Combined [<Superscript>18</Superscript>F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Detection of Recurrent, <Superscript>131</Superscript>I-Negative Thyroid Cancer

Background Whole-body ¹³¹I scintigraphy (WBS) and serial thyroglobulin measurement (Tg) are standard methods for detecting thyroid cancer recurrence after total/near total thyroidectomy and ¹³¹I ablation. Some patients develop elevated Tg (Tg-positive) or there is clinical suspicion of recurrence, but WBS are negative (WBS-negative). This may reflect non-iodine-avid recurrence or metastasis. In 2002, the Centers for Medicare and Medicaid Services (CMS) approved positron emission tomography with [¹⁸F]fluorodeoxyglucose (FDG-PET) for Tg-positive/WBS-negative patients with follicular-cell-origin thyroid cancer. Limited data are available regarding the performance of combined FDG-PET/computed tomography (FDG-PET/CT) for detecting recurrent thyroid cancer in WBS-neg patients. Methods This retrospective review of prospectively collected data analyzed 65 patients who had FDG-PET/CT for suspected thyroid cancer recurrence (April 1998–August 2006). Patients were WBS-negative but were suspected to have recurrence based on Tg levels or clinical grounds. Suspected FDG-PET/CT abnormalities were reported as benign or malignant. Lesions were ultimately declared benign or malignant by surgical pathology or clinical outcome (disease progression). Results Of 65 patients who underwent FDG-PET/CT, 47 had positive FDG-PET/CT. Of the positive FDG-PET/CT, 43 studies were true positives, with 21 (49%) confirmed pathologically by surgical resection. The four false positives (3/4 confirmed pathologically) included an infundibular cyst, an inflamed supraclavicular cyst, pneumonitis, and degenerative disc disease. Of the 18 FDG-PET/CT studies that were negative, 17 were true negatives and one was a false negative (metastatic papillary carcinoma). Thus, FDG-PET/CT demonstrated a patient-based sensitivity of 98%, specificity of 81%, positive predictive value of 91%, and negative predictive value of 94%. Conclusions FDG-PET/CT is useful for detecting thyroid cancer recurrence in WBS-negative patients, and can assist decision making.     

PET/CT in the management of differentiated thyroid cancer

The standard treatment of differentiated thyroid cancer (DTC) consists of surgery followed by iodine-131 (¹³¹I) administration. Although the majority of DTC has a very good prognosis, more aggressive histologic subtypes convey a worse prognosis. Follow-up consists of periodically measurements of serum thyroglobulin, thyroglobulin antibodies and neck ultrasound and ¹²³I/¹³¹I whole-body scan. However, undifferentiated thyroid tumors have a lower avidity for radioiodine and the ability of DTC to concentrate ¹³¹I may be lost in metastatic disease. Positron emission tomography (PET)/computed tomography (CT) has been introduced in the evaluation of patients with thyroid tumors and the 2-[18F]-fluoro-2-deoxyd-glucose (¹⁸F-FDG) has been largely validated as marker of cell's metabolism. According to the 2015 American Thyroid Association guidelines, ¹⁸F-FDG PET/CT is recommended in the follow-up of high-risk patients with elevated serum thyroglobulin and negative ¹³¹I imaging, in the assessment of metastatic patients, for lesion detection and risk stratification and in predicting the response to therapy. It should be considered that well-differentiated iodine avid lesions could not concentrate ¹⁸F-FDG, and a reciprocal pattern of iodine and ¹⁸F-FDG uptake has been observed. Beyond ¹⁸F-FDG, other tracers are available for PET imaging of thyroid tumors, such as Iodine-124 (¹²⁴I), ¹⁸F-tetrafluoroborate and Gallium-68 prostate-specific membrane antigen. Moreover, the recent introduction of PET/MRI, offers now several opportunities in the field of patients with DTC. This review summarizes the evidences on the role of PET/CT in management of patients with DTC, focusing on potential applications and on elucidating some still debating points.     

The role of positron emission tomography scanning in patients with radioactive iodine scan-negative, recurrent differentiated thyroid cancer

An elevated thyroglobulin (Tg) level after total thyroidectomy for differentiated thyroid cancer is often associated with disease recurrence. 131I-whole body scans (131I-WBS) and cross-sectional imaging are commonly used to localize occult metastases in these patients. Localizing disease when 131I-WBS are negative and cross-section imaging is equivocal remains a challenge. The medical records of 12 patients with thyroid cancer undergoing positive positron emission tomography (PET) scans for 131I-WBS-negativeTg elevations or the presence of anti-Tg antibodies were identified and charts were reviewed in a retrospective fashion. All had been treated with total thyroidectomy and 131I ablation in the past. Computed tomography, magnetic resonance imaging, or ultrasound studies revealed suspicious lesions in eight patients. All 12 patients underwent resection of the PET-positive lesions. All resections were positive for thyroid cancer in the regions predicted by the positive PET scan. All nine (100%) patients with elevated preoperative Tg levels experienced a reduction in Tg level after resection. PET scans accurately predict the presence of recurrent thyroid cancer when 131I-WBS are negative. PET scans should be considered in the follow up of 131I-WBS-negative patients with thyroid cancer who are suspected of having recurrent disease.     

Postoperative surveillance of differentiated thyroid carcinoma: a selective approach

This review was conducted to evaluate the selective use of 131I whole-body scanning (WBS) and radioablation (RA) after thyroidectomy for patients with differentiated thyroid carcinoma (DTC). A review of patients undergoing thyroidectomy for DTC between July 1, 1980 and December 31, 1999 was performed. Postoperative surveillance involved a selective RA protocol based on a modification of the AMES criteria (age, metastases, extent of cancer, size, and multifocality of tumor). Lower-risk patients were followed by yearly thyroglobulin (Tg) levels and physical examinations (PE) whereas higher-risk patients additionally underwent WBS and RA when appropriate. Three hundred forty-three patients were identified; of these 27 per cent had positive lymph nodes or metastatic disease at their initial operation. Two hundred thirteen (64%) patients underwent postoperative WBS with 174 (82%) requiring RA. One hundred thirty (36%) low-risk patients were followed with yearly Tg and PE that when abnormal led to WBS and RA. No additional patient morbidity or mortality resulted from this protocol. Factors identified during multivariate analyses as being predictive of occult metastasis and recurrence (P < 0.05) included tumor size and lymph node status. These data support a selective approach to the postoperative surveillance of DTC using Tg and PE to monitor low-risk patients and WBS for those with a higher risk of recurrence.     

Histological verification of positive fluorine-18 fluorodeoxyglucose findings in patients with differentiated thyroid cancer

Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a new imaging modality used in the follow-up of patients with differentiated thyroid cancer if the results of ¹³¹I scintigraphy are negative in spite of an elevated thyroglobulin level. The aim of this retrospective analysis was to estimate the value of FDG-PET regarding the operability of patients with positive findings. From January 1994 to October 1997, we investigated 60 patients with differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on after positive findings. Most of these lesions were suspected of having lymph-node involvement or local recurrences in the thyroid bed. One patient showed a solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13 patients confirmed the suspected involvement of thyroid cancer. The false-positive findings were caused by inflamed lymph nodes in two cases and benign thymus tissue in one case. We conclude that PET is a useful diagnostic tool to guide early surgical therapy in patients with ¹³¹I-negative differentiated thyroid carcinoma. Received: 6 February 1998     

Lymph Node Status Influences Follow-Up Thyroglobulin Levels in Papillary Thyroid Cancer

Background  Elevated thyroglobulin (Tg) levels post surgery are associated with disease recurrence in papillary thyroid carcinoma (PTC). The aim of this study is to determine which clinicopathological factors influence Tg elevation following surgery and radio-iodine ablation (RAI) for PTC. Methods  A retrospective study of consecutive patients undergoing total thyroidectomy and RAI for PTC was carried out. Prophylactic central neck dissection (CND) was performed if the diagnosis of PTC was made preoperatively. Lateral neck dissection (LND) was guided by ultrasound findings. RAI was administered 6 weeks postoperatively. Stimulated Tg levels were measured at 12 months. Results  One hundred patients with PTC were studied. Forty patients had routine CND. The median tumour size was 15 mm. Median stimulated Tg level at 12 months was 0.3 μg/L. On multivariate analysis the number of metastatic lymph nodes removed had a significant positive association with serum Tg levels (P = 0.003). The total number of lymph nodes resected had a significant inverse relationship with serum Tg levels (P = 0.04). Tumour size, multifocality, vascular and capsular invasion did not appear to have significant correlation with Tg levels. Conclusion  Lymph node metastases are associated with increased postablative Tg levels in PTC. More complete lymphadenectomy is associated with lowering of Tg levels.     

Characteristics of Primary Papillary Thyroid Carcinoma with False-Negative Findings on Initial 18F-FDG PET/CT

Background

We often observe that uptake of tracer is not detected in the primary cancer focus in patients with histologically proven papillary thyroid carcinoma (PTC) on preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET/CT). Therefore, we analyzed the clinical and pathologic variables affecting false-negative findings in primary tumors on preoperative ¹⁸F-FDG PET/CT.

Methods

We retrospectively reviewed the medical records of 115 consecutive patients who underwent ¹⁸F-FDG PET/CT for initial evaluation and were diagnosed with PTC by postoperative permanent biopsy. The clinical and pathologic characteristics that influence the ¹⁸F-FDG PET/CT findings in these patients were analyzed with respect to the following variables: age, gender, tumor size, multifocality of the primary tumor, perithyroidal invasion, lymphovascular or capsular invasion, and central lymph node metastasis-based final pathology.

Results

Twenty-six (22.6%) patients had false-negative ¹⁸F-FDG PET/CT findings. In patients with negative ¹⁸F-FDG PET/CT findings, tumor size, and perithyroidal and lymphovascular invasion were significantly less than in patients with positive ¹⁸F-FDG PET/CT findings. Tumors >1 cm in size were correlated with ¹⁸F-FDG PET/CT positivity. On multivariate analysis, perithyroidal invasion (P = 0.026, odds ratio = 7.714) and lymphovascular invasion (P = 0.036, odds ratio = 3.500) were independent factors for ¹⁸F-FDG PET/CT positivity. However, there were no significant differences between ¹⁸F-FDG PET/CT positivity and age, gender, capsular invasion, and central lymph node metastasis based on final pathology.

Conclusions

Tumor size and perithyroidal and lymphovascular invasion of papillary carcinoma can influence ¹⁸F-FDG PET/CT findings. Absence of perithyroidal and lymphovascular invasion were independent variables for false-negative findings on initial ¹⁸F-FDG PET/CT in patients with PTC.     

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.     

Restaging the axilla after neo‐adjuvant chemotherapy for breast cancer: Predictive factors for residual metastatic lymph node disease with negative imaging findings

To evaluate predictive factors for residual metastatic axillary lymph node (ALN) disease in patients with negative imaging findings after neo‐adjuvant chemotherapy (NAC) for breast cancer. From January 2011 to December 2015, 206 patients underwent imaging including ultrasonography, MRI, and PET/CT for restaging the axilla after NAC. Data collected included preoperative information regarding histologic grade, hormone receptor (HR) status, and human epidermal growth factor receptor 2 (HER2) status. Multivariate logistic regression analysis was performed to compare patients with and without residual metastatic ALN disease among patients who showed negative imaging findings after NAC. Of the 181 and 25 patients with initially node‐positive and node‐negative disease, 131 (72.4%) and 23 (92.0%), respectively, showed negative imaging findings after NAC. Among these 131 and 23 patients, 53 (40.5%) and two patients (8.7%), respectively, had residual metastatic ALN disease. Low to moderate tumor grade (odds ratio [OR] = 5.2, P = 0.009), positive HR status (OR = 6.6, P = 0.003), and negative HER2 status (OR = 2.6, P = 0.048) were associated with residual metastatic ALN disease. Low to moderate histologic grade, positive HR status, and negative HER2 status may serve as predictors of residual metastatic ALN disease in patients with negative imaging findings after NAC for breast cancer.     

Incidental and Nonincidental Papillary Thyroid Microcarcinoma

Background  Subtotal thyroidectomy or lobectomy without radioactive iodide (¹³¹I) treatment is sufficient for postoperative treatment of incidental papillary thyroid microcarcinoma (PTMC). Aggressive surgical treatment with ¹³¹I therapy is indicated for nonincidental PTMC. Methods  This is a retrospective analysis of 335 PTMC patients who received primary thyroid surgical treatment and long-term follow-up in a single medical center. All PTMC patients were categorized as incidental (group I) or nonincidental (group II). Group II patients (209 cases) were categorized as intrathyroid (group II A), neck lymph node or local regional soft-tissue invasion (group II B) and distant metastasis (group II C) groups. Results  In group I, 105 of 126 cases received only subtotal thyroidectomy or lobectomy. None died of thyroid cancer. Histological evaluation revealed multicentric PTMC in 12 (9.5%) and 52 (24.9%) cases (P < 0.05) in groups I and II, respectively. In group II, 55 of the 209 patients (26.3%) presented with extrathyroidal involvement. Two cases of relapse occurred in group I and 20 in group II by the end of follow-up. One patient in group II B and two patients in group II C died of thyroid cancer. Nine out of ten patients in group II C were diagnosed with distant metastases before primary thyroid surgical treatment. Conclusion  Subtotal thyroidectomy is effective surgical treatment for incidental PTMC. For nonincidental cases, aggressive treatment is essential for reducing the risk of cancer relapse or mortality following surgery.     

Positron emission tomography with F-18-deoxyglucose in patients with differentiated thyroid carcinoma, elevated thyroglobulin levels, and negative iodine scans

Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastastic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan. Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine-131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8±94.3 ng/ml, range 1.5 – 277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8±32.2 μIU/ml, range 31 – 116 μIU/ml, median 74.6 μIU/ml). Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7±90.1 ng/ml (23 – 277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0±7.6 ng/ml (range 1.5 – 17 ng/ml, median 8.1 ng/ml), P = 0.01. Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative “conventional” diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions. Received: 15 November 1997     

甲状腺球蛋白实验研究进展与临床应用

甲状腺球蛋白(Tg)是由甲状腺滤泡细胞合成分泌的大分子糖蛋白,是合成甲状腺激素的基质。源于甲状腺滤泡上皮细胞的分化型甲状腺癌(DTC)细胞也不同程度分泌Tg。血清Tg作为DTC特异性肿瘤标志物应用于DTC患者术后的危险分层、疗效评估、长期随访监测及预后判断。但Tg分子存在异质性,血液检测值受到检测方法学、Tg自身抗体等多因素的干扰,导致临床应用血清Tg值评估DTC病情时存在诸多实际问题,即使如此,近年来超敏检测方法的使用进一步增加了Tg的临床适用性。笔者就Tg的相关研究及临床应用需注意的一些问题做简要概述。     

Effect of Prophylactic Central Compartment Neck Dissection on Serum Thyroglobulin and Recommendations for Adjuvant Radioactive Iodine in Patients with Differentiated Thyroid Cancer

Background

Controversy exists in the management of patients with differentiated thyroid cancer (DTC). The purpose of this study was to examine the effect of prophylactic central compartment neck dissection (CCND) on serum thyroglobulin (Tg) levels and recommendations for adjuvant radioactive iodine (RAI).

Methods

The records of 103 patients who underwent completion/total thyroidectomy for DTC between January 2009 and November 2010 were reviewed. Prophylactic CCND was defined as removal of central compartment lymph nodes with no preoperative or intraoperative evidence of lymphadenopathy. Institutional protocol included a diagnostic whole-body scan before RAI; patients with a negative scan and Tg?<?2.0 did not receive adjuvant RAI.

Results

Among the 103 patients, therapeutic CCND was performed in 17 (17?%) and prophylactic CCND in 49 (48?%). Of the 49 patients, 20 (41?%) had positive cervical lymph nodes. Positive lymph nodes changed American Joint Committee on Cancer tumor, node, metastasis staging in 17 patients and recommendations for RAI in 14. At a median follow-up of 21?months, there was no difference in Tg level based on the application of CCND; however, 92?% of patients with M0 disease had an undetectable Tg. One patient had recurrent DTC based on serum Tg only.

Conclusions

Prophylactic CCND resulted in detection of unsuspected metastatic lymphadenopathy in 20 (41?%) of 49 patients and changed RAI recommendations in 14 (33?%). To date, most patients have an undetectable Tg. Longer follow-up is needed to detect potential differences in recurrent disease based on the use of CCND or long-term effects of RAI.     

Value of preoperative diagnostic modalities in patients with recurrent thyroid carcinoma

BACKGROUND: Patients with well-differentiated thyroid cancer (WDTC) regularly have an excellent prognosis. However, tumor recurrence either involving the thyroid bed or the regional lymph nodes, or both, can be associated with significant morbidity and even mortality. The aim of the follow-up after primary surgery is to detect recurrent disease at its earliest stage. We assessed the value of different diagnostic methods in detecting locoregional recurrence in patients with WDTC. METHODS: We prospectively identified 150 patients with WDTC. Of those, 43 (28.7%) presented with recurrent disease. Ultrasonography-guided fine needle biopsy (US-FNB), iodine 131 ((131)I) wholebody scintigraphy, thyroglobulin (Tg) measurement, and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were carried out. RESULTS: Ultrasonography detected malignant lesions in 95.3% of the patients. The true positive rate of US-FNB was 95.3%. (131)I scanning had true positive, false negative, and false positive results in 54.2%, 40.0%, and 5.7% of the cases, respectively. In 85.7% of the patients, Tg levels were within pathologic range. Among the 13 patients who underwent FDG-PET, 84.6% showed pathologic uptake indicating malignancy. US and US-FNB provided the highest specificity for detecting recurrence (P <.001). CONCLUSIONS: In patients with WDTC and locoregional recurrence, US and US-FNB are the most sensitive methods in detecting local recurrence or regional lymph node metastases. FDG-PET is valuable in case of negative (131)I scanning results and elevated serum Tg levels. The method has limitations in finding minimal disease.     

Frequency and predictive factors of malignancy in residual thyroid tissue and cervical lymph nodes after partial thyroidectomy for differentiated thyroid cancer

BACKGROUND: The extent of surgery in differentiated thyroid cancer (DTC) has been a controversial issue. Total thyroidectomy potentially carries a higher operative risk, whereas partial thyroidectomy has the risk of leaving significant residual malignancy. The aim of this study was to assess the frequency and potential predictive factors of malignancy in the residual thyroid tissue and the cervical lymph nodes (CLN) in patients with DTC who had partial thyroid surgery and subsequently underwent completion thyroidectomy and/or modified neck dissection. Age, gender, pressure symptoms, duration of symptoms, size of the original tumor, tumor multifocality, perithyroidal tumor extension, soft tissue invasion, and serum thyroglobulin (Tg) level after first surgery were analyzed as potential predictive factors for the presence of malignancy in the thyroid remnant and the CLN. METHODS: We retrospectively reviewed the medical and pathologic data of 101 cases of DTC; 97 had papillary and 4 had follicular thyroid cancer. On the initial surgery, the median tumor size was 2.5 cm (range, 0.5 to 8.5 cm). Tumor multifocality occurred in 28 cases, perithyroidal tumor extension in 26 cases, and soft tissue invasion in 9 cases. Completion thyroidectomy was performed in 100 cases and modified neck dissection in 90 cases. RESULTS: On completion neck surgery, 39 patients had evidence of malignancy in the residual thyroid tissue and 36 patients in the CLN. In 23 (22.7%) cases, malignancy was present in both CLN and residual thyroid tissue. Only tumor multifocality and Tg level greater than 20 ng/mL after first surgery were predictive of the presence of malignancy in the thyroid remnant, whereas age older than 40 years, soft tissue invasion, perithyroidal tumor extension, and Tg level greater than 20 ng/mL were predictive of malignancy in CLN. CONCLUSIONS: Residual malignancy is common after partial thyroid surgery for DTC. Tumor multifocality and Tg level may be predictive of its presence in residual thyroid tissue. Age, perithyroidal tumor extension, soft tissue invasion, and Tg level are predictive of the presence of lymph node metastases.     

SPECT-PET显像在分化型甲状腺癌~(131)I治疗预后中的应用价值

目的探讨SPECT及PET显像在诊断甲状腺癌放射治疗后复发和转移中的应用价值。方法对103例接受131I治疗的分化型甲状腺癌(DTC)患者的核医学显像资料、影像学资料及血浆Tg、TSH的水平测定结果进行分析,其中的85例为有效病例,作为本研究的研究对象,分为实验组和对照组,实验组行131I SPECT/CT、131I-WBS显像,对照组行124I-PET和FDG SPECT/CT显像,并同期测定患者的血浆Tg、TSH水平及常规检查,同时让患者口服重组人促甲状腺激素(rhTSH)后再次显像,分析其显像资料及血浆Tg、TSH水平,结合患者的临床表现,综合分析患者同期的各项影像学检查结果(131I SPECT/CT断层显像、18F-FDG显像、CT、B超、MRI等)及血清TSH、Tg水平测定值,对患者是否发生分化型甲状腺癌术后转移复发进行判断,并以此做出诊断。血浆Tg水平诊断肿瘤复发转移的判断阈值为>10 ng/mL。结果以Tg血浆水平>10 ng/mL做为肿瘤复发转移判断界值得出SPECT/CT较131I全身显像具有更高的灵敏度;124I-PET较131 I-WBS有着更好的空间分辨率和灵敏度,可提高DTC定位诊断的准确性;18F-FDGPET/CT显像对Tg水平明显增高的甲状腺癌复发和转移患者有重要的诊断价值;服rhTSH可进一步提高18F-FDG检查的准确性。结论 131I SPECT-PET显像,可提高病灶定位的准确性,为肿瘤预后的评价提供了更准确的判断依据,将进一步推动分化型甲状腺癌临床诊疗水平的提升。     

Prognostic Implications of Radioiodine Avidity and Serum Thyroglobulin in Differentiated Thyroid Carcinoma with Distant Metastasis

Background

Although differentiated thyroid carcinoma (DTC) rarely develops distant metastases, the present study was performed to evaluate factors that affect the survival of patients with DTC who present with distant metastasis.

Methods

Among 4,989 patients who underwent thyroid surgery for DTC, 82 presenting with distant metastasis were analyzed. Based on radioiodine (¹³¹I) avidity and the thyroid-stimulating hormone-stimulated serum thyroglobulin (sTg) level at the time of metastasis, patients were divided into three groups: group 1 (¹³¹I uptake + sTg ≤ 215 ng/mL, n = 46), group 2 (¹³¹I uptake + sTg > 215 ng/mL, n = 24), group 3 (no ¹³¹I uptake, n = 12). Disease-specific survival (DSS) was estimated using the Kaplan–Meier method. Factors predicting the outcome were evaluated using Cox proportional hazard regression analysis.

Results

The age of patients (p = 0.04), frequency of follicular thyroid carcinoma (p = 0.002), tumor size (p < 0.001), and number of multiple metastatic sites (p = 0.004) differed significantly among the groups. With a median follow-up after surgery of 72 months, the 5- and 10-year DSSs for all patients were 84 and 69 %, respectively. The predictors of survival were age (p = 0.004), symptoms at the time of presentation (p = 0.045), histology (p = 0.01), sites of metastasis (p = 0.03), and ¹³¹I avidity and sTg level at the time of metastasis (p = 0.002). In the multivariate analysis, age, histology, and ¹³¹I avidity and sTg level at the time of metastasis remained significant factors for survival.

Conclusions

Certain DTC patients with distant metastasis demonstrate favorable outcomes dependent on age, histology, and ¹³¹I avidity and sTg level at the time of metastasis.     

Cumulative doses of adjunct 131I treatment depend on location of residual thyroid tissue after total thyroidectomy in differentiated thyroid cancer

Purpose

The aim of this study was to review the outcome after adjunct postoperative ¹³¹I therapy in patients with differentiated thyroid carcinoma (DTC) treated with total thyroidectomy (excluding medullary thyroid carcinoma).

Methods

Retrospective chart review: Management protocol is total thyroidectomy with cervical node sampling, ¹³¹I whole-body scan 3 weeks postoperatively to document residual thyroid tissue or metastasic lesions. Adjunct treatment consists of one or more ¹³¹I (100-200 mci/1.73 m²). Patients are considered disease free if 2 consecutive ¹³¹I whole-body scan are negative with undetectable thyroglobulin level.

Results

Twenty-one patients, 14 females and 7 males, with a mean age of 13.6 years were treated. Whole-body scan postoperatively revealed uptake in the thyroid bed (TB) in 10 patients, in cervical lymph nodes (CLN) in 9 patients, and in CLN and lungs in 2 patients. Patients with residual uptake in TB received a significantly lesser dose of ¹³¹I (mean, 122 ± 53 mci) than those with metastasic CLN (357 ± 182 mci) (P < .004) (t test) or lung mets (523.5 mci). With a mean follow-up of 7.8 years (range, 1-16 years), overall survival is 100% but disease-free survival is 100%, 66%, and 0% respectively for patients with residual disease in TB, CLN, and lungs.

Conclusion

Patient with residual thyroid tissue in the TB required a significantly lesser number of treatments and doses of ¹³¹I compared to patients with cervical node metastases with a 100% disease-free survival. The best management of immediate postoperative residual cervical nodes (surgical excision vs ¹³¹I) remains to be defined. The efficacy of ¹³¹I therapy in patients with lung metastases remains controversial with complete remission unlikely.     

Distribution of Na<Superscript>+</Superscript>/I<Superscript>–</Superscript> Symporter in Thyroid Cancers in an Iodine-deficient Population: An Immunohistochemical Study

Background There are significant differences in the prevalence and behavior of differentiated thyroid cancers (DTC) in the iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) of the world. The sodium iodide symporter (NIS), mediates active transport of iodide across the basolateral aspect of the thyroid follicular cell. However, no study had specifically addressed the issue of expression of sodium iodide symporter (NIS) in thyroid cancer specimens from IDA. The aim of the present study was to find an expression pattern of NIS in DTC in an iodine-deficient population, and to correlate it with histological subtypes, i.e., papillary carcinoma (PTC), follicular carcinoma (FTC), poorly differentiated carcinoma (PDTC), as well as with clinicopathological risk factors and iodine (¹³¹I) uptake by distant metastases. Methods Immunohistochemistry was carried out in 39 cases of thyroid cancer (41 samples) including PTC (15), FTC (10), PDTC (9), anaplastic cancer (5), and resected metastases (2). Expression was correlated with the patient’s age, sex, tumor size, presence or absence of extrathyroidal invasion, distant and lymph node metastases, and whole body radioiodine scan. Results Overall, 61.8% of DTC patients showed NIS expression. There was no significant difference in expression rate between PTC (73.3%) and FTC (70.0%). However, expression was significantly less in PDTC (33.3%). There was no correlation between NIS expression and any clinicopathological risk factor (p > .05). The results of NIS expression were not concordant with ¹³¹I uptake by metastases in 4 of 10 cases. ¹³¹I uptake was absent in one case despite the finding that a metastatic site itself showed NIS expression in that case, whereas in the remaining 9 cases ¹³¹I uptake was present although three cases did not show NIS expression. Conclusions In our experience, overall expression of NIS was comparable to other studies from ISA. We conclude that expression may not accurately predict radioactive iodine (RAI) uptake by metastases. This study was supported by an intramural grant provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.     

Functional imaging in thyroid cancer patients with metastases and therapeutic implications

Functional imaging plays a central role in the management of thyroid cancer patients.In patients with a differentiated thyroid cancer (DTC), radioactive iodine (RAI) is used mostly with a therapeutic intent, either post-operatively or as the first line systemic treatment in patients with known structural disease. A whole body scan is performed a few days after the RAI administration, and this procedure is very sensitive to detect all tumor foci with RAI uptake. PET/CT with ¹⁸F-FDG complements the use of RAI at the initial evaluation of patients with high-risk DTC, during follow-up in those with rising serum thyroglobulin levels over time, for the work-up of patients with documented structural disease and for assessing the efficacy of focal or systemic treatment modalities. ¹⁸F-FDG uptake is a prognostic indicator in all these clinical conditions. A dosimetric approach with ¹²⁴I PET/CT showed encouraging results.Several functional imaging modalities are currently available for medullary thyroid carcinoma (MTC) patients. ¹⁸F-FDG-PET/CT may be sensitive in MTC patients with high FDG uptake that signals aggressive disease. ¹⁸F-DOPA is the most sensitive imaging technique to visualize small tumor foci, and is also highly specific in patients with a known MTC, but should be complemented by a CT scan of the chest and by a MRI of the liver to detect small metastases.