Meta-Analysis Examines Risk for Subsequent Malignancy After Radioiodine Therapy for Thyroid Cancer

More research is still needed to determine the risk of developing a subsequent malignant neoplasm (SMN) following radioactive iodine treatment (RAI) for thyroid cancer, according to findings that were presented during the Annual Meeting of the American Thyroid Association and also published inThyroid.

Along with co-investigators, lead study author Chi Yun Yu, MD, conducted a systematic review and meta-analysis of studies examining whether the risk of SMN was different in patients with thyroid cancer treated with RAI compared with those not treated with RAI. The findings suggested that the body of evidence is highly heterogeneous and complex, amongst both adjusted and unadjusted figures, and more research is still needed on the potential risk of SMNs, which is an important concern in thyroid cancer.

“The heterogeneity of results within the outcome of any SMN and variability in effects observed among various specific SMNs suggest that it may be preferable for future studies to examine the risks of respective second primary cancers, rather than the composite outcome of any SMN,” the investigators wrote. “Our findings also suggest that there may be variable biologic effects associated with RAI treatment in different tissues, although confirmatory research is needed.”

The investigators published an original review in 2009, however, there were very few data available at the time. Due to a recent increase in data published on this topic, they performed the updated systematic review.

The investigators reviewed 3506 unique electronic search citations, 93 full-text papers, and 17 studies. In order to be included in the review the studies were required to be in the English language, have thyroid cancer as the first malignancies and report the rate of any SMN or specific SMNs in patients treated with RAI and not treated with RAI. Studies eligible for inclusion were published clinical trials, observational studies with >50 patients, or systematic reviews/meta-analyses with a similar focus to this study. Investigators did not include narrative reviews, editorials, or letters without original data. In the case of overlapping study groups, for example, multiple reports from the same clinical or registry dataset, the data set with the most thyroid cancer patients was used, or the most recent report with relevant data.

Investigators noted that 2 previously published systematic reviews suggested patients treated with RAI had an increased risk of developing any SMN and 1 meta-analysis suggested a reduced risk of breast SMN after RAI treatment.

A meta-analysis of crude data from this review showed that the risk ratio of any SMN in patients with thyroid cancer treated with RAI was 0.98 (95% CI, 0.76-1.27) (n = 10 studies of 65,539 individuals; heterogeneity Q = 64.26).

The pooled risk ratio for any SMN, adjusted for confounders, was 1.16 (95% CI, 0.97-1.39) (n = 6 studies, data from at least 11,241 patients; heterogeneity Q = 10.86).

In secondary analyses examining specific SMNs, although relatively rare, patients treated with RAI had an increased risk of subsequent leukemia, but a reduced risk of multiple myeloma. The investigators suggested that this could be due to some unintentional therapeutic benefit that patients received from treatment with I-131. On the other hand, RAI treatment status did not have a significant impact on increased relative risk of breast cancer, salivary cancer, and combined hematologic malignancies.

“Further research is clearly needed to better understand the relationship between RAI treatment and I-131 activities with specific SMNs, including multiple myeloma. Such studies must consider the full spectrum of potential of targeted and off-target outcomes,” the investigators wrote.

The authors suggested that further data should include large prospective trials including long-term (>10 years) follow-up.

Reference:

Yun Yu C, Saeed O, Goldberg A, et al. A Systematic Review and Meta-analysis of Subsequent Malignant Neoplasm Risk after Radioactive Iodine Treatment of Thyroid Cancer [published online October 27, 2018].Thyroid. doi: 10.1089/thy.2018.0244.