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Granberg, Dan
Publications (10 of 55) Show all publications
Carlsen, E. A., Fazio, N., Granberg, D., Grozinsky-Glasberg, S., Ahmadzadehfar, H., Grana, C. M., . . . Sorbye, H. (2019). Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study. Endocrine-Related Cancer, 26(2), 227-239
Open this publication in new window or tab >>Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study
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2019 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 26, no 2, p. 227-239Article in journal (Refereed) Published
Abstract [en]

Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1-2 (G1-G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21-54% (n = 125) vs Ki-67 >= 55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3-4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.

Place, publisher, year, edition, pages
Bioscientifica, 2019
Keywords
neuroendocrine tumors, neuroendocrine carcinoma, neuroendocrine neoplasm, high-grade, peptide receptor radionuclide therapy, radiolabeled somatostatin analogues, (177)Lutetium, (90)Yttrium, progression-free survival, overall survival
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-376717 (URN)10.1530/ERC-18-0424 (DOI)000456738400014 ()30540557 (PubMedID)
Available from: 2019-02-12 Created: 2019-02-12 Last updated: 2019-02-12Bibliographically approved
Sandström, M., Fröss-Baron, K., Khan, T. S., Granberg, D., Sundin, A. & Lubberink, M. (2018). Absorbed doses based on a single measurement point versus three measurement points in 600 patients with neuroendocrine tumours receiving 177Lu-DOTATATE therapy. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45(Supplement 1), S31-S31
Open this publication in new window or tab >>Absorbed doses based on a single measurement point versus three measurement points in 600 patients with neuroendocrine tumours receiving 177Lu-DOTATATE therapy
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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 Supplement 1, p. S31-S31Article in journal, Meeting abstract (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-373335 (URN)10.1007/s00259-018-4148-3 (DOI)000449266200039 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Note

Meeting Abstract: OP-076

Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-01-14Bibliographically approved
Sandström, M., Garske, U., Johansson, S., Granberg, D., Sundin, A. & Freedman, N. (2018). Kidney dosimetry during (177)Lu-DOTATATE therapy in patients with neuroendocrine tumors: aspects on calculation and tolerance. Acta Oncologica, 57(4), 516-521
Open this publication in new window or tab >>Kidney dosimetry during (177)Lu-DOTATATE therapy in patients with neuroendocrine tumors: aspects on calculation and tolerance
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 4, p. 516-521Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Fractionated therapy with (177)Lu-DOTATATE has been reported to be an effective treatment for patients with metastasized neuroendocrine tumors. To optimize the treatment, absorbed doses to risk organs are calculated for the individual patient. For each organ, absorbed dose due to activity in the organ itself (self-dose) and that originating from other organs (cross-dose) are calculated from serial measurements to obtain the activity distribution following treatment. The main aim of the present work were to calculate the cross-dose contribution to the total absorbed kidney dose.

METHODS: Five hundred patients with neuroendocrine tumors undergoing therapy with (177)Lu-DOTATATE were included. Scintigraphic planar whole body images and single photon emission computed tomography/computed tomography (SPECT/CT) over the abdomen were acquired at 1, 4 and 7 days after treatment. Kidney self-dose was calculated based on radioactivity distribution obtained from SPECT/CT. Cross-dose to kidneys was estimated using organ-based analysis of planar whole body images and cross-fire dose factors from Olinda/EXM 1.1.

RESULTS: Cross-dose to kidneys in the majority of patients were less than 2% and almost all cross-doses were less than 10%. Cross-dose exceeded 10% only in rare cases of patients with high tumor burden and low absorbed doses to kidneys.

CONCLUSIONS: The absorbed dose from (177)Lu-octreotate to solid organs due to cross-fire is generally low and can usually be neglected.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-329755 (URN)10.1080/0284186X.2017.1378431 (DOI)000427934300011 ()28920501 (PubMedID)
Available from: 2017-09-20 Created: 2017-09-20 Last updated: 2019-06-27Bibliographically 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
Skovgaard, D., Fazio, N., Granberg, D., Grozinsky-Glasberg, S., Ahmadzadehfar, H., Zandee, W., . . . Horbye, H. (2018). Selected For Oral Presentation: Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic Grade 3 Neuroendocrine Neoplasms: A Retrospective International Multicenter Study. Paper presented at 15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 07-09, 2018, Barcelona, SPAIN. Neuroendocrinology, 106(Supplement: 1), 258-258
Open this publication in new window or tab >>Selected For Oral Presentation: Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic Grade 3 Neuroendocrine Neoplasms: A Retrospective International Multicenter Study
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2018 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 258-258Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
KARGER, 2018
Keywords
neuroendocrine neoplasms, who grade 3, prrt, progression-free survival, overall survival
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-354380 (URN)10.1159/000487699 (DOI)000427285300256 ()
Conference
15th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, MAR 07-09, 2018, Barcelona, SPAIN
Note

Meeting Abstract: K20

WoS title: Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic Grade 3 Neuroendocrine Neoplasms: A Retrospective International Multicenter Study

Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-06-29Bibliographically 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
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)000461065100007 ()28717741 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-08-28Bibliographically approved
Casar Borota, O., Botling, J., Granberg, D., Stigare, J., Wikström, J., Boldt, H. B., . . . Trouillas, J. (2017). Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.. American Journal of Surgical Pathology, 41(9), 1238-1246
Open this publication in new window or tab >>Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.
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2017 (English)In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 41, no 9, p. 1238-1246Article in journal (Refereed) Published
Abstract [en]

Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-333688 (URN)10.1097/PAS.0000000000000908 (DOI)000428795500007 ()28719461 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2019-03-29Bibliographically 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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