仑伐替尼±程序性死亡蛋白-1抑制剂新辅助治疗模式在局部进展期甲状腺癌中的应用:一项多中心真实世界研究OA

Background and purpose:Locally advanced thyroid cancer(LATC)accounts for 5%to 15%of all thyroid cancer cases;it frequently involves surrounding critical nerves,blood vessels,and organs,rendering surgical resection difficult and resulting in a poor prognosis.As an emerging strategy,neoadjuvant therapy aims to achieve tumor downstaging through preoperative pharmacological treatment,thereby increasing resectability rates,improving functional preservation,and prolonging survival.The multi-targeted tyrosine kinase inhibitor(mTKI)lenvatinib has demonstrated favorable efficacy in radioiodine-refractory differentiated thyroid cancer(RAIR-DTC).Furthermore,the combination of programmed death-1(PD-1)/programmed death ligand-1(PD-L1)inhibitors with targeted therapy has shown potential in anaplastic thyroid cancer(ATC)and poorly differentiated thyroid cancer(PDTC).This study aimed to explore the application of lenvatinib monotherapy or combined with PD-1 inhibitor neoadjuvant therapy in LATC,evaluating its tumor downstaging and conversion resection efficacy,and analyzing patient prognosis.Methods:In this multicenter real-world study,eligible patients were those with pathologically confirmed unresectable or borderline-resectable DTC,PDTC,or ATC.All enrolled patients received neoadjuvant therapy consisting of lenvatinib±a PD-1 inhibitor.Treatment continued until the criteria for curative surgery were met,disease progression occurred,the patient withdrew informed consent,intolerable toxicities emerged,or the investigator determined that treatment should be terminated.The primary endpoint was the objective response rate(ORR),based on the Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1.Secondary endpoints included the R0/R1 resection rate,overall survival(OS),and progression-free survival(PFS),among others.Results:Between August 17,2019 and April 1,2025,a total of 38 eligible patients were enrolled in this study across three oncology centers nationwide.Histopathological diagnoses confirmed 24 cases of DTC(63.16%),5 cases of PDTC(13.16%),and 9 cases of ATC(23.68%).Twenty patients received lenvatinib monotherapy(13 with DTC,3 with PDTC,and 4 with ATC),while 18 patients(11 with DTC,2 with PDTC,and 5 with ATC)received lenvatinib in combination with a PD-1 inhibitor(including pembrolizumab,camrelizumab and toripalimab).Tumor response was evaluable in all 38 patients;among them,1 achieved a complete response(CR),25 achieved a partial response(PR),10 had stable disease(SD),and the remaining 2 experienced progressive disease(PD).The ORR for the entire patient cohort was 68.42%,specifically 70.83%in the DTC group and 64.29%in the PDTC+ATC group.Following neoadjuvant therapy,33 patients(86.84%)successfully underwent surgical resection,achieving an R0/R1 resection rate of 78.79%.One patient who achieved a CR received radiotherapy as a definitive treatment modality.The median follow-up duration was 29.53 months;in the DTC group,the median PFS and OS had not yet been reached,whereas in the PDTC+ATC group,the median PFS was 19.13 months,and the median OS was 40 months.Conclusion:Neoadjuvant therapy with lenvatinib±a PD-1 inhibitor is a feasible treatment strategy for LATC,enabling the majority of patients to achieve R0/R1 resection.This provides a novel therapeutic option for patients with LATC.