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  • 101. Scardoni, Maria
    et al.
    Vittoria, Emanuele
    Volante, Marco
    Rusev, Borislav
    Bersani, Samantha
    Mafficini, Andrea
    Gottardi, Marisa
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Malleo, Giuseppe
    Butturini, Giovanni
    Cingarlini, Sara
    Fassan, Matteo
    Scarpa, Aldo
    Mixed Adenoneuroendocrine Carcinomas of the Gastrointestinal Tract: Targeted Next-Generation Sequencing Suggests a Monoclonal Origin of the Two Components2014Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 100, nr 4, s. 310-316Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract are rare neoplasms characterized by coexisting exocrine and neuroendocrine neoplastic components. MANECs' histogenetic classification and molecular characterization remain unclear, significantly affecting the identification of innovative therapeutic options for these tumors. Methods: The exocrine and neuroendocrine components of 6 gastrointestinal MANECs were microdissected and subjected to the simultaneous mutation assessment in selected regions of 54 cancer-associated genes using Ion Torrent semiconductor-based next-generation sequencing. Sanger sequencing and immunohistochemistry were used as validation of the mutational status. Results: A total of 20 driver gene somatic mutations were observed among the 12 neoplastic components investigated. In 11 of 12 (91.7%) samples, at least one mutation was detected; 7 samples (58.3%) were found to have multiple mutations. TP53 gene mutations were the most frequent genetic alterations observed in the series, occurring in 11/12 samples (91.7%). Somatic mutations in other genes were detected at lower frequencies: ATM, CTNNB1, ERBB4, JAK3, KDR, KRAS, RB1. Conclusions: Five of the 6 MANECs presented an overlapping mutational profile in both components, suggesting a monoclonal origin of the two MANEC components.

  • 102.
    Selvaraju, Ram Kumar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Velikyan, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Asplund, Veronika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Wu, Zhanhong
    Todorov, Ivan
    Shively, Jack
    Kandeel, Fouad
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Pre-clinical evaluation of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 for imaging of insulinoma2014Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 41, nr 6, s. 471-476Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Insulinoma is the most common form of pancreatic endocrine tumors responsible for hyperinsulinism in adults. These tumors overexpress glucagon like peptide-1 (GLP-1) receptor, and biologically stable GLP-1 analogs have therefore been proposed as potential imaging agents. Here, we evaluate the potential of a positron emission tomography (PET) tracer, [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4, for imaging and quantification of GLP-1 receptors (GLP-1R) in insulinoma.

    METHODS: [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was evaluated for binding to GLP-1R by in vitro autoradiography binding studies in INS-1 tumor from xenografts. In vivo biodistribution was investigated in healthy control mice, INS-1 xenografted and PANC1 xenografted immunodeficient mice at two different doses of peptide: 2.5μg/kg (baseline) and 100μg/kg (block). In vivo imaging of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in xenografted mice was evaluated by small animal PET/CT using a direct comparison with the clinically established insulinoma marker [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP).

    RESULTS: GLP-1 receptor density could be quantified in INS-1 tumor biopsies. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 showed significant uptake (p≤0.05) in GLP1-R positive tissues such as INS-1 tumor, lungs and pancreas upon comparison between baseline and blocking studies. In vivo imaging showed concordant results with higher tumor-to-muscle ratio in INS-1 xenografted mice compared with [(11)C]5-HTP.

    CONCLUSION: [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 has high affinity and specificity for GLP-1R expressed on insulinoma in vitro and in vivo.

  • 103.
    Singh, Simron
    et al.
    Univ Toronto, Toronto, ON, Canada.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Wolin, Edward
    Montefiore Einstein Ctr Canc Care, Bronx, NY USA.
    Warner, Richard
    Mt Sinai Sch Med, New York, NY USA.
    Sissons, Maia
    NET Patient Fdn, Hockley Heath, England.
    Kolarova, Teodora
    APOZ & Friends, Sofia, Bulgaria.
    Goldstein, Grace
    Carcinoid Canc Fdn Inc, White Plains, NY USA.
    Pavel, Marianne
    Charite Univ Med Berlin, Berlin, Germany.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Leyden, John
    Unicorn Fdn, Mosman, NSW, Australia.
    Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs2017Inngår i: Journal of global oncology, ISSN 2378-9506, Vol. 3, nr 1, s. 43-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Despite the considerable impact of neuroendocrine tumors (NETs) on patients' daily lives, the journey of the patient with a NET has rarely been documented, with published data to date being limited to small qualitative studies. NETs are heterogeneous malignancies with nonspecific symptomology, leading to extensive health care use and diagnostic delays that affect survival. A large, international patient survey was conducted to increase understanding of the experience of the patient with a NET and identify unmet needs, with the aim of improving disease awareness and care worldwide.

    METHODS: An anonymous, self-reported survey was conducted (online or on paper) from February to May 2014, recruiting patients with NETs from > 12 countries as a collaboration between the International Neuroendocrine Cancer Alliance and Novartis Pharmaceuticals. Survey questions captured information on sociodemographics, clinical characteristics, NET diagnostic experience, disease impact/management, interaction with medical teams, NET knowledge/awareness, and sources of information. This article reports the most relevant findings on patient experience with NETs and the impact of NETs on health care system resources.

    RESULTS: A total of 1,928 patients with NETs participated. A NET diagnosis had a substantially negative impact on patients' personal and work lives. Patients reported delayed diagnosis and extensive NET-related health care resource use. Patients desired improvement in many aspects of NET care, including availability of a wider range of NET-specific treatment options, better access to NET experts or specialist centers, and a more knowledgeable, better-coordinated/-aligned NET medical team.

    CONCLUSION: This global patient-reported survey demonstrates the considerable burden of NETs with regard to symptoms, work and daily life, and health care resource use, and highlights considerable unmet needs. Further intervention is required to improve the patient experience among those with NETs.

  • 104.
    Staaf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Åkerström, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Ljungström, Viktor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Karlsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hög tid att söka till nya MD/PhD-programmet vid Uppsala universitet: Tidig bro mellan preklinisk forskning och klinik2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 17-18, s. 898-898Artikkel i tidsskrift (Fagfellevurdert)
  • 105.
    Stridsberg, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Janson, Eva Tiensuu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Measurements of secretogranins II, III, V and proconvertases 1/3 and 2 in plasma from patients with neuroendocrine tumours2008Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 148, nr 1-3, s. 95-98Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION:

    Chromogranin (Cg) and secretogranin (Sg) are members of the granin family of proteins, which are expressed in neuroendocrine and nervous tissue. In recent publications we have presented generation of region-specific antibodies against CgA and CgB and also development of several region-specific radioimmunoassays for measurements of specific parts of the Cgs. In this study we describe generation of antibodies against SgII, SgIII, SgV and the proconvertases PC1/3 and PC2 and development of radioimmunoassays for measurements of these proteins.

    MATERIALS AND METHODS:

    Peptides homologous to defined parts of the secretogranin and proconvertase molecules were selected and synthesised. Antibodies were raised, radioimmunoassays were developed and circulating levels of the proteins in plasma samples from 22 patients with neuroendocrine tumours were measured in the assays.

    RESULTS:

    Increased plasma concentrations were recorded in 11, 4 and 3 of the patients with the SgII 154-165 (N-terminal secretoneurin), the SgII 172-186 (C-terminal Secretoneurin) and the SgII 225-242 assays respectively. The SgIII, SgV, PC1/3 and PC2 assays failed to detect increased concentrations in any of the patients.

    CONCLUSION:

    Increased concentrations of SgII, especially the N-terminal part of secretoneurin could be measured in plasma from patients with endocrine pancreatic tumours and in this case this assay was quite comparable to measurements of CgA and CgB. Even though secretoneurin was not as frequently increased as CgA and CgB in patients with carcinoid tumours or pheochromocytoma it may be a useful marker for endocrine pancreatic tumours.

  • 106.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA..
    El-Haddad, G.
    H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA..
    Wolin, E.
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Hendifar, A.
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Yao, J.
    Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA..
    Chasen, B.
    Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA..
    Mittra, E.
    Stanford Univ, Sch Med, Stanford, CA 94305 USA..
    Kunz, P. L.
    Stanford Univ, Sch Med, Stanford, CA 94305 USA..
    Kulke, M. H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Jacene, H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Bushnell, D.
    Univ Iowa, Iowa City, IA USA..
    O'Dorisio, T. M.
    Univ Iowa, Iowa City, IA USA..
    Baum, R. P.
    Zentralklin, Bad Berka, Germany..
    Kulkarni, H. R.
    Zentralklin, Bad Berka, Germany..
    Caplin, M.
    Royal Free Hosp, London, England..
    Lebtahi, R.
    Hop Beaujon, Clichy, France..
    Hobday, T.
    Mayo Clin Coll Med, Rochester, MN USA..
    Delpassand, E.
    Excel Diagnost Imaging Clin, Houston, TX USA..
    Van Cutsem, E.
    Univ Hosp, Leuven, Belgium.;Katholieke Univ Leuven, Leuven, Belgium..
    Benson, A.
    Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA..
    Srirajaskanthan, R.
    Kings Coll Hosp NHS FDN Trust, London, England..
    Pavel, M.
    Charite, Berlin, Germany..
    Mora, J.
    Hosp Univ Bellvitge, Barcelona, Spain..
    Berlin, J.
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Grande, E.
    Hosp Univ Ramon & Cajal, Madrid, Spain..
    Reed, N.
    Beatson Oncol Ctr, Glasgow, Lanark, Scotland..
    Seregni, E.
    Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, M. Lopera
    Adv Accelerator Applicat USA, New York, NY USA..
    Santoro, P.
    Adv Accelerator Applicat USA, New York, NY USA..
    Thevenet, T.
    Adv Accelerator Applicat, St Genis Pouilly, France..
    Erion, J. L.
    Adv Accelerator Applicat USA, New York, NY USA..
    Ruszniewski, P.
    Hop Beaujon, Clichy, France..
    Kwekkeboom, D.
    Erasmus MC, Rotterdam, Netherlands..
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands..
    Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors2017Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 376, nr 2, s. 125-135Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials. gov number, NCT01578239; EudraCT number 2011-005049-11.)

  • 107.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA..
    Wolin, E.
    Markey Canc Ctr, Lexington, KY USA..
    Chasen, B.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Bushnell, D.
    Univ Iowa, Med Ctr, Iowa City, IA USA..
    Caplin, M.
    Royal Free Hosp, London, England..
    Baum, R.
    Zent Klin, Bad Berka, Germany..
    Kunz, P.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Hobday, T.
    Mayo Clin, Coll Med, Rochester, MI USA..
    Hendifar, A.
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, Lopera M.
    Adv Accelerator Applicat, New York, NY USA..
    Kwekkeboom, D.
    Erasmus MC, Rotterdam, Netherlands..
    Ruszniewski, P.
    Hop Beaujon, Clichy, France..
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands..
    NETTER-1 Phase III in Patients with Midgut Neuroendocrine Tumors Treated with 177Lu-DOTATATE: Efficacy and Safety Results2016Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, s. 95-95Artikkel i tidsskrift (Fagfellevurdert)
  • 108.
    Strosberg, J.
    et al.
    Univ S Florida, H Lee Moffitt Canc Ctr, Oncol, Tampa, FL USA..
    Wolin, E.
    Univ Kentucky, Oncol, Lexington, KY USA..
    Chasen, B.
    Univ Texas Hlth Sci Ctr Houston, Nucl Med, Houston, TX 77030 USA..
    Kulke, M.
    Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA..
    Bushnell, D.
    Univ Iowa, Div Nucl Med, Iowa City, IA USA..
    Caplin, M.
    Royal Free Hosp, Sch Med, Neuroendocrine Tumour Unit, Gastroenterol, London, England..
    Baum, R.
    Zent Klin Bad Berka GmbH, Nucl Med, Bad Berka, Germany..
    Kunz, P. L.
    Stanford Univ, Med Ctr, Oncol, Stanford, CA 94305 USA..
    Hobday, T.
    Mayo Clin, Oncol, Rochester, NY USA..
    Hendifar, A.
    Cedars Sinai Med Ctr, Oncol, Los Angeles, CA 90048 USA..
    Öberg, Kjell E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, M. Lopera
    Adv Accelerator Applicat, New York, NY USA..
    Kwekkeboom, D.
    Erasmus Univ, Med Ctr, Nucl Med Dept, Rotterdam, Netherlands..
    Ruszniewski, P.
    Hop Beaujon, Gastroenterol, Clichy, France..
    Krenning, E.
    Erasmus Univ, Med Ctr, Oncol, Rotterdam, Netherlands..
    NETTER-1 phase III in patients with midgut neuroendocrine tumors treated with 177Lu-dotatate: Efficacy, safety, QoL results and subgroup analysis2016Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, nr 6, artikkel-id 420PDArtikkel i tidsskrift (Fagfellevurdert)
  • 109.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
    Wolin, E.
    Montefiore Einstein Ctr Canc Care, Bronx, NY USA.
    Chasen, B.
    Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA USA.
    Bushnell, D.
    Univ Iowa, Iowa City, IA USA.
    Caplin, M.
    Royal Free Hosp, London, England.
    Baum, R. P.
    Zent Klin, Bad Berka, Germany.
    Hobday, T.
    Mayo Clin, Coll Med, Rochester, NY USA.
    Hendifar, A.
    Cedars Sinai Med Ctr, Los Angeles, CA USA.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Ruszniewski, P.
    Hop Beaujon, Clichy, France; Paris Diderot Univ, Clichy, France.
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands.
    Selected For Oral Presentation: Overall Survival, Progression-Free Survival, and Quality of Life Updates from the NETTER-1 Study: 177Lu-Dotatate Vs. High Dose Octreotide In Progressive Midgut Neuroendocrine Tumors2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 260-260Artikkel i tidsskrift (Annet vitenskapelig)
  • 110.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
    Wolin, E.
    Montefiore Einstein Ctr Canc Care, Bronx, NY USA.
    Chasen, B.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Bushnell, D.
    Univ Iowa, Iowa City, IA USA.
    Caplin, M.
    Royal Free Hosp, London, England.
    Baum, R. P.
    Zent Klin Bad Berska, Bad Berska, Germany.
    Kunz, P.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
    Hobday, T.
    Mayo Clin, Coll Med, Rochester, MN USA.
    Hendifar, A.
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, M. Lopera
    Adv Accelerator Applicat, New York, NY USA.
    Ruszniewski, R.
    Hop Beaujon, Clichy, France.
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands.
    Quality of Life Improvements in Patients with progressive Midgut Neuroendocrine Tumors: the NETTER-1 Phase III Trial2017Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, s. S773-S774Artikkel i tidsskrift (Annet vitenskapelig)
  • 111.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA..
    Wolin, E.
    Cedars Sinai Med Ctr, Samuel Oschin Canc Ctr, Carcinoid Neuroendocrine Tumor Program, Los Angeles, CA 90048 USA..
    Chasen, B.
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Kulke, M.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Bushnell, D.
    Univ Iowa, Iowa City, IA USA..
    Chaplin, M.
    Royal Free Hosp, London, England..
    Baum, R.
    Zent Klin Bad Berka, Bad Berka, Germany..
    Kunz, P.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Hobday, T.
    Mayo Clin, Coll Med, Rochester, MN USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, M. Lopera
    Adv Accelerator Applicat, New York, NY USA..
    Kwekkeboom, D.
    Erasmus MC, Rotterdam, Netherlands..
    Ruszniewski, P.
    Hop Beaujon, Clichy, France..
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands..
    Hendifar, A.
    Cedars Sinai Med Ctr, Samuel Oschin Canc Ctr, Los Angeles, CA 90048 USA..
    NETTER-1 phase III: efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177Lu-dotatate2016Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, s. 121-121Artikkel i tidsskrift (Annet vitenskapelig)
  • 112.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA..
    Wolin, E.
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Chasen, B.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Kulke, M. H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Bushnell, D.
    Univ Iowa, Iowa City, IA USA..
    Caplin, M.
    Royal Free Hosp, London, England..
    Baum, R.
    Zent Klin, Bad Berska, Bad Berska, Germany..
    Kunz, P.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Hobday, T.
    Mayo Clin, Coll Med, Rochester, NY USA..
    Hendifar, A.
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, Lopera M.
    Adv Accelerator Applicat, New York, NY USA..
    Kwekkeboom, D.
    Erasmus MC, Rotterdam, Netherlands..
    Ruszniewski, P.
    Hop Beaujon, Clichy, France..
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands..
    NETTER-1 Phase III Trial: Recent Findings on Quality of Life in Patients with Midgut Neuroendocrine Tumors2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, s. 257-257Artikkel i tidsskrift (Annet vitenskapelig)
  • 113.
    Strosberg, J.
    et al.
    Univ S Florida, GI Oncol, H Lee Moffitt Canc Ctr, Tampa, FL USA..
    Wolin, E. M.
    Montefiore Einstein Ctr Canc Care, New York, NY USA..
    Chasen, B.
    Univ Texas MD Anderson Canc Ctr, Nucl Med, Houston, TX USA..
    Kulke, M. H.
    Dana Farber Canc Inst, Gastrointestinal Canc, Boston, MA 02115 USA..
    Bushnell, D.
    Univ Iowa, Nucl Med, Iowa City, IA 52242 USA..
    Caplin, M.
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England..
    Baum, R. P.
    Zentralklin Bad Berka GmbH, Nucl Med, Bad Berka, Germany..
    Kunz, P.
    Stanford Univ, Med Ctr, Oncol, Stanford, CA 94305 USA..
    Hobday, T.
    Mayo Clin, Oncol, Rochester, MN USA..
    Hendifar, A.
    Cedars Sinai Med Ctr, Oncol, Los Angeles, CA 90048 USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, M. Lopera
    Adv Accelerator Applicat, New York, NY USA..
    Ruszniewski, P.
    Hop Beaujon, Oncol, Clichy, France..
    Krenning, E.
    Erasmus MC, Oncol, Rotterdam, Netherlands..
    Improved time to quality of life deterioration in patients with progressive midgut neuroendocrine tumors treated with 177Lu-DOTATATE: The NETTER-1 phase III trial2017Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, nr S5, artikkel-id 438PDArtikkel i tidsskrift (Annet vitenskapelig)
  • 114.
    Strosberg, J.
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
    Wolin, E.
    Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
    Yao, J.
    Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
    Kulke, M.
    4 Boston Med Ctr, Boston, MA USA.
    Bushnell, D.
    Univ Iowa, Iowa City, IA USA.
    Caplin, M.
    Royal Free Hosp, London, England.
    Baum, P.
    Zentralklinik, Bad Berka, Bad Berka, Germany.
    Kunz, P.
    Stanford Univ, Med Ctr, Stanford, CA USA.
    Hobday, T.
    Mayo Clin, Coll Med, Rochester, MN USA.
    Hendifar, A.
    Cedars Sinai Med Ctr, Los Angeles, CA USA.
    Mittra, E.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Ruszniewski, P.
    Hop Beaujon, Clichy, France.
    Polack, B.
    Adv Accelerator Applicat, New York, NY USA.
    He, B.
    Adv Accelerator Applicat, Geneva, Switzerland.
    Santoro, P.
    Adv Accelerator Applicat, New York, NY USA.
    Krenning, E.
    Erasmus MC, Rotterdam, Netherlands.
    Impact of baseline liver tumor burden on treatment outcomes with 177Lu-Dotatate in the Netter-1 study2018Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, nr Supplement 1, s. S60-S60Artikkel i tidsskrift (Annet vitenskapelig)
  • 115. Strosberg, Jonathan R.
    et al.
    Wolin, Edward M.
    Chasen, Beth
    Kulke, Matthew H.
    Bushnell, David L.
    Caplin, Martyn E.
    Baum, Richard P.
    Kunz, Pamela L.
    Hobday, Timothy J.
    Hendifar, Andrew Eugene
    Öberg, Kjell E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, Maribel Lopera
    Kwekkeboom, Dik J.
    Ruszniewski, Philippe B.
    Krenning, Eric
    NETTER-1 phase III: Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate2016Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, nr 4Artikkel i tidsskrift (Annet vitenskapelig)
  • 116.
    Strosberg, Jonathan
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
    Wolin, Edward
    Montefiore Einstein Ctr Canc Care, Bronx, NY USA.
    Chasen, Beth
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
    Kulke, Matthew
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Bushnell, David
    Univ Iowa, Iowa City, IA USA.
    Caplin, Martyn
    Royal Free Hosp, London, England.
    Baum, Richard P.
    Zentralklinik, Bad Berka, Germany.
    Kunz, Pamela
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
    Hendifar, Andrew
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
    Hobday, Timothy
    Mayo Clin, Coll Med, Rochester, MN USA.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, Maribel Lopera
    Adv Accelerator Applicat, Geneva, Switzerland.
    Thevenet, Thomas
    Adv Accelerator Applicat, Geneva, Switzerland.
    Margalet, Ines
    Adv Accelerator Applicat, Geneva, Switzerland.
    Ruszniewski, Philippe
    Paris Diderot Univ, Clichy, France;Hop Beaujon, Clichy, France.
    Krenning, Eric
    Erasmus MC, Rotterdam, Netherlands.
    Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With Lu-177-Dotatate in the Phase III NETTER-1 Trial2018Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, nr 25, s. 2578-2584Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    Neuroendocrine tumor (NET) progression is associated with deterioration in quality of life (QoL). We assessed the impact of Lu-177-Dotatate treatment on time to deterioration in health-related QoL.

    Methods

    The NETTER-1 trial is an international phase III study in patients with midgut NETs. Patients were randomly assigned to treatment with Lu-177-Dotatate versus high-dose octreotide. European Organisation for Research and Treatment of Cancer quality-of-life questionnaires QLQ C-30 and G.I.NET-21 were assessed during the trial to determine the impact of treatment on health-related QoL. Patients completed the questionnaires at baseline and every 12 weeks until tumor progression. QoL scores were converted to a 100-point scale according to European Organisation for Research and Treatment of Cancer instructions, and individual changes from baseline scores were assessed. Time to QoL deterioration (TTD) was defined as the time from random assignment to the first QoL deterioration 10 points for each patient in the corresponding domain scale. All analyses were conducted on the intention-to-treat population. Patients with no deterioration were censored at the last QoL assessment date.

    Results

    TTD was significantly longer in the Lu-177-Dotatate arm (n = 117) versus the control arm (n = 114) for the following domains: global health status (hazard ratio [HR], 0.406), physical functioning (HR, 0.518), role functioning (HR, 0.580), fatigue (HR, 0.621), pain (HR, 0.566), diarrhea (HR, 0.473), disease-related worries (HR, 0.572), and body image (HR, 0.425). Differences in median TTD were clinically significant in several domains: 28.8 months versus 6.1 months for global health status, and 25.2 months versus 11.5 months for physical functioning.

    Conclusion

    This analysis from the NETTER-1 phase III study demonstrates that, in addition to improving progression-free survival, Lu-177-Dotatate provides a significant QoL benefit for patients with progressive midgut NETs compared with high-dose octreotide.

  • 117.
    Strosberg, Jonathan
    et al.
    H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
    Wolin, Edward
    Montefiore Med Ctr, New York, NY USA.
    Chasen, Beth
    Univ Texas MD Anderson Canc Ctr, Houston, TX, USA.
    Kulke, Matthew
    Dana Farber Canc Inst, Boston, MA, USA.
    Bushnell, David
    Univ Iowa, Iowa City, IA USA.
    Caplin, Martyn
    Royal Free Hosp, London, England.
    Baum, Richard P.
    Zent Klin Bad Berka, Bad Berka, Germany.
    Kunz, Pamela
    Stanford Univ, Med Ctr, Stanford, CA, USA.
    Hobday, Timothy
    Mayo Clin, Coll Med, Rochester, MN, USA.
    Hendifar, Andrew
    Cedars Sinai Med Ctr, Los Angeles, CA, USA.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, Maribel Lopera
    Adv Accelerator Applicat, St Genis Pouilly, France.
    Ruszniewski, Philippe
    Hop Beaujon, Clichy, France.
    Krenning, Eric
    Erasmus MC, Rotterdam, Netherlands.
    QOL Improvements in NETTER-1 Phase III Trial in Patients With Progressive Midgut Neuroendocrine Tumors2018Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 47, nr 3, s. 355-355Artikkel i tidsskrift (Annet vitenskapelig)
  • 118.
    Strosberg, Jonathan
    et al.
    Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA..
    Wolin, Edward
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Chasen, Beth
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Kulke, Matthew
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Bushnell, David
    Univ Iowa, Iowa City, IA USA..
    Caplin, Martyn
    Royal Free Hosp, Pond St, London NW3 2QG, England..
    Baum, Richard P.
    Zentralklin, Bad Berka, Germany..
    Mittra, Erik
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Hobday, Timothy
    Mayo Clin, Coll Med, Rochester, MN USA..
    Hendifar, Andrew
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sierra, Maribel Lopera
    Adv Accelerator Applicat, New York, NY USA..
    Kwekkeboom, Dik
    Erasmus MC, Rotterdam, Netherlands..
    Ruszniewski, Philippe
    Hop Beaujon, Clichy, France..
    Krenning, Eric
    Erasmus MC, Rotterdam, Netherlands..
    177-Lu-Dotatate Significantly Improves Progression-Free Survival in Patients with Midgut Neuroendocrine Tumors: Results of the Phase III NETTER-1 Trial2016Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, nr 3, s. 483-483Artikkel i tidsskrift (Annet vitenskapelig)
  • 119.
    Stålberg, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Razmara, Masoud
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Taslica, Diana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Ståhlberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    An Integrative Genomic Analysis of Formalin Fixed Paraffin-Embedded Archived Serous Ovarian Carcinoma Comparing Long-term and Short-term Survivors2016Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 26, nr 6, s. 1027-1032Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    This study aimed to perform an integrative genetic analysis of patients with matched serous ovarian cancer having long-term or short-term survival using formalin fixed paraffin-embedded (FFPE) tissue samples.

    METHODS:

    All patients with serous ovarian carcinoma who underwent surgery between 1998 and 2007 at the Department of Gynaecology, Uppsala University Hospital, Sweden were considered. From this cohort, we selected biomaterial from 2 groups of patients with long-term and short-term survival matched for age, stage, histologic grade, and outcome of surgery. Genomic DNA from FFPE sample was analyzed with SNP array and targeted next-generation sequencing of 26 genes.

    RESULTS:

    Forty-three samples (primary tumors and metastases) from 23 patients were selected for genomic profiling, the survival in the subgroups were 134 and 36 months, respectively. We observed a tendency toward increased genomic instability in those with long-term survival with higher proportion of somatic copy number alterations (P = 0.083) and higher average ploidy (P = 0.037). TP53 mutations were found in 50% of the patients. Frequency of TP53 mutations did not differ between the survival groups (P = 0.629).

    CONCLUSIONS:

    We validated both previous genomic findings in ovarian cancer and the proposed association between increased genomic instability and better survival. These results exemplify that analysis of genomic biomarkers is feasible on archived FFPE tissue.

  • 120.
    Sundin, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Arnold, Rudolf
    Philipps Univ, Dept Gastroenterol & Endocrino.
    Baudin, Eric
    Gustave Roussy Canc Campus, Dept Endocrine Oncol & Nucl Med.
    Cwikla, Jaroslaw B
    Univ Warmia & Mazury, Fac Med Sci, Dept Radiol.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Fanti, Stefano
    Univ Bologna, Policlin S Orsola, Dept Nucl Med.
    Fazio, Nicola
    European Inst Oncol, Unit Gastrointestinal Med Oncol & Neuroendocrine.
    Giammarile, Francesco
    Univ Lyon, Hosp Civils Lyon, Nucl Med Dept.
    Hicks, Rodney J
    Peter MacCallum Canc Ctr, Canc Imaging.
    Kjaer, Andreas
    Rigshosp, Dept Clin Physiol Nucl Med & PET; Rigshosp, Cluster Mol Imaging; Univ Copenhagen.
    Krenning, Eric
    Erasmus MC, Dept Nucl Med.
    Kwekkeboom, Dik
    Erasmus MC, Dept Nucl Med.
    Lombard-Bohas, Catherine
    Hop Edouard Herriot, Hosp Civils Lyon, Inst Canc.
    O'Connor, Juan M
    Gastroenterol Hosp B Udaondo, Alexander Fleming Inst.
    O'Toole, Dermot
    Univ Dublin, St Jamess Hosp, Trinity Coll Dublin; St Vincents Univ Hosp.
    Rockall, Andrea
    Royal Marsden NHS Fdn Trust, Dept Radiol; Imperial Coll London.
    Wiedenmann, Bertram
    Charite Univ Med Berlin, Campus Charite Mitte, Dept Gastroenterol & Hepatol; Charite Univ Med Berlin, Campus Virchow Klinikum.
    Valle, Juan W
    Univ Manchester, Christie NHS Fdn Trust, Inst Canc Sci.
    Vullierme, Marie-Pierre
    Hop Beaujon, Serv Gastroenterol.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging.2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 3, s. 212-244Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Contrast-enhanced computed tomography (CT) of the neckthorax-abdomen and pelvis, including 3-phase examination of the liver, constitutes the basic imaging for primary neuroendocrine tumor (NET) diagnosis, staging, surveillance, and therapy monitoring. CT characterization of lymph nodes is difficult because of inadequate size criteria (short axis diameter), and bone metastases are often missed. Contrast-enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging is preferred for the examination of the liver, pancreas, brain and bone. MRI may miss small lung metastases. MRI is less well suited than CT for the examination of extended body areas because of the longer examination procedure. Ultrasonography (US) frequently provides the initial diagnosis of liver metastases and contrast-enhanced US is excellent to characterize liver lesions that remain equivocal on CT/MRI. US is the method of choice to guide the biopsy needle for the histopathological NET diagnosis. US cannot visualize thoracic NET lesions for which CTguided biopsy therefore is used. Endocopic US is the most sensitive method to diagnose pancreatic NETs, and additionally allows for biopsy. Intraoperative US facilitates lesion detection in the pancreas and liver. Somatostatin receptor imaging should be a part of the tumor staging, preoperative imaging and restaging, for which 68 Ga-DOTA-somatostatin analog PET/CT is recommended, which is vastly superior to somatostatin receptor scintigraphy, and facilitates the diagnosis of most types of NET lesions, for example lymph node metastases, bone metastases, liver metastases, peritoneal lesions, and primary small intestinal NETs. (18)FDG-PET/CT is better suited for G3 and high G2 NETs, which generally have higher glucose metabolism and less somatostatin receptor expression than low-grade NETs, and additionally provides prognostic information.

  • 121.
    Tiensuu Janson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Theodorsson, E
    Wilander, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center1997Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 8, nr 7, s. 685-690Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Little is known about factors related to prognosis in patients with carcinoid disease. In this study we have tried to identify such factors.

    PATIENTS AND METHODS:

    We have evaluated 301 consecutive carcinoid patients (256 midgut, 39 foregut and six hindgut) referred during 15 years for medical treatment with respect to tumor distribution, hormone production, prognostic factors and survival.

    RESULTS:

    Survival was significantly shorter in midgut carcinoid patients with > or = 5 liver metastases or with high levels of urinary 5-hydroxyindoleacetic acid, plasma chromogranin A or neuropeptide K. By univariate analysis, these variables together with the presence of carcinoid syndrome were related to a higher risk of dying. In multivariate analyses, performed in the 71 patients with full information on all variables, advanced age and plasma chromogranin A > 5000 micrograms/l were independent predictors of overall survival.

    CONCLUSIONS:

    Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.

  • 122.
    Tsolakis, Apostolos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    James, P.
    Univ Ottawa, Dept Med, Ottawa, ON, Canada.;Ottawa Hosp Res Inst, Ottawa, ON, Canada..
    Zhang, M.
    Dept Med & Community Hlth Sci, Calgary, AB, Canada..
    Belletrutti, P.
    Dept Med & Community Hlth Sci, Calgary, AB, Canada..
    Mohamed, R.
    Dept Med & Community Hlth Sci, Calgary, AB, Canada..
    Roberts, D.
    Dept Surg & Community Hlth Sci, Calgary, AB, Canada..
    Heitman, S.
    Dept Med & Community Hlth Sci, Calgary, AB, Canada..
    Incremental Benefit of Preoperative Endoscopic Ultrasound for the Detection of Pancreatic Neuroendocrine Tumors: A Meta-Analysis2015Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, nr 1-2, s. 116-116Artikkel i tidsskrift (Annet vitenskapelig)
  • 123.
    Tsolakis, Apostolos V.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Granerus, Goran
    Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden..
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Falkmer, Sture E.
    Ryhov Cty Hosp, Dept Pathol, SE-55185 Jonkoping, Sweden..
    Janson, Eva T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin Onkologi.
    Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours2015Inngår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, nr 47, s. 13240-13249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM:

    To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite.

    METHODS:

    Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients.

    RESULTS:

    In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms.

    CONCLUSION:

    Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

  • 124.
    Van Leeuwaarde, R.
    et al.
    UMC Utrecht, Utrecht, Netherlands.
    Spada, F.
    European Inst Oncol, Milan, Italy.
    Cheung, W.
    Tom Baker Canc Clin, Calgary, AB, Canada.
    Gonzalez-Clavijo, A.
    Univ Nacl Colombia, Bogota, Colombia.
    Pracht, M.
    Ctr Eugene Marquis, Rennes, France.
    Emelianova, G.
    Natl Med Res Ctr Oncol NN Blokhin, Moscow, Russia.
    Thirlwell, C.
    UCL, London, England.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Is the EORTC QLQ-QNET21 Optimal for Patients with Neuroendocrine Tumors?2018Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, nr Supplement: 1, s. 122-122Artikkel i tidsskrift (Annet vitenskapelig)
  • 125.
    Velikyan, Irina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Garske, Ulrike
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Comparison of radiation dosimetry of [Ga-68]Ga-DOTA-TOC and [Ga-68]Ga-DOTA-TATE in patients affected by neuroendocrine tumours2013Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 56, nr S1, s. S270-S270Artikkel i tidsskrift (Annet vitenskapelig)
  • 126.
    Velikyan, Irina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Selvaraju, K. Ram
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Kandeel, Fouad
    Zhanhong, Wu
    Shively, Jack
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Ga-68-labelling of Exendin-4, preclinical evaluation of the resultant tracer for the imaging and quantification of insulinomas, and case patient examination2013Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 56, nr S1, s. S407-S407Artikkel i tidsskrift (Annet vitenskapelig)
  • 127.
    Velikyan, Irina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Selvaraju, Ram Kumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Bulenga, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Espes, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Dosimetry of [Ga-68]Ga-DO3A-VS-Cys(40)-Exendin-4 in rodents, pigs, non-human primates and human2015Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 58, s. S95-S95Artikkel i tidsskrift (Annet vitenskapelig)
  • 128.
    Vyakaranam, Achyut Ram
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Garske-Román, Ulrike
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Sahlgrens Univ Hosp, Dept Nucl Med, Gothenburg, Sweden.
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Fröss-Baron, Katarzyna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Thiis-Evensen, Espen
    Oslo Univ Hosp, Rikshosp, Dept Gastroenterol, Oslo, Norway.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE.2019Inngår i: Cancers, ISSN 2072-6694, Vol. 11, nr 7, artikkel-id 909Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. Radiological response utilized response evaluation criteria in solid tumors 1.1 and toxicity was graded according to common terminology criteria for adverse events version 4. Median 4 (range 3-11) 7.4 GBq cycles of 177Lu-DOTATATE were administered as first-line therapy (n = 13) or because of progressive disease (n = 9). Partial response (PR) was achieved in two and stable disease (SD) in 20 patients. The median overall survival (OS) was 49.6 (range 8.2-139) months and median progression-free survival (PFS) was 21.6 (range 6.7-138) months. Scintigraphic response >50% was achieved in 9/19 (47%) patients. Biochemical response (>50% decrease) of chromogranin A was found in 6/15 (40%) patients and of catecholamines in 3/12 (25%) patients. Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). No hematological or kidney toxicity grade 3-4 was registered. 177Lu-DOTATATE therapy was associated with favorable outcome and low toxicity. High Ki-67 (≥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.

  • 129.
    Vyakaranam, Achyut Ram
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Norlén, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    C-11-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma2019Inngår i: Cancers, ISSN 2072-6694, Vol. 11, nr 6, artikkel-id 847Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing C-11-hydroxy-ephedrine (C-11-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. C-11-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of C-11-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor C-11-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R-2 = 0.22, p = 0.016). C-11-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor C-11-HED uptake were not helpful for tumor characterization.

  • 130.
    Waldum, Helge L.
    et al.
    Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7491 Trondheim, Norway;St Olavs Univ Hosp, Dept Gastroenterol & Hepatol, Trondheim, Norway.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Sördal, Öystein F.
    St Olavs Univ Hosp, Dept Gastroenterol & Hepatol, Trondheim, Norway.
    Sandvik, Arne K.
    Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7491 Trondheim, Norway;St Olavs Univ Hosp, Dept Gastroenterol & Hepatol, Trondheim, Norway.
    Gustafsson, Björn I.
    Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7491 Trondheim, Norway;St Olavs Univ Hosp, Dept Gastroenterol & Hepatol, Trondheim, Norway.
    Mjönes, Patricia
    Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7491 Trondheim, Norway;St Olavs Univ Hosp, Dept Pathol, Trondheim, Norway.
    Fossmark, Reidar
    Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7491 Trondheim, Norway;St Olavs Univ Hosp, Dept Gastroenterol & Hepatol, Trondheim, Norway.
    Not only stem cells, but also mature cells, particularly neuroendocrine cells, may develop into tumours: time for a paradigm shift2018Inngår i: Therapeutic Advances in Gastroenterology, ISSN 1756-283X, E-ISSN 1756-2848, Vol. 11, artikkel-id UNSP 1756284818775054Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Stem cells are considered the origin of neoplasms in general, and malignant tumours in particular, and the stage at which the stem cells stop their differentiation determines the degree of malignancy. However, there is increasing evidence supporting an alternative paradigm. Tumours may develop by dedifferentiation from mature cells able to proliferate. Studies of gastric carcinogenesis demonstrate that mature neuroendocrine (NE) cells upon long-term overstimulation may develop through stages of hyperplasia, dysplasia, and rather benign tumours, into highly malignant carcinomas. Dedifferentiation of cells may change the histological appearance and impede the identification of the cellular origin, as seen with gastric carcinomas, which in many cases are dedifferentiated neuroendocrine tumours. Finding the cell of origin is important to identify risk factors for cancer, prevent tumour development, and tailor treatment. In the present review, we focus not only on gastric tumours, but also evaluate the role of neuroendocrine cells in tumourigenesis in two other foregut-derived organs, the lungs and the pancreas, as well as in the midgut-derived small intestine.

  • 131.
    Weickert, Martin O.
    et al.
    Univ Hosp Coventry, ENETS Ctr Excellence, ARDEN NET Ctr, Coventry CV2 2DX, W Midlands, England;Warwickshire Natl Hlth Serv Trust, Coventry CV2 2DX, W Midlands, England.
    Kaltsas, Gregory
    Univ Hosp Coventry, ENETS Ctr Excellence, ARDEN NET Ctr, Coventry CV2 2DX, W Midlands, England;Warwickshire Natl Hlth Serv Trust, Coventry CV2 2DX, W Midlands, England.
    Hörsch, Dieter
    Zent Klin Bad Berka, Bad Berka, Germany.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Pavel, Marianne
    Friedrich Alexander Univ Erlangen Nurnberg, Erlangen, Germany;Charite, Berlin, Germany.
    Valle, Juan W.
    Univ Manchester, Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England.
    Caplin, Martyn E.
    Royal Free Hosp, European Neuroendocrine Tumor Soc Ctr Excellence, Neuroendocrine Tumour Unit, London, England.
    Bergsland, Emily
    Univ Calif San Francisco, San Francisco, CA 94143 USA.
    Kunz, Pamela L.
    Stanford Univ, Sch Med, Stanford, CA USA.
    Anthony, Lowell B.
    Univ Kentucky, Lexington, KY USA.
    Grande, Enrique
    MD Anderson Int Canc Ctr, Madrid, Spain.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Lombard-Bohas, Catherine
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France.
    Ramage, John K.
    Kings Coll Hosp London, Kings Hlth Partners European Neuroendocrine Tumor, London, England.
    Kittur, Ashwin
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Yang, Qi M.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome2018Inngår i: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 40, nr 6, s. 952-962Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: In the placebo-controlled Phase III TELE-STAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and >= 4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m(2)) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

    Methods: Assessment of the occurrence of weight change >= 3% at week 12 was prespecified in the statistical analysis plan.

    Findings: In 120 patients with weight data available, weight gain >= 3% was observed in 2 of 39 patients (5.1%) taking placebo [1.1), 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss >= 3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.

  • 132.
    Weickert, Martin O.
    et al.
    Univ Hosp Coventry & Warwickshire NHS Trust, Coventry, W Midlands, England.
    Kaltsas, Gregory
    Univ Hosp Coventry & Warwickshire NHS Trust, Coventry, W Midlands, England.
    Hörsch, Dieter
    Zent Klin Bad Berka, Bad Berka, Germany.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Pavel, Marianne
    Charite, Berlin, Germany.;Friedrich Alexander Univ, Nurnberg, Germany.
    Valle, Juan W.
    Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England.
    Caplin, Martyn E.
    Royal Free Hosp, London, England.
    Bergsland, Emily
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
    Kunz, Pamela L.
    Stanford Univ, Stanford, CA USA.
    Anthony, Lowell B.
    Univ Kentucky, Lexington, KY USA.
    Grande, Enrique
    Hosp Univ Ramon y Cajal, Madrid, Spain.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Warner, Richard R. P.
    Icahn Sch Med Mt Sinai, New York, NY USA.
    Lombard-Bohas, Catherine
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France.
    Fleming, Rosanna
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kittur, Ashwin
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Arnold, Karie
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Yang, Qi M.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA.
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA USA.
    Weight Change Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome2018Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 47, nr 3, s. 357-358Artikkel i tidsskrift (Annet vitenskapelig)
  • 133.
    Welin, Staffan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Janson, Eva Tiensuu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Lavenius, Erik
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours2004Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 151, nr 1, s. 107-112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    High-dose somatostatin analogue treatment has shown an antiproliferative effect in one study including patients with neuroendocrine tumours. To explore this therapeutic strategy further, we have studied the effect of a high-dose formula of octreotide, octreotide pamoate, in midgut carcinoid patients.

    DESIGN AND METHODS:

    Twelve patients with advanced midgut carcinoid tumours with a median duration of disease of more than 5 years were included. All were in a progressive state despite several previous treatment modalities. Octreotide pamoate (160 mg) was given as an intramuscular injection every 2 weeks for 2 months and then monthly. Radiological and biochemical responses were monitored.

    RESULTS:

    Tumour size and biochemical markers were stabilised for a median of 12 months in 75% of the patients. Ten patients had symptomatic improvement of flush and diarrhoea.

    CONCLUSION:

    In this group of patients with advanced midgut carcinoid tumours and progressive disease, octreotide pamoate managed to improve symptoms, and stabilise hormone production and tumour growth in 75% of the patients. We believe that high-dose treatment with somatostatin analogues can be an important addition to the therapeutic arsenal for patients with advanced progressive midgut carcinoid tumours.

  • 134.
    Wilking, H.
    et al.
    Uppsala Univ Hosp, Uppsala, Sweden.
    Ilan, Ezgi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Uppsala, Sweden.
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Uppsala, Sweden.
    Andersson, C.
    Uppsala Univ Hosp, Uppsala, Sweden;Uppsala Univ, Uppsala, Sweden.
    Öst, A.
    Uppsala Univ Hosp, Uppsala, Sweden.
    Velikyan, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi. Uppsala Univ Hosp, Uppsala, Sweden.
    Fröss-Baron, Katarzyna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi. Uppsala Univ Hosp, Uppsala, Sweden.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Uppsala, Sweden.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Uppsala, Sweden.
    In-vivo stability of 177Lu-DOTATATE during peptide receptor radionuclide therapy2018Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, nr Supplement 1, s. S592-S592Artikkel i tidsskrift (Annet vitenskapelig)
  • 135. Wolin, Edward M.
    et al.
    Jarzab, Barbara
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Walter, Thomas
    Toumpanakis, Christos
    Morse, Michael
    Tomassetti, Paola
    Weber, Matthias
    Fogelman, David
    Ramage, John
    Poon, Donald
    Huang, Jerry
    Hudson, Michelle
    Li, Jiang
    Pasieka, Janice L.
    Mahamat, Abakar
    Swahn, Fredrik
    Newell-Price, John
    Mansoor, Was
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    A Multicenter, Randomized, Blinded, Phase 3 Study of Pasireotide LAR vs Octreotide LAR in Patients with Metastatic Neuroendocrine Tumors (NET) with Disease-Related Symptoms Inadequately Controlled by Somatostatin Analogs2014Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, nr 3, s. 508-508Artikkel i tidsskrift (Annet vitenskapelig)
  • 136.
    Yao, James C.
    et al.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Pavel, Marianne
    Charite, Berlin, Germany..
    Lombard-Bohas, Catherine
    Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France..
    Van Cutsem, Eric
    Univ Hosp Gasthuisberg, Leuven, Belgium.;Univ Hosp Leuven, Leuven, Belgium.;Katholieke Univ Leuven, Leuven, Belgium..
    Voi, Maurizio
    Novartis, E Hanover, NJ USA..
    Brandt, Ulrike
    Novartis Pharma AG, Basel, Switzerland..
    He, Wei
    Novartis, E Hanover, NJ USA..
    Chen, David
    Novartis, E Hanover, NJ USA..
    Capdevila, Jaume
    Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain..
    de Vries, Elisabeth G. E.
    Univ Groningen, UMCG, Groningen, Netherlands..
    Tomassetti, Paola
    Univ Bologna, Bologna, Italy..
    Hobday, Timothy
    Mayo Clin, Coll Med, Rochester, MN USA..
    Pommier, Rodney
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study2016Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, nr 32, s. 3906-3913Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low-or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to openlabel everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intent-to-treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

  • 137.
    Yu, Di
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Leja, Justyna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Loskog, Angelica S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Giandomenico, Valeria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 1, s. 54-66Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cancer immunotherapy is becoming a cornerstone in the clinical care of cancer patients due to the breakthrough trials with immune checkpoint blockade antibodies and chimeric antigen receptor T cells. The next breakthrough in cancer immunotherapy is likely to be oncolytic viruses engineered to selectively kill tumor cells and deceive the immune system to believe that the tumor is a foreign entity that needs to be eradicated. We have developed AdVince, an oncolytic adenovirus for treatment of liver metastases from neuroendocrine tumor (NET). AdVince includes the gene promoter from human chromogranin A for selective replication in neuroendocrine cells, miR122 target sequences for reduced liver toxicity, and a cell-penetrating peptide in the capsid for increased infectivity of tumor cells and optimized spread within tumors. This paper describes the preclinical evaluation of AdVince on freshly isolated human gastrointestinal NET cells resected from liver metastases and freshly isolated human hepatocytes as well as in fresh human blood. AdVince selectively replicates in and kills NET cells. Approximately, 73-fold higher concentration of AdVince is needed to induce similar level of cytotoxicity in NET cells as in hepatocytes. AdVince did not activate complement or induce considerable amount of proinflammatory cytokines or chemokines in human blood. The data presented herein indicate that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET.

  • 138.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Management of functional neuroendocrine tumors of the pancreas2018Inngår i: Gland surgery, ISSN 2227-684X, E-ISSN 2227-8575, Vol. 7, nr 1, s. 20-27Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.

  • 139.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Medical Therapy of Gastrointestinal Neuroendocrine Tumors2017Inngår i: Visceral Medicine, ISSN 2297-4725, Vol. 33, nr 5, s. 352-356Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium177-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.

  • 140.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    The Genesis of the Neuroendocrine Tumors Concept: From Oberndorfer to 20182018Inngår i: Endocrinology and metabolism clinics of North America (Print), ISSN 0889-8529, E-ISSN 1558-4410, Vol. 47, nr 3, s. 711-731Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The concept of neuroendocrine tumors (NETs) began in the 1900s with Oberndorfer's description of carcinoid tumors, followed by specific cytotoxic agents and the identification of somatostatin. NETs diagnosis was confirmed by World Health Organization classification. Histopathology included immunohistochemistry with specific antibodies. Imaging was refined with molecular imaging. Somatostatin is the leading agent for controlling clinical symptoms related to hormone production. Increasing interest in these tumors, previously thought rare, led to increased incidence and prevalence. Between 1960 and 1970, the true NET concept was established with the development of radioimmunoassays for peptides and hormones and imaging with computerized tomography.

  • 141.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Universal everolimus for malignant neuroendocrine tumours?2016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, nr 10022, s. 924-926Artikkel i tidsskrift (Fagfellevurdert)
  • 142.
    Öberg, Kjell
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Couvelard, Anne
    Hospital Beaujon, Department of Pathology.
    Delle Fave, Gianfranco
    Ospedale Sant’Andrea, Department of Digestive and Liver Disease.
    Gross, David
    Hadassah University Hospital, Department of Endocrinology and Metabolism.
    Grossman, Ashley
    University of Oxford, Churchill Hospital, Oxford Centre for Diabetes, Endocrinology and Metabolism.
    Jensen, Robert T.
    National Institutes of Health, Digestive Diseases Branch.
    Pape, Ulrich-Frank
    Charité University of Berlin, Department of Internal Medicine.
    Perren, Aurel
    niversity Hospital Zurich, Department of Pathology.
    Rindi, Guido
    Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Institute of Anatomic Pathology.
    Ruszniewski, Philippe
    Beaujon Hopital, Department of Gastroenterology.
    Scoazec, Jean-Yves
    Gustave Roussy Institute, Department of Biopathology, Faculty of Medicine Paris Sud.
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Wiedenmann, Bertram
    Charité University Medicine, Department of Hepatology and Gastroenterology.
    Ferone, Diego
    University of Genova, IRCCS AOU San Martino IST, DiMI, CEBR.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers2017Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, nr 3, s. 201-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biomarkers have been the mainstay in the diagnosis and follow-up of patients with neuroendocrine tumors (NETs) over the last few decades. In the beginning, secretory products from a variety of subtypes of NETs were regarded as biomarkers to follow during diagnosis and treatment: serotonin for small intestinal (SI) NETs, and gastrin and insulin for pancreatic NETs. However, it became evident that a large number of NETs were so-called nonfunctioning tumors without secreting substances that caused hormone-related symptoms. Therefore, it was necessary to develop so-called "general tumor markers." The most important ones so far have been chromogranin A and neuron-specific enolase (NSE). Chromogranin A is the most important general biomarker for most NETs with a sensitivity and specificity somewhere between 60 and 90%. NSE has been a relevant biomarker for patients with high-grade tumors, particularly lung and gastrointestinal tract tumors. Serotonin and the breakdown product urinary 5-hydroxyindoleacetic acid (U-5-HIAA) is still an important marker for diagnosing and follow-up of SI NETs. Recently, 5-HIAA in plasma has been analyzed by highperformance liquid chromatography and fluorometric detection and has shown good agreement with U-5-HIAA anal ysis. In the future, we will see new tests including circulating tumor cells, circulating DNA and mRNA. Recently, a NET test has been developed analyzing gene transcripts in circulating blood. Preliminary data indicate high sensitivity and specificity for NETs. However, its precise role has to be validated in prospective randomized controlled trials which are ongoing right now.

  • 143.
    Öberg, Kjell
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Krenning, Eric
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bodei, Lisa
    Kidd, Mark
    Tesselaar, Margot
    Ambrosini, Valentina
    Baum, Richard P
    Kulke, Matthew
    Pavel, Marianne
    Cwikla, Jaroslaw
    Drozdov, Ignat
    Falconi, Massimo
    Fazio, Nicola
    Frilling, Andrea
    Jensen, Robert
    Koopmans, Klaus
    Korse, Tiny
    Kwekkeboom, Dik
    Maecke, Helmut
    Paganelli, Giovanni
    Salazar, Ramon
    Severi, Stefano
    Strosberg, Jonathan
    Prasad, Vikas
    Scarpa, Aldo
    Grossman, Ashley
    Walenkamp, Annemeik
    Cives, Mauro
    Virgolini, Irene
    Kjaer, Andreas
    Modlin, Irvin M
    A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management2016Inngår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 5, nr 5, s. 174-187Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

  • 144.
    Öberg, Kjell
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Lamberts, Steven W. J.
    Erasmus MC, Rotterdam, Netherlands..
    Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumours: past, present and future2016Inngår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 23, nr 12, s. R551-R566Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Acromegaly is a hormonal disorder that arises when the pituitary gland secretes excess growth hormone (GH), which in turn stimulates a concomitant increase in ser