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systemic therapy in gastrointestinal stromal tumors

Oncology and Translational Medicine 2024年第3期10卷 110-118页

作者： Shaoli Li Hui Wang Xiaogang Wang Rui Bai Qunan Sun Sujing Jiang Lifeng Sun Youping Wang Ying Dong Department of Medical Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Cancer Institute Key Laboratory of Cancer Prevention and InterventionMinistry of Educationthe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310009China Department of Pathology the Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Pathology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Respiratory and Critical Care Medicine the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwuChina Colorectal Surgery and Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China.

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal *** GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic *** surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after *** recent years,targeted therapy has significantly improved the prognosis of patients with advanced *** mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this ***,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of ***,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug *** has emerged as a potential approach for the treatment of advanced *** review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

关键词： Gastrointestinal stromal tumors Pathogenesis systemic therapy Drug resistance

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Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

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World Journal of Clinical Oncology 2024年第1期15卷 1-4页

作者： Tao-Wei Ke Yu-Min Liao Sheng-Chi Chang Che-Hung Lin William Tzu-Liang Chen Ji-An Liang Chun-Ru Chien Department of Colorectal Surgery China Medical University HospitalTaichung 40402Taiwan School of Chinese Medicine College of Chinese MedicineChina Medical UniversityTaichung 40402Taiwan Division of Hematology and Oncology Department of Internal MedicineChina Medical University HospitalTaichung 40402Taiwan Department of Colorectal Surgery China Medical University Hsinchu HospitalHsinchu 30272Taiwan School of Medicine College of MedicineChina Medical UniversityTaichung 40402Taiwan Department of Radiation Oncology China Medical University HospitalTaichung 40402Taiwan

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

关键词： Radiotherapy Locally advanced stage rectal cancer Precision medicine systemic therapy Clinical trial

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systemic oncological therapy in breast cancer patients on dialysis

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World Journal of Clinical Oncology 2024年第6期15卷 730-744页

作者： Salman Khan Ghada Araji Ekrem Yetiskul Praneeth Reddy Keesari Fadi Haddadin Zaid Khamis Varun Chowdhry Muhammad Niazi Sarah Afif Meekoo Dhar Suzanne El-Sayegh Department of Internal Medicine Northwell Health-Staten Island University HospitalStaten IslandNY 10305United States Department of Hematology and Oncology Northwell Health-Staten Island University HospitalStaten IslandNY 10305United States Department of Internal Medicine CUNY School of MedicineNew YorkNY 10031United States

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over ***-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast *** cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient ***,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis *** review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and ***,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

关键词： Breast cancer systemic therapy Renal replacement therapy Dialysis End-stage renal disease Hormone therapy Chemotherapy

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Combining local regional therapy and systemic therapy:Expected changes in the treatment landscape of recurrent hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2023年第1期15卷 1-18页

作者： Jing Liang Yi Bai Fu-Shuang Ha Ying Luo Hui-Ting Deng Ying-Tang Gao Department of Hepatology Tianjin Key Laboratory of Extracorporeal Life Support for Critical DiseasesNankai University Affiliated Third Center HospitalTianjin 300170China Department of Hepatobiliary Surgery Tianjin First Central HospitalTianjin 300192China Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Nankai University Affiliated Third Center HospitalTianjin 300170China Tianjin Institute of Hepatobiliary Disease The Third Central Clinical College of Tianjin Medical UniversityTianjin 300170China

Improvements in early screening,new diagnostic techniques,and surgical treatment have led to continuous downward trends in hepatocellular carcinoma(HCC)morbidity and mortality ***,high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of *** clinical characteristics and prognosis of recurrent HCC are heterogeneous,and guidelines on treatment strategies for recurrent HCC are *** such as surgical resection,radiofrequency ablation,and transhepatic arterial chemoembolization are effective for tumors confined to the liver,and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic *** the deepening of the understanding of the immune microenvironment of HCC,blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of *** addition,improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC *** and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent *** paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment,demonstrates the basis for combining local treatment and systemic treatment,and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.

关键词： Recurrent hepatocellular carcinoma Local regional therapy systemic therapy Tumor microenvironment Recurrence type Immune checkpoint inhibitors

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systemic therapy after Radiotherapy Significantly Reduces the Risk of Mortality of Patients with 1-3 Brain Metastases： A Retrospective Study of 250 Patients

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Chinese Medical Journal 2017年第24期130卷 2916-2921页

作者： Bo Li Zhao-Xia Dai Yi-Dong Chen Yan-Wei Liu Shuai Liu Xue-Nan Gu Xiao-Guang Qiu Department of Radiation Oncology Beijing Tiantan Hospital Affiliated to Capital Medical University Beijing 100050 China Department of Medical Oncology The Second Hospital of Dalian Medical University Dalian Liaoning 116027 China Capital Medical University Cancer Center Beijing Shijitan Hospital Capital Medical University Beijing 100038 China

Background：For patients with a brain metastasis （BM）,systemic therapy is usually administered after the completion of radiotherapy,especially in cases of multiple ***,the role of systemic therapy in patients with a limited number of BMs is not ***,we conducted a retrospective study to explore this ***：Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in ***：A total of 250 patients were enrolled;of them,135 received radiotherapy alone and 115 received radiotherapy plus systemic *** patients receiving whole-brain radiation therapy （WBRT） as radiotherapy,28 received WBRT alone and 35 patients received WBRT plus systemic *** the patients treated with stereotactic radiosurgery （SRS）,107 received SRS alone and 80 received SRS plus systemic *** analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone （hazard ratio [HR] =0.294,95% confidence interval [CI] =0.158-0.548）.Further,when the analysis was conducted in subgroups ofWBRT （HR =0.230,95% CI =0.081-0.653） or SRS （HR=0.305,95% CI=0.127-0.731）,systemic therapy still showed the ability to reduce the risk of mortality in patients with ***：systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.

关键词： Brain Metastasis Stereotactic Radiosurgery systemic therapy Whole-brain Radiation therapy

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Treatment Patterns and Economic Assessment of systemic therapy for Metastatic Colorectal Cancer

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Journal of Cancer therapy 2016年第9期7卷 646-655页

作者： Thomas H. Cartwright Lonnie K. Wen Robyn K. Harrell Patricia S. Fox Janet L. Espirito Ed Wang The US Oncology Network McKesson Specialty Health Houston TX USA Bayer Healthcare Whippany NJ USA

Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer deaths in the United States. The goal of this study was to understand treatment patterns, biomarker testing practices, treatment adherence, and the clinical and economic outcomes associated with chemotherapy for metastatic disease. Methods and Materials: We retrospectively examined electronic health records of patients with metastatic CRC who initiated chemotherapy between 01 January 2007 and 30 June 2011, with follow-up to 30 June 2012. Parameters analyzed included demographics and clinical characteristics, treatment patterns, clinical outcomes, and health care resource utilization. Results: In the analysis, 756 patients were included;median age was 61 years (55% male) at start of first line therapy. The most commonly used regimens in the first, second, and third line were FOLFOX + bevacizumab (46%), FOLFIRI + bevacizumab (23%), and irinotecan + cetuximab (23%) respectively. Adherence to guidelines decreased with increasing line of therapy. When assessed by treatment backbone categories in the third line, outcome measures including overall survival (OS), and time to treatment discontinuation (TTD) were not statistically different between groups. In the multivariable model, body mass index (BMI), performance status, and KRAS were significant predictors of survival. Conclusions: This study provides insight into patterns of care and outcomes of mCRC patients for the aforementioned time period. As treatment options for mCRC evolve, it is valuable to understand the continuum of care to help inform future treatment among candidates for continued therapy.

关键词： Metastatic Colorectal Cancer Economic Assessment systemic therapy Treatment Patterns

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Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第19期30卷 2512-2522页

作者： Juan Jose Urquijo-Ponce Carlos Alventosa-Mateu Mercedes Latorre-Sánchez Inmaculada Castelló-Miralles Moisés Diago Hepatology Unit Department of Digestive Diseases Consorcio Hospital General Universitario of ValenciaValencia 46014Spain

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic *** therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at *** the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical *** systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of *** review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative *** also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative ***,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

关键词： Hepatocellular carcinoma Early stage Intermediate stage Neoadjuvant Adjuvant systemic therapy

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New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 15-24页

作者： Jian-Jian Chen Zhi-Cheng Jin Biao Luo Yu-Qing Wang Rui Li Hai-Dong Zhu Gao-Jun Teng Center of Interventional Radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjingJiangsuChina

Background and Aims:Several first-line immune checkpoint inhibitor(ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma(uHCC).This network meta-analysis(NMA)aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for ***:A comprehensive literature search was performed in various databases from database inception to May *** phase 3 trials evaluating first-line single-agent ICIs,molecular-target agents(MTAs),or their combinations in uHCC were *** main endpoints were overall survival(OS)and progression-free survival(PFS).Pooled effect estimates were calculated using a random effects model within the frequentist *** analyses based on etiology were also ***:Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were *** with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305[hazard ratio(HR):1.16;95%confidence interval(CI):0.80–1.68]and camrelizumab plus apatinib(HR:1.06;95%CI:0.75–1.51).The combination therapies,apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS,had higher P-score than single-agent MTAs or *** survival benefits were associated with a high risk of adverse events leading to treatment *** proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages(R2=0.8039,p=0.0155).Conclusion:This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for *** optimal treatment algorithms should consider efficacy,safety,and etiology.

关键词： Hepatocellular carcinoma systemic therapy Immunotherapy Molecular targeted therapy Tyrosine protein kinase inhibitors Overall survival

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Combination approaches in hepatocellular carcinoma:How systemic treatment can benefit candidates to locoregional modalities

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World Journal of Gastroenterology 2022年第28期28卷 3573-3585页

作者： Leonardo Gomes da Fonseca Raphael L C Araujo Department of Medical Oncology Instituto do Cancer do Estado de Sao PauloUniversity of Sao PauloSão Paulo 01246-000São PauloBrazil Hospital e Maternidade Brasil-Rede D'Or São Luiz Santo André09030-590São PauloBrazil Department of Digestive Surgery Escola Paulista de Medicina-UNIFESPSão Paulo 04023-062São PauloBrazil

The management of hepatocellular carcinoma(HCC)is challenging because most patients have underlying cirrhosis,and the treatment provides,historically,a limited impact on the natural history of patients with advanced-stage ***,recurrence rates are high for those patients who receive local and locoregional modalities,such as surgical(resection and transplantation)or imageguided(ablation and intra-arterial)*** research has led to new concepts that are reshaping the current clinical *** advancements were achieved in the understanding of the hallmarks that drive *** has primed a successful incorporation of novel agents with different targets,such as anti-angiogenic drugs,targeted-therapies,and immune-checkpoint *** clinical trials have proven efficacy of systemic agents in advanced stage disease,there is no conclusive evidence to support their use in combination with loco-regional *** novel local modalities are being incorporated(e.g.,radioembolization,microwave ablation,and irreversible electroporation),emerging data indicate that locoregional treatments may induce tumor microenvironment changes,such as hyperexpression of growth factors,release of tumor antigens,infiltration of cytotoxic lymphocytes,and modulation of adaptative and innate immune *** trials that evaluated the use of antiangiogenic drugs in the adjuvant setting after ablation or chemoembolization fail to demonstrate a substantial *** efforts are directed to investigate the role of immunotherapy-based regimens in this *** present review aims to describe the current landscape of systemic and locoregional treatments for HCC,present evidence to support combination approaches,and address future perspectives.

关键词： Liver cancer Hepatocellular carcinoma Immunotherapy systemic therapy Ablation Embolization

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Selection of first-line systemic therapies for advanced hepatocellular carcinoma:A network meta-analysis of randomized controlled trials

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World Journal of Gastroenterology 2021年第19期27卷 2415-2433页

作者： Yue Han Wei-Hua Zhi Fei Xu Chen-Bo Zhang Xiao-Qian Huang Jian-Feng Luo Department of Interventional therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Biostatistics School of Public HealthFudan UniversityShanghai 200034China

BACKGROUND The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma(HCC)used placebo or sorafenib as comparators,and there are limited data providing a cross comparison of treatments in this setting,especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination *** To systematically review and compare response rates,survival outcomes,and safety of first-line systemic therapies for advanced hepatocellular *** We searched PubMed,Science Direct,the Cochrane Database,Excerpta Medica Database,and abstracts from the American Society of Clinical Oncology 2020 annual *** studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable *** of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials.A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments.P value,a frequentist analog to the surface under the cumulative ranking curve,was used to rank *** In total,1398 articles were screened and 27 *** compared were atezolizumab plus bevacizumab,brivanib,donafenib,dovitinib,FOLFOX4,lenvatinib,linifanib,nintedanib,nivolumab,sorafenib,sunitinib,vandetanib,11 sorafenib combination therapies,and three other combination *** overall response rate,lenvatinib ranked 1/19,followed by atezolizumab plus bevacizumab and *** progression-free survival(PFS),atezolizumab+bevacizumab was ranked 1/15,followed by *** the exception of atezolizumab+bevacizumab[hazard ratios(HR)PFS=0.90;95%confidence interval(CI):0.64-1.25],the estimated HRs for PFS for all included treatments vs lenvatinib were>1;however,the associated 95%CI passed through unity for bevacizumab plus erlotinib,linifanib,and *** overall survival,atezolizumab plus bevacizumab was ranked 1/25,followed by

关键词： Hepatocellular carcinoma systemic therapy Meta-analysis Lenvatinib Firstline Immune therapy

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