DISCUSSION

In all thyroid cancer types, the prognosis of ATC is most dismal, and the management of ATC remains most challenging. Although previous analyses have reported that the extent of traditional therapeutics, such as surgery, radiotherapy, and chemotherapy, may be associated with the length of survival,13,14 the overall therapeutic effect is awful.

Our patient was not amenable to the above conventional treatment options considering her old age and locally advanced disease at the time of diagnosis.15 New therapeutic strategies were urgently needed. Since increased VEGFR expression had been found in the microvascular endothelial cells of ATC tumor specimens,16 and agents targeting VEGFR could block the effects of vascular endothelial growth factor and play antiangiogenic and antitumor roles in solid tumors,6,17 we hypothesized that agents targeting VEGFR may also play an antitumor role in ATC patients.


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Apatinib, a novel tyrosine kinase inhibitor that has highly selective competition in the ATP binding site of VEGFR-2, blocks down pathways and inhibits tumor angiogenesis.18,19 It also mildly inhibits c-Kit and c-Src.20 Preclinical studies have also demonstrated that Apatinib plays an important antitumor role in ATC via suppressing the AKT/GSK3β/ANG signal pathway,10,11 which can be activated when VEGFR-2 activates the phosphatidylinositol 3-kinase.21 Moreover, it has been demonstrated that overwhelming efficacy has been achieved in RR-DTC, and ATC tumors evolve from a background of DTC.7,22 All the above evidence favored Apatinib as a choice for this ATC patient. Additionally, the value of gene examinations needs to be thoroughly evaluated in decision-making using an appropriate sample size of ATC patients since they have succeeded in methodology.23

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As a result, gratifying outcomes were achieved regarding a durable response and overall survival of more than 30 and 41 weeks, respectively. Although the degree of tracheal stenosis was slightly more severe than that before treatment due to tumor invasion, the longest diameter of the tumor diminished from 7.6 cm to 6.1 cm. This endeavor may pave a way to new adjuvant therapy for surgery, which has been previously reported in RR-DTC by our team.9 Hypertension, hand-foot syndrome, dental ulcer, fatigue, and decreased appetite were observed, which are known classical side effects of VEGFR-targeted treatments,17 which were lightened with supportive treatment and dose reductions as reported by our group and others.24,25 Pneumonia and respiratory failure beyond of known Apatinib-induced adverse events were considered as the causes of death instead of complications related to the treatment, which may be further explained by decreased cough reflex associated with severely aging, difficulty of expectoration due to tracheal stenosis, and the absence of objective disease progression.17,26

Lenvatinib, another multikinase inhibitor, has been approved for utilization in patients with unresectable ATC in Japan. A phase II clinical trial revealed a median OS of 10.6 months and response rate with partial response and stable disease in 4/17 and 12/17 patients, respectively.27 Another study enrolled 3 patients; 2 were stable, and 1 had a mixed response to Lenvatinib therapy.28 Additionally, for those with BRAF-mutated ATC, the FDA has approved the combination of Dabrafenib and Trametinib for treatment as of May 2018.29 However, these agents are commercially unavailable or unapproved in China by now. In addition, resistance to the above drugs is a common challenge, thereby necessitating second-line or salvage therapies.27,30–33

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