研究者業績

西野 宏

ニシノ ヒロシ  (NISHINO HIROSHI)

基本情報

所属
自治医科大学 附属病院耳鼻咽喉科 教授
東京大学医科学研究所附属病院脳腫瘍外科 非常勤講師
学位
医学博士(自治医科大学)

J-GLOBAL ID
200901012308530180
researchmap会員ID
5000100064

【専門領域】頭頸部癌、頭頸部外科学
【基礎研究】癌細胞の生物学的活性(浸潤能、転移能、幹細胞)、嗅上皮組織の再生
【臨床研究】機能形態温存治療(上顎洞癌集学治療、外科手術)、抗癌薬同時併用化学放射線治療、分子標的薬同時併用放射線治療、導入化学療法、高齢者の癌治療
【主な所属学会】ASCO、AAO-HNS、癌学会、癌治療学会、日本耳鼻咽喉科学会、頭頸部癌学会、頭頸部外科学会、日本鼻学会
【その他】東京大学医科学研究所附属病院脳腫瘍外科と共同研究「進行性嗅神経芽細胞腫患者に対する増殖型遺伝子組換え単純ヘルペスウイルスG47Δを用いたウイルス療法の臨床研究、JCOG「JCOG1008局所進行頭頸部扁平上皮癌術後再発High-Risk患者に対するHigh dose CDDPを同時併用する術後補助化学放射線療法とweekly CDDOPを同時併用する術後補助化学放射線療法ランダム化第II/III相試験

研究キーワード

 1

論文

 104
  • Yusuke Amano, Masayo Hasegawa, Atsushi Kihara, Daisuke Matsubara, Noriyoshi Fukushima, Hiroshi Nishino, Yoshiyuki Mori, Kentaro Inamura, Toshiro Niki
    Annals of diagnostic pathology 75 152439-152439 2025年1月15日  
    The tumor microenvironment is highly heterogeneous and consists of neoplastic cells and diverse stromal components, including fibroblasts, endothelial cells, pericytes, immune cells, local and bone marrow-derived stromal stem and progenitor cells, and the surrounding extracellular matrix. Although the significance of p16 and p53 has been reported in various tumor types, their involvement in the stromal cells of oral squamous cell carcinoma (OSCC) remains unclear. We performed immunohistochemical analyses of p16 and p53 expression in OSCC samples, Of the 116 samples, 74 showed p16-positive stromal cells, and 33 showed p53-positive stromal cells. Both p16 and p53 positivity were associated with an increased histological grade, lymphovascular invasion, an immature stromal pattern with abundant amorphous extracellular matrix material, infiltrative invasion patterns (Yamamoto Kohama classification-4C and 4D), and poor prognosis. Multivariate analyses identified p16 and p53 positivity in the stroma as independent prognostic factors for overall survival (P = 0.032 and P = 0.020, respectively); moreover, stromal p16 positivity correlated with stromal p53 positivity. These findings indicated that p16 and p53 stroma positivity may regulate OSCC tumor aggressiveness.
  • Ryutaro Onaga, Tomohiro Enokida, Susumu Okano, Takao Fujisawa, Nobukazu Tanaka, Yuta Hoshi, Takuma Kishida, Hideki Tanaka, Masanobu Sato, Naohiro Takeshita, Ryo Kuboki, Hiroshi Nishino, Makoto Ito, Makoto Tahara
    International journal of clinical oncology 29(10) 1435-1443 2024年10月  
    BACKGROUND:  Treatment options for patients with differentiated thyroid cancer (DTC) who experience disease progression on lenvatinib treatment are limited. Although dose escalation of treatment with tyrosine kinase inhibitors at disease progression has been reported across cancer types, clinical significance in patients with DTC has not been investigated. METHODS: We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose. RESULTS: Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24 mg/day, and the median dose at initial disease progression was 10 mg/day. In the former, the median dose escalation was 6 mg/day (range: 4-12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9 months (95% confidence interval [CI] 5.71-27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4 months [95% CI 7.0-NA] vs. 3.9 months [95% CI 1.7-7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09-0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess. CONCLUSION: The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC.
  • Hidetoshi Shimizu, Takeshi Kodaira, Naomi Kiyota, Ryuichi Hayashi, Hiroshi Nishino, Yukinori Asada, Hiroki Mitani, Yuuji Hirayama, Yusuke Onozawa, Naoki Nishio, Nobuhiro Hanai, Akira Ohkoshi, Hiroki Hara, Nobuya Monden, Masato Nagaoka, Shujiro Minami, Takashi Fujii, Kaoru Tanaka, Akihiro Homma, Seiichi Yoshimoto, Nobuhiko Oridate, Koichi Omori, Tsutomu Ueda, Kenji Okami, Hirokazu Uemura, Kiyoto Shiga, Mitsuhiko Nakahira, Takahiro Asakage, Yuki Saito, Keita Sasaki, Ryo Kitabayashi, Satoshi Ishikura, Yasumasa Nishimura, Makoto Tahara
    Oral oncology 157 106976-106976 2024年10月  
    BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.
  • Kazutaka Kashima, Takeshi Igarashi, Hiroyuki Fujii, Noriyoshi Fukushima, Hiroshi Nishino, Takeharu Kanazawa
    International journal of surgery case reports 124 110356-110356 2024年9月27日  
    INTRODUCTION: Moderately differentiated neuroendocrine tumors of the larynx are rare malignant tumors that arise from the submucosa of the larynx, for which surgery is the first-line treatment. PRESENTATION OF CASE: We report a case of moderately differentiated neuroendocrine tumor of the larynx, in which the patient, a 74-year-old man, experienced long-term palliation but an unfortunate outcome of death owing to metastasis. Laryngeal endoscopic examination revealed an elevated submucosal lesion on the laryngeal surface of the epiglottis. Computed tomography and magnetic resonance imaging showed a tumor-like lesion demonstrating a contrasting effect in the submucosa of the epiglottis. A biopsy revealed a moderately differentiated neuroendocrine tumor (formerly called an atypical carcinoid), and a horizontal partial laryngectomy was performed. The patient had a good postoperative course; however, three years and ten months after surgery, he experienced recurrence in the upper gastrointestinal tract and carcinoid syndrome and died four years and three months after the surgery. DISCUSSION: The prognosis of laryngeal neuroendocrine tumors remains poor. In this case, local control was possible without irradiation because the resection margins were negative on pathological examination. This case report has been reported in line with the SCARE Criteria. CONCLUSION: Long-term follow-up of this type of tumor is necessary, as distant metastasis is likely to affect prognosis. In addition to surgery, effective adjuvant therapies, including molecular targeted therapies, should be established.
  • Yoshinori Imamura, Naomi Kiyota, Makoto Tahara, Takeshi Kodaira, Ryuichi Hayashi, Hiroshi Nishino, Yukinori Asada, Hiroki Mitani, Shigemichi Iwae, Naoki Nishio, Yusuke Onozawa, Nobuhiro Hanai, Akira Ohkoshi, Hiroki Hara, Nobuya Monden, Masato Nagaoka, Shujiro Minami, Ryo Kitabayashi, Keita Sasaki, Akihiro Homma
    Cancer medicine 13(18) e70235 2024年9月  
    BACKGROUND: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non-inferior to 3-weekly cisplatin (100 mg/m2) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS). METHODS: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5-fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test. RESULTS: The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). CONCLUSIONS: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting.

MISC

 254

講演・口頭発表等

 11

共同研究・競争的資金等の研究課題

 17