دورية أكاديمية
Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.
| العنوان: | Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice. |
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| المؤلفون: | Ma SC; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.; Information Management and Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China., Bai X; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Guo XJ; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Liu L; Information Management and Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.; Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China., Xiao LS; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China., Lin Y; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Tan JL; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Cai XT; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Wen YX; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Ma H; Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China., Fu QJ; Department of Community Health, Tufts University, Medford, USA., Leng MX; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Zhang YP; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.; Information Management and Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China., Long LL; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Guo ZQ; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China., Wu DH; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China. 18602062748@163.com., Zhou JG; Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China. jianguo.zhou@yahoo.com.; Department of Radiation Oncology, Universitätsklinikum Erlangen, Erlangen, Germany. jianguo.zhou@yahoo.com.; Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany. jianguo.zhou@yahoo.com., Dong ZY; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China. dongzy1317@foxmail.com. |
| المصدر: | BMC medicine [BMC Med] 2022 Apr 12; Vol. 20 (1), pp. 120. Date of Electronic Publication: 2022 Apr 12. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101190723 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7015 (Electronic) Linking ISSN: 17417015 NLM ISO Abbreviation: BMC Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : BioMed Central, 2003- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung* , Lung Neoplasms*/pathology, B7-H1 Antigen ; Clinical Trials as Topic ; Humans ; Immunotherapy ; Progression-Free Survival |
| مستخلص: | Background: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). Methods: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. Results: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). Conclusions: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC. (© 2022. The Author(s).) |
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| فهرسة مساهمة: | Keywords: Immune checkpoint inhibitor; Metastatic-organ landscape; Non-small cell lung cancer; Programmed death-(ligand) 1 |
| المشرفين على المادة: | 0 (B7-H1 Antigen) |
| تواريخ الأحداث: | Date Created: 20220412 Date Completed: 20220413 Latest Revision: 20220613 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9004108 |
| DOI: | 10.1186/s12916-022-02315-2 |
| PMID: | 35410334 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1741-7015 |
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| DOI: | 10.1186/s12916-022-02315-2 |