Site-Specific Metastasis and Survival in Papillary Thyroid Cancer: The Importance of Brain and Multi-Organ Disease

Eman A Toraih; Mohammad H Hussein; Mourad Zerfaoui; Abdallah S Attia; Assem Marzouk Ellythy; Arwa Mostafa; Emmanuelle M L Ruiz; Mohamed Ahmed Shama; Jonathon O Russell; Gregory W Randolph; Emad Kandil

doi:10.3390/cancers13071625

Site-Specific Metastasis and Survival in Papillary Thyroid Cancer: The Importance of Brain and Multi-Organ Disease

Cancers (Basel). 2021 Apr 1;13(7):1625. doi: 10.3390/cancers13071625.

Affiliations

¹ Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.
² Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Ismailia 41522, Egypt.
³ Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁴ Division of Head and Neck Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins, Baltimore, MD 21287, USA.
⁵ Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA 02115, USA.

Abstract

Introduction-heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods-patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975-2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results-from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan-Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%, p < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17-2.94, p < 0.001, and HR = 1.90, 95% CI = 1.40-2.57, p = 0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13-25.0, p < 0.001 and HR = 4.76, 95% CI = 3.93-5.76, p < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50-28.39, p = 0.026 and HR = 5.08, 95% CI = 1.21-21.30, p = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15-2.89, p < 0.001 and HR = 4.21, 95% CI = 2.20-8.07, p = 0.010). Conclusion-the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

Keywords: metastasis; multiple organ metastasis; survival; thyroid cancer.