Lee Chien-Lin, Chen Wei-Shan, Wee Yinshen, Wang Ching-Shuen, Chen Wei-Chih, Chiu Tai-Jan, Wang Yu-Ming, Wu Ching-Nung, Yang Yao-Hsu, Luo Sheng-Dean, Wu Shao-Chun
Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Cancers (Basel). 2022 Jan 29;14(3):703. doi: 10.3390/cancers14030703.
Increasing clinical evidence supports the use of direct oral anticoagulants (DOACs) as a potential new therapeutic option for patients suffering from cancer-associated thromboembolism. However, the clinical impact of DOACs compared with traditional anticoagulants on the survival of patients with head and neck cancer has not been well studied. A total of 1025 patients diagnosed as having head and neck cancer, including 92 DOAC users, 113 warfarin users, and 820 nonusers of anticoagulants, were selected from the Chang Gung Research Database between January 2001 and December 2019. The patients were matched using the propensity-score method. The survival rates were estimated among the three groups using the Kaplan-Meier method. The protective effects and side effects of the two anticoagulants were compared using the chi-square test. The death rate (18 patients, 19.57%) in patients using DOACs was significantly lower than that in patients using warfarin (68 patients, 60.18%) and those not using any anticoagulant (403 patients, 49.15%). DOAC users had significantly better disease-specific survival (DSS) than warfarin users ( = 0.019) and those who did not use any anticoagulant ( = 0.03). Further, DOAC users had significantly higher overall survival (OS) rates than warfarin users and those who did not use any anticoagulant ( = 0.003). Patients with oropharyngeal and laryngeal cancer and DOAC users had a significantly lower hazard ratio for survival, whereas patients with American Joint Committee on Cancer stage IV disease and those receiving multidisciplinary treatment (e.g., surgery with radiotherapy or concurrent radiochemotherapy) had a significantly higher hazard ratio for survival. Among them, patients with laryngeal cancer (HR = 0.47, 95% CI = 0.26-0.86, = 0.0134) and DOAC users (HR = 0.53, 95% CI = 0.29-0.98, = 0.042) had the lowest hazard ratio from DSS analysis. Similarly, patients with laryngeal cancer (HR = 0.48, 95% CI = 0.30-0.76, = 0.0018) and DOAC users (HR = 0.58, 95% CI = 0.36-0.93, = 0.0251) had the lowest hazard ratio from OS analysis. As for the protective effects or side effects of anticoagulants, there were no significant differences in the occurrence rate of bleeding or ischemic events between DOAC and warfarin users. In our study, DOACs were found to be better than warfarin in terms of survival in patients with head and neck cancer. As regards thromboembolism prevention and side effects, DOACs were comparable to warfarin in our patients. DOACs can be a treatment choice or prophylaxis for tumor emboli in head and neck cancer patients and they might be a better choice than traditional anticoagulants according to the results of our study.
越来越多的临床证据支持使用直接口服抗凝剂(DOACs)作为癌症相关血栓栓塞患者潜在的新治疗选择。然而,与传统抗凝剂相比,DOACs对头颈癌患者生存的临床影响尚未得到充分研究。2001年1月至2019年12月期间,从长庚研究数据库中选取了1025例诊断为头颈癌的患者,其中包括92例DOAC使用者、113例华法林使用者和820例未使用抗凝剂者。采用倾向评分法对患者进行匹配。使用Kaplan-Meier法估计三组患者的生存率。使用卡方检验比较两种抗凝剂的保护作用和副作用。使用DOACs的患者死亡率(18例,19.57%)显著低于使用华法林的患者(68例,60.18%)和未使用任何抗凝剂的患者(403例,49.15%)。DOAC使用者的疾病特异性生存率(DSS)显著优于华法林使用者(P = 0.019)和未使用任何抗凝剂的患者(P = 0.03)。此外,DOAC使用者的总生存率(OS)显著高于华法林使用者和未使用任何抗凝剂的患者(P = 0.003)。口咽癌和喉癌患者以及DOAC使用者的生存风险比显著较低,而美国癌症联合委员会IV期疾病患者和接受多学科治疗(如手术联合放疗或同步放化疗)的患者生存风险比显著较高。其中,喉癌患者(HR = 0.47,95%CI = 0.26 - 0.86,P = 0.0134)和DOAC使用者(HR = 0.53,95%CI = 0.29 - 0.98,P = 0.042)在DSS分析中的风险比最低。同样,喉癌患者(HR = 0.48,95%CI = 0.30 - 0.76,P = 0.0018)和DOAC使用者(HR = 0.58,95%CI = 0.36 - 0.93,P = 0.0251)在OS分析中的风险比最低。至于抗凝剂的保护作用或副作用,DOAC使用者和华法林使用者之间出血或缺血事件的发生率没有显著差异。在我们的研究中,发现DOACs在头颈癌患者的生存方面优于华法林。在血栓栓塞预防和副作用方面,DOACs在我们的患者中与华法林相当。DOACs可以作为头颈癌患者肿瘤栓塞的治疗选择或预防措施,根据我们的研究结果,它们可能是比传统抗凝剂更好的选择。