Dr Blomain Overviews Novel Uses of RT in TC

Erik Blomain, MD, PhD, Radiation Oncology Resident, Stanford University, and patient advocate, NCCN Thyroid Cancer Guidelines Panel, overviews novel uses of radiotherapy (RT) in thyroid cancer (TC), presented at the virtual 2022 Rare Cancer Series from Great Debates & Updates.

The main treatment modalities for TC include surgery, external beam radiation using X-rays from outside the body to treat an area of clinical concern, and radioiodine in pill form.

“I wanted to highlight that there's a lot of complexities in this TC treatment paradigm because historically radioiodine (RAI) has been used, but emergingly, there's been a move over to external beams,” Dr Blomain said.

RAI treatments are often given after a thyroidectomy for differentiated TC (DTC), Dr Blomain said, and have several clinical benefits. RAI leverages the unique biology of thyroid tissue to concentrate iodine to make thyroid hormones, he said. DTC is retained in that biology and can be leveraged clinically for treatment. The benefits of RAI treatment include ablation of residual normal thyroid tissue, which may be at risk for recurrence, or a second primary. It’s also useful for ablation of occult residual disease, adding therapeutic value in diagnosing residual disease.

There are several guidelines on the use of RAI, including ones by the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN). According to these guidelines, for low-risk patients (tumor > 2 cm, intrathyroidal, no vascular invasion, cN0, negative anti-Tg antibodies, postop Tg <1, negative post-op ultrasound), RAI can be omitted. For high-risk patients (tumor > 4 cm, gross ETE, extensive vascular invasion, postop Tg >10, bulky or <5 positive lymph nodes), RAI is given. For intermediate-risk patients (tumor 2-4 cm, minor vascular invasion, positive LNs, detectable anti-Tg antibodies, 1 < postop Tg < 10, microscopically plus margins), RAI is selectively recommended.

“TC patients typically have an excellent prognosis and can live many decades, particularly in a young patient who has time, unfortunately, to develop secondary side effects from radiation decades later,” Dr Blomain said.

In terms of dosing, there’s multiple paradigms that can be given, Dr Blomain said. For low-risk patients (<4 cm, N0 or N1, minor ETE), a dose of 30-50 mCi is primarily administered. For intermediate-risk patients (higher likelihood of residual disease), the dose is around 50-100 mCi. For high-risk (confirmed unresectable residual or metastatic disease) doses from 100 mCi up to 200 mCi can be given. Doses can also be given multiple times in most cases, Dr Blomain said.

There’s also new data in external beam radiation therapy (EBRT) for TC, Dr Blomain said. Historically, the role for EBRT and TC is limited. There's no perspective evidence for the upfront or advanced setting. However, retrospective data demonstrates local regional control benefits, but no overall survival (OS) benefits, Dr Blomain said.

It’s reasonable to consider taking EBRT for DTC primary site for the following indications: high-risk clinical or pathological features, residual disease that’s not amenable to RAI, recurrent disease, anytime a future recurrence requires salvage surgery would be impossible or highly morbid, and inoperable disease or medically-inoperable patient, he said.

Although RAI has been a mainstay of treatment, in the anaplastic disease setting, the biology is much different, Dr Blomain said, including losing the ability to concentrate iodine. In these cases, EBRT is the mainstay of treatment whether the patient is unresectable and needs definitive radiation, or resectable and getting adjuvant radiation.

“Local control is a major problem for these patients, and they have a major source of morbidity and mortality from local progression. That remains kind of standard of care. It's more in the differentiated setting, and I think there's room to grow,” Dr Blomain said.

A new emerging area, Dr Blomain mentioned, is oligometastatic disease defined as having < 5 metastatic lesions.

He then highlighted a randomized phase 2 open-label trial on the effect of stereotactive ablative radiotherapy (SABR) on survival, outcomes, toxicity, and quality of life in patients with a controlled primary tumor and 1 in 5 oligometastatic lesions. Overall, SABR was associated with an improvement in OS, however, 3 patients (n = 66) in the SABR group had a treatment-related death. A phase 3 trial is needed to conclusively show an OS benefit and to determine the maximum number of metastatic lesions where SABR provides a benefit, he said.

Spine disease and spine metastases have different considerations, such as local control and pain control, depending on the clinical situation. Dr Blomain then overviewed a randomized trial which demonstrated that there was a significantly higher complete pain response at 3 months with stereotactic radiosurgery (SRS) versus conventional EBRT (risk ratio 1-33; 95% CI, 1.14-1.55; P = 0.0002) and good local control.

“Conventionally fractionated EBRT does have a role in the postoperative setting where you're treating a large field for extensive disease or purely for symptom palliation, say from an active cord compression. In other cases where we're worried about getting superior pain control and treatable lesion, or in risk of structural disease and impending cord compression—we prefer SRS in these patients,” Dr Blomain said.

The last indication Dr Blomain overviewed is brain disease, where the standard of care in the NCCN CNS guidelines is to use SRS for a limited (< 10) amount of brain metastases.

Whole brain radiotherapy (WBT) is the other competing treatment used more historically, he said. It is still used for extensive brain metastases and leptomeningeal disease. However, it is used sparingly and usually with other adjuvant treatments because it has debilitating neurocognitive toxicities associated with it. Current treatment guidelines do not support such a universal role for SRS in TC brain metastases.

In the context of supporting the argument for radiation therapy in TC patients, “we decided to look at both our institutional data and a national cohort of the NCDB database to see if thyroid cancer patients are different than the other cancers,” Dr Blomain said.

When comparing modality using Dr Blomain’s institutional data on SRS versus whole brain versus the entire cohort, the whole brain patients did worse overall. However, when you look at the national database, there’s no survival difference between them.

“That goes along with other data that the goal of treating in the brain is not OS. Nothing you do in the brain is going to meaningfully impact OS. The goal is local control, and prevention of neurocognitive toxicity, and neurocognitive progression associated with a decline,” explained Dr Blomain. “That's why generally SRS is favored. Not because patients do better with it, but because they have fewer neurocognitive effects from it, and they still get good local control of their cancers.”

When looking at survival and local control outcomes for RT in TC brain metastases, the study found that local control rates are less than 10% at 1-year risk of incidence of local failure, and about 30% or so 1-year risk of regional failure outside of the treated volume.

An analysis of national practice patterns showed a significant increase in SRS throughout the cohort as well as in an exploratory analysis of the anaplastic cohort, Dr Blomain said.

“That reflects to some extent we are as a field complying with the general trends in oncology in this indication. The guidelines need to catch up and support that. Then we're all giving a unified message that these changing practice patterns are evidence based and guideline based. I'm happy to report that the current years’ edition of the NCCN guidelines are standardized now between thyroid and CNS.”—Emily Bader