IMRT With Chemotherapy Improves Survival, Locoregional Control in Thyroid Cancer

Nancy Y. Lee, MD

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).

&ldquo;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,&rdquo; corresponding author Nancy Y. Lee, MD, vice chair, department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, and colleagues wrote. &ldquo;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.&rdquo;

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 H&uuml;rthle 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 &ge;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.