DISCUSSION
dysphagia, aggressive thyroid cancers, tumor, dyspnea, pembrolizumab, hoarseness, neutropenia, toxicities, Anaplastic thyroid cancer, airway distress, deaths, hypertension, thyroid cancer
DYSPHAGIA, LEUKOCYTOPENIA, TUMOR, NEUTROPENIA, HYPERTENSION, THYROID, DISEASE, ANAPLASTIC THYROID CANCER, SOLID TUMORS, THYROID NODULE, THROMBOCYTOPENIA, MALIGNANCIES, THYROID CANCER, THYROID CANCERS
Anaplastic thyroid cancer is considered the most lethal thyroid cancer, accounting for 38%–50% of all deaths related to thyroid cancers. The overall 5‐year survival rate for ATC is below 10%Anaplastic thyroid cancer often presents with severe symptoms including airway distress, hoarseness, dyspnea, and dysphagia due to a fast‐growing neck mass. A definitive diagnosis is usually made using fine‐needle aspiration biopsy and/or high‐resolution US. The patient in the present case underwent CNB of the prevailing thyroid nodule, which was diagnosed as ATC.According to American Thyroid Association guidelines, a combination of surgery, chemotherapy, and radiotherapy should be used to manage and control local and metastatic ATCs.We attempted experimental therapy involving a combination of famitinib (a tyrosine kinase inhibitor [TKI]) and camrelizumab (an immune checkpoint inhibitor [ICI]). TKIs are currently used to treat aggressive thyroid cancers, as they induce clinical responses and stabilizes the disease. The role of TKIs in the treatment of thyroid cancer is limited to cases wherein progression continues after primary therapy (surgery and radioiodine therapy) and local ablation therapies. Careful evaluation of the risk/efficacy ratio is recommended in such cases. Testing each patient's sensitivity to different TKIs could pave the way for personalized treatment.Famitinib, a sunitinib analog, is a novel and highly potent multi‐target receptor tyrosine kinase inhibitor against c‐Kit, vascular endothelial growth factor receptor, and platelet‐derived growth factor receptor; with antitumor activity in the range of solid tumors.In the present case, the primary thyroid lesion as well as cervical lymph nodes had shrunk following a combination therapy with a TKI and an ICI, which enabled us to perform complete surgical resection. After radiotherapy, the patient received camrelizumab for maintenance. Effective choices for systemic treatment of patients having ATC with wild‐type BRAF are still lacking. The present case report suggests that ATC with wild‐type BRAF could exhibit a substantial response to treatment with a combination of a TKI and an ICI. In a phase II cohort study, 42 patients were enrolled. The overall response rate was 19%, with complete response in 3 patients and partial response (PR) in 5 patients. This shows the reactivity of ATC to PD‐1 blockade.Although we cannot exclude the possibility that the patient might have responded to famitinib or camrelizumab monotherapy, the similarity of famitinib with sunitinib and the course of the disease suggest that the combination of famitinib and camrelizumab is more than just an addition of the two drugs. For patients already resistant to TKI therapy, the addition of pembrolizumab is partially effective with a PFS of only 2.96 months,After neoadjuvant therapy, the patient underwent major surgery including total thyroidectomy, bilateral central compartment dissection, and left neck dissection. The surgery successfully preserved critical functional organs such as the trachea, esophagus, parathyroids, and larynx/recurrent laryngeal nerves. Uruno et al. documented their clinical experience with neoadjuvant chemotherapy for ATC.In the neoadjuvant phase, toxicities related to famitinib were classified as grade I–II and the present study noted a lower incidence of side effects such as thrombocytopenia, leukocytopenia, neutropenia, and hypertension when compared with previous reports involving advanced solid malignancies refractory to standard treatment.In conclusion, ATC is associated with high mortality rates. Exploring new strategies is still needed to improve the survival of ATC patients. In this case, we chose a multidisciplinary method to treat this staging IVB ATC patient, which included the systemic treatment of famitinib and camrelizumab as the inducing therapy, and after the shrinkage of the tumor, surgery was performed and then adjuvant radiotherapy with subsequent maintenance immunotherapy was given. This approach is expected to be an effective therapeutic modality and should be explored prospectively in future clinical trials. Trials exploring combination immunotherapy and targeted therapy are currently ongoing (NCT04521348).