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neoadjuvant treatment of pancreatic ductal adenocarcinoma:Whom,when and how

World Journal of Gastrointestinal Surgery 2024年第5期16卷 1223-1230页

作者： Nebojsa Manojlovic Goran Savic Stevan Manojlovic Clinic for Gastroenterology and Hepatology Military Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia Military Medical Academy Faculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia

Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid *** diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant *** 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer *** important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding *** surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and *** main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical *** this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study *** research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.

关键词： Pancreatic adenocarcinoma neoadjuvant treatment Chemotherapy Upfront surgery Radiotherapy Response evaluation

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neoadjuvant treatment:A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Surgery 2021年第9期13卷 885-903页

作者： Ilaria Trestini Marco Cintoni Emanuele Rinninella Futura Grassi Salvatore Paiella Roberto Salvia Emilio Bria Carmelo Pozzo Sergio Alfieri Antonio Gasbarrini Giampaolo Tortora Michele Milella Maria Cristina Mele Section of Oncology Department of MedicinePancreas InstituteUniversity of Verona Hospital TrustVerona 37126Italy Scuola di Specializzazione in Scienza dell’Alimentazione Universitàdi Roma Tor VergataRoma 00133Italy UOC Nutrizione Clinica Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico A.Gemelli IRCCSRoma 00168Italy Dipartimento di Medicina e Chirurgia Traslazionale UniversitàCattolica del Sacro CuoreRoma 00168Italy General and Pancreatic Surgery Unit Pancreas InstituteUniversity of Verona Hospital TrustVerona 37126Italy Oncologia Medica Unit Comprehensive Cancer CenterFondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy Oncologia Medica Unit UniversitàCattolica del Sacro CuoreRoma 00168Italy Digestive Surgery Unit and Pancreatic Surgery Gemelli Center Director Fondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy UOC di Medicina Interna e Gastroenterologia Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy UOSD Nutrizione Avanzata in Oncologia Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy

Patients affected by pancreatic ductal adenocarcinoma(PDAC)frequently present with advanced disease at the time of diagnosis,limiting an upfront surgical *** treatment(NAT)has become the standard of care to downstage non-metastatic locally advanced ***,this treatment increases the risk of a nutritional status decline,which in turn,may impact therapeutic tolerance,postoperative outcomes,or even prevent the possibility of *** on prehabilitation programs on surgical PDAC patients show a reduction of postoperative complications,length of hospital stay,and readmission rate,while data on prehabilitation in NAT patients are scarce and randomized controlled trials are still ***,appropriate nutritional management represents an important therapeutic strategy to promote tissue healing and to enhance patient recovery after surgical *** this regard,NAT may represent a new interesting window of opportunity to implement a nutritional prehabilitation program,aiming to increase the PDAC patient’s capacity to complete the planned therapy and potentially improve clinical and survival *** these perspectives,this review attempts to provide an in-depth view of the nutritional derangements during NAT and nutritional prehabilitation program as well as their impact on PDAC patient outcomes.

关键词： Pancreatic cancer neoadjuvant treatment Pancreatic cancer surgery Nutritional status Nutritional prehabilitation Malnutrition

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neoadjuvant treatment of pancreatic ductal adenocarcinoma:present and future

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Journal of Cancer Metastasis and treatment 2022年第1期8卷 174-196页

作者： Ioannis M.Koukourakis Dimitra Desse Marios Papadimitriou Manousos Konstadoulakis Anna Zygogianni Christos Papadimitriou Oncology Unit Aretaieio University HospitalNational and Kapodistrian University of AthensAthens 11528Greece Radiation Oncology Unit Aretaieio University HospitalNational and Kapodistrian University of AthensAthens 11528Greece Second Department of Surgery Aretaieio University HospitalNational and Kapodistrian University of AthensAthens 11528Greece

Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with a poor *** treatment with acceptable outcomes is yet to be found,with chemo-and radioresistance comprising major impediments towards this *** upfront surgery is the established therapeutic approach for resectable and borderline resectable disease,neoadjuvant treatment has recently monopolized the interest in clinical *** also applies to locally advanced pancreatic adenocarcinomas that could potentially be rendered *** and chemoradiotherapy are the most utilized therapeutic modalities in the neoadjuvant setting,while immunotherapy and targeting agents have been gaining significant *** critical review focuses on the clinical experience gained from retrospective and phase II/III randomized trials,reporting on the outcomes of neoadjuvant chemotherapy and chemoradiotherapy for pancreatic ***,the ongoing trials,including those that involve immunotherapy and targeting agents,are summarized.

关键词： Pancreatic cancer neoadjuvant treatment chemotherapy radiotherapy surgery immunotherapy

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Nonoperative management of gastrointestinal malignancies in era of neoadjuvant treatment

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Chinese Journal of Cancer Research 2023年第1期35卷 44-57页

作者： Nan Chen Jaffer A Ajani Aiwen Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Bejing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer CenterHouston 77030USA

Cancers derived from the gastrointestinal(GI)tract are often treated with radical surgery to achieve a ***,recent advances in the management of GI cancers involve the use of a combination of neoadjuvant radiation and chemotherapy followed by surgical intervention to achieve improved local control and ***,a small proportion of patients with highly sensitive tumors achieved a pathological complete response(pCR)(no residual tumor cells in the resected specimen)to neoadjuvant chemoradiation therapy(nCRT).The desire for organ preservation and avoidance of surgical morbidity brings the idea of a nonoperative management(NOM)*** of the different nature of tumor biology,GI cancers present diverse responses to nCRT,ranging from high sensitivity(anal cancer)to low sensitivity(gastric/esophageal cancer).There is an increasing attention to NOM of localized GI cancers;however,without the use of biomarkers/imaging parameters to select such patients,NOM will remain a ***,this review intends to summarize some of the recent updates from the aspect of current nCRT regimens,criteria for patient selection and active surveillance *** also hope to review significant sequelae of radical surgery and the complications of nCRT to clarify the directions for optimization of nCRT and NOM for oncologic outcomes and quality of life.

关键词： Nonoperative management gastrointestinal malignancies neoadjuvant treatment

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Role of imaging in evaluating the response after neoadjuvant treatment for pancreatic ductal adenocarcinoma

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World Journal of Gastroenterology 2021年第22期27卷 3037-3049页

作者： Yun Zhang Zi-Xing Huang Bin Song Department of Radiology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive *** the development of multimodality treatments,including surgical resection,radiotherapy,and chemotherapy,the long-term prognosis of patients with PDAC remains ***,the introduction of neoadjuvant treatment(NAT)has made more patients amenable to surgery,increasing the possibility of R0 resection,treatment of occult micro-metastasis,and prolongation of overall *** plays a vital role in tumor response evaluation after ***,conventional imaging modalities such as multidetector computed tomography have limited roles in the assessment of tumor resectability after NAT for PDAC because of the similar appearance of tissue fibrosis and tumor *** computed tomography,using blood perfusion as a biomarker,provides added value in predicting the histopathologic response of PDAC to NAT by reflecting the changes in tumor matrix and fibrosis *** imaging technologies,including diffusion-weighted imaging of magnetic resonance imaging and positron emission tomography,can reveal the tumor response by monitoring the structural changes in tumor cells and functional metabolic changes in tumors after *** addition,with the renewed interest in data acquisition and analysis,texture analysis and radiomics have shown potential for the early evaluation of the response to NAT,thus improving patient stratification to achieve accurate and intensive *** this review,we briefly introduce the application and value of NAT in resectable and unresectable *** also summarize the role of imaging in evaluating the response to NAT for PDAC,as well as the advantages,limitations,and future development directions of current imaging techniques.

关键词： Pancreatic ductal adenocarcinoma neoadjuvant treatment Imaging Resectability Tumor response Prognosis

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Loss of human epidermal receptor-2 in human epidermal receptor-2+breast cancer after neoadjuvant treatment:A case report

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World Journal of Clinical Cases 2022年第17期10卷 5923-5928页

作者： Jing Yu Nan-Lin Li Department of Thyroid Breast and Vascular SurgeryXijing HospitalAir Force Medical UniversityXi’an 710032Shaanxi ProvinceChina

BACKGROUND Human epidermal receptor-2(HER-2)expression has been reported to be discordant between primary tumor and metastatic *** SUMMARY We presented a case diagnosed with the HER-2+breast cancer patient who exhibited changes in the expression of HER-2 receptors on tumour samples from surgical specimens obtained after neoadjuvant treatment(NAT)compared with initial *** patient underwent a HER-2-targeted therapy consequently,in spite of HER+gene *** the surgery,the patient subsequently underwent endocrine therapy and *** Changes in HER-2 expression after NAT should be retested by physicians and pathologists before systemic treatment instead of avoiding further HER-2-targeted therapy,and we will perform immunohistochemical multiple-spot biopsy analyses of other important clinical issues to better define prognosis and tailor subsequent adjuvant therapy.

关键词： Human epidermal receptor-2+breast cancer Human epidermal receptor-2 loss neoadjuvant treatment Case report

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neoadjuvant treatment for Esophageal Cancer

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The Chinese-German Journal of Clinical Oncology 2004年第4期3卷 249-252页

作者： PaulM.Schneider HuanXi StephanE.Baldus JanBrabender RalfMetzger DepartmentofVisceral-andVascularSurgery UniversityofCologneCologneGermany DepartmentofGeneralSurgery BeijingHospitalBeijingChina InstituteofPathology UniversityofCologneCologneGermany

Because the con?icting data currently available from the performed randomized trials it is very di?cult to provide strict guidelines for the treatment of patients with locoregional advanced esophageal cancers. Surgery however, remains the standard of care for potentially resectable disease. Preoperative chemotherapy is still controversial with two large randomized trials resulting in two di?erent conclusions regarding the survival bene?t. Preoperative chemoradiation is also controversial since only one randomized trial showed a clear survival bene?t however, the patients treated with surgery alone in this trial had an unusually poor outcome. And the study by Urba et al was not powered enough to show a clear survival bene?t for patients treated with neoadjuvant chemoradiation. The results of three metaanalysis of these randomized studies show lower rate of resection, higher rate of R0-resection, more often postoperative mortality and better prognosis for patients with neoadjuvant radiochemotherapy. As a consequence one may consider o?ering neoadjuvant chemotherapy or neoadjuvant radiochemotherapy to patients with locally- advanced disease under the premise that patients have a good performance status and understand the controversies about this therapeutic option. Larger trials with su?cient power to clearly detect survival bene?ts for patients treated with neoadjuvant chemotherapy or radiochemotherapy are necessary before this therapeutic option will be the standard of care.

关键词： esophageal cancer neoadjuvant treatment

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Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 72-80页

作者： Dong-Yang Ding Lei Liu He-Lin Li Xiao-Jie Gan Wen-Bin Ding Fang-Ming Gu Da-Peng Sun Wen Li Ze-Ya Pan Sheng-Xian Yuan Wei-Ping Zhou Third Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China Department of Radiodiagnosis Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China

Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical ***,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction ***,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs *** is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these *** present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological ***:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital(EHBH).They all met the surgical indications and underwent radical *** randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and *** analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive ***:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in *** nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and N

关键词： Early-stage hepatocellular carcinoma Singular nodular Radiological features Preoperative prognostic model Recurrence-free survival,Overall survival,Linear equation neoadjuvant treatment

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Predictive value of Ki67 and p53 in locally advanced rectal cancer:Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy

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World Journal of Gastroenterology 2008年第7期14卷 1060-1066页

作者： Christiane Jakob Torsten Liersch Wolfdietrich Meyer Heinz Becker Gustavo B Baretton Daniela E Aust Institute for Pathology University of TechnologyFetscherstr. 74D-01307 DresdenGermany Department of General Visceral and Transplantation SurgeryUniversity Medical Center of GttingenRobert-Koch-Str. 40D-37075 GttingenGermany

AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment ***: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading ***: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.

关键词： p53 Ki67 neoadjuvant treatment Rectal cancer Thymidylate synthase

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Cancer nanomedicine in preoperative therapeutics:Nanotechnology-enabled neoadjuvant chemotherapy,radiotherapy,immunotherapy,and phototherapy

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Bioactive Materials 2023年第6期24卷 136-152页

作者： Xiaogang Qu Dong Zhou Jianpu Lu Duotian Qin Jun Zhou Hai-Jun Liu Department of General Surgery Changshu Hospital Affiliated to Nanjing University of Chinese MedicineChangshu215500China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115USA

Surgical resection remains a mainstay in the treatment of malignant solid ***,the use of neoadjuvant treatments,including chemotherapy,radiotherapy,phototherapy,and immunotherapy,either alone or in combination,as a preoperative intervention regimen,have attracted increasing attention in the last *** randomized,controlled trials in some tumor settings have not shown a significant difference between the survival rates in long-term neoadjuvant therapy and adjuvant ***,this has not hampered the increasing use of neoadjuvant treatments in clinical practice,due to its evident downstaging of primary tumors to delineate the surgical margin,tailoring systemic therapy response as a clinical tool to optimize subsequent therapeutic regimens,and decreasing the need for surgery,with its potential for increased *** recent expansion of nanotechnology-based nanomedicine and related medical technologies provides a new approach to address the current challenges of neoadjuvant therapy for preoperative *** review not only summarizes how nanomedicine plays an important role in a range of neoadjuvant therapeutic modalities,but also highlights the potential use of nanomedicine as neoadjuvant therapy in preclinical and clinic settings for tumor management.

关键词： neoadjuvant treatment Preoperative preparation Surgical resection Nanotechnology

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