Lisa B. Ercolano, MD

Sarcoma is a rare and heterogeneous group of malignancies arising from mesenchymal tissue, which we broadly define as bone sarcomas or soft tissue sarcomas. Further classification is generally based on the cell of origin. The combination of rarity and variety of this disease group contributes to the unfortunate lack of significant progress in treatment over the last 50 years.

Since the discovery of usefulness of chemotherapy in treating patients with sarcoma in the 1970s, there has been minimal improvement in outcomes when treating this disease. While imaging techniques and surgical solutions have improved modestly, there has yet to be a breakthrough in systemic therapy. Furthermore, it remains all too common that 

 diagnosis of sarcomas is extended and fraught with errors, respectively. It is therefore imperative for clinicians to remain vigilant and understand when appropriate referrals should be made to a sarcoma center. It remains well established that patient outcomes are optimized when they are cared for by a multi-disciplinary team specialized in sarcoma care.

Osteosarcoma, while a rare cancer, is the most common primary bone cancer in children and young adults.

 There also exists a second peak in incidence in adults greater than 65 years old, which most often represents secondary cancer arising from such underlying processes as longstanding Paget’s Disease or prior irradiation. Osteosarcoma exemplifies the variety, nuance and challenges of sarcoma care. At the mention of this disease, most automatically envision conventional intramedullary high grade osteosarcoma, and while this is the most common form of this uncommon cancer, there are in fact, many variants of which one must be aware.

Patients with osteosarcoma will present with varying degrees of pain and sometimes fracture or deformity. While conventional osteosarcoma presents radiographically as a destructive bone forming lesion with extraosseous extension, osteosarcoma variants can have different appearances which may be misleading or nonspecific.

 For example, telangiectatic, small-cell, and giant cell-rich osteosarcomas can present as purely lytic lesions with variable periosteal reactions and soft tissue extensions. A low grade parosteal osteosarcoma classically presents as a stuck-on bony lesion at the metaphysis of the distal femur or proximal humerus, and can often mimic such benign processes as myositis ossificans or osteochondroma. Secondary osteosarcomas arising from underlying processes often present as a new focal lesion arising in the background of the baseline abnormality.

The radiographic finding then corresponds to a change or increase in clinical symptoms.It is at this stage that a patient should be referred to a sarcoma center so that proper workup can be initiated. Tissue sampling must be done in a manner to optimize diagnostic accuracy as well as with future surgical resection in mind. In fact, the most common indication for amputation in sarcoma is due to inappropriately performed biopsy by non-sarcoma clinicians, otherwise, limb salvage surgery can be performed greater than 90% of the time.

The initial use of chemotherapy in osteosarcoma was due to the lead times necessary to prepare for limb salvage resections and reconstructions in the 1970s, as reconstructive hardware, allografts, etc, were not available “off the shelf”. Given this lead time, these patients were given chemotherapy and in the case of those presenting with local disease only, survival rates improved dramatically. The standard regimen was and remains methotrexate, doxorubicin, and cisplatin (MAP), and high-dose methotrexate (HDMTX) for children and adults less than 40 years old.

 Unfortunately, there have not been significant discoveries since that time, moreover, for patients presenting with metastatic disease or those who do not have a good response to first-line treatment, we still do not have better options.

Osteosarcoma is a genomically complex disease and the degree of genomic instability suggests that the burden of antigens and neoantigens would provide an immunogenic potential. As of yet, immune checkpoint inhibitors have not met these expected responses.4 However, studies are ongoing to determine the best use of antibody-based or cell therapy approaches that target these overexpressed cell-surface molecules on osteosarcoma cells.

Especially for high-grade osteosarcoma, the development of improved systemic therapies is paramount. However, local control surgical options are also important considerations both for quantity and quality of life. In cases of lower-grade osteosarcomas, proper R0 resections are the curative treatment. Whereas all sarcomas were met with amputations in the past, we have now developed and fine-tuned multiple ways to widely resect these tumors and reconstruct the bony and soft tissue defects. Advanced imaging, custom cutting guides, 3D printing capabilities, computer navigation, and modular implants allow each osteosarcoma patient a personalized and optimized surgical plan.

Developing a surgical plan involves consideration of the patient’s age, function, goals, and likely future therapies. Dependent on the features of each case, an orthopaedic oncologist may partner with multiple surgical colleagues for best results. This can include surgical oncology, vascular, plastic, spine, and thoracic surgery. Again, demonstrating that optimal care for sarcoma patients is best accomplished with a multidisciplinary team of sarcoma experts rather than just alone.

1) Key statistics for osteosarcoma. American Cancer Society. October 8th, 2020. Accessed: July 21, 2022. https://bit.ly/3ctNFmF

2) Ercolano, L. Osteosarcoma Variants. In. Biermann J, Siegel G, eds. Orthopaedic Knowledge Update Musculoskeletal Tumors. 4th ed. Wolters Kluwer. 2020:181-190.

3) Ferrari S, Ruggieri P, Cefalo G, et al. Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1. J Clin Oncol. 2012 Jun 10;30(17):2112-8. doi: 10.1200/JCO.2011.38.4420

4) Wu CC, Beird HC, Andrew Livingston J, et al. Immuno-genomic landscape of osteosarcoma. Nat Commun. 2020 Feb 21;11(1):1008. doi: 10.1038/s41467-020-14646-w

Articles

For sarcoma awareness month, Lisa Ercolano, MD, discusses the need for a multidisciplinary approach to treating patients with osteosarcoma. 

Lisa B. Ercolano, MD | Authors

Articles

Sarcoma Awareness Month: Helping Patients with Osteosarcoma Requires Multidisciplinary Approach