Review
Common Musculoskeletal Tumors of Childhood and Adolescence

https://doi.org/10.1016/j.mayocp.2012.01.015Get rights and content

Abstract

Osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the most common malignant musculoskeletal tumors in children and adolescents. Today, most patients can be cured. Numerous factors have contributed to improved outcome for these patients over the past several decades. These include multidisciplinary care involving oncologists, radiation oncologists, surgeons, pathologists, and radiologists and enrollment of patients in clinical trials. Better understanding of molecular mechanisms of disease have resulted in studies using molecular targets in addition to standard chemotherapeutic agents, which hopefully will lead to better outcomes in the future. Moreover, new orthopedic techniques and devices as well as new technologies in radiation oncology hold promise for better local control of primary tumors and the potential for fewer late adverse effects. Despite this progress, patients must undergo lifelong follow-up for possible late effects of intense chemotherapy and radiation therapy. We review the diagnosis, prognosis, staging, multidisciplinary therapy, new directions in therapy, and long-term complications of treatment for these tumors. For this review, we searched MEDLINE using the terms rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, biology, and humans and limited the search to articles from 2000 to September 2011. Additional references found in these articles were utilized as appropriate, as well as references from the background information in current therapeutic studies of the Children's Oncology Group. The same database and time frame were searched for articles written by leading authorities in the field.

Section snippets

Methods

We searched MEDLINE using the terms rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, biology, and humans and limited the search to articles from 2000 to September 2011. Additional references found in these articles were utilized as appropriate, as well as references from the background information in current therapeutic studies of the Children's Oncology Group (COG). The same database and time frame were searched for articles written by leading authorities in the field. Discussion in this review

Epidemiology and Clinical Features

Osteosarcoma is the most common malignant bone tumor in children and adolescents, with an incidence of 4.4 per million.1 The peak age incidence is in the second decade of life, with a smaller peak in older adults. Ewing sarcoma/PNET is the second most common malignant bone tumor, with an incidence of 2.9 per million,2 and it also occurs in soft tissues. Bone tumors commonly manifest with pain and swelling in a bone or joint. Symptoms are often attributed to sports injuries in active

Osteosarcoma

High-grade OS is most likely derived from mesenchymal stem cells with at least partial osteoblastic lineage commitment, although the exact cell of origin is unclear.4 Patients with hereditary retinoblastoma, Rothmund-Thomson syndrome, Li-Fraumeni syndrome, and Werner syndrome are predisposed to development of OS, suggesting that alterations in the genes associated with these disorders (RB1, RECQL4, TP53, and WRN, respectively [for expansion of gene symbols, use search tool at www.genenames.org

Diagnosis and Staging

Ideally, evaluation of the child and adolescent with a suspected bone or soft tissue tumor should be performed at the institution that ultimately will be providing multidisciplinary care for the patient. For bone tumors, the biopsy needle tract or incision should be placed such that it can be incorporated into the final surgical excision if surgery is the ultimate form of local tumor control.28 Planning of the biopsy should be coordinated between the radiologist and the surgeon for patients

Multidisciplinary Therapy and Prognosis

When evaluating a child or teenager newly diagnosed with one of these malignancies, it is important to involve a multidisciplinary team of oncologists, surgeons, and radiation oncologists from the outset so that the treatment planning can progress seamlessly and the timing of local control can be optimized so as not to delay chemotherapy. Because radiation treatments are based on the extent of tumor at the time of diagnosis, the radiation oncologist must see patients with ES/PNET and RMS

Late Effects

Despite the advances in cure rates for children and adolescents with these tumors, the long-term consequences of aggressive chemotherapy, radiotherapy, and surgery can be substantial. Survivors are much more likely than controls to have at least one, and often multiple, chronic medical conditions. Examples are cardiac toxicity from anthracyclines, hearing loss or tinnitus from cisplatin, infertility from alkylator therapy or radiation to the pelvis, endocrine complications usually from

New Directions

Recently, the importance of insulin-like growth factor receptor in promoting tissue growth and the contribution of the insulin-like growth factor system to cellular proliferation and immortality in a wide variety of cancers have been recognized. Overexpression of IGF1 and IGF2 have been reported in ES, OS, and RMS, and high expression of IGF1R has also been reported in these and other cancers. In vitro data have demonstrated the key roles of IGF1R in pediatric sarcomas in particular.97, 98, 99

Conclusion

Recent advances in the multidisciplinary management of musculoskeletal tumors in children and adolescents have enabled most children and adolescents with nonmetastatic disease to be cured; however, late effects are not inconsequential. It is hoped that during the next decade we will discover which patients can have therapy reduced and still have the same good outcome, and new approaches with targeted agents and new surgical and radiotherapeutic techniques will be developed for patients with

Acknowledgments

The authors would like to thank Karen Fasbender for help in manuscript preparation and submission.

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