Clinical utility of RNA sequencing-based testing for thyroid cancer diagnosis and treatment

Challenges involved in the management of thyroid nodules include: Differentiating benign from malignant thyroid nodules when cytopathology results are indeterminate; determining the extent of initial thyroid surgery needed; and identifying targeted treatments for patients with thyroid cancers that do not respond to standard treatment.

“New advances in genomic technology and our understanding of the genomic underpinnings of thyroid disease are changing the landscape for how physicians diagnose and treat patients with thyroid nodules and cancer,” said William C. Faquin, M.D., Ph.D., pathologist at Massachusetts General Hospital and Editor-in-Chief of Cancer Cytopathology. “In the last 10 years, physicians have increasingly used genomic testing to help reduce unnecessary thyroid surgeries when the cytopathology sample is indeterminate for cancer. Now, genomic technology can identify gene mutation drivers of disease to inform the type of surgery to be performed. Increasingly, molecular testing may also help guide the use of targeted therapies that are available or in development for patients who do not respond to standard treatment.”

Researchers at the Johns Hopkins Hospital, and Veracyte describe the development of and evidence behind the Afirma GSC and XA. Both tests leverage RNA whole-transcriptome sequencing technology to measure gene expression in potentially cancerous thyroid nodules. The authors note that RNA transcriptome technology may provide advantages over DNA-based genomic findings because it reflects a nodule’s current genomic activity, as compared to DNA-based approaches, which may show inactive gene mutations.

Clinical experience with the Afirma Genomic Sequencing Classifier (GSC) from multiple centers


Unoperated GSC benign nodules were counted as true‐negative results. Unoperated GSC suspicious nodules were excluded. Data were obtained from Harrell et al, Ahmed et al, Endo et al, San Martin et al, Livhits et al, and Angell et al.

Two targeted therapies are now approved by the U.S. Food and Drug Administration for treating thyroid cancer patients: a combination of dabrafenib plus trametinib for BRAF V600E-mutated anaplastic thyroid cancer; and larotrectinib for solid tumors harboring a NTRKgene fusion, regardless of cancer type. Additionally, multiple other recent clinical trials have investigated therapies with specific targets that are relevant for thyroid cancer. These include two compounds targeting RET alterations, which were the subject of new data presentations at the recent American Society of Clinical Oncology (ASCO) Annual Meeting. The Afirma XA identifies these gene alterations, which can help physicians determine which patients could benefit from these cutting-edge new treatments.

“We believe that our novel RNA whole-transcriptome sequencing platform uniquely enables our Afirma offering to answer important clinical questions that can guide various points in a patient’s journey, helping to improve outcomes,” said Bonnie Anderson, Veracyte’s chairman and chief executive officer. “Further, by providing this comprehensive information from the original biopsy used in diagnosis, we can streamline workflows and enable patients to get the answers they need faster and more easily.”

Source – BusinessWire

Ali SZ, Siperstein A, Sadow PM, Golding AC, Kennedy GC, Kloos RT, Ladenson PW. (2019) Extending expressed RNA genomics from surgical decision making for cytologically indeterminate thyroid nodules to targeting therapies for metastatic thyroid cancer. Cancer Cytopathol [Epub ahead of print]. [article]

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