Allen S Ho1,2, Michael Luu3,4, Laurel Barrios3, Bonnie L Balzer3,5, Shikha Bose3,5, Xuemo Fan3,5, Evan Walgama3,6, Jon Mallen-St Clair3,6, Usman Alam6, Iram Shafqat6, De-Chen Lin7, Yufei Chen8, Jennifer E Van Eyk9, Ellie G Maghami10, Glenn D Braunstein3,11, Wendy L Sacks3,11, Zachary S Zumsteg12,13. 1. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. allen.ho@cshs.org. 2. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. allen.ho@cshs.org. 3. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 4. Biostatistics and Bioinformatics Research Center, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 5. Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 6. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 8. Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 9. Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 10. Division of Head and Neck Surgery, City of Hope Medical Center, Duarte, CA, USA. 11. Division of Endocrinology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 12. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. zachary.zumsteg@cshs.org. 13. Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. zachary.zumsteg@cshs.org.
Abstract
BACKGROUND: While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade. METHODS: We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed. RESULTS: Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23-3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18-0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17-0.80, p = 0.01). CONCLUSIONS: Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.
BACKGROUND: While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade. METHODS: We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed. RESULTS: Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23-3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18-0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17-0.80, p = 0.01). CONCLUSIONS: Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.
Authors: Bryan R Haugen; Erik K Alexander; Keith C Bible; Gerard M Doherty; Susan J Mandel; Yuri E Nikiforov; Furio Pacini; Gregory W Randolph; Anna M Sawka; Martin Schlumberger; Kathryn G Schuff; Steven I Sherman; Julie Ann Sosa; David L Steward; R Michael Tuttle; Leonard Wartofsky Journal: Thyroid Date: 2016-01 Impact factor: 6.568
Authors: Samantha Tam; Moran Amit; Mongkol Boonsripitayanon; Maria E Cabanillas; Naifa L Busaidy; G Brandon Gunn; Stephen Y Lai; Neil D Gross; Erich M Sturgis; Mark E Zafereo Journal: JAMA Otolaryngol Head Neck Surg Date: 2017-12-01 Impact factor: 6.223
Authors: Allen S Ho; Michael Luu; Cynthia Zalt; Luc G T Morris; Irene Chen; Michelle Melany; Nabilah Ali; Chrysanta Patio; Yufei Chen; Jon Mallen St-Clair; Glenn D Braunstein; Wendy L Sacks; Zachary S Zumsteg Journal: Thyroid Date: 2019-09-24 Impact factor: 6.568
Authors: Allen S Ho; Louise Davies; Iain J Nixon; Frank L Palmer; Laura Y Wang; Snehal G Patel; Ian Ganly; Richard J Wong; R Michael Tuttle; Luc G T Morris Journal: Cancer Date: 2015-02-24 Impact factor: 6.860