Targeted Therapy in Advanced Thyroid Cancer to Resensitize Tumors to Radioactive Iodine.

Abstract

Context:

Many differentiated thyroid cancers (DTC) dedifferentiate and become radioactive iodine (RAI)-refractory (RAIR) with worse outcomes. Targeted therapy (TTx) may downregulate MAPK signaling and sensitize tumors to RAI.

Objective:

We describe patients with RAIR DTC receiving TTx with demonstrated RAI uptake allowing for iodine-131 (I131) administration.

Design:

Charts of patients with metastatic, progressive, RAIR DTC in whom TTx increased RAI uptake on a diagnostic whole-body scan (WBS), were reviewed. Results of WBS, I131 administration, thyroglobulin (TG) panels, and cross-sectional studies were recorded.

Setting:

Thirteen patients [median age (range), 56 (45 to 75) years; seven men] were included; 11 (85%) had DTC, two (15%) had poorly DTC. Nine (69%) had BRAF mutations, three (23%) had RAS mutations, and one (8%) was wild type. Selective BRAF or an MEK inhibitor TTx was continued for a median (range) of 14.3 (1 to 76.4) months before diagnostic WBS.

Results:

Nine (69%) patients were treated with I131 [median (range) activity, 204.4 (150 to 253) mCi], after which TTx was discontinued. Median (range) follow-up was 8.3 (0 to 17.4) months after I131 therapy. All nine patients had durable disease control (three had partial response, six had stable disease). TG and TG antibody levels increased in patients who demonstrated uptake before TTx, and declined in eight of the nine patients after I131 treatment. Adverse events included pneumonitis and sialadenitis.

Conclusion:

TTx in BRAF-/RAS-mutated RAIR DTC resensitizes tumors to iodine. Subsequent I131 administration results in meaningful responses. Patient selection, adverse events, response duration, and survival impact require additional study.

• Authors: Tania Jaber, Steven G Waguespack, Maria E Cabanillas, Mohamed Elbanan, Thinh Vu, Ramona Dadu, Steven I Sherman, Moran Amit, Elmer B Santos, Mark Zafereo, Naifa L Busaidy
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 103 Issue 10 Pg. 3698-3705 (10 01 2018) ISSN: 1945-7197 [Electronic] United States
• PMID: 30032208 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Iodine Radioisotopes
• Protein Kinase Inhibitors
• Radiation-Sensitizing Agents
• Thyroglobulin
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• MAP Kinase Kinase 1

Topics

• Adenocarcinoma, Follicular (drug therapy, pathology, radiotherapy)
• Aged
• Carcinoma, Papillary (drug therapy, pathology, radiotherapy)
• Cross-Sectional Studies
• Female
• Follow-Up Studies
• Humans
• Iodine Radioisotopes (therapeutic use)
• MAP Kinase Kinase 1 (antagonists & inhibitors)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Mutation
• Prognosis
• Prospective Studies
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors, genetics)
• Radiation Tolerance (drug effects)
• Radiation-Sensitizing Agents (therapeutic use)
• Thyroglobulin (blood)
• Thyroid Neoplasms (drug therapy, pathology, radiotherapy)