摘要
目的 探讨肺癌同期放化疗患者全程口服叶酸降低放射性食管炎(RE)发生率及严重程度的效果.方法 前瞻性收集2022年6月至2023年10月于贵州医科大学附属肿瘤医院收治的82例N2～N3期肺癌患者(包括小细胞肺癌和非小细胞肺癌),采用简单随机法按1:1分为试验组(叶酸组)及对照组,两组患者均接受肺部病灶及纵隔转移淋巴结的放射治疗(放疗同期完成≥2个周期一线化疗或分子靶向治疗,接受放疗剂量≥40 Gy,分20次).从两组出现RE开始,每周按美国国家癌症研究所常见不良事件改良分级标准评估RE严重程度,至放疗结束后1周.RE常规处理按照美国肿瘤放射治疗协作组分级标准中的建议进行.叶酸组从放疗开始时口服叶酸至放疗结束,30 mg/d;对照组无药物干预.记录并分析RE的开始时间、程度及持续时间、常规治疗后食管不良反应程度的变化,并测定放疗开始前及放疗结束时患者血清叶酸值、血清维生素B12值及同型半胱氨酸值.对于连续性定量变量,组间比较采用独立样本t检验或独立样本秩和检验.对于计数分类资料,组间比较采用卡方检验或Fisher精确概率法.结果 在观察期间,叶酸组和对照组均未发生4级及以上的RE,0、1、2、3 级 RE 发生率分别为 10％(4/40 例)和 5％(2/41 例)、70％(28/40 例)和 41％(17/41 例)、15％(6/40 例)和51％(21/41例)、5％(2/40例)/和2％(1/41例),差异无统计学意义(P=0.456),但叶酸组0～1级RE的发生率显著高于对照组(Z=2.72,P=0.006).叶酸组和对照组出现RE的中位时间分别为放疗开始后12 d(范围为7～52 d)和15d(范围为11～56 d),差异无统计学意义(x2=-0.75,P=0.456);但个体最严重RE中位持续时间分别为12 d(范围为4～36 d)和21 d(范围为7～38d),差异有统计学意义(x2=2.10,P=0.039).叶酸组在经叶酸干预后的吞咽疼痛及吞咽困难分级均有明显的下降趋势,特别是在RE发生后2周的降低较明显(P=0.001、0.002),且叶酸组在RE发生后的1周缓解率高于对照组,差异有统计学意义(x2=7.36,P=0.012).结论 肺癌同期放化疗期间口服叶酸不能降低RE发生率,但可能降低其严重程度,缩短个体最严重RE的持续时间,具有一定的保护作用.
Abstract
Objective To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis(RE)caused by concurrent chemoradiotherapy.Methods In this randomized,controlled,single-center clinical trial,a total of 82 patients with stage N2-N3 lung cancer including small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC)admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included.All enrolled patients were randomly divided into the experimental group(folic acid group)and control group according to 1 vs.1 of simple random method,and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes[2 cycles of chemotherapy were completed during the same period of radiotherapy(≥40 Gy/20 F)or targeted drugs were given simultaneously].The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy.Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group.Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy,while those in the control group did not receive any drug intervention.The onset time,severity and duration of RE,and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed.Serum folate value,serum vitamin B12 value and homocysteine value were measured before and after radiotherapy.For continuous quantitative variables,independent sample t-test or independent sample rank-sum test was used for comparison among different groups.For categorical data,Chi-square test or Fisher's exact probability method was used for comparison among different groups.Results During the observation period,no grade 4 or above RE was reported between two groups.The incidence of grade 0,1,2 and 3 RE in the folic acid and control groups was 10％(4/40)and 5％(2/41),70％(28/40)and 42％(17/41),15％(6/40)and 51％(21/41),5％(2/40)and 2％(1/41),respectively.The differences were not statistically significant between two groups(P=0.456).However,the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group(Z=2.72,P=0.006).The median time of RE in the folic acid group and control group was 12 d(range 7-52 d)and 15 d(range 11-56 d)after the start of radiotherapy,respectively,with no statistically significant difference(x2=-0.75,P=0.456).However,median duration of the individual's most severe RE was 12 d(range 4-36 d)and 21 d(range 7-38 d)in the folic acid group and control groups,respectively,and the differences were statistically significant(x2=2.10,P=0.039).In the folic acid group,the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention,especially at 2 weeks after the occurrence of RE(P=0.001,P=0.002).The remission rate of RE after 1 week in the folic acid group was higher than that in the control group,and the difference was statistically significant(x2=7.36,P=0.012).Conclusion Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE,but it may reduce its severity,shorten the duration of the most severe RE in individuals,and have a certain protective effect.
维普
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