Epidemiology and therapies for metastatic sarcoma

Clinical Epidemiology Dovepress open access to scientific and medical research R e v ie w Open Access Full Text Article Clinical Epidemiology downloaded from https://www.dovepress.com/ by 51.38.247.138 on 12-Jul-2018 For personal use only. Epidemiology and therapies for metastatic sarcoma This article was published in the following Dove Press journal: Clinical Epidemiology 15 May 2013 Number of times this article has been viewed Ernest K Amankwah 1 Anthony P Conley 2 Damon R Reed 2 Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2 Sarcoma Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA 1 Abstract: Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. Keywords: chemotherapy, pediatric sarcoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, synovial sarcoma Introduction Correspondence: Damon Reed Moffitt Cancer Center, Sarcoma Department, 12902 Magnolia Drive, FOB 1, Tampa, FL 33612, USA Tel +1 813 745 297 Fax +1 813 745 8337 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/CLEP.S28390 Powered by TCPDF (www.tcpdf.org) Sarcomas, cancers of tissues derived from the mesenchymal layer, represent 1% of all cancers in adults, 10% of cancers in children, and 8% of cancer in adolescents and young adults. This rarity and the diversity across ages render diagnosis and treatment difficult. In 2012, 2890 new cases of bone and joint cancer and 11,280 new cases of soft tissue cancer were estimated in the USA.1 In this same year, 1410 and 3900 deaths due to bone and soft tissue cancers, respectively, were also estimated. Despite being rare, sarcomas contribute to a substantial loss of years of life compared to other cancers because of the many children, adolescents, and young adults diagnosed with sarcoma. Sarcomas are broadly classified as either soft tissue or bone neoplasms. There is substantial diversity in the more than 50 histologic soft tissue sarcoma (STS) subtypes.2 Peak incidence differs according to the histologic subtype with rhabdomyosarcoma being the most common type in early childhood, bone sarcomas predominating in Clinical Epidemiology 2013:5 147–162 147 © 2013 Amankwah et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress Clinical Epidemiology downloaded from https://www.dovepress.com/ by 51.38.247.138 on 12-Jul-2018 For personal use only. Amankwah et al adolescence, and multiple histologic types of soft tissue sarcomas predominating in young adulthood (,40 year old) and in older adults. From 2005–2009 approximately 29% of bone and joint cancer cases were diagnosed in patients under 20 years and 15% were diagnosed in 20–34 year olds. Nine percent of soft tissue cancer cases were diagnosed at ,20 years or 20–34 years.3 At present, it should be noted that metastatic sarcomas are defined by the presence of disease to any metastatic site. This definition of metastasis may change over time with the advent of more sensitive measures for detecting metastatic disease. Currently, micrometastases are frequently below the detection limit of modern scans. Perhaps biomarkers such as circulating tumor cells, tumor-specific DNA markers such as translocations, tumor-specific antigens, or microRNAs (miRNAs) may eventually be incorporated into the definition of metastases.4–9 In this report, we will review the epidemiology, current therapy and promising therapeutic directions, and outcomes of patients with metastatic sarcoma. This review will include the common sarcomas of childhood (rhabdomyosarcoma), adolescence and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor), and older adults (leiomyosarcoma, liposarcoma, and undifferentiated sarcoma). We will also discuss patients who present with localized disease but unfortunately relapse at metastatic sites. Epidemiology Incidence and survival Incidence and survival statistics were obtained from Surveillance, Epidemiology, and End Results (SEER) Fast Stats, an interactive tool that allows access to SEER and US cancer statistics.10 In 2009, STS accounted for 85.6% of all sarcomas diagnosed in the USA, whereas bone and joint sarcoma accounted for 14.4%. The incidence of STS is highest in individuals aged 65+ years and lowest in those ,20 years (Figure 1). The 10-year relative survival rate for STS among patients , 20 years old was 70%, but approximately 50% among patients . 65 years old (Figure 2). The incidence of bone and joint cancer is highest in individuals aged 65+ years and lowest in those aged 20–49 years (Figure 3). The 10-year relative survival rate for patients diagnosed at 20–49 years with bone and joint sarcoma is 70% and about 40% for patients diagnosed . 65 years (Figure 4). SEER does not distinguish between metastatic and lower stage sarcomas and, as detailed throughout this report, patients with metastatic sarcoma have a worse prognosis than those listed in the figures. Risk factors Sarcoma most typically presents spontaneously without a demonstrable cause. However, several risk factors have been associated with its development, including exposure to radiation and chemotherapeutic agents, viral infections, occupational factors, hereditary syndromes, certain diseases, and hormones. Radiation and c (...truncated)