Osteosarcoma Management in the Precision Medicine Era: Bibliometric Analysis and Clinical Progress (2015–2024)

Document Type : SCOPING REVIEW

Authors

1 Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Joint Reconstruction Research Center, Department of Orthopedics, Tehran University of Medical Sciences, Iran

3 Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran -Joint Reconstruction Research Center, Department of Orthopedics, Tehran University of Medical Sciences, Iran

10.22038/abjs.2025.87193.3953

Abstract

Objectives: Osteosarcoma, the most common high-grade malignant bone tumor, has experienced only limited progress in therapeutic options, highlighting the urgent need for more effective treatments. This review examines bibliometric trends and clinical developments in osteosarcoma research from 2015 to 2024, with a particular focus on precision medicine and personalized therapy.
Methods: A search in the Web of Science Core Collection identified 17,476 osteosarcoma-related publications for bibliometric analysis. Key metrics, including publication trends, international collaborations, and emerging research topics, were evaluated using the Bibliometrix R package. Additionally, a clinical review examined recent innovations in diagnostic imaging, prognostic biomarkers, chemotherapy resistance, targeted therapies, immunotherapies, and surgical techniques.
Results: Research publications on osteosarcoma steadily increased, peaking at 2,009 in 2021, with significant contributions from China, the United States, Japan, India, and Italy. Key research themes encompassed apoptosis, metastasis, chemotherapy resistance, and immunotherapy. Advances in imaging techniques, such as dynamic MRI and PET/CT, have significantly enhanced tumor staging and prediction of treatment response. Emerging biomarkers, including genetic alterations (TP53, RB1, MYC) and inflammatory markers, have become important prognostic tools. Surgical innovations, including patient-specific instrumentation and limb-sparing techniques, have improved patient outcomes. Furthermore, targeted therapies (kinase inhibitors, antibody-drug conjugates) and immunotherapies (CAR T-cell therapy, immune checkpoint inhibitors) have demonstrated promising results in clinical trials.
Conclusion: Integrating bibliometric insights with clinical advancements underscores the importance of personalized approaches in osteosarcoma management. Predictive imaging biomarkers and precision-targeted therapies play a crucial role, and future research should focus on their clinical validation to enhance patient outcomes.
        Level of evidence: V

Keywords

Main Subjects

References

  1. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009:152:3-13. doi: 10.1007/978-1-4419-0284-9_1.
  2. Han G, Bi WZ, Xu M, Jia JP, Wang Y. Amputation Versus Limb-Salvage Surgery in Patients with Osteosarcoma: A Meta-analysis. World J Surg. 2016;40(8):2016-27. doi: 10.1007/s00268-016-3500-7.
  3. Hu X, Deng K, Ye H, et al. Trends in Tumor Site-Specific Survival of Bone Sarcomas from 1980 to 2018: A Surveillance, Epidemiology and End Results-Based Study. Cancers (Basel). 2021;13(21):5381. doi: 10.3390/cancers13215381.
  4. Kar E, Ammanamanchi A, Yousif M, et al. From bimodal to unimodal: The transformed incidence of osteosarcoma in the United States. J Bone Oncol. 2024:47:100613. doi: 10.1016/j.jbo.2024.100613.
  5. Wedekind MF, Wagner LM, Cripe TP. Immunotherapy for osteosarcoma: Where do we go from here? Pediatr Blood Cancer. 2018;65(9):e27227. doi: 10.1002/pbc.27227.
  6. Meazza C, Giovanna S, Nigro O, et al. Secondary osteosarcoma: a challenge indeed. Int J Clin Oncol. 2023;28(1):184-190. doi: 10.1007/s10147-022-02267-w.
  7. Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol. 2021;18(10):609-624. doi: 10.1038/s41571-021-00519-8.
  8. Patel N, Werenski JO, Gonzalez MR, et al. Tumor necrosis drives prognosis in osteosarcoma: No difference in chemotherapy response and survival between chondroblastic and osteoblastic osteosarcoma. Surg Oncol. 2024:57:102155. doi: 10.1016/j.suronc.2024.102155.
  9. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021:372:n71. doi: 10.1136/bmj.n71.
  10. Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: Current Treatment and a Collaborative Pathway to Success. J Clin Oncol. 2015;33(27):3029-35. doi: 10.1200/JCO.2014.59.4895.
  11. Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;18(11):1493-1501. doi: 10.1016/S1470-2045(17)30624-1.
  12. Ahmed N, Brawley VS, Hegde M, et al. Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma. J Clin Oncol. 2015;33(15):1688-96. doi: 10.1200/JCO.2014.58.0225.
  13. Ferrari C, Magagnoli G, Laranga R, et al. Osteosarcoma and Ewing Sarcoma of Bone: An Italian Mono-Institutional Epidemiological Study. Diagnostics (Basel).2025;15(3):328. doi: 10.3390/diagnostics15030328.
  14. Ogura K, Morizane C, Satake T, et al. Statistics of bone sarcoma in Japan: report from the population-based cancer registry in Japan. Int J Clin Oncol. 2024;29(9):1209-1219. doi: 10.1007/s10147-024-02566-4.
  15. Jeyaraman N, Jeyaraman M, Subramanian P, et al. Advancements in bone malignancy research through next-generation sequencing focussed on osteosarcoma, chondrosarcoma, and Ewing sarcoma. Pathol Res Pract. 2025:269:155908. doi: 10.1016/j.prp.2025.155908.
  16. Chiesa AM, Spinnato P, Miceli M, Facchini G. Radiologic Assessment of Osteosarcoma Lung Metastases: State of the Art and Recent Advances. Cells. 2021;10(3):553. doi: 10.3390/cells10030553.
  17. Kalisvaart GM, Evenhuis RE, Grootjans W, et al. Relative Wash-In Rate in Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Prognostic Biomarker for Event-Free Survival in 82 Patients with Osteosarcoma: A Multicenter Study. Cancers (Basel). 2024;16(11):1954. doi: 10.3390/cancers16111954.
  18. Palmerini E, Colangeli M, Nanni C, et al. The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas. Eur J Nucl Med Mol Imaging. 2017;44(2):215-223. doi: 10.1007/s00259-016-3509-z.
  19. Cè M, Cellina M, Ueanukul T, et al. Multimodal Imaging of Osteosarcoma: From First Diagnosis to Radiomics. Cancers (Basel). 2025;17(4):599. doi: 10.3390/cancers17040599.
  20. Beird HC, Bielack SS, Flanagan AM, et al. Osteosarcoma. Nat Rev Dis Primers. 2022;8(1):77. doi: 10.1038/s41572-022-00409-y.
  21. Lu Y, Wang D, Chen G, Shan Z, Li D. Exploring the molecular landscape of osteosarcoma through PTTG family genes using a detailed multi-level methodology. Front Genet. 2024:15:1431668. doi: 10.3389/fgene.2024.1431668.
  22. Gerstung M, Jolly C, Leshchiner I, et al. The evolutionary history of 2,658 cancers. Nature. 2020;578(7793):122-128. doi: 10.1038/s41586-019-1907-7.
  23. Meltzer PS, Helman LJ. New Horizons in the Treatment of Osteosarcoma. N Engl J Med. 2021;385(22):2066-2076. doi: 10.1056/NEJMra2103423.
  24. Huang X, Liu Y, Liang W, et al. A new model of preoperative systemic inflammatory markers predicting overall survival of osteosarcoma: a multicenter retrospective study. BMC Cancer. 2022;22(1):1370. doi: 10.1186/s12885-022-10477-8.
  25. Koirala P, Roth ME, Gill J, et al. HHLA2, a member of the B7 family, is expressed in human osteosarcoma and is associated with metastases and worse survival. Sci Rep. 2016:6:31154. doi: 10.1038/srep31154.
  26. McEachron TA, Triche TJ, Sorenson L, Parham DM, Carpten JD. Profiling targetable immune checkpoints in osteosarcoma. Oncoimmunology. 2018;7(12):e1475873. doi: 10.1080/2162402X.2018.1475873.
  27. Chen B, Zeng Y, Liu B, et al. Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study. Front Endocrinol (Lausanne). 2021:12:672024. doi: 10.3389/fendo.2021.672024.
  28. Bacci G, Briccoli A, Rocca M, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol. 2003;14(7):1126-34. doi: 10.1093/annonc/mdg286.
  29. Prabowo Y, Setiawan I, Kamal AF, Kodrat E, Labib Zufar ML. Correlation between Prognostic Factors and the Histopathological Response to Neoadjuvant Chemotherapy in Osteosarcoma: A Retrospective Study. Int J Surg Oncol. 2021:2021:8843325. doi: 10.1155/2021/8843325.
  30. Suárez-Mattos A, Arroyave F, Infante AM, et al. Response to neoadjuvant chemotherapy and survival of children and adolescents with high-grade osteosarcoma treated based on the EURAMOS-1 protocol. Bol Med Hosp Infant Mex. 2022;79(1):17-25. doi: 10.24875/BMHIM.21000087.
  31. Richardson SM, Wurtz LD, Collier CD. Ninety Percent or Greater Tumor Necrosis Is Associated With Survival and Social Determinants of Health in Patients With Osteosarcoma in the National Cancer Database. Clin Orthop Relat Res. 2023;481(3):512-522. doi: 10.1097/CORR.0000000000002380.
  32. Habre C, Dabadie A, Loundou AD, et al. Diffusion-weighted imaging in differentiating mid-course responders to chemotherapy for long-bone osteosarcoma compared to the histologic response: an update. Pediatr Radiol. 2021;51(9):1714-1723. doi: 10.1007/s00247-021-05037-4.
  33. Bouhamama A, Leporq B, Khaled W, et al. Prediction of Histologic Neoadjuvant Chemotherapy Response in Osteosarcoma Using Pretherapeutic MRI Radiomics. Radiol Imaging Cancer. 2022;4(5):e210107. doi: 10.1148/rycan.210107.
  34. Farina A, Gasperini C, Aparisi Gómez MP, Bazzocchi A, Fanti S, Nanni C. The Role of FDG-PET and Whole-Body MRI in High Grade Bone Sarcomas With Particular Focus on Osteosarcoma. Semin Nucl Med. 2022;52(5):635-646. doi: 10.1053/j.semnuclmed.2021.10.001.
  35. Oh C, Bishop MW, Cho SY, Im HJ, Shulkin BL. 18F-FDG PET/CT in the Management of Osteosarcoma. J Nucl Med. 2023;64(6):842-851. doi: 10.2967/jnumed.123.265592.
  36. Hashimi M, Hasan O, An Q, Miller BJ. Novel Scoring Criteria for Preoperative Prediction of Neoadjuvant Chemotherapy Response in Osteosarcoma. Iowa Orthop J. 2021;41(2):19-26.
  37. Marina NM, Smeland S, Bielack SS, et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016;17(10):1396-1408. doi: 10.1016/S1470-2045(16)30214-5.
  38. National Comprehensive Cancer Network. NCCN clinical practice guidelines in Oncology (NCCN Guidelines®): breast cancer. National Comprehensive Cancer Network. 2020 .
  39. Alexander JH, Binitie OT, Letson GD, Joyce DM. Osteosarcoma: An Evolving Understanding of a Complex Disease. J Am Acad Orthop Surg. 2021;29(20):e993-e1004. doi: 10.5435/JAAOS-D-20-00838.
  40. Pang K, Guo X, Liu T, et al. The Role of a Multidisciplinary Team in the Diagnosis and Treatment of Bone and Soft Tissue Sarcomas: A Single-Center Experience. J Pers Med. 2022;12(12):2079. doi: 10.3390/jpm12122079.
  41. Strönisch A, Märdian S, Flörcken A. Centralized and Interdisciplinary Therapy Management in the Treatment of Sarcomas. Life (Basel). 2023;13(4):979. doi: 10.3390/life13040979.
  42. Wilson R, Reinke D, van Oortmerssen G, et al. What Is a Sarcoma 'Specialist Center'? Multidisciplinary Research Finds an Answer. Cancers (Basel). 2024;16(10):1857. doi: 10.3390/cancers16101857.
  43. Gaspar N, Marques da Costa ME, Fromigue O, Droit R, Berlanga P, Marchais A. Recent advances in understanding osteosarcoma and emerging therapies. Fac Rev. 2020:9:18. doi: 10.12703/r/9-18.
  44. Brookes MJ, Chan CD, Baljer B, et al. Surgical Advances in Osteosarcoma. Cancers (Basel). 2021;13(3):388. doi: 10.3390/cancers13030388.
  45. Gharbi MA, Zendeoui A, Tborbi A, Bouzidi R, Ezzaouia K, Nefiss M. Conservative surgical management of surface osteosarcoma using 3D printing technology: An unusual case report and literature review. Int J Surg Case Rep. 2023 c:113:109086. doi: 10.1016/j.ijscr.2023.109086.
  46. McCulloch RA, Frisoni T, Kurunskal V, Maria Donati D, Jeys L. Computer Navigation and 3D Printing in the Surgical Management of Bone Sarcoma. Cells. 2021;10(2):195. doi: 10.3390/cells10020195.
  47. Gasparro MA, Gusho CA, Obioha OA, Colman MW, Gitelis S, Blank AT. 3D-Printed Cutting Guides for Resection of Long Bone Sarcoma and Intercalary Allograft Reconstruction. Orthopedics. 2022;45(1):e35-e41. doi: 10.3928/01477447-20211124-07.
  48. Aiba H, Spazzoli B, Tsukamoto S, et al. Current Concepts in the Resection of Bone Tumors Using a Patient-Specific Three-Dimensional Printed Cutting Guide. Curr Oncol. 2023;30(4):3859-3870. doi: 10.3390/curroncol30040292.
  49. Bosma SE, Wong KC, Paul L, Gerbers JG, Jutte PC. A Cadaveric Comparative Study on the Surgical Accuracy of Freehand, Computer Navigation, and Patient-Specific Instruments in Joint-Preserving Bone Tumor Resections. Sarcoma. 2018:2018:4065846. doi: 10.1155/2018/4065846.
  50. Liu X, Liu Y, Lu W, et al. Combined Application of Modified Three-Dimensional Printed Anatomic Templates and Customized Cutting Blocks in Pelvic Reconstruction After Pelvic Tumor Resection. J Arthroplasty. 2019;34(2):338-345.e1. doi: 10.1016/j.arth.2018.10.001.
  51. Abane L, Anract P, Boisgard S, Descamps S, Courpied JP, Hamadouche M. A comparison of patient-specific and conventional instrumentation for total knee arthroplasty: a multicentre randomised controlled trial. Bone Joint J. 2015;97-B(1):56-63. doi: 10.1302/0301-620X.97B1.34440.
  52. Hu H, Liu W, Zeng Q, et al. The Personalized Shoulder Reconstruction Assisted by 3D Printing Technology After Resection of the Proximal Humerus Tumours. Cancer Manag Res. 2019:11:10665-10673. doi: 10.2147/CMAR.S232051.
  53. Liang H, Ji T, Zhang Y, Wang Y, Guo W. Reconstruction with 3D-printed pelvic endoprostheses after resection of a pelvic tumour. Bone Joint J. 2017;99-B(2):267-275. doi: 10.1302/0301-620X.99B2.BJJ-2016-0654.R1.
  54. Nielsen CL, Dybdal DTH, Vester-Glowinski P, et al. Vascularized fibular grafting following tumor resection demonstrates acceptable long-term outcomes in Denmark: a national retrospective cohort study. Acta Orthop. 2025:96:87-93. doi: 10.2340/17453674.2025.42848.
  55. Bläsius F, Delbrück H, Hildebrand F, Hofmann UK. Surgical Treatment of Bone Sarcoma. Cancers (Basel). 2022;14(11):2694. doi: 10.3390/cancers14112694.
  56. Jaffe N, Puri A, Gelderblom H. Osteosarcoma: evolution of treatment paradigms. Sarcoma. 2013:2013:203531. doi: 10.1155/2013/203531.
  57. Li X, Moretti VM, Ashana AO, Lackman RD. Impact of close surgical margin on local recurrence and survival in osteosarcoma. Int Orthop. 2012;36(1):131-7. doi: 10.1007/s00264-011-1230-x.
  58. Quirion JC, Johnson SR, Kowalski BL, et al. Surgical Margins in Musculoskeletal Sarcoma. JBJS Rev. 2024;12(3). doi: 10.2106/JBJS.RVW.23.00224.
  59. Nogaro M-C, Mifsud M, McCarthy C, et al. The safe surgical margin in Ewing’s sarcoma. Surg Oncol. 2022:41:101737. doi: 10.1016/j.suronc.2022.101737.
  60. Bertrand TE, Cruz A, Binitie O, Cheong D, Letson GD. Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma? Clin Orthop Relat Res. 2016;474(3):677-83. doi: 10.1007/s11999-015-4359-x.
  61. Rijs Z, Jeremiasse B, Shifai N, et al. Introducing Fluorescence-Guided Surgery for Pediatric Ewing, Osteo-, and Rhabdomyosarcomas: A Literature Review. Biomedicines. 2021;9(10):1388. doi: 10.3390/biomedicines9101388.
  62. Liu Y, Valji K, Monsky W, Zheng C, Yang X. Optical imaging guidance in oncologic surgery and interventional oncology. Pharmacol Res. 2025:212:107612. doi: 10.1016/j.phrs.2025.107612.
  63. Coventon J. A review of the mechanism of action and clinical applications of sorafenib in advanced osteosarcoma. J Bone Oncol. 2017:8:4-7. doi: 10.1016/j.jbo.2017.07.001.
  64. Davis LE, Bolejack V, Ryan CW, et al. Randomized Double-Blind Phase II Study of Regorafenib in Patients with Metastatic Osteosarcoma. J Clin Oncol. 2019;37(16):1424-1431. doi: 10.1200/JCO.18.02374.
  65. Boye K, Longhi A, Guren T, et al. Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Cancer Immunol Immunother. 2021;70(9):2617-2624. doi: 10.1007/s00262-021-02876-w.
  66. Slemmons KK, Mukherjee S, Meltzer P, Purcell JW, Helman LJ. LRRC15 antibody-drug conjugates show promise as therapeutic agents for osteosarcoma in preclinical studies. Pediatr Blood Cancer. 2021;68(2):e28771. doi: 10.1002/pbc.28771.
  67. Pinto N, Albert CM, Taylor MR, et al. STRIvE-02: A First-in-Human Phase I Study of Systemically Administered B7-H3 Chimeric Antigen Receptor T Cells for Patients With Relapsed/Refractory Solid Tumors. J Clin Oncol. 2024;42(35):4163-4172. doi: 10.1200/JCO.23.02229.

 

 

 

 

The Archives of Bone and Joint Surgery
Volume 13, Issue 11
November 2025
Pages 693-703

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History

  • Receive Date: 09 April 2025
  • Revise Date: 10 June 2025
  • Accept Date: 16 June 2025

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