Adjuvant Radiation Associated with Worse OS, DSS in Papillary Thyroid Cancer

February 28, 2019
Darcy Lewis

Adjuvant external beam radiation therapy was associated with worse overall survival and disease-specific survival in patients with locally invasive papillary thyroid carcinoma, a new retrospective cohort study has found.

Adjuvant external beam radiation therapy (EBRT) was associated with worse overall survival (OS) and disease-specific survival (DSS) in patients with locally invasive papillary thyroid carcinoma, a new retrospective cohort study has found.

“The findings of this current study suggest that the addition of EBRT to total thyroidectomy and radioactive iodine, as part of the initial treatment regimen for patients with locally invasive papillary thyroid cancer, does not provide a survival benefit. These findings support the recent American Thyroid Association recommendation against routine use of EBRT after initial complete surgical resection of tumor,” the authors, led by Uchechukwu C. Megwalu MD, MPH, of Stanford University, wrote inHead & Neck. “…Given that EBRT has the potential to improve local and regional control, it should be used judiciously in selected high-risk patients, by clinicians with considerable experience in managing patients with advanced thyroid cancer.”

The authors used the Surveillance, Epidemiology, and End Results (SEER) 18 Database of the National Cancer Institute to create a cohort of adult thyroid cancer patients who were diagnosed with T4 papillary thyroid cancer between 1988 and 2013.

Included patients had received total or near-total thyroidectomy (with or without neck dissection) and radioactive iodine therapy. Patients who had multiple primary tumors or had received unknown therapy were excluded.

Of the 4246 patients who met the inclusion criteria, 153 patients received EBRT. The authors used propensity score matching to identify 870 patients for analysis. The EBRT group contained 145 patients, while the control group consisted of the remaining 725 patients.

Megwalu et al found that patients who received EBRT were more likely to be male, older, and to have major invasion, nodal metastasis, or distant metastasis than those who did not. Following propensity score matching, these variables were evenly distributed between the groups.

According to unadjusted Kaplan-Meier analysis, patients in the EBRT group had worse OS than those who did not (5-year OS, 79.2% vs 92.3%,P<0.001). Similarly, DSS was worse among patients treated with EBRT (5-year DSS, 84.5% vs 95.1%,P<.001).

Even with propensity score matching, adjusted Kaplan—Meier analysis showed that patients in the EBRT group still had worse OS (5-year OS, 80.2% vs 86.9%,P= 0.002). DSS was comparably worse compared to control patients (5-year DSS, 85.7% vs 89.9%,P= 0.02.)

Unadjusted analysis showed worse OS (HR, 2.92; 95% CI, 2.23-3.82) and DSS (HR, 3.37, 2.42-4.67) for patients treated with EBRT. Propensity score analysis also showed that EBRT was associated with worse OS (HR, 1.60; 95% CI, 1.18-2.16) and DSS (HR 1.58, 1.09-2.30).

When the authors performed various subset analyses, they found that patients with major extrathyroidal invasion had worse OS (HR, 1.53; 95% CI, 1.04-2.25), but not DSS (HR, 1.57; 95% CI, 0.99-2.50). EBRT patients who did not have major extrathyroidal invasion, had worse OS (HR 1.74; 95% CI, 1.07-2.83), but not DSS (HR, 1.64, 0.87-3.07).

In patients 60 or older, EBRT was not associated with OS (HR, 1.26; 95% CI, 0.86-1.85) or DSS (HR, 1.29; 95% CI, 0.77-2.05). However, younger patients who received EBRT had worse OS (HR, 2.47; 95% CI, 1.48-4.10) and DSS (HR, 2.47; 95% CI, 1.36-4.48).

Megwalu et al noted that the presence of unmeasured variables (such as margin status, extra-nodal extension, and comorbidity) could have increased patients’ likelihood of receiving EBRT and their risk of mortality. “The SEER database does not include information on margin status, microscopic extra-nodal extension, or iodine avidity, which may be associated with EBRT use and poor survival,” they wrote. “The SEER database also does not provide information on timing, total dose, fractionation, and technique of radiotherapy, which may impact survival outcomes.”

They also noted that SEER does not include information on disease recurrence or treating hospital. That means Megwalu et al’s findings may be less applicable when considering patients treated at high-volume centers with extensive experience managing advanced thyroid cancers.

“EBRT was used infrequently, more often in patients with poor prognostic features,” they wrote. “Unfortunately, our study did not capture information on positive margins or residual disease, which often influences the decision to treat with EBRT.”

However, the study’s large sample size and diverse patient characteristics are among its strengths.

Wegalu et al suggest that future studies are needed to determine what subset of patients with papillary thyroid cancer may benefit from adjuvant EBRT, “specifically its effect on survival in patients with gross residual disease after resection and patients with noniodine avid tumors.”

Reference:

Megwalu UC, Orloff LA, Ma Y. Adjuvant external beam radiotherapy for locally invasive papillary thyroid cancer.Head & Neck. 2019;1—6. https://doi.org/10.1002/hed.25639