Systematic Review of Recurrent Osteosarcoma Systemic Therapy.

Ioanna Gazouli,Anastasios Kyriazoglou,Anastasios Pantazopoulos,Ioannis Chatzidakis,Panayiotis Papagelopoulos,Panagiota Economopoulou,Maria Prevezanou,Amanda Psyrri,Vasileios Kontogeorgakos,Maria Anastasiou,Ioannis Kotsantis,Georgios Kavourakis

doi:10.3390/cancers13081757

Ioanna Gazouli, Anastasios Kyriazoglou + Show 10 more

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https://doi.org/10.3390/cancers13081757

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Abstract

Simple SummaryOsteosarcoma is the most common primary bone cancer. Its therapeutic approach includes cytotoxic chemotherapy and surgery. However, when recurrence or metastasis occurs the therapeutic options are limited with poor results. Herein we have conducted a systematic review of the systemic treatment options in recurrent and/or metastatic osteosarcoma over the last two decades. Our results indicate the paucity of our therapeutic armamentarium for this entity, with the majority of the studied modalities resulting in limited or no benefits. Intense translational research and future clinical studies reveal the unmet need for new treatment options for osteosarcoma patients with metastatic and/or recurrent disease.Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.

Highlights

Osteosarcoma comprises 1% of all human malignancies
211 additional articles focusing on osteosarcoma diagnosis, prognosis and biology, as well as articles presenting surgical approaches and primary or adjuvant osteosarcoma treatment or preclinical assays, were considered to be outside of the scope of the present review
High dose chemotherapy with carboplatin and etoposide, followed by stem cell transplant, may induce a complete response rate up to 78%, with a 3-year disease-free survival rate up to 12% [29]

Summary

Introduction

Osteosarcoma comprises 1% of all human malignancies. It is the most frequent primary bone cancer, usually arising in the metaphyses of long bones of children and adolescents [1–3]. In older patients, it may arise in the axial skeleton, often complicating. Surgery alone, as applied in the 1960s, resulted in disappointing overall survival rates of 11%. Within one year from treatment up to 90% of operated patients experienced disease relapse, most often with lung metastases. The initiation of adjuvant chemotherapy in the 1970s increased the 5-year overall survival rates up to 68% [2,7,8]. Relapsed as well as primarily inoperable and/or refractory osteosarcoma, continue to be hardly manageable entities, with poor prognosis [9]

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