The medical community and the population it serves should be under no illusion of the poor prognosis of a patient with metastatic cancer; it is, unfortunately, more likely to result in early death than not.
With this clear-eyed view of the limitations of medicine and the ruinous potential of an unwelcome diagnosis, we shall look specifically at medullary thyroid carcinoma (MTC) and the consequence of distant metastases, particularly at the brain.
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Understanding Outcomes of Distant Metastases
While it is a fact universally accepted that a cancer that has metastasized is not good news, it remains the truth that we know little about the prognostic significance of metastatic sites in MTC and the immediate cause of death.
“The significance of differentiating the characteristics according to the site of distant metastasis remains unclear,” Park and colleagues wrote in Cancers.
To understand why this is the case, we merely need to trace the kind of therapeutic options available to patients with MTC. Patients with MTC, where possible, are usually offered a total thyroidectomy with central lymph node dissection. However, unlike differentiated thyroid cancer (DTC), patients with MTC are ineligible for radioactive iodine therapy. This means that there is currently no cure for metastatic MTC.
Existing studies are unanimous in their conclusion that metastatic MTC carries with it a fatal prognosis. Delving deeper, we find that many studies do not differentiate between the sites of distant metastasis, likely due to the rarity of the condition. In addition, Park et al pointed out that there is a paucity of papers considering the timing of the detection of distant metastasis, opening up the possibility of lead-time bias. Lastly, the precise cause of death of metastatic MTC is rarely characterized in detail.
Park and colleagues hence carried out a study to investigate this further. Of the 46 patients under investigation, they found that the most common sites for metastasis was the lungs (52.2%), followed by the bone (28.3%) and the mediastinum (19.6%). Brain metastasis is very rare. Patients who are found to have bone metastasis or multisite metastasis have a poorer prognosis compared to patients with lung metastasis alone (the hazard ratios were significantly higher).
Five-year survival rates from time of metastasis detection was 100% for liver metastasis, followed by 74.6% for lung and 62.5% for mediastinum. The most common cause of death for the 19 deceased patients were complications from distant metastasis (36.8%), followed by complications from chemotherapy (26.3%) and tracheal invasion leading to airway obstruction (21.1%).
Importantly, 19% of patients with MTC were found to have distant metastasis in a follow-up period of 9.7 years; meaning that 1 in 5 patients are likely to experience distant metastasis within a decade. While ontological outcomes differed according to the site of metastasis, mortality can occur from various sources, including complications from the disease itself or the therapeutic used to treat it.
MTC and Brain Metastasis
In a literature review of MTC cases (or any thyroid cancer more generally) with specific brain metastasis using academic search engines, only a handful of cases were available for review despite decades of research. This once again demonstrates the problem that clinicians often face in dealing with rare diseases with even rarer manifestations: a paucity of information, despite global, cross-cultural cooperation.
In Clinical & Experimental Metastasis, Wolff and colleagues conducted a retrospective study to explore the link between thyroid cancer and brain metastases via accessing the Vienna Brain Metastases Registry, containing data on patients with brain metastasis from 1986 to 2020. Of the 6047 patients in the database, only 20 had brain metastasis from thyroid cancer. The research team reported that the overwhelming majority (95%) of patients with brain metastasis were symptomatic upon initial presentation; these include neurological deficits, symptoms related to intracranial pressure, and epileptic seizures.
The most commonly offered treatment for brain metastasis from thyroid cancer was total resection, followed by stereotactic radiosurgery. Systemic therapies were typically offered: these include chemotherapy and lenvatinib (introduced in 2017).
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Wolff et al reported that progression-free survival in their study cohort varied between 2 months (papillary thyroid cancer) to 139 months (MTC). Patients with MTC-related brain metastasis had a median survival of 12 years after diagnosis, which is much longer than patients with anaplastic thyroid cancer, who had a median survival of just 2.6 months after diagnosis. In addition, patients with a singular brain lesion had longer survival than patients with multiple lesions.
“In conclusion, brain metastasis constitute a generally poor prognostic factor in thyroid cancer patients,” the research team concluded. “For the time being, patients should be managed on an individual basis in a tertiary referral center with access to (neuro-) surgery.”
Given the poor prognosis of patients with distant metastases, in the brain or otherwise, it is important for physicians to provide patients with a thorough understanding of their present situation and to offer support where possible. Unless cancer therapeutics advance by leaps and bounds in the years ahead, it is likely that survival will remain poor among this cohort of patients.
References
Park H, Yang H, Heo J, Kim TH, Kim SW, Chung JH. Long-term outcomes and causes of death among medullary thyroid carcinoma patients with distant metastases. Cancers (Basel). Published online September 17, 2021. doi:10.3390/cancers13184670
Wolff L, Steindl A, Popov P, et al. Clinical characteristics, treatment, and long-term outcome of patients with brain metastases from thyroid cancer. Clin Exp Metastasis. Published online May 23, 2023. doi:10.1007/s10585-023-10208-8
