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1. The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation

Author

Backman, Samuel, primary, Botling, Johan, additional, Nord, Helena, additional, Ghosal, Suman, additional, Stalberg, Peter, additional, Juhlin, C Christofer, additional, Almlof, Jonas, additional, Sundin, Anders, additional, Zhang, Liang, additional, Moens, Lotte, additional, Eriksson, Barbro, additional, Welin, Staffan, additional, Hellman, Per, additional, Skogseid, Britt, additional, Pacak, Karel, additional, Mollazadegan, Kazhan, additional, Akerstrom, Tobias, additional, and Crona, Joakim, additional

Published
2024
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7. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids

Author

Caplin, M.E., Baudin, E., Ferolla, P., Filosso, P., Garcia-Yuste, M., Lim, E., Oberg, K., Pelosi, G., Perren, A., Rossi, R.E., Travis, W.D., Bartsch, Detlief, Capdevila, Jaume, Costa, Frederico, Cwikla, Jaroslaw, de Herder, Wouter, Delle Fave, Gianfranco, Eriksson, Barbro, Falconi, Massimo, Ferone, Diego, Gross, David, Grossman, Ashley, Ito, Tetsuhide, Jensen, Robert, Kaltsas, Gregory, Kelestimur, Fahrettin, Kianmanesh, Reza, Knigge, Ulrich, Kos-Kudla, Beata, Krenning, Eric, Mitry, Emmanuel, Nicolson, Marianne, O'Connor, Juan, O'Toole, Dermot, Pape, Ulrich-Frank, Pavel, Marianne, Ramage, John, Raymond, Eric, Rindi, Guido, Rockall, Andrea, Ruszniewski, Philippe, Salazar, Ramon, Scarpa, Aldo, Sedlackova, Eva, Sundin, Anders, Toumpanakis, Christos, Vullierme, Marie-Pierre, Weber, Wolfgang, Wiedenmann, Bertram, and Zheng-Pei, Zeng

Published
2015
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11. Poor outcome after systemic therapy in secondary high-grade pancreatic neuroendocrine tumors

Author

Mollazadegan, Kazhan, Skogseid, Britt, Botling, Johan, Åkerström, Tobias, Eriksson, Barbro, Welin, Staffan, Sundin, Anders, and Crona, Joakim

Subjects
Cancer och onkologi, Kirurgi, Cancer and Oncology, Endokrinologi och diabetes, Surgery, highgrade, treatment outcomes, Endocrinology and Diabetes, pancreatic neuroendocrine tumor, systemic therapy
Abstract

Longitudinal changes in pancreatic neuroendocrine tumor (panNET) cell proliferation correlate with fast disease progression and poor prognosis. The optimal treatment strategy for secondary panNET grade (G)3 that has progressed from a previous low- or intermediate-grade to high-grade panNET G3 is currently unknown. This was a single-center retrospective cohort study aimed to characterize treatment patterns and outcomes among patients with secondary panNET-G3. Radiological responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A total of 22 patients were included and received a median of 2 (range, 1–4) treatment lines in 14 different combinations. Median overall survival (OS) was 9 months (interquartile range (IQR): 4.25–17.5). For the 15 patients who received platinum–etoposide chemotherapy, median OS was 7.5 months (IQR: 3.75–10) and median progression-free survival (PFS) was 4 months (IQR: 2.5–5.5). The 15 patients who received conventional panNET therapies achieved a median OS of 8 months (IQR: 5–16.75) and median PFS was 5.5 months (IQR: 2.75–8.25). We observed one partial response on 177Lu DOTA-TATE therapy. In conclusion, this hypothesis-generating study failed to identify any promising treatment alternatives for patients with secondary panNET-G3. This demonstrates the need for both improved biological understanding of this particular NET entity and for designing prospective studies to further assess its treatment in larger patient cohorts.

Published
2022

15. 177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated With Chemotherapy : Analysis of Outcome, Safety and Their Determinants

Author

Fröss-Baron, Katarzyna, Garske, Ulrike, Welin, Staffan, Granberg, Dan, Eriksson, Barbro, Khan, Tanweera Shaheena, Sandström, Mattias, and Sundin, Anders

Subjects
Cancer och onkologi, Cancer and Oncology
Abstract

Objective: To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS) and their determinants in patients with advanced pancreatic neuroendocrine tumors (panNETs), previously pretreated with chemotherapy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Methods: In total, 102 patients with advanced panNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy were included, of whom 90 % had progressive disease and the majority (74.5%) with grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6 to 8 weeks interval, in 88 % of patients utilizing a dosimetry-guided protocol, until an absorbed dose of 23 Gy to the kidneys was reached. Results: Mean 32±10.9 GBq per patient was administered in 1-10 cycles starting median 36 months after panNET diagnosis. Median follow-up was 34 months. Median PFS was 24 months and median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy and elevated alkaline phosphatase (ALP). Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3-4 occurred in 10.8%. One patient (1.0 %) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity and absorbed dose to the bone marrow. Conclusion: 177Lu-DOTATATE therapy was feasible, highly effective and safe in patients with advanced panNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy related independent risk factor for shorter PFS and OS.

Published
2021

26. Contributors

Author

Aiello, Lloyd Paul, primary, Alexander, Erik K., additional, Allan, Carolyn A., additional, Allolio, Bruno, additional, Angelos, Peter, additional, Appu, Sree, additional, Auchus, Richard J., additional, Avruch, Joseph, additional, Axelrod, Lloyd, additional, Bahn, Rebecca S., additional, Baker, H.W.G., additional, Barnes, Randall B., additional, Bastepe, Murat, additional, Baxter, John D., additional, Beck-Peccoz, Paolo, additional, Bell, Graeme I., additional, Bilezikian, John P., additional, Bloom, Stephen R., additional, Blum, Manfred, additional, Bonnema, Steen J., additional, Botero, Diego, additional, Bouillon, Roger, additional, Boulton, Andrew J.M., additional, Braunstein, Glenn D., additional, Bringhurst, F. Richard, additional, Broekmans, Frank J., additional, Bronstein, Marcello D., additional, Brown, Edward M., additional, Bui, Chuong, additional, Burch, Col. Henry B., additional, Burger, Henry G., additional, Burney, Richard O., additional, Buse, John B., additional, Butler, Peter C., additional, Cappabianca, Paolo, additional, Caramori, Maria Luiza Avancini, additional, Carey, Robert M., additional, Carlton, Esther, additional, Carmody, David, additional, Caro, Jose F., additional, Cavagnini, Francesco, additional, Cavallerano, Jerry, additional, Cavallo, Luigi M., additional, Chan, Shu Jin, additional, Chang, R. Jeffrey, additional, Chapurlat, Roland D., additional, Chatterjee, V. Krishna, additional, Chiovato, Luca, additional, Cho, Kyung J., additional, Christophe, Daniel, additional, Chung, Teng-Teng, additional, Cidlowski, John A., additional, Clark, Adrian J.L., additional, Clark, Peter E., additional, Clemmons, David R., additional, Considine, Robert V., additional, Copinschi, Georges, additional, Copps, Kyle D., additional, Courtney, C. Hamish, additional, Cuttler, Leona, additional, Daley, Melita L., additional, Dattani, Mehul, additional, Davis, Stephen N., additional, de Divitiis, Oreste, additional, De Felice, Mario, additional, DeFronzo, Ralph A., additional, J. De Groot, Leslie, additional, de Kretser, David, additional, Delli, Ahmed J., additional, Delmas, Pierre D., additional, Demay, Marie B., additional, Devroey, Paul, additional, Di Lauro, Roberto, additional, Dinneen, Sean F., additional, Dumont, Jacques E., additional, Dungan, Kathleen M., additional, Drucker, Daniel J., additional, Econs, Michael J., additional, Ehrmann, David A., additional, Eisenhofer, Graeme, additional, Erickson, Gregory F., additional, Eriksson, Barbro, additional, Espiner, Eric, additional, Esposito, Felice, additional, Esser, Victoria, additional, Eugster, Erica A., additional, Farooqi, Sadaf, additional, Fassnacht, Martin, additional, Fauser, Bart C.J.M., additional, Fenzi, Gianfranco, additional, Ferrannini, Ele, additional, Findlay, David M., additional, Finlayson, Courtney, additional, Fisher, Delbert A., additional, Forest, Maguelone G., additional, Foster, Daniel W., additional, Freeman, Mason Wright, additional, Frydenberg, Mark, additional, Fuller, Peter, additional, Gagel, Robert F., additional, Gaglia, Jason L., additional, Galizia, Gianluigi, additional, Gao, Chuanyun, additional, Gardella, Thomas J., additional, Gaylinn, Bruce D., additional, Genant, Harry K., additional, German, Michael S., additional, Ghatei, Mohammad A., additional, Giudice, Linda C., additional, Glasier, Anna, additional, Glorieux, Francis H., additional, González-Maeso, Javier, additional, Gooren, Louis J., additional, Gordon, David F., additional, Gregerson, Karen A., additional, Gross, Milton D., additional, Grossman, Ashley, additional, Guimarães, Valéria C., additional, Gurnell, Mark, additional, Haddad, Nadine, additional, Haisenleder, Daniel J., additional, Handelsman, David J., additional, Hanks, John B., additional, Hannon, Mark John, additional, Hayward, Simon W., additional, Hebrok, Matthias, additional, Hegedüs, Laszlo, additional, Hennemann, Georg, additional, Herndon, Maria K., additional, Hindmarsh, Peter, additional, Ho, Ken K.Y., additional, Horseman, Nelson D., additional, Horwitz, Mara J., additional, Hu, Mimi, additional, Hughes, Ieuan A., additional, Hupfeld, Christopher J., additional, Hussain, Hero K., additional, Illingworth, Peter, additional, Jameson, J. Larry, additional, Josso, Nathalie, additional, Jüppner, Harald, additional, Kalish, Jeffrey, additional, Kaplan, Edwin L., additional, Kerr, Jeffrey B., additional, Klein, Ronald, additional, Knobel, Meyer, additional, Kolibianakis, Efstratios, additional, Kopchick, John J., additional, Kopp, Peter, additional, Korbonits, Márta, additional, Korobkin, Melvyn, additional, Krane, Stephen M., additional, Krohn, Knut, additional, Kronenberg, Henry M., additional, Kyriakis, John M., additional, Lau, Sue Lynn, additional, Lazarus, John H., additional, Learoyd, Diana L., additional, Lebovitz, Harold E., additional, Lee, Paul, additional, Lernmark, Åke, additional, Lewis-Tuffin, Laura J., additional, Lu, Zhi-Liang, additional, Macchia, Paolo Emidio, additional, Maclaren, Noel K., additional, Maenhaut, Carine, additional, Maes, Christa, additional, Main, Katharina M., additional, Malchoff, Carl D., additional, Malchoff, Diana Mark, additional, Malik, Rayaz A., additional, Mandel, Susan J., additional, Mantzoros, Christos, additional, Maratos-Flier, Eleftheria, additional, Marchisotta, Stefania, additional, Marinò, Michele, additional, Marshall, John C., additional, Martin, Thomas F.J., additional, Martin, T. John, additional, Martos-Moreno, Gabriel Á., additional, Mathias, Christopher J., additional, Mauer, Michael, additional, McGee, Elizabeth A., additional, McKenna, Neil J., additional, McLachlan, Robert I., additional, Medeiros-Neto, Geraldo, additional, Meier, Juris J., additional, Melmed, Shlomo, additional, Metzger, Boyd E., additional, Millar, Robert, additional, Miller, Walter L., additional, Misra, Madhusmita, additional, Molitch, Mark E., additional, Moore, David D., additional, Morris, Damian G., additional, Munck, Allan U., additional, Nakamoto, Jon, additional, Náray-Fejes-Tóth, Anikó, additional, Nass, Ralf, additional, Nathan, David M., additional, New, Maria I., additional, Nguyen, Carolyn, additional, Nieman, Lynnette K., additional, Nilson, John H., additional, Norton, Jeffrey A., additional, Oakley, Robert H., additional, Öberg, Kjell, additional, Olefsky, Jerrold M., additional, O’Rahilly, Stephen, additional, Ozcan, Umut, additional, Pacak, Karel, additional, Pacini, Furio, additional, Padia, Shetal H., additional, Paschke, Ralf, additional, Pawson, Adam, additional, Peck, Alison C., additional, Giraldi, Francesca Pecori, additional, Persani, Luca, additional, Phelps, Richard L., additional, Philipson, Louis H., additional, Phillips, Kevin, additional, Pinchera, Aldo, additional, Pomposelli, Frank B., additional, Potts, John T., additional, Quigley, Charmian A., additional, Quinkler, Marcus, additional, Quirk, Christine Campion, additional, Rademaker, Miriam T., additional, Meyts, Ewa Rajpert-De, additional, Ravussin, Eric, additional, Ray, David W., additional, Reame, Nancy King, additional, Refetoff, Samuel, additional, Retnakaran, Ravi, additional, Rey, Rodolfo A., additional, Rhodes, Christopher J., additional, Ridgway, E. Chester, additional, Risbridger, Gail P., additional, Rizza, Robert A., additional, Robinson, Bruce, additional, Roger, Pierre P., additional, Rosenfeld, Michael G., additional, Rosenfield, Robert L., additional, Rosing, James H., additional, Rossing, Peter, additional, Rubin, Robert T., additional, Ruderman, Neil, additional, Russo, Irma H., additional, Russo, Jose, additional, Salameh, Wael Antoine, additional, Salusky, Isidoro B., additional, Samuels, Mary H., additional, Santen, Richard J., additional, Santoro, Nanette, additional, Sarapura, Virginia D., additional, Sealfon, Stuart C., additional, Sexton, Patrick M., additional, Shulman, Gerald I., additional, Silva, Paolo S., additional, Silverberg, Shonni J., additional, Singer, Frederick R., additional, Skakkebaek, Niels E., additional, Skowronska-Krawczyk, Dorota, additional, Smith, Carolyn L., additional, Smith, Philip W., additional, Smith, Roger, additional, Smith, Steven R., additional, Snyder, Peter J., additional, Stanhope, Richard, additional, St-Arnaud, René, additional, Steiner, Donald F., additional, Stevens, Adam, additional, Stewart, Andrew F., additional, Stewart, Paul M., additional, St. Germain, Donald L., additional, Stockigt, Jim, additional, Strauss, Jerome F., additional, Swiersz, Lillian Marie, additional, Tacon, Lyndal J., additional, Taheri, Shahrad, additional, Thakker, Rajesh V., additional, Thompson, Chris, additional, Thorner, Michael O., additional, Timmers, Henri J.L.M., additional, Toppari, Jorma, additional, Traggiai, Cristina, additional, Traub, Michael L., additional, Tseng, Yolanda, additional, Turek, Fred W., additional, Van Cauter, Eve, additional, Van den Berghe, Greet, additional, Van Steirteghem, André C., additional, Vassart, Gilbert, additional, Vilain, Eric, additional, Visser, Theo J., additional, Wajnrajch, Michael P., additional, Wand, Gary, additional, Webb, Paul, additional, Weetman, Anthony P., additional, Weigel, Nancy L., additional, Weir, Gordon C., additional, Weiss, Roy E., additional, Wesseling-Perry, Katherine, additional, White, Anne, additional, White, Kenneth E., additional, White, Morris F., additional, Whyte, Michael P., additional, Wiersinga, Wilmar M., additional, Wolfsdorf, Joseph I., additional, and Zinman, Bernard, additional

Published
2010
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33. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine and Hybrid Imaging

Author

Sundin, Anders, Arnold, Rudolf, Baudin, Eric, Cwikla, Jaroslaw B, Eriksson, Barbro, Fanti, Stefano, Fazio, Nicola, Giammarile, Francesco, Hicks, Rodney J, Kjaer, Andreas, Krenning, Eric, Kwekkeboom, Dik, Lombard-Bohas, Catherine, O'Connor, Juan M, O'Toole, Dermot, Rockall, Andrea, Wiedenmann, Bertram, Valle, Juan W, Vullierme, Marie-Pierre, Ferone, D, Sundin A, Arnold R, Baudin E, Cwikla JB, Eriksson B, Fanti S, Fazio N, Giammarile F, Hicks RJ, Kjaer A, Krenning E, Kwekkeboom D, Lombard-Bohas C, O'Connor JM, O'Toole D, Rockall A, Wiedenmann B, Valle JW, Vullierme MP, Erasmus MC other, and Radiology & Nuclear Medicine

Subjects
Positron emission tomography, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Single photon emission computed tomography, Single-photon emission computed tomography, Neuroendocrine tumors, Scintigraphy, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, Magnetic resonance imaging, Hybrid imaging, NET, 0302 clinical medicine, Endocrinology, Neuroendocrine tumor, Ultrasound, Biopsy, medicine, Computed tomography, Lymph node, medicine.diagnostic_test, Manchester Cancer Research Centre, Endocrine and Autonomic Systems, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Somatostatin receptor imaging, medicine.disease, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Radiology, Nuclear medicine, business, Preclinical imaging
Abstract

Contrast-enhanced computed tomography (CT) of the neck-thorax-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 CT-guided 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 68Ga-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. 18FDG-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.

Published
2017

42. Treatment with cisplatin and etoposide in patients with neuroendocrine tumors

Author

Fjallskog, Marie-Louise, Granberg, Dan P.K., Welin, Staffan L.V., Eriksson, Christopher, Oberg, Kjell E., Janson, Eva T., and Eriksson, Barbro K.

Subjects
Endocrine gland tumors, Nervous system tumors, Chemotherapy, Combination -- Evaluation, Cisplatin -- Health aspects, Etoposide -- Health aspects, Pancreatic tumors, Health
Published
2001

43. 177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated with Chemotherapy: Analysis of Outcome, Safety, and Their Determinants.

Author

Fröss-Baron, Katarzyna, Garske-Roman, Ulrike, Welin, Staffan, Granberg, Dan, Eriksson, Barbro, Khan, Tanweera, Sandström, Mattias, and Sundin, Anders

Subjects
NEUROENDOCRINE tumors, PANCREATIC tumors, CANCER chemotherapy, ACUTE myeloid leukemia, PEPTIDE receptors, RADIATION dosimetry, ABSORBED dose
Abstract

Objective: To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS), and their determinants in patients with advanced pancreatic neuroendocrine tumors (PanNETs), previously pretreated with chemothe-r-apy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Methods: A total of 102 patients with advanced PanNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy, were included, of whom 90% had progressive disease and the majority (74.5%) had grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6- to 8-week intervals in 88% of patients utilizing a dosimetry-guided protocol until an absorbed dose of 23 Gy to the kidneys was reached. Results: A mean dose of 32 ± 10.9 GBq per patient was administered in 1–10 cycles starting a median of 36 months after PanNET diagnosis. The median follow-up was 34 months, the median PFS was 24 months, and the median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy, and elevated alkaline phosphatase. Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3–4 occurred in 10.8%. One patient (1.0%) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity, and absorbed dose to the bone marrow. Conclusion: 177Lu-DOTATATE therapy was feasible, highly effective, and safe in patients with advanced PanNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy-related independent risk factor for shorter PFS and OS. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids

Author

Caplin, M. E., Baudin, E., Ferolla, P., Filosso, P., Garcia-Yuste, M., Lim, E., Oberg, K., Pelosi, G., Perren, A., Rossi, R. E., Travis, W. D., Bartsch, Detlief, Capdevila, Jaume, Costa, Frederico, Cwikla, Jaroslaw, de Herder, Wouter, Delle Fave, Gianfranco, Eriksson, Barbro, Falconi, Massimo, Ferone, Diego, Gross, David, Grossman, Ashley, Ito, Tetsuhide, Jensen, Robert, Kaltsas, Gregory, Kelestimur, Fahrettin, Kianmanesh, Reza, Knigge, Ulrich, Kos-Kudla, Beata, Krenning, Eric, Mitry, Emmanuel, Nicolson, Marianne, O'Connor, Juan, O'Toole, Dermot, Pape, Ulrich-Frank, Pavel, Marianne, Ramage, John, Raymond, Eric, Rindi, Guido, Rockall, Andrea, Ruszniewski, Philippe, Salazar, Ramon, Scarpa, Aldo, Sedlackova, Eva, Sundin, Anders, Toumpanakis, Christos, Vullierme, Marie-Pierre, Weber, Wolfgang, Wiedenmann, Bertram, and Zheng-Pei, Zeng

Abstract

This is an expert consensus from the European Neuroendocrine Tumor Society recommending best practice for the management of pulmonary neuroendocrine tumors including typical and atypical carcinoids. It emphasizes the latest discussion on nomenclature, advances and utility of new diagnostic techniques as well as the limited evidence and difficulties in determining the optimal therapeutic strategy

Published
2017

50. High-Grade Progression Confers Poor Survival in Pancreatic Neuroendocrine Tumors.

Author

Botling, Johan, Lamarca, Angela, Bajic, Duska, Norlén, Olov, Lönngren, Vincent, Kjaer, Josefine, Eriksson, Barbro, Welin, Staffan, Hellman, Per, Rindi, Guido, Skogseid, Britt, and Crona, Joakim

Subjects
NEUROENDOCRINE tumors, PANCREATIC tumors, ABSOLUTE value, TUMOR grading, UNIVERSITY hospitals
Abstract

Introduction: Little is known about how pancreatic neuroendocrine tumors (PanNETs) evolve over time and if changes toward a more aggressive biology correlate with prognosis. The purpose of this study was to characterize changes in PanNET differentiation and proliferation over time and to correlate findings to overall survival (OS). Patients and Methods: In this retrospective cohort study, we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were reevaluated with regard to tumor histopathology and Ki-67 index. Results: Forty-six patients with 106 tumor samples (56 available for pathology reevaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1–38%), grade 1 n = 8, grade 2 n = 36, and grade 3 n = 2. The median change in Ki-67 index (absolute value; follow-up – baseline) was +14% (range –11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n = 24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (hazard ratio 3.89, 95% CI 1.91–7.94, p < 0.001). Conclusions: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET. [ABSTRACT FROM AUTHOR]

Published
2020
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