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Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAr:A systematic literature review

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World Journal of Gastroenterology 2015年第6期21卷 1945-1955页

作者： Michael S Broder David Beenhouwer jonathan r strosberg Maureen P Neary Dasha Cherepanov Partnership for Health Analytic research LLC Beverly Hills H. Lee Moffitt Cancer Center and research Institute Novartis Pharmaceuticals Corporation

AIM:To review literature on efficacy and safety of octreotide-long-acting repeatable(LAr)used at doses higher than the Food and Drug Administration(FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors(NETs).METHODS:We searched Pub Med and Cochrane Library from 1998-2012,5 conferences(American Society of Clinical Oncology,Endocrine Society,European Neuroendocrine Tumor Society,European Society for Medical Oncology,North American Neuroendocrine Tumor Society)from 2000-2013 using Me SH and keyterms including neuroendocrine tumors,carcinoid tumor,carcinoma,neuroendocrine,and *** of accepted articles were also *** reviewers reviewed titles,abstracts,and full-length *** that reported data on efficacy and safety of≥30 mg/mo octreotide-LAr for NETs in human subjects,published in any language were included in the ***:The search identified 1086 publications,of which 238 underwent full-text review(20 were translated into English);17 were included in the *** varied in designs,subjects,octreotide-LAr regimens,and definition of *** studies reported use of higher doses to control symptoms and tumor progression,although symptom severity and formal quality-of-life analysis were not quantitatively *** studies reported efficacy,describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/*** studies reported expert clinical opinion that supported dose escalation of octreotide-LAr up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor *** studies reported safety;there was no evidence of increased toxicity associated with doses of octreotide-LAr>30 mg/***:As reported in this review,octreotide-LAr at doses>30 mg/mo is being prescribed for symptom and tumor control in NET ***,expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal sy

关键词： Carcinoma Neuroendocrine Carcinoid syndrome Carcin

Multimodality approach for locally advanced esophageal cancer

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World Journal of Gastroenterology 2012年第40期18卷 5679-5687页

作者： Khaldoun Almhanna jonathan r strosberg Department of Gastrointestinal Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States

Carcinoma of the esophagus is an aggressive and lethal malignancy with an increasing incidence *** rates vary internationally,with the highest rates found in Southern and Eastern Africa and Eastern Asia,and the lowest in Western and Middle Africa and Central *** with locally advanced disease face a poor prognosis,with 5-year survival rates ranging from 15%-34%.recent clinical trials have evaluated different strategies for management of locoregional cancer;however,because of stage migration and changes in disease epidemiology,applying these trials to clinical practice has become a daunting *** searched Medline and conference abstracts for randomized studies published in the last 3 *** restricted our search to articles published in *** chemoradiotherapy followed by surgical resection is an accepted standard of care in the United *** remains an essential component of treatment and can lead to improved overall survival,especially when performed at high volume *** role of adjuvant chemotherapy following curative resection is still *** beam radiation therapy alone is considered palliative and is typically reserved for patients with a poor performance status.

关键词： Esophageal cancer Adjuvant Neoadjuvant Chemotherapy Chemoradiation

Metastatic type 1 gastric carcinoid:A real threat or just a myth?

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World Journal of Gastroenterology 2013年第46期19卷 8687-8695页

作者： Simona Grozinsky-Glasberg Dimitrios Thomas jonathan r strosberg Ulrich-Frank Pape Stephan Felder Apostolos V Tsolakis Krystallenia I Alexandraki Merav Fraenkel Leonard Saiegh Petachia reissman Gregory Kaltsas David J Gross Neuroendocrine Tumor Unit Endocrinology and Metabolism ServiceDepartment of MedicineHadassah-Hebrew University Medical Center Endocrine Unit Department of PathophysiologyNational University of Athens Moffitt Cancer Center Tampa Department of Internal Medicine Division of HepatologyGastroenterologyEndocrinology and MetabolismCharité Universit tsmedizin Department of Medical Sciences Section of Endocrine OncologyUppsala University Institute of Endocrinology Soroka Ben Gurion University Hospital Department of Surgery Shaare-Zedek Medical CenterThe Hebrew University School of Medicine

AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological findings,the extent of the disease,as well as the use of different therapeutic modalities and the long-term outcome were ***’data were assessed at presentation,and thereafter at 6 to 12 monthly intervals both clinically and biochemically,but also endoscopically and *** were evaluated for the presence of specific symptoms;the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also *** evaluation of response to treatment was defined using established WHO ***:We studied twenty consecutive patients with a mean age of 55.1 *** mean follow-up period was 83 *** patients had regional lymph node metastases and 8 patients had liver *** primary tumor mean diameter was 20.13±10.83mm(mean±SD).The mean Ki-67 index was 6.8%±11.2%.All but one patient underwent endoscopic or surgical excision of the *** disease was stable in all but 3 patients who had progressive liver *** patients remained alive during the follow-up ***:Metastatic GCA1 carries a good overall prognosis,being related to a tumor size of≥1 cm,an elevated Ki-67 index and high serum gastrin levels.

关键词： Metastatic gastric carcinoids Gastrin Chro-mogranin A Somatostatin analogues Stomach neuro-endocrine tumor

Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2015年第8期21卷 2450-2459页

作者： jonathan r strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center and Research Institute Department of Medicine Division of Oncology Stanford University Medical Center Stanford robert H. Lurie Comprehensive Cancer Center of Northwestern University Department of Internal Medicine Division of Medical Oncology University of Kentucky Markey Cancer Center rush University Medical Center Department of Surgery University at Buffalo - State University of New York Department of Medicine Division of Hematology Oncology and Transplantation University of Minnesota Department of Medical Oncology Roswell Park Cancer Institute Department of Medicine Gastroenterology Mount Sinai School of Medicine Mission Health System Asheville Department of Oncology Karmanos Cancer Institute Partnership for Health Analytic research LLC

AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment ***:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic *** this time,there is little data to guide treatment selection and *** therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment *** appropriateness ratings were collected using the rAND/UCLA modified Delphi *** studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 *** were done both before and after an extended discussion of the *** measurements of agreement were made and consensus statements developed from the second round ***:Specialties represented were medical and surgical oncology,interventional radiology,and *** had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)*** the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were *** statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be *** patients with uncontrolled secretory symptoms,octreotide LAr doses can be titrated u

关键词： Unresectable Neuroendocrine carcinomas Neuroendocr

北美神经内分泌肿瘤学会和核医学与分子影像学会有关177Lu-DOTATATE肽受体放射性核素治疗患者选择和合理应用共识

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中华核医学与分子影像杂志 2020年第11期40卷 679-685页

作者：邓艳(译) 张伟(审校) Thomas A.Hope Lisa Bodei Jennifer A.Chan Ghassan El-Haddad Nicholas Fidelman Pamela L.Kunz Josh Mailman Yusuf Menda David C.Metz Erik S.Mittra Daniel A.Pryma Diane L.reidy-Lagunes Simron Singh jonathan r.strosberg 西南医科大学附属医院儿科泸州646000 西南医科大学附属医院核医学科、核医学与分子影像四川省重点实验室泸州646000 Department of radiology and Biomedical Imaging University of CaliforniaSan FranciscoSan FranciscoCalifornia Department of radiology San Francisco VA Medical CenterSan FranciscoCalifornia Molecular Imaging and Therapy Service Department of RadiologyMemorial Sloan Kettering Cancer CenterNew YorkNew York Department of Medicine Dana-Farber Cancer InstituteBostonMassachusetts Department of radiology Moffitt Cancer CenterTampaFlorida Department of Medicine Stanford University School of MedicineStanfordCalifornia NorCal CarciNET Community RiponCalifornia Department of radiology Carver College of MedicineUniversity of IowaIowa CityIowa Division of Gastroenterology Department of MedicinePerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPennsylvania Department of Diagnostic radiology Division of Nuclear Medicine&Molecular ImagingOregon Health&Science UniversityPortlandOregon Division of Nuclear Medicine&Clinical Molecular Imaging Department of RadiologyPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPennsylvania Department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNew York Department of Medical Oncology Odette Cancer CentreSunnybrook Health Sciences CentreTorontoOntario Department of Gastrointestinal Oncology Moffitt Cancer CenterTampaFlorida

随着177Lu-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(DOTATATE)肽受体放射性核素治疗(PrrT)的日益普及,有关患者合理选择的问题日益增多。该文回顾了有关177Lu-DOTATATE在不同原发性神经内分泌肿瘤... 详细信息

随着177Lu-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(DOTATATE)肽受体放射性核素治疗(PrrT)的日益普及,有关患者合理选择的问题日益增多。该文回顾了有关177Lu-DOTATATE在不同原发性神经内分泌肿瘤(NETs)中的应用文献,讨论了一些有争议的问题,并回顾了治疗的潜在禁忌证。此共识是由北美神经内分泌肿瘤学会(NANETS)和核医学与分子影像学会(SNMMI)共同制定的。NANETS是成立于2005年的北美多学科神经内分泌专家专业学会,目的在于通过增加研究和教育机会改善对NETs的管理。NANETS致力于多学科研究,由NETs涉及的不同专业的医师和科学家组成。SNMMI成立于1954年,旨在促进核医学科学、技术和实践应用的国际性科学专业组织,除了出版期刊、时事通讯和书籍外,还主办提高核医学从业人员能力和促进核医学科学新发展的国际会议及讲习班。

关键词： 177Lu-DOTATATE 肽受体放射性核素治疗神经内分泌肿瘤共识

Progress in TNM staging of pancreatic neuroendocrine tumors

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Hepatobiliary Surgery and Nutrition 2021年第2期10卷 238-240页

作者： Taymeyah Al-Toubah jonathan strosberg lee moffitt cancer center department of gi oncologytampaflusa

In recent years,staging classifications for well-differentiated pancreatic neuroendocrine tumors(NETs)have evolved significantly(1-3).Historical classifications,which attempted to combine clinical,pathological,and radiographic findings,were found to be overly *** was not until 2006 that rindi et *** a standard four-stage TNM classification,which was subsequently endorsed by the European Neuroendocrine Tumor Society(ENETS)(4).The T stage distinguished between tumors smaller than 2 cm(T1),2-4 cm(T2),>4 cm or invading duodenum/bile ducts(T3),and invading adjacent structures(T4).N and M stages were defined simply by the presence or absence of regional lymph nodes and distant metastases(Figure 1A).The American Joint Committee on Cancer(AJCC)seventh edition adopted a different TNM classification in 2010,derived from the staging for pancreatic *** this classification,T1 referred to a tumorreferred to a tumor>2 cm,T3 referred to disease extending beyond the pancreas,and T4 referred to the invasion of the celiac axis or SMA(unresectable).As in the ENETS classification,N and M stage were defined simply by the presence or absence of metastases(Figure 1B).

关键词： staging invasion Figure

Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2010年第24期16卷 2963-2970页

作者： jonathan strosberg Larry Kvols H. Lee Moffitt Cancer Center and research Institute

Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAr) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAr 30 mg, supporting the early use of octreotide LAr in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.

关键词： Somatostatin analogues Neuroendocrine tumors Antiproliferative

United States-based practice patterns and resource utilization in advanced neuroendocrine tumor treatment

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World Journal of Gastroenterology 2013年第15期19卷 2348-2354页

作者： jonathan strosberg roman Casciano Lee Stern rohan Parikh Maruit Chulikavit Jacob Willet Zhimei Liu Xufang Wang Krzysztof J Grzegorzewski H Lee Moffitt Cancer Center and research Institute Gastrointestinal Tumor DepartmentTampaFL 33612United States LA-SEr Analytica New YorkNY 10018United States Novartis Oncology Florham Park Novartis Oncology Florham ParkNJ 07932United States

AIM: To assess advanced neuroendocrine tumor (NET) treatment patterns and resource utilization by tumor progression stage and tumor site in the United States. METHODS: United States Physicians meeting eligibility criteria were provided with online data extraction forms to collect patient chart data on recent NET patients. resource utilization and treatment pattern data were collected over a baseline period (after diagnosis and before tumor progression), as well as initial and secondary progression periods, with progression defined according to measureable radiographic evidence of tumor progression. resource categories used in the analysis include: Treatments (e.g. , surgery, chemotherapy, radiotherapy, targeted therapies), hospitalizations and physician visits, diagnostic tests (biomarkers, imaging, laboratory tests). Comparisons between categories of resource utilization and tumor progression status were examined using univariate (by tumor site) and multivariate analyses (across all tumor sites). rESULTS: Fifty-five physicians were included in the study and completed online data extraction forms using the charts of 110 patients. The physician sample showed a relatively even distribution for those affiliated with academic versus community hospitals (46% vs 55%). Forty (36.3%) patients were reported to have pancreatic NET (pNET), while 70 (63.6%) patients had gastrointestinal tract (GI)/Lung as the primary NET site. Univariate analysis showed the proportion of patients hospitalized increased from 32.7% during baseline to 42.1% in the progression stages. While surgeries were performed at similar proportions overall at baseline and progression, pNET patients, were more likely than GI/Lung NET patients to have undergone surgery during the baseline (33.3% vs 25.0%) and any progression periods (26.7% vs 23.4%). While peptide-receptor radionuclide and targeted therapy utilization was low across NET types and tumor stages, GI/Lung types exhibited greater utilization of thes

关键词： Gastrointestinal cancers Neuroendocrine tumors resource utilization Health economics Clinical practice patterns