Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
SWOG Statistics and Data Management Center, Seattle, WA, USA.
JNCI Cancer Spectr. 2021 Oct 30;5(6). doi: 10.1093/jncics/pkab087. eCollection 2021 Dec.
Almost one-half of aromatase inhibitor (AI)-treated breast cancer patients experience AI-associated musculoskeletal symptoms (AIMSS); 20%-30% discontinue treatment because of severe symptoms. We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from previously conducted trials.
We pooled patient-level data from 3 randomized trials testing interventions (omega-3 fatty acids, acupuncture, and duloxetine) for AIMSS that had similar eligibility criteria and the same patient-reported outcome measures. Only patients with a baseline Brief Pain Inventory average pain score of at least 4 of 10 were included. The primary outcome examined was 2-point reduction in average pain from baseline to week 12. Variable cut-point selection and logistic regression were used. Risk models were built by summing the number of factors statistically significantly associated with pain reduction. Analyses were stratified by study and adjusted for treatment arm.
For the 583 analyzed patients, the 4 factors statistically significantly associated with pain reduction were Functional Assessment of Cancer Therapy Functional Well-Being greater than 24 and Physical Well-Being greater than 14 (higher scores reflect better function), and Western Ontario and McMaster Universities Osteoarthritis Index less than 50 and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands less than 33 (lower scores reflect less pain). Patients with all 4 factors were greater than 6 times more likely to experience at least a 2-point pain reduction (odds ratio = 6.37, 95% confidence interval = 2.31 to 17.53, 2-sided < .001); similar results were found for secondary 30% and 50% pain reduction endpoints.
Patients with AIMSS who have lower symptom and functional distress at study entry on AIMSS intervention trials are more likely to experience meaningful pain reduction. Baseline symptom and functional status should be considered as stratification factors in future interventional trials.
约一半接受芳香化酶抑制剂（AI）治疗的乳腺癌患者出现 AI 相关肌肉骨骼症状（AIMSS）；20%-30%因严重症状而停止治疗。我们假设，通过合并先前进行的试验的数据，我们可以确定 AIMSS 干预试验中疼痛减轻的预测因素。
我们汇集了 3 项随机试验的患者水平数据，这些试验测试了针对 AIMSS 的干预措施（ω-3 脂肪酸、针灸和度洛西汀），这些试验具有相似的入选标准和相同的患者报告结局测量。仅纳入基线Brief Pain Inventory 平均疼痛评分至少为 10 的 4 分的患者。主要结局是从基线到第 12 周平均疼痛降低 2 分。使用变量切点选择和逻辑回归进行分析。通过对与疼痛减轻有统计学显著关联的因素进行求和来构建风险模型。分析按研究分层，并根据治疗组进行调整。
对于分析的 583 名患者，与疼痛减轻有统计学显著关联的 4 个因素是癌症治疗功能评估功能性健康状况评分大于 24 分和身体状况评分大于 14 分（得分越高表示功能越好），以及西部安大略省和麦克马斯特大学骨关节炎指数评分小于 50 分和改良的评估和量化慢性类风湿关节炎手部病变评分小于 33 分（得分越低表示疼痛越轻）。具有所有 4 个因素的患者至少有 2 点疼痛减轻的可能性大于 6 倍（比值比=6.37，95%置信区间=2.31 至 17.53，双侧<.001）；对于次要的 30%和 50%疼痛减轻终点，也得到了类似的结果。
在 AIMSS 干预试验中，研究入组时 AIMSS 相关症状和功能障碍较低的患者更有可能经历有意义的疼痛减轻。在未来的干预试验中，应考虑基线症状和功能状态作为分层因素。
