The Importance of Age over Radioiodine Avidity as a Prognostic Factor in Differentiated Thyroid Carcinoma with Distant Metastases
Differentiated thyroid carcinoma (DTC) usually has a good prognosis and rarely develops distant metastases. Although it might be expected that avid radioiodine uptake in distant metastases would be associated with a favorable outcome, there are few long-term studies regarding this. The present study was performed to evaluate the influence of radioiodine uptake in distant metastases on the disease-specific survival (DSS) in DTC patients.
This retrospective study included 77 DTC patients with distant metastases (M1) who were treated with (131)I therapy from 1977 to the end of 2000 in our institution. The median follow-up of patients was 6.1 years. Univariate and multivariate analysis were performed using the Kaplan-Meier method and log rank test, and Cox Regression model, respectively.
Seventy-seven patients with M1 included 51 (66.2%) women and 26 (33.8%) men; 32 (41.6%) patients were <45 years old and 45 (58.4%) patients were >or=45 years old (range: 8-70 years; mean age: 45.4 years); histologically, there were 54 (70.1%) papillary carcinomas, 22 (28.6%) follicular carcinomas, and one case (1.3%) with an inconclusive histological report. The probability of DSS after appearance of M1 was 57.95% after 5 years, 48.31% after 10 years, and 39.46% after 15 and 20 years. In patients with iodine-avid distant metastases the 5-year DSS was 66.54%, the 10-year DSS was 55.09%, and the 15- and 20-year DSS were 44.99%. In contrast, patients with non-iodine-avid lesions had a 5- and 10-year DSS of 18.33%. This difference relating to the relationship between (131)I uptake in distant metastases and survival was significant (p = 0.0006). The proportion of patients with non-iodine-avid distant metastases that were >or=45 years old was significantly greater than the proportion of patients with non-iodine-avid distant metastases that were <45 years old (p < 0.01). If patients were matched for age, iodine non-avidity significantly shortened the survival in patients <45 years old (p < 0.001). According to multivariate analysis age had significantly greater influence on survival compared with iodine avidity (p < 0.001, p = 0.078, respectively).
Patients with distant metastases have a long-term survival that depends, in addition to other factors, on age and the degree of radioiodine uptake in distant metastases.
Available from: Eleonore Froehlich
- "Independent of the applied dose, the success of RAI treatment is strongly linked to the ability of metastases to concentrate iodine. While RAI treatment improved disease-specific survival rates in patients with iodine-avid metastases  , it had no beneficial effects on patients with metastases that did not take up iodine avidly  . "
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ABSTRACT: Targeted therapy pinpointing specific alteration in cancer cells has gained an important role in the treatment of cancer. Compounds that re-induce thyroid-specific functions could be particularly useful in differentiated thyroid cancers by rendering them susceptible to radioiodine treatment, which is relatively specific and has few adverse effects. This review describes the rationale for radioiodine treatment, considering the targets of compounds with differentiation-inducing effects, and the impact of these drugs on the expression of thyroid-specific proteins and on iodine-uptake. We survey the results from the clinical trials thus far performed. We conclude that although retinoids, thiazolidinediones, histone deacetylase inhibitors and DNA methyltransferase inhibitors do increase the expression of thyroid-specific proteins, their clinical efficacy is limited. The relatively low rate of remissions in clinical trials with re-differentiating compounds could be due to low levels of the target, heterogeneity of iodine uptake into the tumor, poor correlation of radioiodine uptake and clinical remission, and/or the slow onset of the therapeutic effect. Although the mode of action is not clear, the combination of tyrosine kinase inhibitors and RAI treatment could improve clinical responses in non-radioiodine avid metastatic thyroid carcinoma.
Available from: Kai Pun Wong
- "RAI avidity was found to be the other independent prognostic factor for CSS, a finding consistent with other studies.4,9,10 The reasons why RAI avidity might have been a significant prognostic factor are 2-fold. "
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Because patients with differentiated thyroid carcinoma (DTC) presenting with distant metastasis (DM) have a particularly poor prognosis, examining the prognostic factors in this group is essential. We aimed to evaluate the prognostic factors affecting cancer-specific survival (CSS) in DTC patients presenting with DM.
Of the 1227 DTC patients, 51 (4.2 %) presented with DM at diagnosis. All patients underwent a total thyroidectomy, followed by radioiodine (RAI) ablation and postablation whole body scan (WBS). Patients were considered to have an osseous metastasis if one of the metastatic sites involved a bone, while RAI avidity was determined by any visual uptake in a known metastatic site on the first WBS. Factors predictive of CSS were determined by univariate and multivariate analyses by the Cox proportional hazard model.
In univariate analysis, older age (relative risk [RR] 1.050, 95 % confidence interval [CI] 1.010–1.091, P = 0.014), DM discovered before WBS (RR 3.401, 95 % CI 1.127–10.309, P = 0.030), follicular thyroid carcinoma (RR 3.095, 95 % CI 1.168–8.205, P = 0.025), osseous metastasis (RR 4.695, 95 % CI 1.379–15.873, P = 0.013), non-RAI avidity (RR 3.355, 95 % CI 1.280–8.772, P = 0.014), and external beam radiotherapy to DM (RR 3.241, 95 % CI 1.093–9.614, P = 0.034) were significant poor prognostic factors for CSS. In the multivariate analysis, after adjusting for other factors, osseous metastasis (RR 6.849, 95 % CI 1.495–31.250, P = 0.013) and non-RAI avidity (RR 7.752, 95 % CI 2.198–27.027, P = 0.001) were the two independent poor prognostic factors for CSS. Older age almost reached statistically significance (RR 1.055, 95 % CI 0.996–1.117, P = 0.068).
DTC patients presenting with DM accounted for 4.2 % of all patients. Because osseous metastasis and RAI avidity were independent prognostic factors, future therapy should be directed at improving the treatment efficacy of osseous and/or non-RAI-avid metastases.
Available from: thyroid.org
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