Hankui Lu

Incremental Value of 131I SPECT/CT in the Management of Patients with Differentiated Thyroid Carcinoma

131I whole-body scintigraphy (WBS) is a highly sensitive method for the detection of differentiated thyroid tumors and metastases. However, a lack of anatomic landmarks and the physiologic accumulation of the tracer complicate interpretation of the images. This prospective study was designed to evaluate the incremental value of 131I SPECT/CT over planar WBS in the management of patients with differentiated thyroid carcinoma (DTC). Methods: Planar imaging was performed on 66 consecutive DTC patients who were considered to have locally advanced or metastatic disease after total or nearly total thyroidectomy. SPECT/CT was added for patients whose planar findings were inconclusive. The planar images were interpreted by 2 experienced nuclear medicine physicians. Interpretation of the SPECT/CT images was a consensus opinion of one of the nuclear medicine physicians and an experienced radiologist. Fusion images were considered to improve image interpretation when they better localized sites of increased 131I uptake. The final diagnosis was verified by pathologic findings, other imaging modalities, and clinical follow-up. Both site-based and patient-based analyses were performed, and the impact of SPECT/CT results on therapeutic strategy was assessed. Results: A total of 232 foci were observed by 131I WBS, including 33.2% of foci localized in the thyroid bed, 62.1% due to malignant lesions, and 4.7% caused by nonthyroidal physiologic or benign uptake or a contaminant. Overall, 37 SPECT/CT studies were performed on 23 patients, whose planar images showed 81 inconclusive lesions. Precise localization and characterization of 131I-avid foci were achieved through 131I SPECT/CT in 69 (85.2%) and 67 (82.7%) of the 81 foci, respectively. Fusion images were considered to be of benefit in 17 (73.9%) of 23 patients. The therapeutic strategy was changed in 8 (47.1%) of 17 patients. Uncommon metastatic lesions were found in 9 (13.6%) of 66 patients with regard to SPECT/CT fusion images. Conclusion: Fusion of SPECT and CT images was of incremental value over WBS in increasing diagnostic accuracy, reducing pitfalls, and modifying therapeutic strategies in 73.9% of DTC patients. As SPECT/CT techniques emerge, 131I SPECT/CT may demonstrate higher value than WBS in the management of DTC.

The role of radionuclide lymphoscintigraphy in extremity lymphedema

The characteristics of lymphedema on radionuclide lymphoscintigraphy were studied, and the diagnostic value of radionuclide lymphoscintigraphy in lymphedema was evaluated. In this report radionuclide lymphoscintigraphy was performed in 110 cases of clinically suspected lymphedema. A retrospective study method was used to analyze the imaging results. The typical pattern of lymphedema on radionuclide lymphoscintigraphy was summarized. It was found that the characteristics of lymphedema on radionuclide lymphoscintigraphy were diverse. The most common pattern was increased radiotracer accumulation in the soft tissue and lymphatic webs. Surgery and infection dominated as the causes of lymphedema in this study. It was concluded that radionuclide lymphoscintigraphy is a useful noninvasive method for diagnosing lymphedema. It is easy to operate and provides reliable results.

Response to Sorafenib at a Low Dose in Patients with Radioiodine-Refractory Pulmonary Metastases from Papillary Thyroid Carcinoma

BACKGROUND Sorafenib has shown promise in the treatment of patients with advanced or metastatic thyroid carcinoma. However, the optimal dose has not been established and data on Chinese population are not available. We conducted a study to assess the responses to sorafenib at a low dose of 200 mg twice daily in patients with progressive radioiodine-refractory pulmonary metastases from papillary thyroid carcinoma (PTC). PATIENTS AND METHODS Eligible patients received sorafenib 200 mg orally twice daily. Responses were assessed using Response Evaluation Criteria in Solid Tumors and adverse events were assessed periodically. The end points included response rate and progression-free survival. RESULTS Nine patients with radioiodine-refractory PTC were enrolled in the study and treated for a minimum of 13 weeks. The objective partial response rate was 33%. The stable disease rate was 44%. The mean progression-free survival was 42 weeks (95% confidence interval, 29.5 to 53.9). Two patients showed disease progression, and one of them died at 4 months after beginning of treatment. There was a marked and rapid change in the serum thyroglobulin level after start of treatment, with a mean decrease of 60% within 12 weeks, consistent with radiographic findings. Although the types of toxicities were consistent with other sorafenib trials, their severity was relatively mild. None of the patients discontinued sorafenib or reduced their dose because of treatment-related adverse events. CONCLUSION Sorafenib at a dose of 200 mg twice daily has a potential therapeutic effect and is well tolerated in Chinese patients with PTC and radioiodine-refractory pulmonary metastases. Further study is warranted with a larger cohort of patients.

Brain Metastasis from Follicular Thyroid Carcinoma: Treatment with Sorafenib

BACKGROUND Sorafenib has shown promise in the treatment of patients with advanced or metastatic thyroid carcinoma. However, its therapeutic effect has not been assessed in patients with brain metastases from follicular thyroid carcinoma (FTC). Here, we report a patient in whom this treatment was employed with a relatively favorable response. PATIENT AND METHODS A 56-year-old woman had a thyroidectomy 8 years previously for FTC. She subsequently developed lung metastases, for which she received seven courses of radioiodine ((131)I) therapy. She developed right hemiplegia and other symptoms and was found to have a ≈ 5-cm lesion in the left parietal lobe. Radiosurgery with a total dose of 28 Gy (7 Gy/day, for 4 days) to treat her brain metastatic lesion was ineffective, and she was referred to us. We treated her with sorafenib, 200 mg orally, on a twice-daily basis. The effect of this intervention was assessed clinically and radiographically using Response Evaluation Criteria in Solid Tumors (RECIST). SUMMARY Symptoms and signs improved dramatically and continuously after initiation of sorafenib treatment. Partial response (PR) in the brain metastasis and stable disease (SD) in lung metastatic lesions were verified by consecutive imaging findings for more than one year. Despite alopecia, other treatment-related adverse events did not occur. CONCLUSIONS Targeted therapy such as with sorafenib could be an effective alternative therapeutic strategy in the treatment of progressive brain metastasis from differentiated thyroid carcinoma (DTC) when surgery, external beam radiation, and (131)I are not suitable or give poor outcomes. A paradigm of sustained low dose of sorafenib (200 mg,twice a day) may be well-tolerated without compromising maintenance of the therapeutic effect.

Comparison of free plasma metanephrines enzyme immunoassay with (131)I-MIBG scan in diagnosis of pheochromocytoma.

Measurement of free plasma metanephrines (metanephrine and normetanephrine), usually performed by high-performance liquid chromatography with electrochemical detection (HPLC-ECD), has been recommended as the single biochemical test of choice for the diagnosis of pheochromocytoma. Alternatively, a widely available, simple means to measure these biomarkers with enzyme immunoassay (EIA) needs to be studied. The aim of this study was to investigate the diagnostic efficacy of such a method in comparison with 131I-metaiodobenzylguanidine (MIBG) whole body scan (WBS) in patients with pheochromocytoma. We enrolled patients undergoing 131I-MIBG WBS due to clinical findings suggestive of pheochromocytoma (n = 45), and patients with primary hypertension (n = 36). All subjects had blood tests for free plasma metanephrine (MN) and normetanephrine (NM) with a commercially available EIA kit. WBS was positive in 30 pheochromocytoma patients and negative in 15 refuted ones, with 100% accuracy. The sensitivity, specificity and accuracy of MN and NM in combination (either or both positive) were 96.7%, 86.3% and 90.1%, showing comparable diagnostic performance both to 131I-MIBG WBS (all p > 0.1), and also to the same markers measured with HPLC-ECD reported in the literature. These results showed that the EIA method may be eligible as an alternative to HPLC-ECD for plasma metanephrine determination in the identification of pheochromocytoma.

Localization of Concomitant Metastases to Kidney and Erector Spinae from Papillary Thyroid Carcinoma Using 131I-SPECT and CT

Whole-body I scanning plays an important role in the management of patients with differentiated thyroid cancer (DTC). Areas of uptake demonstrated following diagnostic or therapeutic I administration indicate the need for further I therapy (1,2). The minor sites of the distant metastases of DTC have been documented in the literature (3). A diversity of organs, such as brain, liver, kidney, skin, and muscle, has been reported. Here, we describe an incidentally detected kidney and erector spinae metastasis of papillary thyroid carcinoma (PTC) that was found by I–single photon emission computed tomography (I-SPECT) and computed tomography (CT) scans. Concomitant kidney and erector spinae metastasis of DTC is extremely rare in the clinical setting. A 29-year-old man who presented with locoregional lymph nodes and pulmonary metastases from PTC was treated with I for ablation of the postsurgical thyroid remnant and metastases. The posttherapy whole-body scan revealed two abdominal foci of I uptake in addition to the cervical and pulmonary uptake (Fig. 1). The cervical I uptake was due to residual thyroid tissue after surgery, and the pulmonary uptake was due to lung metastases confirmed by the chest CT scans. To differentiate the two abdominal foci of I uptake, the co-registered SPECT and low-dose CT scan was performed using GE Hawkeye Millennium VG. The coregistered SPECT=CT fusion images showed that the abdominal foci located in the area of right kidney (Fig. 2A, solid-line arrow in Fig. 1) and right low-back muscle (Fig. 2B, dashed-line arrow in Fig. 1), respectively. Further examination with high-resolution CT revealed solitary lesion on the upper pole of right kidney (Fig. 3A, B; solid-line arrow) and the right erector spinae (Fig. 3C, D; dashed-line arrow), respectively. The right erector spinae lesion was pathologically diagnosed as PTC metastasis by biopsy. The right renal lesion was suggested to be a thyroid carcinoma metastasis based on the CT and I scan findings. DTC usually remains localized to the thyroid gland. At the time of initial diagnosis, however, there may be cervical lymph node metastases and distant metastases. The most common sites of the distant metastases of DTC are the lungs and bones. Rare sites of distant metastases include the brain, liver, peritoneum, kidney, skin, and muscle (3). Clinically detectable differentiated metastatic thyroid carcinoma to the kidney and muscle is rare. To the best of our knowledge, fewer than 20 cases of renal metastases and 3 cases of muscular metastases from DTC were reported in the literature (4). Among them, only one elderly patient with poorly differentiated follicular thyroid carcinoma concomitantly metastasized to the kidney and thigh muscle (5). A unique case of unusual metastasis sites in the kidney and erector spinae from PTC occurring in a young man is herein presented. The practical interest in this case is that young patients with PTC may occasionally develop muscular, renal, and other unusual metastases concomitantly. It should be kept in mind that all suspected tumors are likely to be considered as potential metastases from thyroid carcinomas in the clinical setting. Integrated I-SPECT=CT has been found to have an additional value over planar imaging in patients with thyroid cancer for correct characterization of equivocal tracer uptake seen on planar imaging as well as for precise localization of malignant lesions in the neck, chest, and skeleton. SPECT=CT optimized the localization of I uptake to lymph node metastases versus remnant thyroid tissue, to lung versus mediastinal metastases, and to the skeleton (6). This case also demonstrated the clinical usefulness of I-SPECT=CT fusion images in the management of thyroid carcinoma. It may improve the anatomically limited interpretation of I scintigraphy alone for patients with DTC (7,8).

Pulmonary fibrosis following radioiodine therapy of pulmonary metastases from differentiated thyroid carcinoma.

Lung metastases from differentiated thyroid carcinoma (DTC) are potentially curable, particularly in children and young adults who often live for decades with diffuse pulmonary metastases that have been appropriately treated. Moreover, radioiodine (I) therapy, also with high cumulative activity, can lead to longer survival time or complete recovery (1). Up to the present time, I was the only available systemic modality to treat patients with metastatic disease and for this reason was repeatedly administered, even when it was not clearly effective (2). Since effective therapeutic strategies are scarce at present, severe complications of radioiodine treatment of pulmonary metastases from thyroid cancer, including radiation pneumonitis and fibrosis, cannot be ignored. Herein, we present a patient with DTC lung metastases, who developed pulmonary fibrosis following repeated high-dose radioiodine therapy with high cumulative I activity. A 12-year-old girl, who had a near-total thyroidectomy and functional lymph node resection for papillary thyroid carcinoma in November 2001, presented to our clinic due to suspected extensive pulmonary metastases from thyroid carcinoma. On computed tomography (CT) plain scan of the chest, the pulmonary lesions were described as ‘‘innumerable micro-nodules scattered throughout the lungs’’ (Fig. 1). In January 2002, 3.7 GBq (100 mCi) of I was initially given, since miliary tuberculosis had been excluded. Four weeks before I therapy, L-thyroxine replacement therapy was withdrawn and low iodine diet protocols were applied. Serum thyroid-stimulating hormone, thyroglobulin (Tg), and Tg autoantibody levels, which were measured by chemiluminescent immunoassay system just before the radioiodine administration, were 125 ng=mL, 5120 ng=mL, and 26 U=mL, respectively. A high retention of radioiodine in the lungs was observed 5 days after radioiodine therapy via I scintigraphy, which revealed minimal uptake in the neck and intense uptake throughout both lung fields (Fig. 2). I treatment was then repeated periodically with an interval of 6 months using a high fixed dose of 5.55 GBq (150 mCi) due to persistent lung uptake and continuous decrease of serum Tg level. Thyroxine treatment was given at suppressive doses between I treatment courses. In July 2007, when cumulative activity of I achieved 64.75 GBq (1750 mCi), her stimulated serum Tg decreased to 514 ng=mL and minimal uptake in both lung fields was noticed, suggesting obvious reduction of functional metastases (Fig. 3). Blood cell counts and liver enzymes were always within normal ranges. Unfortunately, a few months later, she developed dyspnea on exertion, and radioiodine therapy was stopped. Over the next 6 months, her shortness of breath progressively increased. Her hypoxia continued to worsen to the point where she could not walk upstairs more than a few meters without becoming severely short of breath. Pulmonary function test revealed a significant decrement in total lung capacity, suggesting interstitial pulmonary fibrosis and restrictive lung disease. Chest CT scan also demonstrated pulmonary fibrosis and thickness of the pleura, in agreement with radiation fibrosis (Fig. 4). Approximately 10% of adults and 20% of children with DTC develop lung metastases sometime in the course of their disease. Fortunately, long-term survival is especially high when lung metastases are too small to be seen on the standard chest radiograph or CT. Ten-year survival rates are 100% when the metastases are only evident on the posttreatment whole body scan. The 10-year survival rates steadily decline as the metastases become larger, falling to about 40% when there are micronodules (<1 cm) on the chest X-ray and about 15% when the nodules are larger than 1 cm (3). Although management strategies for lung metastases vary, I will continue to be a major weapon in the fight against metastatic disease from DTC (4). Most centers use a fixed-dose approach to radioiodine therapy and prescribe 7.4 GBq (200 mCi) of radioiodine for adults, regardless of the extent or size of the lung metastases. Treatment of children with lung metastases is done in the same way, except that the amount of radioiodine administered is adjusted to the child’s size (body surface area). An elegant study by Tuttle et al. showed that this empiric dosing strategy frequently results in administered I doses exceeding the maximum tolerable activity safety limit of 200 cGy to the blood or bone marrow in patients who are 70 years old or older. The authors suggested that dosimetryguided radioactive iodine (RAI) therapy be preferable to fixeddose RAI treatment strategies in older patients with thyroid

Tumor Markers in Thyroid Carcinoma With Pulmonary Metastases After Thyroidectomy

Background The present study investigated several tumor markers in patients receiving multiple radioiodine treatments after thyroidectomy for differentiated thyroid carcinoma (DTC). Methods Serological tests for tumor markers (Tg, CFEA, CA125, CA19-9, CA72-4, and Cyfra 21-1) were performed in 57 patients with pulmonary metastases (subjects) and 76 patients without distant metastases (controls). Results Serum thyroglobulin was much higher in the subjects than in the controls (median, 595.0 versus 5.4 μg/L, P 0.05). CA72-4 was positive in 20.3% with more positive cases in those having received higher doses (cutoff dose 25.9 GBq, 36.8% versus 13.7%, P =0.003). Conclusion These tumor markers are not likely progression-related and are not recommended for the follow up of DTC patients unless other malignancies are indicated. The high sensitivity of CA72-4 may be related to radiation damage to the gastrointestinal mucosa.