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Annual Report 2022

Department of Musculoskeletal Oncology and Rehabilitation

Akira Kawai, Shintaro Iwata, Eisuke Kobayashi, Koichi Ogura, Shuhei Osaki, Suguru Fukushima, Tetsuya Sekita, Yu Toda, Shin Ishihara, Takaya Funada, Shudai Muramatsu, Noriko Watanabe, Takuro Sakurai, Mami Oki, Yusuke Okita, Shota Yokota, Risa Abe, Kaneyuki Ichikawa, Aiko Matsuoka

Introduction

 Malignant tumors arising from connective tissues (malignant bone and soft tissue tumors) are very rare, accounting for only 1% 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 the standardized therapeutic approaches. Since 1962, our department has accumulated a vast array of clinical knowledge regarding musculoskeletal tumors in collaboration with radiologists and pathologists who specialize 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 for bone and soft tissue tumors: surgery, chemotherapy, and radiation therapy.

The Team and What We Do

 Our department consists of 6 staff doctors, 5 residents, 5 physiotherapists, 2 occupational therapists, and 3 speech therapist. 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 FY2022 was 335, of which 184 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 with tumors involving the trunk, pelvis, and retroperitoneum, which are particularly considered difficult procedures. For extensive soft tissue defects or resection of major vessels caused by musculoskeletal tumor resection, plastic surgery offers reconstructive options.

 As for chemotherapy, we have been conducting neoadjuvant and adjuvant chemotherapies for high-grade bone and soft tissue sarcomas, and chemotherapy for advanced disease, where necessary, in collaboration with medical and pediatric oncologists.

 As for rehabilitation, in addition to musculoskeletal and cerebrovascular rehabilitation, we actively provide rehabilitation for cancer patients in the perioperative period and post-chemotherapy and post-radiotherapy.

Table 1. Operative procedures
Table 1. Operative procedures

Table 1. Operative procedures
Table 1. Operative procedures

Research Activities

 Given that we have one of the largest numbers of sarcoma cases in Japan, we actively participate in multicenter studies that are considered necessary for treating sarcomas. In FY2022, we participated in 16 national multi-institutional studies and 3 international studies with research groups in Europe and the United States, and have registered many cases. In FY2022, our department has published 9 peer-reviewed papers.

 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 approaches to predicting diagnosis, treatment efficacy, and prognosis for sarcomas through a comprehensive analysis of sarcoma-specific gene mutation and gene expression analyses.

Education

 In FY2022, we have accepted a total of 5 residents for training in diagnosis, surgery, and chemotherapy of bone and soft tissue tumors. The training included topics on the design, planning, and implementation of clinical research and in the preparation of scientific papers, and we 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 continuing 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 2022

Journal

1. Morii T, Anazawa U, Sato C, Iwata S, Nakagawa M, Endo M, Nakamura T, Ikuta K, Nishida Y, Nakayama R, Udaka T, Kawamoto T, Kito M, Sato K, Imanishi J, Akiyama T, Kobayashi H, Nagano A, Outani H, Toki S, Nishisho T, Sasa K, Suehara Y, Kawano H, Ueda T, Morioka H. Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG). European journal of surgical oncology, 49:353-361, 2023

2. Christ AB, Bartelstein MK, Kenan S, Ogura K, Fujiwara T, Healey JH, Fabbri N. Operative management of metastatic disease of the acetabulum: review of the literature and prevailing concepts. Hip international, 33:152-160, 2023

3. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Osaki J, Adachi Y, Ono T, Tsuchiya R, Sato C, Iwata S, Kojima N, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-PLPS2-C1: a novel cell line of pleomorphic liposarcoma. Human cell, 36:468-475, 2023

4. Saito Y, Shimoi T, Iwata S, Maejima A, Abe K, Udagawa R, Yonemori K, Furukawa T, Wakao F. Impact of relative dose intensity of trabectedin with pegfilgrastim support: a single-centre retrospective study. Journal of chemotherapy (Florence, Italy), 1-8, 2023

5. Ishihara S, Ogura K, Maejima A, Shimoi T, Sudo K, Kojima Y, Fukushima S, Osaki S, Kobayashi E, Iwata S, Matsui Y, Yonemori K, Kawai A. Predictive value of peripheral blood markers in soft tissue sarcoma patients treated with eribulin. Japanese journal of clinical oncology, 53:494-500, 2023

6. Hirayama T, Ikezawa S, Okubo R, Mizuta T, Iwata S, Suzuki T. Mental health care use and related factors in adolescents and young adults with cancer. Supportive care in cancer, 31:247, 2023

7. Araki Y, Yamamoto N, Tanzawa Y, Higashi T, Kuchiba A, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Endo M, Kobayashi E, Tsuchiya H, Kawai A. Family cancer history and smoking habit associated with sarcoma in a Japanese population study. Scientific reports, 12:17129, 2022

8. Yoshida A, Satomi K, Kobayashi E, Ryo E, Matsushita Y, Narita Y, Ichimura K, Kawai A, Mori T. Soft-tissue sarcoma with MN1-BEND2 fusion: A case report and comparison with astroblastoma. Genes, chromosomes & cancer, 61:427-431, 2022

9. Nakayama S, Kobayashi E, Nishio J, Toda Y, Yotsukura M, Watanabe SI, Yamamoto T, Kawai A. Prognostic Factors of Pulmonary Metastasectomy for Soft Tissue Sarcomas Arising in the Trunk Wall and Extremities. Cancers, 14:3329, 2022

10. Asano N, Saito M, Kobayashi E, Morii T, Kikuta K, Watanabe I, Anazawa U, Takeuchi K, Suzuki Y, Susa M, Nishimoto K, Ishii R, Miyazaki N, Mrioka H, Kawai A, Horiuchi K, Nakayama R. Preoperative Denosumab Therapy Against Giant Cell Tumor of Bone is Associated with an Increased Risk of Local Recurrence After Curettage Surgery. Annals of surgical oncology, 29:3992-4000, 2022

11. Acem I, van Houdt WJ, Grünhagen DJ, van der Graaf WTA, Rueten-Budde AJ, Gelderblom H, Verhoef C, van de Sande MAJ. The role of perioperative chemotherapy in primary high-grade extremity soft tissue sarcoma: a risk-stratified analysis using PERSARC. European journal of cancer (Oxford, England : 1990), 165:71-80, 2022

12. Kawai A. The Shape of Tumor Treatment in this Country. Journal of orthopaedic science, 27:511-513, 2022

13. Kawai A, Araki N, Ae K, Akiyama T, Ozaki T, Kawano H, Kunisada T, Sumi M, Takahashi S, Tanaka K, Tsukushi S, Naka N, Nishida Y, Miyachi M, Yamamoto N, Yoshida A, Yonemoto T, Yoshida M, Iwata S. Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020 - Secondary publication. Journal of orthopaedic science, 27:533-550, 2022

14. Kojima Y, Shimoi T, Seo T, Yazaki S, Okuya T, Ohtake Y, Okuma HS, Shimomura A, Nishikawa T, Tanioka M, Sudo K, Noguchi E, Tamura K, Yoshida A, Iwata S, Kobayashi E, Kawai A, Fujiwara Y, Yonemori K. Poor Treatment Outcomes with Second-Line Chemotherapy in Advanced Synovial Sarcoma. Oncology, 100:370-375, 2022

15. Kozawa E, Nishida Y, Kawai A, Hayakawa K, Setsu N, Kawashima H, Iwata S, Tsuchiya H, Tsukushi S, Takenaka S, Imanishi J, Baba I, Nagano A, Morii T, Shirai T, Shimizu K, Kawano H. Clinical features and treatment outcomes of dedifferentiated and grade 3 chondrosarcoma: A multi-institutional study. Cancer science, 113:2397-2408, 2022

16. Kawai A, Narahara H, Takahashi S, Nakamura T, Kobayashi H, Megumi Y, Matsuoka T, Kobayashi E. Safety and effectiveness of eribulin in Japanese patients with soft tissue sarcoma including rare subtypes: a post-marketing observational study. BMC cancer, 22:528, 2022

17. Noh S, Nessim C, Keung EZ, Roland CL, Strauss D, Sivarajah G, Fiore M, Biasoni D, Cioffi SPB, Mehtsun W, Cananzi FCM, Sicoli F, Quagliuolo V, Chen J, Luo C, Gladdy RA, Swallow C, Johnston W, Ford SJ, Evenden C, Tirotta F, Almond M, Nguyen L, Rutkowski P, Krotewicz M, Pennacchioli E, Cardona K, Gamboa A, Hompes D, Renard M, Kollár A, Ryser CO, Vassos N, Raut CP, Fairweather M, Krakorova DA, Quildrian S, Perhavec A, Nizri E, Farma JM, Greco SH, Vincenzi B, Lopez JAG, Solerdecoll MS, Iwata S, Fukushima S, Kim T, Tolomeo F, Snow H, Howlett-Jansen Y, Tzanis D, Nikulin M, Gronchi A, Sicklick JK. Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group. Annals of surgery, 10.1097/SLA.0000000000005625, 2022

18. Hirai T, Kobayashi H, Kobayashi E, Saito M, Akiyama T, Kikuta K, Nakai T, Endo M, Tsukamoto S, Hakozaki M, Takenaka S, Nishimura S, Kawashima H, Tanzawa Y, Kawano H, Tanaka S. Dedifferentiation in low-grade osteosarcoma: a Japanese Musculoskeletal Oncology Group (JMOG) study. International journal of clinical oncology, 27:1758-1766, 2022

19. Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Akiyama T, Sato C, Kobayashi E, Kojima N, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-MFS6-C1: a novel patient-derived cell line of myxofibrosarcoma. Human cell, 35:1993-2001, 2022

20. Ogura K, Elkrief A, Bowman AS, Koche RP, de Stanchina E, Benayed R, Mauguen A, Mattar MS, Khodos I, Meyers PA, Healey JH, Tap WD, Hameed M, Zehir A, Shukla N, Sawyers C, Bose R, Slotkin E, Ladanyi M. Prospective Clinical Genomic Profiling of Ewing Sarcoma: ERF and FGFR1 Mutations as Recurrent Secondary Alterations of Potential Biologic and Therapeutic Relevance. JCO precision oncology, 6:e2200048, 2022

21. Akiyama T, Yoshimatsu Y, Noguchi R, Sin Y, Tsuchiya R, Ono T, Sugaya J, Kobayashi E, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-PS1-C1: a novel cell line of pleomorphic sarcoma from a patient after neoadjuvant radiotherapy. Human cell, 35:2011-2019, 2022