Evidence map›Paper›PMID 23406027›Full record

Trial reportThe New England journal of medicine2013

Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.

Alan L Ho, Ravinder K Grewal, Rebecca Leboeuf, Eric J Sherman, David G Pfister, Desiree Deandreis, Keith S Pentlow, Pat B Zanzonico, Sofia Haque, Somali Gavane and 7 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00970359 (Reacquisition of RAI Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244), which is not on this map. Cited by 375 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
375citing papers in PubMed, 6 pooled it
50.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00970359 nacompletednot on this map

Reacquisition of RAI Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244: A Pilot Study

TypeinterventionalSponsorMemorial Sloan Kettering Cancer CenterRan2009 to 2013Enrolled24ConditionsThyroid CancerArmsAZD6244
3 · Its place in the literature

Who cites it

375 citing papers in PubMed, 6 syntheses or guidelines pooled it, 817 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Guideline
  4. SEOM-GETNE-TTCC Clinical guideline thyroid cancer (2023).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Guideline
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Enhancing Radioiodine Incorporation inThyroid : official journal of the American Thyroid Association · 2022
    Trial
  11. Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131).Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
  12. Review
  13. Targeted Radionuclide Therapy: Current Landscape and Combination Approaches to Improve Oncology Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  14. Article
  15. Article
  16. Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer.International journal of molecular sciences · 2026
    Review
  17. Review
  18. Review
  19. Article
  20. Review

315 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 1 institution in 1 country.

Alan L HoHead and Neck Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA.
Ravinder K Grewal
Rebecca Leboeuf
Eric J Sherman
David G Pfister
Desiree Deandreis
Keith S Pentlow
Pat B Zanzonico
Sofia Haque
Somali Gavane
Ronald A Ghossein
Julio C Ricarte-Filho
José M Domínguez
Ronglai Shen
R Michael Tuttle
Steve M Larson
James A Fagin
Memorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
MOLECULAR PATHOPHYSIOLOGY OF THYROID CELL GROWTHR01CA050706 · NCI · UNIVERSITY OF CINCINNATI · PI FAGIN, JAMES A · 1995 to 2023
$7.5M
MAMMARY CARCINOGENESIS IN RATS--HORMONAL PREVENTIONR01CA072598 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI NANDI, SATYABRATA · 1997 to 2001
$562k
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA050706NCI NIH HHS R01-CA50706NCI NIH HHS R01-CA72598PHS HHS P50 086438-10
6 · The paper itself

Abstract

backgroundMetastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine. Their effects in humans are not known.

methodsWe conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib.

resultsOf 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia.

conclusionsSelumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.).

Indexed as

AdultAgedBenzimidazolesFemaleHumansIodine RadioisotopesMaleMAP Kinase Kinase 1MAP Kinase Kinase 2Middle AgedMitogen-Activated Protein KinasesMultimodal ImagingMutationNeoplasm MetastasisPositron-Emission TomographyRadiometryAZD 6244BenzimidazolesIodine RadioisotopesMAP Kinase Kinase 1MAP Kinase Kinase 2Mitogen-Activated Protein KinasesSodium-Iodide SymportersSymportersThyrotropin Alfa

Identifiers

PMID23406027
PMCPMC3615415
OpenAlexW2113637323

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.