BETHESDA, MD — Patients who survive cancer often face second malignant neoplasms (SMN), which are among their most serious long-term adverse health conditions.
A study in Therapeutic Advances in Endocrinology and Metabolism sought to characterize clinical findings of patients who developed thyroid cancers as SMN, and to examine genomic alterations in thyroid cancer tissue.1
Researchers from Walter Reed National Military Medical Center and the Uniformed Services University of Health Sciences, both in Bethesda, MD, performed retrospective analysis of medical records from patients seen for management of thyroid cancer over a 10-year period. The study team retrieved clinical and pathologic data from medical charts, while also extracting tumor DNA and RNA from formalin-fixed, paraffin-embedded tissue and subjecting them to next-generation sequencing (NGS) using Ion Torrent Oncomine Focus Assay. At the same time, microfluidic digital polymerase chain reactions (PCRs) were performed using QIAcuity Digital PCR System to identify BRAF V600E mutations and RET/PTC fusions.
Results indicated that 16 of 620 patients receiving thyroid cancer surgery had a history of previously diagnosed malignancy. Eight patients were male, and eight patients were female, with a median age at diagnosis of 58.5 years (range, 4-78). Four patients had history of pediatric malignancy (PedCa), and 12 patients had a history of prior malignancy as an adult (AdCa).
Researchers determined that the latency periods for development of SMN in PedCa and AdCa patients were 10.8 (±5.2) years and 9.5 (±5.2) years, respectively.
The authors advised that histopathology revealed papillary thyroid cancers in 15 cases, and follicular thyroid cancer in one case; all tumors were classified as T1 or T2, and there were no patients presenting with metastases at the time of surgery.
Most, 81.2%, of the patients’ tumors had genomic alterations, including eight gene mutations (BRAF V600E (N = 4), RAS (N = 2), PI3CA (N = 2) and five gene fusions (RET/PTC1 (N = 4) and STRN/ALK (N = 1).
“In patients with PedCa and AdCa, mutations were detected in 1/4 (25%) and 7/12 (58.3%), respectively, p= 0.56; and fusions were detected in 3/4 (75%) and 2/12 (16.6%), respectively, p = 0.06,” the researchers reported. “In patients with and without history of therapeutic irradiation, mutations were detected with the same frequencies (5/10 (50%), and 3/6 (50%), respectively, p = 1.0). Gene fusions were detected in patients with and without history of irradiation in 5/10 (55.5%) and 0/6 (0%), respectively, p = 0.09.”
They suggested that “monitoring of cancer survivors for thyroid disorders allowed diagnosis of second thyroid cancers at early stages. Second, thyroid cancers harbor genomic alterations that are typical for sporadic as well as for radio-induced thyroid cancers.”
- Romanelli K, Wells J, Patel A, Mendonca Torres M, Costello J, Jensen K, Vasko V. Clinical and molecular characterization of thyroid cancer when seen as a second malignant neoplasm. Ther Adv Endocrinol Metab. 2021 Nov 24;12:20420188211058327. doi: 10.1177/20420188211058327. PMID: 35154635; PMCID: PMC8832328.