Annual Report 2020
Department of Musculoskeletal Oncology and Rehabilitation
Akira Kawai, Shintaro Iwata, Fumihiko Nakatani, Eisuke Kobayashi, Shuhei Osaki, Suguru Fukushima, Jun Sugaya, Chiaki Sato, Suguru Yokoo, Yutaka Nezu, Noriko Watanabe, Takurou Sakurai, Sachiko Yahiro, Mami Oki, Yusuke Okita, Takuya Fukushima, Shouta Yokota, Aiko Matsuoka, Kazuhiro Kojima
Introduction
Malignant tumors arising from connective tissue are extremely rare, accounting for only 0.01% of newly developed cancers. The rarity itself sometimes causes 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, our department has accumulated a vast array of clinical knowledge regarding musculoskeletal tumors in collaboration with radiologists and pathologists specializing in sarcomas, enabling 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 data to establish novel diagnostic methods and therapeutic approaches for treating musculoskeletal tumors. In addition, we have given weight to clinical trials in three different but inseparable fields: surgery, chemotherapy, and radiation therapy for bone and soft tissue tumors.
The Team and What We Do
Our department consists of six staff doctors, four residents 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 surgery, chemotherapy, or radiation therapy. Six to 10 major surgeries for musculoskeletal tumors are routinely performed every week. The number of surgeries in our department in 2020 was 317, of which 183 were for resection of malignant bone and soft tissue tumors (Table 1). In addition to patients with conditions involving the extremities, we collaborate with other surgeons to perform joint operations for patients involving the trunk, pelvis, and retroperitoneum, which are particularly difficult procedures. For extensive soft tissue defects or resection of major vessels caused by musculoskeletal tumor resection, plastic surgery offers reconstructive options.
In terms of drug therapy, we have been conducting neoadjuvant and adjuvant chemotherapy for high-grade bone and soft tissue sarcomas, and palliative chemotherapy for advanced disease, where necessary, in collaboration with medical oncologists. We have also been collaborating with pediatric oncologists for chemotherapeutic treatment of children and adolescents with sarcomas.
As for rehabilitation, in addition to musculoskeletal and cerebrovascular rehabilitation, we actively provide rehabilitation for cancer patients in the perioperative period and after chemotherapy and radiotherapy.
Research activities
Given that we have one of the largest numbers of sarcoma cases in Japan, we actively participate in multicenter studies considered necessary for treating sarcomas. In 2020, we participated in 8 studies in Japan, including 3 JCOG clinical trials and 7 international studies with research groups in Europe and the United States, and have registered many cases.
We are also working with the National Cancer Center Research Institute to create mouse xenografts of sarcoma tissue and novel sarcoma cell lines and to develop a diagnosis, treatment efficacy, and prognosis prediction for sarcomas through a comprehensive analysis of sarcoma-specific gene mutation analysis and gene expression analysis.
Education
In 2020, we accepted a total of 5 residents, who are receiving training in diagnosis, surgery, and chemotherapy of bone and soft tissue tumors. They have been instructed in the design, planning, and implementation of clinical research and in the preparation of scientific papers, and have achieved many outstanding results, including scientific awards.
Future Prospects
To further improve the outcome of malignant bone and soft tissue tumors, we must continue to promote innovative approaches, including surgery using advanced technologies and the development of new drugs, as well as to establish and disseminate standard treatments not only in Japan but also worldwide by conducting multicenter clinical studies led by our hospital.
List of papers published in 2020
Journal
1. Nishida Y, Urakawa H, Nakayama R, Kobayashi E, Ozaki T, Ae K, Matsumoto Y, Tsuchiya H, Goto T, Hiraga H, Naka N, Takahashi S, Ando Y, Ando M, Kuwatsuka Y, Hamada S, Ueda T, Kawai A. Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors. Int J Cancer, 148:140-149, 2021
2. Outani H, Kobayashi E, Wasa J, Saito M, Takenaka S, Hayakawa K, Endo M, Takeuchi A, Kobayashi H, Kito M, Morii T, Imanishi J, Ueda T. Clinical Outcomes of Patients with Metastatic Solitary Fibrous Tumors: A Japanese Musculoskeletal Oncology Group (JMOG) Multiinstitutional Study. Ann Surg Oncol, 28:3893-3901, 2021
3. Hirozane T, Masuda M, Sugano T, Sekita T, Goto N, Aoyama T, Sakagami T, Uno Y, Moriyama H, Sawa M, Asano N, Nakamura M, Matsumoto M, Nakayama R, Kondo T, Kawai A, Kobayashi E, Yamada T. Direct conversion of osteosarcoma to adipocytes by targeting TNIK. JCI Insight, 6:2021
4. Kim Y, Kobayashi E, Suehara Y, Ito A, Kubota D, Tanzawa Y, Endo M, Nakatani F, Nakatsura T, Kawai A, Kaneko K, Kitano S. Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma. Oncol Lett, 21:212, 2021
5. Toki S, Sone M, Yoshida A, Nishisho T, Gokita T, Kobayashi E, Nakatani F, Chuman H, Sugawara S, Arai Y, Kawai A. Image-guided core needle biopsy for musculoskeletal lesions. J Orthop Sci, 2021
6. Zhang L, Akiyama T, Fukushima T, Iwata S, Tsuda Y, Takeshita K, Kawai A, Tanaka S, Kobayashi H. Prognostic factors and impact of surgery in patients with metastatic soft tissue sarcoma at diagnosis: A population-based cohort study. Jpn J Clin Oncol, 51:918-926, 2021
7. SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study. Br J Surg, 2021
8. Frezza AM, Ravi V, Lo Vullo S, Vincenzi B, Tolomeo F, Chen TW, Teterycz P, Baldi GG, Italiano A, Penel N, Brunello A, Duffaud F, Hindi N, Iwata S, Smrke A, Fedenko A, Gelderblom H, Van Der Graaf W, Vozy A, Connolly E, Grassi M, Benjamin RS, Broto JM, Grignani G, Jones RL, Kawai A, Tysarowski A, Mariani L, Casali PG, Stacchiotti S. Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature. Cancer Med, 10:2645-2659, 2021
9. Tsuchiya R, Yoshimatsu Y, Noguchi R, Ono T, Sei A, Takeshita F, Sugaya J, Iwata S, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-SS4-C1: a novel patient-derived cell line of synovial sarcoma. Hum Cell, 34:998-1007, 2021
10. Kohsaka S, Hirata M, Ikegami M, Ueno T, Kojima S, Sakai T, Ito K, Naka N, Ogura K, Kawai A, Iwata S, Okuma T, Yonemoto T, Kobayashi H, Suehara Y, Hiraga H, Kawamoto T, Motoi T, Oda Y, Matsubara D, Matsuda K, Nishida Y, Mano H. Comprehensive molecular and clinicopathological profiling of desmoid tumours. Eur J Cancer, 145:109-120, 2021
11. Zhang L, Akiyama T, Fukushima T, Iwata S, Takeshita K, Kawai A, Tanaka S, Kobayashi H. Surgical resection of the primary lesion for osteosarcoma patients with metastasis at initial diagnosis. Jpn J Clin Oncol, 51:416-423, 2021
12. Iwata S, Kawai A, Ueda T, Ishii T. Symptomatic Venous Thromboembolism in Patients with Malignant Bone and Soft Tissue Tumors: A Prospective Multicenter Cohort Study. Ann Surg Oncol, 28:3919-3927, 2021
13. Iwata S. ASO Author Reflections: Venous Thromboembolism in a Patient with Musculoskeletal Tumor: Fact or Fiction? Ann Surg Oncol, 28:3928-3929, 2021
14. Tsuchiya R, Yoshimatsu Y, Noguchi R, Ono T, Sei A, Takeshita F, Sugaya J, Fukushima S, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-DDLPS3-C1: a novel patient-derived cell line of dedifferentiated liposarcoma. Hum Cell, 34:1008-1018, 2021
15. Ogura K, Somwar R, Hmeljak J, Magnan H, Benayed R, Momeni Boroujeni A, Bowman AS, Mattar MS, Khodos I, de Stanchina E, Jungbluth A, Asher M, Odintsov I, Hartono AB, LaQuaglia MP, Slotkin E, Pratilas CA, Lee SB, Spraggon L, Ladanyi M. Therapeutic Potential of NTRK3 Inhibition in Desmoplastic Small Round Cell Tumor. Clin Cancer Res, 27:1184-1194, 2021
16. Ogura K, Yakoub MA, Christ AB, Fujiwara T, Nikolic Z, Boland PJ, Athanasian EA, Healey JH. The critical difference in the DASH (Disabilities of the Arm, Shoulder, and Hand) outcome measure after essential upper extremity tumor surgery. J Shoulder Elbow Surg, 2021
17. Bartelstein MK, Yerramilli D, Christ AB, Kenan S, Ogura K, Fujiwara T, Fabbri N, Healey JH. Postradiation Fractures after Combined Modality Treatment in Extremity Soft Tissue Sarcomas. Sarcoma, 2021:8877567, 2021
18. Ogura K, Fujiwara T, Healey JH. Patients with increased time to treatment initiation have poorer survival after definitive surgery for localized high-grade soft tissue sarcoma in the extremity and trunk: Report from the National Cancer Database (NCDB). Bone Joint J, 103-B:1142-1149, 2021
19. Fujiwara T, Healey J, Ogura K, Yoshida A, Kondo H, Hata T, Kure M, Tazawa H, Nakata E, Kunisada T, Fujiwara T, Ozaki T. Role of Tumor-Associated Macrophages in Sarcomas. Cancers (Basel), 13:2021
20. Fukushima T, Ogura K, Akiyama T, Takeshita K, Kawai A. Soft tissue sarcoma in adolescent and young adult patients: a retrospective study using a nationwide bone and soft tissue tumor registry in Japan. Jpn J Clin Oncol, 2021
21. Watanabe S, Shimomura A, Kubo T, Sekimizu M, Seo T, Watanabe SI, Kawai A, Yamamoto N, Tamura K, Kohno T, Ichikawa H, Yoshida A. BRAF V600E mutation is a potential therapeutic target for a small subset of synovial sarcoma. Mod Pathol, 33:1660-1668, 2020
22. Kawai A, Higashi T, Shibata T, Yoshida A, Katoh Y, Fujiwara Y, Nishida T. Rare cancers in Japan: definition, clinical features and future perspectives. Jpn J Clin Oncol, 50:970-975, 2020
23. Sekita T, Yamada T, Kobayashi E, Yoshida A, Hirozane T, Kawai A, Uno Y, Moriyama H, Sawa M, Nagakawa Y, Tsuchida A, Matsumoto M, Nakamura M, Nakayama R, Masuda M. Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma. Cancers (Basel), 12:2020
24. Nakayama R, Hayakawa K, Kobayashi E, Endo M, Asano N, Yonemoto T, Kawashima H, Hamada K, Watanabe I, Futani H, Goto T, Nishida Y, Ozaki T. What Factors Are Associated with Treatment Outcomes of Japanese Patients with Clear Cell Chondrosarcoma? Clin Orthop Relat Res, 478:2537-2547, 2020
25. Nishida Y, Hamada S, Kawai A, Kunisada T, Ogose A, Matsumoto Y, Ae K, Toguchida J, Ozaki T, Hirakawa A, Motoi T, Sakai T, Kobayashi E, Gokita T, Okamoto T, Matsunobu T, Shimizu K, Koike H. Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan. Cancer Sci, 111:2935-2942, 2020
26. Urakawa H, Kawai A, Goto T, Hiraga H, Ozaki T, Tsuchiya H, Nakayama R, Naka N, Matsumoto Y, Kobayashi E, Okuma T, Kunisada T, Ando M, Ueda T, Nishida Y. Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study. Cancer Sci, 111:3303-3312, 2020
27. Shinoda Y, Kobayashi E, Kobayashi H, Mori T, Asano N, Nakayama R, Morioka H, Iwata S, Yonemoto T, Ishii T, Hiruma T, Kawai A, Kawano H. Prognostic factors of metastatic myxoid liposarcoma. BMC Cancer, 20:883, 2020
28. Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Sugaya J, Iwata S, Sugiyama M, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-ssRMS1-C1: a novel patient-derived spindle-cell/sclerosing rhabdomyosarcoma cell line. Hum Cell, 33:886-893, 2020
29. Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Sugaya J, Iwata S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-SS3-C1: a novel patient-derived cell line of synovial sarcoma. Hum Cell, 33:877-885, 2020
30. Yoshimatsu Y, Noguchi R, Tsuchiya R, Kito F, Sei A, Sugaya J, Nakagawa M, Yoshida A, Iwata S, Kawai A, Kondo T. Establishment and characterization of NCC-CDS2-C1: a novel patient-derived cell line of CIC-DUX4 sarcoma. Hum Cell, 33:427-436, 2020
31. Oyama R, Kito F, Takahashi M, Hattori E, Noguchi R, Takai Y, Sakumoto M, Qiao Z, Toki S, Sugawara M, Tanzawa Y, Kobayashi E, Nakatani F, Iwata S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors. Cancer Cell Int, 20:58, 2020
32. Ogura K, Boland PJ, Fabbri N, Healey JH. Rate and risk factors for wound complications after internal hemipelvectomy. Bone Joint J, 102-B:280-284, 2020
33. 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. Minimal clinically important differences in Toronto Extremity Salvage Score for patients with lower extremity sarcoma. J Orthop Sci, 25:315-318, 2020
34. Doi T, Matsubara N, Kawai A, Naka N, Takahashi S, Uemura H, Yamamoto N. Phase I study of TAS-115, a novel oral multi-kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs, 38:1175-1185, 2020
35. Ogura Y, Ogura K, Kobayashi Y, Kitagawa T, Yonezawa Y, Takahashi Y, Yoshida K, Yasuda A, Shinozaki Y, Ogawa J. Minimum clinically important difference of major patient-reported outcome measures in patients undergoing decompression surgery for lumbar spinal stenosis. Clin Neurol Neurosurg, 196:105966, 2020
36. Ogura K, Bartelstein MK, Yakoub MA, Nikolic Z, Boland PJ, Healey JH. Minimal clinically important differences in SF-36 global score: Current value in orthopedic oncology. J Orthop Res, 2020