Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies

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Orthopedic Tissue Engineering Basic Science and Practice

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Conceived and designed the experiments: Y. Performed the experiments: X.


Biology and Therapeutic Advances for Pediatric Osteosarcoma

Recruited the participants and collected medical information and samples: X. Prepared Figures and Tables: X. Wrote the main manuscript: X. All authors reviewed the manuscript and approved this submission. Correspondence to Yingguang Wu. Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Experimental and Molecular Pathology By submitting a comment you agree to abide by our Terms and Community Guidelines.

If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Advanced search. Skip to main content. Subjects Bone cancer Cancer genetics.

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Table 1 Clinical characteristics of OS patients and normal controls. Full size table. Table 3 The association of rs with clinicopathological characteristics in OS patients. Figure 1. Full size image. Figure 2. Methods Participants A 2-stage case-control study was conducted. Protein isolation and Western blot analysis According to the distribution of the rs genotype, all OS patients were divided into 3 groups. Statistical analysis Categorical data from OS patients and normal controls were compared using a Chi-square test. Other commonly referenced prognostic indicators include LDH elevation and Huvos tumor necrosis grade, 38 following standard neoadjuvant chemotherapy administration and wide surgical resection.

Interestingly, modifications of neoadjuvant treatment regimens to achieve better tumor necrosis thus far have not affected survival outcomes.


Accurate diagnosis and staging are fundamental prerequisites for appropriate treatment planning, patient education and guidance, and patient participation in clinical trials. It is important that the treating team be experienced in the diagnosis and treatment of bone sarcomas to minimize iatrogenic morbidity and maximize diagnostic accuracy. Osteosarcomas are often treated at tertiary care facilities, which evaluate and treat these rare malignancies in multidisciplinary settings that serve to improve communication between physicians and coordination of patient care.

Imaging studies include plain radiographs of the involved bone and adjacent joint. Osteosarcoma typically appears as a mixed radiodense and lytic lesion arising in an eccentric manner from the metaphyseal bone. Figures 1 and 2. There is frequently mass extension into the adjacent tissue. Cortical destruction and periosteal reaction are common, and typically manifest in a sunburst pattern. Osteosarcoma mineralizes in a centrifugal manner and should not be confused with myositis ossificans, which has an overall benign appearance and which ossifies in a centripetal fashion.

The plain radiograph is very suggestive, and classic radiographic features should prompt the assumption that the lesion is a primary bone sarcoma until otherwise proven. Pain at rest, night pain, and progressive pain all warrant radiographic examination. Given the relative ease and safety of radiography, clinicians should maintain a low threshold for obtaining plain films.

A magnetic resonance imaging MRI study of the entire bone is warranted for anatomic evaluation of soft tissue extension, to assess proximity to surrounding structures, and to identify skip metastases Figures 3 and 4. MRI studies can also suggest the rare but recognized phenomenon of tumor extension into the adjacent joint, which in the knee more commonly occurs by tumor growth along the cruciate ligaments. Computed tomography CT scans are rarely obtained for the primary tumor, since soft tissue extension, local intramedullary extension, and intramedullary skip metastases are all better visualized using MRI.

However, a CT scan of the thorax is currently the most sensitive noninvasive diagnostic modality available for the detection of metastatic disease within the lungs. Current diagnostic limitations preclude accurate detection of metastatic nodules under 5 mm in size, and therefore, a repeat CT scan for assessment of interval change in 6—12 weeks time is often recommended. CT scans have been shown to be inferior to manual tactile examination during open thoracotomies, with metastatic disease identified in up to one-third more cases using manual palpation.

Bone scintigraphy using technetium 99 is employed for the detection of distant bone disease, which is the second most likely location for metastatic spread. Positive findings on bone scan may warrant additional imaging of the area of concern and, ultimately, a biopsy may be necessary to prove the definitive presence of distant bone disease. The role of positron emission tomography PET in the setting of osteosarcoma continues to evolve. At least 1 report has concluded that total lesion glycolysis before chemotherapy correlates with poor overall survival and that an increase in total lesion glycolysis after chemotherapy correlates with worse PFS.

Currently, the exact role for PET imaging within the formal staging scheme remains unclear. Biopsies should be performed at a tertiary care medical center with experience in sarcoma diagnosis and treatment. Ideally, the biopsy should be obtained either by the surgeon who will ultimately render definitive care or, in some instances, by a radiologist well versed in sarcoma core needle biopsy techniques.

This concept is critical to oncologic and functional outcomes, and adverse effects associated with deviation from this approach have been well documented. Biopsies may be performed in the operating room in an incisional open manner or as an outpatient procedure using a core needle technique. Careful hemostasis is critical to minimize hematoma formation. Incision and drain site location are vital, as they ultimately need to be resected with the tumor in an en bloc manner. Surgical staging is performed using the Musculoskeletal Tumor Society staging scheme, originally developed and described by Enneking.

The American Joint Committee on Cancer 6th edition has put forth a tumor, lymph nodes, metastases staging system, which arguably is of less surgical utility.

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Surgical treatment demands complete extirpation of the tumor together with any previously placed biopsy tract, drain tract, or potentially contaminated tissue. This should be a wide excision, meaning a normal cuff of tissue should surround or envelope the tumor, ensuring complete containment of malignant cells. Wide excisions may be realized through more ablative means such as an amputation or a disarticulation, or through more conservative means.


The latter approach spares many of the uninvolved structures and allows for limb-salvage reconstruction. The decision as to whether a limb salvage procedure is appropriate needs to be objectively and accurately stated, and should be considered by the treating sarcoma team in advance of surgery. Though limb salvage surgery is often the preferred choice for many patients and families, it is not always the proper oncologic procedure, and optimizing oncologic outcomes takes priority over functional outcomes.

As most osteosarcomas arise within the metaphyseal bone and do not extend into the joint, intra-articular resections are most commonly offered. In the case of rare intra-articular tumor extension, an extra-articular resection becomes necessary. In the uncommon advent of a small tumor, a hemicortical or partial metaphyseal resection may be possible, which in some instances can yield much better long-term limb function. In the case of a purely diaphyseal lesion, intercalary resection of the involved diaphysis also offers excellent reconstructive and functional outcomes, sparing the adjacent joints and obviating the joint reconstruction typically required Figure 5.