Chapter 094. Soft Tissue and Bone Sarcomas and Bone Metastases (Part 7) Cancer in the bone may produce osteolysis, osteogenesis, or both. Osteolytic lesions result when the tumor produces substances that can directly elicit bone resorption (vitamin D–like steroids, prostaglandins, or parathyroid hormone–related peptide) or cytokines that can induce the formation of osteoclasts (interleukin 1 and tumor necrosis factor). Osteoblastic lesions result when the tumor produces cytokines that activate osteoblasts. In general, purely osteolytic lesions are best detected by plain radiography, but they may not be apparent until they are >1 cm. These lesions are more commonly associated with hypercalcemia and with the excretion of hydroxyproline-containing peptides indicative of matrix destruction. When osteoblastic activity is prominent, the lesions may be readily detected using radionuclide bone scanning (which is sensitive to new bone formation), and the radiographic appearance may show increased bone density or sclerosis. Osteoblastic lesions are associated with higher serum levels of alkaline phosphatase and, if extensive, may produce hypocalcemia. Although some tumors may produce mainly osteolytic lesions (e.g., kidney cancer) and others mainly osteoblastic lesions (e.g., prostate cancer), most metastatic lesions produce both types of lesion and may go through stages where one or the other predominates. In older patients, particularly women, it may be necessary to distinguish metastatic disease of the spine from osteoporosis. In osteoporosis, the cortical bone may be preserved, whereas cortical bone destruction is usually noted with metastatic cancer. Metastatic Bone Disease: Treatment Treatment of metastatic bone disease depends on the underlying malignancy and the symptoms. Some metastatic bone tumors are curable (lymphoma, Hodgkin's disease), and others are treated with palliative intent. Pain may be relieved by local radiation therapy. Hormonally responsive tumors are responsive to hormone inhibition (antiandrogens for prostate cancer, antiestrogens for breast cancer). Strontium 89 and samarium 153 are bone-seeking radionuclides that can exert antitumor effects and relieve symptoms. Bisphosphonates such as pamidronate may relieve pain and inhibit bone resorption, thereby maintaining bone mineral density and reducing risk of fractures in patients with osteolytic metastases from breast cancer and multiple myeloma. Careful monitoring of serum electrolytes and creatinine is recommended. Monthly administration prevents bone-related clinical events and may reduce the incidence of bone metastases in women with breast cancer. When the integrity of a weight-bearing bone is threatened by an expanding metastatic lesion that is refractory to radiation therapy, prophylactic internal fixation is indicated. Overall survival is related to the prognosis of the underlying tumor. Bone pain at the end of life is particularly common; an adequate pain relief regimen including sufficient amounts of narcotic analgesics is required. The management of hypercalcemia is discussed in Chap. 347. Further Readings Borden EC et al: Soft tissue sarcomas of adults: State of the translational science. Clin Cancer Res 9:1941, 2003 [PMID: 12796356] Helman LJ, Meltzer P: Mechanisms of sarcoma development. Nat Rev Cancer 3:685, 2003 [PMID: 12951587] Mocellin S et al: Adult soft tissue sarcomas: Conventional therapies and molecularly targeted approaches. Cancer Treat Rev 32:9, 2006 [PMID: 16338075] Pisters PW et al: Evidence-based recommendations for loc al therapy for soft tissue sarcomas. J Clin Oncol 25:1003, 2007 [PMID: 17350950] Scurr M, Judson I: How to treat the Ewing's family of sarcomas in adult patients. Oncologist 11:65, 2006 [PMID: 16401715] Verweij J et al: Progression-free survival in gas trointestinal stromal tumors with high- dose imatinib: Randomized trial. Lancet 364:1127, 2004 [PMID: 15451219] Bibliography Burgert EO et al: Multimodal therapy for the management of nonpelvic localized Ewing's sarcoma of bone: IESS II. J Clin Oncol 8:15 14, 1990 [PMID: 2099751] Cangir A et al: Ewing's sarcoma metastatic at diagnosis— results and comparisons of two intergroup studies. Cancer 66:887, 1990 [PMID: 2201433] Hayden JB, Hoang BH: Osteosarcoma: basic science and clinical implications. Orthop Clin North Am 37:1, 2006 [PMID: 16311106] Jablons D et al: Metastasectomy for soft tissue sarcoma— further evidence for efficacy and prognostic indicators. J Thorac Cardiovasc Surg 97:695, 1989 [PMID: 2709861] Lindberg RD et al: Conservative surgery and post- operative radiotherapy in 300 adults with soft tissue sarcomas. Cancer 47:2391, 1981 [PMID: 7272893] NIH Consensus Development Panel on Limb Sparing Treatment of Adult Soft Tissue Sarcomas and Osteosarcomas. JAMA 254:1791, 1985 Roth JA: Resection of pulmonary metastases from osteogenic sarcoma. Cancer Bull 42:244, 1990 Wittig JC et al: Osteosarcoma: A multidisciplinary approach to diagnosis and treatment. Am Fam Physician 65:1123, 2002 [PMID: 11925089] . Chapter 094. Soft Tissue and Bone Sarcomas and Bone Metastases (Part 7) Cancer in the bone may produce osteolysis, osteogenesis, or both 300 adults with soft tissue sarcomas. Cancer 47:2391, 1981 [PMID: 7272893] NIH Consensus Development Panel on Limb Sparing Treatment of Adult Soft Tissue Sarcomas and Osteosarcomas. JAMA 254:1791,. may relieve pain and inhibit bone resorption, thereby maintaining bone mineral density and reducing risk of fractures in patients with osteolytic metastases from breast cancer and multiple myeloma.