Brain metastases from differentiated thyroid carcinoma are uncommon, reported in only 1–2 % of all patients [1–3]. They are typically identified in older patients, with the median age of detection of brain metastases in these recent reports ranging from 61 to 63 years, and the median time interval between initial cancer diagnosis and brain metastasis ranges from 4 to 10 years. Although most cases have been reported arising from papillary carcinomas, there may be a particular predisposition for the oxyphilic or Hürthle cell variant [1]. Usually, patients have had evidence of distant metastatic disease detected previously, such as in the lungs or bones [4], though some patients may present with symptomatic brain metastasis at their initial diagnosis . A majority of patients are initially identified with oligometastatic brain disease, with three or fewer lesions detected by imaging [1, 3]. Historically, imaging to detect these lesions was triggered by symptoms ; however, with the introduction of systemic therapy options and more comprehensive staging examinations for patients with progressive distant metastatic disease, patients are now also being identified with brain metastases at an earlier, presymptomatic phase [3].

Compared with most patients with differentiated thyroid carcinoma, the prognosis of patients with brain metastases is poor. Median overall survival after the diagnosis of brain metastases has been reported as between 7 and 21 months [2, 3], with almost all patients dying of complications of disease and/or treatment. Prognostic factors for prolonged survival include disease amenable to localized intervention such as surgical excision or stereotactic radiosurgery (which is likely to be oligometastatic) and good performance status [1–3]. Median survival for patients with Karnofsky performance status at least 70 was 31 months in one series and for patients with WHO performance status of zero or one was 27 months in another [2, 3].

Treatment options for patients with brain metastases include surgical resection and various modalities of radiotherapy including radioactive iodine, TSH-suppressive thyroid hormone therapy, and systemic therapy. Supportive care must also be considered, particularly for patients with poor performance status and/or widespread intracranial disease [5]. Of note, there have been no randomized clinical trials specifically devoted to treatment of brain metastases from differentiated thyroid carcinoma, and thus recommendations rely primarily upon trials that included patients with various solid tumors or retrospective case series of thyroid patients (with their inherent risk for bias in selection of treatments).

Surgical excision is the traditional approach to treatment for solitary or oligometastatic brain lesions and has been associated with improved survival. In one series, median overall survival was nearly five times longer (16.7 versus 3.4 months) for patients who underwent surgical excision of one or more intracranial lesions compared with those who did not [1]. Resection may be preferred for patients whose metastatic tumors are greater than 3 cm in diameter [6]. Surgical excision can provide diagnostic information when there is uncertainty about the histologic diagnosis (e.g., patients with another primary malignancy as well as thyroid) and can be beneficial for relief of acute intracranial swelling if high-dose glucocorticoids are insufficiently effective. On the other hand, surgery requires time for recovery both before and after hospital discharge, carries a degree of risk, and may not be appropriate for patients with an expected short survival time due to rapidly progressive systemic metastases or poor performance status. Whether surgery should be followed by adjuvant whole-brain radiotherapy (WBRT ) is controversial, as randomized studies in patients with metastatic solid tumors have failed to demonstrate an improvement in overall survival or performance status with combination treatment despite improvements in intracerebral recurrence-free survival [7].

The development of stereotactic radiosurgery (SRS ) provided an attractive new option for patients with multiple small intracerebral metastases by allowing the delivery of a highly focused radiation dose to the tumors while minimizing radiation damage to surrounding uninvolved brain tissue [6]. In one series of thyroid cancer patients, median overall survival was 37.4 months after SRS [2], and in a second series, median overall survival was prolonged more than threefold after SRS [3]. Multiple lesions can be treated simultaneously with a limited number of outpatient treatment sessions, and recovery can be rapid. SRS is most appropriate for patients with tumors up to 3 cm in diameter, minimal intracerebral shift as evidence of mass effect, and good performance status [6]. Due to the highly focused radiation dosimetry of SRS, necrosis of surrounding brain tissue is uncommon and usually asymptomatic. Like surgery, there is no evidence to support an overall survival advantage by adding WBRT after SRS for metastases from solid tumors, although intracerebral recurrence-free survival may be enhanced by the combination [6].

WBRT can be of benefit in the local control of multifocal brain metastases [5, 8]. A standard treatment approach to deliver 3000 cGy in ten fractions is commonly employed. Studies in other solid tumors have failed to demonstrate a significant advantage to the use of altered dosing strategies or concomitant radiosensitizers [5]. Combining WBRT with subsequent SRS or using WBRT following either surgery or SRS has been associated with improved intracerebral recurrence-free survival, but overall survival has not been improved in multiple trials for either oligometastatic or widely metastatic disease [5, 8]. Unfortunately, eventual development of broad cognitive decline has been associated with WBRT, limiting the attractiveness of this intervention in patients anticipated to have longer survival.