No abstract
No abstract
All…can see these tactics whereby I conquer, but what none can see is the strategy out of which victory is evolved. Sun Tzu, The Art of War In times of war, every piece of intelligence is gathered, processed and weighed into whether it should help direct strategy against the enemy. The fight against cancer is a war, and the perception in thyroid cancer is that we are winning. Of the more than 10 variants of thyroid carcinoma, by far the most prevalent is classic papillary thyroid carcinoma (PTC), which is treatable and almost universally survivable. Even in the setting of metastatic disease at diagnosis, most patients respond well to a combination of therapies. A small minority succumb to progressive, sometimes treatment-refractory disease. While mortality is low, local recurrence is significantly more common and can occur many years later. Traditional staging systems have been effective in predicting the mortality risk but have been less useful in predicting the risk of recurrence. Beginning in 2009, the American Thyroid Association's (ATA) risk stratification system for persistent and/or recurrent structural disease was proposed, validated, widely embraced and recently revised. 1 It is dynamic, allowing for refinement of an individual's perceived risk over a long period. For example, a patient whose tumor has concerning features resulting in initial ATA classification of intermediate risk may eventually be restratified to low risk as clinical observation over time reveals an excellent response to therapy. Patients who are classified as ATA high risk are targeted for more aggressive interventions aimed at reducing both risk of recurrence and death. With an increase in the diagnosis of thyroid cancer in recent decades, mainly owing to the incidental radiologic discovery of low-risk tumors, the number of patients who have favorable outcomes is increasing. It is important to avoid unnecessary interventions in this favorable-risk group. Thus, the challenge for clinicians is to identify that small but higher-risk population while not overtreating the majority of patients. More aggressive therapy should be reserved for those who truly require it.The role of tumor biomarkers is expanding rapidly for diagnosis, treatment and prognostication across cancer types. In patients with breast cancer, consideration of additional adjuvant chemotherapy is aided with biomarker prognostic tools, such as Oncotype DX (Genomic Health, Inc), and treatment is directed by biomarkers, such as ERBB2/HER2 or hormone status. Lung cancer treatment has rapidly evolved to include standard testing of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) for specific patients who would have previously received systemic cytotoxic chemotherapy. In patients with thy-Related article page 202
e18083 Background: The value of sequencing cell-free DNA (cfDNA) from patients with papillary carcinoma of the thyroid (PTC) is controversial. Studies utilizing whole-exome sequencing (WES) or single-gene detection methods have reported lower mutational yield in cfDNA in PTC compared with other cancers. Alternatively, mutational analyses of anaplastic thyroid carcinoma (ATC), which is thought to evolve from PTC, demonstrate high levels of mutated cfDNA. We report on mutations in tumor and cfDNA at initial surgery for PTC, correlate with clinicopathologic status and further characterize the mutational landscape of these tumors in tissue and blood utilizing deep-sequencing panel testing. Methods: 50 patients were enrolled 2017-2020. Tempus xT (648 genes) and xF (105 genes) panels were used to prepare next generation sequencing libraries from tissue and blood samples, respectively. Cell-free DNA (cfDNA) sequencing depth average is 20,000x (raw reads)/5,000x (unique reads). Results: More than half of the patients had pT3-T4 tumors and/or local metastases and one had distant metastasis. 47/47 (100%) of processable tissue samples and 40/49 (81.6%) of blood samples yielded at least one relevant mutation. BRAF V600E was found in 77% of tissue and 8% of cfDNA, while mutated TERT was detected in 17% of tissue and none of the blood samples. The most frequently mutated genes in cfDNA were KMT2A (18% of blood samples, 6 % tissue), ATM (12% blood, 6% tissue), and TP53 (12% blood, 2 % tissue). There was marked mutational heterogeneity among samples, and a range of alterations representing multiple oncogenic pathways. Conclusions: Patients at initial surgery demonstrated highly mutated tissue DNA, including BRAF, TERT and other mutations known to be found in PTC. The most frequent tissue mutations were found at higher rates than previously reported by WES, which may reflect the sensitivity of targeted deep sequencing versus WES, and possibly a selection bias of more advanced PTC. A high percentage of cfDNA samples yielded mutations relevant to thyroid cancer, and the absence of TERT is consistent with prior studies. Mutations and co-mutations associated with de-differentiation and worse outcomes were demonstrated in both tissue and cfDNA. Interestingly, mutations more common in ATC than PTC, such as TP53, were detected in cfDNA, often without primary tumor correlate. Since mutations associated with aggressive behavior may be found in metastatic foci while not detected in the primary tumor, we conclude that cfDNA may reveal prognostic information important for the development of surveillance strategies in selected patients with residual PTC after surgery who may be at risk for poor outcomes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.