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- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 3. |
- Cederkrantz, Elin, et al.
(författare)
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Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients.
- 2015
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 93:3, s. 569-76
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of (211)At-MX35 F(ab')2.
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| 6. |
- Lomsky, Milan, 1948, et al.
(författare)
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A new automated method for analysis of gated-SPECT images based on a three-dimensional heart shaped model
- 2005
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Ingår i: Clin Physiol Funct Imaging. - 1475-0961. ; 25:4, s. 234-40
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Tidskriftsartikel (refereegranskat)abstract
- A new automated method for quantification of left ventricular function from gated-single photon emission computed tomography (SPECT) images has been developed. The method for quantification of cardiac function (CAFU) is based on a heart shaped model and the active shape algorithm. The model contains statistical information of the variability of left ventricular shape. CAFU was adjusted based on the results from the analysis of five simulated gated-SPECT studies with well defined volumes of the left ventricle. The digital phantom NURBS-based Cardiac-Torso (NCAT) and the Monte-Carlo method SIMIND were used to simulate the studies. Finally CAFU was validated on ten rest studies from patients referred for routine stress/rest myocardial perfusion scintigraphy and compared with Cedar-Sinai quantitative gated-SPECT (QGS), a commercially available program for quantification of gated-SPECT images. The maximal differences between the CAFU estimations and the true left ventricular volumes of the digital phantoms were 11 ml for the end-diastolic volume (EDV), 3 ml for the end-systolic volume (ESV) and 3% for the ejection fraction (EF). The largest differences were seen in the smallest heart. In the patient group the EDV calculated using QGS and CAFU showed good agreement for large hearts and higher CAFU values compared with QGS for the smaller hearts. In the larger hearts, ESV was much larger for QGS than for CAFU both in the phantom and patient studies. In the smallest hearts there was good agreement between QGS and CAFU. The findings of this study indicate that our new automated method for quantification of gated-SPECT images can accurately measure left ventricular volumes and EF.
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| 7. |
- Montelius, Mikael, 1979, et al.
(författare)
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Tumour size measurement in a mouse model using high resolution MRI.
- 2012
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Ingår i: BMC medical imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (102-101g). The aim of this study was to assess the accuracy of MRI based tumour size measurements in small tumours on mice. METHODS: 2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm3, using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis. RESULTS: Strong correlations were demonstrated between MRI-and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter-and intraobserver variation. In 3D images, the voxel sizes could be increased from 1603um3 to 2403um3 without affecting the results significantly, thus reducing acquisition time substantially. CONCLUSIONS: 2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session.
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| 8. |
- Sundlöv, Anna, et al.
(författare)
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Feasibility of simplifying renal dosimetry in Lu-177 peptide receptor radionuclide therapy
- 2018
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Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, Lu-177-dotatate therapy for neuroendocrine tumours has received regulatory approval. Dosimetry can be used to optimize treatment on an individual basis, but there is no international consensus as to how it should be done. The aim of this study is to determine a feasible and accurate dosimetry method to guide individualized peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumours. As part of a clinical trial on Lu-177-dotatate therapy, renal dosimetry was performed for all patients in each treatment cycle, using a hybrid planar-SPECT/CT method. In the present study, we use the image data acquired from 22 patients and 119 cycles and define a set of alternative treatment planning strategies, each representing a simplification in terms of image acquisition and dosimetric calculations. The results from the simplified strategies are compared to the results from the protocol-prescribed hybrid planar-SPECT/CT-based method by analysing differences both in per-cycle and total cumulative absorbed dose (AD) analyses. Results: In general, the SPECT-based methods gave results that were largely consistent with the protocol-specified hybrid method, both in the per-cycle and cumulative AD analyses. Notably, performing one SPECT/CT per cycle at 96 h yielded ADs that were very similar to the protocol method. The methods using planar dosimetry resulted in larger variations, as expected, while giving 4 cycles to all patients resulted in the largest inter-individual differences in cumulative AD. Conclusions: Performing one SPECT/CT at 96 h in every treatment cycle gives sufficiently reliable dosimetric results to base individualized treatment planning on, with a reasonable demand on resources.
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| 9. |
- Sundlöv, Anna, et al.
(författare)
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Individualised Lu-177-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry
- 2017
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 44:9, s. 1480-1489
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED). Method Treatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 +/- 2 Gy (alpha/beta = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 +/- 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR). Results Fifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function. Conclusions Individualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.
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| 10. |
- Sundlöv, Anna, et al.
(författare)
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Phase II trial demonstrates the efficacy and safety of individualized, dosimetry-based Lu-177-DOTATATE treatment of NET patients
- 2022
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 49:11
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Radionuclide therapy with Lu-177-DOTATATE is well established for patients with advanced somatostatin receptor-positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized Lu-177-DOTATATE for which the number of cycles varied based on renal dosimetry. Methods Patients were eligible if they had a progressive, somatostatin receptor-positive neuroendocrine tumor with a Ki 67 labeling index <20%. They received cycles of 7.4 GBq of Lu-177-DOTATATE at 10 +/- 2-week intervals until a predefined radiation dose to the kidneys was reached. The primary endpoint was objective tumor response (RECIST v 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v. 4.0). Results Ninety-six patients who had received a median of 5 cycles (range 1-9) were evaluable for efficacy. The objective tumor response was 16% partial response, 66% stable disease, and 19% progressive disease. The median PFS and OS were 29 months and 47 months, respectively, and were significantly associated with kidney dose, performance status, and Ki 67 levels but not with tumor origin. The overall toxicity was mild, and the most common events were grade 1-2 anemia, thrombocytopenia, fatigue, nausea, and diarrhea. Grade 3-4 toxicity occurred in <10% of patients and was mostly hematological, with no grade 3-4 renal toxicity. Conclusion Individualized treatment with Lu-177-DOTATATE based on renal dosimetry is clearly feasible with low toxicity and promising efficacy, showing the potential to further improve outcome beyond the standard approach, and should be further assessed in randomized trials.
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