Can patients with papillary thyroid carcinoma and low postoperative thyroglobulin in the presence of clinically apparent lymph node metastases (cN1) be spared from radioiodine?

BACKGROUND: The study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and clinically apparent lymph node metastases (LNM) (cN1) who had low thyroglobulin (Tg) after total thyroidectomy and who were not submitted to adjuvant therapy with 131I. METHODS: This was a prospective study. It included 82 cN1 patients (≤3 LNM ≤1.5 cm without macroscopic extracapsular extension) with tumors ≤4 cm without macroscopic extrathyroid invasion (T1-2) and who after thyroidectomy had unstimulated Tg (u-Tg) < 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. The patients were not submitted to therapy with 131I. RESULTS: The time of follow-up ranged from 24 to 156 months (median 84 months). Seventy-nine patients (96.3%) continued to have u-Tg < 0.3 ng/ml and negative US. Three patients (3.6%) exhibited an increase in Tg and structural recurrence was detected in two. After treatment, these patients achieved u-Tg < 1 ng/ml and the imaging methods revealed no apparent tumor. CONCLUSIONS: The results suggest that even cN1 patients, given the absence of extensive LNM or other adverse findings, who have low Tg and neck US showing no anomalies after thyroidectomy do not require radioiodine.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b)

ABSTRACT Objective To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). Subjects and methods The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). Results One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. Conclusion Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b).

OBJECTIVE: To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). SUBJECTS AND METHODS: The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). RESULTS: One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. CONCLUSION: Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants)

ABSTRACT Objective The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. Subjects and methods Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. Results A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. Conclusions Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants).

OBJECTIVE: The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. SUBJECTS AND METHODS: Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. RESULTS: A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. CONCLUSIONS: Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Low postoperative nonstimulated thyroglobulin as a criterion to spare radioiodine ablation.

This study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) who had low nonstimulated thyroglobulin (Tg), measured with a second-generation assay, after total thyroidectomy and who were not submitted to ablation with (131)I. The objective was to define whether low postoperative nonstimulated Tg can be used as a criterion to spare patients with PTC from therapy with (131)I. This was a prospective study including 222 patients with PTC (except for microcarcinoma restricted to the thyroid and tumor with extensive extrathyroid invasion (pT4), aggressive histology, extensive lymph node (LN) involvement, or known residual disease). After thyroidectomy, all patients had nonstimulated Tg<0.3 ng/ml, negative antithyroglobulin antibodies (TgAb) and neck ultrasonography (US) showing no anomalies. Because of this finding, the patients were not submitted to ablation with (131)I. The time of follow-up ranged from 15 to 102 months (median 62 months). Of the 222 patients, 217 (97.7%) continued to have nonstimulated Tg <0.3 ng/ml and negative US. Tg was undetectable in the last assessment in 185 of these patients and detectable in 32. Five patients (2.2%) exhibited an increase in Tg, and LN metastases were detected in 4 (structural recurrence). One patient progressed to an increase in Tg, but disease was not detected by the imaging methods (biochemical recurrence). The results obtained here suggest that patients with PTC who have low nonstimulated Tg (measured with a second-generation assay and in the absence of TgAb) and negative neck US after thyroidectomy do not require ablation with (131)I.

Persistent and recurrent disease in patients with papillary thyroid carcinoma with clinically apparent (cN1), but not extensive, lymph node involvement and without other factors for poor prognosis.

OBJECTIVE: Lymph node metastases (LNM) are frequent in patients with papillary thyroid cancer (PTC). The risk of persistent disease (PD) and tumor recurrence (TR) is increased when factors for poor prognosis other than LNM exist, when LNM are numerous, large, detected by preoperative ultrasonography (US), or exhibit extranodal extension. This study evaluated the risk of PD and TR in patients with LNM not exhibiting these characteristics. SUBJECTS AND METHODS: Eighty-six patients with 5 or fewer LNM detected during intraoperative inspection, but not by preoperative US, who had no other factors for poor prognosis [tumors > 4 cm, extensive extrathyroid invasion, vascular invasion, aggressive histological subtype, distant metastases, incomplete tumor resection], were studied. All patients underwent total thyroidectomy followed by radioiodine ablation. PD was defined as metastases on initial post-therapy whole-body scans (RxWBS) or detected by imaging methods up to 12 months after ablation. TR was defined as structural disease diagnosed more than one year after ablation in patients without PD. RESULTS: PD was diagnosed in 3/86 patients (3.5%). TR was observed in 2/83 patients (2.5%) after 62 months of follow-up. There was no case of death due to the disease. A correlation was observed between pre-ablation Tg and PD or TR [1/48 (2%) with Tg ≤ 2 ng/mL versus 2/22 (9%) with Tg > 2 ≤ 10 ng/mL versus 2/7 (28.5%) with Tg ≥ 10 ng/ml)]. It is noteworthy that 38 patients had up to 3 positive LN and pre-ablation Tg ≤ 2 ng/ml, and none of them had PD or TR. CONCLUSIONS: The frequency of PD and TR was low in patients with PTC with 5 or fewer LNM and without other factors for poor prognosis. Low postoperative stimulated Tg was predictive of the absence of PD and TR in these patients.

Persistent and recurrent disease in patients with papillary thyroid carcinoma with clinically apparent (cN1), but not extensive, lymph node involvement and without other factors for poor prognosis

Objective Lymph node metastases (LNM) are frequent in patients with papillary thyroid cancer (PTC). The risk of persistent disease (PD) and tumor recurrence (TR) is increased when factors for poor prognosis other than LNM exist, when LNM are numerous, large, detected by preoperative ultrasonography (US), or exhibit extranodal extension. This study evaluated the risk of PD and TR in patients with LNM not exhibiting these characteristics.Subjects and methods Eighty-six patients with 5 or fewer LNM detected during intraoperative inspection, but not by preoperative US, who had no other factors for poor prognosis [tumors > 4 cm, extensive extrathyroid invasion, vascular invasion, aggressive histological subtype, distant metastases, incomplete tumor resection], were studied. All patients underwent total thyroidectomy followed by radioiodine ablation. PD was defined as metastases on initial post-therapy whole-body scans (RxWBS) or detected by imaging methods up to 12 months after ablation. TR was defined as structural disease diagnosed more than one year after ablation in patients without PD.Results PD was diagnosed in 3/86 patients (3.5%). TR was observed in 2/83 patients (2.5%) after 62 months of follow-up. There was no case of death due to the disease. A correlation was observed between pre-ablation Tg and PD or TR [1/48 (2%) with Tg ≤ 2 ng/mL versus 2/22 (9%) with Tg > 2 ≤ 10 ng/mL versus 2/7 (28.5%) with Tg ≥ 10 ng/ml)]. It is noteworthy that 38 patients had up to 3 positive LN and pre-ablation Tg ≤ 2 ng/ml, and none of them had PD or TR.Conclusions The frequency of PD and TR was low in patients with PTC with 5 or fewer LNM and without other factors for poor prognosis. Low postoperative stimulated Tg was predictive of the absence of PD and TR in these patients.

Thyroid ablation with 1.1 GBq (30 mCi) iodine-131 in patients with papillary thyroid carcinoma at intermediate risk for recurrence.

BACKGROUND: Little is known about the medium- and long-term outcomes of thyroid ablation with 1.1 GBq (30 mCi) ¹³¹I in patients with papillary thyroid carcinoma who have a tumor >4 cm or accompanied by extrathyroid invasion or clinically detected lymph node metastases (cN1). The objective of this study was to evaluate the efficacy of ablation with 30 mCi ¹³¹I in this subgroup of patients and to report the medium-term outcomes. METHODS: We studied 152 patients with papillary thyroid carcinoma submitted to total thyroidectomy with apparently complete tumor resection, who had a tumor >4 cm or 2-4 cm accompanied by extrathyroid invasion or lymph node metastases, or ≤2 cm accompanied by both extrathyroid invasion and lymph node metastases. Patients with extensive extrathyroid invasion by the primary tumor were excluded. Lymph node involvement was detected by ultrasonography or palpation (cN1). RESULTS: Forty-two patients were prepared by administration of recombinant human thyrotropin and 110 by levothyroxine withdrawal. Posttherapy whole-body scanning revealed unequivocal ectopic uptake in three patients. When evaluated 9-12 months after ablation, 123 patients had achieved complete ablation (stimulated thyroglobulin [Tg] <1 ng/mL, negative anti-Tg antibodies, and neck ultrasonography); a new posttherapy whole-body scanning revealed persistent disease in 2 patients whose initial posttherapy whole-body scanning (obtained at the time of ablation) had already shown ectopic uptake; 12 patients presented with a Tg >1 ng/mL and 14 had positive anti-Tg antibodies without apparent metastases; 1 patient had metastases not detected at the time of ablation. Recurrence was observed in an additional 6 patients during follow-up (median 76 months). There was no case of death related to the disease. Therefore, an activity of 30 mCi failed in only 9 (6%) patients with persistent disease or recurrence after ablation. None of the variables analyzed (sex, age, tumor size, multicentricity, extrathyroid invasion, lymph node metastases, preparation [recombinant human thyrotropin or levothyroxine withdrawal]) was a predictor of ablation failure. CONCLUSIONS: An activity of 30 mCi ¹³¹I is effective in thyroid ablation in patients with stage T3 and/or N1 papillary thyroid carcinoma.