基于问卷的 PD-1/PD-L1 免疫检查点抑制剂治疗癌症患者免疫相关不良事件的检测。
Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors.
机构信息
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, 91054, Erlangen, Germany.
Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
出版信息
BMC Cancer. 2021 Mar 24;21(1):314. doi: 10.1186/s12885-021-08006-0.
BACKGROUND
Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far.
METHODS
The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE.
RESULTS
Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire.
CONCLUSION
Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.
背景
免疫检查点抑制剂（ICI）已成为不同肿瘤实体的标准治疗方法。然而，安全地使用针对 PD-1/PD-L1 轴的 ICI 治疗需要早期检测免疫相关不良反应（irAE）。目前存在不同制造商的用于检测 irAE 的调查问卷，但尚未得到验证。
方法
前瞻性非干预性 ST-ICI 试验研究了单独使用 PD-1/PD-L1 ICI 或联合放疗的治疗方法。在当前分析中，比较了包含 41 个不同问题的患者问卷中自我报告的 irAE 的检出率与临床医生报告的 irAE。
结果
2017 年 4 月至 2019 年 8 月期间，共前瞻性纳入 104 例患者。非小细胞肺癌（44%）和头颈部鳞状细胞癌（42%）是最常见的肿瘤实体。共收集了 784 份问卷。临床医生报告了 29 例 irAE。最常见的 irAE 是甲状腺功能减退症（9%），其次是皮肤反应（5%）、肝炎（4%）、腹泻（3%）和肺炎（3%）。在临床医生报告 irAE 的时间点，“体重变化”、“难以抓握东西”、“血性或黏液性粪便”和“失眠”等问题的阳性率显著增加。自我报告的器官特异性问题至少可以检测到胃肠道、肺部、内分泌和皮肤 irAE 的 50%的临床医生报告的 irAE。使用问卷无法检测到肝 irAE。
结论
问卷可以帮助检测胃肠道、肺部、内分泌或皮肤 irAE，但不能检测肝 irAE。除了器官特异性问题外，关于“体重变化”和“失眠”的问题可能有助于提高 irAE 的检出率。这些结果为未来开发用于癌症患者在接受 ICI 治疗期间早期自我报告检测 irAE 的特定且实用的问卷提供了有价值的贡献。
试验注册
ClinicalTrials.gov，NCT03453892。于 2018 年 3 月 5 日注册。
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