Abstract
We read with great interest the article published by Wang et al. (1) about the extraordinary response to neoadjuvant treatment with dabrafenib plus trametinib (D–T) in patients with unresectable anaplastic thyroid carcinoma (ATC) with a BRAFV600E mutation. The management of patients with ATC represents a real challenge in Latin America, considering the underlying resource limitations. This prompted us to comment on our experience with a 62-year-old woman with a rapidly growing cervical mass who was referred to our division (Fig. 1A, B). A baseline computed tomography scan revealed a 12 × 10 × 8 cm unresectable thyroid mass with bilateral pulmonary nodules (Fig. 1E–G). It was confirmed to be ATC with a BRAFV600E . Since D–T were not immediately available, lenvatinib 10 mg once a day was used off-label as a bridge therapy, with tumor stability after 20 days of treatment. The combination of D–T was then administered orally at doses of 150 mg twice daily and 2 mg daily, respectively. After four weeks of therapy, the patient had a dramatic locoregional response with total resolution of compressive symptoms. However, a pulmonary nodule exhibited a 46% growth in size as the patient experienced temporary treatment interruption due to the unavailability of D–T for 1 week. As a consequence, 12 weeks after the beginning of treatment, a slight increase in the neck mass was evident but a reduction by 60% of the target lung nodule was observed with a disappearance of the remaining lung lesions after reinstating treatment with D–T (Fig. 1C, D, H–J). Similar to the reported series by Wang et al., after 13 weeks of treatment with D–T, the patient was able to undergo total thyroidectomy with central neck dissection (Fig. 1K, L). Histologic examination showed an R1 resection. One month later, local external beam radiotherapy was given. Three months after surgery, with D–T treatment, she had no clinical evidence of disease.
Sixty-two-year-old female patient with anaplastic thyroid carcinoma before and after treatment with dabrafenib and trametinib (D–T).
The aggressive behavior of ATC confers rapidly fatal outcome, and a complete surgical resection with or without other treatment is currently the only approach that has been associated with improved survival. The area of knowledge about the therapeutic management of ATC has been expanding with the emergence of the first targeted combination regimen of D–T approved for BRAFV600E -mutated ATC: high response rates and significant improvement in survival (2). Furthermore, the study by Wang et al. showed that neoadjuvant treatment allowed a complete surgical resection, even in patients with distant metastasis (1). This is particularly true in the context of developed countries where the access to molecular tests and target therapies is widely available. We believe that our experience adds to previous findings, since we observed a response to neoadjuvant therapy with D–T even in a setting where there is poor access to the health care system (1). While the number of cumulative patients reported is still small, the current encouraging results should advocate that physicians promptly refer patients with ATC to a highly experienced center to impact the prognosis of the disease.