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Eriksson, Barbro
Alternative names
Publications (10 of 90) Show all publications
Garske, U., Sandström, M., Fröss-Baron, K., Lundin, L., Hellman, P., Welin, S., . . . Granberg, D. (2018). Lu-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
Open this publication in new window or tab >>Lu-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 1619-7089Article in journal (Refereed) Epub ahead of print
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.

Keyword
177Lu-DOTA-octreotate, Dosimetry, Neuroendocrine tumour, Outcome, PRRT, Toxicity
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346995 (URN)10.1007/s00259-018-3945-z (DOI)29497803 (PubMedID)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-04-13Bibliographically 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.

Keyword
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: 2017-04-25Bibliographically 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.

Keyword
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).

Keyword
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.

Keyword
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
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: 2017-05-11Bibliographically approved
Antonodimitrakis, P. C., Olofsson, H., Grimelius, L., Sundin, A., Wassberg, C., Granberg, D., . . . Eriksson, B. (2017). Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study. International Journal of Endocrine Oncology, 4(1), 9-22
Open this publication in new window or tab >>Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study
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2017 (English)In: International Journal of Endocrine Oncology, Vol. 4, no 1, p. 9-22Article in journal (Refereed) Published
Abstract [en]

Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.

Keyword
chemotherapy, IFN-α, neuroendocrine tumors, pancreas, somatostatin analogs, survival, vasoactive intestinal polypeptide
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-342674 (URN)10.2217/ije-2016-0012 (DOI)000426222300003 ()
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-03-23Bibliographically approved
Ilan, E., Sandström, M., Velikyan, I., Sundin, A., Eriksson, B. & Lubberink, M. (2017). Parametric Net Influx Rate Images of Ga-68-DOTATOC and Ga-68-DOTATATE: Quantitative Accuracy and Improved Image Contrast. Journal of Nuclear Medicine, 58(5), 744-749
Open this publication in new window or tab >>Parametric Net Influx Rate Images of Ga-68-DOTATOC and Ga-68-DOTATATE: Quantitative Accuracy and Improved Image Contrast
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2017 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no 5, p. 744-749Article in journal (Refereed) Published
Abstract [en]

(68)Ga-DOTATOC and (68)Ga-DOTATATE are radiolabelled somatostatin analogs used for diagnosis of somatostatin receptor expressing neuroendocrine tumors (NETs) and SUV -measurements are suggested for treatment monitoring. However, changes in net-influx rate (Ki) may better reflect treatment effects than those of the SUV, and accordingly there is a need to compute parametric images showing Ki at the voxel level. The aim of this study was to evaluate parametric methods for computation of parametric Ki images by comparison to volume of interest based methods and to assess image contrast in terms of tumor-to-liver ratio.

METHODS: Ten patients with metastatic NETs underwent a 45-min dynamic PET examination followed by whole-body PET/CT at 1 h post injection of (68)Ga-DOTATOC and (68)Ga-DOTATATE on consecutive days. Parametric Ki images were computed using a basis function method (BFM) implementation of the two tissue irreversible compartment model and the Patlak method using a descending aorta image-derived input function, and mean tumor Ki values were determined for 50% isocontour VOIs and compared to Ki values based on non-linear regression (NLR) of the whole-VOI time-activity curve. A subsample of healthy liver was delineated in the whole-body and Ki images and tumor-to-liver ratios were calculated in order to evaluate image contrast. Correlation and agreement between VOI-based and parametric Ki values were assessed using regression and Bland-Altman analysis.

RESULTS: Correlation (R2) between NLR-based and parametric image-based (BFM) tumor Ki values was 0.98 (slope 0.81) and 0.97 (slope 0.88) for (68)Ga-DOTATOC and (68)Ga DOTATATE, respectively. For Patlak analysis, correlation between NLR-based and parametric based (Patlak) tumor Ki were 0.95 (slope 0.71) and 0.92 (slope 0.74) for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively. There was no bias between NLR and parametric based Ki-values. Tumor-to-liver contrast was 1.6 and 2.0 times higher in the parametric BFM-Ki images, and 2.3 and 3.0 times in the Patlak images, than in the whole-body images for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively.

CONCLUSION: A high correlation and agreement between NLR- and parametric based Ki values was found, showing that parametric net influx rate images are quantitatively accurate. In addition, tumor-to-liver contrast was superior in the parametric Ki images compared to whole-body images both for (68)Ga-DOTATOC and (68)Ga DOTATATE.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-308417 (URN)10.2967/jnumed.116.180380 (DOI)27789716 (PubMedID)
Available from: 2016-11-25 Created: 2016-11-25 Last updated: 2017-11-14
Eriksson, O., Rosenström, U., Selvaraju, R. K., Eriksson, B. & Velikyan, I. (2017). Species differences in pancreatic binding of DO3A-VS-Cys40-Exendin4. Acta Diabetologica, 54(11), 1039-1045
Open this publication in new window or tab >>Species differences in pancreatic binding of DO3A-VS-Cys40-Exendin4
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2017 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 54, no 11, p. 1039-1045Article in journal (Refereed) Published
Abstract [en]

AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed.

METHODS: -Exendin4 Positron Emission Tomography (PET) in the same species. In vitro, ex vivo, and in vivo data formed the basis for calculating the theoretical in vivo contribution of each pancreatic compartment.

RESULTS: -Exendin4.

CONCLUSIONS: IPR as well as the exocrine GLP-1R density is the main determinants of the species variability in pancreatic uptake. Thus, the IPR in human is an important factor for assessing the potential of GLP-1R as an imaging biomarker for pancreatic beta cells.

Keyword
Animal models, Beta cell imaging, Beta cell mass, Exendin4, GLP-1R, Positron emission tomography
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-342527 (URN)10.1007/s00592-017-1046-2 (DOI)000413142300008 ()28891030 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-02-23Bibliographically approved
Carlbom, L., Caballero-Corbalán, J., Granberg, D., Sörensen, J., Eriksson, B. & Ahlström, H. (2017). Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors. Upsala Journal of Medical Sciences, 122(1), 43-50
Open this publication in new window or tab >>Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors
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2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 43-50Article in journal (Refereed) Published
Abstract [en]

AIM: We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison.

MATERIALS AND METHODS: Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT.

RESULTS: There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT.

CONCLUSION: Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT.

National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-311309 (URN)10.1080/03009734.2016.1248803 (DOI)000396476600006 ()27894208 (PubMedID)
Funder
Swedish Cancer Society, 15-0725
Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2017-11-29Bibliographically approved
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