OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

OBJECTIVE: Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. METHODS: Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. RESULTS: The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. CONCLUSION: Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. ABBREVIATIONS: DTC = differentiated thyroid cancer; LASA = linear analog self-assessment; PR = partial response; QOL = quality of life; RAI = radioactive iodine; RAIR = RAI-resistant; RECIST = Response Evaluation Criteria In Solid Tumors; Tg = thyroglobulin; VEGFR = vascular endothelial growth factor receptor.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

OBJECTIVE: Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. METHODS: This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. RESULTS: From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. CONCLUSION: The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. ABBREVIATIONS: AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

Differentiated thyroid carcinoma: Incremental diagnostic value of 131I SPECT/CT over planar whole body scan after radioiodine therapy.

The purpose of this prospective study was to determine the incremental diagnostic value of single photon emission computed tomography/computed tomography with iodine-131 over planar whole body scan in the staging of patients with differentiated thyroid carcinoma. A total of 365 patients (270 female, 95 male) with differentiated thyroid carcinoma were treated with radioiodine therapy for thyroid remnant ablation with radical intent after thyroidectomy between January 2013 and November 2014. In addition to planar whole body scan, single photon emission computed tomography/computed tomography of neck and chest were performed. Each radioactive focus at whole body scan was classified as positive or equivocal with respect of specific territories: thyroid bed, cervical lymph nodes and distant metastases.Whole-body scan detected focal uptake in 353 patients and no uptake in 12. The location was considered equivocal in 100. Single photon emission computed tomography/computed tomography detected focal uptake in 356 patients and no uptake in nine. In three patients with negative wholebody scan, single photon emission computed tomography/computed tomography provided information about residual activity in the thyroid bed. By single photon emission computed tomography/computed tomography the location was equivocal in 18 patients only. Single photon emission computed tomography/computed tomography was helpful in 82 out of 100 patients with equivocal findings by whole body scan allowing a correct identification of the uptake sites. In a great number of equivocal whole body scan, due to high remnant activity, single photon emission computed tomography/computed tomography was able to differentiate between thyroid remnant and lymph nodes uptake. In 22 out of 100 patients with doubtful whole body scan, single photon emission computed tomography/computed tomography correctly identified nodal or distant metastases, and in 2/100 patients, focal uptake classified as metastatic by whole body scan was reclassified as para-physiological by single photon emission computed tomography/computed tomography. The TNM classification changed in 13 out of 22 patients. Single photon emission computed tomography/computed tomography improves detection and localization of the iodine-131 uptake after thyroidectomy in patients with differentiated thyroid carcinoma and it is more accurate than whole body scan to evaluate lymph nodes and to identify and characterize distant metastases. Single photon emission computed tomography/computed tomography aids assessment of lower/upper stage in a significant number of patients with differentiated thyroid carcinoma and it can affect therapy decision-making and patient management.

Comparison of histopathological features and prognosis of classical and follicular variant papillary thyroid carcinoma.

PURPOSE: To compare the histopathological features and the outcomes of the follicular variant and classical variant of papillary thyroid carcinoma. MATERIAL AND THE METHODS: Demographic data, histopathological features (tumor size, thyroid capsule invasion, extrathyroidal extension, vascular invasion and multicentricity), lymph node metastasis, local recurrence, distant metastasis and mortality during the follow-up of 258 C-PTC and 153 FVPTC patients who underwent total thyroidectomy were compared. The dynamic risk assessment system was used to refine postoperative risk estimates based on the assessment of response to initial treatment. RESULTS: The demographic data showed no significant difference between the two groups. The mean tumor size showed no significant difference between the two groups. The rate of thyroid capsule invasion, extrathyroidal extension, and lymph node metastasis was significantly higher in C-PTC than in FVPTC group, whereas multicentricity and bilobar involvement were significantly higher in FVPTC group than in C-PTC group. Central lymph node metastasis was significantly more frequent in patients with C-PTC than in those with FVPTC (p < 0.0001). Local recurrence was found in 22 (5.3 %) patients overall and was significantly more common in C-PTC group than in FVPTC group. In patients ≥45 years, the local recurrence rate was significantly higher in patients with CPTC than in those with FVPTC. The local recurrence rate in patients <45 years was not significantly different between the two groups of patients. The multicentricity rate was significantly higher in the FVPTC group for both age groups. Dynamic risk assessment showed that the rate of intermediate- and high-risk groups showed no significant difference between C-PTC and FVPTC patients but the rate of low risk patients was higher in FVPTC group than in C-PTC group (p = 0.04). The recurrence rate in low-risk group was found higher in C-PTC compared to FVPTC patients (4.7 vs. 0.7 %, p = 0.04, respectively). The recurrence rate showed no significant difference in both intermediate- and high-risk groups in C-PTC and FVPTC patients. During the follow-up, the rate of distant metastasis and disease-specific mortality was not significantly different between the two groups (p = 0.25). CONCLUSION: FVPTC is a common subtype of PTC and has a higher rate of multicentricity with bilobar involvement. Although aggressive histopathologic features, such as thyroid capsule invasion, extrathyroidal extension, and lymph node metastasis, are significantly more frequent in CPTC than in FVPTC, the long-term outcome is similar in both subtypes after appropriate initial surgery and postoperative RAI ablation treatment.

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

OBJECTIVE: To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. STUDY DESIGN: Analytical series. PLACE AND DURATION OF STUDY: Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. METHODOLOGY: Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. RESULTS: There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. CONCLUSION: For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

Thyroglobulin flare response after radioiodine ablation in 2 patients with differentiated thyroid cancer.

Serum thyroglobulin (Tg) measurement facilitates monitoring differentiated thyroid cancer. We describe 2 patients with papillary thyroid cancer who developed dramatic transient serum Tg level elevations within 1 week of I radioiodine (RAI) ablation without cancer recurrence on follow-up. The first patient received recombinant human thyroid-stimulating hormone injections. The pre-injection Tg level was 3.8 µg/L and increased to 3060 µg/L 3 days post-RAI. In the second patient, the serum Tg level increased from 1.3 µg/L to 209.9 µg/L 7 days after RAI. This transient early serum Tg "flare response" could be misleading if interpreted as suggesting more extensive high-risk thyroid cancer.

Long-term survival and low effective cumulative radioiodine doses to achieve remission in patients with 131Iodine-avid lung metastasis from differentiated thyroid cancer.

OBJECTIVE: To evaluate long-term survival and response to RAI treatment in patients with differentiated thyroid cancer (DTC) and 131Iodine-avid metastatic lung disease. PATIENTS AND METHODS: A retrospective review of 639 DTC patients followed-up at the Hospital de Clínicas, Buenos Aires, Argentina, showed that 42 (6%) patients had lung metastasis, and 24 patients were included for analysis. RESULTS: Seventeen were women, and 7 were men (F:M=2.4:1). Eighteen patients (75%) had PTC, and 6 (25%) had FTC. The median age at diagnosis was older than 45 years in 50%, and the median follow-up was 13 years. Good response to treatment (GRT: no evidence of disease or biochemical persistence without structural correlate) was observed in 46% of patients (all with diffuse postdose radioiodine uptake and no structural images higher than 1 cm in diameter); and 21% patients died from disseminated lung metastasis. Overall survival at 5 and 10 years was 100% and 88.4%, respectively. The Cox proportional hazard ratio showed that extrathyroidal invasion, positive uptake of 18-FDG, and metachronous diagnosis of the lung metastasis were variables that significantly predicted death. Those patients who had a GRT did with a mean effective cumulative RAI dose of 457.3±29.7 mCi 131I (range, 300-600 mCi 131I). CONCLUSIONS: Lung metastasis showed a slow progression with a high long-term overall survival. The presence of synchronous lung metastasis, the absence of nodules larger than 1 cm, and the lack of uptake of FDG were predictive factors for an early response to treatment with RAI cumulative doses lower than 600 mCi 131I.

Prognosis and prognostic factors of differentiated thyroid carcinoma after the appearance of metastasis refractory to radioactive iodine therapy.

Differentiated thyroid carcinomas (DTCs) are generally indolent, but few therapeutic strategies are available after a metastatic recurrence that is refractory to radioactive iodine (RAI) therapy. Molecular-target therapy has shown promising results for DTCs with RAI-refractory recurrence. However, not all RAI-refractory recurrences are progressive, and even those that are progressive may not be immediately life-threatening. Here we investigated the prognosis and prognostic factors of 74 DTC patients (52 females, 22 males) in whom RAI-refractory metastases appeared. The five-year and 10-year cause-specific survival (CSS) rates of the 74 patients (8-82 yrs of age; median age at the detection of metastases, 61 yrs) were 95% and 70%, respectively, and the older patients (≥ 60 yrs, n=38) and male patients were significantly more likely to die of carcinoma. Also in multivariate analysis, older age (≥ 60 years) and male gender were independent predictors of carcinoma-related death. Taken together, our data indicate that RAI-refractory metastases of older patients and male patients are more progressive than those of other patients. Further studies are necessary to clarify the appropriate indications for molecular-target therapy for RAI-refractory and progressive metastases.

Vitamin B12 levels are not affected by radioiodine ablation of the thyroid.

OBJECTIVE: Radioiodine administered for the treatment of hyperthyroidism and thyroid cancer can be taken up by many non-thyroid tissues which express sodium iodide symporter. Though gastric mucosa takes up radioiodine, its impact on parietal cell has not been evaluated. The aim of the present study was to compare vitamin B12 and homocysteine concentrations in patients with thyroid disorders treated by radioiodine ablation with those in control population without radioiodine exposure. METHODS: Patients with Graves' disease, toxic multinodular goiter (TMNG), toxic adenoma (TA) or differentiated thyroid cancer (DTC) who had received 131I were included as "patients". Healthy persons and patients having Graves' disease but without exposure to radioiodine were recruited as "controls". A total of 35 patients and 35 controls were included. Patients were divided into Graves' disease and non-Graves' disease (TMNG, TA, DTC) groups. Graves' disease patients were compared with Graves' disease controls while non-Graves' disease patients were compared with healthy controls. RESULTS: In the Graves' disease group, median vitamin B12 concentration was 240 pg/ml (IQR: 148 - 371) in patients (n=23) and 195 pg/ml (IQR: 140 - 291 pg/ml) (p=0.13, ns) in controls (n=24). In the non-Graves' disease group, median serum vitamin B12 concentration was 147 pg/ml (IQR: 124 - 325pg/ml) in patients (n=12) and 190 pg/ml (IQR: 157 - 373 pg/ml) (p=0.34, ns) in healthy controls (n=11). Homocysteine concentrations were also similar in compared groups of patients and controls. CONCLUSIONS: Radioiodine ablation does not cause vitamin B12 deficiency. However, a prospective study with a larger number of patients is required to confirm this finding.

Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer.

PURPOSE: The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. METHODS: We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. RESULTS: Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). CONCLUSION: The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.

No adverse affect in clinical outcome using low preablation diagnostic (131)i activity in differentiated thyroid cancer: refuting thyroid-stunning effect.

CONTEXT: Published studies of thyroid stunning due to preablation (131)I scanning in the treatment of differentiated thyroid cancer after thyroidectomy had shown inconsistent clinical impact. OBJECTIVE: The objective of the study was to evaluate the clinical outcome in patients who were given a low diagnostic (131)I activity (1.1 mCi or 40 MBq) 6 days prior to radioiodine ablation (RAI). DESIGN/SETTING: Two cohorts of patients were treated in a cancer referral center in 2004-2011. The eligibility criteria were as follows: 1) diagnosis of differentiated thyroid cancer; 2) total or near total thyroidectomy; 3) no distant metastasis; and 4) receiving 82.4 mCi or greater (3050 MBq) therapeutic (131)I activity. PATIENTS/INTERVENTIONS: Three hundred five consecutive patients treated in 2004-2008 (group A) had a diagnostic activity 1.1 mCi of (131)I prior to RAI. The second cohort treated in 2009-2011 (group B) consisted of 237 patients who did not undergo diagnostic (131)I scanning prior to RAI. MAIN OUTCOME MEASURES: The tumor recurrence rate at 3 years and quantitative assessment using diagnostic whole-body radioiodine scans and TSH-stimulated thyroglobulin levels at 3-12 months after RAI were measured. RESULTS: The 3-year recurrence-free survival rates were 96.4% in both groups, with 4.3% in group A and 3.4% in group B having tumor recurrence (P = .91). The ablation success rates measured by diagnostic whole-body radioiodine scans were 97.6% and 100% and by stimulated thyroglobulin were 85.3% and 85.8% in group A and B, respectively (P = .62). CONCLUSIONS: The use of low diagnostic (131)I activity (1.1 mCi) given 6 days prior to RAI was safe and convenient without adversely affecting the long-term clinical outcome.

Impact of early vs late postoperative radioiodine remnant ablation on final outcome in patients with low-risk well-differentiated thyroid cancer.

OBJECTIVE: Postoperative radioiodine remnant ablation (RRA) represents an adjunctive therapeutic modality in patients with differentiated thyroid cancer (DTC). The impact of late vs early RRA on the outcome of DTC is currently unclear. The aim of the study was to evaluate the outcome of patients with DTC according to RRA timing. DESIGN RETROSPECTIVE STUDY PATIENTS: A total of 107 TNM stage 1 DTC patients were divided into two groups. In group A (n = 50), RRA was administered in less than 4·7 months median 3·0 (range 0·8-4·7), while in group B (n = 57) in more than 4·7 months median 6 (4·8-30·3) after thyroidectomy. Remission was achieved when stimulated serum Tg levels were undetectable, in the absence of local recurrence or cervical lymph node metastases on the neck ultrasound. RESULTS: All patients underwent near-total thyroidectomy. The mean age at diagnosis was 49·3 years (range: 18-79 years). There were no statistically significant differences in the histological subtype, the TNM stage, the dose of radioiodine and the time of follow-up, between the two groups. After the RRA treatment, 44 group A patients (88%) were in remission and 6 (12%) in persistence; while in group B, 52 (91·2%) were in remission, 1 (1·8%) in persistence and 4 (7%) in recurrence. At their latest follow-up median 87·3 (23·3-251·6 months), all patients were in remission, either as a result of further iodine radioiodine therapy (in 11 patients) or watchful monitoring. CONCLUSIONS: The timing of RRA seems to have no effect on the long-term outcome of the disease. Therefore, urgency for radioiodine ablation in patients with low-risk thyroid cancer is not recommended.

Efficacy analysis of (131)I therapy and predictive value of preablation stimulated thyroglobulin for lung metastases from differentiated thyroid cancer.

OBJECTIVE: Our objective was to investigate the clinical efficacy of (131)I therapy for lung metastases from differentiated thyroid cancer (DTC) and assess whether the preablation stimulated thyroglobulin (Tg) could have predictive value for the outcome. METHODS AND MATERIALS: Fifty-two DTC patients (mean 44.5±19.2years; 33 females and 19 males) with lung metastases treated with (131)I were retrospectively analysed. The therapeutic efficacy was evaluated based on the change in serum Tg. Fifty patients' preablation stimulated Tg were collected with negative Tg antibody levels and estimated using the t-test method. RESULTS: After (131)I therapy, a significant decrease in serum Tg was seen in 30 patients (effective rate, 57.6%), and changes in serum Tg that indicated stabilization and ineffectiveness were both seen in 11 patients (21.2%). Only patients with age under 45years were more likely to respond to serum Tg changes (P=0.046). But binary logistic regression revealed that none of the six factors (age, patient gender, pathological type, local lymph node involvement, size of metastases, and (131)I uptake by metastases) had statistically significant impacts on the efficacy analysis (all P>0.05). For analysing with the preablation stimulated Tg, the "Fine miliaric" and (131)I uptake positive with great prognosis group was much lower than any other group (all the P<0.05). CONCLUSION: (131)I therapy is a feasible and effective treatment for DTC lung metastases. A better prognosis would be accomplished in those who had low level of preablation stimulated Tg in DTC patient with lung metastases.

Radioiodine post-surgical remnant ablation in patients with differentiated thyroid cancer: news from the last 10 years.

Due to the growing incidence of differentiated thyroid carcinoma (DTC) and in particular of small papillary thyroid cancer observed in the last few decades, the indications, the activity of radioiodine (131I) to be administered, and the efficacy of post surgical thyroid 131I remnant ablation (RRA) have been widely discussed. In the last 10 years, the use of recombinant human TSH (rhTSH) or thyroid hormone withdrawal (THW) to stimulate the 131I remnant uptake has also interested many authors. The general agreement is that small (≤1 cm) intrathyroidal unifocal DTC with a favorable histology and no node metastases should not be submitted to RRA because of the low risk of relapse and cancer specific mortality. Conversely, RRA is indicated in patients with a higher risk level since it seems to reduce recurrence rates and mortality. The recent demonstration that the RRA preparation with rhTSH is as effective as THW using either high (100 mCi) or low (30 mCi) 131I activities suggests that rhTSH preparation and low activity of 131I should be considered as the standard of care for both low- and intermediate-risk DTC patients in the near future. Moreover, the use of low 131I activities and rhTSH reduces whole body radiation exposure and improves the quality of life which are very important advantages for DTC patients.

Radioiodine therapy of metastatic lesions of differentiated thyroid cancer.

Seventy years after the first successful radioiodine treatment of metastatic differentiated thyroid cancer (DTC), radioiodine (131I) therapy for this type of tumor is still without alternative. During the last decade, some key issues such as individual dosimetry, and preparation of 131I therapy by recombinant human TSH have been addressed, but this has not yet lead to conclusive results; furthermore a number of questions related to indication, preparation, and treatment protocol of 131I therapy still remain unanswered. In this review, we will address the literature pertaining to the latest developments in the field of 131I therapy of advanced DTC and we will give an overview of the state of the art regarding patient preparation, dosimetry, and therapy.

Target therapies for radioiodine refractory advanced thyroid tumors.

A small but not irrelevant percentage of differentiated thyroid cancers become refractory to radioiodine treatment either because they lose the ability of taking up iodine over the time or because, despite a persistent uptaking ability, the effect of the radioiodine is lost in terms of tumor burden reduction. These patients receive only few and transient benefits from other conventional therapies and particularly from chemotherapy. In the last decade, several new drugs have been discovered as potentially useful and tested in clinical trials. They are mainly represented by protein kinase inhibitor molecules that should be proposed to advanced and progressive 131I refractory thyroid cancer patients by enrolling them in clinical trials or by the "off label" use of the drug.

Thyroid lobe ablation with radioactive iodine as an alternative to completion thyroidectomy after hemithyroidectomy in patients with follicular thyroid carcinoma: long-term follow-up.

BACKGROUND: Radioactive iodine lobe ablation (RAI-L-ABL) is a possible alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma (FTC), but no long-term outcome data are available after lobe ablation. We analyzed the long-term outcome of lobe ablation in a series of patients with FTC. METHODS: This was a retrospective study of patients who were treated with lobe ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe ablation with (131)I (30-32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%) had initial total thyroidectomy (T-Tx). The main outcomes analyzed were (131)I uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid-stimulating hormone (TSH), long-term disease-specific mortality, and disease-free survival. RESULTS: After lobe ablation, radioiodine uptake was significantly lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p<0.005) or T-Tx group (1.3%, p=0.054). Subsequent remnant ablation was performed in 12 of 37 (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx group, and in 25 of 29 (86.2%) patients in the T-Tx group (p<0.01). With median follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and 53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one death in the T-Tx group. No other RAI-L-ABL patients had detectable disease, whereas patients in the C-Tx group and two patients in the T-Tx group had detectable disease (p=0.18). Long-term stimulated or suppressed Tg of <1 ng/mL were found in 87.5% of the RAI-L-ABL group (n=28), 86.3% of the C-Tx group (n=57), and 77.8% of the T-Tx group (n=21). Tg was detectable in 40.6% of the RAI-L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups (p<0.05, between groups). CONCLUSIONS: RAI-L-ABL, C-Tx, and T-Tx are equally effective in achieving serum TSH concentrations of >25 mIU/L and preparing patients for conventional (131)I treatment and whole body scanning with similar long-term outcomes. However, persistent measurable Tg (range 0.2-2.2 ng/mL) is more common after RAI-L-ABL.