Abstract
Primary and metastatic malignant bone lesions result in significant pain and disability in oncology patients. Targeted bone-seeking radioisotopes including 153Samarium ethylene-diamine-tetramethylene-phosphonic acid (153Sm-EDTMP) have been shown to effectively palliate bone pain, often when external beam radiotherapy (EBRT) is not feasible. However, recent evidence also suggests 153Sm-EDTMP has cytotoxic activity either alone or in combination with chemotherapy or EBRT. 153Sm-EDTMP may be useful as anti-neoplastic therapy apart from pain palliation in a variety of malignancies. For prostate cancer patients, several phase I and II clinical trials have shown that combined 153Sm-EDTMP and docetaxel-based chemotherapy can result in >50% decrease in prostate-specific antigen with manageable myelosuppression. In hematologic malignancies, 153Sm-EDTMP produced clinical responses when combined with bortezomib in multiple myeloma. 153Sm-EDTMP also can be used with myeloablative chemotherapy for marrow conditioning prior to stem cell transplant. In osteosarcoma, 153Sm-EDTMP infusion delivers radiation to multiple unresectable lesions simultaneously and provides local cytotoxicity without soft tissue damage that can be combined with chemotherapy or radiation. Prior to routine incorporation of 153Sm-EDTMP into therapeutic regimens, we must learn how to ensure optimal delivery to tumors, determine which patients are likely to benefit, improve our ability to assess clinical response in bone lesions and further evaluate the efficacy 153Sm-EDTMP in combination with chemotherapy, radiation and novel targeted agents.
Highlights
Malignant bone lesions are widely encountered in medical oncology patients and related pain and skeletal events, such as pathologic fracture, spinal cord compression, hypercalcemia, pancytopenia from bone marrow infiltration and immobility lead to poor performance status, impaired quality of life and inability to tolerate further treatment [1]
Three-dimensional SPECT/CT dosimetry data can be translated to effective biologic dose, converted to traditional external beam radiotherapy (EBRT) fraction equivalents and incorporated into a subsequent intensity-modulated radiotherapy (IMRT) treatment plan [89]
In primary bone tumors such as osteosarcoma, the ability to provide definitive local therapy is limited for patients with multiple lesions, unresectable metastases, or tumors in locations that prohibit tumoricidal-dose EBRT
Summary
Malignant bone lesions are widely encountered in medical oncology patients and related pain and skeletal events, such as pathologic fracture, spinal cord compression, hypercalcemia, pancytopenia from bone marrow infiltration and immobility lead to poor performance status, impaired quality of life and inability to tolerate further treatment [1]. Even modern conformal techniques such as intensity-modulated radiotherapy (IMRT) have limited utility in the setting of multiple or diffuse lesions. Another challenge is local management of unresectable osteosarcoma, the most common primary bone tumor in children and young adults. 153samarium ethylene-diamine-tetramethylenephosphonic acid (153Sm-EDTMP) is more clinically useful due to a shorter half-life. This remarkably well-tolerated radiopharmaceutical is administered and displays impressive specificity for bone lesions with toxicity limited to transient myelosuppression.
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