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Advances of stereotactic body radiotherapy in pancreatic cancer

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Chinese Journal of Cancer Research 2015年第4期27卷 349-357页

作者： Qichun Wei Wei Yu Lauren M.Rosati Joseph M.Herman department of radiation oncology the Second Affiliated Hospital Zhejiang University School of Medicine Department of Radiation Oncology & Molecular Radiation Sciences Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine

Pancreatic cancer（PCA） is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy（SBRT） era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma.

关键词： Stereotactic body radiation therapy（SBRT） pancreatic cancer（PCA）

Strategies to tackle the challenges of external beam radiotherapy for liver tumors

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World Journal of Hepatology 2017年第14期9卷 645-656页

作者： Michael I Lock Jonathan Klein Hans T Chung Joseph M Herman Edward Y Kim William Small Nina A Mayr Simon S Lo department of radiation oncology London Regional Cancer ProgramUniversity of Western Ontario department of radiation oncology Odette Cancer CentreSunnybrook Health Sciences Centre department of radiation oncology the University of Texas department of radiation oncology University of Washington School of Medicine department of radiation oncology Loyola University Medical Center

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.

关键词： Hepatocellular 癌肝转移 4DCT 指导图象的放射疗法 Stereotactic 身体放射治疗

Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2374-2383页

作者： Yang Gao Jie Gao Ganen Mu Yumin Zhang Fan Huang Wenxue Zhang Chunhua Ren Cuihong Yang Jianfeng Liu Tianjin Key Laboratory of radiation Medicine and molecular Nuclear Medicine Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China radiation oncology department Tianjin Medical University General HospitalTianjin 300052China

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.

关键词： In situ enzyme-instructed self-assembly(EISA) Pre-assembly Alkaline phosphatase(ALP) Peptide Cancer radiotherapy Nanofiber Histone deacetylases inhibitor(HDACI) Radiosensitizer

Radiotherapy-induced heart disease:a review of the literature

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Precision Clinical Medicine 2019年第4期2卷 270-282页

作者： Bingwen Zou Julius Philipp Schuster Kerun Niu Qianyi Huang Alexander Rühle Peter Ernst Huber department of radiation oncology Heidelberg University HospitalIm Neuenheimer Feld 400Heidelberg 69120Germany department of molecular radiation oncology German Cancer Research CenterIm Neuenheimer Feld 280Heidelberg 69120Germany Heidelberg Institute for radiation oncology(HIRO)and National Center for radiation oncology(NCRO) Im Neuenheimer Feld 280Heidelberg 69120Germany

Radiotherapy as one of the four pillars of cancer therapy plays a critical role in the multimodal treatment of thoracic cancers.Due to significant improvements in overall cancer survival,radiotherapy-induced heart disease(RIHD)has become an increasingly recognized adverse reaction which contributes to major radiationassociated toxicities including non-malignant death.This is especially relevant for patients suffering from diseases with excellent prognosis such as breast cancer or Hodgkin’s lymphoma,since RIHD may occur decades after radiotherapy.Preclinical studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart injury.Epidemiological findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously assumed.Recent preclinical studies have identified non-invasive methods for evaluation of RIHD.Furthermore,potential options preventing or at least attenuating RIHD have been developed.Ongoing research may enrich our limited knowledge about biological mechanisms of RIHD,identify non-invasive early detection biomarkers and investigate potential treatment options that might attenuate or prevent these unwanted side effects.Here,we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in RIHD.Biological mechanisms and treatment options are outlined,and challenges in RIHD treatment are summarized.

关键词： Radiotherapy heart injury thoracic cancer radiation-induced heart injury cancer treatment

Identification of Factors Influencing Radiotherapy Errors during radiation Treatments Using Quality Management Tools

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肿瘤预防与治疗 2022年第1期35卷 7-13页

作者： Li Lintao Lucia Clara Orlandini Wang Xianliang Fan Ming Lu Shun Kang Shengwei Zhang Dekang Heng Li department of radiation oncology Sichuan Cancer HospitalChengdu 610041China department of radiation Oncol ogy and molecular radiation sciences Johns Hopkins University School of MedicineBaltimoreMD 21205USA

Objective:To investigate factors that may cause radiotherapy errors during radiation treatments using quality management tools.Methods:The Delphi method was used to sort out the factors that cause radiotherapy errors which were then clasified by the Kaiser model.Results:In the first round of brainstorming,33 types of influencing factors were put forward,which were further reduced to 19 through the Delphi method.The recruited factors were,then,divided into four types by the Kaiser model,radiotherapyspecific factors with the mean weight of 49.49%,patient-related factors with the mean weight of 42.27%,therapist-related factors with the mean weight of 35.64% and hardware-related factors with the mean weight of 19.72%.Conclusion:Delphi plus Kaiser may be a promising method for predicting factors that may cause radiotherapy errors,which is worthy of further research.

关键词： Radiotherapy errors Delphi method Kaiser model Radiotherapy

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

Commensal microbiota in the digestive tract:a review of its roles in carcinogenesis and radiotherapy

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Cancer Biology & Medicine 2022年第1期19卷 43-55页

作者： Jiali Dong Yuan Li Huiwen Xiao Ming Cui Saijun Fan Tianjin Key Laboratory of radiation Medicine and molecular Nuclear Medicine Institute of Radiation MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China department of Microbiology College of Life SciencesNankai UniversityTianjin 300071China

The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body,including the mouth,lung,intestines,skin,and vagina.These microbial communities are involved in many essential functions,such as metabolism,immunity,host nutrition,and diseases.Recent studies have focused on the microbiota associated with cancers,particularly the oral and intestinal microbiota.Radiotherapy,the most effective cytotoxic modality available for solid tumors,contributes to the treatment of cancer patients.Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy.Here,we review current research on the microbiota and cancer development,and describe knowledge gaps in the study of radiotherapy and the microbiota.Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.

关键词： Oral microbiome gut microbiome cancer radiotherapy

PI3K/AKT/mTOR pathway,hypoxia,and glucose metabolism:Potential targets to overcome radioresistance in small cell lung cancer

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Cancer Pathogenesis and Therapy 2023年第1期1卷 56-66页

作者： Huan Deng Yamei Chen Peijing Li Qingqing Hang Peng Zhang Ying Jin Ming Chen department of Medical oncology The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiang 310022China department of radiation oncology Zhejiang Key Laboratory of Radiation OncologyHangzhouZhejiang 310022China department of radiation oncology Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China College of Life sciences University of the Chinese Academy of SciencesBeijing 100049China department of radiation oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen UniversityGuangzhouGuangdong 510060China

Small cell lung cancer(SCLC)is a highly aggressive tumor type for which limited therapeutic progress has been made.Platinum-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment,but most patients with SCLC acquire therapeutic resistance.Given the need for more effective therapies,better elucidation of the molecular pathogenesis of SCLC is imperative.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid tumors.This pathway is an important regulator of cancer cell glucose metabolism,and its activation probably effects radioresistance by influencing bioenergetic processes in SCLC.Glucose metabolism has three main branches-aerobic glycolysis,oxidative phosphorylation,and the pentose phosphate pathway-involved in radioresistance.The interaction between the PI3K/AKT/mTOR pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1(HIF-1)signaling.The PI3K/AKT/mTOR pathway also influences glucose metabolism through other mechanisms to participate in radioresistance,including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate pathway.This review summarizes our understanding of links among the PI3K/AKT/mTOR pathway,hypoxia,and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating disease.

关键词： Small cell lung cancer PI3K/AKT/mTOR pathway Glucose metabolism Radioresistance

Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas

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World Journal of Gastrointestinal oncology 2016年第4期8卷 358-365页

作者： Crystal S Seldon Lauren E Colbert William A Hall Sarah B Fisher David S Yu Jerome C Landry department of radiation oncology Winship Cancer Institute Emory University School of Medicine department of radiation oncology Memorial Sloan Kettering Cancer Center department of radiation oncology the Medial College of Wisconsin Division of Surgical oncology Department of Surgery Emory University School of Medicine

Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.

关键词： Chromodomain-helicase-DNA binding protein 5 Chromodomain-helicase-DNA binding protein 7 Mixed lineage kinase domain-like protein Pancreatic adenocarcinoma Biomarker