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Granberg, Dan
Publications (10 of 49) Show all publications
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)
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 6Article 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
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: 2018-04-27Bibliographically 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.

Keywords
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
Singh, S., Granberg, D., Wolin, E., Warner, R., Sissons, M., Kolarova, T., . . . Leyden, J. (2017). Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs. Journal of global oncology, 3(1), 43-53
Open this publication in new window or tab >>Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs
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2017 (English)In: Journal of global oncology, ISSN 2378-9506, Vol. 3, no 1, p. 43-53Article in journal (Refereed) Published
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.

National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-342488 (URN)10.1200/JGO.2015.002980 (DOI)28717741 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-03-23Bibliographically 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
Ebeling Barbier, C., Garske-Román, U., Sandström, M., Nyman, R. & Granberg, D. (2016). Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. European Journal of Nuclear Medicine and Molecular Imaging, 43(8), 1425-1431
Open this publication in new window or tab >>Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases
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2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 8, p. 1425-1431Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs).

METHODS: This retrospective study included 40 patients with progressive NETLMs (22 women, 18 men, mean age 61.6 years) who underwent SIRT with (90)Y-labelled resin microspheres. Tumour response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on CT or MR images. Medical records were reviewed.

RESULTS: In the 40 patients, 54 evaluable SIRT procedures were performed, 33 to the right liver lobe (mean activity 1.31 GBq), 13 to the left lobe (mean activity 0.85 GBq), and 8 to both lobes (mean activity 1.61 GBq). Late follow-up imaging (mean 20 months) was performed after 44 of the treatments. Objective tumour response and disease control rates were 54 % (29 of 54 treatments) and 94 % (51 treatments), respectively, at the early follow-up examination (mean 3 months) and 34 % (15 treatments) and 57 % (25 treatments), respectively at the late follow-up examination. Mean overall survival from the first SIRT was 34,8 months and survival rates at 1, 2, 3 and 5 years were 76 %, 59 %, 52 % and 35 % respectively. Adverse effects were generally mild and easily manageable, except in one patient who died from radiation-induced liver failure. Of the 45 patients, 18 (45 %) had received peptide receptor radionuclide therapy (PRRT) prior to SIRT.

CONCLUSION: SIRT with (90)Y-labelled resin microspheres is a safe and effective treatment for patients with progressive NETLM, and also for those who have received prior PRRT.

Keywords
Selective internal radiation therapy; Neuroendocrine liver metastases; Transarterial; Yttrium
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-268834 (URN)10.1007/s00259-015-3264-6 (DOI)000378005000006 ()26631239 (PubMedID)
Available from: 2015-12-10 Created: 2015-12-10 Last updated: 2017-12-01Bibliographically approved
Antonodimitrakis, P., Sundin, A., Wassberg, C., Granberg, D., Skogseid, B. & Eriksson, B. (2016). Streptozocin and 5-FU for the treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity. Neuroendocrinology, 103(3-4), 345-353
Open this publication in new window or tab >>Streptozocin and 5-FU for the treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity
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2016 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, no 3-4, p. 345-353Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In our center, the combination of streptozocin (STZ) and 5-fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU.

PATIENTS AND METHODS: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated.

RESULTS: Median survival from start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100) progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from start of treatment, respectively. Having either a G3 tumor or stage IV tumor were significant prognostic factors for shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side-effects, of which kidney toxicity (mainly grade 1-2) was the most frequent.

CONCLUSION: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response, and has an acceptable toxicity profile.

National Category
Endocrinology and Diabetes Neurology
Identifiers
urn:nbn:se:uu:diva-261212 (URN)10.1159/000439086 (DOI)000375766500016 ()26279284 (PubMedID)
Available from: 2015-08-31 Created: 2015-08-31 Last updated: 2017-09-18Bibliographically approved
Granberg, D. (2015). Biochemical Testing in Patients with Neuroendocrine Tumors. In: Papotti, M; DeHerder, WW (Ed.), Neuroendocrine Tumors: A Multidisciplinary Approach (pp. 24-39). Krager
Open this publication in new window or tab >>Biochemical Testing in Patients with Neuroendocrine Tumors
2015 (English)In: Neuroendocrine Tumors: A Multidisciplinary Approach / [ed] Papotti, M; DeHerder, WW, Krager , 2015, p. 24-39Chapter in book (Refereed)
Abstract [en]

Neuroendocrine tumors are usually slow-growing tumors. Many of these are capable of secreting peptide hormones or biogenic amines that may lead to endocrine syndromes. Nonfunctioning tumors can either secrete no hormones at all, or secrete hormones not giving rise to endocrine symptoms, such as chromogranin A, chromogranin B or pancreatic polypeptide. Chromogranin A is produced by the majority of endocrine tumors, both functioning and nonfunctioning, and is the best available marker for diagnosis, follow-up and treatment monitoring of patients with differentiated neuroendocrine tumors. Examples of endocrine syndromes are classical carcinoid syndrome caused by serotonin (measured in the urine as its metabolite 5-HIAA), insulinoma syndrome caused by insulin or proinsulin, Zollinger-Ellison syndrome resulting from gastrin secretion, glucagonoma syndrome caused by glucagon, WDHA syndrome caused by vasoactive intestinal peptide, or Cushing's syndrome resulting from ectopic production of adrenocorticotropic hormone or corticotropin-releasing hormone. In case there is uncertainty about the diagnosis, specific tests can be applied, such as the secretin test for diagnosis of gastrinomas and the 72-hour fast for diagnosis of an insulinoma. In patients with suspicion of an inherited syndrome, such as multiple endocrine neoplasia (MEN) 1 and MEN2 syndromes, genetic testing is indicated.

Place, publisher, year, edition, pages
Krager, 2015
Series
Frontiers of Hormone Research, ISSN 0301-3073 ; 44
National Category
Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-284906 (URN)10.1159/000381981 (DOI)000370334100003 ()26303702 (PubMedID)978-3-318-02773-0; 978-3-318-02772-3 (ISBN)
Available from: 2016-04-19 Created: 2016-04-19 Last updated: 2016-04-19Bibliographically approved
Ilan, E., Sandström, M., Wassberg, C., Sundin, A., Garske-Román, U., Eriksson, B., . . . Lubberink, M. (2015). Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE. Journal of Nuclear Medicine, 56(2), 177-182
Open this publication in new window or tab >>Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE
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2015 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 56, no 2, p. 177-182Article in journal (Refereed) Published
Abstract [en]

UNLABELLED: Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE.

METHODS: Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors.

RESULTS: Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy.

CONCLUSION: The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-244162 (URN)10.2967/jnumed.114.148437 (DOI)000349324300015 ()25593115 (PubMedID)
Available from: 2015-02-12 Created: 2015-02-12 Last updated: 2017-12-04Bibliographically approved
Sandström, M., Garske-Roman, U., Granberg, D., Sundin, A. & Lubberink, M. (2015). Fractional contribution of extrapolations after 96 h in absorbed dose calculation to kidneys in 450 patients with neuroendocrine tumours receiving Lu-177-DOTATATE therapy. Paper presented at 28th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 10-14, 2015, Hamburg, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 42(S1), S7-S8
Open this publication in new window or tab >>Fractional contribution of extrapolations after 96 h in absorbed dose calculation to kidneys in 450 patients with neuroendocrine tumours receiving Lu-177-DOTATATE therapy
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2015 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 42, no S1, p. S7-S8Article in journal, Meeting abstract (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-269144 (URN)000363013201003 ()
Conference
28th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 10-14, 2015, Hamburg, GERMANY
Note

Meeting Abstract: OP011

Available from: 2015-12-18 Created: 2015-12-14 Last updated: 2017-12-01Bibliographically approved
Granberg, D., Sissons, M., Kolarova, T., Goldstein, G. & Leyden, J. (2015). Lung neuroendocrine tumor (NET) patient (pt)-reported experience: Results from the first global NET pt surveyA collaboration between the international neuroendocrine cancer alliance (INCA) and Novartis pharmaceuticals.. Paper presented at Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), MAY 29-JUN 02, 2015, Chicago, IL. Journal of Clinical Oncology, 33(15)
Open this publication in new window or tab >>Lung neuroendocrine tumor (NET) patient (pt)-reported experience: Results from the first global NET pt surveyA collaboration between the international neuroendocrine cancer alliance (INCA) and Novartis pharmaceuticals.
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2015 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-261478 (URN)000358036903684 ()
Conference
Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), MAY 29-JUN 02, 2015, Chicago, IL
Available from: 2015-09-03 Created: 2015-09-01 Last updated: 2017-12-04Bibliographically approved
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