Diagnostic 131I whole body scanning after thyroidectomy and ablation for differentiated thyroid cancer

OBJECTIVE: To assess the value of the diagnostic whole body (131)I scan after thyroidectomy and (131)I ablation. DESIGN: Retrospective analysis of all patients with differentiated thyroid cancer treated in one centre between 1990 and 2000. RESULTS: A total of 153 consecutive patients who underwent diagnostic scanning following ablative therapy were identified. This diagnostic scan was positive in 20 patients (13%) and faintly positive in 16 patients (11%). The majority (117 patients) had negative scans. Of the 20 patients with positive scans, four received no further treatment, nine showed no abnormal uptake following a second ablative (131)I dose and seven had uptake in the thyroid bed (six) or in neck nodes (one) after repeat ablation. OUTCOME: In the group with positive scans, the four patients who received no further treatment and the nine with a negative second ablation scan remained disease free during follow-up. No patient with a positive diagnostic scan received additional (131)I therapy which would not otherwise have been given based on the clinical findings, serum thyroglobulin (Tg) values or the presence of anti-Tg antibodies. Ten of the patients with negative scans developed recurrent disease which was always detected clinically or by a rising serum Tg value. CONCLUSIONS: Diagnostic whole body (131)I scans add little extra information and in our experience do not influence patient management. They should be reserved for patients in whom serum Tg levels are unreliable because of the presence of antibodies or when there is clinical suspicion of tumour.     

Outcome of differentiated thyroid cancer with detectable serum Tg and negative diagnostic (131)I whole body scan: comparison of patients treated with high (131)I activities versus untreated patients.

Detectable serum Tg levels associated with negative diagnostic (131)I whole body scan are not infrequently found in patients with differentiated thyroid cancer. Several researchers have shown that in these patients the administration of high (131)I activity (100 mCi or more) increases the sensitivity of a posttherapy diagnostic (131)I whole body scan performed a few days later and allows the detection of neoplastic foci not seen with diagnostic doses of (131)I. Empirical radioiodine treatment has also been advocated by some researchers, but its therapeutic effect is controversial. In our institute, positive serum Tg/negative diagnostic (131)I whole body scan patients were not treated with high (131)I activities before 1984; afterward, almost all patients with positive serum Tg/negative diagnostic (131)I whole body scan patients were treated with radioiodine, and a posttherapy diagnostic (131)I whole body scan was performed. In the present retrospective study we compared the outcome of these two groups of patients, 42 treated and 28 untreated, followed for mean periods of 6.7 +/- 3.8 and 11.9 +/- 4.4 yr, respectively. In the treated group the first posttherapy diagnostic (131)I whole body scan was negative in 12 patients and positive in 30 patients. (131)I treatment was further administered only in the latter group. At the end of follow-up in treated patients a complete remission (normalization of serum Tg off L-thyroxine and negative diagnostic (131)I whole body scan) was observed in 10 patients (33.3%). In 9 cases (30%) posttherapy diagnostic (131)I whole body scan became negative, and serum Tg was reduced but still detectable; in 11 patients (36.6%) serum Tg was detectable, and posttherapy diagnostic (131)I whole body scan was positive. The resolution of (131)I uptake in lung metastases was observed in 8 of 9 cases (88.8%) and in cervical node metastases in 11 of 18 cases (61.1%). In patients treated only once because the posttherapy diagnostic (131)I whole body scan was negative (n = 12), 2 patients (16.7%) were in apparent remission, 7 (58.3%) had detectable Tg values without evidence of disease, 2 (16.7%) showed lymph node metastases in the mediastinum, and 1 patient (8.3%) died because of lung metastases. Of the 28 untreated patients, none with radiological evidence of disease, serum Tg off L-thyroxine therapy became undetectable in 19 cases (67.9%), significantly reduced in 6 cases (21.4%), and unchanged or increased in 3 patients (10.7%), 1 of whom developed lung metastases 14 yr after the diagnosis. In summary, our results indicate that in patients with detectable serum Tg and negative diagnostic (131)I whole body scan, treatment with high doses of (131)I may have therapeutic utility in patients with lung metastases and, to a lesser extent, in those with lymph node metastases. However, in view of the frequent normalization of Tg values in untreated patients, we believe that treatment with (131)I should be considered according to the result of the first posttherapy scan. If positive in the lung, (131)I treatment should be continued up to total remission; surgical treatment should be preferred in patients with node metastases, and no treatment should be used in those with thyroid bed uptake or no uptake.     

Lithium as a potential adjuvant to 131I therapy of metastatic, well differentiated thyroid carcinoma

As lithium inhibits the release of iodine from the thyroid but does not change iodine uptake, it may potentiate 131I therapy of thyroid cancer. The effects of lithium on the accumulation and retention of 131I in metastatic lesions and thyroid remnants were evaluated in 15 patients with differentiated thyroid carcinoma. Two 131I turnover studies were performed while the patients were hypothyroid. One was performed while the patient received lithium; the second served as a control study. From a series of gamma-camera images, it was found that lithium increased 131I retention in 24 of 31 metastatic lesions and in 6 of 7 thyroid remnants. A comparison of 131I retention during lithium with that during the control period showed that the mean increase in the biological or retention half-life was 50% in tumors and 90% in remnants. This increase occurred in at least 1 lesion in each patient and was proportionally greater in lesions with poor 131I retention. When the control biological half life was less than 3 days, lithium prolonged the effective half-life, which combines both biological turnover and isotope decay, in responding metastases by more than 50%. More 131I also accumulated during lithium therapy, probably as a consequence of its effect on iodine release. The increase in the accumulated 131I and the lengthening of the effective half-life combined to increase the estimated 131I radiation dose in metastatic tumor by 2.29 +/- 0.58 (mean +/- SEM) times. These studies suggest that lithium may be a useful adjuvant for 131I therapy of thyroid cancer, augmenting both the accumulation and retention of 131I in lesions.     

123I isotope as a diagnostic agent in the follow-up of patients with differentiated thyroid cancer: comparison with post 131I therapy whole body scanning.

Radioactive iodine (131I) plays a major role in the diagnosis and management of differentiated thyroid cancer (DTC); however, data on the use of the 123I isotope in DTC are limited. We compared 238 diagnostic whole body scans performed 24 h after oral ingestion of 185-555 MBq 123I with their corresponding 131I posttherapy whole body scans obtained 4-5 d after 131I therapy. We studied scans in 3 clinical situations: with the first 131I therapy, with the second 131I therapy, and in cases of elevated Tg and negative diagnostic scan. One hundred and seventy-seven pairs were obtained with the first 131I therapy and showed complete concordance between pretreatment and posttreatment scans in 166 pairs (concordance rate, 93.8%). Six other posttreatment scans showed more foci in the thyroid bed than the pretreatment scans, but no evidence of uptake in new areas. Only 5 posttreatment scans showed foci in new locations: 3 in cervical lymph nodes (CLN), 1 in the lung, and 1 new bone metastasis in a patient with known skeletal metastases. With the second 131I therapy, 34 pairs were obtained and showed complete concordance in 28 pairs (concordance rate, 82.4%). Five discordant pairs showed additional foci in areas that were already positive on pretreatment scans. Only 1 posttreatment scan showed a new bone metastasis in a different site from the bone metastases that were seen on its corresponding pretreatment scan. Of 27 pairs of scans in patients with elevated Tg and negative pretreatment scans, 15 posttreatment scans remained negative, 6 posttreatment scans showed an uptake in the thyroid bed, and 3 other posttreatment scans showed lung uptake in patients whose computed tomography scans of the chest showed only bronchiectasis (in 2 patients) and lung scarring (in the third patient) without evidence of lung metastases. Three posttreatment scans showed definite uptake (in thyroid bed, thyroid bed and lung, and CLN) compared with their corresponding pretreatment scans, which were initially reported negative but were retrospectively thought to have had faint uptake. In 56 pretreatment scans, the 123I diagnostic activity was 185 MBq, and the results showed complete concordance in 54 pairs. Two posttreatment scans showed additional uptake: 1 in the bone and 1 in CLN. These data suggest that pretreatment scanning using 123I is highly comparable to 131I posttreatment scanning and that 123I is an excellent diagnostic agent in DTC.     

Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer

131I continues to be one of the safest and most effective methods of diagnosing and treating metastatic well differentiated thyroid cancer. It is not without risk, however, and must be judiciously applied to carefully prepared and selected patients.     

131I therapy for differentiated thyroid cancer leads to an earlier onset of menopause: results of a retrospective study

Treatment with 131I for differentiated thyroid cancer may give a follicle-damaging radiation dose to the ovaries. This damage to the ovarian function could shorten the fertile life span and advance the natural menopause. To address this issue, we studied retrospectively the menopausal age of 130 women treated with 131I for differentiated thyroid cancer in our institution from 1974-1993. The menopausal age of women treated with 131I for differentiated thyroid cancer after total thyroidectomy and subjected to suppressive L-T4 therapy was compared with the menopausal age of a control group including 127 goitrous women who were treated with suppressive L-T4 for a comparable period of time. The cumulative therapeutic 131I dose to cancer patients ranged from 1,110-40,700 MBq (mean +/- SD, 5,308 +/- 5,483 MBq; median, 3700 MBq). All patients chosen for the study were younger than 45 yr when first treated (i.e. first administration of 131I and L-T4 for cancer patients, and institution of L-T4 therapy for goitrous patients), and older than 45 yr at the end of the study period. The menopausal status of both groups was assessed from the clinical records and compared using Kaplan-Meier survival analysis. The menopausal age of cancer women treated with 131I and suppressive L-T4 therapy was less than that of goitrous patients treated with suppressive L-T4 therapy (P < 0.001). We could not detect any relationship between menopausal age and the age at the first or last 131I dose or to the cumulative 131I dose received. These data indicate that 131I treatment is probably associated with an earlier ovarian failure in thyroid cancer patients. Conceivably, the ovarian irradiation by 131I might contribute to the process of the follicular atresia, thus inducing earlier menopause.     

Phase II study of celecoxib in metastatic differentiated thyroid carcinoma

CONTEXT: There is increased cyclooxygenase-2 (COX-2) expression in malignant thyroid nodules compared with nonneoplastic and benign thyroid tissue. OBJECTIVE: The objective of the study was to evaluate the efficacy of celecoxib, a selective COX-2 inhibitor, in treating patients with progressive metastatic differentiated thyroid cancer (DTC) and to explore the relationship of clinical response to tumor COX-2 expression with immunohistochemistry in a subset of patients. DESIGN: The study was a prospective phase II trial with Fleming single-stage design powered at 80% with a 5% rejection error to detect more than 20% progression-free survival at 12 months. SETTING: Ambulatory patients were from tertiary referral academic medical centers. PATIENTS: Patients in the study had progressive metastatic DTC and had failed prior standard therapy. INTERVENTION: Patients were treated with celecoxib 400 mg orally twice a day for 12 months. MAIN OUTCOME MEASURE: The main outcome measure was progression-free survival at 12 months of treatment using Response Evaluation Criteria in Solid Tumors and/or serum thyroglobulin. RESULTS: Twenty-three of 32 patients experienced progressive disease or stopped therapy due to toxicity, thus fulfilling the intent-to-treat study endpoint for celecoxib failure. One patient achieved partial response, and one patient completed 12 months of therapy progression-free. The patient with partial response was on therapy along with seven other patients when the study was terminated. CONCLUSIONS: Celecoxib 400 mg orally twice per day fails to halt progressive metastatic DTC in most patients.     

Ablation of the thyroid remnant and 131I dose in differentiated thyroid cancer

AIMS: To compare the efficacy of remnant ablation following a single low dose (specific activity of 131I administered, 1074-1110 MBq) vs. a single high dose (mostly 2775-3700 MBq) of 131I in patients with differentiated thyroid cancer and to determine whether or not the extent of surgery influences outcome. METHODS: Nineteen studies have reported the results of low dose 131I ablation. Of these, 11 met our criteria for a comparative analysis. Two additional cohorts of ours were added and these were analysed in two groups based on the extent of surgery (near-total [NT; Woodhouse1] vs. sub-total [ST; Woodhouse2]). There were 518 low dose and 449 high dose patients in all. RESULTS: The average failure of a single low dose was 46 +/- 28% (SD). Meta-analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P < 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near-total as opposed to sub-total thyroidectomy (summary relative risk (RR) 1.4; P < 0.05). CONCLUSION: High dose 131I is more efficient than low dose for remnant ablation particularly after less than total thyroidectomy. Results suggest that patients with differentiated thyroid cancer should routinely have a total thyroidectomy followed by high dose 131I (2775-3700MBq) for ablation of the remnant.     

Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer

OBJECTIVE: The 'standard' postoperative follow-up of patients with differentiated thyroid cancer (DTC) has been based upon serum thyroglobulin (Tg) measurement and (131)I whole body scan ((131)I-WBS) after thyroid hormone (T(4)) treatment withdrawal. However, (131)I-WBS sensitivity has been reported to be low. Thyroid hormone withdrawal, often associated with hypothyroidism-related side effects, may now be replaced by recombinant human thyroid stimulating hormone (rhTSH). The aim of our study was to evaluate the diagnostic accuracy of (131)I-WBS and serum Tg measurement obtained after rhTSH stimulation and of neck ultrasonography in the first follow-up of DTC patients. DESIGN: Ninety-nine consecutive patients previously treated with total thyroidectomy and (131)I ablation, with no uptake outside the thyroid bed on the post-ablative (131)I-WBS (low-risk patients) were enrolled. METHODS: Measurement of serum Tg and (131)I-WBS after rhTSH stimulation, and ultrasound examination (US) of the neck. RESULTS: rhTSH-stimulated Tg was 1 ng/ml (Tg+) in 21 patients, including 6 patients with Tg levels >5 ng/ml. (131)I-WBS was negative for persistent or recurrent disease in all patients (i.e. sensitivity = 0%). US identified lymph-node metastases (confirmed at surgery) in 4/6 (67%) patients with stimulated Tg levels >5 ng/ml, in 2/15 (13%) with Tg >1<5 ng/ml, and in 2/78 (3%) who were Tg-negative. CONCLUSIONS: (i) diagnostic (131)I-WBS performed after rhTSH stimulation is useless in the first follow-up of DTC patients; (ii) US may identify lymph node metastases even in patients with low or undetectable serum Tg levels.     

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such, serum thyroglobulin determinations on and off thyroid hormone (T₄) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (< 1 ng/ml). Values during T₄ therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T₄ withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T₄. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T₄ therapy or less than 10 ng/ml off T₄ therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.     

Location of functioning metastases from differentiated thyroid carcinoma by simultaneous double isotope acquisition of I-131 whole body scan and bone scan

In a young patient with differentiated thyroid carcinoma (DTC), previously submitted to total thyroidectomy and I-131 therapy for ablation of thyroid remnant, a follow-up 1-131 diagnostic whole body scan (WBS) demonstrated four small abnormal I-131 uptake areas. Two of these were projected over the thoracic region and corresponded to lung nodules, as later demonstrated by lung computerized tomography (CT)-scan. The remaining two areas were found in the lumbar-pelvic region, but their precise location could not be determined. Standard bone Rx examination and bone scan were negative. After I-131 therapy, we simultaneously acquired a I-131 WBS and a Tc-99m oxidronate bone scan by setting a dual window on the gamma camera. Comparing the I-131 and bone images we were able to identify the 4th lumbar vertebra and right ilium as the bone segments to be studied by a radiological approach. Eventually, the thin slice CT-scan demonstrated the presence of two small osteolytic lesions in these areas. In conclusion, the simultaneous acquisition of images both from I-131 and a bone-seeking agent may be useful to locate functioning bone metastases from DTC.     

不同放射性活度131I清除分化型甲状腺癌患者残留甲状腺的荟萃分析

目的 使用荟萃分析方法汇总所有的随机对照研究,比较不同放射性活度131I清除术后残留甲状腺(清甲)的成功率,明确最佳的清甲剂量.方法 以‘thyroid’+‘cancer or carcinoma’+‘ablat$’(包括了ablation、ablative和ablate)为关键词检索2014年3月前Cochrane Library、MEDLINE、EMBASE和SCOPUS等数据库评估不同放射性活度”1 I清甲成功率的随机对照研究文献,并用Google学术查找相关文献.用RevMan 5.2进行统计学分析,依据Cochrane质量评价标准进行文献质量评估.纳入标准如下:(1)已发表的比较不同剂量131I对分化型甲状腺癌(DTC)清甲成功率的研究.(2)患者均行甲状腺切除术.(3)均为术后首次131I治疗.(4)服131I后3～12个月行清甲成功率评估.(5)服131I剂量为888 ～4 440 MBq(24～120 mCi).本研究定义低剂量为888～1 443 MBq(24～39 mCi)、中剂量为1 480～2 923 MBq(40 ～79 mCi)、高剂量为2 960～4 440 MBq(80～120 mCi).当研究间存在异质性时(I2＞50％)、采用随机效应模型进行荟萃分析,否则采用固定效应模型进行荟萃分析.结果 共纳入17个随机对照研究,包括3 737例患者(低剂量1 514例、中剂量811例、高剂量1 412例).5项研究比较了低剂量与中剂量的成功率,研究间有异质性(I2 =67％,P=0.02)、采用随机效应模型,荟萃分析结果显示两组的清甲成功率差异无统计学意义[风险比(RR) =0.89(0.80～1.00),P=0.06].7项研究比较了中剂量与高剂量的成功率,研究间无异质性(I2=34％,P=0.17),采用固定效应模型,荟萃分析结果显示两组剂量的清甲成功率差异无统计学意义[RR =0.94(0.89～1.00),P=0.05].11项研究比较了低剂量与高剂量的成功率,研究间有异质性(I2=70％,P=0.0002),采用随机效应模型,荟萃分析结果显示高剂量的清甲成功率显著高于低剂量[RR=0.89(0.81 ～0.97),P=0.008].结论 对于术后DTC患者,低剂量与中剂量131I以及中剂量与高剂量131I的清甲成功率无明显差异,但高剂量131I的清甲成功率显著高于低剂量.     

分化型甲状腺癌患者术后首次行131I清除残余甲状腺组织的疗效及其影响因素

目的探讨分化型甲状腺癌(DTC)患者术后首次行131I清除残余甲状腺组织(清甲)的疗效,并分析其疗效影响因素。方法选择DTC术后患者102例,首次行131I清甲治疗前停服甲状腺激素,空腹一次性口服131I 100～120 mCi;清甲治疗后3～5 d行甲状腺激素长期替代治疗。治疗前用化学发光免疫分析法检测患者的血清促甲状腺激素(TSH)、甲状腺球蛋白(Tg);治疗前后行甲状腺摄取131I率及131I甲状腺显像检查。采用单因素和多因素Lo-gistic回归分析方法,分析患者性别、年龄、病理类型、清甲前血清TSH、Tg、甲状腺摄取131I率和131I治疗剂量对清甲疗效的影响。结果 102例患者中,首次清甲成功37例、未成功65例,清甲成功患者的131I治疗剂量明显低于未成功患者(P=0.000)。单因素分析显示,131I治疗剂量(P=0.020)越大,治疗前血清TSH(P=0.000)越高、Tg(P=0.000)越低,清甲疗效越高;患者的年龄、性别、病理类型及清甲前残余甲状腺摄取131I率对首次清甲疗效无明显影响(P分别为0.119、0.315、0.835、0.375)。多因素分析显示,131I治疗剂量、清甲治疗前血清TSH及Tg水平是影响清甲疗效的影响因素(P分别为0.049、0.014、0.001)。结论131I治疗剂量、治疗前血清TSH及Tg水平是影响DTC患者术后首次清甲疗效的重要影响因素。     

Relationship of sodium/iodide symporter expression with I131 whole body scan uptake between primary and metastatic lymph node papillary thyroid carcinomas

The aim of the present study was to evaluate total and membranous Na+/I- symporter (NIS) expressions in papillary thyroid carcinoma (PTC) tissue, correlation of NIS expression between primary and metastatic lymph node (LN) PTC tissues, and relationship of NIS expression with I131 whole body scan (WBS) uptake between primary and metastatic LN PTC tissues by analyzing 17 pairs of primary and metastatic LN PTC tissues. Staining positivity was calculated, and staining intensity was graded as negative (0), weak (1+), moderate (2+) and strong (3+). In primary PTC tissues, positivities and intensities of normal cells were higher than those of carcinoma cells but had no correlation with those in matched metastatic LN PTC tissues. In classic type, positivities, intensities and membranous intensities (mIS) were correlated between primary and matched metastatic LN PTC tissues. In patients aged younger than 45 yr, positivities and intensities in primary PTC tissues had correlation with those in matched metastatic LN PTC tissues. Positivities, intensities, mIS and pathological subtype of carcinoma cells in primary PTC tissues were not correlated with age, tumor size, TNM stage, MACIS score and thyroglobulin (Tg) levels at the time of I131 WBS. Sensitivity, specificity, as well as positive and negative predicted values of mIS in patients with I131 WBS uptake were 69.2, 75, 90 and 42.9% in primary PTC tissues, and 92.3, 100, 100 and 80% in metastatic LN PTC tissues. The results of mIS taken either as positive or negative were correlated with those of I131 WBS after controlling for age. Our results demonstrate that PTC tissues have altered total and membranous NIS expressions, suggesting that NIS expression in primary PTC tissues may predict NIS expression and I131 WBS uptake in matched metastatic LN PTC tissues.     

131I activity for remnant ablation in patients with differentiated thyroid cancer: A systematic review

CONTEXT: Radioiodine ablation of the thyroid remnant after thyroidectomy is commonly performed in the management of patients with differentiated thyroid cancer. Although many centers administer an activity of 100 mCi, there is uncertainty over using a lower activity. OBJECTIVE: A systematic review of the published literature was used to compare the success rates of remnant ablation using approximately 30 mCi with approximately 100 mCi (1.1 vs. 3.7 GBq). DATA SOURCES: Data were obtained from MEDLINE and EMBASE for the years 1966 to March 2006. STUDY SELECTION: All studies that reported rates of successful ablation associated with approximately 30 or approximately 100 mCi of radioiodine were reviewed. DATA EXTRACTION: Studies were based on reviews of patient case notes (n = 41), prospective cohorts (n = 12), and randomized trials (n = 6). We obtained the success of thyroid remnant ablation according to different administered activities of radioiodine. Where a study reported on two or more activities, the risk ratio of having a successful ablation (approximately 30 vs. approximately 100 mCi) was calculated and combined in a meta-analysis. DATA SYNTHESIS: Observational studies confirmed the high ablation success rate ( approximately 80%) using approximately 100 mCi, although 22% of studies reported a rate of 90% or greater. The pooled ablation success rate in these studies was 10% lower using 30 mCi compared with 100 mCi (95% confidence interval, 3-17%; P = 0.01). The meta-analysis of the randomized trials produced equivocal results. For example, the rate of successful ablation in patients given 30 mCi was 8% lower compared with 100 mCi (95% confidence interval, 29% lower or up to 20% greater, P = 0.58), consistent with there being no difference or that 30 mCi is much less effective. CONCLUSIONS: From the published data, it is not possible to reliably determine whether ablation success rates using 30 mCi are similar to using 100 mCi. Large randomized trials are needed to resolve the issue and guide clinical practice.