Faculty Profiles - KUNISADA Toshiyuki

Papers - KUNISADA Toshiyuki

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国定俊之, 中田英二, 藤原智洋, 尾崎敏文

日本臨床 79 ( 増刊1 希少がん ) 454 - 461 2021.3

(IV章)骨軟部骨腫瘍原発性悪性骨腫瘍の治療指針

国定俊之, 中田英二, 尾崎敏文

整形外科学レビュー 2021-'22 228 - 232 2021.3

The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas. Reviewed

Hiromasa Yamamoto, Kei Namba, Haruchika Yamamoto, Tomohiro Toji, Junichi Soh, Kazuhiko Shien, Ken Suzawa, Takeshi Kurosaki, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Toshiyuki Kunisada, Takahiro Oto, Shinichi Toyooka

Surgery today 51 ( 1 ) 127 - 135 2021.1

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas. METHODS: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis. RESULTS: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies. CONCLUSION: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

DOI： 10.1007/s00595-020-02093-5

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PRRX1 promotes malignant properties in human osteosarcoma. Reviewed International journal

Ryoji Joko, Daisuke Yamada, Masahiro Nakamura, Aki Yoshida, Shota Takihira, Tomoka Takao, Ming Lu, Kohei Sato, Tatsuo Ito, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada

Translational oncology 14 ( 1 ) 100960 - 100960 2021.1

Language：English Publishing type：Research paper (scientific journal)

Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.

DOI： 10.1016/j.tranon.2020.100960

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Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. Reviewed International journal

Toshinori Omori, Hiroshi Tazawa, Yasuaki Yamakawa, Shuhei Osaki, Joe Hasei, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

PloS one 16 ( 4 ) e0250643 2021

Language：English Publishing type：Research paper (scientific journal)

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

DOI： 10.1371/journal.pone.0250643

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Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors. Reviewed International journal

Toshiyuki Kunisada, Joe Hasei, Tomohiro Fujiwara, Eiji Nakata, Suguru Yokoo, Koji Demiya, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 21578 - 21578 2020.12

Language：English Publishing type：Research paper (scientific journal)

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

DOI： 10.1038/s41598-020-78409-9

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What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities? Reviewed

Eiji Nakata, Toshiyuki Kunisada, Joe Hasei, Ryuichi Nakahara, Hiroyuki Yanai, Tomohiro Toji, Hirofumi Inoue CT, Toshifumi Ozaki

Clinical Orthopaedics & Related Research 478 ( 11 ) 2550 - 2561 2020.11

軟部肉腫に対するトラベクテジン投与時の腫瘍反応および有害事象発現の時間経過分析

遠藤誠, 高橋俊二, 荒木信人, 杉浦英志, 上田孝文, 米本司, 高橋満, 森岡秀夫, 平賀博明, 比留間徹, 国定俊之, 松峯昭彦, 合田風人, 川井章

日本癌治療学会学術集会抄録集 58回 O39 - 1 2020.10

【肉腫-基礎・臨床の最新知見-】肉腫の外科的治療その他術後リハビリテーション

杉原進介, 国定俊之, 尾崎敏文

日本臨床 78 ( 増刊5 肉腫 ) 415 - 419 2020.10

【肉腫-基礎・臨床の最新知見-】肉腫の外科的治療切除ナビゲーションサージェリー

国定俊之, 中田英二, 長谷井嬢, 尾崎敏文

日本臨床 78 ( 増刊5 肉腫 ) 315 - 320 2020.10

Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. Reviewed International journal

Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Toshiyuki Kozuki, Daijiro Harada, Naoyuki Nogami, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Toshifumi Ozaki

Oncology letters 20 ( 3 ) 2977 - 2986 2020.9

Language：English Publishing type：Research paper (scientific journal)

The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

DOI： 10.3892/ol.2020.11856

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Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study. Reviewed International journal

Hiroshi Urakawa, Akira Kawai, Takahiro Goto, Hiroaki Hiraga, Toshifumi Ozaki, Hiroyuki Tsuchiya, Robert Nakayama, Norifumi Naka, Yoshihiro Matsumoto, Eisuke Kobayashi, Tomotake Okuma, Toshiyuki Kunisada, Masahiko Ando, Takafumi Ueda, Yoshihiro Nishida

Cancer science 111 ( 9 ) 3303 - 3312 2020.9

Language：English Publishing type：Research paper (scientific journal)

Alveolar soft part sarcoma (ASPS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS) are known to be chemoresistant tumors. The aim of this study was to investigate the effect of pazopanib on these chemoresistant tumors. This study is designed as a single-arm, multicenter, investigator-initiated phase II trial. Patient enrollment was undertaken between July 2016 and August 2018 at 10 hospitals participating in the Japanese Musculoskeletal Oncology Group. The primary end-point is the CBR (CBR, including complete or partial response and stable disease) at 12 weeks after treatment with pazopanib according to RECIST. Eight patients were enrolled within the period. The histological subtypes were 5 ASPS, 2 ES, and 1 CCS. The median follow-up period was 22.2 (range, 4.9-24.9) months. All patients initially received pazopanib 800 mg once daily. The CBRs were 87.5% (7 of 8) and 75.0% (6 of 8) according to RECIST and Choi criteria at 12 weeks after pazopanib treatment, respectively. The CBRs at 12 weeks according to RECIST were 80.0%, 100.0%, and 100.0% in ASPS, ES, and CCS, respectively. Partial response was observed in 1 ASPS according to RECIST and 3 ASPS and 1 ES according to Choi criteria at 12 weeks after pazopanib treatment. This study documented antitumor activity of pazopanib, especially in ASPS. These results support the frontline use of pazopanib for ASPS. Prospective data collection is desired using both RECIST and Choi criteria for these rare chemoresistant tumors.

DOI： 10.1111/cas.14542

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Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan. Reviewed International journal

Yoshihiro Nishida, Shunsuke Hamada, Akira Kawai, Toshiyuki Kunisada, Akira Ogose, Yoshihiro Matsumoto, Keisuke Ae, Junya Toguchida, Toshifumi Ozaki, Akihiro Hirakawa, Toru Motoi, Tomohisa Sakai, Eisuke Kobayashi, Tabu Gokita, Takeshi Okamoto, Tomoya Matsunobu, Koki Shimizu, Hiroshi Koike

Cancer science 111 ( 8 ) 2935 - 2942 2020.8

Language：English Publishing type：Research paper (scientific journal)

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

DOI： 10.1111/cas.14528

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【がんロコモ:がん診療のニューフロンティア】(Part7)オートメーションのニューフロンティア(がんロコモ診療のオートメーション化) 脊椎転移による麻痺の予防レッドフラッグ

中田英二, 国定俊之, 杉原進介, 尾崎敏文

Bone Joint Nerve 10 ( 3 ) 447 - 457 2020.7

Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma. Reviewed International journal

Takuya Morita, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 9414 - 9414 2020.6

Language：English Publishing type：Research paper (scientific journal)

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

DOI： 10.1038/s41598-020-66120-8

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Time lapse analysis of tumor response in patients with soft tissue sarcoma treated with trabectedin: A pooled analysis of two phase II clinical trials. International journal

Makoto Endo, Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Mitsuru Takahashi, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Kazato Goda, Akira Kawai

Cancer medicine 9 ( 11 ) 3656 - 3667 2020.6

Language：English Publishing type：Research paper (scientific journal)

The time course of the response to each drug is important to avoid inappropriate termination of treatment by misjudging tumor progression; however, little is known about soft tissue sarcoma (STS) regarding this matter. This study aimed to perform a time-lapse analysis of tumor response in patients with STS treated with trabectedin from 2 phase II clinical trials. We examined 66 patients with translocation-related sarcoma registered in 2 Japanese phase II clinical trials. All patients previously received standard therapy before the administration of trabectedin at 1.2 mg/m2 every 3 weeks. Imaging evaluation was performed according to the study protocol. The sum of the maximum diameters of the target lesions was calculated and analyzed over time. Among the 66 patients, 9 (13.6%) showed partial response (PR) to trabectedin. Histological diagnoses of these 9 responders comprised 6 myxoid liposarcoma, 2 synovial sarcoma, and a mesenchymal chondrosarcoma. The median period from treatment initiation to the first PR was 123 (range, 34-328) days. The pattern of tumor response to trabectedin showed an increasing tendency in size in the initial stage, usually followed by a size decrease with repeated administration. STS response to trabectedin was characterized as delayed and potentially persistent. Clinicians treating STS with trabectedin should know the features of the response pattern to avoid interrupting the treatment before maximal efficacy is achieved.

DOI： 10.1002/cam4.2991

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整形トピックス骨肉腫に対する抗PD-1抗体の効果増強をめざした腫瘍融解ウイルス併用複合免疫療法の開発

望月雄介, 田澤大, 出宮光二, 久禮美穂, 長谷井嬢, 中田英二, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

整形外科 71 ( 7 ) 786 - 786 2020.6

Definitive radiation therapy in patients with unresectable desmoid tumors: a systematic review. Reviewed International journal

Tomoya Matsunobu, Toshiyuki Kunisada, Toshifumi Ozaki, Yukihide Iwamoto, Masahiro Yoshida, Yoshihiro Nishida

Japanese journal of clinical oncology 50 ( 5 ) 568 - 573 2020.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Desmoid tumors are rare soft tissue tumors. Wide local excision has been the standard surgical treatment for desmoid tumors. However, this procedure results in high local recurrence rates, so non-surgical treatments should be considered. The aim of this systematic review was to evaluate the effect of radiation therapy on patients with desmoid tumors, especially those with unresectable disease. METHODS: We evaluated studies published between 1 January 1990 and 31 August 2017 and cited in PubMed and Ichushi (in Japanese). All studies evaluating the effect of radiation therapy on desmoid tumors were included. Data regarding radiation dose, recurrence and adverse events were recorded. RESULTS: Among 218 identified studies, only 6 were finally included in this review. Local control was achieved in 253 of 317 patients with unresectable or unresected tumors who underwent definitive radiation therapy (the crude rate of local control was 79.8%). Toxicity was evaluated in patients who underwent definitive radiation therapy or surgery plus radiation therapy. One of the most common acute complications was skin toxicity. Frequent late complications of radiation therapy included fibrosis/contracture/joint stiffness, skin disorders, lymphedema and pain. Six patients developed secondary malignancies in the radiation field. CONCLUSIONS: In patients treated unsuccessfully with surgery, watchful waiting and pharmacotherapy, radiation therapy may be an option as salvage therapy because of the high rate of local control. Because desmoid tumors frequently develop in young individuals, children and young patients who receive radiation therapy for the treatment of desmoid tumors should be followed up on a long-term basis with periodic monitoring for late radiation toxicities.

DOI： 10.1093/jjco/hyaa007

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Multidisciplinary treatment system for bone metastases for early diagnosis, treatment and prevention of malignant spinal cord compression. Reviewed International journal

Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Kazuo Nakanishi, Yoshiteru Akezaki, Toshifumi Ozaki

Oncology letters 19 ( 4 ) 3137 - 3144 2020.4

Language：English Publishing type：Research paper (scientific journal)

Malignant spinal cord compression (MSCC) is a serious complication of cancers. The present study aimed to establish a multidisciplinary treatment system for urgent magnetic resonance imaging (MRI) and referral to orthopedists in order to prevent neurological deficits caused by MSCC. In the present study, the extent to which this system achieved early diagnosis and treatment and prevented MSCC-caused neurological deficits was examined. The records from patients with neurological deficits caused by MSCC before (between April 2007 and March 2012; group A) and after (between April 2012 and March 2017; group B) the establishment of the multidisciplinary system at the Shikoku Cancer Center (Ehime, Japan) were retrospectively evaluated. The numbers of patients with neurological deficits were 38 and 7 in groups A and B, respectively. All patients received radiotherapy. The incidence of neurological deficits was 13.2 and 3.4% in groups A and B, respectively (P<0.001). The proportion of patients with improvement in the severity of neurological deficits was 5.3 and 28.6% in groups A and B, respectively (P<0.001). The interval between physicians' recognition of a neurological deficit and MRI and the start of treatment, the number of cases, and the severity of neurological deficits were evaluated in groups A and B. The median interval between recognition of a neurological deficit by physicians and MRI was 3 and 0 days in groups A and B, respectively (P<0.001). The median interval between physicians' recognition of a neurological deficit and the start of treatment was 3 and 0 days in groups A and B, respectively (P<0.001). By using a multidisciplinary treatment system, the incidence and severity of neurological deficits following treatment were significantly improved. Therefore, the multidisciplinary treatment system used in the present study may be useful for early diagnosis, treatment and prevention of MSCC in patients with bone metastases.

DOI： 10.3892/ol.2020.11415

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Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients Reviewed

Akihito Nagano, Seiichi Matsumoto, Akira Kawai, Tomotake Okuma, Hiroaki Hiraga, Yoshihiro Matsumoto, Yoshihiro Nishida, Tsukasa Yonemoto, Masami Hosaka, Mitsuru Takahashi, Hideki Yoshikawa, Toshiyuki Kunisada, Kunihiro Asanuma, Norifumi Naka, Makoto Emori, Tadahiko Kubo, Hiroyuki Kawashima, Teruya Kawamoto, Ryohei Yokoyama, Satoshi Tsukushi, Kenji Sato, Takeshi Okamoto, Koji Hiraoka, Hideo Morioka, Kazuhiro Tanaka, Tatsuya Takagi, Yukihide Iwamoto, Toshifumi Ozaki

Journal of Orthopaedic Science 25 ( 2 ) 319 - 323 2020.3

Language：English Publishing type：Research paper (scientific journal)

© 2019 The Japanese Orthopaedic Association Background: Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined. Methods: This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone. Results: Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis. Conclusions: The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear.

DOI： 10.1016/j.jos.2019.04.008

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Papers - KUNISADA Toshiyuki