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Eriksson, Barbro
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Publications (10 of 94) Show all publications
Mollazadegan, K., Skogseid, B., Botling, J., Åkerström, T., Eriksson, B., Welin, S., . . . Crona, J. (2022). Poor outcome after systemic therapy in secondary high-grade pancreatic neuroendocrine tumors. Endocrine Connections, 11(3), Article ID e210604.
Open this publication in new window or tab >>Poor outcome after systemic therapy in secondary high-grade pancreatic neuroendocrine tumors
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2022 (English)In: Endocrine Connections, E-ISSN 2049-3614, Vol. 11, no 3, article id e210604Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioscientificaBioscientifica, 2022
Keywords
pancreatic neuroendocrine tumor, highgrade, systemic therapy, treatment outcomes
National Category
Surgery Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-475551 (URN)10.1530/EC-21-0604 (DOI)000793356700013 ()35148276 (PubMedID)
Funder
Swedish Cancer SocietyTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseÅke Wiberg Foundation
Available from: 2022-06-10 Created: 2022-06-10 Last updated: 2024-01-15Bibliographically approved
Fröss-Baron, K., Garske, U., Welin, S., Granberg, D., Eriksson, B., Khan, T. S., . . . Sundin, A. (2021). 177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated With Chemotherapy: Analysis of Outcome, Safety and Their Determinants. Neuroendocrinology, 111(4), 330-343
Open this publication in new window or tab >>177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated With Chemotherapy: Analysis of Outcome, Safety and Their Determinants
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2021 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 111, no 4, p. 330-343Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
S. Karger, 2021
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-415908 (URN)10.1159/000506746 (DOI)000632578200004 ()32097917 (PubMedID)
Available from: 2020-07-08 Created: 2020-07-08 Last updated: 2024-01-15Bibliographically approved
Botling, J., Lamarca, A., Bajic, D., Norlén, O., Lönngren, V., Kjaer, J., . . . Crona, J. (2020). High-grade progression confers poor survival in pancreatic neuroendocrine tumors. Neuroendocrinology, 110(11-12), 891-898
Open this publication in new window or tab >>High-grade progression confers poor survival in pancreatic neuroendocrine tumors
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2020 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 110, no 11-12, p. 891-898Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Little is known about how Pancreatic Neuroendocrine Tumors (PanNETs) evolve over time and if changes towards a more aggressive biology correlates with prognosis. The purpose of this study was to characterize changes 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 re-evaluated with regard to tumor histopathology and Ki-67 index.

RESULTS: Forty-six patients with 106 tumor samples (56 available for pathology re-evaluation) 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 (HR 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.

Keywords
Pancreatic neuroendocrine tumor, Ki-67, Tumor grade, Proliferation, Prognosis, Evolution
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Oncology; Pathology
Identifiers
urn:nbn:se:uu:diva-399943 (URN)10.1159/000504392 (DOI)000576042600001 ()31658459 (PubMedID)
Funder
Torsten Söderbergs stiftelseRagnar Söderbergs stiftelseÅke Wiberg Foundation
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2021-01-14Bibliographically approved
Garske, U., Sandström, M., Fröss-Baron, K., Lundin, L., Hellman, P., Welin, S., . . . Granberg, D. (2018). Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. European Journal of Nuclear Medicine and Molecular Imaging, 45(6), 970-988
Open this publication in new window or tab >>Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no 6, p. 970-988Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.

METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).

RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.

CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.

Keywords
177Lu-DOTA-octreotate, Dosimetry, Neuroendocrine tumour, Outcome, PRRT, Toxicity
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-346995 (URN)10.1007/s00259-018-3945-z (DOI)000430832400010 ()29497803 (PubMedID)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-11-12Bibliographically approved
Backman, S., Norlén, O., Eriksson, B., Skogseid, B., Stålberg, P. & Crona, J. (2017). Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing. Anticancer Research, 37(2), 705-712
Open this publication in new window or tab >>Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing
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2017 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 2, p. 705-712Article in journal (Refereed) Published
Abstract [en]

Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.

PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.

RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.

CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.

Keywords
MTOR, PNET, biomarker, next-generation sequencing
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-320669 (URN)10.21873/anticanres.11367 (DOI)000396901200038 ()28179320 (PubMedID)
Available from: 2017-04-23 Created: 2017-04-23 Last updated: 2019-10-30Bibliographically approved
Pavel, M., Valle, J. W., Eriksson, B., Rinke, A., Caplin, M., Chen, J., . . . Garcia-Carbonero, R. (2017). ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Biotherapy and Novel Targeted Agents. Neuroendocrinology, 105(3), 266-280
Open this publication in new window or tab >>ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Biotherapy and Novel Targeted Agents
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2017 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 266-280Article in journal (Refereed) Published
Abstract [en]

Systemic therapies established in the management of patients with neuroendocrine tumors (NETs) include somatostatin analogs and interferon-alpha, also referred to as biotherapy. Recent randomized controlled studies have extended the knowledge on the frequency of side effects associated with biotherapy. More recently, novel targeted drugs, such as the mammalian target of rapamycin inhibitor everolimus and the multiple tyrosine kinase inhibitor sunitinib, have been introduced in the management of NETs. Although targeted drugs are generally well tolerated, with most adverse events being of mild to moderate severity and manageable, novel targeted drugs exhibit a distinct adverse event profile that warrants guidance for appropriate diagnostic and therapeutic management. This is particularly important given the widespread and potentially long-term use of everolimus in a broad spectrum of NETs and of sunitinib in pancreatic NETs. This review will focus on the most relevant toxicities associated with biotherapy and novel targeted drugs and on their management. For each drug class indication, administration and dosing schedule, most frequent adverse events, actions and dose adjustments for adverse events as well as their monitoring are presented. This review further covers the evaluation of treatment effect, patient information, drug interactions, and information on pregnancy.

Keywords
Somatostatin analogs, Interferon-alpha, Everolimus, Sunitinib, Tolerability, Toxicity, Dose adjustment, Drug interaction, Patient information
National Category
Endocrinology and Diabetes Neurosciences
Identifiers
urn:nbn:se:uu:diva-336663 (URN)10.1159/000471880 (DOI)000411501200007 ()28351033 (PubMedID)
Available from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-01-13Bibliographically approved
Garcia-Carbonero, R., Rinke, A., Valle, J. W., Fazio, N., Caplin, M., Gorbounova, V., . . . Pavel, M. (2017). ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Chemotherapy. Neuroendocrinology, 105(3), 281-294
Open this publication in new window or tab >>ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy - Chemotherapy
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2017 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 281-294Article in journal (Refereed) Published
Abstract [en]

Systemic chemotherapy is indicated in progressive or bulky advanced pancreatic neuroendocrine tumors (NETs) and in grade 3 (G3) neuroendocrine neoplasms (NENs) as per ENETS guidelines. Chemotherapy may be considered in NETs of other sites (lung, thymus, stomach, colon, and rectum) under certain conditions (e.g., when Ki-67 is at a high level [upper G2 range], in rapidly progressive disease and/or after failure of other therapies, or if somatostatin receptor imaging is negative). An ENETS Consensus Conference was held in Antibes (2015) to elaborate guidelines on the standards of care of different diagnostic procedures and therapeutic interventions in NENs. This article provides guidance on chemotherapy including therapeutic indications, dosing schedules, adverse events (including prevention and management), drug interactions, and evaluation of treatment effect for the chemotherapy agents most commonly used in NENs (streptozocin, dacarbazine, fluoropyrimidines, platinum compounds, etoposide, and irinotecan).

Keywords
Neuroendocrine tumors, Chemotherapy, Standard of care, Dosing schedules, Toxicity, Drug interactions
National Category
Endocrinology and Diabetes Neurosciences Neurology
Identifiers
urn:nbn:se:uu:diva-336664 (URN)10.1159/000473892 (DOI)000411501200008 ()28380493 (PubMedID)
Available from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-01-13Bibliographically approved
Sundin, A., Arnold, R., Baudin, E., Cwikla, J. B., Eriksson, B., Fanti, S., . . . Vullierme, M.-P. (2017). ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging.. Neuroendocrinology, 105(3), 212-244
Open this publication in new window or tab >>ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging.
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2017 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 212-244Article in journal (Refereed) Published
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.

Keywords
Neuroendocrine tumor, Computed tomography, Magnetic resonance imaging, Ultrasound, Positron emission tomography, Scintigraphy, Single photon emission computed tomography, Somatostatin receptor imaging
National Category
Medical and Health Sciences Endocrinology and Diabetes Neurosciences
Identifiers
urn:nbn:se:uu:diva-319611 (URN)10.1159/000471879 (DOI)000411501200004 ()28355596 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-01-13Bibliographically approved
Sandström, M., Ilan, E., Fröss-Baron, K., Garske, U., Granberg, D., Eriksson, B., . . . Lubberink, M. (2017). Gender-related differences in absorbed dose to risk organs in patients receiving Lu-177-Octreotate therapy. European Journal of Nuclear Medicine and Molecular Imaging, 44, S158-S158
Open this publication in new window or tab >>Gender-related differences in absorbed dose to risk organs in patients receiving Lu-177-Octreotate therapy
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2017 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S158-S158Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2017
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-377088 (URN)000455019400056 ()
Available from: 2019-02-19 Created: 2019-02-19 Last updated: 2019-02-19Bibliographically approved
Crona, J., Norlén, O., Antonodimitrakis, P., Welin, S., Stålberg, P. & Eriksson, B. (2017). Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumors. Pancreas, 46(3), 441-441
Open this publication in new window or tab >>Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumors
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2017 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, p. 441-441Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-321065 (URN)10.1097/MPA.0000000000000812 (DOI)000394448600077 ()
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2019-10-30Bibliographically approved
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