射線学会総会抄録集 71st S375  2012年02月29日 [査読無し][通常論文]
  • 木下留美子, 清水伸一, 西岡健太郎, 原田慶一, 小野寺俊輔, 田口大志, 細田充主, 田口和典, 高橋弘昌, 白土博樹
    日本医学放射線学会総会抄録集 71st S318  2012年02月29日 [査読無し][通常論文]
  • Miyamoto Naoki, Sutherland Kenneth, Suzuki Ryusuke, Matsuura Taeko, Toramatsu Chie, Takao Seishin, Nihongi Hideaki, Kinoshita Rumiko, Shimizu Shinichi, Onimaru Rikiya, Umegaki Kikuo, Shirato Hiroki, Ishikawa Masayori
    MEDICAL IMAGING 2012: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING 8316 83160  2012年 [査読有り][通常論文]
  • Toramatsu C, Katoh N, Shimizu S, Nihongi H, Matsuura T, Takao S, Miyamoto N, Kinoshita R, Umegaki K, Shirato H
    International Journal of Radiation Oncology Biology Physics 84 3 S327 - S328 2012年 [査読有り][通常論文]
  • Nishioka K, Shimizu S, Onimaru R, Kinoshita R, Harada K, Nishikawa N, Abe T, Maruyama S, Shinohara N, Shirato H
    International Journal of Radiation Oncology Biology Physics 84 3 S769  2012年 [査読有り][通常論文]
  • Toramatsu C, Matsuura T, Nihongi H, Takao S, Miyamoto N, Shimizu S, Kinoshita R, Umegaki K, Shirato H
    Medical Physics 39 6 3821 - 3822 2012年 [査読有り][通常論文]
  • 木下留美子, 清水伸一, 土屋和彦, 加藤徳雄, 田口大志, 高橋將人, 高橋弘昌, 白土博樹
    臨床放射線 56 13 1813 - 1818 2011年12月10日 [査読無し][通常論文]
  • 土屋和彦, 木下留美子, 清水伸一, 森崇, 原田慶一, 白土博樹
    日本医学放射線学会総会抄録集 70th S371  2011年02月28日 [査読無し][通常論文]
  • 木下留美子, 清水伸一, 土屋和彦, 加藤徳雄, 田口大志, 高橋将人, 高橋弘昌, 白土博樹
    日本医学放射線学会秋季臨床大会抄録集 46th S506  2010年08月25日 [査読無し][通常論文]
  • 香泉和寿, 安田耕一, 長谷川雅一, 鬼丸力也, 清水伸一, 木下留美子, 井上哲也, 加藤徳雄, 小野寺俊輔, 田口大志, 溝口史樹, 青山英史, 白土博樹, 西岡健, 武島嗣英
    Jpn J Radiol 28 Supplement 1 7 - 7 (公社)日本医学放射線学会 2010年07月25日 [査読無し][通常論文]
  • 安田耕一, 長谷川雅一, 鬼丸力也, 木下留美子, 加藤徳雄, 田口大志, 清水伸一, 井上哲也, 小野寺俊輔, 溝口史樹, 青山英史, 白土博樹, 志賀哲, 岡本祥三, 玉木長良, 石川正純, SUTHERLAND Kenneth, BENGUA Gerard, 宮本直樹, 鈴木隆介
    Jpn J Radiol 28 Supplement 1 14 - 14 (公社)日本医学放射線学会 2010年07月25日 [査読無し][通常論文]
  • 田口大志, 清水伸一, 木下留美子, 白土博樹, 高橋弘昌, 高橋將人, 細田充主, 藤堂省
    北海道外科雑誌 54 2 188  2009年12月20日 [査読無し][通常論文]
  • 鬼丸力也, 木下留美子, 長谷川雅一, 安田耕一, 白土博樹
    ENTONI 103 14 - 20 (株)全日本病院出版会 2009年06月15日 [査読無し][通常論文]
     
    頭頸部癌に対する放射線治療は形態・機能温存を目的とした治療であるが、晩期反応に苦しむ患者さんも多かった。従来の放射線治療の欠点を解消すべく発展してきた強度変調放射線治療(intensity modulated radiotherapy;IMRT)は腫瘍には十分な線量を、リスク臓器には少ない線量を照射することを可能にした。IMRTを行う際には、CTで標的体積を設定する必要があるが、その際には正確な病期診断が必要である。また、治療計画の最適化や検証などの作業が必要であり、人手と時間を要する治療である。IMRTにより視神経などのリスク臓器のそばまで浸潤した腫瘍を従来の放射線治療よりも合併症を少なく治療できると期待されている一方、リスク臓器と指定しなかった臓器には高線量が照射される可能性があり注意が必要である。(著者抄録)
  • 鬼丸 力也, 長谷川 雅一, 安田 耕一, 木下 留美子, 白土 博樹, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部癌 = Head and neck cancer 35 3 245 - 249 2009年 [査読無し][通常論文]
     
    We evaluated the clinical outcome of 37 patients who had received intensity modulated radiation therapy (IMRT) in Hokkaido University Hospital from May 2002 to December 2007. Thirteen patients had nasopharyngeal cancer, 19 had oropharyngeal cancer, 3 had hypopharyngeal cancer, 1 had maxillary sinus cancer, and 1 had oral cancer. One patient who had oropharyngeal cancer died of pharyngeal abscess which was a treatment-related complication. Three patients died of other cancers. One patient with nasopharyngeal cancer had local recurrence. In patients with oropharyngeal cancer, recurrence at the primary site occurred in 3 patients, and residual/recurrence at neck lymph nodes occurred in 2 patients. One patient with hypopharyngeal cancer had residual neck lymph node metastasis. Some patients experienced severe reactions to the radiation. One patient had pharyngeal abscess and died of this treatment complication. One patient who had nasopharyngeal cancer experienced hearing loss and angle closure glaucoma. © 2009, Japan Society for Head and Neck Cancer. All rights reserved.
  • 白土博樹, 鬼丸力也, BENGUA Gerard, 石川正純, 井上哲也, 清水伸一, 木下留美子, 青山英史
    定位放射線治療による予後改善に関する研究 平成20年度 総括研究報告書 12-13  2009年 [査読無し][通常論文]
  • 小野寺俊輔, 白土博樹, 青山英史, 田口大志, 加藤徳雄, 木下留美子, 鬼丸力也, 清水伸一, 井上哲也, 安田耕一
    日本医学放射線学会秋季臨床大会抄録集 44th S521 - S521 (公社)日本医学放射線学会 2008年09月24日 [査読無し][通常論文]
  • 鬼丸力也, 加藤徳雄, 井上哲也, 田口大志, 清水伸一, 長谷川雅一, 安田耕一, 小野寺俊輔, 木下留美子, 青山英史, 白土博樹
    日本放射線腫よう学会誌 20 Supplement 1 128  2008年09月22日 [査読無し][通常論文]
  • 清水伸一, 大坂康博, 鬼丸力也, 長谷川雅一, 田口大志, 加藤徳雄, 木下留美子, 青山英史, 白土博樹
    日本放射線腫よう学会誌 20 Supplement 1 143  2008年09月22日 [査読無し][通常論文]
  • 木下留美子, 田口大志, 加藤徳雄, 清水伸一, 溝口史樹, 米坂祥朗, 北原利博, 白土博樹
    日本放射線腫よう学会誌 20 Supplement 1 146  2008年09月22日 [査読無し][通常論文]
  • 木下留美子, 小野寺祐也, 白土博樹, 清水伸一, 鬼丸力也, 青山英史
    画像診断 28 6 560 - 566 (株)学研メディカル秀潤社 2008年04月25日 [査読無し][通常論文]
  • 遠藤将吾, 飛騨一利, 矢野俊介, 伊東雅基, 山口秀, 柏崎大奈, 木下留美子, 白土博樹, 岩崎喜信
    Neurol Surg 36 4 345 - 349 2008年04月 [査読無し][通常論文]
     
    Objectives Intramedurally spinal cord metastasis (ISCM) tends to be seen in the end period of the malignant tumor, so it is important to choose a therapeutic method regarding the QOL (quality of life) of the patient. In this study, we reported three cases of ISCM treated by radiation therapy alone, and demonstrated the utility of this therapeutic procedure. Patients and Methods From 2005 to 2006, 3 cases of ISCM underwent radiotherapy in our institution. The mean age of the patients was 64.0 years old, and all patients were men, having lung carcinoma as their primary lesions. The lesions were located at the cervical cord in one case and the conus medullaris in the other two cases. They were treated by radiotherapy at the department of radiology in our institute. Results The tumor size and intramedullary high signal area on MR images after the radiotherapy were reduced in all patients. During the clinical course, neurological symptoms were improved in two patients, and progression of the symptoms was stopped in one patient. All of the patients obtained a better ADL due to the radiotherapy. Conclusions Radiotherapy has an advantage over surgical treatment in that it involves less invasion. The treatment brought improvements of clinical symptoms and radiological findings in the patients with ISCM. So, radiotherapy could be used as one of the major treatments for patients with ISCM who desire a better QOL after treatment.
  • 下咽頭癌における(化学)放射線療法後の救済手術の治療成績
    瀧 重成, 本間 明宏, 古田 康, 折舘 伸彦, 鈴木 章之, 古沢 純, 坂下 智博, 木下 留美子, 白戸 博樹, 福田 諭
    頭頸部癌 33 2 163 - 163 (一社)日本頭頸部癌学会 2007年05月 [査読無し][通常論文]
  • 小野寺俊輔, 木下留美子, 藤野賢治, 加藤徳雄, 田口大志, 鬼丸力也, 大阪康博, 清水伸一, 鈴木恵士郎, 西岡健, 白土博樹
    Radiat Med 25 15  2007年04月25日 [査読無し][通常論文]
  • 木下留美子, 清水伸一, 加藤徳雄, 藤野賢治, 鬼丸力也, 白土博樹
    日本医学放射線学会学術集会抄録集 66th S212  2007年02月28日 [査読無し][通常論文]
  • 木下留美子, 土屋和彦, 大森桂一, 小日向謙一, 藤田勝久, 青山英史, 笈田将皇, 西岡健, 鈴木恵士郎, 白土博樹
    日本放射線腫瘍学会誌 18 4 191 - 197 一般社団法人 日本放射線腫瘍学会 2006年12月 [査読無し][通常論文]
     
    【背景】強度変調放射線治療（IMRT）は標的体積の三次元形状に合わせて線量集中度を高めることが可能である．頭頸部領域においては耳下腺線量低減を主目的としてIMRTが行われている．一般的にIMRTでは治療時間が長いこと，および線量勾配が照射野内に存在することより，従来の放射線治療と比較し，より精度の高いセットアップが必要とされる．
    【目的】われわれの施設で開発した動体追跡放射線治療装置の 2 方向Ｘ線透視を頭頸部癌に対するIMRTのセットアップに用い，その安全性を検証する．
    【対象・方法】2002年 5 月から2004年10月まで当院でIMRTを施行した 9 例．PTV-marginは 3 mmで治療を行った．口腔内乾燥症はVAS（visual analogue scale）を用い自覚症状で評価した．
  • Oita M, Ohmori K, Obinata K, Kinoshita R, Onimaru R, Tsuchiya K, Suzuki K, Nishioka T, Ohsaka H, Fujita K, Shimamura T, Shirato H, Miyasaka K
    International journal of radiation oncology, biology, physics 64 5 1581 - 1588 5 2006年04月 [査読有り][通常論文]
  • Shirato H, Suzuki K, Sharp GC, Fujita K, Onimaru R, Fujino M, Kato N, Osaka Y, Kinoshita R, Taguchi H, Onodera S, Miyasaka K
    International journal of radiation oncology, biology, physics 64 4 1229 - 1236 4 2006年03月 [査読有り][通常論文]
     
    BACKGROUND: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. METHODS AND MATERIALS: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. RESULTS: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. CONCLUSION: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology.
  • Kinoshita R, Shimizu S, Katoh N, Onimaru R, Shirato H, Miyasaka
    International Journal of Radiation Oncology Biology Physics 66 3 S608  2006年 [査読有り][通常論文]

MISC

  • 安田 耕一, 志藤 元泰, 小泉 富基, 高橋 周平, 藤田 祥博, 大塚 愛美, 宮﨑 智彦, 西川 昇, 打浪 雄介, 森 崇, 西岡 健太郎, 木下 留美子, 田口 大志, 加藤 徳雄, 橋本 孝之, 青山 英史 腫瘍内科 = Clinical oncology / 腫瘍内科編集委員会 編 30 (1) 23 -28 2022年07月
  • 橋本孝之, 森崇, 西岡健太郎, 打浪雄介, 安田耕一, 木下留美子, 田口大志, 加藤徳雄, 清水伸一, 青山英史 日本小児血液・がん学会雑誌(Web) 58 (2) 2021年
  • 田口大志, 橋本孝之, 橋本孝之, 加藤徳雄, 木下留美子, 安田耕一, 西岡健太郎, 西岡健太郎, 森崇, 打浪雄介, 宮本直樹, 高尾聖心, 清水伸一, 清水伸一, 青山英史 日本癌治療学会学術集会(Web) 58th 2020年
  • 乳癌眼窩尖部転移により視力低下をきたし、放射線治療により著明な改善を認めた1例
    湊川 英樹, 安田 耕一, 打浪 雄介, 白土 博樹, 土屋 和彦, 加藤 徳雄, 木下 留美子, 石田 直子, 山下 啓子, 石嶋 漢 Japanese Journal of Radiology 36 (Suppl.) 11 -11 2018年02月 [査読無し][通常論文]
  • 木下留美子, 長江伸樹, 西岡健太郎, 橋本孝之, 清水伸一, 白土博樹, 加藤扶美, 石田直子, 山下啓子, 清水薫子, 鈴木雅, 今野哲 北海道外科雑誌 63 (2) 2018年
  • 安田耕一, 加藤徳雄, 岡本祥三, 木下留美子, 志賀哲, 水町貴諭, 畠山博充, 本間明宏, 田口純, 清水康, 森崇, 土屋和彦, 白土博樹 頭けい部癌 43 (2) 221 -221 2017年05月10日 [査読無し][通常論文]
  • 長江伸樹, 森崇, 木下留美子, 鬼丸力也, 白土博樹, 西村真智子, 畑中佳奈子, 木村鉄宣 Japanese Journal of Radiology 35 (Supplement) 4 2017年02月25日 [査読無し][通常論文]
  • R. Kinoshita, S. Shimizu, Y. Nishikawa, K. Nishioka, T. Hashimoto, R. Suzuki, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 96 (2) E17 -E18 2016年10月 [査読無し][通常論文]
  • YOSHIMURA Takaaki, ONODERA Shunsuke, TORAMATSU Chie, KINOSHITA Rumiko, SHIMIZU Shinichi, UMEGAKI Kikuo, SHIRATO Hiroki 医学物理 Supplement 34 (1) 143 2014年04月01日 [査読無し][通常論文]
  • 吉村 高明, 安田 耕一, 寅松 千枝, 高尾 聖心, 松浦 妙子, 二本木 英明, 木下 留美子, 鬼丸 力也, 白土 博樹, 石川 正純 Japanese Journal of Radiology 32 (Suppl.) 7 -7 2014年02月 [査読無し][通常論文]
  • 土屋和彦, 安田耕一, 木下留美子, 鬼丸力也, 白土博樹, 本間明宏, 福田諭, 清水康, 秋田弘俊 頭けい部癌 39 (2) 218 -218 2013年05月21日 [査読無し][通常論文]
  • 土屋 和彦, 安田 耕一, 西川 由記子, 木下 留美子, 鬼丸 力也, 原田 慶一, 井上 哲也, 加藤 徳雄, 清水 伸一, 白土 博樹, 西岡 健, 鈴木 恵士郎, 田口 大志, 長谷川 雅一, 折舘 伸彦, 本間 明宏, 鈴木 清護, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 福田 諭, 竹内 啓, 田口 純 耳鼻咽喉科展望 56 (補冊2) 174 -175 2013年05月 [査読無し][通常論文]
  • K. Tsuchiya, K. Yasuda, Y. Nishikawa, R. Kinoshita, R. Onimaru, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 84 (3) S484 -S485 2012年11月 [査読無し][通常論文]
  • S. Shimizu, K. Nishioka, R. Onimaru, R. Kinoshita, K. Harada, N. Nishikawa, T. Abe, S. Maruyama, N. Shinohara, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 84 (3) S181 -S181 2012年11月 [査読無し][通常論文]
  • R. Kinoshita, J. Nam, M. Hosoda, C. Kubota K, M. Tanino, A. Hashimoto, Y. M. Ito, S. Tanaka, H. Sabe, H. Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 84 (3) S227 -S228 2012年11月 [査読無し][通常論文]
  • Naoki Miyamoto, Kenneth Sutherland, Ryusuke Suzuki, Taeko Matsuura, Chie Toramatsu, Seishin Takao, Hideaki Nihongi, Rumiko Kinoshita, Shinichi Shimizu, Rikiya Onimaru, Kikuo Umegaki, Hiroki Shirato, Masayori Ishikawa Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8316 2012年05月01日 [査読無し][通常論文]
     
    In the real-time tumor-tracking radiotherapy (RTRT) system, the fiducial markers are inserted in or near the target tumor in order monitor the respiratory-induced motion of tumors. During radiation treatment, the markers are detected by continuous fluoroscopy operated at 30 frames/sec. The marker position is determined by means of a template pattern matching technique which is based on the normalized cross correlation. With high tube voltage, large current and long exposure, the fiducial marker will be recognized accurately, however, the radiation dose due to X-ray fluoroscopy increases. On the other hand, by decreasing the fluoroscopy parameter settings, the fiducial marker could be lost because the effect of statistical noise is increased. In the respiratory-gated radiotherapy, the error of the image guidance will induce the reduction of the irradiation efficiency and accuracy. In order to track the marker stably and accurately in low dose fluoroscopy, we propose the application of a recursive filter. The effectiveness of the image processing is investigated by tracking the static marker and the dynamic marker. The results suggest that the stability and the accuracy of the marker tracking can be improved by applying the recursive image filter in low dose imaging. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).
  • 橋本あり, 橋本茂, 吉河歩, 杉野弘和, 半田悠, 木下留美子, 畑中佳奈子, 三上修治, 谷野美智枝, 味藤静, 佐藤宏紀, 大塚勇太郎, 芳野日南子, 加戸由加里, NAM Jin‐Min, 小野寺康仁, 田中伸哉, 白土博樹, 佐邊壽孝 日本分子生物学会年会プログラム・要旨集(Web) 35th 2W10II-1 (WEB ONLY) 2012年 [査読無し][通常論文]
  • TGFβ1はGEP100-Arf6-AMAP1経路の活性化によりEMTを誘導し、この活性化は癌幹細胞性と関連する(TGFβ1 activates GEP100-Arf6-AMAP1 pathway to induce EMT, and possible relationship of this activation to cancer stemness)
    橋本 あり, 平野 真理子, 谷野 美智枝, 梅本 勉, 小野寺 康仁, 佐藤 宏紀, 木下 留美子, 南 ジンミン, 大塚 勇太郎, 福田 諭, 白土 博樹, 相沢 慎一, 橋本 茂, 田中 伸哉, 佐邊 壽孝 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 83回・33回 2P -0237 2010年12月 [査読無し][通常論文]
  • 若年者子宮頸癌の放射線治療成績 日本放射線腫瘍学会研究課題全国調査
    新部 譲, 戸板 孝文, 楮本 智子, 西村 哲夫, 古平 毅, 江藤 英博, 鈴木 修, 木下 留美子, 山下 英臣, 辻野 佳世子, 大西 洋, 兼安 祐子, 武本 充広, 山内 智香子, 早川 和重 日本婦人科腫瘍学会雑誌 27 (3) 277 -277 2009年06月 [査読無し][通常論文]
  • 木下留美子, 長谷川雅一, 安田耕一, 田口大志, 鬼丸力也, 土屋和彦, 西岡健, 本間明宏, 折館伸彦, 福田諭, 白土博樹 頭けい部癌 35 (2) 93 -93 2009年05月20日 [査読無し][通常論文]
  • 強度変調放射線治療(IMRT)の中長期成績 北海道大学病院での頭頸部癌に対する強度変調放射線治療の成績
    鬼丸 力也, 長谷川 雅一, 安田 耕一, 木下 留美子, 白土 博樹, 本間 明宏, 折舘 伸彦, 福田 諭 頭頸部癌 35 (2) 65 -65 2009年05月 [査読無し][通常論文]
  • 藤野賢治, 田口大志, 加藤徳雄, 木下留美子, 鬼丸力也, 長谷川雅一, 溝口史樹, 青山英史, 白土博樹, 志賀哲, 玉木長良, 加藤千恵次, 梶智人 Radiat Med 27 (Supplement 1) 6 2009年04月25日 [査読無し][通常論文]
  • 放射線治療におけるFDG-PETでのSUVと正確な標的体積設定への影響因子
    藤野 賢治, 田口 大志, 加藤 徳雄, 木下 留美子, 鬼丸 力也, 長谷川 雅一, 溝口 史樹, 青山 英史, 白土 博樹, 志賀 哲, 玉木 長良, 加藤 千恵次, 梶 智人 Japanese Journal of Radiology 27 (Suppl.) 6 -6 2009年04月 [査読無し][通常論文]
  • 鈴木恵士郎, 木下留美子, 鬼丸力也, 安田耕一, 小野寺俊介, 加藤徳雄, 田口大志, 藤野賢治, 青山英史, 白上博樹, 宮坂和男 Radiat Med 26 (Suppl.I) 3 -3 2008年04月25日 [査読無し][通常論文]
  • 石川正純, 鈴木恵士朗, 木下留美子, 藤田勝久, 山崎理衣, 笈田将皇, 白土博樹 頭けい部癌 33 (2) 64 2007年05月15日 [査読無し][通常論文]
  • 大坂康博, 青山英史, 田口大志, 加藤徳雄, 木下留美子, 藤野賢治, 鬼丸力也, 鈴木恵士郎, 白土博樹 日本医学放射線学会学術集会抄録集 66th S247 -S247 2007年02月28日 [査読無し][通常論文]
  • 鬼丸力也, 藤野賢治, 田口大志, 加藤徳雄, 木下留美子, 安田耕一, 鈴木恵士郎, 白土博樹, 宮坂和男 日本医学放射線学会学術集会抄録集 66th S233 -S233 2007年02月28日 [査読無し][通常論文]
  • 藤野賢治, 田口大志, 加藤徳雄, 青山英史, 鈴木恵士郎, 鬼丸力也, 木下留美子, 安田耕一, 白土博樹, 加藤知恵次, 志賀哲, 玉木長良, 小野寺俊輔 臨床放射線 52 (1) 137 -144 2007年01月10日 [査読無し][通常論文]
     
    肺癌の放射線治療計画にFDG-PETを用いstandardized uptake value(SUV)の数値で腫瘍の局在範囲を決定できるようにするための基礎的研究として、現在一般に行われているCT-planningと比較して劣らずにgross tumor volumeを設定できるか否かをファントム実験で検討した。結果、息止め下でのFDG-PET施行は、肺のように体内で呼吸性移動する臓器の癌においてSUVを真の値に近づけるうえでCT-planningより優れている可能性が示唆された。
  • 鬼丸力也, 白土博樹, 藤野賢治, 田口大志, 加藤徳雄, 木下留美子, 鈴木恵士郎, 青山英史, 宮坂和男 日本放射線腫よう学会誌 18 (Supplement 1) 217 2006年10月25日 [査読無し][通常論文]
  • 安田耕一, 加藤徳雄, 青山英史, 田口大志, 藤野賢治, 木下留美子, 鬼丸力也, 鈴木恵士朗, 白土博樹, 宮坂和男 日本放射線腫よう学会誌 18 (Supplement 1) 170 2006年10月25日 [査読無し][通常論文]
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    木下 留美子, 土屋 和彦, 田口 大志, 鈴木 恵士郎, 西岡 健, 白土 博樹, 大森 桂一 頭頸部癌 32 (2) 200 -200 2006年05月 [査読無し][通常論文]
  • 大坂康博, 青山英史, 田口大志, 加藤徳雄, 木下留美子, 藤野賢治, 鬼丸力也, 鈴木恵士郎, 白土博樹, 宮坂和男 日本医学放射線学会学術集会抄録集 65th S211 -S211 2006年02月25日 [査読無し][通常論文]
  • H. Taguchi, S. Takao, Y. Kogure, H. Shirato, S. Tadano, K. Suzuki, R. Onimaru, N. Katoh, R. Kinoshita INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 66 (3) S596 -S596 2006年 [査読無し][通常論文]
  • 鬼丸力也, 藤野賢治, 田口大志, 加藤徳雄, 木下留美子, 鈴木恵士郎, 青山英史, 白土博樹 日本放射線腫よう学会誌 17 (Supplement 1) 61 -61 2005年10月25日 [査読無し][通常論文]
  • 白土博樹, 大坂康博, 篠原信雄, 鬼丸力也, 鈴木恵士郎, 加藤紀雄, 山崎浩一, 藤野賢治, 木下留美子, 田口大志 日本癌治療学会誌 40 (2) 208 2005年09月22日 [査読無し][通常論文]
  • M Oita, R Onimaru, K Suzuki, H Aoyama, M Fujino, N Kato, R Kinoshita, K Fujita, H Shirato, K Miyasaka RADIOTHERAPY AND ONCOLOGY 76 S147 -S147 2005年09月 [査読無し][通常論文]
  • バルーン閉塞下TAEを施行した腎動静脈奇形の1例
    澤田 明宏, 清水 匡, 藤野 賢治, 木下 留美子, 阿保 大介, 作原 祐介, 児玉 芳尚, 船窪 正勝, 渡辺 佳明, 宮坂 和男 IVR: Interventional Radiology 20 (3) 319 -319 2005年07月
  • 鬼丸力也, 藤野賢治, 白土博樹, 鈴木恵士郎, 田口大志, 加藤徳雄, 木下留美子, 宮坂和男 日本医学放射線学会学術集会抄録集 64th S344 2005年02月25日 [査読無し][通常論文]
  • 大坂康博, 青山英史, 鬼丸力也, 田口大志, 木下留美子, 加藤徳雄, 鈴木恵士郎, 白土博樹, 宮坂和男 日本放射線腫よう学会誌 16 (Supplement 1) 91 2004年11月 [査読無し][通常論文]
  • 回結腸静脈経由,門脈血栓溶解術を施行した1例
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  • 血管造影が診断に最も有用であった小インスリノーマの1例
    阿保 大介, 澤田 明宏, 清水 匡, 児玉 芳尚, 作原 祐介, 吉田 慶之, 木下 留美子, 宮坂 和男 IVR: Interventional Radiology 18 (4) 396 -396 2003年10月
  • PTCDカテーテル断裂をきたした1例
    木下 留美子, 児玉 芳尚, 清水 匡, 澤田 明宏, 作原 祐介, 阿保 大介, 吉田 慶之, 宮坂 和男 IVR: Interventional Radiology 18 (4) 397 -397 2003年10月
  • 子宮動脈塞栓術 片側子宮動脈塞栓症例の検討
    作原 祐介, 清水 匡, 児玉 芳尚, 澤田 明宏, 阿保 大介, 吉田 慶之, 木下 留美子, 宮坂 和男 IVR: Interventional Radiology 18 (4) 398 -398 2003年10月
  • 肝細胞癌に対する動注化学療法の検討
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共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 清水 伸一, 宮本 直樹, 高尾 聖心, 梅垣 菊男, 橋本 孝之, 木下 留美子, 吉村 高明, 西岡 健太郎, 加藤 徳雄, 田口 大志, 松浦 妙子
     
    動体追跡放射線治療は、体内特徴点情報をX線透視画像によって得ているため(1)治療用放射線とは別のX線被ばくが生じる (2) 特徴点として金マーカ等の挿入が必要となる、等が問題となる。情報取得のためにX線透視する領域を極限まで微小とする、X線透視を用いずMRI技術で体内情報を得て用いる、などX線被ばくの低減もしくは排除を目標とした。動体追跡のため必要な体内情報をリアルタイムで取得するにはX線が未だ最適であるが、その範囲を限局する手法が本研究で模索された。また治療準備に際してX線を用いず、MRI画像データで臓器位置を描出する試みに成功し、今後の研究の推進に期待が持たれた。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2015年04月 -2018年03月 
    代表者 : 清水 伸一, 梅垣 菊男, 高尾 聖心, 松浦 妙子, 宮本 直樹, 西岡 健太郎, 木下 留美子, 加藤 徳雄
     
    陽子線治療ガントリー内に設置した動体追跡装置の2軸X線透視装置を活用し、腫瘍の空間的・時間的変動や呼吸性移動を考慮したがん治療ができる4D-IGRT放射線治療システム構築を目的として、動体追跡装置の透視画像から4次元コーンビームCT(4D-CBCT)画像を得て、複数の呼吸位相で構成される4D-CBCT画像群の中から、治療計画に用いたCT画像と同じ呼吸位相にあるCT画像から選択するとともに、選択されたCBCT画像を構成する元画像群を用いてマーカーレス4D-RTを目指す発展的画像誘導システムを開発することを目標とした。
  • 文部科学省：科学研究費補助金(若手研究(B))
    研究期間 : 2015年 -2017年 
    代表者 : 木下 留美子
     
    婦人科癌の術後全骨盤照射についてX線によるIMRTとspot scanning proton therapy(SSPT) による治療計画の比較・検討を行った。SSPTではIMRTと比較しターゲットに対する照射線量を損なうことなく骨髄の線量が低減可能であり、Grade3以上の血液毒性のNTCP値も有意に低減されることが示された。 乳癌の術後照射については温存乳房に対する術後照射及び温存乳房及び領域リンパ節に対する術後照射を行った症例の線量体積評価を行った。温存乳房に対する照射では内胸リンパ節への照射は不十分であることが示された。
  • 文部科学省：科学研究費補助金(若手研究(B))
    研究期間 : 2012年 -2014年 
    代表者 : 木下 留美子
     
    1988年1月から2008年12月の20年間に北海道大学病院第一外科で乳房温存術を施行し、温存乳房に対し術後照射を行った約400症例の中で、局所再発を来した20症例中19例について、手術時の検体から、未染色標本を切り出し、HER2,EGFR,AMAP1,GEP100の免疫染色を行った。各々の免疫染色標本を2人の病理専門医が独立して評価しスコア化を行った。年齢、リンパ節転移の有無といった従来局所再発と関係があると考えられてきた臨床データと再発時期の相関関係及び免疫染色の結果と再発時期の相関関係について統計解析を行った。初期解析の結果を第54回米国放射線腫瘍学会（2012年10月28ｰ31日 ボストン）で示説展示発表を行った。更に統計解析を加えた結果、AMAP1とGEP100がともに発現していると早期に再発する事が示された。一方、従来、局所再発のリスク因子として知られてきた年齢、手術時の断端状況は再発時期と有意な関係は認められなかった。現在この結果を英文学術誌に投稿中である。これまでMamma Print等の遺伝子解析によって遠隔転移のリスク因子が明らかになってきたが、局所因子のマーカーは確立されていなかった。今回、AMAP1とGEP100の発現が早期再発に関わる事が示されたことによって、これらのマーカーが局所再発そのものに関わっている可能性が示唆された。局所再発そのものに関連がある事が示されると治療前に局所再発リスクの診断が可能となり、治療法に影響を与える可能性がある。
  • 文部科学省：科学研究費補助金(基盤研究(C))
    研究期間 : 2012年 -2014年 
    代表者 : 谷野 美智枝, 渡利 英道, 田中 伸哉, 木下 留美子
     
    子宮頸癌の治療法としては、その進行期分類に応じて、手術療法、放射線療法、化学療法などが行われている。そのうち、放射線療法は高い治療効果と低侵襲性が特徴であり根治的治療法としてあるいは術後補助治療としても応用されている。近年、腫瘍の特性に応じた個別化診断を元に様々な分子標的治療が行われているが、放射線療法に関しては腫瘍の性質に応じない一律な治療が行われている。また、他の固形腫瘍の一部では放射線照射による上皮間葉移行(epithelial-mesenchymal transition: EMT)に伴う腫瘍の性質の悪性化も報告されており、放射線治療に関しても個別に効果を判定する必要があると考えた。今回我々は４種類の子宮頸癌細胞株（扁平上皮癌:Caski、C33A、腺癌：Siha, Hela)を用いて、4Gyと10GyのX線照射を行った。照射48時間後及び21日後にmRNA, proteinを回収し間葉系マーカーであるVimentin、EMT関連分子であるSnai, Slug, TwistmRNA及びproteinの発現、MMP-2、9mRNAの発現及び活性をreal time PCR法、免疫沈降法、zymographyを用いて定量した。放射線照射後いずれも細胞株においてもvimentinの発現は増加したが、EMT関連分子の発現はそれぞれの細胞株で異なっていた。また、21日後の表現型の解析ではtranswell migrationがいずれも亢進していた。以上の結果から、放射線照射によりEMT様の現象が起きることを確認したが、その過程で介在するEMT関連分子は異なっていた。よって、それぞれの細胞株で重要と思われたEMT関連分子のノックダウンを行い表現型の評価を今後行う予定である
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2009年 -2012年 
    代表者 : 白土 博樹, 本間 さと, 玉木 長良, 久下 裕司, 水田 正弘, 伊達 広行, 田中 真樹, 芳賀 永, 西岡 健, 加藤 元嗣, 茶本 健司, 大泉 聡史, 松永 尚文, 沖本 智昭, 早川 和重, 西尾 禎治, 但野 茂, 石川 正純, 小野寺 康仁, 澁谷 景子, 浜田 俊幸, 鬼丸 力也, 清水 伸一, 土屋 和彦, 加藤 徳雄, 木下 留美子, 井上 哲也, 小野寺 俊輔, 高尾 聖心, 加賀 基知三, 寺江 聡, 小野寺 祐也, 作原 祐介, 真鍋 徳子, 阿保 大介, 加藤 扶美, キンキン ター, 南 ジンミン, 佐邊 壽孝, 犬伏 正幸, 品川 尚文, ケネス サザランド
     
    ミクロレベルから動物レベルまで種々の生体を対象にして、定位技術や動体追跡技術を加えることで、生命の空間的な情報を経時的に定量的に扱うことが可能となり、そのデータに基づく新たな病因の追及や治療法の開発につながった。"生命の動き"の膨大なデータ処理が可能になり、新たに生体内の腫瘍の実際の動きをもとにした、新たなリアルタイム放射線治療装置や正確な4次元CT装置の開発につながりつつある。

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