Cella David, Eton David T, Fairclough Diane L, Bonomi Philip, Heyes Anne E, Silberman Cheryl, Wolf Michael K, Johnson David H
Evanston Northwestern Healthcare & Northwestern University, 1001 University Place, Suite 100, Evanston, IL 60201, USA.
J Clin Epidemiol. 2002 Mar;55(3):285-95. doi: 10.1016/s0895-4356(01)00477-2.
To assess the impact of disease and treatment on patients with advanced non-small cell lung cancer (NSCLC), we set out to determine a clinically meaningful change (CMC) on the Lung Cancer Subscale (LCS) and the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire. We used data from Eastern Cooperative Oncology Group study 5592 (E5592), a randomized trial comparing three chemotherapeutic regimens in 599 advanced NSCLC patients. Patients completed the FACT-L at baseline (pretreatment), 6 weeks, 12 weeks, and 6 months. Comparing across baseline performance status (0 vs. 1), prior weight loss (<5% vs. > or = 5%), and primary disease symptoms (< or = 1 vs. >1), LCS and TOI score differences ranged from 2.4 to 3.6 and 6.5 to 9.2, respectively (all Ps <.001). Mean improvement in LCS score from baseline to 12 weeks was 2.4 points in patients who had responded to treatment versus 0.0 points in patients who had progressive disease. Twelve-week LCS change scores for patients progressing early were 3.1 points worse than those of patients progressing later (mean = -1.2 vs.1.9, respectively). Similarly, the average TOI change score from baseline to 12 weeks was -6.1 for patients who had progressive disease versus -0.8 points for patients who had responded to treatment. Twelve-week TOI change scores for patients progressing early (mean = -8.1) were 5.7 points worse than those of patients progressing later (mean = -8.1 vs. -2.4, respectively). Analyses assuming nonrandom missing data resulted in slightly larger differences. Clinically relevant change scores were estimated as two to three points for the LCS and five to seven points for the TOI, setting upper limits for minimal CMCs. These values were comparable to suggested distribution-based criteria of a minimally important difference. These results support use of a two to three point change in the LCS and five to six point change on the TOI of the FACT-L as a CMC, and offer practical direction for inclusion of important patient-based endpoints in lung cancer clinical trials.
为评估疾病和治疗对晚期非小细胞肺癌（NSCLC）患者的影响，我们着手确定癌症治疗功能评估-肺癌（FACT-L）问卷中肺癌子量表（LCS）和试验结果指数（TOI）具有临床意义的变化（CMC）。我们使用了东部肿瘤协作组5592研究（E5592）的数据，这是一项在599例晚期NSCLC患者中比较三种化疗方案的随机试验。患者在基线（治疗前）、6周、12周和6个月时完成FACT-L问卷。比较基线表现状态（0对1）、既往体重减轻情况（<5%对≥5%）和主要疾病症状（≤1对>1），LCS和TOI得分差异分别为2.4至3.6分和6.5至9.2分（所有P值<0.001）。从基线到12周，治疗有反应的患者LCS得分平均改善2.4分，而疾病进展的患者为0.0分。早期进展患者的12周LCS变化得分比晚期进展患者低3.1分（平均分别为-1.2对1.9）。同样，从基线到12周，疾病进展患者的平均TOI变化得分是-6.1分，而治疗有反应的患者为-0.8分。早期进展患者的12周TOI变化得分（平均=-8.1）比晚期进展患者低5.7分（平均分别为-8.1对-2.4）。假设数据非随机缺失的分析导致差异略大。LCS的临床相关变化得分估计为2至3分，TOI为5至7分，设定了最小CMC的上限。这些值与基于分布的最小重要差异建议标准相当。这些结果支持将FACT-L的LCS中2至3分的变化和TOI中5至6分的变化作为CMC，并为在肺癌临床试验中纳入基于患者的重要终点提供了实际指导。
