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国立がん研究センター 中央病院

Home > Clincal depts. > Department of Musculoskeletal Oncology and Rehabilitation

Department of Musculoskeletal Oncology and Rehabilitation

 Akira Kawai, Fumihiko Nakatani, Eisuke Kobayashi, Shintaro Iwata, Tomoaki Mori, Takeshi Hirose, Kim Yonji, Tadashi Komatsubara, Jun Sugaya, Noriko Watanabe, Takurou Sakurai, Park Muna, Masumi Tsuruno, Shou Kurosawa, Sachiko Yahiro, Mami Oki, Aiko Matsuoka, Kazuhiro Kojima

Introduction

 Malignant tumors arising from connective tissue are extremely rare; they are estimated to account for only 0.01% of newly developed cancers. The rarity itself sometimes causes several problems in treating patients with bone and soft tissue tumors, including retardation of accurate diagnoses and a lack of understanding regarding standardized therapeutic approaches. Since 1962, the Musculoskeletal Oncology Division of the National Cancer Center Hospital (NCCH) has been accumulating a vast array of clinical knowledge regarding musculoskeletal tumors in collaboration with radiologists and pathologists specializing in sarcomas, which has enabled us to offer well-organized treatment strategies to patients with various types of bone and soft tissue tumors. We have also been conducting basic and clinical studies using accumulated clinical samples and information to establish novel diagnostic methods and therapeutic approaches for treating musculoskeletal tumors. In addition, we have given weight to clinical trials on three different but inseparable fields: surgery, chemotherapy and radiation therapy for bone and soft tissue tumors.

The Team and What We Do

 The Musculoskeletal Oncology Division of the NCCH consists of six staff doctors, three residents and four physiotherapists, three occupational therapists and two speech therapists. Occasionally, several fellows from Japan and overseas join our group. Outpatient consultations are held every weekday. A constant number of over 25 patients are hospitalized for operation, chemotherapy or radiation therapy. Six to 10 major operations are routinely performed every week. In 2018, 369 operations were performed, including palliative operations for pathological fractures from metastatic bone tumors. Sarcomas in the trunk, including 49 of soft tissue sarcoma, 17 of bone sarcomas and two in the retroperitoneal space were excised in cooperation with thoracic, general or urological surgeons. A total of 64 reconstructive operations were conducted in collaboration with plastic surgeons to achieve adequate soft tissue coverage after the resection of malignant tumors of the trunk or limb-salvage operations for sarcomas of the extremities. As a result, almost 90% of the operations were performed with a limbsparing approach. With regard to the patients' postoperative course, we have been collaborating with a physical therapist to rehabilitate the musculoskeletal system in cancer-bearing patients.

 As for chemotherapy, we have been conducting neo-adjuvant and adjuvant chemotherapy for high-grade bone and soft tissue tumors, palliative chemotherapy for metastatic bone and soft tissue sarcomas, where necessary in collaboration with medical oncologists. We have been collaborating with pediatric oncologists for chemotherapeutic treatment of children and adolescents with sarcomas.

Table 1. Type of surgical procedure (2018)
Table 1. Type of surgical procedure (2018)(Full Size)

Research activities

 Since 2004, we have been collaborating with the NCC Research Institute to develop novel molecular target therapies or tailor-made treatments for sarcoma patients. With a genomewide miRNA array system or a new generation sequence system, we have been analyzing the complete expression levels of miRNA and genomic alteration in the tumor samples or serum samples from patients with various types of bone and soft tissue sarcoma. Combined with each patient's clinical information, we have been establishing novel biomarkers for prediction of patients' prognoses or effects of the chemotherapeutic agents. We also have been developing mouse xenograft models and sarcoma cell lines using the clinical samples of biopsied or resected tumors with the aim to create novel molecular targeted therapies or biomarkers.

Clinical trials

 We also have been focusing on the standardization of adjuvant and second-line chemotherapy regimens for bone and soft tissue sarcomas. Several multi-institutional clinical trials were conducted as follows:

1) A multi-institutional phase III clinical trial of multi-drugs adjuvant chemotherapy for osteosarcomas (The Japan Clinical Oncology Group (JCOG 0905) since 2010.

2) A multi-institutional phase III clinical trial of multi-drugs adjuvant chemotherapy for osteosarcomas (JCOG 1306) since 2014.

3) A multi-institutional phase III clinical trial of preoperative denosumab for giant cell tumor (JCOG 1610) since 2017.

Education

 Each resident performs 60 to 70 operations supervised by staff members every year, joins many domestic and international conferences and publishes several medical articles or reports during training courses.

Future prospects

 Our division continues to focus on the development of novel therapeutic tools for the patients with bone and soft tissue tumors collaborating with other clinical divisions and research institutes.

List of papers published in 2018

Journal

1.Asano N, Matsuzaki J, Ichikawa M, Kawauchi J, Takizawa S, Aoki Y, Sakamoto H, Yoshida A, Kobayashi E, Tanzawa Y, Nakayama R, Morioka H, Matsumoto M, Nakamura M, Kondo T, Kato K, Tsuchiya N, Kawai A, Ochiya T. A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes. Nat Commun, 10時12分99, 2019

2.Makise N, Sekimizu M, Konishi E, Motoi T, Kubo T, Ikoma H, Watanabe SI, Okuma T, Hiraoka N, Fukayama M, Kawai A, Ichikawa H, Yoshida A. h2K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with characteristic clinicopathological features. Mod Pathol, 32:435-445, 2019

3.Nakamura Y, Shida D, Shibayama T, Yoshida A, Matsui Y, Shinoda Y, Iwata S, Kanemitsu Y. Giant multilocular prostatic cystadenoma. World J Surg Oncol, 17時42分, 2019

4.Oyama R, Kito F, Qiao Z, Sakumoto M, Shiozawa K, Toki S, Yoshida A, Kawai A, Kondo T. Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1. In Vitro Cell Dev Biol Anim, 55:62-73, 2019

5.Koike H, Nishida Y, Kohno K, Shimoyama Y, Motoi T, Hamada S, Kawai A, Ogose A, Ozaki T, Kunisada T, Matsumoto Y, Matsunobu T, Ae K, Gokita T, Sakai T, Shimizu K, Ishiguro N. Is immunohistochemical staining for beta-catenin the definitive pathological diagnostic tool for desmoid-type fibromatosis? A multi-institutional study. Hum Pathol, 84:155-163, 2019

6.Tashiro K, Arikawa M, Fukunaga Y, Nakatani F, Kobayashi E, Kawai A, Miyamoto S. Free latissimus dorsi musculocutaneous flap for external hemipelvectomy reconstruction. Microsurgery, 39:138-143, 2019

7.Takeuchi A, Nomura A, Yamamoto N, Hayashi K, Igarashi K, Tandai S, Kawai A, Matsumine A, Miwa S, Nishida Y, Nakamura T, Terauchi R, Hoshi M, Kunisada T, Endo M, Yoshimura K, Murayama T, Tsuchiya H. Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: a study protocol. BMC Musculoskelet Disord, 20:68, 2019

8.Ogura K, Uehara K, Akiyama T, Shinoda Y, Iwata S, Tsukushi S, Kobayashi E, Hirose T, Yonemoto T, Endo M, Tanzawa Y, Nakatani F, Kawano H, Tanaka S, Kawai A. Development of a patient-oriented disease specific outcome measure of health-related quality of life (HRQOL) for musculoskeletal oncology patients. J Orthop Sci, 24:539-547, 2019

9.Frezza AM, Jones RL, Lo Vullo S, Asano N, Lucibello F, Ben-Ami E, Ratan R, Teterycz P, Boye K, Brahmi M, Palmerini E, Fedenko A, Vincenzi B, Brunello A, Desar IME, Benjamin RS, Blay JY, Broto JM, Casali PG, Gelderblom H, Grignani G, Gronchi A, Hall KS, Mir O, Rutkowski P, Wagner AJ, Anurova O, Collini P, Dei Tos AP, Flucke U, Hornick JL, Lobmaier I, Philippe T, Picci P, Ranchere D, Renne SL, Sbaraglia M, Thway K, Wagrodzki M, Wang WL, Yoshida A, Mariani L, Kawai A, Stacchiotti S. Anthracycline, Gemcitabine, and Pazopanib in Epithelioid Sarcoma: A Multi-institutional Case Series. JAMA Oncol, 4:e180219, 2018

10.Kito F, Oyama R, Sakumoto M, Takahashi M, Shiozawa K, Qiao Z, Sakamoto H, Hirose T, Setsu N, Yoshida A, Kawai A, Kondo T. Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line. In Vitro Cell Dev Biol Anim, 54:528-536, 2018

11.Makise N, Sekimizu M, Kubo T, Wakai S, Watanabe SI, Kato T, Kinoshita T, Hiraoka N, Fukayama M, Kawai A, Ichikawa H, Yoshida A. Extraskeletal osteosarcoma: MDM2 and h2K27me3 analysis of 19 cases suggest disease heterogeneity. Histopathology, 73:147-156, 2018

12.Ogura K, Hosoda F, Arai Y, Nakamura H, Hama N, Totoki Y, Yoshida A, Nagai M, Kato M, Arakawa E, Mukai W, Rokutan H, Kawai A, Tanaka S, Shibata T. Integrated genetic and epigenetic analysis of myxofibrosarcoma. Nat Commun, 9時27分65, 2018

13.Oyama R, Kito F, Sakumoto M, Shiozawa K, Toki S, Endo M, Yoshida A, Kawai A, Kondo T. Establishment and proteomic characterization of a novel synovial sarcoma cell line, NCC-SS2-C1. In Vitro Cell Dev Biol Anim, 54:392-399, 2018

14.Toki S, Motoi T, Miyake M, Kobayashi E, Kawai A, Yoshida A. Minute mesenchymal chondrosarcoma within osteochondroma: an unexpected diagnosis confirmed by HEY1-NCOA2 fusion. Hum Pathol, 81:255-260, 2018

15.Toki S, Wakai S, Sekimizu M, Mori T, Ichikawa H, Kawai A, Yoshida A. PAX7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours. Histopathology, 73:645-652, 2018

16.Xing Z, Wei L, Jiang X, Conroy J, Glenn S, Bshara W, Yu T, Pao A, Tanaka S, Kawai A, Choi C, Wang J, Liu S, Morrison C, Yu YE. Analysis of mutations in primary and metastatic synovial sarcoma. Oncotarget, 9時36分878-36888, 2018

17.Aiba H, Yamada S, Mizutani J, Yamamoto N, Okamoto H, Hayashi K, Kimura H, Takeuchi A, Miwa S, Kawai A, Yoshimura K, Tsuchiya H, Otsuka T. Clinical outcomes of radio-hyperthermo-chemotherapy for soft tissue sarcoma compared to a soft tissue sarcoma registry in Japan: a retrospective matched-pair cohort study. Cancer Med, 7時15分60-1571, 2018

18.Ogura K, Susa M, Morioka H, Matsumine A, Ishii T, Hamada K, Ueda T, Kawai A. Reconstruction using a constrained-type hip tumor prosthesis after resection of malignant periacetabular tumors: A study by the Japanese Musculoskeletal Oncology Group (JMOG). J Surg Oncol, 117時14分55-1463, 2018

19.Kito F, Oyama R, Takai Y, Sakumoto M, Shiozawa K, Qiao Z, Uehara T, Yoshida A, Kawai A, Kondo T. Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line. Hum Cell, 31:167-174, 2018

20.Yoshida A, Makise N, Wakai S, Kawai A, Hiraoka N. INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma. Mod Pathol, 31:744-752, 2018

21.Makise N, Sekimizu M, Kubo T, Wakai S, Hiraoka N, Komiyama M, Fukayama M, Kawai A, Ichikawa H, Yoshida A. Clarifying the Distinction Between Malignant Peripheral Nerve Sheath Tumor and Dedifferentiated Liposarcoma: A Critical Reappraisal of the Diagnostic Utility of MDM2 and h2K27me3 Status. Am J Surg Pathol, 42:656-664, 2018

22.Crompton JG, Ogura K, Bernthal NM, Kawai A, Eilber FC. Local Control of Soft Tissue and Bone Sarcomas. J Clin Oncol, 36:111- 117, 2018

23.Akiyama T, Ogura K, Gokita T, Tsukushi S, Iwata S, Nakamura T, Matsumine A, Yonemoto T, Nishida Y, Saita K, Kawai A, Matsumoto S, Yamaguchi T. Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes. Ann Surg Oncol, 25:912-919, 2018

24.Kawai A, Goto T, Shibata T, Tani K, Mizutani S, Nishikawa A, Shibata T, Matsumoto S, Nagata K, Narukawa M, Matsui S, Ando M, Toguchida J, Monden M, Heike T, Kimura S, Ueda R. Current state of therapeutic development for rare cancers in Japan, and proposals for improvement. Cancer Sci, 19時17分31-1737, 2018

25.Tsuda Y, Ogura K, Shinoda Y, Kobayashi H, Tanaka S, Kawai A. The outcomes and prognostic factors in patients with osteosarcoma according to age: a Japanese nationwide study with focusing on the age differences. BMC Cancer, 18:614, 2018

26.Minami Y, Kobayashi E, Kawai A. Unusual subcutaneous invasion of myxoid liposarcoma. J Dermatol, 45:e130-e131, 2018

27.Hirakawa A, Nishikawa T, Yonemori K, Shibata T, Nakamura K, Ando M, Ueda T, Ozaki T, Tamura K, Kawai A, Fujiwara Y. Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma. Ther Innov Regul Sci, 52:334-338, 2018

28.Ohara A, Furui T, Shimizu C, Ozono S, Yamamoto K, Kawai A, Tatara R, Higuchi A, Horibe K. Correction to: Current situation of cancer among adolescents and young adults in Japan. Int J Clin Oncol, 23時12分12-1216, 2018

29.Fukushima T, Ogura K, Akiyama T, Takeshita K, Kawai A. Descriptive epidemiology and outcomes of bone sarcomas in adolescent and young adult patients in Japan. BMC Musculoskelet Disord, 19時29分7, 2018

30.Kagaya Y, Arikawa M, Kobayashi E, Kawai A, Miyamoto S. Successful Pregnancy and Delivery after Autologous Abdominal Wall Reconstruction using Anterolateral-Thigh and Iliotibial-Tract Flap. Plast Reconstr Surg Glob Open, 6:e1819, 2018

31.Tanaka K, Ogawa G, Mizusawa J, Naka N, Kawai A, Takahashi M, Hiruma T, Matsumoto Y, Tsuchiya H, Nakayama R, Hatano H, Emori M, Hosaka M, Yoshida Y, Toguchida J, Abe S, Asanuma K, Yokoyama R, Hiraga H, Yonemoto T, Morii T, Matsumoto S, Nagano A, Yoshikawa H, Fukuda H, Ozaki T, Iwamoto Y. Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304. World J Surg Oncol, 16時16分2, 2018

32.Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T. Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. World J Surg Oncol, 16時16分0, 2018

33.Ohara A, Furui T, Shimizu C, Ozono S, Yamamoto K, Kawai A, Tatara R, Higuchi A, Horibe K. Current situation of cancer among adolescents and young adults in Japan. Int J Clin Oncol, 23時12分01-1211, 2018

34.Joo MW, Kang YK, Ogura K, Iwata S, Kim JH, Jeong WJ, Niu X, Chinder PS, Kim HS, Seo SW, Chung YG. Post-radiation sarcoma: A study by the Eastern Asian Musculoskeletal Oncology Group. PLoS One, 13:e0204927, 2018

35.Iwata S, Araki A, Funatsu H, Yonemoto T, Kamoda H, Itami M, Ishii T. Optimal surgical margin for infiltrative soft tissue sarcomas: Assessing the efficacy of excising beyond the infiltration. J Surg Oncol, 118時52分5-531, 2018

36.Itoh H, Kadomatsu T, Tanoue H, Yugami M, Miyata K, Endo M, Morinaga J, Kobayashi E, Miyamoto T, Kurahashi R, Terada K, Mizuta H, Oike Y. TET2-dependent IL-6 induction mediated by the tumor microenvironment promotes tumor metastasis in osteosarcoma. Oncogene, 37:2903-2920, 2018