Intensity-Modulated Radiation Therapy With or Without Concurrent Chemotherapy in Nonanaplastic Thyroid Cancer with Unresectable or Gross Residual Disease

Abstract

Background: Differentiated thyroid cancer typically has an indolent clinical course but can cause significant morbidity by local progression. Oncologic surgical resection can be technically difficult due to the proximity to critical normal structures in the neck. Our objective was to review the safety, feasibility, and outcomes of definitive-intent intensity-modulated radiation therapy (IMRT) and to analyze whether patients receiving concurrent chemotherapy (CC-IMRT) had higher rates of disease control and survival over IMRT alone in patients with unresectable or gross residual disease (GRD).

Methods: Eighty-eight patients with GRD or unresectable nonanaplastic, nonmedullary thyroid cancer treated with definitive-intent IMRT between 2000 and 2015 were identified. Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses using cox regression were used to determine the impact of clinical conditions and treatment on LPFS, DMFS, and OS.

Results: Of the 88 patients identified, 45 (51.1%) were treated CC-IMRT and 43 (48.9%) were treated with IMRT alone. All patients treated with CC-IMRT received weekly doxorubicin (10 mg/m²). The median follow-up among surviving patients was 40.3 months and 29.2 months for all patients. The LPFS at 4 years was 77.3%. Patients receiving CC-IMRT had higher LPFS compared with IMRT alone (CC-IMRT 85.8% vs. IMRT 68.8%, p = 0.036). The 4-year OS was 56.3% for all patients. Patients treated with CC-IMRT had higher OS compared to patients treated with IMRT alone (CC-IMRT 68.0% vs. IMRT 47.0%, p = 0.043). On multivariate analysis, receipt of concurrent chemotherapy was associated with a lower risk of death (HR 0.395, p = 0.019) and lower risk of local failure (HR 0.306, p = 0.042). Grade 3+ acute toxicities occurred in 23.9% of patients, the most frequent being dermatitis (18.2%) and mucositis (9.1%). 17.1% of patients required a percutaneous endoscopic gastrostomy (PEG) tube during or shortly after completion of RT, with 10.1% of patients needing a PEG more than 12 months after therapy. The rates of acute and late toxicities were not statistically higher in the CC-IMRT cohort, although trends towards higher toxicity in the CC-IMRT were present for dermatitis and PEG requirement.

Conclusions: IMRT is a safe and effective means to achieve local control in patients with unresectable or incompletely resected nonanaplastic, nonmedullary thyroid cancer. Concurrent doxorubicin was not associated with worse toxicity and should be considered in these patients given its potential to improve local control and overall survival.

Keywords: IMRT; concurrent chemoradiation therapy; thyroid cancer.

FIG. 1.

Kaplan-Meier estimates of locoregional progression free survival. (A) Kaplan–Meier estimate of locoregional progression free survival. (B) Kaplan-Meier estimate of locoregional progression free survival based on IMRT versus CC-IMRT. Blue line represents IMRT and green line CC-IMRT (p = 0.036). CC-IMRT, concurrent chemoradiation with intensity-modulated radiation therapy; IMRT, intensity-modulated radiation therapy. Color images are available online at www.liebertpub.com/thy

FIG. 2.

Kaplan-Meier estimates of distant metastasis free survival. (A) Kaplan-Meier estimate of distant metastasis free survival. (B) Kaplan–Meier estimate of distant metastasis free survival based on IMRT versus CC-IMRT. Blue line represents IMRT and green line CC-IMRT (p = 0.546). Color images are available online at www.liebertpub.com/thy

FIG. 3.

Kaplan-Meier estimates of overall survival. (A) Kaplan–Meier estimate of overall survival. (B) Kaplan–Meier estimate of distant overall survival based on IMRT versus CC-IMRT. Blue line represents IMRT and green line CC-IMRT (p = 0.043). (C) Kaplan–Meier estimate of overall survival based on metastases (M) status. Blue line represents M0 status and green line M1 status (p = 0.009). Color images are available online at www.liebertpub.com/thy

FIG. 4.

Gross tumor volume and local failures. (A) Column plot of the GTV (y axis) with each column representing a single patient. Blue bars depict patients without local progression, red bars depict the patients with local progression. (B) Kaplan–Meier estimate of locoregional progression free survival based on GTV. Blue line represents the 1st–3rd quartiles and green line represents 4th quartile (p = 0.885). (C) Kaplan—Meier estimate of overall survival based on GTV. Blue line, 1st–3rd quartile; green line, 4th quartile (p = 0.365). (D) Kaplan–Meier estimate of distant metastasis free survival on GTV. Blue line, 1st–3rd quartile; green line, 4th quartile (p = 0.892). GTV, gross tumor volume. Color images are available online at www.liebertpub.com/thy