Postoperative external beam radiotherapy for differentiated thyroid cancer: outcomes and morbidity with conformal treatment

Abstract

Purpose: To review institutional outcomes for patients treated for differentiated thyroid cancer with postoperative conformal external beam radiotherapy (EBRT).

Methods and materials: This is a single-institution retrospective review of 131 consecutive patients with differentiated thyroid cancer who underwent EBRT between January 1996 and December 2005. Histologic diagnoses included 104 papillary, 21 follicular, and six mixed papillary-follicular types. American Joint Committee on Cancer stage distribution was Stage III in 2 patients, Stage IVa-IVc in 128, and not assessable in 1. Thirty-four patients (26%) had high-risk histologic types and 76 (58%) had recurrent disease. Extraglandular disease spread was seen in 126 patients (96%), microscopically positive surgical margins were seen in 62 patients (47%), and gross residual disease was seen in 15 patients (11%). Median EBRT dose was 60 Gy (range, 38-72 Gy). Fifty-seven patients (44%) were treated with intensity-modulated radiotherapy (IMRT) to a median dose of 60 Gy (range, 56-66 Gy). Median follow-up was 38 months (range, 0-134 months).

Results: Kaplan-Meier estimates of locoregional relapse-free survival, disease-specific survival, and overall survival at 4 years were 79%, 76%, and 73%, respectively. On multivariate analysis, high-risk histologic features and gross residual disease predicted for inferior locoregional relapse-free survival, whereas high-risk histologic features, M1 disease, and gross residual disease predicted for inferior disease-specific and overall survival. The IMRT did not impact on survival outcomes, but was associated with less frequent severe late morbidity (12% vs. 2%).

Conclusions: Postoperative conformal EBRT provides durable locoregional disease control for patients with high-risk differentiated thyroid cancer if disease is reduced to microscopic burden. Patients with gross disease face significantly worse outcomes. The IMRT may significantly reduce chronic radiation morbidity, but requires additional study.

Figure 1. Representative IMRT treatment plan

IMRT treatment plan for a 52 year old female patient with papillary thyroid carcinoma initially treated via thyroidectomy, bilateral paratracheal dissection, left-sided cervical neck dissection, and radioactive iodine ablation at an outside hospital. Patient presented to our institution with a recurrent 7.5 cm paratracheal mass inferior to the right clavicular head, which was grossly resected via a combined neck and thoracic surgical approach. Surgical margins were close, and disease was noted to infiltrate into soft tissues. An accompanying right-sided cervical neck dissection confirmed 5/22 sampled nodes from levels 3–4 to contain metastatic disease with extracapsular extension. Patient subsequently received 63 Gy IMRT to a CTV1 (demarcated red) encompassing the surgical bed directly involved with gross disease, 60 Gy (blue) to a CTV2 encompassing adjacent soft tissues and right-sided neck dissection bed, and 57 Gy to a CTV3 encompassing the high right-sided cervical neck, previously dissected left cervical neck, and superior mediastinum. All doses were delivered over 30 daily fractions.

Figure 2. Survival outcomes of study cohort

Kaplan-Meier curves demonstrating (A) LRFS, (B) DSS, and (C) OS. Open circles designate events.

Figure 3. Univariate analysis of the interaction between presence of gross disease and survival outcomes

Kaplan-Meier curves are shown with p-values determined by log-rank test for (A) LRFS, (B) DSS, and (C) OS. Absence of gross disease at the time of radiation treatment is indicated by heavy solid line (), while presence of gross disease is indicated by thin solid line (). Circles designate events.

Figure 4. Timing of severe late radiation-related morbidity

Solid bars indicate number and timing of morbid events.