Allen S Ho1,2, Michael Luu1,3, Laurel Barrios1, Irene Chen1,4, Michelle Melany1,4, Nabilah Ali1,2, Chrysanta Patio1,2, Yufei Chen1,5, Shikha Bose1,6, Xuemo Fan1,6, Jon Mallen-St Clair1,5, Glenn D Braunstein1,7, Wendy L Sacks1,7, Zachary S Zumsteg1,8. 1. Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California. 2. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California. 3. Biostatistics and Bioinformatics Research Center, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California. 4. Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, California. 5. Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California. 6. Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California. 7. Division of Endocrinology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. 8. Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
Abstract
Importance: While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases. Objective: To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC). Design, Setting, and Participants: This cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019. Main Outcomes and Measures: Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates. Results: Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching. Conclusions and Relevance: An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.
Importance: While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases. Objective: To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC). Design, Setting, and Participants: This cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019. Main Outcomes and Measures: Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates. Results: Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching. Conclusions and Relevance: An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.
Authors: Valentina B Ignjatović; Jelena R Janković Miljuš; Jelena V Rončević; Svetislav B Tatić; Tijana M Išić Denčić; Ilona Đ Đorić; Sonja A Šelemetjev Journal: Histochem Cell Biol Date: 2021-11-24 Impact factor: 4.304
Authors: Allen S Ho; Sungjin Kim; Cynthia Zalt; Michelle L Melany; Irene E Chen; Joan Vasquez; Jon Mallen-St Clair; Michelle M Chen; Missael Vasquez; Xuemo Fan; Welmoed K van Deen; Robert W Haile; Timothy J Daskivich; Zachary S Zumsteg; Glenn D Braunstein; Wendy L Sacks Journal: JAMA Oncol Date: 2022-09-15 Impact factor: 33.006
Authors: Allen S Ho; Michael Luu; Laurel Barrios; Bonnie L Balzer; Shikha Bose; Xuemo Fan; Evan Walgama; Jon Mallen-St Clair; Usman Alam; Iram Shafqat; De-Chen Lin; Yufei Chen; Jennifer E Van Eyk; Ellie G Maghami; Glenn D Braunstein; Wendy L Sacks; Zachary S Zumsteg Journal: Ann Surg Oncol Date: 2020-08-17 Impact factor: 5.344