Progression and dormancy in metastatic thyroid cancer: concepts and clinical implications
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REVIEW
Progression and dormancy in metastatic thyroid cancer: concepts and clinical implications Neel Rajan1 Tilak Khanal1 Matthew D. Ringel ●
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Received: 26 June 2020 / Accepted: 1 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Distant metastasis classically has been defined as a late-stage event in cancer progression. However, it has become clear that metastases also may occur early in the “lifetime” of a cancer and that they may remain stable at distant sites. This stability of metastatic cancer deposits has been termed “metastatic dormancy” or, as we term it, “metastatic progression dormancy” as the progression either may reflect growth of already existing metastases or new cancer spread. Biologically, dormancy is the presence of nongrowing, static metastatic cells that survive over time. Clinically, dormancy is defined by stability in tumor markers, imaging, and clinical course. Metastatic well-differentiated thyroid cancer offers an excellent tumor type to understand these processes for several reasons: (1) primary therapy often includes removal of the entire gland with ablation of residual normal tissue thereby removing one source for new metastases; (2) the presence of a sensitive biochemical and radiographic monitoring tests enabling monitoring of metastasis throughout the progression process; and (3) its tendency toward prolonged clinical dormancy that can last for years or decades be followed by progression. This latter factor provides opportunities to define therapeutic targets and/or markers of progression. In this review, we will discuss concepts of metastatic progression dormancy and the factors that drive both long-term stability and loss of dormancy with a focus on thyroid cancer. Keywords Metastasis Dormancy Progression Thyroid cancer ●
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Brief clinical case In 1991, a 40-year-old woman was diagnosed with a 2.2 × 1.3 × 1.4 cm intrathyroidal well-differentiated papillary thyroid cancer (PTC). She was treated with total thyroidectomy and 81 mCi of I-131 following levothyroxine withdrawal. Pre and post-therapy scans demonstrated thyroid bed uptake. Thyroglobulin (Tg) level on levothyroxine with TSH ~0.1 mU/L was 50% in size and increased in number.
Endocrine
She was started on Sorafenib and after initial period of stable disease, the lung nodules increased in size. Since 2018 she has been managed on Lenvatinib with stable disease, albeit with side effects that require occasional “drug holidays.”
Introduction Classical cancer models describe metastatic progression as a late-stage event in the “lifetime” of a malignancy, and that when it occurs it leads to rapid growth that results in patient mortality [1]. The development of more sensitive biochemical markers, such as Tg in thyroid cancer; PSA in prostate cancer, circulating tumor cell detection, circulating free DNA assays, and more sensitive imaging tests have challenged this model [1–6]. Data from multiple tumor types demonstrate that some cancer cells have the
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