Intermediate-risk Papillary Thyroid Cancer Research Articles

Total vs hemithyroidectomy for intermediate risk papillary thyroid cancer: A 23 year retrospective study in a tertiary center.

There is much debate in the literature over the extent of surgery for patients with intermediate risk papillary thyroid cancer. We herein report our results in a local tertiary hospital. We identify from our database patients with papillary thyroid cancer who underwent surgery in our hospital and were stratified to be of intermediate risk from the GAMES stratification system. Patients' demographic data, surgical and pathological details were recorded. Primary end points were disease specific survival (DSS) and recurrence free survival (RFS). From January 1993 to December 2016, 231 patients with papillary thyroid cancer underwent surgery of which 137 (59%) were of intermediate risk. 45 (33%) patients had hemithyroidectomy and 92 (67%) patients had total thyroidectomy. In the total thyroidectomy group, patients had a higher tumor (T) (p value = 0.009) and nodal (N) staging (p value = 0.001). They were also predicted to have a higher risk of recurrence according to the American Thyroid Association (ATA) classification (p value = 0.005). The 5 year DSS in both groups were 100%. The 5 year RFS in the total thyroidectomy and hemithyroidectomy groups were 92% and 100% respectively and were significantly different by the log rank test (p value = 0.02). The median follow up time was 54 months (range 4-276 months). The 5 year survival in intermediate risk papillary thyroid cancer is favorable. Hemithyroidectomy is an acceptable choice of operation in intermediate risk patients with a better risk profile.

Is it Worth Suppressing Tsh in low- and Intermediate-Risk Papillary Thyroid Cancer Patients Before the First Disease Assessment?

Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment. A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 4 >2 μUI/mL. This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups. TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment. ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography.

Intermediate-Risk Papillary Thyroid Cancer: Risk Factors for Early Recurrence in Patients with Excellent Response to Initial Therapy.

Patients with excellent response to initial therapy have a low rate of tumor recurrence. The objectives of this study were to evaluate the rate of early tumor recurrence in patients with intermediate-risk papillary thyroid cancer who had an excellent response to initial treatment and to identify risk factors. This retrospective cohort study included 217 patients with American Thyroid Association intermediate-risk papillary thyroid cancer who had a documented excellent response to initial treatment (total thyroidectomy and adjuvant therapy with 100-150 mCi [3.7-5.5 GBq] of radioactive iodine [RAI]). The assessed outcome was recurrence, defined as new evidence of disease after any disease-free period. Multivariate logistic regression and Cox regression models were used to determine the factors associated with recurrence upon recording clinical, surgical, and pathology variables. Sixteen (7.4%) cases of recurrent disease were documented after a median follow-up period of 42 months (range 17-88 months). Structural recurrence was documented in 10 (62.5%) patients, and biochemical recurrence was documented in the remaining six patients. The logistic regression model identified a significant association between early recurrence and pN1b involvement (odds ratio [OR] = 10.81 [confidence interval (CI) 1.87-62.59]), lateral neck RAI uptake (OR = 6.06 [CI 1.67-22]), and pre-ablation thyroglobulin >10 ng/mL (OR = 4.01 [CI 1.16-13.85]). Variables that proved significant in the Cox regression model were: pN1b involvement (hazard ratio = 9.6 [CI 1.91-48.52]) and lateral neck RAI uptake (hazard ratio = 5.95 [CI 1.86-18.97]). The observed early recurrence rate of 7.4% is uncharacteristically high for a population of patients who had an excellent response to initial treatment. The significant association that was found between recurrent disease and lateral neck lymph node metastasis, lateral neck I131 uptake in post-therapy whole-body scan, and pre-ablation thyroglobulin levels >10 ng/mL indicates that early recurrence (<5 years) most likely indicates progression of micrometastatic disease already present at diagnosis and unsuccessfully eradicated with initial therapy.

Is postoperative radioactive iodine associated with a survival advantage among…

Abstract Aim This trial aimed to determine wether postoperative radioactive iodine(RAI) associated with a survival benefit among intermediate-risk Papillary Thyroid Cancer patients or not. Methods this study is a retrospective study of intermediate-risk papillary thyroid cancer patients that were treated with or without post operative RAI from 1st January 2002 till 1st January 2012. Overall survival (OS) and multivariate regression analyses were measured for all patients. Results 100 patients were included in this trial : 70 patients received postoperative RAI and 30 patients did not. The mean follow-up time was 7.1 (4.8 -15.1 years), and a median survival time could not be estimated. Overall survival at 10 years was 96% in the RAI vs 93% in the group without RAI (P &lt; .001). RAI reduced risk of death by a 27% [hazard risk (HR) 0.73, confidence interval (CI) 0.64 - 0.84, P &lt; .001]. Older patient age, male gende, larger tumor size, multifocal tumors, lymph node metastases, aggressive histology, vascular invasion, positive surgical margin, minimal extrathyroidal extension and absence of postoperative RAI were accompanied by compromised OS (all P ≤ .001). Conclusion This representative study addresses the survival advantage of RAI for with intermediate risk PTC patients but conducting of large prospective randomized controlled trial is still warranted.

Use of Personalized Post-Total Thyroidectomy Criteria in Low and Intermediate Risk Papillary Thyroid Cancer Patients to avoid Routine Radioactive Iodine Administration

Use of Personalized Post-Total Thyroidectomy Criteria in Low and Intermediate Risk Papillary Thyroid Cancer Patients to avoid Routine Radioactive Iodine Administration

Development of prognostic signatures for intermediate-risk papillary thyroid cancer.

BackgroundThe incidence of Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, has risen rapidly worldwide. PTC usually has an excellent prognosis. However, the rising incidence of PTC, due at least partially to widespread use of neck imaging studies with increased detection of small cancers, has created a clinical issue of overdiagnosis, and consequential overtreatment. We investigated how molecular data can be used to develop a prognostics signature for PTC.MethodsThe Cancer Genome Atlas (TCGA) recently reported on the genomic landscape of a large cohort of PTC cases. In order to decrease unnecessary morbidity associated with over diagnosing PTC patient with good prognosis, we used TCGA data to develop a gene expression signature to distinguish between patients with good and poor prognosis. We selected a set of clinical phenotypes to define an ‘extreme poor’ prognosis group and an ‘extreme good’ prognosis group and developed a gene signature that characterized these.ResultsWe discovered a gene expression signature that distinguished the extreme good from extreme poor prognosis patients. Next, we applied this signature to the remaining intermediate risk patients, and show that they can be classified in clinically meaningful risk groups, characterized by established prognostic disease phenotypes. Analysis of the genes in the signature shows many known and novel genes involved in PTC prognosis.ConclusionsThis work demonstrates that using a selection of clinical phenotypes and treatment variables, it is possible to develop a statistically useful and biologically meaningful gene signature of PTC prognosis, which may be developed as a biomarker to help prevent overdiagnosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2771-6) contains supplementary material, which is available to authorized users.

Is postablation whole-body 131 I scintigraphy still necessary in intermediate-risk papillary thyroid cancer patients with pre-ablation stimulated thyroglobulin

Postablation whole-body scintigraphy, which is performed 5-7 days after administration of ablation activity of radioactive iodine-131 (131 I) in patients with thyroid cancer, is considered a routine procedure for remnant ablation and a useful tool for disease staging. However, the relationship of pre-ablation stimulated thyroglobulin (s-Tg) levels with postablation scintigraphic findings has not been evaluated. The current study was designed to determine the diagnostic value of postablation 131 I scintigraphy during initial staging and risk stratification in intermediate-risk papillary thyroid cancer (PTC) patients with pre-ablation s-Tg < 1 ng/ml at the time of ablation. From January 2013 to July 2015, consecutive PTC patients at intermediate-risk of recurrence according to American Thyroid Association criteria were prospectively recruited. Patients had to have pre-ablation s-Tg < 1 ng/ml in the absence of anti-Tg antibody at the time of ablation. Systematic pre-ablation neck ultrasonography was performed for each patient. Postablation whole-body planar scintigraphy was obtained 5 days after administration of ablation activity of 131 I. Single photon emission computed tomography/low-dose computed tomography was added for patients whose planar findings were inconclusive. Among 756 patients ablated, 240 (31·7%) patients were eligible for the analysis. Pre-ablation neck ultrasonography revealed lymph node metastases in eight of the 240 patients. Postablation scintigraphy showed ectopic neck uptake corresponding to the lymph nodes seen by ultrasonography in four patients and revealed neck lymph node metastases in another two patients whose ultrasonography findings were negative. None of the 240 patients showed distant metastasis on postablation scintigraphy. Neither staging nor initial risk stratification was altered by postablation scintigraphy in the included patients with pre-ablation s-Tg < 1 ng/ml. As postablation whole-body scintigraphy played a minimal role in improving staging or initial risk stratification in intermediate-risk PTC patients with pre-ablation s-Tg < 1 ng/ml, we propose that postablation scintigraphy may be omitted in this group of patients. Multi-institutional larger studies are necessary to draw definitive conclusions.

Ablative RAI Therapy Improves Overall Survival of Patients with Intermediate-Risk Papillary Thyroid Cancer

Clinical ThyroidologyVol. 27, No. 6 SummariesAblative RAI Therapy Improves Overall Survival of Patients with Intermediate-Risk Papillary Thyroid CancerJerome M. HershmanJerome M. HershmanSearch for more papers by this authorPublished Online:9 Jun 2015https://doi.org/10.1089/ct.2015;27.147-149AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 27Issue 6Jun 2015 InformationCopyright 2015 American Thyroid Association, Inc.To cite this article:Jerome M. Hershman.Ablative RAI Therapy Improves Overall Survival of Patients with Intermediate-Risk Papillary Thyroid Cancer.Clinical Thyroidology.Jun 2015.147-149.http://doi.org/10.1089/ct.2015;27.147-149Published in Volume: 27 Issue 6: June 9, 2015PDF download

Post-operative stimulated thyroglobulin and neck ultrasound as personalized criteria for risk stratification and radioactive iodine selection in low- and intermediate-risk papillary thyroid cancer.

The purpose of this study was to demonstrate the utility of a personalized risk stratification and radioactive iodine (RAI) selection protocol (PRSP) using post-operative stimulated thyroglobulin (Stim-Tg) and neck ultrasound in low- and intermediate-risk papillary thyroid carcinoma (PTC) patients. Patients with PTC tumors ≥1 cm were prospectively followed after total thyroidectomy and selective therapeutic central compartment neck dissection. Low/intermediate risk was defined as PTC confined to the thyroid or central (level VI) lymph nodes. Stim-Tg and neck ultrasound were performed approximately 3 months after surgery and used to guide RAI selection. Patients with Stim-Tg < 1 µg/L did not receive RAI, while those with Stim-Tg >5 µg/L routinely did. Those with Stim-Tg 1-5 µg/L received RAI on the basis of several clinical risk factors. Patients were followed for >6 years with serial neck ultrasound and basal/stimulated thyroglobulin. Among the 129 patients, 84 (65 %) had undetectable Stim-Tg after initial surgery, 40 (31 %) had Stim-Tg of 1-5 µg/L, and 5 (4 %) had Stim-Tg >5 µg/L. RAI was administered to 8 (20 %) patients with Stim-Tg 1-5 µg/L and 5 (100 %) with Stim-Tg >5 µg/L. Using this approach, RAI therapy was avoided in 17/20 (85 %) patients with tumors >4 cm, in 72/81 (89 %) patients older than 45 years, and in 6/9 (67 %) patients with central lymph node involvement. To date, 116 (90 %) patients in this cohort have not received RAI therapy with no evidence of residual/recurrent disease, whereas among the 13 patients who received RAI, 1 (8 %) had pathologic residual/recurrence disease. Using the proposed PRSP, RAI can be avoided in the majority of low/intermediate-risk PTC patients. Moreover, traditional risk factors considered to favor RAI treatment were not always concordant with the PRSP and may lead to overtreatment.

Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998-2006, participated in the study. Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1-3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. A total of 21 870 patients were included; 15 418 (70.5%) received RAI and 6452 (29.5%) did not. Mean follow-up was 6 years, with the longest follow-up of 14 years. In an unadjusted analysis, RAI was associated with improved OS in all patients (P < .001) as well as in a subgroup analysis among patients younger than 45 years (n = 12 612, P = .002) and 65 years old and older (median OS 140 vs 128 mo, n = 2122, P = .008). After a multivariate adjustment for demographic and clinical factors, RAI was associated with a 29% reduction in the risk of death, with a hazard risk 0.71 (95% confidence interval 0.62-0.82, P < .001). For age younger than 45 years, RAI was associated with a 36% reduction in risk of death, with a hazard risk 0.64 (95% confidence interval 0.45- 0.92, P = .016). This is the first nationally representative study of intermediate-risk PTC patients and RAI therapy demonstrating an association of RAI with improved overall survival. We recommend that this patient group should be considered for RAI therapy.

Acute-on-Chronic Kidney Injury in Thyroid Hormone Withdrawal: A Case with Possible Implications for Radioactive Iodine Planning.

The association between renal dysfunction and hypothyroidism is of increasing clinical importance as thyroid hormone replacement may attenuate decline in renal function and improve cardiovascular outcomes in patients with chronic kidney disease (CKD). Although multiple mechanisms for the induction of renal insufficiency in hypothyroidism have been described, the renal impact of short-term, acute hypothyroidism is unknown, which has possible implications for thyroid cancer patients preparing to receive radioactive iodine (RAI). A 56-year-old gentleman with history of unilateral renal agenesis and CKD stage III presented with intermediate-risk papillary thyroid cancer. In preparation for RAI, he underwent thyroid hormone withdrawal (THW) associated with acute kidney injury (AKI), as marked by a decrease in his estimated GFR from 53 to 32 mL/min/1.73 m2. Upon resumption of thyroid hormone, renal function returned to baseline within months. Although AKI in this case was not otherwise associated with adverse outcome and reversed upon resumption of thyroid hormone, it is possible that this phenomenon could result in potential harm, particularly in the patient with baseline renal insufficiency. In CKD patients, preparation for RAI therapy may require special consideration; future studies should address the role of recombinant TSH to mitigate deleterious renal effects of acute hypothyroidism in this setting.

Radioactive Iodine Use in Patients with Low- and Intermediate-Risk Papillary Thyroid Cancer

Radioactive Iodine Use in Patients with Low- and Intermediate-Risk Papillary Thyroid Cancer

Selective Use of Radioactive Iodine in Intermediate-Risk Papillary Thyroid Cancer

OBJECTIVE To describe the outcomes with the selective use of radioactive iodine (RAI) in patients who are at intermediate risk of death from papillary thyroid cancer, focusing on 2 subgroups: patients older than 45 years with low-risk tumors and patients younger than 45 years with high-risk tumors. DESIGN Retrospective case review. SETTING Tertiary referral US cancer center. PATIENTS The study incluced 532 consecutive patients who were surgically treated between 1986 and 2005. INTERVENTIONS All patients underwent total thyroidectomy; 307 also received RAI. MAIN OUTCOME MEASURES Disease-specific survival (DSS) and recurrence-free survival (RFS). RESULTS Of 344 patients older than 45 years with low-risk tumors, 148 (43%) received RAI and 196 (57%) were selected not to receive RAI. The patients who were treated without RAI were more likely to be female and have pT1N0 disease. The 5-year DSS and RFS were 100% and 98%, respectively. The presence of nodal metastases predicted poorer 5-year RFS within this group (99% vs 91%; P=.004). Of 188 patients younger than 45 years with high-risk tumors, 159 (85%) received RAI, and only 29 (15%) were selected not to receive RAI. The 5-year DSS and RFS for these patients were 100% and 95%, respectively. The presence of nodal metastases predicted poorer 5-year RFS within this group (100% vs 86%; P=.02). CONCLUSION Our study shows that the subgroup of patients who are older than 45 years with tumors that are smaller than 4 cm in greatest dimension and confined to the thyroid gland and who do not have nodal metastases can safely be treated without RAI.

Undetectable thyroglobulin after total thyroidectomy in patients with low- and intermediate-risk papillary thyroid cancer— is there a need for radioactive iodine therapy?

The efficacy of radioactive iodine therapy (RAI) in patients who have an undetectable thyroglobulin (Tg) level after total thyroidectomy in well-differentiated papillary thyroid cancer (PTC) is questionable. The objectives of this study were to report the risk of recurrence in patients with PTC who had an undetectable Tg level after total thyroidectomy managed with postoperative RAI and without RAI. After approval by the institutional review board, 751 consecutive patients who had total thyroidectomy for PTC as well as postoperative Tg measurement were identified from our institutional database of 1163 patients treated for well-differentiated thyroid carcinoma at Memorial Sloan Kettering Cancer Center between 1999 and 2005. Of these, 424 patients had an undetectable postoperative Tg (defined as a Tg <1 ng/mL) of whom 80 were classified as low, 218 intermediate, and 126 high risk via use of the GAMES (grade, age, distant metastasis, extrathyroidal extension, and size of the neoplasm) criteria. Patient, neoplasm, and treatment characteristics were recorded on the low- and intermediate-risk patients. Recurrence was defined as any structural abnormality on examination or imaging and confirmed by fine-needle aspiration biopsy. Disease-specific survival and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Univariate analysis was carried out by the log rank test and multivariate analysis by Cox proportional hazards method. In the low-risk group (n = 80), 35 patients received postoperative RAI and 45 did not. Comparison of patient and tumor characteristics showed patients treated without RAI were more likely to have T1 tumors (82% vs 60%, P = .027). There were no disease-specific deaths in either group. There was 1 neck recurrence in the group that did not receive RAI. Patients managed without RAI had a similar RFS to patients managed with RAI (96% vs 100%, P = .337). In the intermediate risk group (n = 218), 135 were managed with RAI and 83 without. Comparison of patient and tumor characteristics showed patients managed without RAI were more likely to be older patients (≥ 45 years: 90% vs 39%, P < .0005) with smaller tumors (pT1T2: 97% vs 62%, P < .0005) and negative neck disease (N0: 56% vs 30%, P < .0005). There were no disease specific deaths in either group. There were 7 recurrences, of which 6 were in the RAI cohort (5 regional, 1 distant) and 1 in the non-RAI cohort (1 regional). Patients managed without RAI had a similar RFS to patients managed with RAI (97% vs 96%, P = .234). Select low- and intermediate-risk group patients who have undetectable Tg after total thyroidectomy for PTC can be managed safely without adjuvant RAI with no increase in risk of recurrence.

Surgical Treatment of Low- and Intermediate-Risk Papillary Thyroid Cancer with Minimally Invasive Video-Assisted Thyroidectomy

Minimally invasive video-assisted thyroidectomy (MIVAT) was introduced in the clinical practice to treat small benign thyroid nodules. This method has recently been demonstrated to produce the same completeness as a conventional thyroidectomy in patients with papillary thyroid cancer (PTC). The low number of treated cases and the limited follow-up of these patients represent the major limitations of these studies. The aim of the study was to compare the outcome of two groups of PTC patients, one treated with MIVAT and the other with conventional thyroidectomy, after a median follow-up of 5 yr. A total of 221 PTC patients were enrolled in this study according to the following criteria: 171 were treated with MIVAT (group A), and 50 were treated with conventional thyroidectomy (group B). The outcome and the cumulative (131)I activity administered to achieve curative status were compared. After a mean follow-up of 3.6 +/- 1.5 yr (range, 1-8 yr; median, 5 yr), no differences were found between group A and group B. A similar rate of permanent hypoparathyroidism and/or nerve cord palsy was found in both groups. We demonstrated that PTC patients operated on with MIVAT had a good outcome after 5 yr. This was similar to the outcome of patients treated with conventional thyroidectomy and the same degree of exposure to (131)I. These results, together with the evidence of a similar degree of completeness and rate of complications between the two surgical techniques, show that MIVAT is a valid option to treat low- and intermediate-risk PTC patients.