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The promise of precision medicine:how biomarkers are shaping the future of cholangiocarcinoma treatment

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 457-461页

作者： Rocio I.R.Macias lorenza rimassa Angela Lamarca Experimental Hepatology and Drug Targeting(HEVEPHARM) IBSALUniversity of SalamancaSalamancaSpain National Institute for the Study of Liver and Gastrointestinal Diseases(CIBERehd) Carlos III National Health InstituteMadridSpain Department of Biomedical Sciences Humanitas UniversityPieve Emanuele(Milan)Italy Medical Oncology and Hematology Unit Humanitas Cancer CenterIRCCS Humanitas Research HospitalRozzano(Milan)Italy Department of Oncology OncoHealth InstituteFundación Jiménez Díaz University HospitalMadridSpain Department of Medical Oncology The Christie NHS FoundationManchesterUK Division of Cancer Sciences University of ManchesterManchesterUK

Cholangiocarcinoma(CCA)is the second most frequent primary malignant neoplasm of the hepatobiliary ***,CCA is often diagnosed at an advanced stage,when potentially curative surgical treatments are not *** probability of achieving complete resection in patients who undergo surgery is about 25%(1)and even when complete tumor removal is achieved,the risk of recurrence is greater than 50%.Identification and validation of reliable biomarkers is crucial for the early detection,accurate diagnosis,appropriate staging/prognosis,therapy selection and effective monitoring of patients with biliary tract cancers(BTCs)(Figure 1).Achieving early diagnosis remains a challenge to improve survival and,although many promising biomarkers have been identified(2),to date none have reached clinical practice.

关键词： Biliary cancer biomarker immunotherapy precision medicine targeted therapy

Targeted agents for second-line treatment of advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 788-803页

作者： Nicola Personeni Tiziana Pressiani Silvia Bozzarelli lorenza rimassa Medical Oncology and Hematology Unit Humanitas Cancer CenterHumanitas Clinical and Research CenterIRCCSRozzano 20089MilanItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090MilanItaly

Over the past ten years,sorafenib,a multikinase inhibitor,has been the standard of care for patients with unresectable hepatocellular carcinoma(HCC)and wellpreserved liver ***,lenvatinib,a different multikinase inhibitor,was shown to be non-inferior to sorafenib,in terms of survival,while all other agents previously tested failed to prove non-inferiority(or superiority)when compared to ***,in the second-line setting,most investigational drugs failed to provide better survival outcomes than ***,in the last 2 years three positive phase III trials have been published in this *** RESORCE trial,a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib,showed better outcomes with regorafenib compared to *** recently,the phase III CELESTIAL trial demonstrated the superiority of cabozantinib,a multikinase inhibitor targeting vascular endothelial growth factor receptor,MET,and AXL,vs placebo in the second-and third-line setting in patients progressing on or intolerant to *** survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein ***,the adverse events reported in these trials were in line with the known safety profiles of the tested *** nearly a decade of a certain degree of stagnation,we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.

关键词： Hepatocellular carcinoma Advanced-metastatic Second-line Third-line

Unravel hepatic artery infusion chemotherapy in patients with resected colorectal liver metastases

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Hepatobiliary Surgery and Nutrition 2021年第2期10卷 257-260页

作者： Matteo Donadon lorenza rimassa Guido Torzilli Department of Biomedical Sciences Humanitas UniversityPieve EmanueleMilanItaly Department of Hepatobiliary and General Surgery IRCCS Humanitas Research HospitalRozzanoMilanItaly Humanitas Cancer Center IRCCS Humanitas Research HospitalRozzanoMilanItaly

Over the past years,important progresses have been made in the treatment of patients with colorectal liver metastases(CLM).Now,5-year overall survival rate may exceed 50%by using the combination of multimodality therapies among which modern systemic chemotherapy,with or without monoclonal antibodies,and hepatic resection are the cornerstones(1,2).In such multimodality,hepatic artery infusion(HAI)has been proposed since many years with the rationale of increasing the concentration of chemotherapy agents in the liver(3).However,HAI still remains infrequently used,in particular in the adjuvant setting mainly because of the requirement of a multidisciplinary team to manage therapy,and the more widespread use of systemic chemotherapy-in particular following the perioperative“sandwich”schema(4).

关键词： infusion chemotherapy hepatic

lmmunotherapy in hepatobiliary tumors: search for the missing pieces of the puzzle

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Hepatobiliary Surgery and Nutrition 2020年第1期9卷 86-88页

作者： Matteo Donadon Federica Marchesi lorenza rimassa Guido Torzilli Department of Hepatobiliary and General Surgery Humanitas Clinical and Research Center-IRCCSRozzanoMilanItaly Department of Biomedical Sciences Humanitas UniversityPieve EmanueleMilanItaly Department of Immunology and Inflammation Humanitas Clinical and Research Center-IRCCSRozzanoMilanItaly Department of Biotechnology and Translational Medicine University of MilanMilanItaly Humanitas Cancer Center Humanitas Clinical and Research Center-IRCCSRozzanoMilanItaly

In the current era of immunotherapy, the treatment of hepatobiliary cancers is rapidly evolving. The use of immunotherapeutic approaches, which include peptide-based vaccines, checkpoint inhibitors and antibodies, particularly applies to advanced hepatobiliary cancers, for which the availability of limited therapeutic options encourages the adoption of alternative strategies. Thanks to the published/presented, although conflicting, results of some of the clinical trials on this topic together with the incoming results of some other trials, clinicians involved in the cure of hepatobiliary cancer patients need to understand the basic and advanced applications of immunotherapies (1-6).

关键词： hepato biliary therapeutic

Optimized management of advanced hepatocellular carcinoma:Four long-lasting responses to sorafenib

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World Journal of Gastroenterology 2011年第19期17卷 2450-2453页

作者： Giovanni Abbadessa lorenza rimassa Tiziana Pressiani Cynthia Carrillo-Infante Emanuele Cucchi Armando Santoro Department of Medical Oncology and Hematology Istituto Clinico Humanitas Department of Human Pathology and Oncology Program of Genetic OncologyUniversity of Siena Department of Human Pathology and Oncology Program of Molecular PathologyUniversity of Siena Department of Radiology and Ultrasound Polidiagnostico CAM

The therapeutic options for hepatocellular carcinoma (HCC) have been so far rather *** has shown an overall survival benefit and has become the new standard of care for advanced ***,in clinical practice,some patients are discontinuing this drug because of side effects,and misinterpretation of radiographic response may contribute to *** highlight the importance of prolonged sorafenib ad-ministration,even at reduced dose,and of qualitative and careful radiographic *** observed two partial and two complete responses,one histologically confirmed,with progression-free survival ranging from 12 to 62 *** of the responses were achieved following substantial dose reductions,and a gradual change in lesion density preceded or paralleled tumor shrinkage,as seen by computed *** report supports the feasibility of dose adjustments to allow prolonged administration of sorafenib,and highlights the need for new imaging criteria for a more appropriate characterization of response in HCC.

关键词：化管理肝癌晚期计算机断层扫描治疗方案肝细胞癌临床实践影像学

Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 570-574页

作者： Marco Spadaccini Ana Lleo Roberto Ceriani Giovanni Covini lorenza rimassa Guido Torzilli Luca Di Tommaso Alessio Aghemo Internal Medicine and Liver Unit Humanitas Research Hospital Department of Biomedical Sciences Humanitas University Medical Oncology and Hematology Unit Humanitas Clinical and Research Center Humanitas University Division of Hepatobiliary and General Surgery Department of Surgery Humanitas Clinical and Research Center - IRCCS Humanitas University Pathology Unit Humanitas Research Hospital

To the Editor:Hepatocellular carcinoma (HCC) is the most common primary livertumorandthethirdcauseofcancer-relateddeathsworldwide. HCC is the consequence of malignant transformation of hepatocytes and mainly occurs in patients with cirrhosis. Hepatitis C virus (HCV) chronic infection is a leading cause of end-stage liver diseaseandHCCintheWesterncountries[1].Theapprovalof direct-acting antiviral agents (DAAs) for the treatment of HCV has revolutionized the management of the disease, as no absolute contraindication to treatment exists and sustained virological response

关键词： HCC AFP SVR Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2023年第11期15卷 1900-1912页

作者： Sirish Dharmapuri UmutÖzbek Hiren Jethra Tomi Jun Thomas U Marron Anwaar Saeed Yi-Hsiang Huang Mahvish Muzaffar Matthias Pinter Lorenz Balcar Claudia Fulgenzi Suneetha Amara Arndt Weinmann Nicola Personeni Bernhard Scheiner Tiziana Pressiani Musharraf Navaid Bertram Bengsch Sonal Paul Uqba Khan Dominik Bettinger Naoshi Nishida Yehia Ibrahim Mohamed Arndt Vogel Anuhya Gampa James Korolewicz Antonella Cammarota Ahmed Kaseb Peter R Galle Anjana Pillai Ying-Hong Wan Alessio Cortellini Masatoshi Kudo Antonio D’Alessio lorenza rimassa David James Pinato Celina Ang Tisch Cancer Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Population Health Science and Policy Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Data Analytics Harrisburg Harrisburg University of Science and TechnologyHarrisburdPA 17101United States SEMA4 StamfordCT 06902United States Division of Medical Oncology Kansas University of Kansas Cancer CenterKansasMO 66160United States Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipei 11217Taiwan Department of Internal Medicine Brody School of MedicineEast Carolina UniversityGreenvilleNC 27858United States Department of Internal Medicine III Division of Gastroenterology and HepatologyMedical University of ViennaVienna 1090Austria Department of Surgery and Cancer Imperial College LondonHammersmith Hospital LondonLondon W120HSUnited Kingdom Department of Hepatology Johannes Gutenberg-University Medical CentreNiedersachsen 30625Germany Medical Oncology Unit ASST GardaVia Lungomella ValsecchiBresciaManerbio 25025Italy Medical Oncology and Hematology Unit Humanitas Cancer CenterIRCCS Humanitas Research HospitalMilanRozzano 20089Italy Department of Medicine II Univ Med Ctr FreiburgHugstetter Str 55University Hospital FreiburgFreiburg D-79106Germany Department of Oncology Baltimore LifeBridge HealthBaltimoreMD 21215United States Division of Hematology and Oncology Weill Cornell Medical CollegeNY 10065United States Department of Gastroenterology and Hepatology Kindai University Faculty of MedicineOsaka 577-8502Japan Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Gastroenterology Hepatology and Endocrinology HannoverArndt VogelMedical School HannoverCarl-Neubergstr.Hannover 30659Germany Department of Hepatology Rush University Medical Group 1725 W Harrison St Ste 158ChicagoIL 60612United States Department of Biomedica

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of *** are reported in300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)*** use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of gr

关键词： Neutrophil-lymphocyte ratio Platelet-lymphocyte ratio Inflammatory biomarkers Immunotherapy Immune toxicity

Tumor biopsy and patient enrollment in clinical trials for advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第13期23卷 2448-2452页

作者： lorenza rimassa Maria Reig Giovanni Abbadessa Markus Peck-Radosavljevic William Harris Vittorina Zagonel Davide Pastorelli Elena Rota Caremoli Camillo Porta Nevena Damjanov Hitendra Patel Bruno Daniele Maria Lamar Brian Schwartz Terri Goldberg Armando Santoro Jordi Bruix Medical Oncology and Hematology Unit Humanitas Cancer CenterHumanitas Clinical and Research Center Barcelona Clinic Liver Cancer Group Liver UnitHospital ClinicUniversity of BarcelonaIDIBAPSCIBERehd Clinical Development Ar QuleInc Department of Gastroenterology HepatologyEndrocrinologyand NephrologyKlinikum Klagenfurt am Worthersee Department of Medicine Oncology DivisionUniversity of Washington School of Medicine Department of Clinical and Experimental Oncology Medical Oncology 1Veneto Institute of Oncology-IRCCS Department of Oncology Santa Maria del Prato Hospital Department of Oncology Papa Giovanni XXIII Hospital Department of Oncology Fondazione IRCCS Policlinico San Matteo Division of Gastrointestinal Oncology Abramson Cancer Center of the University of Pennsylvania Department of Medicine The University of Arizona Cancer Center Department of Oncology G.Rummo Hospital Clinical Development Daiichi Sankyo Medical Oncology and Hematology Unit Humanitas Cancer CenterHumanitas Clinical and Research CenterHumanitas University

Tumor biopsies may help to reliably distinguish hepatocellular carcinoma(HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.

关键词： Liver neoplasms Biopsy Biomarkers Clinical trial Tumor