Pretargeted radioimmunotherapy in rapidly progressing, metastatic, medullary thyroid cancer

Abstract

Medullary thyroid cancer (MTC) patients with localized residual disease and/or distant metastases may survive for several years or rapidly progress and die of their disease. Thus, highly reliable prognostic factors are needed for an early distinction between high-risk patients who need to be treated and low-risk patients who warrant a watch-andwait approach. Calcitonin doubling time is an independent predictor of survival, with a high predictive value in a population of patients who have not normalized their calcitonin, even after repeated surgery. Several imaging methods should be proposed for patients with abnormal residual calcitonin levels persisting after complete surgery: ultrasonography and computed tomography (CT) for neck exploration, and CT for chest, abdomen, and pelvis. Magnetic resonance imaging (MRI) appears to have an advantage over CT for the detection of liver metastases from endocrine tumors. Moreover, MRI appears to be a sensitive imaging technique for detecting the spread of MTC to bone/bone marrow. 2-Fluoro-2-deoxy-D-glucose positron emission tomography/CT could be used for staging patients with progressive MTC, with possible prognostication by standard uptake value quantification. For systemic treatment of patients with rapidly progressing metastatic MTC, chemotherapy is not considered a valid therapeutic option. It is too early to evaluate the potential effectiveness of multikinase inhibitors, although interesting results of phase 2 studies have shown a transient stabilization in 30% to 50% of patients. Pretargeted radioimmunotherapy has been the only innovative treatment modality convincingly showing some survival benefit when compared with a historical untreated control group. Cancer 2010;116(4 suppl):1118-25. V C 2010 American Cancer Society.KEYWORDS: radioimmunotherapy, medullary thyroid carcinoma, pretargeting, calcitonin, carcinoembryonic antigen.Medullary thyroid carcinoma (MTC) accounts for <8% of thyroid cancers. The primary treatment of hereditary or sporadic MTC is total thyroidectomy with dissection of ipsilateral and central lymph nodes, extended in some cases to contralateral dissection. Many patients are cured by this surgical intervention, especially those with familial hereditary MTC and who were operated on before tumor metastatic spread. However, a non-negligible number of patients show persistent disease after primary surgery, as documented by measurable serum calcitonin. 1 Pentagastrin stimulation makes the test extremely sensitive. Three months after surgery, serum calcitonin level is not detectable in >60% of patients without lymph node involvement, as opposed to <20% of patients with lymph node involvement. 2 When a recurrence is localized in the neck or mediastinum, a new surgery can be performed, but is followed by a decrease of calcitonin serum level to undetectable levels in < 1 = 3 of patients. 3 In patients with MTC, the rate of overall survival 10 years after primary surgery is 69%, but it decreases to 10% when distant metastases are present. 4 Patients with ...

Antibody-Radionuclide Conjugates for Cancer Therapy: Historical Considerations and New Trends

“…Antibody-based pretargeting strategies have produced spectacular biodistribution results in tumor-bearing animals [with tumor uptake as high as 278 AE 130%ID/g and tumor/blood ratios > 30 at 1 hour postinjection (30)] and promising results in cancer patients (31,32).…”

Complementary Roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in Medullary Thyroid Cancer

“…Prognostic factors include postoperative tumor burden and serum calcitonin concentration (2). Recently, promising results with systemic therapy including multikinase inhibitors (3) and pretargeted radioimmunotherapy have been reported (4). The primary treatment is total thyroidectomy, often including modified neck lymph node dissection.…”

Management of Postoperative Hypercalcitoninemia in MTC

“…Distant metastases at presentation are found in 7-23 % of patients [ 4 -8 ]. The main distant metastatic sites are the bone, liver, and lung [ 9 ]. In general, when MTC has spread out of the neck, there are no established therapies that can offer the possibility of a cure, and the 10-year survival rate drops below 40 % [ 10 ].…”