IMRT With Chemotherapy Improves Survival, Locoregional Control in Thyroid Cancer

October 8, 2018
Jason Harris

Patients with nonanaplastic thyroid cancer who received concurrent chemotherapy with intensity-modulated radiation therapy had superior local progression-free survival and distant metastasis-free survival (DMFS) compared with those who received only IMRT, according to recently published results.

Nancy Y. Lee, MD

Patients with nonanaplastic thyroid cancer who received concurrent chemotherapy with intensity-modulated radiation therapy (CC-IMRT) had superior local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) compared with those who received only IMRT, according to recently published results.

In a retrospective study of patients treated at Memorial Sloan Kettering Cancer Center from 2000 to 2015, patients with gross residual disease or unresectable nonanaplastic, nonmedullary thyroid cancer were assigned to CC-IMRT (n = 45; 51.1%) or IMRT alone (n = 43; 48.9%). At a median follow-up of 40.3 months among surviving patients and 29.2 months among all patients, the 4-year LPFS was 85.5% in the CC-IMRT group versus 68.8% for IMRT alone (P= .036).

CC-IMRT was also associated with superior 4-year overall survival (68.0% vs 47.0%;P= .043). Investigators found no difference in OS by nodal status (N1 vs. N0,P= .913), timing of radiation (<3 months vs >3 months after surgery;P= 0.889), tumor stage (T4 vs. T1—3;P= .908), or high- versus low-risk histology (P= .955).

Forty-seven patients were free of distant metastases at baseline. Twenty-one of those subsequently developed metastases at a median of 21.4 months after starting radiation treatment. CC-IMRT was associated with a superior DMFS compared with IMRT (58.1% vs 34.1%;P= .546).

“IMRT is well tolerated in patients with unresectable or incompletely resected non-medullary differentiated thyroid cancer and should be considered in appropriate patients who may benefit from long-term locoregional disease control,” corresponding author Nancy Y. Lee, MD, vice chair, department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “Concurrent chemotherapy with radiosensitizing doxorubicin was associated with higher rates of OS and LPFS compared to IMRT alone. Prospective trials are warranted to evaluate the value of CC-IMRT in this patient population.”

All patients in the study received IMRT. High-risk areas including the operative or tumor bed, operative thyroid gland volume, tracheoesophageal grooves and central nodal compartment received 60 Gy while low-risk areas received 54 Gy. Areas of gross disease received 70 Gy and close or microscopically positive margins received 66 Gy. IMRT was administered at a median dose of 70.0 Gy (range, 69.96-72.08) in a median of 33 fractions (range 33-35).

Patients in the CC-IMRT group also received 10 mg/m2of weekly doxorubicin, usually following 1 to 3 fractions of radiation.

The median patient age was 64.7 years (range, 30.0-87.7). Most patients (64.8%) had papillary disease, while 23.9% had poorly differentiated histology and 11.4% had Hürthle cell carcinoma. Forty-one (46.6%) patients had high-risk pathology.

Patients had received a median of 2 surgeries (range, 0-5) prior to IMRT. Surgeons did not attempt resection in 20 patients with recurrent disease.

Sixty patients received radioactive iodine before IMRT, 14 before and after IMRT, and 3 post-IMRT. The median number of radioactive iodine doses prior to IMRT was 1 (range, 1-5). Patients also received a median of 1 post-IMRT doses (range, 1-3).

Forty percent of patients received a tyrosine kinase inhibitor (TKI), most often sorafenib (Nexavar) or pazopanib (Votrient). TKIs were not administered alongside IMRT.

Thirteen (30.2%) patients in the IMRT group had local failure compared with 4 (8.9%) in the CC-IMRT cohort. Investigators found no difference in LPFS by tumor stage (T4 vs. T1—3;P= .908), high- versus low-risk histology (P= .101), timing of radiation (<3 months vs >3 months after surgery;P= 0.860), or nodal status (N1 vs. N0,P= .954).

On univariate analysis, CC-IMRT (HR, 0.314;P= .047) and high-risk pathology were associated with a lower rate of local progression. That association did not hold on multivariate analysis for high-risk pathology, but did for CC-IMRT (HR, 0.306;P= .042). On both univariate (HR 0.468;P= .048) and multivariate analysis (HR, 0.395;P= .019), CC-IMRT was associated with a lower risk for death.

Multivariate analysis showed that concurrent chemotherapy was associated with a 59.5% lower risk for death (HR, 0.395,P= .019) and a 69.4% lower risk for local failure (HR, 0.306,P= .042).

The most common adverse events were acute grade 3 dermatitis (18.2%) and mucositis (9.1%). Patients assigned to CC-IMRT were more likely to experience grade ≥3 dermatitis (26.7% vs 9.3%), but investigators observed no other differences in acute toxicity.

Reference:

Beckham TH, Romesser PB, Groen AH, et al. Intensity-modulated radiation therapy with or without concurrent chemotherapy in nonanaplastic thyroid cancer with unresectable or gross residual disease [published online September 1, 2018].Thyroid.doi: 10.1089/thy.2018.0214.

Fifteen (17.1%) patients required placement of a percutaneous endoscopic gastrostomy (PEG) tube following the start of radiation therapy, 14 due to toxicity and 1 due to toxicity and local progression. Patients in the CC-IMRT cohort were more likely to need a PEG tube during or within 60 days of treatment (10 vs 3;P=.070). Two more patients in the CC-IMRT group required a tube >60 days after the end of therapy.