Adjuvant External Beam Radiotherapy and Histopathologic Prognostic Factors in Tall Cell Papillary Thyroid Carcinoma

Abstract

Differentiated thyroid cancer is a diverse disease, with histopathologic characteristics contributing to prognosis and treatment decisions. Tall cell variant of papillary thyroid cancer (TCV-PTC) carries a poor prognosis relative to other histologies, with first site of failure most often in the neck. Several small studies suggest there may be a disease control benefit to adjuvant external beam radiotherapy (EBRT) for certain high-risk DTC populations; however, data is limited. In this study we aim to shed light on both histopathologic prognostic factors and survival outcomes of patients with TCV-PTC carcinoma treated with surgery followed by EBRT and Radioactive Iodine (RAI) or RAI alone. We hypothesize that EBRT with RAI leads to better disease control than RAI alone. Patients with TCV-PTC diagnosed between 1997-2020 at a single institution were included in the analysis. TNM staging was standardized to AJCC 8th edition. Demographics, staging, and histologic characteristics were compared between the two treatment groups using T-tests and Fisher's exact tests. Kaplan-Meier survival analyses were performed between patients receiving EBRT vs. RAI alone for disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS), along with Cox Proportional Hazards analysis. A total of 93 patients were included. Of these patients, 22 received adjuvant RAI and EBRT, and 71 received RAI alone. There was no statistical difference in race, gender, tall cell percentage in the pathology specimen, TNM stage, AJCC group stage, or disease recurrence in patients receiving EBRT vs. RAI alone. However, those receiving EBRT were significantly older (RAI mean age (SD): 50.6 (18.7), EBRT mean age (SD): 59.7 (14.4), p = 0.02) and length of follow-up was shorter for the EBRT cohort (RAI mean (SD): 8.80 (5.81) years, EBRT mean (SD): 4.53 (2.14) years, p < 0.01). Multifocal disease (HR: 3.04, 95% CI: 1.30 - 7.08, p = 0.01) and soft tissue invasion (HR: 2.93, 95% CI: 1.28 - 6.75, p = 0.01) were associated with decreased DFS, whilst age (HR 1.08, 1.01 - 1.15: p = 0.03) was associated with decreased CSS; tall cell percentage in the pathology specimen, extra-thyroidal extension, vascular invasion, and positive surgical margin were not significant for either metric. There was no statistical difference in DFS (p = 0.5), CSS (p = 0.3), or OS (p = 0.6) between patients that received EBRT and RAI vs. RAI alone. DFS, CSS, and OS were not different between patients who received EBRT compared to RAI only in this high-risk subgroup of patients. Short interval follow-up for the EBRT group and significant age differences between the EBRT and RAI cohorts may confound results. Given the significant association of advanced age with CSS, an expanded, age-matched cohort analysis is underway.