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Advances in regional nodal management of early-stage breast cancer

Chinese Journal of cancer Research 2024年第2期36卷 215-225页

作者： Zhao Bi Yongsheng Wang Breast cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

关键词： Breast cancer sentinel lymph node biopsy internal mammary lymph node radiotherapy surgery

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Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell lung cancer:a retrospective analysis

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Frontiers of Medicine 2022年第4期16卷 610-617页

作者： Yaru Tian Hairong Tian Xiaoyang Zhai Hui Zhu Jinming Yu Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical ScienceJinan 250117China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong UniversityJinan 250117China

Bevacizumab,an anti-VEGF monoclonal antibody,has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC(ns-NSCLC).However,the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation.Thus,59 patients were included in the present retrospective study,22 patients in the bevacizumab plus pemetrexed and platinum(B+PP)group,and 37 patients in the pemetrexed and platinum(PP)group.For the entire cohort of patients,the median OS was 33.3 months,and the 1-year and 2-year overall survival rates were 88.5%and 67.8%,respectively.The median OS and 1-year and 2-year OS rates were 20.5 months,70.3%and 0%,respectively,in the B+PP group and 33.4 months,97.0%and 89.4%,respectively,in the PP group(P<0.001).The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group(27.3%vs.10.8%,respectively;P=0.204).Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS,whereas the addition of bevacizumab was an unfavorable prognostic factor.With increased toxicities,the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.

关键词： bevacizumab elderly patient advanced non-small-cell lung cancer overall survival toxicity

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Optimization of regional nodal irradiation in the era of sentinel lymph node biopsy

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cancer Biology & Medicine 2023年第2期20卷 89-92页

作者： Zhao Bi Xue’er Wang Pengfei Qiu Peng Chen Yongsheng Wang Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China Tianjin Medical University cancer institute&hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China

Historically,axillary lymph node dissection(ALND)was the standard management for axillary sentinel lymph node(SLN)-positive patients,because it enables full assessment of overall axillary lymph node(ALN)metastasis sta... 详细信息

关键词： lymph metastasis dissection

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The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

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cancer Biology & Medicine 2020年第3期17卷 599-611页

作者： Xiaoyang Zhai Jian Zhang Yaru Tian Ji Li Wang Jing Hongbo Guo Hui Zhu Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Thoracic Surgery Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Radiation Oncology Shandong Cancer Hospital and Institute affiliated with Shandong UniversityJinan 250012China

Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse events.Checkpoint inhibitor pneumonitis(CIP)has been reported to have a morbidity rate of 3%to 5%and a mortality rate of 10%to 17%.Moreover,the incidence of CIP in NSCLC is higher than that in other tumor types,reaching 7%to 13%.With the increased use of ICIs in NSCLC,CIP has drawn extensive attention from oncologists and cancer researchers.Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events.In this review,the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease,prior thoracic irradiation,and combinations with other drugs.Our review also explored potential mechanisms closely related toCIP,including increasedT cell activity against associated antigens in tumor and normal tissues,preexisting autoantibodies,and inflammatory cytokines.

关键词： Immune checkpoint inhibitor non-small-cell lung cancer pneumonitis risk factors

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Pivotal roles of tumor-draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy

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cancer Communications 2022年第10期42卷 971-986页

作者： Zhaoyun Liu Zhiyong Yu Dawei Chen Vivek Verma Chenxi Yuan Minglei Wang Fei Wang Qing Fan Xingwu Wang Yang Li Yuequn Ma Meng Wu Jinming Yu Department of Oncology Shandong University Cancer CenterJinanShandong 250117P.R.China Department of Radiation Oncology and shandong Provincial Key Laboratory of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Breast cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Department of Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTexas 77030United States Department of Pharmacy Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117P.R.China Research Unit of Radiation Oncology Chinese Academy of Medical SciencesJinanShandong 250117P.R.China

Background:Currently,due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects,combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1)immune checkpoint inhibition(immuno-radiotherapy,iRT)has revolutionized the therapeutic guidelines.It has been demonstrated that tumor-draining lymph nodes(TDLN)are essential for effective antitumor immunity induced by radiotherapy,immunotherapy,or iRT.Given that the function of TDLN in iRT remains unclear,this study aimed to investigate the function and mechanism of TDLN in iRT-induced abscopal effects.Methods:The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN.The flow cytometry,multiple immunofluorescence analysis,and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment.Additionally,we tempted to interrogate the possible mechanisms via RNA-sequencing of tumor-infiltrating lymphocytes and TDLN.Results:TDLN deficiency impaired the control of tumor growth by monotherapy.Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT-stimulated anti-tumor and abscopal effects.Furthermore,in the absence of TDLN,the infiltration of CD45+and CD8+T cells was substantially reduced in both primary and abscopal tumors,and the anti-tumor function of CD8+T cells was attenuated as well.Additionally,the polarization of tumor-associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN.RNA-sequencing data indicated that impaired infiltration and anti-tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment.Conclusions:TDLN play a critical role in iRT by promoting the infiltration of CD8+T cells and maintaining the M1/M2 macrophage ratio.

关键词： immuno-radiotherapy tumor-draining lymph node T cells tumor-associated macrophage

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Primary tumor location in lung cancer:the evaluation and administration

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Chinese Medical Journal 2022年第2期135卷 127-136页

作者： Xueqi Xie Xiaolin Li Wenjie Tang Peng Xie Xuefen Tan School of Medicine and Life Sciences Shandong First Medical UniversityJinanShandong 250117China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117China

Lung cancer continues to be the leading cause of cancer-related death in the world,which is classically subgrouped into two major histological types:Non-small cell lung cancer(NSCLC)(85%of patients)and small-cell lung cancer(SCLC)(15%).Tumor location has been reported to be associated with the prognosis of various solid tumors.Several types of cancer often occur in a specific region and are more prone to spread to predilection locations,including colorectal cancer,prostate cancer,gastric cancer,ovarian cancer,cervical cancer,bladder cancer,lung tumor,and so on.Besides,tumor location is also considered as a risk factor for lung neoplasm with chronic obstructive pulmonary disease/emphysema.Additionally,the primary lung cancer location is associated with specific lymph node metastasis.And the recent analysis has shown that the primary location may affect metastasis pattern in metastatic NSCLC based on a large population.Numerous studies have enrolled the“location”factor in the risk model.Anatomy location and lobe-specific location are both important in prognosis.Therefore,it is important for us to clarify the characteristics about tumor location according to various definitions.However,the inconsistent definitions about tumor location among different articles are controversial.It is also a significant guidance in multimode therapy in the present time.In this review,we mainly aim to provide a new insight about tumor location,including anatomy,clinicopathology,and prognosis in patients with lung neoplasm.

关键词： lung anatomy metastasis

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A machine learning model to predict efficacy of neoadjuvant therapy in breast cancer based on dynamic changes in systemic immunity

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cancer Biology & Medicine 2023年第3期20卷 218-228页

作者： Yusong Wang Mozhi Wang Keda Yu Shouping Xu Pengfei Qiu Zhidong Lyu Mingke Cui Qiang Zhang Yingying Xu Department of Breast Surgery The First Hospital of China Medical UniversityShenyang 110001China Department of Breast Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Breast Surgery Harbin Medical University Cancer HospitalHarbin 150081China Breast cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical ScienceJinan 250117China Breast Center The Affliated Hospital of Qingdao UniversityQingdao 266003China Department of Breast Surgery Liaoning Cancer Hospital and InstituteShenyang 110801China

Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.

关键词： Breast cancer neoadjuvant therapy peripheral blood lymphocytes machine learning prediction model

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Development and validation of radiomics model built by incorporating machine learning for identifying liver fibrosis and early-stage cirrhosis

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Chinese Medical Journal 2020年第22期133卷 2653-2659页

作者： Qing-Tao Qiu Jing Zhang Jing-Hao Duan Shi-Zhang Wu Jia-Un Ding Yong Yin Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117China Department of Radiation Oncology Cancer Institute and HospitalTianjin Medical UniversityTianjin 300060China School of Physics and Electronics Shandong Normal UniversityJinanShandong 250358China

Background:Liver fibrosis(LF)continues to develop and eventually progresses to cirrhosis.However,LF and early-stage cirrhosis(ESC)can be reversed in some cases,while advanced cirrhosis is almost impossible to cure.Advances in quantitative imaging techniques have made it possible to replace the gold standard biopsy method with non-invasive imaging,such as radiomics.Therefore,the purpose of this study is to develop a radiomics model to identify LF and ESC.Methods:Patients with LF(n=108)and ESC(n=116)were enrolled in this study.As a control,patients with healthy livers were involved in the study(n=145).Diffusion-weighted imaging(DWI)data sets with three b-values(0,400,and 800 s/mm2)of enrolled cases were collected in this study.Then,radiomics features were extracted from manually delineated volumes of interest.Two modeling strategies were performed after univariate analysis and feature selection.Finally,an optimal model was determined by the receiver operating characteristic area under the curve(AUC).Results:The optimal models were built in plan 1.For model 1 in plan 1,the AUCs of the training and validation cohorts were 0.973(95%confidence interval[CI]0.946-1.000)and 0.948(95%CI 0.903-0.993),respectively.For model 2 in plan 1,the AUCs of the training and validation cohorts were 0.944,95%CI 0.905 to 0.983,and 0.968,95%CI 0.940 to 0.996,respectively.Conclusions:Radiomics analysis of DWI images allows for accurate identification of LF and ESC,and the non-invasive biomarkers extracted from the functional DWI images can serve as a better alternative to biopsy.

关键词： Diffusion-weighted imaging Liver fibrosis Early-stage cirrhosis Radiomics Machine learning

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Progress of radiation oncology： known and unknown

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Chinese Medical Journal 2014年第11期127卷 2173-2179页

作者： Liu Jing Yu Jinming Department of Radiation Oncology Shandong Cancer Hospital and Institute Shandong University Jinan Shandong 250117 China

Objective To elaborate known and unknown aspects of radiation oncology.Data sources Data cited in this review were obtained mainly from PubMed and Medline in English from 1999 to 2013,with keywords ＂individualized medicine＂,＂personalized medicine＂,＂radiation dose＂,＂radiation target＂,＂molecular targeted therapy＂,＂molecular imaging＂ and ＂functional imaging＂.Study selection Articles regarding radiation target delineation,radiation doses,new technology and equipment,combination of radiotherapy and molecular targeted therapy as well as other aspects were identified,retrieved and reviewed.Results A larger radiation field and a higher radiation dose are not always better.New equipment and technology are also not always better than conventional equipment and technologies.Effectiveness of radiotherapy combined with molecular targeted therapy needs more data to verify.Conclusion Personalized radiotherapy is the direction for the future.

关键词： individualized medicine radiotherapy positron-emission tomography targeted molecular therapy

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New insights into the suppression of inflammation and lipid accumulation by JAZF1

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Genes & Diseases 2023年第6期10卷 2457-2469页

作者： Wujun Chen Yingjie Zhong Yang Yuan Meng Zhu Wenchao Hu Ning Liu Dongming Xing cancer institute Department of NeurosurgeryThe Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao Cancer InstituteQingdaoShandong 266071China Department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdaoShandong 266035China School of Life Sciences Tsinghua UniversityBeijing 100084China

Atherosclerosis is one of the leading causes of disease and death worldwide.The identification of new therapeutic targets and agents is critical.JAZF1 is expressed in many tissues and is found at particularly high levels in adipose tissue(AT).JAZF1 suppresses inflammation(including IL-1β,IL-4,IL-6,IL-8,IL-10,TNFα,IFN-γ,IAR-20,COL3A1,laminin,and MCP-1)by reducing NF-κB pathway activation and AT immune cell infiltration.JAZF1 reduces lipid accumulation by regulating the liver X receptor response element(LXRE)of the SREBP-1c promoter,the cAMP-response element(CRE)of HMGCR,and the TR4 axis.LXRE and CRE sites are present in many cytokine and lipid metabolism gene promoters,which suggests that JAZF1 regulates these genes through these sites.NF-κB is the center of the JAZF1-mediated inhibition of the inflammatory response.JAZF1 suppresses NF-κB expression by suppressing TAK1 expression.Interestingly,TAK1 inhibition also decreases lipid accumulation.A dual-targeting strategy of NF-κB and TAK1 could inhibit both inflammation and lipid accumulation.Dual-target compounds(including prodrugs)1–5 exhibit nanomolar inhibition by targeting NF-κB and TAK1,EGFR,or COX-2.However,the NF-κB suppressing activity of these compounds is relatively low(IC50>300 nM).Compounds 6–14 suppress NF-κB expression with IC50 values ranging from 1.8 nM to 38.6 nM.HS-276 is a highly selective,orally bioavailable TAK1 inhibitor.Combined structural modifications of compounds using a prodrug strategy may enhance NF-κB inhibition.This review focused on the role and mechanism of JAZF1 in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.

关键词： Atherosclerosis CRE JAZF1 LXRE NF-κB TAK1

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