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Cancers
Special Issues
Clinical Treatment of Osteosarcoma
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Clinical Treatment of Osteosarcoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 7172

Special Issue Editor

Dr. Masanori Okamoto

E-Mail Website
Guest Editor
Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
Interests: drug design for osteosarcoma; bone biology

Special Issue Information

Dear Colleagues,

Curative treatment for high-grade osteosarcoma consists of pre- and postoperative chemotherapy and surgery. Surgery often requires reconstruction. Microscopically negative (R0) resection margins are required, but limb-sparing surgery is possible in many cases. Patients with pathological fractures do not necessarily require amputation. Most current protocols for localised disease include preoperative chemotherapy. MAP regimens with doxorubicin, cisplatin and high-dose methotrexate are the most commonly used first-line agents in paediatric and adolescent patients, but no new agents have been shown to be effective in the last 40 years in addition to MAP regimens. Treatment of recurrent osteosarcoma is primarily surgical in cases of solitary pulmonary metastases or local recurrence. As the 5-year survival rate for patients who achieve complete surgical remission is over 30%, all resectable complete resections should be attempted. For patients who do not achieve a complete resection, stereotactic radiotherapy, radiofrequency ablation, and cryotherapy are used. For relapsed and advanced osteosarcoma, no standard treatment regimen has been established and chemotherapy with cytotoxic agents such as ifosfamide, cyclophosphamide, etoposide, carboplatin, gemcitabine, and docetaxel is used. More recently, novel treatment options such as chemotherapy with tyrosine kinase inhibitors such as regorafenib and cabozantinib and immunotherapy have improved survival, but clinical needs remain unmet. In this Special Issue, we welcome original or review articles that provide an overview of the latest findings and future challenges in high-grade osteosarcoma.

Dr. Masanori Okamoto
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (3 papers)

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Research

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13 pages, 6829 KiB  
Article
Joint-Sparing Resection around the Knee for Osteosarcoma: Long-Term Outcomes of Biologic Reconstruction with Vascularized Fibula Graft Combined with Massive Allograft
by Roberto Scanferla, Federico Scolari, Francesco Muratori, Angela Tamburini, Luca Delcroix, Guido Scoccianti, Giovanni Beltrami, Marco Innocenti and Domenico Andrea Campanacci
Cancers 2024, 16(9), 1672; https://doi.org/10.3390/cancers16091672 - 26 Apr 2024
Cited by 2 | Viewed by 1724
Abstract
(1) Background: We aim to address the following questions. What was the complication rate of vascularized fibula graft (VFG) combined with massive allograft in patients treated with joint-sparing resection around the knee for a high-grade osteosarcoma? What was the long-term survivorship of VFG [...] Read more.
(1) Background: We aim to address the following questions. What was the complication rate of vascularized fibula graft (VFG) combined with massive allograft in patients treated with joint-sparing resection around the knee for a high-grade osteosarcoma? What was the long-term survivorship of VFG free from revision and graft removal? What were the functional results as assessed by the Musculoskeletal Tumor Society (MSTS) score? (2) Methods: 39 patients treated in our unit for osteosarcoma around the knee with intercalary resection and reconstruction with VFG combined with massive allograft were included; 26 patients underwent intercalary tibial resection, while 13 underwent intercalary femoral resection. (3) Results: Mean Follow-Up was 205 months (28 to 424). Complications that required surgery were assessed in requiring surgical revision in 19 patients (49%) after a mean of 31 months (0 to 107), while VFG removal was necessary in three patients (8%). The revision-free survival of the reconstructions was 59% at 5 years and 50% at 10 to 30 years. The overall survival of the reconstructions was 95% at 5 to 15 years and 89% at 20 to 30 years. The mean MSTS score was 29.3 (23 to 30). (4) Conclusions: VFG represents an effective reconstructive option after joint-sparing intercalary resection around the knee for osteosarcoma. Full article
(This article belongs to the Special Issue Clinical Treatment of Osteosarcoma)
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16 pages, 788 KiB  
Article
Primary Multi-Systemic Metastases in Osteosarcoma: Presentation, Treatment, and Survival of 83 Patients of the Cooperative Osteosarcoma Study Group
by Vanessa L. Mettmann, Claudia Blattmann, Godehard Friedel, Semi Harrabi, Thekla von Kalle, Leo Kager, Matthias Kevric, Thomas Kühne, Michaela Nathrath, Benjamin Sorg, Mathias Werner, Stefan S. Bielack and Stefanie Hecker-Nolting
Cancers 2024, 16(2), 275; https://doi.org/10.3390/cancers16020275 - 8 Jan 2024
Cited by 6 | Viewed by 2475
Abstract
Background: To evaluate patient and tumour characteristics, treatment, and their impact on survival in patients with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma. Precedure: Eighty-three consecutive patients who presented with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma were retrospectively reviewed. In [...] Read more.
Background: To evaluate patient and tumour characteristics, treatment, and their impact on survival in patients with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma. Precedure: Eighty-three consecutive patients who presented with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma were retrospectively reviewed. In cases of curative intent, the Cooperative Osteosarcoma Study Group recommended surgical removal of all detectable metastases in addition to complete resection of the primary tumour and chemotherapy. Results: Eighty-three eligible patients (1.8%) were identified among a total of 4605 individuals with high-grade osteosarcoma. Nine (10.8%) of these achieved complete surgical remission, of whom seven later had recurrences. The median follow-up time was 12 (range, 1–165) months for all patients. Actuarial event-free survival after 1, 2, and 5 years was 9.6 ± 3.2%, 1.4 ± 1.4%, and 1.4 ± 1.4%, and overall survival was 54.0 ± 5.6%, 23.2 ± 4.9%, and 8.7 ± 3.3%. In univariate analyses, elevated alkaline phosphatase before chemotherapy, pleural effusion, distant bones as metastatic sites, and more than one bone metastasis were negative prognostic factors. Among treatment-related factors, the microscopically complete resection of the primary tumour, a good response to first-line chemotherapy, the macroscopically complete resection of all affected tumour sites, and local treatment (surgery ± radiotherapy) of all bone metastases were associated with better outcomes. Tumour progression under first-line treatment significantly correlated with shorter survival times. Conclusion: The outlook for patients with multi-systemic primary metastases from osteosarcoma remains very poor. The utmost importance of surgical resection of all tumour sites was confirmed. For unresectable bone metastases, radiotherapy might be considered. In the patient group studied, standard chemotherapy was often insufficiently effective. In the case of such advanced disease, alternative treatment options are urgently required. Full article
(This article belongs to the Special Issue Clinical Treatment of Osteosarcoma)
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Review

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19 pages, 3776 KiB  
Review
Surface Markers and Chemokines/Cytokines of Tumor-Associated Macrophages in Osteosarcoma and Other Carcinoma Microenviornments—Contradictions and Comparisons
by Rikito Tatsuno, Yoshihiro Komohara, Cheng Pan, Tomonori Kawasaki, Atsushi Enomoto, Takahiro Jubashi, Hiroyuki Kono, Masanori Wako, Tomoyuki Ashizawa, Hirotaka Haro and Jiro Ichikawa
Cancers 2024, 16(16), 2801; https://doi.org/10.3390/cancers16162801 - 8 Aug 2024
Cited by 3 | Viewed by 2184
Abstract
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Prognosis is improving with advances in multidisciplinary treatment strategies, but the development of new anticancer agents has not, and improvement in prognosis for patients with pulmonary metastases has stalled. In [...] Read more.
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Prognosis is improving with advances in multidisciplinary treatment strategies, but the development of new anticancer agents has not, and improvement in prognosis for patients with pulmonary metastases has stalled. In recent years, the tumor microenvironment (TME) has gained attention as a therapeutic target for cancer. The immune component of OS TME consists mainly of tumor-associated macrophages (TAMs). They exhibit remarkable plasticity, and their phenotype is influenced by the TME. In general, surface markers such as CD68 and CD80 show anti-tumor effects, while CD163 and CD204 show tumor-promoting effects. Surface markers have potential value as diagnostic and prognostic biomarkers. The cytokines and chemokines produced by TAMs promote tumor growth and metastasis. However, the role of TAMs in OS remains unclear to date. In this review, we describe the role of TAMs in OS by focusing on TAM surface markers and the TAM-produced cytokines and chemokines in the TME, and by comparing their behaviors in other carcinomas. We found contrary results from different studies. These findings highlight the urgency for further research in this field to improve the stalled OS prognosis percentages. Full article
(This article belongs to the Special Issue Clinical Treatment of Osteosarcoma)
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