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Third-line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases:A post hoc analysis of ALTER1202,a randomized,double-blind phase 2 study

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Cancer Innovation 2023年第3期2卷 181-190页

作者： Ying Cheng Qiming Wang Kai Li Jianhua Shi Baohui Han Lin Wu Gongyan Chen Jianxing He Jie Wang Haifeng Qin Xiaoling Li Department of Thoracic Medical Oncology Jilin Cancer HospitalChangchunChina department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina department of Pulmonary oncology Tianjin Medical University Cancer HospitalTianjinChina department of medical oncology Linyi Cancer HospitalLinyiChina department of Respiratory Medicine Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina Department of Thoracic Medical Oncology Hunan Cancer HospitalChangshaChina department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbinChina department of thoracic Surgery The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Thoracic Medical Oncology Cancer Hospital Chinese Academy of Medical SciencesBeijingChina department of Pulmonary oncology The Fifth Medical Centre of Chinese PLA General HospitalBeijingChina department of medical oncology Liaoning Cancer Hospital and InstituteShenyangChina

Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.

关键词： anlotinib angiogenesis inhibitors brain metastasis advanced small cell lung cancer safety

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The cutting-edge progress of immune-checkpoint blockade in lung cancer

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Cellular & Molecular Immunology 2021年第2期18卷 279-293页

作者： Fei Zhou Meng Qiao Caicun Zhou department of medical oncology Shanghai Pulmonary HospitalThoracic Cancer InstituteTongji University School of MedicineShanghaiChina

Great advances in immune checkpoint blockade have resulted in a paradigm shift in patients with lung cancer.Immune-checkpoint inhibitor(ICI)treatment,either as monotherapy or combination therapy,has been established as the standard of care for patients with locally advanced/metastatic non-small cell lung cancer without EGFR/ALK alterations or extensive-stage small cell lung cancer.An increasing number of clinical trials are also ongoing to further investigate the role of ICIs in patients with early-stage lung cancer as neoadjuvant or adjuvant therapy.Although PD-L1 expression and tumor mutational burden have been widely studied for patient selection,both of these biomarkers are imperfect.Due to the complex cancer-immune interactions among tumor cells,the tumor microenvironment and host immunity,collaborative efforts are needed to establish a multidimensional immunogram to integrate complementary predictive biomarkers for personalized immunotherapy.Furthermore,as a result of the wide use of ICIs,managing acquired resistance to ICI treatment remains an inevitable challenge.A deeper understanding of the underlying biological mechanisms of acquired resistance to ICIs is helpful to overcome these obstacles.In this review,we describe the cutting-edge progress made in patients with lung cancer,the optimal duration of ICI treatment,ICIs in some special populations,the unique response patterns during ICI treatment,the emerging predictive biomarkers,and our understanding of primary and acquired resistance mechanisms to ICI treatment.

关键词： lung cancer immune-checkpoint inhibitor predictive biomarker acquired resistance

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Modified ALPPS as an individual rescue treatment strategy for resection of Klatskin tumors

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 85-87页

作者： Gregor A Stavrou Dimitrios Kardassis Laura Ann Blatt Akram Gharbi Marcello Donati department of General Visceral and Thoracic SurgerySurgical OncologyKlinikum SaarbrueckenSaarbrueckenGermany department of Surgery and medical-Surgical Specialties University of CataniaCataniaItaly

Surgery for Klatskin tumors is a complex procedure often requiring extended hepatectomy combined with vascular and bileduct reconstruction in the setting of cholestasis,cholangitis,impaired liver regeneration and small future liver remnant(FLR)usually measured on computed tomography(CT)volumetry in a standardized(s FLR)fashion.Major morbidity is as high as 70%,andpublished literature estimates mortality around 15%[1].Carefulstrategic planning and modulation of the FLR are factors improving outcomes.

关键词： Surgery tumors mortality

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Current status and future perspectives of bispecific antibodies in the treatment of lung cancer

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Chinese medical Journal 2023年第4期136卷 379-393页

作者： Wanying Wang Tianyu Qiu Fei Li Shengxiang Ren department of medical oncology Shanghai Pulmonary Hospital and Institute of Thoracic CancerSchool of MedicineTongji UniversityShanghai 200433China department of Pathology School of Basic Medical SciencesFudan UniversityShanghai 200032China

Monoclonal antibodies have been successfully incorporated into the current therapeutical landscape of lung cancer in the last decades.Recently,with technological advances,bispecific antibodies(bsAbs)have also shown robust efficacy in the treatment of malignant cancers,including lung cancer.These antibodies target two independent epitopes or antigens and have been extensively explored in translational and clinical studies in lung cancer.Here,we outline the mechanisms of action of bsAbs,related clinical data,ongoing clinical trials,and potent novel compounds of various types of bsAbs in clinical studies,especially in lung cancer.We also propose future directions for the clinical development of bsAbs,which might bring a new era of treatment for patients with lung cancer.

关键词： Bispecific antibodies Lung cancer Immunotherapy Targeted therapy

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Role of Recursive Partitioning Analysis and Graded Prognostic Assessment on Identifying Non-Small Cell Lung Cancer Patients with Brain Metastases Who May Benefit from Postradiation Systemic Therapy

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Chinese medical Journal 2018年第10期131卷 1206-1213页

作者： Shuai Liu Peng Chen Yan-Wei Liu Xue-Nan GU Xiao-Guang Qiu Bo Li department of Radiation oncology BeijLng Tiantan Hospital Capital Medical University Beijing 100050 China department of thoracic oncology Tianjin Medical University Cancer Institute and Hospital Tianjin 300060 China

Background：The role ofpostradiation systemic therapy in non-small cell lung cancer （NSCLC） patients with brain metastasis （BM） was controversial.Thus,we explored the role of Radiation Therapy oncology Group recursive partitioning analysis （RTOG-RPA） and graded prognostic assessment （GPA） in identifying population who may benefit from postradiation systemic therapy.Methods：The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively.Cox regression was used for multivariate analysis.Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.Results：Of 216 included patients,67.1% received stereotactic radiosurgery （SRS）,24.1% received whole-brain radiation therapy （WBRT）,and 8.8% received both.After radiotherapy,systemic therapy was administered in 58.3% of patients.Multivariate analysis found that postradiation systemic therapy （yes vs.no）（hazard ratio [HR] =0.36 l,95% confidence interval [CI] =0.202-0.648,P =0.001）,radiation technique （SRS vs.WBRT）（HR =0.462,95% CI =0.238-0.849,P =0.022）,extracranial metastasis （yes vs.no）（HR =3.970,95% CI =1.757-8.970,P =0.001）,and Kamofsky performance status （〈70 vs.≥70）（HR =5.338,95% CI =2.829-10.072,P 〈 0.001） were independent factors for survival.Further analysis found that subsequent tyrosine kinase inhibitor （TKI） therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class IⅡ （HR =0.411,95% CI =0.183-）.923,P =0.031） or with a GPA score of 1.5-2.5 （HR =0.420,95% CI =0.182-0.968,P =0.042）.However,none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.Conclusion：RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM ifTKIs were chosen as postradiation systemic therapy.

关键词： Chemotherapy Non-Small Cell Lung Cancer Recursive Partitioning Analysis Stereotactic Radiosurgery Tyrosine Kinase Inhibitors Whole-Brain Radiation Therapy

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Prognostic role of C-reactive protein to albumin ratio in lung cancer:An updated systematic review and meta-analysis

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Chronic Diseases and Translational Medicine 2024年第1期10卷 31-39页

作者： Zhendong Lu Siyun Fu Wei Li Xiang Gao Jinghui Wang department of medical oncology Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing Chest HospitalCapital Medical UniversityBeijingChina Cancer Research Center Beijing Chest HospitalBeijing Tuberculosis and Thoracic Tumor Research InstituteCapital Medical UniversityBeijingChina

Background: C-reactive protein to albumin ratio(CRP/Alb ratio,CAR)has been suggested as a potential prognostic biomarker in lung cancer.This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature.Methods: A systematic search of databases was conducted to identify relevant studies published up to April 2023.Pooled hazard ratios(HRs)and 95%confidence intervals(CIs)were calculated to assess the association between CAR and overall survival(OS)and progression-free survival(PFS)and recurrence-free survival(RF)in lung cancer patients.Results: This meta-analysis includes 16 studies with a total of 5337 patients,indicating a significant association between higher CAR and poorer OS,PFS,and RFS in lung cancer patients,with a pooled HR of 1.78(95%CI=1.60-1.99),1.57(95%CI=1.36-1.80),and 1.97(95%CI=1.40-2.77),respectively.Conclusions: This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer,suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner.However,further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.

关键词： C-reactive protein to albumin ratio inflammation:biomarker lung cancer prognosis

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Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)

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Frontiers of Medicine 2022年第5期16卷 766-772页

作者： Jianhua Shi Ying Cheng Qiming Wang Kai Li Lin Wu Baohui Han Gongyan Chen Jianxing He Jie Wang Haifeng Qin Xiaoling Li department of medical oncology Linyi Cancer HospitalLinyi 276002China Department of Thoracic Medical Oncology Jilin Cancer HospitalChangchun 130012China department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhou 450003China department of Pulmonary oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Thoracic Medical Oncology The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University(Hunan Cancer Hospital)Changsha 410031China department of Respiratory Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbin 150081China department of thoracic Surgery The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of Pulmonary oncology The Fifth Medical Centre of Chinese PLA General HospitalBeijing 100039China department of medical oncology Liaoning Cancer HospitalShenyang 110042China

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.

关键词： anlotinib chemotherapy short-term relapsed small-cell lung cancer

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Chemotherapy in non-small cell lung cancer: opportunities for advancement

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Chinese Journal of Cancer 2016年第9期35卷 438-440页

作者： Mani Akhtari Eric H.Bernicker Bin S.Teh department of Radiation oncology Houston Methodist Hospital Cancer Center and Research Institute Weil Cornell Medical College department of Radiation oncology The University of Texas Medical Branch at Galveston Cancer Center Thoracic Medical Oncology Houston Methodist Hospital

Locally advanced non-small cell lung cancer(NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is signiicant interest in inding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical oncology entitled "PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer", compared two diferent chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received consolidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no diference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not ofer a clinical advantage over standard cisplatin plus etoposide. There are some subpopulations who might still beneit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.

关键词：非小细胞肺癌化疗放射治疗临床医生疾病控制 III 生物活性生物制剂

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Anti-programmed death 1 antibody in the treatment of coexistent Mycobacterium fortuitum and lung cancer: A case report

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World Journal of Clinical Cases 2022年第12期10卷 3801-3807页

作者： Cui-Cui Zhang Peng Chen department of thoracic oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Nontuberculous mycobacterium(NTM) refers to all mycobacteria except Mycobacterium tuberculosis and Mycobacterium leprae, also known as environmental Mycobacterium. The patients with lung cancer and NTM are somewhat special;the two diseases are inevitably influenced by each other. It brings difficulties and challenges to the choice of treatment. Recently, cancer immunotherapy has been considered one of the pillars for the treatment of lung cancer. However, the clinical experience in the application of immune checkpoint inhibitors is scarce for lung cancer patients with pulmonary tuberculosis, and lung cancer with NTM is even more rare. Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors presents complications of infectious diseases, including tuberculosis and NTM.CASE SUMMARY A 61-year-old male patient visited a doctor in May 2019. His admitting diagnoses were:(1) Cancer of the left lung with a pathological diagnosis of poorly differentiated non-small cell carcinoma, likely poorly differentiated adenocarcinoma, clinical stage Ⅲb(T3N3M0);and(2) Mycobacterium fortuitum(M. fortuitum) infection. We chose to proceed with pembrolizumab treatment. After two treatment cycles, a chest computed tomography scan showed a new irregular subpleural mass in the anterior segment of the left upper lobe of the lung, a reduction in the mediastinal enlarged lymph node, and no other obvious changes. Next, an ultrasound-guided biopsy of the new tumor was performed. Pathological examination showed that a large number of carbon particles were deposited in the alveolar tissue with histiocyte reaction and multinucleated giant cell formation. The tuberculosis(TB) specialist suggested that anti-TB therapy be combined with continued antitumor treatment. The patient continued to be treated with pembrolizumab. After 14 cycles, the lesion shrunk by 79%, there was no recurrence of M. fortuitum infection, and there were no intolerable adverse reactions.CONCLUSION We have observed that in cases of lung can

关键词： Mycobacterium fortuitum Nontuberculous mycobacterium Non-small cell lung cancer Immune checkpoint inhibitors Case report

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Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy

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Genes & Diseases 2023年第3期10卷 848-863页

作者： Peng Ding Zhiqiang Ma Yizeng Fan Yingtong Feng Changjian Shao Minghong Pan Yimeng Zhang Di Huang Jing Han Yi Hu Xiaolong Yan department of thoracic Surgery Tangdu HospitalThe Air Force Military Medical UniversityXi'anShaanxi 710038China department of medical oncology Senior Department of OncologyThe Fifth Medical Center of PLA General HospitalBeijing 100853China department of Urology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi 710061China department of Ophthalmology Tangdu HospitalThe Air Force Medical UniversityXi'anShaanxi 710038China

As members of the immune checkpoint family, PD-1 and its ligand PD-L1 play critical roles in maintaining the balance between autoimmunity and tolerance. The interaction of PD-1/PD-L1 is also involved in tumor evasion inside the tumor microenvironment, caused by reduced T cell activation, proliferation, cytotoxic secretion, and survival. Previous research has shown that the expression level of PD-1/PD-L1 may be regulated by ubiquitin-mediated proteasome degradation, which is an important mode of post-translational modification (PTM). PD-1/PD-L1 ubiquitin modification research in tumor immunotherapy is the subject of the present review, which aims to assess the most recent developments in this area. We offer a short explanation of PD-1/PD-L1 as well as some basic background information on the UPS system and discuss many routes that target E3s and DUBs, respectively, in the regulation of PD-1/PD-L1 in tumor immunotherapy. In addition, we offer numerous innovative prospective research areas for the future, as well as novel immunotherapy concepts and ideas. Taken together, the information compiled herein should serve as a comprehensive repository of information about tumor immunotherapy that is currently available, and it should be useful in the design of future studies, as well as the development of potential targets and strategies for future tumor immunotherapy.

关键词： Cancer Deubiquitination Immunotherapy PD-1 PD-L1 Ubiquitination

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