Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context
Summary: Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. Methods: This propensity score-matched analysis recruited non-small cell lung c...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-05-01
|
| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023001645 |
| _version_ | 1797837733421383680 |
|---|---|
| author | Yifei Ma Nianqi Liu Yanqi Wang Ao Zhang Zirui Zhu Zhiying Zhang Yiming Li Guangmin Jian Guangzhen Fu Mingming Dong Guoxing Zheng Pengfei Zhu Guanqing Zhong Shenrui Bai Shuqin Chen Xiaolong Wei Jifan Tan Xinjia Wang |
| author_facet | Yifei Ma Nianqi Liu Yanqi Wang Ao Zhang Zirui Zhu Zhiying Zhang Yiming Li Guangmin Jian Guangzhen Fu Mingming Dong Guoxing Zheng Pengfei Zhu Guanqing Zhong Shenrui Bai Shuqin Chen Xiaolong Wei Jifan Tan Xinjia Wang |
| author_sort | Yifei Ma |
| collection | DOAJ |
| description | Summary: Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan–Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE). Findings: Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were −4.26 ± 8.54 (3rd month), −4.72 ± 11.83 (6th month), −6.16 ± 15.41 (9th month), −6.07 ± 15.71 (12th month), and −7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables. Interpretation: ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment. Funding: The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project. |
| first_indexed | 2024-04-09T15:30:33Z |
| format | Article |
| id | doaj.art-cd9abe7d5df346809735cec2d65bd5b9 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-04-09T15:30:33Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-cd9abe7d5df346809735cec2d65bd5b92023-04-28T08:56:16ZengElsevierEClinicalMedicine2589-53702023-05-0159101987Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in contextYifei Ma0Nianqi Liu1Yanqi Wang2Ao Zhang3Zirui Zhu4Zhiying Zhang5Yiming Li6Guangmin Jian7Guangzhen Fu8Mingming Dong9Guoxing Zheng10Pengfei Zhu11Guanqing Zhong12Shenrui Bai13Shuqin Chen14Xiaolong Wei15Jifan Tan16Xinjia Wang17Department of Orthopedics and Spine Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China; Department of Bone and Soft Tissue Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, ChinaFaculty of Psychology, Institute of Educational Science, Huazhong University of Science and Technology, Wuhan, Hubei Province, ChinaDepartment of Bone and Soft Tissue Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China; School of Public Health, Shantou University, Shantou, Guangdong Province, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China; Corresponding author. Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.Department of Thoracic Surgery, Hainan Hospital of People's Liberation Army General Hospital, Sanya, Hainan Province, ChinaDepartment of Bone and Soft Tissue Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China; School of Public Health, Shantou University, Shantou, Guangdong Province, China; Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital Capital Medical University, Beijing, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province, Zhengzhou, Henan Province, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province, Zhengzhou, Henan Province, ChinaDepartment of Bone and Soft Tissue Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, ChinaDepartment of Orthopedics and Spine Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province, Zhengzhou, Henan Province, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, ChinaDepartment of Hematological Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, ChinaDepartment of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, ChinaDepartment of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, ChinaReproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, ChinaDepartment of Orthopedics and Spine Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China; Department of Bone and Soft Tissue Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China; Corresponding author. Department of Orthopedics and Spine Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.Summary: Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan–Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE). Findings: Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were −4.26 ± 8.54 (3rd month), −4.72 ± 11.83 (6th month), −6.16 ± 15.41 (9th month), −6.07 ± 15.71 (12th month), and −7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables. Interpretation: ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment. Funding: The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project.http://www.sciencedirect.com/science/article/pii/S2589537023001645Checkpoint inhibitorCognitive adverse eventsMinimal clinically important differencePropensity score matchingImmune-related adverse events |
| spellingShingle | Yifei Ma Nianqi Liu Yanqi Wang Ao Zhang Zirui Zhu Zhiying Zhang Yiming Li Guangmin Jian Guangzhen Fu Mingming Dong Guoxing Zheng Pengfei Zhu Guanqing Zhong Shenrui Bai Shuqin Chen Xiaolong Wei Jifan Tan Xinjia Wang Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context EClinicalMedicine Checkpoint inhibitor Cognitive adverse events Minimal clinically important difference Propensity score matching Immune-related adverse events |
| title | Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context |
| title_full | Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context |
| title_fullStr | Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context |
| title_full_unstemmed | Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context |
| title_short | Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysisResearch in context |
| title_sort | cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy a propensity score matched analysisresearch in context |
| topic | Checkpoint inhibitor Cognitive adverse events Minimal clinically important difference Propensity score matching Immune-related adverse events |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023001645 |
| work_keys_str_mv | AT yifeima cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT nianqiliu cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT yanqiwang cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT aozhang cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT ziruizhu cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT zhiyingzhang cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT yimingli cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT guangminjian cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT guangzhenfu cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT mingmingdong cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT guoxingzheng cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT pengfeizhu cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT guanqingzhong cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT shenruibai cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT shuqinchen cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT xiaolongwei cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT jifantan cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext AT xinjiawang cognitiveadverseeventsinpatientswithlungcancertreatedwithcheckpointinhibitormonotherapyapropensityscorematchedanalysisresearchincontext |