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Multi-cancer blood testing combined with PET-CT:road for hope to screen for cancer and guide intervention

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1628-1629页

作者： Tao Jiang Shengxiang Ren caicun zhou Department of Medical Oncology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghaiChina

In a recent study published in Science,Lennon et al.1 investigated the feasibility and safety of multi-cancer peripheral blood testing in combination with positron emission tomography-computed tomography(PET-CT)imaging to detect cancer in 10,006 women not previously known to have *** findings reveal that multi-cancer blood testing coupled with diagnostic PET-CT can be safely incorporated into routine clinical care to screen for cancer without discouraging patients from engaging in other forms of standard-of-care(SOC)screening;moreover,it is possible to intervene on the basis of blood testing results,in some cases leading to surgery with intent to cure(Fig.1).

关键词： routine cancer al

Non-small cell lung cancer in China

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Cancer Communications 2022年第10期42卷 937-970页

作者： Peixin Chen Yunhuan Liu Yaokai Wen caicun zhou School of Medicine Tongji UniversityShanghai 200092P.R.China Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai 200433P.R.China Department of Respiratory and Critical Care Medicine Huadong HospitalFudan UniversityShanghai 200040P.R.China

In China,lung cancer is a primary cancer type with high incidence and mor*** factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung *** early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical ***-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in *** understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive *** the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in *** the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after *** immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable *** this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。

关键词： non-small cell lung cancer screening targeted therapy immunotherapy epidermal growth factor receptor(EGFR)mutation programmed cell death protein 1(PD-1) programmed deathligand 1(PD-L1) clinical trials clinical guidelines

Recent advances in immunotherapy for lung cancer

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Cancer Innovation 2023年第1期2卷 18-24页

作者： Qi Wang Chunxia Su caicun zhou Department of Oncology Shanghai Pulmonary HospitalTongji UniversityShanghaiChina

Lung cancer is the malignant tumor with the highest morbidity andmortality in China, and nonsmall cell lung cancer is a common form oflung cancer. After undergoing chemotherapy and molecular targetedtherapy, the treatment of lung cancer has now fully entered the era ofimmunotherapy. Immunotherapy‐based treatment has become one of thestandard treatments for lung cancer. Immunotherapy has also graduallymoved from the back line to the front line, from advanced to earlypatients. This article focuses on the latest developments in perioperativeand advanced lung cancer immunotherapy, discusses the problems andchallenges at the current stage, and explores new directions for futuredevelopment.

关键词： nonsmall cell lung cancer small cell lung cancer perioperative period late stage new immunotherapy

PD-L1 expression and its effect on clinical outcomes of EGFRmutant NSCLC patients treated with EGFR-TKIs

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Cancer Biology & Medicine 2018年第4期15卷 434-442页

作者： Yuchen Bai Xiaoxia Chen Likun Hou Jun Qian Tao Jiang caicun zhou Maciej Ciebiada Department of General and Oncological Pulmonology University Clinical Hospital Norbert BarlickiMedical University of LodzLodz 50243Poland Department of Urology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Medical Oncology Department of Pathology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghai 200433China Department of Medical Oncology Suzhou Cancer Centerthe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215000China

Objective:Epidermal growth factor receptor(EGFR)activation was reported to upregulate programmed death-ligand 1(PD-L1)expression in lung cancer cells and subsequently contribute to immune escape,indicating its critical role in EGFR-driven lung *** study characterized PD-L1 expression in patients with surgically resected EGFR-mutant non-small cell lung cancer(NSCLC).The effect of PD-L1 expression on clinical outcomes was also investigated in advanced EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors(TKIs).Methods:In total,73 patients with surgically resected NSCLC and EGFR mutations were ***-L1 expression and CD8+tumor-infiltrating lymphocyte(TIL)density were assessed by immunohistochemistry.A literature review of publications that assessed the predictive and prognostic value of PD-L1 expression in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs was ***:Nineteen(26.0%)patients were positive for PD-L1 expression,which was significantly associated with concomitant KRAS mutation(P=0.020)and marginally associated with higher CD8+TILs density(P=0.056).Positive PD-L1 expression was associated with markedly inferior overall survival(OS)in multivariate analysis(P=0.032).The combination of PD-L1 and CD8+TILs expression could be used to stratify the population into three groups with distinct prognoses.A meta-analysis of six publications showed that positive PD-L1 expression was not associated with OS[hazard ratio(HR)=0.90;95%confidence interval(CI),0.42–1.38]or progression-free survival(HR=1.03;95 CI,0.73–1.33)in advanced EGFR-mutant NSCLC patients receiving ***:PD-L1 expression tended to correlate with CD8+TIL expression,concomitant KRAS mutation,and poor survival in surgically resected EGFR-mutant ***-L1 expression was neither the predictive nor the prognostic factor in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs.

关键词： Non-small cell lung cancer EGFR mutation PD-L1 CD8 survival

Alterations of DNA damage response pathway:Biomarker and therapeutic strategy for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2021年第10期11卷 2983-2994页

作者： Minlin Jiang Keyi Jia Lei Wang Wei Li Bin Chen Yu Liu Hao Wang Sha Zhao Yayi He caicun zhou Department of Medical Oncology Shanghai Pulmonary HospitalTongji University Medical School Cancer InstituteTongji University School of MedicineShanghai 200433China Medical School Tongji UniversityShanghai 200433China

Genomic instability remains an enabling feature of cancer and promotes malignant *** of DNA damage response(DDR)pathways allow genomic instability,generate neoantigens,upregulate the expression of programmed death ligand 1(PD-L1)and interact with signaling such as cyclic GMPe AMP synthase-stimulator of interferon genes(cGASe STING)***,we review the basic knowledge of DDR pathways,mechanisms of genomic instability induced by DDR alterations,impacts of DDR alterations on immune system,and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.

关键词： DNA damage response DNA repair Immunotherapy Genomic instability Tumor microenvironment PD-1 PD-L1 cGASe STING

Brain Metastasis of Non-small-cell Lung Cancer

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Clinical Cancer Bulletin 2022年第1期1卷 24-31页

作者： Tao JIANG Shengxiang REN caicun zhou Department of Medical Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China

Non-small-cell lung cancer(NSCLC)is the major histological type of lung cancers and is characterized by a high incidence of brain metastasis(BrM),which remains an intractable *** is a multi-step and complex biological *** formation and outgrowth of BrM involve co-evolution and cross-talk among metastatic cells,immune cells,astrocytes,and the brain *** date,patients with NSCLC BrM are treated with multimodal treatments including neurosurgery,radiotherapy,chemotherapy,anti-angiogenic treatment,molecular targeted therapy,and immune checkpoint ***,the overall prognosis remains dismal,with a median overall survival of<1 *** the detailed processes and mechanisms of NSCLC BrM including the phenotypic and genotypic heterogeneity of primary lung cancer and matched BrM and the specific immune microenvironment features of BrM would be helpful for developing effective therapeutic *** these novel findings into new treatments and integrating them with paradigms in traditional therapies could improve the overall prognosis of patients with NSCLC ***,we summarize the epidemiology,known mechanisms,and current systemic treatments for NSCLC *** the basis of recent clinical and translational advances,we discuss the future research directions for NSCLC BrM.

关键词： NSCLC brain metastasis epidemiology mechanism management

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循环肿瘤标志物在肺癌中的应用

中国肺癌杂志 2015年第12期18卷 770-780页

作者：周彩存上海市肺科医院肿瘤科上海200433

近年来,"液态活检"概念异军突起,不仅可以辅助诊断某些类型实体肿瘤,而且能够监测复发,评估疗效及肺癌分子表达,更是无创肿瘤筛查方法。其来源主要分为循环肿瘤细胞(circulating tumor cells,CTCs),循环肿瘤DNA(circulating tumor DNA,c... 详细信息

近年来,"液态活检"概念异军突起,不仅可以辅助诊断某些类型实体肿瘤,而且能够监测复发,评估疗效及肺癌分子表达,更是无创肿瘤筛查方法。其来源主要分为循环肿瘤细胞(circulating tumor cells,CTCs),循环肿瘤DNA(circulating tumor DNA,ct DNA)等。本文讨论了肺癌领域中CTCs、ct DNA及其他肿瘤标志物的生物学特征、检测方法及临床应用,总结了保证特异性前提下的高敏感度、便于临床应用、可重复性好三个重要评判标准的"液态活检"技术,尤其是肺癌I期敏感度可达67%的靶向PCR CTC技术的应用,以期使"液态活检"真正从科研探索走向临床应用。

关键词：液态活检循环肿瘤细胞循环肿瘤DNA 靶向PCR

Gefitinib in the treatment of 41 cases with refractory non-small cell lung cancer

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The Chinese-German Journal of Clinical Oncology 2009年第6期8卷 314-316页

作者： Jianfang Xu caicun zhou Aiwu Li Department of Oncology Shanghai Pulmonary Hospital Tongji University Shanghai 200433 China

Objective： We observe the curative effect, median survival time, time to progression, quality of life and adverse effect of patients with advanced refractory non-small cell lung cancer （NSCLC） after gefitinib （Iressa） treatment. Methods： Forty-one patients with grade Ⅲb to Ⅳ NSCLC previously treated with two chemotherapy including 85.4% of patients after second line therapy were chosen. The regimen was oral intake of gefitinib 250 mg once daily until the disease progression or toxic reaction has become intolerable. The patients were required to receive tumor evaluation before the treatment, one month, two month and every three months after Iressa administration. Results： All of 41 patients were evaluable for therapeutic effect. Without complete regression being observed, partial response rate （PR）, stable disease （SD） and progression of disease （PD） were 43.9% （18/41）, 34.1% （14/41） and 22.1% （9/41）, respectively. The overall response rate was 43.9% （18141） and disease control rate （PR ＋ SD） was 78% （32/41）. The response rate in male was 42.1%, while it in female was 45.5% （P 〉 0.05）. Twenty-two of them （53.7%, 22/41） were still alive with 10.1 months of MST when the follow-up ended in November 2006. TTP and MST of patients who died was 2.7 and 5.0 months, respectively. The rate of symptom improvement was 78% of all patients with 13 months of MST of PR patients. The Karnofsky enhanced 20 ＋ 5 after 28 days treatment without 3-4 degree of reactive toxicity. Conclusion： Iressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. Iressa is effective and safe for patients with poor performance status.

关键词： gefitinib non-small cell lung cancer (NSCLC) epidermal growth factor receptor

Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based chemotherapy

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Chinese Journal of Cancer Research 2017年第6期29卷 543-552页

作者： Jinpeng Shi Hui Yang Tao Jiang Xuefei Li Chao Zhao Limin Zhang Sha Zhao Xiaozhen Liu Yijun Jia Yan Wang Lei Xi Shijia Zhang Chunxia Su Shengxiang Ren caicun zhou Department of Medical Oncology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghai 200433China Department of Lung Cancer and Immunology Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China

Objective： Data on the clinical activity of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in patients with non-small-cell lung cancer （NSCLC） and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods： We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC. Results： Seventy patients （13.9%） harboring uncommon EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy. The objective response rate （ORR） and median progression-free survival （mPFS） of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group （ORR： 23.3% vs. 51.8%, P=0.003; mPFS： 7.1 vs. 10.9 months, P〈0.001）. In the uncommon group, mPFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy （7.1 vs. 6.1 months, P=0.893）. In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant （G719X： 8.2 vs. 5.8 months, P=0.061; L861Q： 7.6 vs. 4.1 months, P=0.872）. Multivariate analyses identified adenocarcinoma （P=0.003） as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions： The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC. Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFR- TKIs.

关键词： EGFR uncommon mutation tyrosine kinase inhibitors chemotherapy