Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment

Yifei Ma; Jiling Zeng; Fadian Ding; Yiwei Xu; Youlong Wang; Guanqing Zhong; Nianqi Liu; Yanqi Wang; Yiming Li; Shuqin Chen; Xiaolong Wei; Pengfei Zhu; Guangmin Jian; Yu Si Niu; Guangzhen Fu; Cantong Liu; Guiqiang Li; Xiaotong Zhou; Ao Zhang; Shangeng Weng

doi:10.2967/jnumed.123.267025

Cerebral ¹⁸F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment

J Nucl Med. 2024 May 2:jnumed.123.267025. doi: 10.2967/jnumed.123.267025. Online ahead of print.

Authors

Yifei Ma¹, Jiling Zeng^{2

3}, Fadian Ding¹, Yiwei Xu⁴, Youlong Wang⁵, Guanqing Zhong⁶, Nianqi Liu⁷, Yanqi Wang^{8

9}, Yiming Li¹⁰, Shuqin Chen¹¹, Xiaolong Wei¹¹, Pengfei Zhu¹², Guangmin Jian¹², Yu Si Niu¹³, Guangzhen Fu¹⁴, Cantong Liu⁴, Guiqiang Li⁸, Xiaotong Zhou¹⁵, Ao Zhang^{16

6}, Shangeng Weng¹⁷

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Institute of Abdominal Surgery, Fujian Provincial Key Laboratory of Precision Medicine for Cancer, and Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
² Department of Nuclear Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
³ State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
⁴ Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China.
⁵ Department of General Surgery, Hainan Hospital of People's Liberation Army General Hospital, Sanya, China.
⁶ 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.
⁷ Faculty of Psychology, Institute of Educational Science, Huazhong University of Science and Technology, Wuhan, China.
⁸ Department of Orthopedics and Spine Surgery, Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
⁹ School of Public Health, Shantou University, Shantou, China.
¹⁰ Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University, Beijing, China.
¹¹ Department of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, China.
¹² Department of Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹³ Acute Communicable Disease Epidemiology Division, Dallas County Health and Human Services, Dallas, Texas.
¹⁴ Key Clinical Laboratory of Henan Province, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; and.
¹⁵ Department of Bone and Soft Tissue Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China.
¹⁶ State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China; shangeng@sina.com zhangao@sysucc.org.cn.
¹⁷ Department of Hepatobiliary and Pancreatic Surgery, Institute of Abdominal Surgery, Fujian Provincial Key Laboratory of Precision Medicine for Cancer, and Department of Hepatobiliary and Pancreatic Surgery, National Regional Medical Center Binhai Campus, First Affiliated Hospital of Fujian Medical University, Fuzhou, China; shangeng@sina.com zhangao@sysucc.org.cn.

PMID: 38697671
DOI: 10.2967/jnumed.123.267025

Abstract

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of ¹⁸F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUV_mean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUV_mean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic ¹⁸F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional ¹⁸F-FDG PET/CT SUV_mean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUV_mean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUV_mean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by ¹⁸F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

Keywords: 18F-FDG PET/CT brain imaging; differential diagnosis; immune-related CNS toxicity; immunotherapy; regional metabolism.