| 1. |
- Andersson, Martin, et al.
(författare)
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IDAC-ALPHA: AN ALPHA DOSIMETRY SOFTWARE FOR NORMAL ORGANS AND TISSUES
- 2021
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 195:3-4, s. 327-333
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Tidskriftsartikel (refereegranskat)abstract
- Radiopharmaceuticals have been used for the treatment of various forms of cancer since the 1940s. In recent years, the advantages of alpha emitting radionuclides have emerged as a favourable treatment option. However, most alpha emitting radionuclides have long decay chains with long-lived daughter radionuclides. This leads to uncertainties in the dosimetry for normal organs and tissues, when established dosimetry models are employed. The aim of this project is to assign each progeny its own biokinetic behaviour. The novel dosimetry model was applied to Ra-223-dichloride, frequently used for the treatment of patients with metastatic bone disease from castration-resistant prostate cancer. In this dosimetry model, individual biokinetics for each daughter radionuclide was included. This resulted in a decrease in absorbed dose to bone surfaces and red marrow and increased absorbed dose to liver and kidney, when compared with dosimetry models assuming that the daughter nuclides follow the biokinetics of the parent radionuclide.
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| 2. |
- Carlsson, Göran, 1951, et al.
(författare)
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A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer
- 2022
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: 5-fluorouracil (5-FU) combined with a folate remains an essential treatment component for metastatic colorectal cancer (mCRC). Leucovorin is the folate most often used, but requires intracellular conversion to a reduced folate, and has high pharmacokinetic variability and limited bioavailability in patients with low folate pathway gene expression. Arfolitixorin is an immediately active form of folate, [6R]-5,10-methylenetetrahydrofolate ([6R]-MTHF), and may improve outcomes.Patients and methods: This open-label, multicenter, phase I/II study in patients with mCRC (NCT02244632) assessed the tolerability and efficacy of first-or second-line arfolitixorin (30, 60, 120, or 240 mg/m2 intravenous) with 5-FU alone, or in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan, every 14 days. Safety, efficacy, and pharmacokinetics were assessed before and after four cycles (8 weeks) of treatment.Results: In 105 treated patients, investigators reported 583 adverse events (AEs) in 86 patients (81.9%), and 256 AEs (43.9%) were potentially related to arfolitixorin and 5-FU. Dose adjustments were required in 16 patients (15.2%). At 8 weeks, 9 out of 57 patients assessed for efficacy achieved an objective response (15.8%), and all 9 achieved a partial response. Six of these nine patients had received arfolitixorin as a first-line treatment. A further 33 patients (57.9%) achieved stable disease. Pharmacokinetics were assessed in 35 patients. The average tmax was 10 min, and area under the plasma concentrationetime curve from time 0 to 1 h increased linearly between 30 and 240 mg/m2. No accumulation was observed for [6R]-MTHF following repeated administration, and there were no major pharmacokinetic differences between cycle 1 and cycle 4 at any dose.Conclusions: Arfolitixorin is a well-tolerated moderator of 5-FU activity. It is suitable for further investigation in mCRC and has the potential to improve treatment outcomes in patients with low folate pathway gene expression. Arfolitixorin can easily be incorporated into current standard of care, requiring minimal changes to chemotherapy regimens.
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| 3. |
- Tsoli, M., et al.
(författare)
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The efficacy of above-label doses of long-acting somatostatin analogues for the management of patients with gastroenteropancreatic tumors
- 2021
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Ingår i: Journal of neuroendocrinology (Print). - : European Neuroendocrine Association. - 0953-8194 .- 1365-2826. ; 33:S1, s. 146-146
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Above-label doses of long-acting somatostatin analogues (SSAs) are increasingly used for the control of secretory syndrome or as anti-proliferative treatment in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).Aim(s): The aim of this study was to evaluate the anti-proliferative effect of increased dose of SSAs in patients with GEP-NETs.Materials and methods: We collected retrospectively the data of patients with GEP-NETs that received SSAs every 3 or 2 weeks, after disease progression on standard 4-weekly doses. We analysed clinical, biochemical and radiographic response data and identified factors that may influence the outcome.Results: We analysed the data of 16 patients. 7 patients suffered from pancreatic NET (pNET) and 9 from small intestinal NET (si-NET). Indications for dose increase were radiographic progression (62,5%), increasing biomarkers (12,5%) or inadequate syndrome control (25%). Among patients with radiographic progression before the escalation of SSA dose, 3 had disease stabilization and 7 eventually progressed radiographically. Median PFSwas 36 months. PNETs were associated with a significantly lower PFS compared to si-NETs (P= 0.041). Patients with NET with a Ki-67 labelling index≤5 displayed a significantly higher PFS (P= 0.047). No significant difference was observed between patients who received above-label SSAs due to clinical/biochemical or radiographic response (P=0.1). In univariate analysis, the Ki-67≤5 was marginally associated with significantly longer PFS (P=0.05).Conclusion: The administration of above-label doses of SSAs maybe a valuable option in patients who progress on the standard 4-weekly regimen, especially in patients with si-NETs or a Ki-67 labelling index≤5.
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| 4. |
- Wedin, M., 1977-, et al.
(författare)
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Virchow's node metastasis from small intestinal neuroendocrine neoplasms : A bi-center cohort study
- 2022
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Ingår i: Journal of neuroendocrinology (Print). - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 34:Suppl. 1, s. 88-88
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Small Intestinal Neuroendocrine Neoplasms (SI-NENs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s node metastasis (VM).Aim(s): Data on prevalence, prognostic significance and clinical course of disease for SI-NEN patients with VM is limited.Materials and methods: In this retrospective analysis of 231 SI-NEN patients treated at two tertiary referal centers we found nine patients with VM. We used a control group of 18 age-and sex-matched SI-NEN patients from the same cohort with stage IV disease, but no extrahepatic metastases.Results: VM prevalence was 3.9% (9/231; 5 females, median age at VM diagnosis 65 years). Two patients had G1, 5 G2 tumours and 2 of unspecified grade. Four patients presented with synchronous VM, whereas 3 developed metachronous VM after a median of 24 months (range: 4.8–117.6 months). Hepatic metastases were present in 7 patients, extrahepatic metastases (EM) in 8 (6 para-aortic distant lymph node metastases, 1 lung and 1 pancreatic metastasis) and peritoneal carcinomatosis in 2 patients. There was no difference in best-recorded responses to 1st line treatment according to RECIST 1.1 as well as progression-free (PFS) and overall survival rates (PFS) between patients with VM and those in the control group (Chi-square p=0.516; PFS: 71.7 vs. 106.9 months [95%CI 38.1-175.8]; log-rank p=0.855; OS: 138.6 [95%CI 17.2–260] vs. 109.9 [95%CI 91.7–128] months; log-rank p=0.533).Conclusion: VM is relatively rare in patients with SI-NENs. It is more often encountered in patients withG2 tumors and EM, mainly to distant para-aortic lymph nodes. Its presence does not seem to impact patients’ survival outcomes and treatment responses, when compared to age-and sex-matched patients with stage IV disease.
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