The skeleton is one of the most common sites for metastatic cancer, and tumors arising from the breast or prostate possess an increased propensity to spread to this site. The growth of disseminated tumor cells in the skeleton requires tumor cells to inhabit the bone marrow, from which they stimulate local bone cell activity. Crosstalk between tumor cells and resident bone and bone marrow cells disrupts normal bone homeostasis, which leads to tumor growth in bone. The metastatic tumor cells have the ability to elicit responses that stimulate bone resorption, bone formation or both. The net result of these activities is profound skeletal destruction that can have dire consequences for patients. The molecular mechanisms that underlie these painful and often incurable consequences of tumor metastasis to bone are beginning to be recognized, and they represent promising new molecular targets for therapy.
Background
Patients with Ewing sarcoma require local primary tumor control with surgery, radiation, or both. Optimal choice of local control for overall and local disease control remains unclear.
Methods
Patients with localized Ewing sarcoma of bone treated on three consecutive protocols with standard dose 5-drug chemotherapy every 3 weeks were included (n = 465). We used propensity scores to control for differences between local control groups by constructing multivariate models to assess the impact of local control type on clinical endpoints [event-free survival (EFS); overall survival; local failure; distant failure] independent of differences in propensity to receive each local control type.
Results
Patients treated with surgery were younger (p=0.02) and had more appendicular tumors (p<0.001). Radiation, compared to surgery, had a higher unadjusted risk of any event (HR 1.70; 95% CI 1.18–2.44), death (HR 1.84; 95% CI 1.18–2.85), or local failure (HR 2.57; 95% CI 1.37–4.83). On multivariate analysis, radiation, compared to surgery, had a higher risk of local failure (2.41; 95% CI 1.24–4.68), though there were no significant differences in EFS (HR 1.42; 95% CI 0.94–2.14), overall survival (HR 1.37; 95% CI 0.83–2.26), or distant failure (HR 1.13; 95% CI 0.70–1.84) between local control groups.
Conclusions
In this large group of similarly treated patients, choice of local control was not significantly related to EFS, overall survival, or distant failure, though risk of local failure was greater for radiation compared to surgery. These data support surgical resection when appropriate, while radiotherapy remains a reasonable alternative in selected patients.
Giant cell tumor of bone is a benign albeit aggressive tumor commonly affecting the bones of the knee. Patients with these tumors present with pain, swelling, and inability to bear weight on the involved extremity. These destructive tumors typically arise in the metaphyseal region of the long bones in individuals in the second, third, and fourth generations of life. Histologically, the multinucleated giant cells are the hallmark of the lesion, easily recognized on histological review, which recently have become therapeutic targets for medical management of the disease. For decades, surgical management has been the primary treatment for giant cell tumor of the bone. Some tumors can be treated with excision and filling of the osseous void with bone cement or allograft. This is an effective treatment option with a low to moderate risk of local recurrence while preserving limb function. For more destructive tumors, wide excision and reconstruction with prosthetic, structural allograft or combined allograft prosthetic components are utilized. Advances in medical management of the disease have also demonstrated promise as an effective treatment; however, its use has usually been limited to the treatment of metastatic disease, recurrent disease or when advanced local disease would require surgical treatment felt to be overly morbid.
Topotecan had limited activity in patients with Ewing sarcoma or PNET metastatic at diagnosis. The topotecan-cyclophosphamide combination was active. Amifostine was not myeloprotective. Overall results showed no improvement compared with previous studies.
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