Efficacy of redifferentiation therapy in radioactive iodine refractory thyroid cancer: a systematic review and meta-analysis
- 1Department of Advanced Biomedical Sciences, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy
- 2Department of Radiology, University of Sassari, Sassari, Italy
- 3IRCCS SYNLAB SDN, Naples, Italy
Abstract
Purpose: To systematically review and meta-analyze the efficacy of redifferentiation therapy in patients with radioactive iodine (RAI)-refractory thyroid cancer.
Methods: PubMed and Scopus databases were comprehensively searched up to January 2026 to identify clinical studies evaluating patients with RAI-refractory thyroid cancer who received targeted therapies to restore radioiodine uptake. Eligible studies reported either the rate of successful iodine re-uptake or treatment response evaluated according to RECIST 1.1 criteria. The primary endpoint was the pooled rate of successful redifferentiation, while secondary endpoints were objective response rate (ORR) and disease control rate (DCR), each stratified by redifferentiation status.
Results: Fifteen studies comprising 234 patients (cohort sizes: 3–33) were included. The pooled rate of successful redifferentiation was 51% (95% confidence interval, CI: 30%-71%), with no significant publication bias. Treatment response according to RECIST 1.1 was evaluated in 11 studies (93 patients). The pooled ORR was 28% (95% CI: 13%-44%) in redifferentiated patients compared to 8% (95% CI: 0%-44%) in non-redifferentiated individuals (P = 0.33). The pooled DCR was significantly higher, reaching 93% (95% CI: 79%-100%) in redifferentiated patients compared to 54% (95% CI: 15%-91%) in non-redifferentiated patients (P = 0.04).
Conclusions: In patients with RAI-refractory thyroid tumors, redifferentiation therapy using mitogen-activated protein kinase inhibitors successfully restores radioiodine avidity in approximately half of the cases. Although short-term disease control rates are promising, statistically significant prognostic differences and long-term survival benefits remain to be demonstrated in larger, standardized trials with extended follow-up.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08115-7.
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BibTeX
@article{zampella2026efficacy,
title = {{Efficacy of redifferentiation therapy in radioactive iodine refractory thyroid cancer: a systematic review and meta-analysis}},
author = {Emilia Zampella and Valeria Cantoni and Roberta Green and Valeria Gaudieri and Federica Volpicelli and Leandra Piscopo and Mariano Scaglione and Alberto Cuocolo and Michele Klain},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
year = {2026},
month = aug,
doi = {10.1007/s00259-026-08115-7},
url = {https://doi.org/10.1007/s00259-026-08115-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Efficacy of redifferentiation therapy in radioactive iodine refractory thyroid cancer: a systematic review and meta-analysis
AU - Emilia Zampella
AU - Valeria Cantoni
AU - Roberta Green
AU - Valeria Gaudieri
AU - Federica Volpicelli
AU - Leandra Piscopo
AU - Mariano Scaglione
AU - Alberto Cuocolo
AU - Michele Klain
PY - 2026
DA - 2026/08/06
JO - European Journal of Nuclear Medicine and Molecular Imaging
DO - 10.1007/s00259-026-08115-7
UR - https://doi.org/10.1007/s00259-026-08115-7
AB - Purpose: To systematically review and meta-analyze the efficacy of redifferentiation therapy in patients with radioactive iodine (RAI)-refractory thyroid cancer. Methods: PubMed and Scopus databases were comprehensively searched up to January 2026 to identify clinical studies evaluating patients with RAI-refractory thyroid cancer who received targeted therapies to restore radioiodine uptake. Eligible studies reported either the rate of successful iodine re-uptake or treatment response evaluated according to RECIST 1.1 criteria. The primary endpoint was the pooled rate of successful redifferentiation, while secondary endpoints were objective response rate (ORR) and disease control rate (DCR), each stratified by redifferentiation status. Results: Fifteen studies comprising 234 patients (cohort sizes: 3–33) were included. The pooled rate of successful redifferentiation was 51% (95% confidence interval, CI: 30%-71%), with no significant publication bias. Treatment response according to RECIST 1.1 was evaluated in 11 studies (93 patients). The pooled ORR was 28% (95% CI: 13%-44%) in redifferentiated patients compared to 8% (95% CI: 0%-44%) in non-redifferentiated individuals (P = 0.33). The pooled DCR was significantly higher, reaching 93% (95% CI: 79%-100%) in redifferentiated patients compared to 54% (95% CI: 15%-91%) in non-redifferentiated patients (P = 0.04). Conclusions: In patients with RAI-refractory thyroid tumors, redifferentiation therapy using mitogen-activated protein kinase inhibitors successfully restores radioiodine avidity in approximately half of the cases. Although short-term disease control rates are promising, statistically significant prognostic differences and long-term survival benefits remain to be demonstrated in larger, standardized trials with extended follow-up. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08115-7.
SN - 1619-7070
SN - 1619-7089
ER -