| 1. |
- Heggebo, L. C., et al.
(författare)
-
Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
-
Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
|
|
| 2. |
- Bernson, Elin, 1987, et al.
(författare)
-
Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia
- 2017
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:12, s. 2552-2559
-
Tidskriftsartikel (refereegranskat)abstract
- Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), that is, a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells. Little is known regarding the impact of such genotypes in untransplanted acute myeloid leukemia (AML). For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996). We observed that presence of unlicensed NK cells impacted favorably on clinical outcome, in particular among patients harboring functional NK cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Genotype analyses suggested that the clinical benefit of high NCR expression was restricted to patients with a missing ligand genotype and/or a KIR B/x genotype. These data imply that functional NK cells are significant anti-leukemic effector cells in patients with KIR/HLA genotypes that favor NK cell autoreactivity.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Werlenius, Katja, et al.
(författare)
-
Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma: A Randomized Clinical Trial.
- 2023
-
Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 6:3
-
Tidskriftsartikel (refereegranskat)abstract
- Disulfiram has demonstrated broad antitumoral effect in several preclinical studies. One of the proposed indications is for the treatment of glioblastoma.To evaluate the efficacy and safety of disulfiram and copper as add-on to alkylating chemotherapy in patients with recurrent glioblastoma.This was a multicenter, open-label, randomized phase II/III clinical trial with parallel group design. Patients were recruited at 7 study sites in Sweden and 2 sites in Norway between January 2017 and November 2020. Eligible patients were 18 years or older, had a first recurrence of glioblastoma, and indication for treatment with alkylating chemotherapy. Patients were followed up until death or a maximum of 24 months. The date of final follow-up was January 15, 2021. Data analysis was performed from February to September 2022.Patients were randomized 1:1 to receive either standard-of-care (SOC) alkylating chemotherapy alone, or SOC with the addition of disulfiram (400 mg daily) and copper (2.5 mg daily).The primary end point was survival at 6 months. Secondary end points included overall survival, progression-free survival, adverse events, and patient-reported quality of life.Among the 88 patients randomized to either SOC (n=45) or SOC plus disulfiram and copper (n=43), 63 (72%) were male; the mean (SD) age was 55.4 (11.5) years. There was no significant difference between the study groups (SOC vs SOC plus disulfiram and copper) in 6 months survival (62% [26 of 42] vs 44% [19 of 43]; P=.10). Median overall survival was 8.2 months (95% CI, 5.4-10.2 months) with SOC and 5.5 months (95% CI, 3.9-9.3 months) with SOC plus disulfiram and copper, and median progression-free survival was 2.6 months (95% CI, 2.4-4.6 months) vs 2.3 months (95% CI, 1.7-2.6 months), respectively. More patients in the SOC plus disulfiram and copper group had adverse events grade 3 or higher (34% [14 of 41] vs 11% [5 of 44]; P=.02) and serious adverse events (41% [17 of 41] vs 16% [7 of 44]; P=.02), and 10 patients (24%) discontinued disulfiram treatment because of adverse effects.This randomized clinical trial found that among patients with recurrent glioblastoma, the addition of disulfiram and copper to chemotherapy, compared with chemotherapy alone, resulted in significantly increased toxic effects, but no significant difference in survival. These findings suggest that disulfiram and copper is without benefit in patients with recurrent glioblastoma.ClinicalTrials.gov Identifier: NCT02678975; EUDRACT Identifier: 2016-000167-16.
|
|
