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- Elf, Anna-Karin, et al.
(author)
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Radioembolization Versus Bland Embolization for Hepatic Metastases from Small Intestinal Neuroendocrine Tumors: Short-Term Results of a Randomized Clinical Trial.
- 2018
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 42:2, s. 506-513
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Journal article (peer-reviewed)abstract
- Radioembolization (RE) with intra-arterial administration of 90Y microspheres is a promising technique for the treatment of liver metastases from small intestinal neuroendocrine tumors (SI-NET) not amenable to surgery or local ablation. However, studies comparing RE to other loco-regional therapies are lacking. The aim of this randomized study was to compare the therapeutic response and safety after RE and bland hepatic arterial embolization (HAE), and to investigate early therapy-induced changes with diffusion-weighted MRI (DWI-MRI).Eleven patients were included in a prospective randomized controlled pilot study, six assigned to RE and five to HAE. Response according to RECIST 1.1 using MRI or CT at 3 and 6months post-treatment was recorded as well as changes in DWI-MRI parameters after 1month. Data on biochemical tumor response, toxicity, and side effects were also collected.Three months after treatment, all patients in the HAE group showed partial response according to RECIST while none in the RE group did (p=0.0022). After 6months, the response rates were 4/5 (80%) and 2/6 (33%) in the HAE and RE groups, respectively (NS). DWI-MRI metrics could not predict RECIST response, but lower pretreatment ADC(120-800) and larger ADC(0-800) increase at 1month were related to larger decrease in tumor diameter when all tumors were counted.HAE resulted in significantly higher RECIST response after 3months, but no difference compared to RE remained after 6months. These preliminary findings indicate that HAE remains a safe option for the treatment of liver metastases from SI-NET, and further studies are needed to establish the role of RE and the predictive value of MR-DWI.
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| 2. |
- Elf, Anna-Karin
(author)
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Targeted radiotherapy in metastatic neuroendocrine tumours: clinical and experimental studies
- 2018
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Doctoral thesis (other academic/artistic)abstract
- ABSTRACT Neuroendocrine tumours (NET) often present at a metastatic stage, which diminishes the possibility for curative surgery. Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE targets somatostatin receptors, which are overexpressed on NET cells. PRRT results in symptom relief and often tumour control of NETs, but rarely cure. Tumour response is variable and renal and haematological toxicity are dose-limiting side effects. In metastatic small intestinal NET (SI-NET) hepatic metastases are often a clinical problem. Several treatment options exist and radioembolization (RE) of the liver is a recently introduced therapy. Diffusion weighted MRI (DWI) is a new imaging technique reflecting the microenvironment of tumours and is maybe useful for treatment response evaluation. Aims of the thesis project were to identify predictive factors for response and long-term outcome after PRRT, and investigate a possibility for radiosensitization. Further, RE was compared to hepatic artery embolization (HAE) for SI-NET hepatic metastases, and the utility of DWI as a predictor for morphologic treatment response was investigated. A retrospective study of 51 NET patients treated with 177Lu-DOTATATE revealed an objective response rate of 13%, however most patients responded with halted tumour growth. High tumour proliferation rate, but not diagnosis, was associated with shorter survival. Overall long-term toxicity was low. The absorbed tumour dose varied considerably within and between patients, but the median absorbed tumour dose was correlated with tumour shrinkage. In a retrospective study on stage IV SI-NET, patients with low somatostatin receptor 2 (SSTR2) expression did not have an inferior outcome after PRRT. In contrast, a tendency was found towards both higher activity uptake after PRRT and longer survival. In an experimental animal study, the NAMPT inhibitor GMX1778 enhanced the efficacy of 177Lu-DOTATATE and almost eradicated all tumours. In a clinical prospective study on SI-NET hepatic metastases, HAE resulted in earlier tumour shrinkage than RE, and the response at 3 months was correlated with DWI after 1 month. A low baseline apparent diffusion was correlated with a larger tumour shrinkage at 6 months. In conclusion, tumour grade can predict long-term outcome after PRRT in metastatic NET and tumour dosimetry can be useful for response prediction. Low SSTR2 expression should not exclude patients from PRRT. GMX1778 might be used as a radiosensitizer in PRRT for SI-NET. DWI can be useful for prediction and early evaluation of treatment response after RE and HAE for liver metastasized SI-NET.
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| 3. |
- Jalnefjord, Oscar, 1989, et al.
(author)
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Comparison of methods for estimation of the intravoxel incoherent motion (IVIM) diffusion coefficient (D) and perfusion fraction (f)
- 2018
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In: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 31:6, s. 715-723
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Journal article (peer-reviewed)abstract
- Objective: Intravoxel incoherent motion (IVIM) shows great potential in many applications, e.g., tumor tissue characterization. To reduce image-quality demands, various IVIM analysis approaches restricted to the diffusion coefficient (D) and the perfusion fraction (f) are increasingly being employed. In this work, the impact of estimation approach for D and f is studied. Materials and methods: Four approaches for estimating D and f were studied: segmented IVIM fitting, least-squares fitting of a simplified IVIM model (sIVIM), and Bayesian fitting of the sIVIM model using marginal posterior modes or posterior means. The estimation approaches were evaluated in terms of bias and variability as well as ability for differentiation between tumor and healthy liver tissue using simulated and in vivo data. Results: All estimation approaches had similar variability and ability for differentiation and negligible bias, except for the Bayesian posterior mean of f, which was substantially biased. Combined use of D and f improved tumor-to-liver tissue differentiation compared with using D or f separately. Discussion: The similar performance between estimation approaches renders the segmented one preferable due to lower numerical complexity and shorter computational time. Superior tissue differentiation when combining D and f suggests complementary biologically relevant information.
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| 5. |
- Lesén, Eva, et al.
(author)
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Real-world treatment patterns, resource use and costs of treating uncontrolled carcinoid syndrome and carcinoid heart disease : a retrospective Swedish study
- 2018
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:12, s. 1509-1518
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Journal article (peer-reviewed)abstract
- Objectives: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns.Materials and methods: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group.Results: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500€/patient during controlled CS (8 months), rising to 21,700€/patient during uncontrolled CS (8 months), representing an increase of ∼40% (6200€/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100€/patient without CHD, compared to 4600€/patient with CHD, a difference of 3500€/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography.Conclusions: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.
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