Halperin7e_CH29

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S E C T I O N I I  Techniques, Modalities, and Modifiers in Radiation Oncology

ment of bone pain, all bone-seeking radiopharmaceuticals can exhibit a flare in pain within 24 to 72 hours post injection that may last for 5 to 7 days. Appropriate analgesic manage- ment must be provided during this period. In the treatment of metastatic prostate cancer, prostate-specific antigen (PSA) levels may begin to decline within several days; however, the rapidity of decline, nadir of the PSA level, and duration of PSA response are not satisfactory predictors of improved outcomes. 86 The bone-seeking agents have been and continue to be used primarily in metastatic prostate cancer, and evi- dence of effectiveness in breast and lung cancer is limited with responses noted primarily in osteoblastic metastases. Plain radiographs of symptomatic metastatic sites should be obtained prior to the use of systemic agents for palliation of bone pain. If there is evidence of possible impending fracture, stabilization and/or EBRT should be initiated prior to sys- temic radionuclide therapy. If painful vertebral metastasis is apparent clinically, CT or magnetic resonance imaging (MRI) of the painful vertebral segments should be obtained prior to administration of isotope to ensure that no epidural disease is present. If this pathology is discovered, EBRT or surgery should be carried out prior to systemic isotope therapy. IV administration of all agents should be carried out slowly over 1 to 5 minutes, through indwelling catheters with clear and unobstructed flow clearly validated, adequate hydration, and careful radiation precautions for patients and staff. Radiopharmaceuticals Iodine 131 Physical Properties : t ½ = 8.0 days; radiation decay: β (606 keV maximum and 190 keV mean); γ (364 keV). Clinical Utility : Radioiodine 131 I was first used to treat benign thyroid disease in the late 1920s and early 1930s. The first reports of using 131 I to treat well-differentiated thyroid cancer (WDTC) were published in the 1940s. 91 To date, 131 I has become the standard of care, in conjunction with surgery, for the management of WDTC; its use and indications have been extensively reviewed. 92–94 Benign thyroid tissue (follicular cells) and certain thyroid carcinomas (follicular, papillary, and Hürthle cell carcinoma) will actively transport iodine into the cell via the sodium iodide symporter to initiate the synthe- sis thyroid hormone. As a result, this innate targeting system has been exploited for many decades to treat locally persis- tent, recurrent, or metastatic thyroid carcinoma. The major- ity of data concerning the treatment of WDTC with 131 I has been generated by large retrospective series of patients, with the resulting clinical data often spanning several decades. Frequently, these institutions used unchanged protocols and fixed activities for therapy. Regardless, considerable evidence exists concerning local control, decreased metastases, and a survival benefit when 131 I is used as part of the treatment regimen. 95–97 In general, 131 I therapy for WDTC is considered either abla- tion or treatment. Ablation is the use of 131 I to sterilize normal remnant thyroid tissue or microscopic disease that remains after thyroidectomy. Treatment refers to the therapeutic application of 131 I against cancer persistence, local recur- rence, or distant metastatic disease. Whereas the treatment aspect of 131 I is well accepted, ablation is more controversial. 98 Recent decades have revealed a decrease in mortality for WDTC, owing to the early diagnosis and aggressive treatment of WDTC with near-total thyroidectomy and 131 I ablation in selected patients at high risk for recurrence and mortality, fol- lowed by thyroid-stimulating hormone (TSH) suppression. 99 If it is determined that ablation will be performed, patients are placed on a low-iodine diet and TSH stimulation is performed by withholding thyroid hormone. 94 Standard fixed activities of

been for primary and secondary malignancies of bone and bone marrow. Other target sites, however, have been con- sidered. In some instances, these alternative uses have remained a part of the therapeutic armamentarium; how- ever, for many indications, the use of URT has yielded to nonradioactive approaches (corticosteroids, systemic che- motherapy, hormone therapy, analgesia, and surgery) and to EBRT. The lack of access to innovative candidate radionu- clides, diminished trial participation, and absence of utiliza- tion and teaching from many training programs have further exacerbated the problem. 76 Regardless, a review of 15 ran- domized controlled trials (1,146 analyzed patients) compar- ing URT to placebo or another radionuclide for the treatment of metastatic bone pain confirms the efficacy of URT for pain management. This review also provides evidence that URT resulted in significant and complete pain relief during a 1- to 6-month period. 88 Practice guidelines have been established for URT, 89 and evidence-based guidelines for palliation of bone metastases include URT as a reasonable therapeutic option. 90 The most common malignant sites that develop bone metastases are prostate, breast, and lung cancer. 78 URT exhib- its increased targeting of bone in areas of osteoblastic activity and exerts this propensity because of a chemical similarity to calcium, which is classified as an alkaline earth metal in the periodic table (as are 89 Sr and 223 Ra). These therapeutic agents may either directly substitute for stable analogues in hydroxyapatite or may be chemisorbed on the hydroxyapatite surface of the phosphate moiety of phosphonate chelates. 86 Radionuclide decay profiles that include gamma emissions may be utilized for imaging and for documentation of ther- apeutic uptake in regions of bone pathology. Bone scans (technetium 99m [ 99m Tc]) are typically performed to verify disseminated osseous disease. The intensity of uptake on pretherapeutic scanning does not necessarily coincide with therapeutic efficacy, and widely disseminated disease may actually produce “dilution” of dose and potentially reduced effectiveness. 86 Regardless of the precise method of chemical or physical affinity, the agents studied for palliation of osseous metastatic bone pain fared better than placebos in randomized trials. 90 There is, however, limited evidence that the response or mor- bidity profile of the different radiopharmaceuticals varies significantly among themselves. Additionally, there is little evidence that dose escalation either in individual or cumula- tive doses will improve effectiveness. Sequenced administra- tion has been investigated; however, if an initial intervention has not produced a significant level or duration of response, there is little evidence that additional administrations will increase effectiveness, but they may potentially increase morbidity. 86 Rapid and significant localization in bone by all agents will generally limit potential morbidity to myelosuppression, which in patients with adequate marrow reserve will usually be mild and be manifest initially within 1 week post admin- istration with evidence of thrombocytopenia. Leukopenia may develop somewhat later; however, all side effects typi- cally reverse without intervention within 8 to 10 weeks. Circulating isotope not immediately incorporated into bone is typically excreted in urine; therefore, patients with reduced renal function may not be ideal candidates for the agents and, if used, should have blood counts monitored carefully. Administration is routinely on an outpatient basis; thus, radi- ation protection measures for low-level radiation in urine should be practiced. Palliative effects may be observed within 3 to 5 days but usually peak at approximately 7 to 10 days, and the beneficial effects may last for months. At this point in time, subsequent administrations may be considered. When used for manage-