Social Epidemiology Research Unit, Social Behavioral Research Branch, National Human Genome Research Institute, National Institute of Health, Bethesda, MD; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX.
Clin Colorectal Cancer. 2020 Mar;19(1):48-56.e2. doi: 10.1016/j.clcc.2019.10.006. Epub 2019 Oct 23.
The survival of patients with metastatic colorectal cancer (mCRC) is influenced by the genetic and epigenetic changes that might influence the patient experience of symptom burden. Understanding the association of molecular changes with the symptom burden could help clinicians gain insight into the molecular basis of symptom burden and improve treatment tolerance. To date, no studies have compared the patient-reported symptom burden with these molecular subsets among patients with mCRC.
We recruited patients with mCRC that was refractory to ≥ 1 line of therapy who had been enrolled in the Assessment of Targeted Therapies Against Colorectal Cancer trial at The University of Texas MD Anderson Cancer Center. All patients completed a baseline gastrointestinal symptom inventory (MD Anderson Symptom Inventory, gastrointestinal). The symptom burden across key demographic variables and molecular changes, including CRC-associated mutations, microsatellite instability (MSI) status, and the CpG island methylator phenotype (CIMP) were compared using χ tests. Association of the symptom burden with overall survival was examined using Cox regression models.
Patients with an MSI-high (MSI-H) phenotype reported greater pain (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.61-5.84), fatigue (OR, 2.78; 95% CI, 1.41-5.49), sleep (OR, 2.52; 95% CI, 1.32-4.08); and drowsiness (OR, 2.51; 95% CI, 1.32-4.78) compared with microsatellite stable patients. Patients with an MSI-H phenotype also had greater odds of overall symptom burden (OR, 2.48; 95% CI, 1.29-4.74) compared with microsatellite stable patients. The CIMP-high patients experienced greater odds of pain compared with the CIMP-negative patients (OR, 1.72; 95% CI, 1.06-2.80). A greater overall symptom burden was associated with poor overall survival (hazard ratio, 1.42; 95% CI, 0.98-2.06]), although the difference was not significant (P = .06).
Correlation of MSI-H-associated tumor features with the symptom burden could help provide a better understanding of underlying mechanisms associated with our findings.
转移性结直肠癌（mCRC）患者的生存受到遗传和表观遗传变化的影响，这些变化可能会影响患者的症状负担体验。了解分子变化与症状负担的关联有助于临床医生深入了解症状负担的分子基础，并提高治疗耐受性。迄今为止，尚无研究比较 mCRC 患者中这些分子亚群与患者报告的症状负担。
我们招募了在德克萨斯大学 MD 安德森癌症中心参加靶向治疗评估结直肠癌试验的难治性 mCRC 患者，这些患者对≥1 线治疗无反应。所有患者均完成基线胃肠道症状量表（MD Anderson 症状量表，胃肠道）。使用 χ 检验比较关键人口统计学变量和分子变化（包括 CRC 相关突变、微卫星不稳定性 (MSI) 状态和 CpG 岛甲基化表型 (CIMP)）之间的症状负担。使用 Cox 回归模型检查症状负担与总生存的关系。
MSI 高（MSI-H）表型的患者报告疼痛（比值比 [OR]，3.06；95%置信区间 [CI]，1.61-5.84）、疲劳（OR，2.78；95% CI，1.41-5.49）、睡眠（OR，2.52；95% CI，1.32-4.08）和嗜睡（OR，2.51；95% CI，1.32-4.78）均高于微卫星稳定患者。MSI-H 表型患者的总症状负担也高于微卫星稳定患者（OR，2.48；95% CI，1.29-4.74）。与 CIMP-阴性患者相比，CIMP 高患者经历疼痛的可能性更大（OR，1.72；95% CI，1.06-2.80）。总体症状负担与总生存不良相关（风险比，1.42；95% CI，0.98-2.06]），尽管差异无统计学意义（P=0.06）。
MSI-H 相关肿瘤特征与症状负担的相关性有助于更好地了解与我们的发现相关的潜在机制。
