Radioiodine and Multimodal Therapy Increases Survival Over Radioiodine Monotherapy in Metastatic DTC

A small retrospective study has found that patients who had differentiated thyroid cancer (DTC) with bone metastasis and received radioiodine (¹³¹I) treatment in combination with one or more non-¹³¹I direct and systemic treatments experienced increased overall survival (OS) compared with patients who received only¹³¹I treatment.

The study, which was conducted at MedStar Washington Hospital Center in Washington, DC, was published recently inThyroid. Of 77 patients, 30% (n = 23) received¹³¹I treatment alone, and 70% (n = 54) received combination treatment. In the combined-treatment group, the median survival was 7.7 years (95% CI, 5.4-9.9). This compared with a median survival of 3.9 years with¹³¹I treatment alone (95% CI, 2.0-5.8;P= .03).

The authors measured OS rates at 1 year, 2 years, 3 years, 5 years, and 10 years. In the combination group, OS rates ranged from 96% at 1 year to 30% at 10 years. This compared with OS rates ranging from 86% at 1 year to 23% at 10 years in the radioiodine-only group.

“Based on the data supporting improved OS from the combination of localized therapy with systemic¹³¹I therapy, reconsideration and discussion of conventional management approaches are warranted,” wrote the authors, led by Di Wu, MD, of MedStar Health Research Institute in Hyattsville, Maryland.

Patients in this study were evaluated at MedStar Washington Hospital Center between 2001 and 2018. They all had DTC including papillary, follicular variant of papillary, follicular, Hürthle cell, tall cell, columnar cell, diffuse sclerosing, and hobnail variants. Additionally, all patients had bone metastasis and had received at least 1 radioiodine treatment for those metastases.

The category of non-¹³¹I treatments included surgery, radiofrequency ablation, cryotherapy, arterial embolization, external beam radiation, Cyberknife, systemic targeted therapy, and anti-resorptive medication. Patients were then categorized by¹³¹I therapy timing: less than 6 months post-thyroidectomy or ≥6 months following thyroidectomy. The study’s primary endpoint was all-cause mortality, measured as the time from initial diagnosis of bone metastasis to death.

About half the study patients died during the course of follow-up (n = 40; 52%). Following the diagnosis of bone metastasis, the median OS was 6.4 years (95% CI, 4.3-8.4).

Wu et al also performed several subgroup analyses. For example, they found that the OS rate in patients who received more than one¹³¹I treatment (median, 9.4 years) was significantly improved compared to the OS in those who received only a single¹³¹I treatment (median, 4.3 years;P= 0.001).

The study authors also identified 5 prognostic factors for improved survival: younger age at DTC diagnosis, younger age at bone metastasis diagnosis, initial¹³¹I therapy within 6 months of thyroidectomy, multiple¹³¹I treatments, and increased cumulative¹³¹I activity. &ldquo;The study presented here evaluated the prognostic variables affecting survival and found that younger age (<55 years) was the only independent prognostic factor associated with better survival in patients treated with¹³¹I for bone metastases,&rdquo; they wrote.

Patients who had started radioiodine therapy less than 6 months postoperatively had a significantly better median OS than those who started after 6 months: 6.5 vs 0.5 years (P<.001). Patients who received external beam radiation therapy experienced better median survival than those who did not (7.8 vs 4.4 years;P= .016). Patients who received denosumab (Xgeva) had a better median OS than those who did not (7.7 vs 5.2 years;P= .03).

Wu et al also identified factors that were not prognostic: sex, surgical extent (thyroidectomy vs lobectomy), histology (papillary vs follicular), presence of other metastasis or tumor, relative timing of DTC and bone metastasis diagnosis (synchronous vs metachronous), symptomatic bone metastasis, and number of bone metastases sites at initial diagnosis.

The authors noted several limitations with their study. These include its retrospective nature, relatively small sample size, and their inability to control for factors like individualized, rather than standardized, treatment plans. &ldquo;Finally, although the data support improved OS with additional localized or systemic non-¹³¹I treatments, the study could not specifically evaluate which specific patients with bone metastases should receive non-¹³¹I localized or systemic treatment or which specific non-¹³¹I localized or systemic treatment should be used,&rdquo; they wrote.

Wu et al noted that conventional clinical management would suggest that¹³¹I treatment should be given first to a patient with DTC and bone metastasis but no evidence of distant metastases. &ldquo;If the patient has a bone metastasis with significant pain or an impending fracture, then additional localized treatment may be considered for palliation,&rdquo; they wrote. &ldquo;However, in rethinking the management approach, perhaps localized treatment should be combined with and administered first before¹³¹I treatment, with the objective of improving OS and not just palliation.&rdquo;

Reference:

Wu D, Gomes Lima CJ, Moreau SL, et al. Improved survival after multimodal approach with¹³¹I treatment in patients with bone metastases secondary to differentiated thyroid cancer [published online July 17, 2019].Thyroid.doi: 10.1089/thy.2018.0582.