靶向药物治疗对碘难治性分化型甲状腺癌患者生命质量的短期影响

Short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer

目的分析靶向药物治疗对碘难治性分化型甲状腺癌(RAIR-DTC)患者生命质量的短期影响。方法前瞻性收集2020年2月至2022年4月间于天津医科大学总医院接受索拉非尼、仑伐替尼或安罗替尼治疗的19例RAIR-DTC患者[男10例、女9例,年龄(54.5±14.5)岁]。测量患者靶向治疗前及治疗后1、3、6个月甲状腺球蛋白(Tg)水平;记录靶向治疗后患者不良事件。采用实体瘤疗效评价标准(RECIST)1.1进行疗效评价。根据欧洲生命质量学会五维度健康量表(EQ-5D-5L)获取患者靶向治疗前及治疗后3个月的健康状态,计算其行动能力、自我照顾、日常活动、疼痛或不适、焦虑或沮丧5个维度受影响的发生率,并进行自身健康状态评分。采用配对样本t检验、Kruskal-Wallis秩检验及χ2检验分析数据。结果靶向治疗后3个月,在行动能力、自我照顾、日常活动、疼痛或不适、焦虑或沮丧方面受影响者分别为8(8/19)、6(6/19)、10(10/19)、10(10/19)和12(12/19)例,均明显多于靶向治疗前[1(1/19)、1(1/19)、1(1/19)、2(2/19)和2(2/19)例],各维度受影响的发生率差异均有统计学意义(χ2值:4.38~11.31,均P<0.05)。治疗前和治疗后3个月,患者自身健康状态评分分别为(84.37±6.25)和(71.63±9.14)分,差异有统计学意义(t=5.02,P=0.001)。患者接受靶向治疗后,出现皮肤毒性10例、高血压8例、体质量下降8例、腹泻7例、疲乏6例、肝功能异常5例、蛋白尿2例、肌痛2例、口腔溃疡1例;其中有17例患者坚持继续治疗,2例患者终止治疗。治疗前及治疗后1、3、6个月,患者Tg分别为110.16(49.63,294.50)及56.26(44.60,210.50)、53.36(41.25,203.07)、54.35(34.71,223.52) mg/L,治疗后Tg水平虽较治疗前有所下降,但差异无统计学意义(H=2.42,P=0.490)。治疗后3个月,患者无进展生存(PFS)率为16/17,其中7例部分缓解(PR),9例疾病稳定(SD),1例疾病进展(PD);治疗后6个月,患者PFS率为10/17,其中5例PR,5例SD,7例PD。结论靶向治疗3~6个月后,多数患者血清学或影像学有所改善,但药物不良事件对患者生命质量影响较大。

Objective To analyze the short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC).Methods From February 2020 to April 2022,19 RAIR-DTC patients(10 males,9 females;age(54.5±14.5)years)who received targeted drugs therapy(sorafenib,lenvatinib or anlotinib)in Tianjin Medical University General Hospital were prospectively enrolled.The thyroglobulin(Tg)levels prior and 1,3,6 months post the targeted treatment,and the adverse events were measured and recorded.Response evaluation criteria in solid tumors(RECIST)1.1 version was used to evaluate the treatment response.The quality of life based on five-level EuroQol five-dimensional questionnaire(EQ-5D-5L)was monitored prior and 3 months post the targeted treatment,and the prevalence rates of mobility,self-care,usual activities,pain/discomfort,and anxiety/depression were analyzed,and the scores of health assessment were assessed.Paired t test,Kruskal-Wallis rank sum test andχ2 test were used to analyze data.Results The prevalence rates of mobility(8/19),self-care(6/19),usual activities(10/19),pain/discomfort(10/19),and anxiety/depression(12/19)in 3 months post treatment were higher than those prior treatment(1/19,1/19,1/19,2/19,2/19;χ2 values:4.38-11.31,all P<0.05).The score of health assessment prior treatment was(84.37±6.25),which was higher than that at 3 months post treatment(71.63±9.14;t=5.02,P=0.001).After targeted treatment,10 patients were with skin toxicity,8 patients were with hypertension,8 patients were with weight loss,7 patients were with diarrhea,6 patients were with fatigue,5 patients were with hepatic dysfunction,2 patients were with proteinuria,2 patients were with muscle pain and 1 patient was with oral ulcer.Of 19 patients,17 insisted on continuing treatment,and the other two stopped treatment.The Tg levels at 1,3 and 6 months post treatment were 56.26(44.60,210.50),53.36(41.25,203.07)and 54.35(34.71,223.52)mg/L,respectively,which were lower than the level prior treatment with no significant difference(110.16(49.63,294.50)mg/L;H=2.42,P=0.490).After 3 months of targeted treatment,the progression-free survival(PFS)rate was 16/17,including 7 patients with partial response(PR),9 patients with stable disease(SD),and 1 patient with progression of disease(PD).After 6 months of targeted treatment,the PFS rate was 10/17,including 5 patients with PR,5 patients with SD,and 7 patients with PD.Conclusion After 3-6 months of targeted treatment,the tumor markers of most patients are decreased with metastases improved,but the adverse events of targeted drugs have a great impact on quality of life in patients with RAIR-DTC.