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| 2. |
- Heggebo, L. C., et al.
(författare)
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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
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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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).
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| 4. |
- Saeter, G, et al.
(författare)
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Prognostic factors in bone sarcomas
- 1997
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Ingår i: Acta Orthopaedica Scandinavica. Supplementum. - 0300-8827. ; 68:273, s. 156-160
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Tidskriftsartikel (refereegranskat)abstract
- Based on a literature review and the SSG experience, the most important prognostic factors in high-grade osteosarcoma appear to be the presence of detectable metastases at diagnosis, tumour volume, old age, sex, histologic response, and possibly tumoral P-glycoprotein expression. However, for an adolescent patient with non-metastatic extremity disease, there is no consensus regarding prognostic factors at initial presentation, and currently there is thus no established method for dividing them into high- and low risk groups for the purpose of treatment differentiation. It should also be remembered that available prognostic factors have been identified only in a retrospective manner, following aggressive treatment of all patients. Thus patients in "favourable" prognostic groups may simply be patients who have had a good effect from aggressive treatment, and how they would have done with reduced treatment remains to be shown. Obviously the best method for prognostication would be the direct demonstration of micrometastatic disease in the lungs or in peripheral blood. In the relatively near future, this may become possible with immunoscintigrapy or immunohistochemistry utilizing monoclonal antibodies [29-31]. In Ewing's sarcoma, the most powerful factors indicating poor prognosis are metastases at diagnosis, poor histologic response, large tumour size and possibly pelvic localisation. There appears to be a somewhat better international consensus regarding prognostic factors in Ewing's sarcoma than in osteosarcoma. Although several studies have implemented intensified treatment for poor prognostic groups [8, 32], the role (if any) of high-dose treatment with stem cell rescue remains to be proven. The same factors are prognostic both for the development of metastases and local recurrence, but in addition, surgical treatment as opposed to radiotherapy appears to reduce local failure rate [12, 17, 33, 34]. As in osteosarcoma, the near future offers promise regarding the detection and quantification of micrometastatses and minimal residual disease, by means of PCR techniques recognizing specific genetic changes in the Ewing family of tumors [35].
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| 5. |
- Werlenius, Katja, et al.
(författare)
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Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma: A Randomized Clinical Trial.
- 2023
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 6:3
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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.
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| 7. |
- Bartek, J, et al.
(författare)
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Surgery for chronic subdural hematoma in nonagenarians: A Scandinavian population-based multicenter study.
- 2017
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 136:5, s. 516-520
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Tidskriftsartikel (refereegranskat)abstract
- Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90years or older. The aim of this study was to investigate outcome after cSDH surgery in nonagenarians (≥90 y/o group) compared to younger adult patients (<90 y/o group).In a Scandinavian population-based cohort we conducted a retrospective review of 1,254 patients undergoing primary burr-hole procedures for cSDH between January 1, 2005 and December 31, 2010 at three neurosurgical centers. In a comparative analysis, the primary end-point was difference in hematoma recurrence rates between the ≥90 y/o and <90 y/o groups. The secondary end-points were differences in perioperative morbidity and mortality between groups.75 patients were 90years or older. There was no significant difference in recurrences resulting in reoperation between the age groups (10.7% vs 13.6%, P=.47). There was also no significant difference in overall complication rate (4.1% vs 8.1%, P=.21) or severe complications (1.4% vs 2.0%, P=.68). There were three (4.0%) perioperative deaths within 30days in the ≥90 y/o group and 40 (3.4%) in the <90 y/o group (P=.78).Patients 90years or older had similar rates of recurrence, perioperative morbidity and perioperative mortality as compared to younger patients. Age alone should not be a contraindication for surgery in patients with cSDH.
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| 8. |
- Bouget, D., et al.
(författare)
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Preoperative Brain Tumor Imaging: Models and Software for Segmentation and Standardized Reporting
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- For patients suffering from brain tumor, prognosis estimation and treatment decisions are made by a multidisciplinary team based on a set of preoperative MR scans. Currently, the lack of standardized and automatic methods for tumor detection and generation of clinical reports, incorporating a wide range of tumor characteristics, represents a major hurdle. In this study, we investigate the most occurring brain tumor types: glioblastomas, lower grade gliomas, meningiomas, and metastases, through four cohorts of up to 4,000 patients. Tumor segmentation models were trained using the AGU-Net architecture with different preprocessing steps and protocols. Segmentation performances were assessed in-depth using a wide-range of voxel and patient-wise metrics covering volume, distance, and probabilistic aspects. Finally, two software solutions have been developed, enabling an easy use of the trained models and standardized generation of clinical reports: Raidionics and Raidionics-Slicer. Segmentation performances were quite homogeneous across the four different brain tumor types, with an average true positive Dice ranging between 80 and 90%, patient-wise recall between 88 and 98%, and patient-wise precision around 95%. In conjunction to Dice, the identified most relevant other metrics were the relative absolute volume difference, the variation of information, and the Hausdorff, Mahalanobis, and object average symmetric surface distances. With our Raidionics software, running on a desktop computer with CPU support, tumor segmentation can be performed in 16-54 s depending on the dimensions of the MRI volume. For the generation of a standardized clinical report, including the tumor segmentation and features computation, 5-15 min are necessary. All trained models have been made open-access together with the source code for both software solutions and validation metrics computation. In the future, a method to convert results from a set of metrics into a final single score would be highly desirable for easier ranking across trained models. In addition, an automatic classification of the brain tumor type would be necessary to replace manual user input. Finally, the inclusion of post-operative segmentation in both software solutions will be key for generating complete post-operative standardized clinical reports.
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| 9. |
- Carstam, Louise, et al.
(författare)
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Long-term follow up of patients with WHO grade 2 oligodendroglioma
- 2023
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Ingår i: Journal of Neuro-Oncology. - 0167-594X .- 1573-7373. ; 165, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival.Methods All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival.Results 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6).Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival.Conclusion Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.
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| 10. |
- Cornelissen, Johannes H C, et al.
(författare)
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Global negative vegetation feedback to climate warming responses of leaf litter decomposition rates in cold biomes
- 2007
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 10:7, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Whether climate change will turn cold biomes from large long-term carbon sinks into sources is hotly debated because of the great potential for ecosystem-mediated feedbacks to global climate. Critical are the direction, magnitude and generality of climate responses of plant litter decomposition. Here, we present the first quantitative analysis of the major climate-change-related drivers of litter decomposition rates in cold northern biomes worldwide.Leaf litters collected from the predominant species in 33 global change manipulation experiments in circum-arctic-alpine ecosystems were incubated simultaneously in two contrasting arctic life zones. We demonstrate that longer-term, large-scale changes to leaf litter decomposition will be driven primarily by both direct warming effects and concomitant shifts in plant growth form composition, with a much smaller role for changes in litter quality within species. Specifically, the ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across cold biomes would constitute a negative feedback to global warming. Depending on the strength of other (previously reported) positive feedbacks of shrub expansion on soil carbon turnover, this may partly counteract direct warming enhancement of litter decomposition.
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