J Natl Compr Canc Netw. 2018 Dec;16(12):1481-1488. doi: 10.6004/jnccn.2018.7069.
Current toxicity evaluation is primarily focused on high-grade adverse events (AEs) reported by clinicians. However, the cumulative effect of multiple lower-grade AEs may also impact patients' quality of life (QoL). Further, patient-reported toxicity may be more representative of patients' treatment experiences. This study aimed to determine whether cumulative toxicity comprising all-grade AEs is more associated with QoL than cumulative toxicity comprising high-grade AEs only, and whether patient-reported cumulative toxicity is more associated with QoL than clinician-reported cumulative toxicity. Patients with metastatic castration-naïve prostate cancer participating in the phase III GETUG-AFU 15 trial completed questionnaires on AEs (at 3 and 6 months) and QoL (at baseline and 3 and 6 months). Clinicians reported AEs during clinical visits. Cumulative toxicity scores were calculated for clinicians and patients in 3 ways: total number of high-grade AEs, total number of all-grade AEs, and total number of all AEs multiplied by their grade (severity score). Relationships between cumulative toxicity scores and QoL were studied using longitudinal regression analyses; unstandardized (B) and standardized regression coefficients (β) are reported. Of 385 patients, 184 with complete QoL and toxicity data were included. Clinician-reported all-grade AEs (B, -2.2; 95% CI, -3.3 to -1.1; <.01) and severity score (B, -1.4; 95% CI, -2.2 to -0.7; <.01) were associated with deteriorated physical QoL, whereas the total number of high-grade AEs was not. All patient-reported scores were significantly (<.01 for all) associated with deteriorated physical and global QoL. Standardized regression coefficients indicated that patient-reported toxicity scores were more associated with QoL outcomes than clinician-reported scores, with the strongest association found for the all-grade AEs and severity cumulative toxicity scores. Patient- and clinician-based cumulative toxicity scores comprising all-grade AEs better reflect impact on patient QoL than toxicity scores comprising high-grade AEs only. To assess the effect of toxicity on QoL, patient-reported cumulative toxicity scores are preferred.
目前的毒性评估主要集中在临床医生报告的高级别不良事件（AE）上。然而，多种低级别 AE 的累积效应也可能影响患者的生活质量（QoL）。此外，患者报告的毒性可能更能代表患者的治疗体验。本研究旨在确定包含所有级别 AE 的累积毒性是否比仅包含高级别 AE 的累积毒性更能与 QoL 相关，以及患者报告的累积毒性是否比临床医生报告的累积毒性更能与 QoL 相关。 参加 III 期 GETUG-AFU 15 试验的转移性去势敏感前列腺癌患者完成了关于 AE（在 3 个月和 6 个月时）和 QoL（在基线和 3 个月和 6 个月时）的问卷。临床医生在就诊时报告 AE。以三种方式为临床医生和患者计算累积毒性评分：高级别 AE 的总数、所有级别 AE 的总数以及所有 AE 的总数乘以其等级（严重程度评分）。使用纵向回归分析研究累积毒性评分与 QoL 之间的关系；报告未标准化（B）和标准化回归系数（β）。 在 385 名患者中，有 184 名患者具有完整的 QoL 和毒性数据被纳入。临床医生报告的所有级别 AE（B，-2.2；95%CI，-3.3 至-1.1；<.01）和严重程度评分（B，-1.4；95%CI，-2.2 至-0.7；<.01）与身体 QoL 恶化相关，而高级别 AE 的总数则没有。所有患者报告的评分均与身体和全球 QoL 恶化显著相关（所有评分<.01）。标准化回归系数表明，患者报告的毒性评分与 QoL 结果的相关性大于临床医生报告的评分，与所有级别 AE 和严重程度累积毒性评分的相关性最强。 基于患者和临床医生的包含所有级别 AE 的累积毒性评分比仅包含高级别 AE 的毒性评分更能反映对患者 QoL 的影响。为了评估毒性对 QoL 的影响，患者报告的累积毒性评分是首选。
