Patients with low-risk thyroid cancer can be safely and effectively treated with low doses of radiotherapy after surgery, with no difference in recurrence rates compared with the standard dose, confirms the longest-running randomized trial of lower-dose treatment.
With a median follow-up of 6.5 years, among 434 patients with low-risk thyroid cancer, the HiLo trial showed that low-activity radioactive iodine (RAI) was just as effective as standard-activity RAI, with no significant difference in recurrence rates between treatments during the study period.
Moreover, the results demonstrated that giving exogenous recombinant thyrotropin (multiple brands), which stimulates the absorption of RAI by thyroid cancer cells, improves quality of life and activities of daily living compared to withdrawing thyroid hormone tablets to achieve the same effect.
The study was presented at the National Cancer Research Institute (NCRI) 2018 Cancer Conference.
Jonathan Wadsley, MD, chair of the NCRI Thyroid Cancer Subgroup, expects that the results will reinforce recommendations in international guidelines that selected patients with low-risk thyroid cancer be treated with low-activity RAI. Earlier recommendations had relied on short-term follow-up data.
Wadsley, who is also a consultant clinical oncologist at the Weston Park Hospital, Sheffield, United Kingdom, said in a press release that the new data show that "use of the lower activity is acceptable and in fact preferable."
Speaking to Medscape Medical News, Wadsley explained: "At the moment, there are number of national and international guidelines which weren't terribly strongly recommending the low-dose arm when they were published."
The next iteration of those guidelines can be stronger and more confident in recommending the lower dose in this setting, he said.
Wadsley personally recommends low-activity RAI with recombinant thyrotropin "on the grounds that we know that improves quality of life significantly for patients."
Martin Forster, MD, PhD, from University College London, United Kingdom, who is chair of the NCRI Head and Neck Clinical Studies Group, also said that the international guidelines can be updated to reflect the new, longer-term data.
Forster, who was not involved with the study, pointed out that "for many patients, the treatment and how it is delivered, as well as the short- and long-term side effects, can have a big impact on their lives."
The current study is "a good example of a well-conducted clinical trial that can make a real difference to the quality of life for these patients," he added.
Thyroid cancer is rare, and patients with low-risk disease have a good prognosis; 10-year survival is around 99%.
The High Dose vs Low Dose I 131 +/- rhTSH for Differentiated Thyroid Cancer (HiLo) trial randomly assigned 438 patients to receive low administered RAI activity, at 1.1 GBq, or the standard high activity, at 3.7 GBq.
"Activity is a measure of the amount of radiation that is administered to the patient in the form of a radioactive isotope of iodine," Wadsley explained.
Generally, to prevent recurrence, it is desirable to give the lowest quantity of radiation possible, he said.
He explained why: "This is to reduce the risk of longer-term side effects from the treatment, most importantly, reducing the risk of the treatment causing another cancer in the future."
In addition to being assigned to low- or standard-activity RAI, the patients, who were recruited between 2007 and 2010, were also randomly assigned to either recombinant thyrotropin treatment or thyroid hormone withdrawal.
Hormone withdrawal achieves the same effect as recombinant thyrotropin treatment by allowing thyroid-stimulating hormone levels to rise naturally.
As previously reported by Medscape Medical News, the trial showed that 6- to 9-month postablation success rates were similar between the low-activity and standard-activity RAI groups.
Although these results led to international guidelines recommending the lower dose in selected low-risk patients, there was a lack of long-term data to support the move.
Study Details
Now, the researchers report results for a much longer follow-up period of more than 6 years.
They found that the recurrence rates were similar between the low-dose and the standard-dose treatments. There were 11 recurrences among patients given low-activity RAI, and 10 among those given the standard dose.
This equates to 3-, 5-, and 7-year recurrence rates in low-activity RAI patients of 1.5%, 2.1%, and 5.9%, respectively. Among standard-activity RAI patients, the equivalent recurrence rates were 2.1%, 2.7% and 7.3%, respectively.
Overall, there was no significant difference in recurrence rates between the groups (hazard ratio [HR], 1.10; P = .83).
The team also reported that there was no appreciable association between RAI activity and recurrence rates with respect to T and N stage, even among patients with T3 disease.
However, one patient died from thyroid cancer during the study period. That patient had T3/N0 disease at baseline and was treated with low-activity RAI.
Comparing patients who received recombinant thyrotropin with those assigned to hormone withdrawal, the team also found that there was no significant difference in recurrence rates.
Among patients given recombinant thyrotropin, 3-, 5-, and 7-year recurrence rates were 1.5%, 2.1%, and 8.3%, respectively; among patients in the hormone withdrawal group, the rates were 2.1%, 2.7%, and 5.0%, respectively (HR, 1.62; P = .28).
Wadsley noted that patients who received low-activity RAI experienced fewer adverse effects, in particular, nausea and salivary gland damage.
"The use of a lower activity also raises the possibility of giving the treatment in 1 day rather than having to admit patients to be nursed in isolation for 2 to 3 nights," he said.
"This is required for the higher activity, due to radiation protection regulations to avoid exposing the general public to unnecessary radiation, but can be particularly distressing for patients, as they can only have very limited contact with other people during this time," he said.
Wadsley also said that patients given recombinant thyrotropin had better quality of life and were more able to continue activities of daily living in comparison with those assigned to hormone withdrawal.
"If thyroid hormone withdrawal is used, patients have to come off their regular medication for at least 2 weeks," he explained. "This leaves them feeling extremely tired and, in some cases, quite depressed."
Having completed the current study, the researchers have already started the IoNtrial, which will allocate patients with very-low-risk thyroid cancer to RAI or careful observation alone.
Forster commented that he is looking forward to the results of this trial, "which could determine whether some patients have such a low risk of their cancer returning that they could be spared radioiodine treatment completely," he said.
Wadsley said that recruitment for the IoN trial should finish in late 2018 or early 2019.
Pointing out that the primary endpoint will be 5-year local recurrences rates, he said that "it'll be at least 2 or 3 years until we have any readout."
The study was funded by Cancer Research UK. Genzyme provided the thyrotropin. Dr Wadsley has received consulting fees from Sanofi Genzyme.
National Cancer Research Institute (NCRI) 2018 Cancer Conference. Abstract LBA 2148, presented November 6, 2018.
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