Treatment and Outcomes in pT4 Well-Differentiated Thyroid Carcinoma

Abstract

Locally advanced, pT4 well differentiated thyroid carcinoma is a relatively rare entity and the benefit of external beam radiotherapy (EBRT) is unclear. The purpose of this study is to evaluate locoregional control (LRC) and cancer specific survival (CSS) of patients with pT4 well differentiated thyroid carcinoma in the largest retrospective cohort to date. Electronic records of patients with pT4 well-differentiated thyroid carcinoma treated at our institution from 2001 to 2013 were reviewed. Log-rank test and multivariable Cox regression were used to establish factors impacting locoregional control and cancer specific survival. A total of 232 patients were treated during this time period. The most common histologies were papillary carcinoma (n=192) and follicular carcinoma (n=11). The median age was 58 and 61% were female. Median follow up time was 11 years. The median tumor size was 3.1cm (interquartile range: 2.0-5.0cm), 60% had multifocal disease, 33% lymphovascular invasion, 9% perineural invasion and 64% had node positive disease. Local invasion into the strap muscles was seen in 51%, trachea 33%, larynx 4%, pharynx 3%, and recurrent laryngeal nerve 1%. 22% patients had an R0 resection, 55% R1 and 23% R2. 92% patients received adjuvant radioactive iodine therapy. A total of 88 patients received external beam radiotherapy with a median dose of 60Gy. There were 7 acute grade 3 toxicities (3 dysphagia, 2 nausea, and 2 pain) and 7 late grade 3 toxicities in the cohort (2 dysphagia, 3 esophageal stricture, 1 pain, 1 laryngeal stenosis). There were no grade 4 toxicities observed. Ten year LRC was 65%, CSS was 85%, and OS was 75%. On multivariate analysis, older age (p=0.02, HR 1.02, 95% CI 1.0-1.04), larynx invasion (p=0.05, HR 3.32, 95% CI 1.0-11.0) and larger tumor size (p=0.01, HR 1.17, 95% CI 1.04-1.32) were associated with worse LRC. Older age (p<0.001, HR 1.10, 95% 1.06-1.15), lymphovascular invasion (p=0.002, HR 3.3, 95% 1.5-7.2), perineural invasion (p=0.02, HR 2.9, 95% 1.19-7.48), and tracheal invasion (p=0.009, HR 2.7, 95% CI 1.3-5.5) were associated with worse CSS. Adjuvant RT was not associated with improved LRC and CSS when the entire cohort was assessed. However, for patients with microscopic or macroscopic residual disease (R1 and R2 resection), adjuvant radiotherapy was associated with improved LRC on multivariable analysis (p=0.02, HR 0.45, 95% CI 0.23-0.90). Despite locally advanced disease; 10 year CSS was 85% in this cohort of patients with pT4 DTC. Adjuvant radiotherapy improved LRC for patients with R1 and R2 resections. There was a low rate of toxicity from EBRT for the cohort.