Adjuvant External Beam Radiotherapy Reduces Local Recurrence in Poorly Differentiated Thyroid Cancer : A Multicenter Retrospective Cohort Study Describing Outcomes in the Treatment of Resectable Poorly Differentiated Thyroid Cancer

Abstract

Background: Poorly differentiated thyroid carcinoma (PDTC) accounts for 5% of all thyroid cancers and is responsible for a large proportion of thyroid cancer-related deaths. The optimal treatment approach is not clear. This study aimed to evaluate the effect of postoperative intensity-modulated radiotherapy (IMRT) on the treatment of resectable PDTC. Additionally, treatment-related morbidity, characteristics of ¹³¹I-refractory disease, and factors affecting survival were assessed.

Methods: The study included consecutive PDTC cases from 1997 to 2018, defined according to Turin criteria and treated in two tertiary referral centers. Surgery, IMRT, ¹³¹I, and systemic therapies were administered based on multidisciplinary team recommendations. The primary study outcome was 5-year local control after IMRT in cases with positive resection margins (micro- and macroscopic). The secondary outcomes were treatment-related morbidity within 30-days after completion of treatment (Clavien-Dindo and Common Terminology Criteria for Adverse Events [CTC-AE] 5.0), ¹³¹I-refractory disease characteristics using standardized definitions, and factors influencing survival.

Results: Among 51 PDTC cases, 53% presented with metastatic disease. Adjuvant IMRT improved 5-year local control (100% vs. 17.5%; p = 0.02), with a higher number of grades 1 to 3 complications (p = 0.005) versus cases without IMRT. Within 13 months, ¹³¹I-refractory disease occurred in 62.7% of the patients and was more common in non-survivors (86.6% vs. 52.8%; p = 0.01). Positive resection margins and extrathyroidal extension were associated with poor survival in the univariate analysis, but were not significant in the multiple regression analysis.

Conclusion: Adjuvant IMRT may reduce thyroid bed recurrence in resectable PDTC with positive resection margins, but is associated with increased treatment-related complications. ¹³¹I-refractory disease occurs frequently, with non-survivors progressing earlier to ¹³¹I resistance.

Keywords: 131I-refractory; Cancer; PDTC; Poorly differentiated; Radiotherapy; Surgery; Thyroid; Turin.

Fig. 1

*, microscopic or macroscopic involved margins; **, Chemosensitizer during radiotherapy; ***,1 patient received RCVP for non-hodgkin lymphoma and no chemotherapy for PDTC. Following RCVP, lenvatinib was initiated for progressive 131I refractory PDTC. Abbreviations: PDTC, poorly differentiated thyroid cancer; IMRT, intensity modulated radiotherapy; CTx, chemotherapy; 131I, adjuvant radioiodine; TKI, tyrosine kinase inhibitor

Fig. 2

Overview of local (A), regional (B) and distant (C) progression free survival of 51 patients with poorly differentiated thyroid cancer included for the analysis. The disease specific survival of the cohort is depicted in Fig. 2D

Fig. 3

A shows an improvement (p = 0.02) in 5-year local progression free survival of 8 patients with a positive resection margin that underwent postoperative intensity modulated radiotherapy (IMRT, red line) versus patients with a positive resection margin without adjuvant IMRT (n = 16, blue line). B confirms the beneficial effect of IMRT followed by adjuvant treatment with TKI’s (p = 0.04) in a subcategory of patients with a positive resection margin treated with IMRT on the thyroid bed and adjuvant TKI’s for progressive distant metastasis (n = 6) versus patients not treated with IMRT and TKI’s (n = 13)