Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis

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Abstract

Background

Regarding the longer-term recurrence rate the optimal activity for the remnant thyroid ablation in patients with differentiated thyroid cancer (DTC) is discussed controversially. For the short-term ablation success rate up to 12 months there are already several meta-analyses. In this study we performed the first meta-analysis regarding the longer-term recurrence rate after radioactive 131-I administration.

Methods

We conducted an electronic search using PubMed/MEDLINE, EMBASE and the Cochrane Library. All randomized controlled trials (RCTs) assessed the recurrence rate after radioactive iodine ablation in patients with DTC, with a follow-up of at least two years were selected. Statistics were performed by using Review Manager version 5.3 and Stata software.

Results

Four RCTs were included in the study, involving 1501 patients. There was no indication for heterogeneity ( I ² = 0%) and publication bias. The recurrence rate among patients who had a low dose 131-iodine ablation was not higher than for a high dose activity (odds ratio (OR) 0.93 [95% confidence interval (CI) 0.53–1.63]; P = 0.79). The mean follow-up time was between 4.25 and 10 years. The subgroup analysis regarding the TSH stimulated thyroglobulin values (< 10 ng/mL versus < 2 ng/mL versus ≤1 ng/mL) showed no influence on recurrence rate.

Conclusions

For the first time we showed that the longer-term, at least 2-year follow-up, recurrence rate among patients who had 131-iodine ablation with 1.1 GBq was not higher than with 3.7 GBq.

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Most cited references 14

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Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial

Ellen Benhamou, Claire Schvartz, Pierre Vera … (2018)

In ESTIMABL1, a randomised phase 3 trial of radioactive iodine (131I) administration after complete surgical resection in patients with low-risk thyroid cancer, 92% of patients had complete thyroid ablation at 6-10 months, defined as a recombinant human thyroid-stimulating hormone (rhTSH)-stimulated serum thyroglobulin concentration of 1 ng/mL or less and normal findings on neck ultrasonography. Equivalence was shown between low-activity (1·1 GBq) and high-activity (3·7 GBq) radioactive iodine and also between the use of rhTSH injections and thyroid hormone withdrawal. Here, we report outcomes after 5 years of follow-up.

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Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial

Hakim-Moulay Dehbi, Ujjal Mallick, Jonathan Wadsley … (2019)

Summary Background Two large randomised trials of patients with well-differentiated thyroid cancer reported in 2012 (HiLo and ESTIMABL1) found similar post-ablation success rates at 6–9 months between a low administered radioactive iodine (131I) dose (1·1 GBq) and the standard high dose (3·7 GBq). However, recurrence rates following radioactive iodine ablation have previously only been reported in observational studies, and recently in ESTIMABL1. We aimed to compare recurrence rates between radioactive iodine doses in HiLo. Methods HiLo was a non-inferiority, parallel, open-label, randomised controlled factorial trial done at 29 centres in the UK. Eligible patients were aged 16–80 years with histological confirmation of differentiated thyroid cancer requiring radioactive iodine ablation (performance status 0–2, tumour stage T1–T3 with the possibility of lymph-node involvement but no distant metastasis and no microscopic residual disease, and one-stage or two-stage total thyroidectomy). Patients were randomly assigned (1:1:1:1) to 1·1 GBq or 3·7 GBq ablation, each prepared with either recombinant human thyroid-stimulating hormone (rhTSH) or thyroid hormone withdrawal. Patients were followed up at annual clinic visits. Recurrences were diagnosed at each hospital with a combination of established methods according to national standards. We used Kaplan-Meier curves and hazard ratios (HRs) for time to first recurrence, which was a pre-planned secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT00415233. Results Between Jan 16, 2007, and July 1, 2010, 438 patients were randomly assigned. At the end of the follow-up period in Dec 31, 2017, median follow-up was 6·5 years (IQR 4·5–7·6) in 434 patients (217 in the low-dose group and 217 in the high-dose group). Confirmed recurrences were seen in 21 patients: 11 who had 1·1 GBq ablation and ten who had 3·7 GBq ablation. Four of these (two in each group) were considered to be persistent disease. Cumulative recurrence rates were similar between low-dose and high-dose radioactive iodine groups (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 5·9% vs 7·3%; HR 1·10 [95% CI 0·47–2·59]; p=0·83). No material difference in risk was seen for T3 or N1 disease. Recurrence rates were also similar among patients who were prepared for ablation with rhTSH and those prepared with thyroid hormone withdrawal (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 8·3% vs 5·0%; HR 1·62 [95% CI 0·67–3·91]; p=0·28). Data on adverse events were not collected during follow-up. Interpretation The recurrence rate among patients who had 1·1 GBq radioactive iodine ablation was not higher than that for 3·7 GBq, consistent with data from large, recent observational studies. These findings provide further evidence in favour of using low-dose radioactive iodine for treatment of patients with low-risk differentiated thyroid cancer. Our data also indicate that recurrence risk was not affected by use of rhTSH. Funding Cancer Research UK.

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Low vs. High Radioiodine Activity to Ablate the Thyroid after Thyroidectomy for Cancer: A Randomized Study

Hanna Mäenpää, Jorma Heikkonen, Leila Vaalavirta … (2008)

Background Radioactive iodine is commonly administered following thyroidectomy for differentiated thyroid carcinoma to ablate the thyroid remnant. The optimal administered activity of radioiodine is unknown. Methodology/Principal Findings Adult subjects (n = 160) diagnosed with papillary or follicular thyroid carcinoma were randomly allocated to receive either 1100 MBq (30 mCi) or 3700 MBq (100 mCi) activity of radioiodine (131I) following thyroidectomy. The study participants were prepared for ablation using thyroid hormone withdrawal. Ablation was considered successful when serum thyroglobulin concentration was less than 1 ng/mL and no uptake was present in 131I scan. Ablation was successful following one administration of radioiodine in 42 (52%; 95% CI, 41% to 63%) of the 81 evaluable study participants who received 1100 MBq, and in 43 (56%, 45% to 67%) of the 77 subjects who received 3700 MBq activity (P = .61). There was no difference between the groups in the numbers of repeat radioiodine treatments needed to complete ablation (P = .27). The higher activity was associated with more nausea and taste disturbances, and a longer stay in a radioprotected isolation unit. None of the participants died from thyroid cancer during a median follow up of 51 months; three subjects in the 3700 MBq group and none in the 1100 MBq group were diagnosed with distant metastases during follow-up. In a meta-analysis of four randomized studies that compared the 1100 and 3700 MBq activities, the 1100 MBq activity tended to be associated with a higher risk of unsuccessful ablation (relative risk 1.148, 95% CI 0.974 to 1.353, P = .10). Conclusions/Significance The results provide no conclusive evidence that 3700 MBq activity is more effective for ablation of the thyroid remnant than 1100 MBq activity. The 3700 MBq activity is associated with more adverse effects. Trial Registration ClinicalTrials.gov NCT00115895

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Author and article information

Contributors

I. Vardarli: irfan.vardarli@alumni.uni-heidelberg.de

F. Weidemann: Frank.Weidemann@klinikum-vest.de

M. Aboukoura: Mohamad.Aboukoura@klinikum-vest.de

K. Herrmann: Ken.Herrmann@uk-essen.de

R. Görges: rainer.goerges@uni-due.de

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 15 June 2020

Publication date PMC-release: 15 June 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 550

Affiliations

[1 ]GRID grid.5570.7, ISNI 0000 0004 0490 981X, Department of Medicine I, Klinikum Vest GmbH, Knappschaftskrankenhaus Recklinghausen, Academic Teaching Hospital, , Ruhr-University Bochum, ; Dorstener Str. 151, 45657 Recklinghausen, Germany

[2 ]GRID grid.410718.b, ISNI 0000 0001 0262 7331, Department of Nuclear Medicine, , University Hospital Essen, ; Hufelandstraße 55, 45147 Essen, Germany

Article

Publisher ID: 7029

DOI: 10.1186/s12885-020-07029-3

PMC ID: 7296693

PubMed ID: 32539683

SO-VID: 48682438-e0d2-4818-8bc7-01bc2024511b

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 24 March 2020

Date accepted : 1 June 2020

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: longer-term,outcome,radioactive iodine ablation,differentiated thyroid carcinoma,meta-analysis

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: longer-term, outcome, radioactive iodine ablation, differentiated thyroid carcinoma, meta-analysis

Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis

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Abstract

Background

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Karger: Oncology

Most cited references 14

Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial

Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial

Low vs. High Radioiodine Activity to Ablate the Thyroid after Thyroidectomy for Cancer: A Randomized Study

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