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Penault-Llorca F, Socinski MA. Emerging molecular testing paradigms in non-small cell lung cancer management-current perspectives and recommendations. Oncologist 2025; 30:oyae357. [PMID: 40126879 PMCID: PMC11966107 DOI: 10.1093/oncolo/oyae357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 11/20/2024] [Indexed: 03/26/2025] Open
Abstract
Advances in molecular testing and precision oncology have transformed the clinical management of lung cancer, especially non-small cell lung cancer, enhancing diagnosis, treatment, and outcomes. Practical guidelines offer insights into selecting appropriate biomarkers and assays, emphasizing the importance of comprehensive testing. However, real-world data reveal the underutilization of biomarker testing and consequently targeted therapies. Molecular testing often occurs late in diagnosis or not at all in clinical practice, leading to delayed or inadequate treatment. Enhancing precision requires adherence to best practices by all health care professionals involved, which can ultimately improve lung cancer patient outcomes. The future of precision oncology for lung cancer will likely involve a more personalized approach, starting increasingly from earlier disease settings, with novel and more complex targeted therapies, immunotherapies, and combination regimens, and relying on liquid biopsies, muti-detection advanced genomic technologies and data integration, with artificial intelligence as a central orchestrator. This review presents the currently known actionable mutations in lung cancer and new upcoming ones that are likely to enter clinical practice soon and provides an overview of established and emerging concepts in testing methodologies. Challenges are discussed and best practice recommendations are made that are relevant today, will continue to be relevant in the future, and are likely to be relevant for other cancer types too.
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Affiliation(s)
- Frédérique Penault-Llorca
- Department of Pathology, Centre Jean Perrin, Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Clermont Ferrand F-63000, France
| | - Mark A Socinski
- Oncology and Hematology, AdventHealth Cancer Institute, Orlando, FL 32804, United States
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Wang L, Zheng G, Hu Y, Maolan A, Luo Y, Li Y, Liu R. Comparative efficacy and safety of first-line neoadjuvant therapy for early-stage non-small cell lung cancer based on immune checkpoint inhibitor therapy: a systematic review and network meta-analysis. BMC Pulm Med 2025; 25:49. [PMID: 39885491 PMCID: PMC11781062 DOI: 10.1186/s12890-025-03479-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 01/02/2025] [Indexed: 02/01/2025] Open
Abstract
INTRODUCTION Although there are a number of neoadjuvant immunotherapy combinations that can be applied to the treatment of perioperative non-small cell lung cancer patients, the optimal treatment combination strategy has not yet been determined. METHODS We searched PubMed, EMBASE, Cochrane Library, ClinicalTrials.go and randomised controlled trials (RCTs) from major international conferences for literature related to neoadjuvant immunotherapy combinations published as first-line treatment options for non-small cell lung cancer from the start of the library to 20 February 2024, and performed a systematic review and network meta-analysis. RESULTS We analyzed nine studies involving 3431 patients, including eight perioperative neoadjuvant immunotherapy combinations for non-small cell lung cancer. For patients without programmed death-ligand 1(PD-L1) selection, Toripalimab plus chemotherapy provided the best Pathological complete response (PCR) benefit (OR = 32.89,95% CI:7.88-137.32), best Major Pathological response (MPR) benefit (OR = 10.25, 95% CI: 5.81-18.10) and best Event-free survival (EFS) benefit (HR = 0.40,95% CI: 0.28-0.57). Nivolumab plus chemotherapy provided the best surgical resection rate (OR = 1.71, 95% CI:0.87-3.40) and pembrolizumab plus chemotherapy provided the best R0 surgical resection rate (OR = 2.20, 95% CI:1.28-3.79). In contrast, the combination of ipilimumab, nivolumab and chemotherapy, and the combination of toripalimab and chemotherapy were associated with the lowest incidence of adverse events of grade 3 or above during neoadjuvant therapy. CONCLUSIONS Our findings suggest that: Toripalimab plus chemotherapy showed better neoadjuvant efficacy and may have an overall survival benefit, but also increased the incidence of serious adverse events during neoadjuvant therapy.
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Affiliation(s)
- Linfeng Wang
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Guangda Zheng
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Yue Hu
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Ayidana Maolan
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Yue Luo
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Yue Li
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Rui Liu
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
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Zhang Q, Duan J, Zhang Y, Yang L, Li D. Perioperative or neo/adjuvant chemoimmunotherapy versus chemotherapy for resectable non-small cell lung cancer: a systematic review and network meta-analysis. Syst Rev 2025; 14:24. [PMID: 39856765 PMCID: PMC11760710 DOI: 10.1186/s13643-025-02767-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 01/12/2025] [Indexed: 01/27/2025] Open
Abstract
INTRODUCTION Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths globally. Despite surgery being the main treatment for resectable NSCLC, many patients experience postoperative recurrence. Neoadjuvant chemotherapy may shrink tumors and improve surgical outcomes, while adjuvant chemotherapy targets residual disease post-surgery. Recent advancements in immunotherapy have introduced its use in the perioperative phase for resectable NSCLC. This study investigates the relative benefits and potential complications of neoadjuvant, adjuvant, and perioperative immunotherapy combined with chemotherapy compared to chemotherapy alone, focusing on event-free survival (EFS), overall survival (OS), and adverse events (AEs). METHODS This systematic review and network meta-analysis followed PRISMA guidelines and was registered with PROSPERO. The authors searched PUBMED, Embase, and Cochrane databases for randomized controlled trials (RCTs) involving patients with resectable NSCLC treated with neoadjuvant/adjuvant immunotherapy or chemotherapy. Statistical analyses were performed using a frequentist network meta-analysis method in R software. RESULTS From an initial 5902 articles, 13 RCTs involving 6704 patients were included after extensive filtering. PFS: Neoadjuvant and perioperative immunotherapy combined with chemotherapy showed significant benefits compared to chemotherapy alone. OS: Perioperative immunotherapy was notably more effective than adjuvant immunotherapy and standard chemotherapy. Chemotherapy generally had fewer severe adverse effects compared to neoadjuvant and perioperative immunotherapy. However, these immunotherapy combinations are generally well tolerated. CONCLUSIONS The findings indicate that neoadjuvant and perioperative immunotherapy combined with chemotherapy can significantly improve overall survival in patients with resectable NSCLC compared to standard chemotherapy. However, additional adverse effects associated with long-term immunotherapy require careful management. The lack of significant benefits in specific subgroups suggests a need for further research. The study stresses the importance of optimizing treatment strategies and potentially reassessing immunotherapy's role in certain patient populations. Future clinical trials are anticipated to clarify these results further.
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Affiliation(s)
- Qiong Zhang
- Department of Geriatrics, Neijiang First People's Hospital, , Sichuan Province, Neijiang, China
| | - Jia Duan
- Department of Intensive Care Medicine, Neijiang Hospital of Traditional Chinese Medicine, Neijiang, Sichuan Province, China
| | - Yuanmei Zhang
- Department of Geriatrics, Neijiang First People's Hospital, , Sichuan Province, Neijiang, China
| | - Lei Yang
- Department of Geriatrics, Neijiang First People's Hospital, , Sichuan Province, Neijiang, China.
| | - Duo Li
- Department of Nosocomial Infection Management, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, 646000, China.
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Chen Y, Qi F, Sun C, Jiang P, Xue X, Yang X, Li X, He X, Wang Y, Zhang T. Navigating the landscape of neoadjuvant immunotherapy for NSCLC: progress and controversies. Ther Adv Med Oncol 2025; 17:17588359241312501. [PMID: 39781239 PMCID: PMC11707791 DOI: 10.1177/17588359241312501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 12/18/2024] [Indexed: 01/12/2025] Open
Abstract
Recently, attention has increasingly centered on non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors application. Numerous clinical studies have underscored the potential of immunotherapy in treating resectable NSCLC, highlighting its role in improving patient outcomes. However, despite these promising results, there is ongoing debate regarding the efficacy of immunological combination therapy strategies, the prevalence of treatment-related side effects, the identification of predictive biomarkers, and various other challenges within the neoadjuvant context. Careful consideration is essential to maximize the benefits of immunotherapy for patients with resectable NSCLC. This article offers a detailed overview of recent advancements in neoadjuvant immunotherapy for resectable NSCLC. By examining these developments, we aim to provide new perspectives and valuable insights into the benefits and challenges of applying neoadjuvant immunotherapy in clinical settings.
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Affiliation(s)
- Yuzhu Chen
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
| | - Fei Qi
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
| | - Chenhao Sun
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Peng Jiang
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Xiangyu Xue
- Department of Biochemistry and Molecular Biology, Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University, Harbin, China
| | - Xiaomei Yang
- Beijing Key Laboratory for Tumor Invasion and Metastasis, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China
- Joint Laboratory for Precision Diagnosis and Treatment Translational Research in Malignant Tumors, Gynecologic Oncology Basic and Clinical Research Laboratory, Capital Medical University, Beijing, China
| | - Xiaomi Li
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Xin He
- Department of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Yishuo Wang
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
| | - Tongmei Zhang
- Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 9 Beiguan Street, Tongzhou District, Beijing 101149, China
- Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
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Yan Y, Sun D, Hu J, Chen Y, Sun L, Yu H, Xiong Y, Huang Z, Xia H, Zhu X, Bian D, Sun F, Hou L, Wu C, Fan OR, Hu H, Zeng A, Zhang L, Sun YE, Wang C, Zhang P. Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer. Nat Genet 2025; 57:126-139. [PMID: 39658657 DOI: 10.1038/s41588-024-01998-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 10/18/2024] [Indexed: 12/12/2024]
Abstract
Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB-chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis. We also reveal distinct states of tertiary lymphoid structures (TLSs) in the TME. Activated TLSs are associated with improved prognosis, whereas a hypoxic microenvironment appears to suppress TLS development and is associated with poor prognosis. Our study provides novel insights into different cellular and molecular components corresponding to NSCLC ICB-chemotherapeutic responsiveness, which will benefit future individualized immuno-chemotherapy.
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Affiliation(s)
- Yilv Yan
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Dongqing Sun
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Junjie Hu
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yue Chen
- State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
| | - Liangdong Sun
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Huansha Yu
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yicheng Xiong
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zhida Huang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Haoran Xia
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xinsheng Zhu
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Dongliang Bian
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Fenghuan Sun
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Likun Hou
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chunyan Wu
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Orion R Fan
- Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Haiyang Hu
- Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - An Zeng
- State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
| | - Lele Zhang
- Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
| | - Yi Eve Sun
- Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
| | - Chenfei Wang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
- National Key Laboratory of Autonomous Intelligent Unmanned Systems, Tongji University, Shanghai, China.
- Frontier Science Center for Intelligent Autonomous Systems, Tongji University, Shanghai, China.
| | - Peng Zhang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
- Department of Thoracic Surgery, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China.
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Yu Y, Chen H, Huang Z, Yuan Z, Liu L, Zhao J, Wei Q. Anti-PD-(L)1-Based Neoadjuvant Therapy in Head and Neck Carcinoma: a Meta-analysis of Prospective Clinical Trials. Otolaryngol Head Neck Surg 2024; 171:1321-1340. [PMID: 38943451 DOI: 10.1002/ohn.867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 04/02/2024] [Accepted: 06/03/2024] [Indexed: 07/01/2024]
Abstract
OBJECTIVE This meta-analysis aims to evaluate the efficacy and safety of antiprogressive disease (PD)-(L)1-based neoadjuvant therapy in head and neck squamous cell carcinoma (HNSCC) patients and identify potential prognostic biomarkers. DATA SOURCES Databases were systematically searched for prospective clinical trials evaluating the efficacy and safety of anti-PD-(L)1-based neoadjuvant therapy for HNSCC before January 12, 2024. REVIEW METHODS We estimated the efficacy and safety of neoadjuvant immune checkpoint inhibitors. Subgroup and sensitivity analyses were further performed. RESULTS A total of 570 patients from 20 studies were included. The pooled major pathological response (MPR), pathological complete response (pCR), and partial pathological response (PPR) rates were 30.7%, 15.3%, and 68.2%, respectively. Surgical complications, surgical delayed rate, all grade treatment-related adverse effects (TRAEs) and ≥Grade 3 TRAEs were 0.6%, 0.3%, 82.6%, and 9.7%, respectively. Best MPR or pCR rate was detected in patients receiving neoadjuvant anti-PD-(L)1 therapy + radiotherapy (with MPR rate of 75.5% and pCR rate of 51.1%) and neoadjuvant anti-PD-(L)1 therapy + chemotherapy groups (with MPR rate of 57.5% and pCR rate of 26.7%). No differences were detected in subgroups stratified by neoadjuvant treatment cycles, human papillomavirus (HPV) status, and tumor location. Patients with baseline Combined Positive Score (CPS) ≥ 20 have higher MPR and pCR rates compared to patients with CPS < 20. High Tumor Cell Proportion Score was also associated with MPR and pCR. Objective response rate is a strong predictor of MPR (odds ratio [OR] = 7.78, 95% confidence interval [CI] = 3.20%-18.91%) and pCR (OR = 3.24, 95% CI = 1.40%-7.48%). CONCLUSION Anti-PD-(L)1-based neoadjuvant therapy was effective and safe for HNSCC patients.
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Affiliation(s)
- Yaner Yu
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Clinical Research Center for Cancer, Cancer Center of Zhejiang University, Hangzhou, China
| | - Haiyan Chen
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Clinical Research Center for Cancer, Cancer Center of Zhejiang University, Hangzhou, China
| | - Zhifei Huang
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Zhijun Yuan
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Clinical Research Center for Cancer, Cancer Center of Zhejiang University, Hangzhou, China
| | - Lihong Liu
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Clinical Research Center for Cancer, Cancer Center of Zhejiang University, Hangzhou, China
| | - Jian Zhao
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Qichun Wei
- Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Clinical Research Center for Cancer, Cancer Center of Zhejiang University, Hangzhou, China
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Li Z, Wu L, Wang C, Wang S, Chen Q, He W. Outcomes After Neoadjuvant Therapy With or Without Immunotherapy Followed By Pneumonectomy in Non-Small Cell Lung Cancer Patients. Ann Thorac Surg 2024:S0003-4975(24)00879-8. [PMID: 39490501 DOI: 10.1016/j.athoracsur.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/24/2024] [Accepted: 10/07/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND There are limited data concerning pneumonectomy after preoperative induction therapy. Our study aimed to evaluate feasibility and safety of pneumonectomy after neoadjuvant immunotherapy in patients with non-small cell lung cancer by assessing postoperative outcomes. METHODS A total of 1187 patients who underwent pneumonectomy for non-small cell lung cancer were retrospectively analyzed from 3 hospitals in China. Propensity score matching was adopted to form a balanced cohort between neoadjuvant therapy and non-neoadjuvant therapy groups. Univariable and multivariable logistic regression analyses were used to identify risk factors for postoperative morbidity. Efficacy and survival were compared for neoadjuvant therapy with or without immunotherapy. RESULTS The neoadjuvant group had larger tumors (4.7 ± 2.2 cm vs 3.9 ± 1.9 cm [P < .001]; cT4, 36.3% vs 19.1% [P < .001]), had a greater rate of N2 metastases (64.5% vs 33.3%; P < .001), and were at a more advanced clinical TNM stage (stage III, 89.4% vs 58.6%; P < .001). No significant difference in postoperative morbidity was observed between the groups before and after propensity score matching (43.5% vs 42.9% [P = .975]; 49.4% vs 41.9% [P = .162]). The complete pathologic response rate of neoadjuvant chemoimmunotherapy was significantly superior to that of chemotherapy alone (27.7% vs 2.0%; P < .001), and no significant difference in postoperative morbidity was observed in neoadjuvant therapy with or without immunotherapy. The neoadjuvant chemoimmunotherapy group also obtained a survival benefit with a 3-year overall survival (79.8% vs 67.5%; P = .001) and a 3-year event-free survival (63.3% vs 41.2%; P = .004). CONCLUSIONS After neoadjuvant therapy with immunotherapy, pneumonectomy can be safely performed in selected patients without increased postoperative morbidity.
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Affiliation(s)
- Zhixin Li
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Leilei Wu
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chong Wang
- Minimally Invasive Treatment Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Shaodong Wang
- Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
| | - Qiankun Chen
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Wenxin He
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
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Li YN, Su JL, Tan SH, Chen XL, Cheng TL, Jiang Z, Luo YZ, Zhang LM. Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy. World J Clin Cases 2024; 12:4091-4107. [PMID: 39015934 PMCID: PMC11235537 DOI: 10.12998/wjcc.v12.i20.4091] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 05/10/2024] [Accepted: 05/28/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.
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Affiliation(s)
- Yu-Ning Li
- School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, Hunan Province, China
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
| | - Jia-Lin Su
- School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, Hunan Province, China
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
| | - Shu-Hua Tan
- School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, Hunan Province, China
| | - Xing-Long Chen
- School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, Hunan Province, China
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
| | - Tian-Li Cheng
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
| | - Zhou Jiang
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
| | - Yong-Zhong Luo
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
| | - Le-Meng Zhang
- Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410013, Hunan Province, China
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Adugna A, Muche Y, Jemal M, Habtegiorgis SD, Belew H, Azanaw Amare G. Gut microbes as medical signature for the effectiveness of immunotherapy in patients with advanced non-small cell lung cancer. Aging Med (Milton) 2024; 7:121-130. [PMID: 38571678 PMCID: PMC10985778 DOI: 10.1002/agm2.12292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 04/05/2024] Open
Abstract
Lung cancer (LC) is the most common cause of cancer-related death worldwide and poses a severe threat to public health. Immunotherapy with checkpoint blockers has improved the outlook for advanced non-small cell lung cancer (NSCLC) therapy. For the treatment of patients with advanced NSCLC, antibodies such as anti-programmed death 1 (anti-PD1), anti-programmed death ligand 1 (anti-PD-L1), and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) are of paramount importance. Anti-PD-1 and anti-PD-L1 monoclonal antibody therapies are used to block the PD-1/PD-L1 pathway and identify cancerous cells to the body's defenses. Antibodies directed against CTLA-4 (anti-CTLA-4) have also been shown to improve survival rates in patients with NSCLC. Currently, other immunotherapy approaches like neoadjuvant immune checkpoint inhibitors (NAICIs) and chimeric antigen receptor T-cell (CAR-T) therapies are applied in NSCLC patients. NAICIs are used for resectable and early stage NSCLC and CAR-T is used to find more useful epitope sites for lung tumors and destroy cancer cells. A patient's gut microbiota might influence how their immune system reacts to NSCLC immunotherapy. The majority of intestinal microbes stimulate helper/cytotoxic T cells, induce natural killer (NK) cells, activate various toll-like receptors (TLR), build up cluster of differentiation 8 (CD8), increase PD-1 production, and attract chemokine receptors towards cancer cells. Thus, they serve as immune inducers in NSCLC immunotherapy. Nonetheless, certain bacteria can function as immune suppressors by inhibiting DC proliferation, stopping CD28 trafficking, restoring CD80/CD86, increasing immunological tolerance, and upsetting Th17 cells. Therefore, they are prevalent in non-responders with NSCLC immunotherapy.
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Affiliation(s)
- Adane Adugna
- Medical Laboratory Sciences, College of Health SciencesDebre Markos UniversityDebre MarkosEthiopia
| | - Yalew Muche
- Medical Laboratory Sciences, College of Health SciencesDebre Markos UniversityDebre MarkosEthiopia
| | - Mohammed Jemal
- Department of Biomedical Sciences, School of Medicine, College of Health SciencesDebre Markos UniversityDebre MarkosEthiopia
| | | | - Habtamu Belew
- Medical Laboratory Sciences, College of Health SciencesDebre Markos UniversityDebre MarkosEthiopia
| | - Gashaw Azanaw Amare
- Medical Laboratory Sciences, College of Health SciencesDebre Markos UniversityDebre MarkosEthiopia
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10
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Feng Y, Guo K, Jin H, Jiang J, Wang M, Lin S. Adverse events of neoadjuvant combination immunotherapy for resectable cancer patients: a systematic review and meta-analysis. Front Immunol 2024; 14:1269067. [PMID: 38250059 PMCID: PMC10796654 DOI: 10.3389/fimmu.2023.1269067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Accepted: 12/18/2023] [Indexed: 01/23/2024] Open
Abstract
Background Neoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations. Methods This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model. Results Sixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle. Conclusion This study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier CRD42023387969.
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Affiliation(s)
- Yuqian Feng
- Hangzhou School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Kaibo Guo
- Department of Oncology, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, China
| | - Huimin Jin
- Department of Oncology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jing Jiang
- The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Menglei Wang
- The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Shengyou Lin
- Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
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11
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Wu Y, Hu L, Zhang S, Zhang H. The Value of Perioperative Immunotherapy for Non-Small Cell Lung Cancer: A Pool- and Meta-Analysis. Technol Cancer Res Treat 2024; 23:15330338241258164. [PMID: 38872482 PMCID: PMC11179512 DOI: 10.1177/15330338241258164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 04/21/2024] [Accepted: 04/23/2024] [Indexed: 06/15/2024] Open
Abstract
Purpose: This study aimed to analyze the efficacy and safety of neoadjuvant and adjuvant immunotherapies for non-small cell lung cancer (NSCLC). Methods: Electronic literature searches were conducted in PubMed, OVID, Web of SCI, Embase, Cochrane Library, and the Chinese National Knowledge Infrastructure databases. The deadline for literature update and retrieval is February 16, 2024. Studies presented at meetings were also screened. Randomized controlled trials (RCTs) and single-arm trials were included, and the data were extracted according to the inclusion and exclusion criteria. Data analysis was performed using Stata (16.0) software. Results: A total of 5850 patients in 11 RCTs and 6 single-arm trial studies involving neoadjuvant and/or adjuvant immune checkpoint inhibitor (ICI)-based therapies were included. Regarding neoadjuvant therapy, the overall complication rate after surgery reached 35% (95% CI, 0.21-0.49). Higher rates of pathological complete response (OR = 7.83; 95% CI, 5.95-10.31; P < .001) and major pathological response (OR = 5.13; 95% CI, 3.56-7.40; P < .001) were found in the resectable NSCLC patients who received neoadjuvant therapy with ICIs combined with chemotherapy compared with patients treated with chemotherapy alone. Of note, compared with chemotherapy, neoadjuvant ICIs combined with chemotherapy significantly improved the overall survival (OS) (HR = 0.65; 95% CI, 0.52-0.82; P < .001) and event-free survival (EFS) (HR = 0.59; 95% CI, 0.52-0.67; P < .001) in patients with resectable NSCLC. Regarding adjuvant therapy, a lower risk of disease progression or death (HR = 0.78; 95% CI, 0.69-0.90; P < .001) was found in the adjuvant ICI group compared with the adjuvant chemotherapy-alone group. In terms of safety, perioperative immunotherapy combined with chemotherapy did not increase toxicity compared with chemotherapy alone. Conclusion: In patients with resectable NSCLC, perioperative immunotherapy was safe and efficacious. Perioperative immunotherapy combined with chemotherapy improved the pathologic response and EFS/DFS/OS over chemotherapy alone without increasing toxicity.
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Affiliation(s)
- Yanmeng Wu
- China Medical University, Shenyang, China
| | - Lin Hu
- China Medical University, Shenyang, China
| | - Shuling Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hui Zhang
- Traditional Chinese Medicine Department, Shengjing Hospital of China Medical University, Shenyang, China
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12
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Jachowski A, Marcinkowski M, Szydłowski J, Grabarczyk O, Nogaj Z, Marcin Ł, Pławski A, Jagodziński PP, Słowikowski BK. Modern therapies of nonsmall cell lung cancer. J Appl Genet 2023; 64:695-711. [PMID: 37698765 PMCID: PMC10632224 DOI: 10.1007/s13353-023-00786-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/01/2023] [Accepted: 09/01/2023] [Indexed: 09/13/2023]
Abstract
Lung cancer (LC), particularly nonsmall cell lung cancer (NSCLC), is one of the most prevalent types of neoplasia worldwide, regardless of gender, with the highest mortality rates in oncology. Over the years, treatment for NSCLC has evolved from conventional surgery, chemotherapy, and radiotherapy to more tailored and minimally invasive approaches. The use of personalised therapies has increased the expected efficacy of treatment while simultaneously reducing the frequency of severe adverse effects (AEs). In this review, we discuss established modern approaches, including immunotherapy and targeted therapy, as well as experimental molecular methods like clustered regularly interspaced short palindromic repeat (CRISPR) and nanoparticles. These emerging methods offer promising outcomes and shorten the recovery time for various patients. Recent advances in the diagnostic field, including imaging and genetic profiling, have enabled the implementation of these methods. The versatility of these modern therapies allows for multiple treatment options, such as single-agent use, combination with existing conventional treatments, or incorporation into new regimens. As a result, patients can survive even in the advanced stages of NSCLC, leading to increased survival indicators such as overall survival (OS) and progression-free survival (PFS).
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Affiliation(s)
- Andrzej Jachowski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Mikołaj Marcinkowski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Jakub Szydłowski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Oskar Grabarczyk
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Zuzanna Nogaj
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Łaz Marcin
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Andrzej Pławski
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32 Street, 60-479, Poznań, Poland
| | - Paweł Piotr Jagodziński
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland
| | - Bartosz Kazimierz Słowikowski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Święcickiego 6 Street, 60-781, Poznań, Poland.
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13
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Sponholz S, Koch A, Mese M, Becker S, Sebastian M, Fischer S, Trainer S, Schreiner W. Lung Cancer Resection after Immunochemotherapy Versus Chemotherapy in Oligometastatic Nonsmall Cell Lung Cancer. Thorac Cardiovasc Surg 2023; 71:656-663. [PMID: 36746400 DOI: 10.1055/a-2028-7955] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Neoadjuvant immunochemotherapy is currently being tested in pivotal trials for stage I to III nonsmall cell lung cancer (NSCLC). The impact of immunochemotherapy in patients with oligometastatic disease (OMD) remains undefined. This study aimed to compare the outcomes of radical treatment after the neoadjuvant course of immunochemotherapy versus chemotherapy. METHODS We retrospectively analyzed patients with OMD who were treated with immunochemotherapy or chemotherapy combined with local ablation of metastases and radical primary tumor resection between 2017 and 2021. Group A included eight patients with immunochemotherapy; Group B included seven patients with chemotherapy. Descriptive statistical analysis included the characteristics of the patients, tumors, and outcomes. RESULTS There was no difference in postoperative morbidity rates between the groups (p = 0.626). The 30-day mortality in both groups was 0%. The median overall survival for Group A was not reached, with a median follow-up time of 25 (range: 13-35) months; the median overall survival for Group B was 26 (range: 5-53) months. In Group A, all patients remained alive; in contrast, in Group B, four patients died (p = 0.026). There was no local thoracic recurrence in either group. In Group B, the recurrent disease was identified significantly more often (12.5 vs. 85.75%; p = 0.009). The rates of complete and major pathologic response were 37.5 and 0% in Group A and 42.85 and 14.25% in Group B, respectively. CONCLUSION Despite the small patient number and short-term results, the progression-free and overall survival in patients with OMD after local therapy for metastases and primary tumor resection following a neoadjuvant course of immunochemotherapy might be promising compared with chemotherapy.
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Affiliation(s)
- Stefan Sponholz
- Department of Thoracic Surgery, Agaplesion Markus Krankenhaus Frankfurt, Frankfurt, Germany
| | - Agnes Koch
- Department of Thoracic Surgery, Agaplesion Markus Krankenhaus Frankfurt, Frankfurt, Germany
| | - Mesut Mese
- Department of Thoracic Surgery, Agaplesion Markus Krankenhaus Frankfurt, Frankfurt, Germany
| | - Silvan Becker
- Department of Oncology, Agaplesion Markus Krankenhaus Frankfurt, Frankfurt, Germany
| | - Martin Sebastian
- Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Frankfurt, Germany
- German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany
- Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany
| | | | - Stephan Trainer
- Department of Thoracic Surgery, Agaplesion Markus Krankenhaus Frankfurt, Frankfurt, Germany
| | - Waldemar Schreiner
- Department of Thoracic Surgery, University Hospital Frankfurt, Frankfurt, Germany
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14
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Jin W, Tian Y, Xuzhang W, Zhu H, Zou N, Shen L, Dong C, Yang Q, Jiang L, Huang J, Yuan Z, Ye X, Luo Q. Non-linear modifications enhance prediction of pathological response to pre-operative PD-1 blockade in lung cancer: A longitudinal hybrid radiological model. Pharmacol Res 2023; 198:106992. [PMID: 37977237 DOI: 10.1016/j.phrs.2023.106992] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/29/2023] [Accepted: 11/13/2023] [Indexed: 11/19/2023]
Abstract
Major pathologic remission (MPR, residual tumor <10%) is a promising clinical endpoint for prognosis analysis in patients with lung cancer receiving pre-operative PD-1 blockade therapy. Most of the current biomarkers for predicting MPR such as PD-L1 and tumor mutation burden (TMB) need to be obtained invasively. They cannot overcome the spatiotemporal heterogeneity or provide dynamic monitoring solutions. Radiomics and artificial intelligence (AI) models provide a practical tool enabling non-invasive follow-up observation of tumor structural information through high-throughput data analysis. Currently, AI-based models mainly focus on the single baseline scan or pipeline, namely sole radiomics or deep learning (DL). This work merged the delta-radiomics based on the slope of classic radiomics indexes within a time interval and the features extracted by deep networks from the subtraction between the baseline and follow-up images. The subtracted images describing the tumor changes were based on the transformation generated by registration. Stepwise optimization of components was performed by repeating experiments among various combinations of DL networks, registration methods, feature selection algorithms, and classifiers. The optimized model could predict MPR with a cross-validation AUC of 0.91 and an external validation AUC of 0.85. A core set of 27 features (eight classic radiomics, 15 delta-radiomics, one classic DL features, and three delta-DL features) was identified. The changes in delta-radiomics indexes during the treatment were fitted with mathematic models. The fitting results revealed that over half of the features were of non-linear dynamics. Therefore, non-linear modifications were made on eight features by replacing the original features with non-linear fitting parameters, and the modified model achieved an improved power. The dynamic hybrid model serves as a novel and promising tool to predict the response of lesions to PD-1 blockade, which implies the importance of introducing the non-linear dynamic effects and DL approaches to the original delta-radiomics in the future.
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Affiliation(s)
- Weiqiu Jin
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Yu Tian
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Wendi Xuzhang
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Hongda Zhu
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Ningyuan Zou
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Leilei Shen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Institute of Medical Imaging, Shanghai 200032, China; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Changzi Dong
- Department of Bioengineering, School of Engineering and Science, University of Pennsylvania, Philadelphia 19104, USA
| | - Qisheng Yang
- School of Integrated Circuits & Beijing National Research on Information Science and Technology (BNRist), Tsinghua University, Beijing 100084, China
| | - Long Jiang
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Jia Huang
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
| | - Zheng Yuan
- Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
| | - Xiaodan Ye
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Institute of Medical Imaging, Shanghai 200032, China; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
| | - Qingquan Luo
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
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15
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Yang N, Yue H, Zhang B, Chen J, Chu Q, Wang J, Yu X, Jian L, Bin Y, Liu S, Liu J, Zeng L, Yang H, Zhou C, Jiang W, Liu L, Zhang Y, Xiong Y, Wang Z. Predicting pathological response to neoadjuvant or conversion chemoimmunotherapy in stage IB-III non-small cell lung cancer patients using radiomic features. Thorac Cancer 2023; 14:2869-2876. [PMID: 37596822 PMCID: PMC10542462 DOI: 10.1111/1759-7714.15052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 07/12/2023] [Accepted: 07/14/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND To develop a radiomics model based on chest computed tomography (CT) for the prediction of a pathological complete response (pCR) after neoadjuvant or conversion chemoimmunotherapy (CIT) in patients with non-small cell lung cancer (NSCLC). METHODS Patients with stage IB-III NSCLC who received neoadjuvant or conversion CIT between September 2019 and July 2021 at Hunan Cancer Hospital, Xiangya Hospital, and Union Hospital were retrospectively collected. The least absolute shrinkage and selection operator (LASSO) were used to screen features. Then, model 1 (five radiomics features before CIT), model 2 (four radiomics features after CIT and before surgery) and model 3 were constructed for the prediction of pCR. Model 3 included all nine features of model 1 and 2 and was later named the neoadjuvant chemoimmunotherapy-related pathological response prediction model (NACIP). RESULTS This study included 110 patients: 77 in the training set and 33 in the validation set. Thirty-nine (35.5%) patients achieved a pCR. Model 1 showed area under the curve (AUC) = 0.65, 64% accuracy, 71% specificity, and 50% sensitivity, while model 2 displayed AUC = 0.81, 73% accuracy, 62% specificity, and 92% sensitivity. In comparison, NACIP yielded a good predictive value, with an AUC of 0.85, 81% accuracy, 81% specificity, and 83% sensitivity in the validation set. CONCLUSION NACIP may be a potential model for the early prediction of pCR in patients with NSCLC treated with neoadjuvant/conversion CIT.
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Affiliation(s)
- Nong Yang
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
- Lung Cancer and Gastrointestinal Unit, Department of Medical Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
| | - Hai‐Lin Yue
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Bai‐Hua Zhang
- Department of Thoracic SurgeryHunan Cancer HospitalChangshaChina
| | - Juan Chen
- Department of Pharmacy, Xiangya HospitalCentral South UniversityChangshaChina
| | - Qian Chu
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Jian‐Xin Wang
- Lung Cancer and Gastrointestinal Unit, Department of Medical Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
| | - Xiao‐Ping Yu
- Department of Diagnostic Radiology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
| | - Lian Jian
- Department of Diagnostic Radiology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
| | - Ya‐Wen Bin
- Cancer Center, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Si‐Ye Liu
- Department of Diagnostic Radiology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
| | - Jin Liu
- Lung Cancer and Gastrointestinal Unit, Department of Medical Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
| | - Liang Zeng
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Hai‐Yan Yang
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Chun‐Hua Zhou
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Wen‐Juan Jiang
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Li Liu
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Yong‐Chang Zhang
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Yi Xiong
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
| | - Zhan Wang
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and EngineeringCentral South UniversityChangshaChina
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16
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Yin C, Hu B, Yang X, Kou L, Tian B, Wang C, Li S, Liu B, Ge J. Neoadjuvant sintilimab combined with chemotherapy in resectable locally advanced non-small cell lung cancer: case series and literature review. World J Surg Oncol 2023; 21:304. [PMID: 37749594 PMCID: PMC10521519 DOI: 10.1186/s12957-023-03194-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 09/19/2023] [Indexed: 09/27/2023] Open
Abstract
BACKGROUND In recent years, neoadjuvant immunotherapy with chemotherapy has shown increasing promise for locally advanced non-small cell lung cancer (NSCLC). However, to establish its clinical efficacy and safety, it is imperative to amass more real-world clinical data. This retrospective study aims to assess the safety and effectiveness of combing sintilimab, a PD-1 inhibitor, with chemotherapy as a neoadjuvant treatment modality in patients diagnosed with potentially resectable NSCLC. METHODS We retrospectively reviewed patients with stage II-III NSCLC receiving neoadjuvant chemoimmunotherapy in Sichuan Cancer Hospital between February 2021 and February 2023. Sintilimab injection (intravenously,200 mg, iv, d1, q3w) and platinum-based chemotherapy were administered intravenously every 3 weeks, with radical lung cancer resection planned approximately 4-11 weeks after the last dose. The primary endpoint of the study was pathologic complete response (pCR). The secondary endpoints were objective response rate (ORR), and safety. RESULT Thirteen patients were enrolled, they were mostly diagnosed with stage III NSCLC (IIB 15.4% IIIA 38.5%; IIIB 46.2%). Most of them had pathologically confirmed squamous cell carcinoma (69.2%). All patients received sintilimab combined with platinum-based chemotherapy for 2 to 4 cycles. Notably, none of the patients necessitated a reduction in initial dosages or treatment postponement due to intolerable adverse events. Then, all of them underwent surgical operation. Impressively, nine patients (69.2%) achieved a pathologic complete response. The objective response rate (ORR) stood at 46.15%. Nine patients experienced neoadjuvant treatment-related adverse events (TRAEs), with only one patient (7.6%) encountering a grade 4 neoadjuvant TRAE. CONCLUSION Therefore, the current study suggested that neoadjuvant sintilimab plus platinum-based chemotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.
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Affiliation(s)
- Cunli Yin
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Bin Hu
- Department Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Xi Yang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, China
| | - Lingna Kou
- Department of Medical Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Bo Tian
- Department Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Chenghao Wang
- Department Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Siru Li
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Bin Liu
- Department of Medical Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China
| | - Jun Ge
- Department of Medical Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China.
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17
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Liu Y. Perioperative immunotherapy for esophageal squamous cell carcinoma: Now and future. World J Gastroenterol 2023; 29:5020-5037. [PMID: 37753366 PMCID: PMC10518742 DOI: 10.3748/wjg.v29.i34.5020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/19/2023] [Accepted: 08/15/2023] [Indexed: 09/08/2023] Open
Abstract
Esophageal cancer (EC) ranks among the most prevalent malignant tumors affecting the digestive tract. Esophageal squamous cell carcinoma (ESCC) stands as the prevailing pathological subtype, encompassing approximately 90% of all EC patients. In clinical stage II-IVA locally advanced ESCC cases, the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection. Despite concerted efforts, the long-term outcomes for ESCC patients remain unsatisfactory, with dismal prognoses. However, recent years have witnessed remarkable strides in immunotherapy, particularly in the second- and first-line treatment of advanced or metastatic ESCC, with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies, including ESCC. This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC, focusing specifically on the role of immune checkpoint inhibitors during the perioperative period. Additionally, the review will explore promising biomarkers and offer insights into future prospects.
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Affiliation(s)
- Yong Liu
- Department of Thoracic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430011, Hubei Province, China
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Wu Y, Verma V, Gay CM, Chen Y, Liang F, Lin Q, Wang J, Zhang W, Hui Z, Zhao M, Wang J, Chang JY. Neoadjuvant immunotherapy for advanced, resectable non-small cell lung cancer: A systematic review and meta-analysis. Cancer 2023; 129:1969-1985. [PMID: 36994945 DOI: 10.1002/cncr.34755] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 02/16/2023] [Accepted: 02/22/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes. METHODS Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel-Haenszel fixed-effect or random-effect model was used, depending on the heterogeneity (I2 ). RESULTS Sixty-six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49-12.97; p < .001), progression-free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38-0.67; p < .001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36-0.74; p = .0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67-1.52; p = .97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15-0.43; p < .001) and OS (HR, 0.26; 95% CI, 0.10-0.67; p = .005). PD-L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22-7.03; p = .02). CONCLUSIONS In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD-L1, without increasing toxicities. PLAIN LANGUAGE SUMMARY This meta-analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non-small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand-1, without increasing toxicities.
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Affiliation(s)
- Yajing Wu
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Vivek Verma
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Carl M Gay
- Department of Head/Neck and Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yujia Chen
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Fei Liang
- Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qiang Lin
- Department of Oncology, North China Petroleum Bureau General Hospital, Hebei Medical University, Renqiu, China
| | - Jianing Wang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Wei Zhang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Zhouguang Hui
- Department of VIP Medical Services & Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical, Beijing, China
| | - Min Zhao
- Department of Oncology, Hebei Chest Hospital, Shijiazhuang, China
| | - Jun Wang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Joe Y Chang
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Wang Y, Huang S, Feng X, Xu W, Luo R, Zhu Z, Zeng Q, He Z. Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer. Front Oncol 2023; 13:1145128. [PMID: 37265800 PMCID: PMC10229830 DOI: 10.3389/fonc.2023.1145128] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 05/03/2023] [Indexed: 06/03/2023] Open
Abstract
The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors.
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Affiliation(s)
- Yunzhen Wang
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Sha Huang
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiangwei Feng
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wangjue Xu
- Department of Thoracic Surgery, Longyou County People’s Hospital, Longyou, China
| | - Raojun Luo
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ziyi Zhu
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qingxin Zeng
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhengfu He
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Li S, Chen Y, Ma R, Du Y, Han B. Cationic lipid-assisted nanoparticles for simultaneous delivery of CD47 siRNA and R848 to promote antitumor immune responses. Front Pharmacol 2023; 14:1142374. [PMID: 37063284 PMCID: PMC10102467 DOI: 10.3389/fphar.2023.1142374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/15/2023] [Indexed: 04/05/2023] Open
Abstract
Graphical AbstractThe PEG-PLGA nanoparticles effectively delivered R848 and CD47 siRNA into tumor cells, resulting in simultaneous activation of DCs and downregulation of CD47 expression on tumor cells, thereby enhancing antitumor immune responses by T cells.
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Udelsman BV, Blasberg JD. Advances in Surgical Techniques for Lung Cancer. Hematol Oncol Clin North Am 2023; 37:489-497. [PMID: 36964110 DOI: 10.1016/j.hoc.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
Abstract
Thoracic surgery for non-small cell lung cancer has evolved tremendously in the past two decades. Improvements have come on multiples fronts and include a transition to minimally invasive techniques, an incorporation of neoadjuvant treatment, and a greater utilization of sublobar resection. These advances have reduced the morbidity of thoracic surgery, while maintaining or improving long-term survival. This review highlights major advances in the surgical techniques of lung cancer and the keys to optimizing outcomes from a surgical perspective.
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Affiliation(s)
- Brooks V Udelsman
- Division of Thoracic Surgery, Yale-New Haven Hospital, New Haven, CT, USA; Yale University School of Medicine, New Haven, CT, USA
| | - Justin D Blasberg
- Division of Thoracic Surgery, Yale-New Haven Hospital, New Haven, CT, USA; Yale University School of Medicine, New Haven, CT, USA.
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Hu J, Zhang L, Xia H, Yan Y, Zhu X, Sun F, Sun L, Li S, Li D, Wang J, Han Y, Zhang J, Bian D, Yu H, Chen Y, Fan P, Ma Q, Jiang G, Wang C, Zhang P. Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing. Genome Med 2023; 15:14. [PMID: 36869384 PMCID: PMC9985263 DOI: 10.1186/s13073-023-01164-9] [Citation(s) in RCA: 122] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 02/15/2023] [Indexed: 03/05/2023] Open
Abstract
BACKGROUND Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored. METHODS We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8). RESULTS Distinct therapy-induced cancer cell transcriptomes were associated with clinical response. Cancer cells from MPR patients exhibited a signature of activated antigen presentation via major histocompatibility complex class II (MHC-II). Further, the transcriptional signatures of FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were enriched in MPR patients and are predictors of immunotherapy response. Cancer cells from NMPR patients exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. In all patients, therapy promoted expansion and activation of cytotoxic T cells and CD16+ NK cells, reduction of immunosuppressive Tregs, and activation of memory CD8+T cells into an effector phenotype. Tissue-resident macrophages were expanded after therapy, and tumor-associated macrophages (TAMs) were remodeled into a neutral instead of an anti-tumor phenotype. We revealed the heterogeneity of neutrophils during immunotherapy and identified an aged CCL3+ neutrophil subset was decreased in MPR patients. The aged CCL3+ neutrophils were predicted to interact with SPP1+ TAMs through a positive feedback loop to contribute to a poor therapy response. CONCLUSIONS Neoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance.
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Affiliation(s)
- Junjie Hu
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Lele Zhang
- Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - Haoran Xia
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Yilv Yan
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Xinsheng Zhu
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Fenghuan Sun
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Liangdong Sun
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Shuangyi Li
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Dianke Li
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Jin Wang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China
| | - Ya Han
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China
| | - Jing Zhang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Dongliang Bian
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Huansha Yu
- Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - Yan Chen
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Pengyu Fan
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Qiang Ma
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Gening Jiang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China
| | - Chenfei Wang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
- Frontier Science Center for Stem Cells, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
| | - Peng Zhang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China.
- The 1st School of Medicine, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
- Department of Thoracic Surgery, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, 832000, Xinjiang, China.
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Xu J, Yan C, Li Z, Cao Y, Duan H, Ke S. Efficacy and Safety of Neoadjuvant Chemoimmunotherapy in Resectable Esophageal Squamous Cell Carcinoma: A Meta-analysis. Ann Surg Oncol 2023; 30:1597-1613. [PMID: 36380254 DOI: 10.1245/s10434-022-12752-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 10/19/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE This study aimed to summarize the efficacy and safety of neoadjuvant chemoimmunotherapy in resectable esophageal squamous cell carcinoma (ESCC). METHODS Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in resectable ESCC published before June 2022 was retrieved from PubMed, Embase, Cochrane Library, and Web of Science. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool. Subgroup and sensitivity analyses were further performed. RESULTS A total of 452 patients from 15 studies were included in this meta-analysis. All of the studies explored the efficacy and safety of neoadjuvant chemoimmunotherapy. The pooled major pathological response (MPR) rate and pathological complete response (PCR) rate were 58.3% and 32.9%, respectively. The pooled incidence of treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were 91.6% and 19.4%, respectively. The pooled R0 resection rate was 92.8%, and the resection rate was 81.1%. Incidence of anastomotic leakage, pulmonary infection, and postoperative hoarseness were 10.7%, 21.3%, and 13.0%, respectively. Compared with 2 cycles of neoadjuvant therapy, patients who received > 2 cycles of neoadjuvant therapy showed higher MPR rate (57.3% vs. 61.1%) and PCR rate (30.6% vs. 37.9%), and the incidence of TRAEs (89.2% vs. 98.9%) tended to be higher. However, no significant difference was found (P > 0.05). Two cycles of neoadjuvant therapy showed higher R0 resection rate and resection rate (R0 resection rate: 96.0% vs. 87.8%, P = 0.02; resection rate: 85.6% vs. 74.7%, P = 0.01). Pembrolizumab- and tislelizumab-based neoadjuvant therapy showed higher MPR rate (72.4% and 72.2%) and PCR rate (41.5 % and 50.0%). Compared with other ICIs, tislelizumab-based neoadjuvant therapy showed lower R0 resection rate (80.5%). The pooled incidence of SAEs for pembrolizumab-based neoadjuvant therapy (2.0%) was lower. Camrelizumab-based neoadjuvant therapy showed lower incidence of pulmonary infection (11.5%). CONCLUSIONS Neoadjuvant chemoimmunotherapy is effective and safe for resectable ESCC.
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Affiliation(s)
- Jinxin Xu
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Chun Yan
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Zhe Li
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Yunpeng Cao
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Hongbing Duan
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Sunkui Ke
- Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, China.
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Zeng L, Zhou Y, Zhang X, Xu Q, Zhou C, Zeng F, Jiang W, Wang Z, Deng L, Yang H, Liu L, Xiong Y, Zhang B, Yang N, Zhang Y. Copy number variations mediate major pathological response to induction chemo-immunotherapy in unresectable stage IIIA-IIIB lung cancer. Lung Cancer 2023; 178:134-142. [PMID: 36858002 DOI: 10.1016/j.lungcan.2023.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/05/2023] [Accepted: 02/21/2023] [Indexed: 03/02/2023]
Abstract
INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Despite this, evidence supporting optimal management of certain stages remains a topic of debate. In this retrospective study we examine the efficacy and safety, as well as exploring the biomarkers of neoadjuvant induction immuno-chemotherapy, in Chinese patients with unresectable stage III NSCLC. METHODS Patients with unresectable stage III NSCLC who were identified as driver mutation-negative and who received neoadjuvant chemo-immunotherapy were enrolled from three Chinese hospitals between Jan. 17, 2019, and Jan.17, 2022. Perioperative outcomes and survival data were collected. Retrospective biomarker exploration was performed in available baseline tumor samples and surgical specimens. RESULTS 94 patients were enrolled and received chemo-immunotherapy as neoadjuvant treatment. 80 patients had squamous cell carcinoma, and 26 had stage IIIB disease. Surgery conversion rate was 74.4%, R0 resection rate was 98.4%. Of 64 patients who underwent surgery, major pathological response (MPR) rate was 65.6% and pathologic complete response (pCR) rate was 42.2%. 73% of patients with N2 disease demonstrated down-staging to N0. Treatment-related adverse events (TRAEs) occurred in 43 patients (45.7%) with anemia was the most common. The Grade ≥ 3 TRAEs rate was 3.2% (3/94). A significant association between copy number variation (CNV) ploidy was also found. CONCLUSION The combination treatment of immuno-chemotherapy for unresectable stage III NSCLC is not only effective but also has a favourable safety profile. For the first time we provide evidence that CNV status may be a predictive biomarker of MPR.
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Affiliation(s)
- Liang Zeng
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Yuling Zhou
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Xiangyu Zhang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Qinqin Xu
- Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining 810000, China
| | - Chunhua Zhou
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Fanxu Zeng
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Wenjuan Jiang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Zhan Wang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Li Deng
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Haiyan Yang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Li Liu
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Yi Xiong
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Baihua Zhang
- Department of Thoracic Surgery, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan 410008, China
| | - Nong Yang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Yongchang Zhang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
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Xu Z, Zou Z, Hao X, Xing P, Li J. Adjuvant and neo-adjuvant immunotherapy in resectable non-small cell lung cancer (NSCLC): Current status and perspectives. CANCER INNOVATION 2023; 2:65-78. [PMID: 38090369 PMCID: PMC10686139 DOI: 10.1002/cai2.49] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/04/2022] [Accepted: 12/18/2022] [Indexed: 10/15/2024]
Abstract
Surgery followed by adjuvant chemotherapy is the standard of care for selected patients with early-stage or locally advanced non-small cell lung cancer (NSCLC). However, many of these patients still experience postoperative recurrence at 5 years. At present, peri-operative treatment methods are emerging to prevent early relapse, such as targeted therapy and immunotherapy. Investigation on predictive biomarkers of responses to adjuvant and neoadjuvant therapies is also continuously ongoing. Immunotherapy represented by immune checkpoint inhibitors (ICIs), either by monotherapy or in combination with chemotherapy, has shown benefit in promoting pathological responses and prolonging survival for patients with NSCLC without oncogenic mutations. Exploratory studies have also provided evidence regarding the selection of patients who benefit from ICI-based perioperative treatment. This review focuses on the existing data of current clinical trials of adjuvant and neoadjuvant strategies with ICIs in resectable NSCLC, the exploration of predictive biomarkers, and the perspectives and urgent challenges in the future.
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Affiliation(s)
- Ziyi Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zihua Zou
- Department of Medical OncologyFujian Provincial Cancer HospitalFuzhouChina
| | - Xuezhi Hao
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Puyuan Xing
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Junling Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Zhao M, Chen S, Li C, Du Y, Li P. Neoadjuvant Immune Checkpoint Inhibitors for Resectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:600. [PMID: 36765557 PMCID: PMC9913451 DOI: 10.3390/cancers15030600] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Resectable hepatocellular carcinoma (HCC) has poor prognosis because of its high recurrence rate. Immunotherapy has been tried for neoadjuvant therapy as it has shown excellent performance in the treatment of advanced HCC. This systematic review and meta-analysis aimed to assess the reported efficacy and safety of neoadjuvant immune checkpoint inhibitors (ICIs) for resectable HCC. Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify published and ongoing studies evaluating the efficacy and safety of neoadjuvant ICIs for resectable HCC up to October 2022. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Heterogeneity and subgroup analyses were performed, and data quality was assessed. The study was registered with PROSPERO (registration number: CRD42022371495). A total of 193 patients from 9 studies were included in this meta-analysis. The overall pathological complete response (pCR) rate was 12.9% (95%CI, 6.7-19.1%), and major pathological response (MPR) rate was 27.3% (95%CI, 15.1-39.4%), indicating a favorable association with neoadjuvant ICIs (pCR: OR = 0.17, p < 0.00001; MPR: OR = 0.38, p = 0.001). The pooled OR values for the incidence of grade 3 to 4 treatment-related adverse events and surgical delay rate were 0.26 and 0.05, respectively, which were significantly in favor of neoadjuvant ICIs (p < 0.0001; p < 0.00001, respectively). The subgroup analyses did not demonstrate superiority of one ICI over another ICI or combination therapy. The present study found that neoadjuvant ICIs were well tolerated by patients with resectable HCC and conferred therapeutic benefits in view of histopathological response results.
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Affiliation(s)
- Mei Zhao
- Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
- Department of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei 230032, China
| | - Shanwen Chen
- Department of Otorhinolaryngology—Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
| | - Conggui Li
- Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
| | - Yingying Du
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
| | - Ping Li
- Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
- Department of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei 230032, China
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Liu W, Zhang T, Zhang Q, Li L, Xu C. A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer. BMC Pulm Med 2022; 22:490. [PMID: 36582007 PMCID: PMC9798701 DOI: 10.1186/s12890-022-02292-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 12/20/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. Currently, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety. METHODS We searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant. RESULTS Nine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI 0.39-0.72) and of pCR was 39% (95%CI 0.28-0.51). The pooled rate of TRAEs was 65% (95%CI 0.17-0.99) and SAEs was 24% (95%CI 0.05-0.49). CONCLUSION Compared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC.
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Affiliation(s)
- Wei Liu
- grid.89957.3a0000 0000 9255 8984Department of Respiratory Medicine, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing, 210029 Jiangsu Province China ,Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029 Jiangsu China
| | - Tiantian Zhang
- grid.89957.3a0000 0000 9255 8984Department of Respiratory Medicine, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing, 210029 Jiangsu Province China ,Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029 Jiangsu China
| | - Qian Zhang
- grid.89957.3a0000 0000 9255 8984Department of Respiratory Medicine, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing, 210029 Jiangsu Province China ,Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029 Jiangsu China
| | - Li Li
- grid.89957.3a0000 0000 9255 8984Department of Respiratory Medicine, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing, 210029 Jiangsu Province China ,Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029 Jiangsu China
| | - Chunhua Xu
- grid.89957.3a0000 0000 9255 8984Department of Respiratory Medicine, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing, 210029 Jiangsu Province China ,Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029 Jiangsu China
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Woodford K, Koo K, Reynolds J, Stirling RG, Harden SV, Brand M, Senthi S. Persisting Gaps in Optimal Care of Stage III Non-small Cell Lung Cancer: An Australian Patterns of Care Analysis. Oncologist 2022; 28:e92-e102. [PMID: 36541690 PMCID: PMC9907057 DOI: 10.1093/oncolo/oyac246] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 10/20/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Wide variation exists globally in the treatment and outcomes of stage III patients with non-small cell lung cancer (NSCLC). We conducted an up-to-date patterns of care analysis in the state of Victoria, Australia, with a particular focus on the proportion of patients receiving treatment with radical intent, treatment trends over time, and survival. MATERIALS AND METHODS Stage III patients with NSCLC were identified in the Victorian Lung Cancer Registry and categorized by treatment received and treatment intent. Logistic regression was used to explore factors predictive of receipt of radical treatment and the treatment trends over time. Cox regression was used to explore variables associated with overall survival (OS). Covariates evaluated included age, sex, ECOG performance status, smoking status, year of diagnosis, Australian born, Aboriginal or Torres Strait Islander status, socioeconomic status, rurality, public/private status of notifying institution, and multidisciplinary meeting discussion. RESULTS A total of 1396 patients were diagnosed between 2012 and 2019 and received treatment with radical intent 67%, palliative intent 23%, unknown intent 5% and no treatment 5%. Radical intent treatment was less likely if patients were >75 years, ECOG ≥1, had T3-4 or N3 disease or resided rurally. Surgery use decreased over time, while concurrent chemoradiotherapy and immunotherapy use increased. Median OS was 38.0, 11.1, and 4.4 months following radical treatment, palliative treatment or no treatment, respectively. CONCLUSION Almost a third of stage III patients with NSCLC still do not receive radical treatment. Strategies to facilitate radical treatment and better support decision making between increasing multimodality options are required.
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Affiliation(s)
- Katrina Woodford
- Corresponding author: Katrina Woodford, PhD, Department of Radiation Oncology, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia. Tel: +61 3 8559 6067; Fax: +61 3 85596009; E-mail:
| | - Kendrick Koo
- Alfred Health Radiation Oncology, The Alfred Hospital, Melbourne, VIC, Australia,Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia,Department of Epidemiology & Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - John Reynolds
- Department of Epidemiology & Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Robert G Stirling
- Department of Medicine, Monash University, Clayton, VIC, Australia,Department of Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia
| | - Susan V Harden
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia,Department of Epidemiology & Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Margaret Brand
- Department of Epidemiology & Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - Sashendra Senthi
- Alfred Health Radiation Oncology, The Alfred Hospital, Melbourne, VIC, Australia,Department of Surgery, Central Clinical School, Monash University, Melbourne, VIC, Australia
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Chen X, Li Z, Zhou J, Wei Q, Wang X, Jiang R. Identification of prognostic factors and nomogram model for patients with advanced lung cancer receiving immune checkpoint inhibitors. PeerJ 2022; 10:e14566. [PMID: 36540802 PMCID: PMC9760026 DOI: 10.7717/peerj.14566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 11/22/2022] [Indexed: 12/23/2022] Open
Abstract
Background and aim Some patients with lung cancer can benefit from immunotherapy, but the biomarkers that predict immunotherapy response were not well defined. Baseline characteristic of patients may be the most convenient and effective markers. Therefore, our study was designed to explore the association between baseline characteristics of patients with lung cancer and the efficacy of immunotherapy. Methods A total of 216 lung cancer patients from Tianjin Medical University Cancer Institute & Hospital who received immunotherapy between 2017 and 2021 were included in the retrospective analysis. All baseline characteristic data were collected and then univariate log-rank analysis and multivariate COX regression analysis were performed. Kaplan-Meier analysis was used to evaluate patients' progression-free survival (PFS). A nomogram based on significant biomarkers was constructed to predict PFS rate of patients receiving immunotherapy. We evaluated the prediction accuracy of nomogram using C-indices and calibration curves. Results Univariate analysis of all collected baseline factors showed that age, clinical stage, white blood cell (WBC), lymphocyte (LYM), monocyte (MON), eosinophils (AEC), hemoglobin (HB), lactate dehydrogenase (LDH), albumin (ALB) and treatment line were significantly associated with PFS after immunotherapy. Then these 10 risk factors were included in a multivariate regression analysis, which indicated that age (HR: 1.95, 95% CI [1.01-3.78], P = 0.048), MON (HR: 1.74, 95% CI [1.07-2.81], P = 0.025), LDH (HR: 0.59, 95% CI [0.36-0.95], P = 0.030), and line (HR: 0.57, 95% CI [0.35-0.94], P = 0.026) were significantly associated with PFS in patients with lung cancer receiving immunotherapy. Patients with higher ALB showed a greater trend of benefit compared with patients with lower ALB (HR: 1.58, 95% CI [0.94-2.66], P = 0.084). Patients aged ≥51 years, with high ALB, low LDH, first-line immunotherapy, and high MON had better response rates and clinical benefits. The nomogram based on age, ALB, MON, LDH, line was established to predict the prognosis of patients treated with immune checkpoint inhibitor (ICI). The C-index of training cohort and validation cohort were close, 0.71 and 0.75, respectively. The fitting degree of calibration curve was high, which confirmed the high prediction value of our nomogram. Conclusion Age, ALB, MON, LDH, line can be used as reliable predictive biomarkers for PFS, response rate and cancer control in patients with lung cancer receiving immunotherapy. The nomogram based on age, ALB, MON, LDH, line was of great significance for predicting 1-year-PFS, 2-year-PFS and 3-year-PFS in patients with advanced lung cancer treated with immunotherapy.
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Affiliation(s)
- Xiuqiong Chen
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Tianjin’s Clinical Research Center for Cancer, Tianjin, China,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Zhaona Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Tianjin’s Clinical Research Center for Cancer, Tianjin, China,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Jing Zhou
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Tianjin’s Clinical Research Center for Cancer, Tianjin, China,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Qianhui Wei
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Tianjin’s Clinical Research Center for Cancer, Tianjin, China,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Xinyue Wang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Tianjin’s Clinical Research Center for Cancer, Tianjin, China,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Richeng Jiang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China,Tianjin’s Clinical Research Center for Cancer, Tianjin, China,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
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Shannon AH, Ruff SM, Pawlik TM. Expert Insights on Current Treatments for Hepatocellular Carcinoma: Clinical and Molecular Approaches and Bottlenecks to Progress. J Hepatocell Carcinoma 2022; 9:1247-1261. [PMID: 36514693 PMCID: PMC9741819 DOI: 10.2147/jhc.s383922] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 11/18/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary liver tumor that typically occurs in the setting of chronic liver disease/cirrhosis. Treatment modalities for HCC have evolved and given the variety of treatment options, a multi-disciplinary approach requiring input from surgical, medical, and radiation oncology, hepatology, and interventional radiology is necessary. Multiple advances have been made over the last decade regarding treatment of HCC, especially advanced disease. Resection and transplantation remain as cornerstone curative-intent treatment options. For patients who are not candidates for curative-intent therapy, exciting progress has been made in molecular and cellular approaches to systemic therapy for HCC including immunotherapies and tyrosine kinase inhibitors. Although the prognosis for advanced HCC remains poor, the armamentarium of therapies has increased, and valuable years of life can be gained with these therapies. While the main therapeutic modality for early-stage disease remains resection, multimodal immunotherapy has emerged as first-line treatment for advanced disease. We herein review different clinical and molecular treatment modalities related to the treatment of HCC, as well as provide insights into future directions for HCC treatment. We highlight how research and progress are needed to move into a new era of molecular and cellular treatments.
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Affiliation(s)
- Alexander H Shannon
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Samantha M Ruff
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Correspondence: Timothy M Pawlik, Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Professor of Surgery, Oncology, Health Services Management and Policy, The Ohio State University, Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA, Tel +1 614 293 8701, Fax +1 614 293 4063, Email
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31
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Denlinger CE. With a Grain of Salt. Ann Thorac Surg 2022; 114:2048-2049. [PMID: 35460621 DOI: 10.1016/j.athoracsur.2022.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/09/2022] [Indexed: 12/31/2022]
Affiliation(s)
- Chadrick E Denlinger
- Division of Cardiothoracic Surgery, Indiana University, 545 Barnhill Dr, EH 215, Indianapolis, IN 46202.
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Wu J, Bao C, Liu G, Meng S, Lu Y, Li P, Zhou J. Research Trends and Emerging Hotspots of Lung Cancer Surgery during 2012-2021: A 10-Year Bibliometric and Network Analysis. HEALTH DATA SCIENCE 2022; 2022:9797842. [PMID: 38487481 PMCID: PMC10880176 DOI: 10.34133/2022/9797842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 09/30/2022] [Indexed: 03/17/2024]
Abstract
Background. Lung cancer remains the leading cause of death because of cancer globally in the past years. To inspire researchers with new targets and path-breaking directions for lung cancer research, this study is aimed at exploring the research trends and emerging hotspots in the lung cancer surgery literature in the recent decade.Methods. This cross-sectional study combined bibliometric and network analysis techniques to undertake a quantitative analysis of lung cancer surgery literature. Dimensions database was searched using keywords in a 10-year period (2012-2021). Publications were characterized by publication year, research countries, field citation ratio, cooperation status, research area, and emerging hotspots.Results. Overall, global scholarly outputs of lung cancer surgery had almost doubled during the recent decade, with China, Japan, and the United States leading the way, while Denmark and Belgium predominated in terms of scientific influence. Network analysis showed that international cooperation accounted for a relatively small portion in lung cancer surgery research, and the United States, China, and Europe were the prominent centers of international cooperation network. In the recent decade, research of lung cancer surgery majored in prevention, biomedical imaging, rehabilitation, and genetics, and the emerging research hotspots transformed into immunotherapy. Research on immunotherapy showed a considerable increase in scientific influence in the latest year.Conclusions. The study findings are expected to provide researchers and policymakers with interesting insights into the changing trends of lung cancer surgery research and further generate evidence to support decision-making in improving prognosis for patients with lung cancer.
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Affiliation(s)
- Jingyi Wu
- Advanced Institute of Information Technology, Peking University, Hangzhou 311215, China
| | - Chenlu Bao
- Advanced Institute of Information Technology, Peking University, Hangzhou 311215, China
| | - Ganwei Liu
- Department of Thoracic Surgery, Peking University People’s Hospital, Beijing 100044, China
| | - Shushi Meng
- Department of Thoracic Surgery, Beijing Haidian Hospital, Beijing 100000, China
| | - Yunwei Lu
- Department of Thoracic Surgery, Peking University People’s Hospital, Beijing 100044, China
| | - Pengfei Li
- Advanced Institute of Information Technology, Peking University, Hangzhou 311215, China
- National Institute of Health Data Science, Peking University, Beijing 100191, China
| | - Jian Zhou
- Department of Thoracic Surgery, Peking University People’s Hospital, Beijing 100044, China
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Neoadjuvant Immunotherapy Improves Treatment for Early Resectable Non-Small-Cell Lung Cancer: A Systematic Review and Meta-analysis. JOURNAL OF ONCOLOGY 2022; 2022:2085267. [PMID: 36213828 PMCID: PMC9546650 DOI: 10.1155/2022/2085267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/03/2022] [Accepted: 08/11/2022] [Indexed: 12/04/2022]
Abstract
Objective Immunotherapy has shown better efficacy and less toxicity than chemotherapy in the treatment of non-small-cell lung cancer (NSCLC) at advanced stage. This study evaluates the safety and efficacy of neoadjuvant immunotherapy for resectable NSCLC. Methods Literature examination was performed by searching the PubMed, the Cochrane Library, and Embase for articles evaluating the efficacy and safety of neoadjuvant immunotherapy for resectable NSCLC. The 95% confidence interval (CI) and effect sizes (ES) were evaluated. Heterogeneity and subgroup analysis were performed. Meta-analysis was carried out using Stata BE17 software. Results In total, 678 patients from eighteen studies were recruited in this meta-analysis. The pathological complete response (pCR) and major pathological response (MPR) were used to evaluate the efficacy of neoadjuvant immunotherapy. Significantly higher MPR values were observed in neoadjuvant immunotherapy (MPR : ES = 0.44; 95% CI: 0.33–0.55; pCR : ES = 0.22; 95% CI: 0.15–0.30) compared with neoadjuvant chemotherapy (MPR < 25% and PCR : ES = 2%–15%). Treatment-related adverse events (TRAE), surgical resection rate, surgical delay rate, and incidence of surgical complications were used to evaluate the safety. In summary, ES values for the incidence of TRAE, incidence of surgical complications, and surgical delay rate were 0.4, 0.24, and 0.04, respectively, that were significantly lower than those for neoadjuvant chemotherapy (95% CI: 0.04–0.90; 0.22–0.75; and 0.01–0.10, respectively). The mean surgical resection rate of 89% was similar to the reported 75%–90% resection rate with neoadjuvant chemotherapy (OR = 7.61, 95% CI: 4.90–11.81). Conclusion Neoadjuvant immunotherapy is safe and effective for resectable NSCLC.
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Wang H, Liu T, Chen J, Dang J. Neoadjuvant immunotherapy and neoadjuvant chemotherapy in resectable non-small cell lung cancer: A systematic review and single-arm meta-analysis. Front Oncol 2022; 12:901494. [PMID: 36212419 PMCID: PMC9533019 DOI: 10.3389/fonc.2022.901494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/02/2022] [Indexed: 12/25/2022] Open
Abstract
Background It remains uncertain whether neoadjuvant immune checkpoint inhibitor (nICI) is superior to neoadjuvant chemotherapy (nCT) in resectable non-small cell lung cancer. In addition, there are outstanding questions for nICI such as the ideal treatment mode and predictors. Methods PubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible single-arm or multi-arm trials until 31 December 2021. The primary outcomes of interest were major pathological response (MPR) and pathological complete response (pCR). The random-effect model was used for statistical analysis. Results Twenty-four trials of nICI (n = 1,043) and 29 trials of nCT (n = 2,337) were identified. nICI combination therapy was associated with higher MPR (63.2%, 95% CI: 54.2%-72.1%) and pCR (35.3%, 95% CI: 27.4%-43.3%) rates compared to nCT (16.2%, 95% CI: 7.5%-25.0%, P < 0.001 and 5.5%, 95% CI: 3.5%-7.5%, P < 0.001) and nICI monotherapy (23.3%, 95% CI: 12.7%-33.8%, P < 0.001, and 6.5%, 95% CI: 1.7%-11.2%, P < 0.001). As for safety, nICI monotherapy had the best tolerability; nICI combination showed a similar surgical resection rate and higher R0 resection rate compared to nCT. PD-1 inhibitor and high PD-L1 expression (≥1% or ≥50%) were correlated with higher MPR and pCR rates compared to PD-L1 inhibitor and PD-L1 expression <1%. Conclusions nICI combination therapy is associated with higher MPR and pCR rates compared to nCT and nICI monotherapy. PD-1 inhibitor seems to be superior to PD-L1 inhibitor. PD-L1 status appears to be predictive of MPR and pCR for patients receiving nICI. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=278661, CRD42021278661.
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Affiliation(s)
- He Wang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Tingting Liu
- Department of Radiation Oncology, Anshan Cancer Hospital, Anshan, China
| | - Jun Chen
- Department of Radiation Oncology, Shenyang Tenth People’s Hospital, Shenyang, China
| | - Jun Dang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
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Wang J, Zhang K, Liu T, Song Y, Hua P, Chen S, Li J, Liu Y, Zhao Y. Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis. Front Oncol 2022; 12:974684. [PMID: 36158679 PMCID: PMC9495441 DOI: 10.3389/fonc.2022.974684] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022] Open
Abstract
ObjectiveThe progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated.MethodsOriginal articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis.ResultsIn total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44–0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25–0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09–0.22) and 0.86 (95% CI: 0.83–0.89), respectively.ConclusionNeoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.
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Affiliation(s)
- Jincheng Wang
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Kun Zhang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, China
| | - Tianzhou Liu
- Department of the Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Ying Song
- Gastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin University, Changchun, China
| | - Peiyan Hua
- Gastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin University, Changchun, China
| | - Shu Chen
- Gastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin University, Changchun, China
| | - Jindong Li
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Yang Liu
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Yinghao Zhao
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, China
- *Correspondence: Yinghao Zhao,
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Zhang F, Guo W, Zhou B, Wang S, Li N, Qiu B, Lv F, Zhao L, Li J, Shao K, Xue Q, Gao S, He J. Three-Year Follow-Up of Neoadjuvant Programmed Cell Death Protein-1 Inhibitor (Sintilimab) in NSCLC. J Thorac Oncol 2022; 17:909-920. [PMID: 35550174 DOI: 10.1016/j.jtho.2022.04.012] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/05/2022] [Accepted: 04/09/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Programmed cell death protein-1 (PD-1) inhibitors have been proved to be feasible and to have efficacy in multiple cancers, including NSCLC. But few studies have evaluated the effectiveness of PD-1 inhibitor as neoadjuvant therapy with a long-term follow-up. Here, in this phase 1b study with a 3-year follow-up, we reported the clinical outcomes of patients who received the PD-1 inhibitor as neoadjuvant therapy. METHODS Two doses of sintilimab (intravenously, 200 mg) were used for patients with stages IA to IIIB NSCLC (registration number: ChiCTR-OIC-17013726). Then, surgery was performed within 29 to 43 days after the first dose. All patients underwent positron emission tomography-computed tomography at enrolment and before surgery to evaluate tumor metabolism after administration of PD-1 inhibitor. We also evaluated the expression of programmed death-ligand 1 (PD-L1) as an exploratory analysis in 32 eligible patients. Safety was the primary end point. Overall survival (OS), disease-free survival (DFS), event-free survival, and major pathologic response were the key secondary end points. RESULTS With the mean follow-up of 37.8 months, 3-year OS rate was 88.5% and the 3-year DFS rate was 75.0% among patients who underwent R0 resection. In patients with positive PD-L1 expression, 3-year OS and DFS rates were 95.5% and 81.8%, respectively. Eight patients had recurrent tumors, including local recurrence, lung metastasis, brain metastasis, and bone metastasis. Patients with PD-L1 greater than or equal to 1% had more favorable clinical outcomes than the other subgroup (hazard ratio = 0.275, 95% confidence interval: 0.078-0.976). No more new adverse events have occurred in the 3-year follow-up because we first reported them in the former publication. CONCLUSIONS This is the first study to report the long-term survival probability of patients with NSCLC receiving PD-1 inhibitors as the neoadjuvant treatment. The 3-year follow-up results revealed that patients with positive PD-L1 expression and high tumor mutation burden have favorable clinical outcomes.
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Affiliation(s)
- Fan Zhang
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Wei Guo
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Bolun Zhou
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Shuhang Wang
- GCP Center, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Ning Li
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; GCP Center, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Bin Qiu
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Fang Lv
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Liang Zhao
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Jian Li
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Kang Shao
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Qi Xue
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Shugeng Gao
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
| | - Jie He
- Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
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Li F, Chen Y, Wu J, Li C, Chen S, Zhu Z, Qin W, Liu M, Hu B, Liu S, Zhong W. The earlier, the better? A review of neoadjuvant immunotherapy in resectable non-small-cell lung cancer. Chronic Dis Transl Med 2022; 8:100-111. [PMID: 35774424 PMCID: PMC9215714 DOI: 10.1002/cdt3.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 01/19/2022] [Indexed: 12/24/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.
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Affiliation(s)
- Fajiu Li
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Ying Chen
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Juanjuan Wu
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Chenghong Li
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Shi Chen
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Ziyang Zhu
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Wei Qin
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Min Liu
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Bingzhu Hu
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Shuang Liu
- Department of Pulmonary and Critical Care MedicineAffiliated Hospital of Jianghan UniversityWuhanHubeiChina
| | - Wenzhao Zhong
- Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical SciencesGuangzhouGuangdongChina
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Igaue S, Okuno T, Ishibashi H, Nemoto M, Hiyoshi M, Kawasaki H, Saitoh H, Saitoh M, Akagi K, Yamamoto J. A pathological complete response after nivolumab plus ipilimumab therapy for DNA mismatch repair‑deficient/microsatellite instability‑high metastatic colon cancer: A case report. Oncol Lett 2022; 24:211. [PMID: 35720492 PMCID: PMC9178690 DOI: 10.3892/ol.2022.13332] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 04/28/2022] [Indexed: 12/24/2022] Open
Abstract
The standard treatment for colorectal cancer has always been surgery and chemotherapy, which may be used in combination to treat patients. Immune checkpoint inhibitors have been a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair. However, little information is available about their use in neoadjuvant and conversion settings with only a few case reports and only one phase 2 trial. The present study reports the case of a large, locally advanced right-sided metastatic deficient mismatch repair/microsatellite instability-high colon cancer, which showed a pathological complete response after combination treatment with nivolumab and ipilimumab. To the best of our knowledge, resected metastatic colon cancer with a pathological complete response after treatment using dual immune checkpoint inhibitors has not been previously reported. Overall, this case report suggests the use of immune checkpoint inhibitors before colorectal surgery.
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Affiliation(s)
- Shota Igaue
- Department of Gastrointestinal Surgery, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Takayuki Okuno
- Department of Gastrointestinal Surgery, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Hajime Ishibashi
- Department of Gastroenterology, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Masaru Nemoto
- Department of Gastrointestinal Surgery, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Masaya Hiyoshi
- Department of Gastrointestinal Surgery, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Hiroshi Kawasaki
- Department of Gastrointestinal Surgery, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Hitoaki Saitoh
- Department of Pathology, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Makoto Saitoh
- Center for Clinical Genetics and Genomics, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
| | - Kiwamu Akagi
- Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Kitaadachi‑gun, Saitama 362‑0806, Japan
| | - Junji Yamamoto
- Department of Gastrointestinal Surgery, Ibaraki Cancer Center, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki 309‑1793, Japan
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Ballman M, Zhao C, McAdams MJ, Rajan A. Immunotherapy for Management of Thymic Epithelial Tumors: A Double-Edged Sword. Cancers (Basel) 2022; 14:2060. [PMID: 35565190 PMCID: PMC9105984 DOI: 10.3390/cancers14092060] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/15/2022] [Accepted: 04/17/2022] [Indexed: 02/01/2023] Open
Abstract
Thymic epithelial tumors (TETs) are rare thoracic cancers that are broadly classified as thymomas and thymic carcinomas. Surgery is the cornerstone of management for early-stage disease. There are a limited number of effective treatment options for patients with advanced or recurrent disease. The occurrence of paraneoplastic autoimmune disorders in patients with TETs, especially thymomas, creates significant challenges for the development of immunotherapy, including immune checkpoint inhibitors, as a feasible treatment option. In addition, patients with TETs are at increased risk for the development of immune-mediated toxicity with a predilection for musculoskeletal and neuromuscular adverse events upon treatment with immunotherapy. The identification of biomarkers of response and toxicity is expected to play a key role in harnessing the benefits of immunotherapy for patients with TETs. In this paper we review the biology of TETs and the potential effects on the tolerability of immunotherapy. The results of clinical trials of immune checkpoint inhibitors for the treatment of advanced TETs are described to understand the potential risks and benefits of immunotherapy. We also provide an overview of future avenues for treatment with novel immunotherapeutic modalities and opportunities to develop biomarkers to improve the safety and tolerability of immunomodulatory treatments in patients with TETs.
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Affiliation(s)
| | | | | | - Arun Rajan
- Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (M.B.); (C.Z.); (M.J.M.)
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Effectiveness and Safety of Neoadjuvant Immunotherapy Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer: A Meta-Analysis. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03389-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Luginbuhl AJ, Johnson JM, Harshyne LA, Linnenbach AJ, Shukla SK, Alnemri A, Kumar G, Cognetti DM, Curry JM, Kotlov N, Antysheva Z, Degryse S, Mannion K, Gibson MK, Netterville J, Brown B, Axelrod R, Zinner R, Tuluc M, Gargano S, Leiby BE, Shimada A, Mahoney MG, Martinez-Outschoorn U, Rodeck U, Kim YJ, South AP, Argiris A. Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2022; 28:915-927. [PMID: 34911681 PMCID: PMC8898272 DOI: 10.1158/1078-0432.ccr-21-1816] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/07/2021] [Accepted: 12/10/2021] [Indexed: 01/07/2023]
Abstract
PURPOSE We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis. RESULTS Neoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery. CONCLUSIONS Preoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil.
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Affiliation(s)
- Adam J. Luginbuhl
- Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania
| | - Jennifer M. Johnson
- Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Larry A. Harshyne
- Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Alban J. Linnenbach
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University; Philadelphia, Pennsylvania
| | - Sanket K. Shukla
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University; Philadelphia, Pennsylvania
| | - Angela Alnemri
- Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania
| | - Gaurav Kumar
- Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - David M. Cognetti
- Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania
| | - Joseph M. Curry
- Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania
| | | | | | | | - Kyle Mannion
- Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Michael K. Gibson
- Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - James Netterville
- Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Brandee Brown
- Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Rita Axelrod
- Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Ralph Zinner
- Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Madalina Tuluc
- Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Stacey Gargano
- Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Benjamin E. Leiby
- Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Ayako Shimada
- Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - My G. Mahoney
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University; Philadelphia, Pennsylvania
| | - Ubaldo Martinez-Outschoorn
- Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Ulrich Rodeck
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University; Philadelphia, Pennsylvania
| | - Young J. Kim
- Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Andrew P. South
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University; Philadelphia, Pennsylvania
| | - Athanassios Argiris
- Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
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[Biomarkers for Neoadjuvant Immune Checkpoint Inhibitors
in Non-small Cell Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2022; 25:130-136. [PMID: 35224967 PMCID: PMC8913284 DOI: 10.3779/j.issn.1009-3419.2022.102.04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Surgery is the standard treatment for resectable non-small cell lung cancer (NSCLC). Neoadjuvant and adjuvant therapy have been widely used for preventing recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have brought long-term survival benefits in advanced NSCLC and showed higher downstage rates and pathological remission in the neoadjuvant setting. Predictive biomarkers are of great significance to identify the beneficiaries of neoadjuvant ICIs. At present, the biomarkers are still inconclusive. We summarized the clinical trials of neoadjuvant immune checkpoint inhibitors that have been disclosed so far, and reviewed the progress of the biomarkers associated with those trials.
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Neoadjuvant Sintilimab and Chemotherapy for Resectable Stage IIIA Non-small-cell Lung Cancer. Ann Thorac Surg 2022; 114:949-958. [PMID: 35176262 DOI: 10.1016/j.athoracsur.2022.01.039] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 12/13/2021] [Accepted: 01/15/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND Evidence of neoadjuvant chemoimmunotherapy for locally advanced non-small-cell-lung-cancer remains investigational and requires prospective validation. This phase II trial (ChiCTR1900023758) aimed to investigate the safety and effectiveness of neoadjuvant PD-1 inhibitor, sintilimab, in addition to chemotherapy in the management of resectable stage IIIA non-small-cell-lung-cancer. METHODS Eligible patients received two to four 21-day-cycles of neoadjuvant therapy: sintilimab (200mg) and carboplatin (area under the curve5) on day1, gemcitabine (1000mg/m2) on day1 and day8 for squamous-cell-carcinoma or pemetrexed (500mg/m2) on day1 for adenocarcinoma and non-small-cell-lung-cancer-not otherwise specified. The primary endpoints were adverse events and major pathological response. The secondary endpoint was disease-free-survival at 1 year. RESULTS Fifty patients were enrolled, and 23 (46%) achieved partial response after neoadjuvant chemoimmunotherapy. Four (8%) patients experienced grade 3-5 adverse events. Thirty patients received surgery, none of whom experienced treatment-related-surgery-delays, and 13 (13/30, 43.3%) patients achieved major pathological response (viable tumor ≤10%). With a median follow-up of 13.6 months, 85.3% of patients were disease-free at 1 year (N=50). CONCLUSIONS Neoadjuvant sintilimab with platinum-containing dual-agent chemotherapy was feasible and safe for patients with resectable stage IIIA non-small-cell-lung-cancer.
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Xu J, Wu Y, Xu Y, Qiu Y, Li X, Song Y, Zhang L. Safety of Neoadjuvant Immunotherapy in Resectable Cancers: A Meta-Analysis. Front Immunol 2022; 13:802672. [PMID: 35173721 PMCID: PMC8841351 DOI: 10.3389/fimmu.2022.802672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 01/13/2022] [Indexed: 11/23/2022] Open
Abstract
Background Neoadjuvant immunotherapy has preliminarily been effective in multiple resectable cancers. However, its safety is still largely unknown. Methods A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library up to February 28th, 2021. Pooled incidence and risk ratio (RR) of adverse events were calculated using the R software. Results Twenty-eight studies involving 2863 patients were included. First, the incidence for all-grade treatment-related adverse events (trAEs) was 94% (95% CI, 81%-98%), with 43% (95% CI, 24%-64%) for high-grade trAEs. For different treatment groups, neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy was associated with a higher incidence of all-grade [99% (95% CI, 98%-99%) vs. 76% (95% CI 47%-92%); P < 0.001] and high-grade [80% (58%-92%) vs. 15% (9%-24%); P < 0.001] trAEs compared with neoadjuvant ICIs alone. The most common high-grade trAEs were lipase increased (5%; 95% CI, 2%-10%), colitis (3%; 95% CI, 0-7%) and transaminitis (3%; 95% CI, 0-7%) for neoadjuvant ICIs, and neutropenia (53%; 95% CI, 31%-74%), anemia (8%; 95% CI, 3%-15%) and AST increased (4%; 95% CI, 2%-7%) for neoadjuvant ICIs plus chemotherapy. Furthermore, the incidence rates of progressive disease while on treatment, treatment-related surgical delays and deaths were 6% (95% CI, 4%-10%), 3.2% (12 of 377 patients) and 0.47% (5 of 1075 patients), respectively. Conclusion Compared with neoadjuvant ICIs alone, neoadjuvant ICIs plus chemotherapy had a higher incidence of trAEs. In addition, neoadjuvant immunotherapy had a low rate of progressive diseases, surgical delays and deaths.
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Affiliation(s)
- Jiawei Xu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Yongfeng Wu
- Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yuedan Xu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Yuan Qiu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Xiaobo Li
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Yumeng Song
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
| | - Ling Zhang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
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Deng H, Zhao Y, Cai X, Chen H, Cheng B, Zhong R, Li F, Xiong S, Li J, Liu J, He J, Liang W. PD-L1 expression and Tumor mutation burden as Pathological response biomarkers of Neoadjuvant immunotherapy for Early-stage Non-small cell lung cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2022; 170:103582. [PMID: 35031441 DOI: 10.1016/j.critrevonc.2022.103582] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/16/2021] [Accepted: 01/05/2022] [Indexed: 12/17/2022] Open
Abstract
To date, there is no approved biomarker for predicting pathological response in neoadjuvant programmed cell death (ligand) 1 (PD-(L)1) blockades treated early-stage non-small cell lung cancer (NSCLC). Databases including PubMed, Embase, ClinicalTrials.gov, and Conference abstracts were searched for clinical trials of neoadjuvant PD-1/PD-L1 blockades for resectable NSCLC. Data regarding major pathological response (MPR), pathological complete response (pCR) in patients with high/low pretreatment PD-L1 expression, and tumor mutation burden (TMB) were synthesized using fixed-model meta-analysis and evaluated by odds ratio with 95% confidence interval. This analysis included 10 studies involving 461 NSCLC patients. Compared with PD-L1 expression <1%, PD-L1 expression ≥1% is associated with a higher rate of MPR and pCR. High-TMB associated with MPR and pCR. Similar findings were observed in subgroup analyses despite mono-PD-1/PD-L1 blockade or their combination with chemotherapy. Notably, 50% as the cutoff value for PD-L1 expression demonstrated better prediction efficacy for MPR than that of 1%.
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Affiliation(s)
- Hongsheng Deng
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Yi Zhao
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Xiuyu Cai
- Department of General Internal Medicine, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 510060, China
| | - Hualin Chen
- Department of Medical Oncology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Bo Cheng
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Ran Zhong
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Feng Li
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Shan Xiong
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Jianfu Li
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Jun Liu
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | - Jianxing He
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.
| | - Wenhua Liang
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.
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The Immunotherapy for Colorectal Cancer, Lung Cancer and Pancreatic Cancer. Int J Mol Sci 2021; 22:ijms222312836. [PMID: 34884642 PMCID: PMC8657810 DOI: 10.3390/ijms222312836] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 11/24/2021] [Accepted: 11/26/2021] [Indexed: 12/12/2022] Open
Abstract
Immunotherapy is a novel anti-cancer method which employs a different mechanism to conventional treatment. It has become a significant strategy because it provides a better or an alternative option for cancer patients. Recently, immunotherapy has been increasingly approved for the treatment of cancer; however, it has various limitations; for instance, it is only suitable for specific patients, the response rate is still low in most cases, etc. Colorectal cancer, lung cancer and pancreatic cancer are known as three major death-causing cancers in most countries. In this review, we discuss immunotherapeutic treatment for these three cancers, and consider the option, prospects and limitations of immunotherapy. The development of immunotherapy should focus on the discovery of biomarkers to screen suitable patients, new targets on tumors, neoadjuvant immunotherapy and the combination of immunotherapy with conventional therapeutic methods. We can expect that immunotherapy potentially will develop as one of the best therapies for patients with advanced cancer or poor responses to traditional methods.
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Hu Y, Ren SY, Wang RY, Zeng C, Li JN, Xiao P, Wu F, Yu FL, Liu WL. Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer. Front Oncol 2021; 11:684070. [PMID: 34692476 PMCID: PMC8526888 DOI: 10.3389/fonc.2021.684070] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 09/16/2021] [Indexed: 12/25/2022] Open
Abstract
Background Neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) represents an important research topic. Despite the potential benefits of this approach, the inflammatory responses and adverse events associated with neoadjuvant chemoimmunotherapy can present technical challenges and compromise a planned resection. This study assessed the safety and feasibility of neoadjuvant chemoimmunotherapy followed by surgery for resectable NSCLC. Methods The study was conducted from May 2019 to March 2021. Patients who were age 18 years or older, were diagnosed with stage Ib-IIIb NSCLC, and received neoadjuvant chemoimmunotherapy followed by surgery were included. Demographic information, clinical and pathologic characteristics, data about neoadjuvant therapy, and surgical details were collected by retrospective chart review. Toxicity profiles were collected retrospectively or by telephone follow-up. Results Twenty patients were included in this study. The median age was 56 years (range, 48-72 years), and 18 patients (90%) were men. Squamous carcinoma (14/20, 70%) was the most common cancer type, followed by adenocarcinoma (4/20, 20%), adenosquamous carcinoma (1/20, 5%), and large cell neuroendocrine carcinoma (1/20, 5%). All patients received two to four cycles of neoadjuvant therapy, and the median interval between final therapy and surgery was 49 days (range, 23-133 days). Computed tomography evaluation after neoadjuvant therapy showed partial response in 15 patients (75%) and stable disease in 5 (25%). Final pathologic examinations showed major pathologic response in eight patients, including pathologic complete response in five (25%). Most patients (18/20, 90%) had reduced pathologic staging. Twelve patients (60%) underwent open thoracotomy; the other eight patients underwent minimally invasive surgery, which was uneventful and without intraoperative conversion to open thoracotomy. No perioperative deaths occurred, and only seven patients (35%) developed postoperative complications. Most patients experienced only grade 1-2 adverse effects and laboratory abnormalities during neoadjuvant therapy, and no grade 3 or worse adverse effects or laboratory abnormalities occurred. No patients experienced surgical delays as a result of immune-related adverse events. Conclusions Preoperative administration of chemoimmunotherapy for patients with resectable NSCLC was safe and feasible.
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Affiliation(s)
- Yan Hu
- Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Si-Ying Ren
- Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Ruo-Yao Wang
- Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Chao Zeng
- Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Ji-Na Li
- Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Peng Xiao
- Department of Cardiothoracic Surgery, the Third Xiangya Hospital of Central South University, Changsha, China
| | - Fang Wu
- Department of Oncology, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Feng-Lei Yu
- Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Wen-Liang Liu
- Department of Thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, China
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Zhang F, Qiu B, Ji Y, Guo W, Li N, Xue Q, Gao S, He J. Comparison of surgical difficulty in patients with resectable non-small cell lung cancer under different neoadjuvant treatment modes: a retrospective cohort study. J Thorac Dis 2021; 13:5604-5616. [PMID: 34795911 PMCID: PMC8575808 DOI: 10.21037/jtd-21-1007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 09/10/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Previous studies have reported on the efficacy and safety of neoadjuvant use of a programmed cell death 1 (PD-1) antibody, sintilimab, in patients with non-small cell lung cancer (NSCLC). This study aimed to further evaluate the difficulty of this surgery and the postoperative complication rates in patients with NSCLC receiving neoadjuvant sintilimab. METHODS Patients who received neoadjuvant sintilimab (200 mg) in the Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital from March 2018 to March 2019 were enrolled in the neoadjuvant immunotherapy group (NI group). Another two cohorts who did not receive sintilimab were retrospectively selected by propensity score matching (PSM) at a ratio of 1:1 in the upfront surgery (M-US) and neoadjuvant chemotherapy (M-NC) groups. The postoperative complication rate, postoperative days (PODs), and other detailed objective indicators were compared by t-test or χ2 test. RESULTS Thirty-seven patients were enrolled in each group. Postoperative complications were greater in the NI group (37.8%) than in the M-US (10.8%; P=0.013) or in the M-NC group (16.2%; P=0.036). The number of PODs (7) was greater in the NI group than in the M-US group (P=0.005). The total number of dissected lymph nodes was lower in the NI group than in the M-US group (P<0.001) or in the M-NC group (P<0.001). Lymph node dissection (LND) in the NI group was more difficult than in the M-US group (P=0.015), but intrathoracic adhesion, tumor invasion, and whole procedure difficulty were similar. CONCLUSIONS The administration of neoadjuvant sintilimab increased complications but did not increase the difficulty of surgery. Fewer lymph nodes were dissected in the NI group.
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Affiliation(s)
- Fan Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bin Qiu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying Ji
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Guo
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Xue
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shugeng Gao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie He
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Masarwy R, Kampel L, Horowitz G, Gutfeld O, Muhanna N. Neoadjuvant PD-1/PD-L1 Inhibitors for Resectable Head and Neck Cancer: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg 2021; 147:871-878. [PMID: 34473219 DOI: 10.1001/jamaoto.2021.2191] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance The emerging approach of neoadjuvant immunotherapy for solid cancers has set the ground for the integration of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors into the neoadjuvant setting of head and neck squamous cell carcinoma (HNSCC) treatment. Objective To assess the reported efficacy and safety of neoadjuvant immunotherapy for resectable HNSCC. Data Sources and Study Selection Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and ClinicalTrials.gov were systematically searched for published and ongoing cohort studies and randomized clinical trials that evaluate neoadjuvant immunotherapy for resectable HNSCC. The search results generated studies from 2015 to July 2021. Data Extraction and Synthesis Two investigators (R.M. and L.K.) independently identified and extracted articles for potential inclusion. Random and fixed models were used to achieve pooled odds ratios. All results are presented with 95% CIs. Data quality was assessed by means of the Cochrane Collaboration's risk of bias tool. Main Outcomes and Measures The primary outcomes were reported efficacy, evaluated by major pathological response and pathological complete response in the primary tumors and lymph nodes separately, and safety, assessed by preoperative grade 3 to 4 treatment-related adverse events and surgical delay rate. Results A total of 344 patients from 10 studies were included. In 8 studies, neoadjuvant immunotherapy only was administered, and the other 2 studies combined immunotherapy with neoadjuvant chemotherapy and/or radiotherapy. The overall major pathological response rate in the primary tumor sites from studies reporting on neoadjuvant immunotherapy only was 9.7% (95% CI, 3.1%-18.9%) and the pathological complete response rate was 2.9% (95% CI, 0%-9.5%). Preoperative grade 3 to 4 treatment-related adverse events were reported at a rate of 8.4% (95% CI, 0.2%-23.2%) and surgical delay at a rate of 0% (95% CI, 0%-0.9%). There was a favorable association of neoadjuvant immunotherapy with all outcome measures. The subgroup analyses did not find one specific anti-PD-1/PD-L1 agent to be superior to another, and the favorable association was demonstrated by either immunotherapy alone or in combination with anti-CTLA-4. Conclusions and Relevance In this systematic review and meta-analysis, neoadjuvant anti-PD-1/PD-L1 immunotherapy for resectable HNSCC was well tolerated and may confer therapeutic advantages implied by histopathological response. Long-term outcomes are awaited.
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Affiliation(s)
- Razan Masarwy
- Department of Otolaryngology-Head and Neck and Maxillofacial Surgery, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Liyona Kampel
- Department of Otolaryngology-Head and Neck and Maxillofacial Surgery, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gilad Horowitz
- Department of Otolaryngology-Head and Neck and Maxillofacial Surgery, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Orit Gutfeld
- Institute of Radiation Therapy, Division of Oncology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nidal Muhanna
- Department of Otolaryngology-Head and Neck and Maxillofacial Surgery, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Ren S, Xu A, Lin Y, Camidge DR, Di Maio M, Califano R, Hida T, Rossi A, Guibert N, Zhu C, Shen J. A narrative review of primary research endpoints of neoadjuvant therapy for lung cancer: past, present and future. Transl Lung Cancer Res 2021; 10:3264-3275. [PMID: 34430363 PMCID: PMC8350086 DOI: 10.21037/tlcr-21-259] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 05/28/2021] [Indexed: 12/25/2022]
Abstract
Objective This review summarizes the current status of neoadjuvant therapy and discusses the choice of new clinical research endpoints for non-small cell lung cancer. Background Neoadjuvant chemotherapy is a recognized practice in patients with resectable and locally advanced lung cancer. With the introduction of molecular targeted drugs and immune checkpoint inhibitors (ICIs), the overall survival (OS) of patients with lung cancer has been significantly improved, and the original traditional clinical research endpoints are no longer suitable for existing clinical research. In order to accelerate the process of clinical trials and the development and approval of drugs, it is necessary to find suitable alternative indicators as the main indicators of clinical research. Methods Therefore, this article focuses on clinical trials using disease-free survival (DFS), progression free survival, and pathological evaluation indicators, pathologic complete response and major pathologic response, as surrogate endpoints. We search related literature through PubMed database and clinical trials through clinicaltrials.gov. Conclusions Pathologic complete response and major pathologic response are recommended as surrogate endpoints in the era of neoadjuvant immunotherapy, and secondary endpoints are listed for the prediction of pathological results. In addition, the definitions of major pathological response (MPR) and PCR should be standardized, and a new pathological evaluation standard should be developed, which is applicable to all current treatment methods. Keywords Neoadjuvant therapy; resectable lung cancer; clinical research endpoint; pathological response.
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Affiliation(s)
- Sijia Ren
- Taizhou Hospital, Zhejiang University, Taizhou, China
| | - Anyi Xu
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, China
| | - Yilian Lin
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, China
| | - D Ross Camidge
- Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Massimo Di Maio
- Department of Oncology, University of Turin/Division of Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy
| | - Raffaele Califano
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.,Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Toyoaki Hida
- Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan
| | - Antonio Rossi
- Oncology Center of Excellence, Therapeutic Science & Strategy Unit, IQVIA, Milan, Italy
| | - Nicolas Guibert
- Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, Toulouse, France
| | - Chengchu Zhu
- Taizhou Hospital, Zhejiang University, Taizhou, China
| | - Jianfei Shen
- Taizhou Hospital, Zhejiang University, Taizhou, China
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