| 1. |
- Malmström, Annika, et al.
(författare)
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Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
- 2012
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 13:9, s. 916-926
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Tidskriftsartikel (refereegranskat)abstract
- Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.
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| 2. |
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| 3. |
- Weller, Michael, et al.
(författare)
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EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:9, s. E395-E403
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Forskningsöversikt (refereegranskat)abstract
- This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.
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| 4. |
- Malmström, Annika, 1957-
(författare)
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Studies for Better Treatment of Patients with Glioma
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.
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| 5. |
- Rydén, Isabelle, et al.
(författare)
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Return to work following diagnosis of low-grade glioma: A nationwide matched cohort study.
- 2020
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 95:7, s. e856-e866
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Tidskriftsartikel (refereegranskat)abstract
- Return-to-work (RTW) following diagnosis of infiltrative low-grade gliomas (LGG) is unknown.Swedish patients with histopathological verified WHO grade II diffuse glioma diagnosed between 2005-2015 were included. Data were acquired from several Swedish registries. A total of 381 patients aged 18-60 were eligible. A matched control population (n=1900) was acquired. Individual data on sick leave, compensations, comorbidity and treatments assigned were assessed. Predictors were explored using multivariable logistic regression.One year before surgery/index date, 88 % of cases were working compared to 91 % of controls. The proportion of controls working remained constant, while patients had a rapid increase in sick leave approximately six months prior to surgery. After one and two years respectively, 52 % and 63 % of the patients were working. Predictors for no-RTW after one year were previous sick leave (OR 0.92, 95 % CI 0.88-0.96, p <0.001), older age (OR 0.96, 95 % CI 0.94-0.99, p=0.005) and lower functional level (OR 0.64 95% CI, 0.45-0.91 p=0.01). Patients receiving adjuvant treatment were less likely to RTW within the first year. At two years, biopsy (as opposed to resection), female sex and comorbidity were also unfavorable, while age and adjuvant treatment were no longer significant.Approximately half of the patients RTW within the first year. Lower functional status, previous sick leave, older age and adjuvant treatment were risk factors for no-RTW at one year after surgery. Female sex, comorbidity and biopsy only were also unfavorable for RTW at two years.
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| 6. |
- Rodriguez-Wallberg, Kenny A., et al.
(författare)
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Prevalence and predictors for fertility-related distress among 1010 young adults 1.5 years following cancer diagnosis - results from the population-based Fex-Can Cohort study
- 2023
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 62:12, s. 1599-1606
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer treatment during reproductive ages may negatively impact fertility and there is a need of firm knowledge about the prevalence and predictors of fertility-related distress. The aim was to examine fertility-related distress in a population-based sample of young women and men recently treated for cancer and to identify predictors for this outcome.Material and methods: This nationwide cohort study included 1010 individuals (694 women and 316 men), mean age 34.5 +/- 4.9 and 32.1 +/- 5.5, respectively, diagnosed with breast, cervical, ovarian, testicular cancers, brain tumors or lymphoma at ages 18-39 in Sweden. Participants completed a survey 1.5-year post-diagnosis to assess fertility-related distress (RCAC), emotional distress (HADS) and self-efficacy, as well as sociodemographic and clinical factors and fertility preservation. Logistic regression was used to examine associations between explanatory factors and high fertility-related distress (RCAC subscale mean >4).Results: Many participants (69% of women and 47% of men) had previous children and about half reported a wish for future children. High fertility-related distress was more prevalent among women (54%) than men (27%), and women were more likely than men to report distress concerning all but one RCAC dimension after adjustment for sociodemographic factors. Use of fertility preservation was unevenly distributed (15% of women and 71% of men) and was not associated with decreased fertility-related distress. In multivariable logistic regression models, a wish for future children, being single, not having previous children, symptoms of anxiety and low self-efficacy regarding one's ability to handle threats of infertility were associated with high fertility-related distress.Conclusion: This nationwide study found a high prevalence of fertility-related distress in young women and men recently treated for cancer and identified sociodemographic and psychological predictors. Fertility preservation was not found to act as a buffer against fertility-related distress, indicating the continuous need to identify strategies to alleviate fertility distress following cancer.
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| 7. |
- Rydén, Isabelle, et al.
(författare)
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Psychotropic and anti-epileptic drug use, before and after surgery, among patients with low-grade glioma: a nationwide matched cohort study
- 2021
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-grade glioma (LGG) is a relatively rare type of brain tumour. The use of antidepressant, sedative and anti-epileptic drugs can reflect the burden of the disease. While epilepsy is well-described in patients with LGG, less is known about depression and anxiety.Methods: We used nationwide registers to study the use (dispense) of antidepressants, sedatives, and anti-epileptic drugs (AEDs) before and after histopathological LGG diagnosis (WHO grade II). A total of 485 adult patients with a first-time diagnosis and a matched control cohort (n = 2412) were included. Patterns of use were analysed from one year prior to until one year following index date (date of surgery). Logistic regression analysis identified predictors for postoperative use.Results: At one year before index date, patients were dispensed AEDs 4 times more than controls, while antidepressants and sedatives were similar. Sedatives and AED peaked shortly after index date at 25 and 69%, respectively. AEDs then stabilized while sedatives decreased rapidly. For antidepressants, a delayed increase was seen after index date, stabilizing at 12%. At one year after index date, the use of antidepressants, sedatives, and AEDs among patients was 2, 3, and 26 times higher, respectively, compared to controls. Predictor for use of AEDs and sedatives at one year following index was previous use and/or a related diagnosis. Female sex and later index year were additional predictors for antidepressants.Conclusions: Use of antidepressants, sedatives and AEDs is elevated following diagnosis of LGG. Antidepressants were more commonly dispensed to female patients and in recent years.
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| 8. |
- Woltmann, Andrea, et al.
(författare)
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Systematic Pathway Enrichment Analysis of a Genome-Wide Association Study on Breast Cancer Survival Reveals an Influence of Genes Involved in Cell Adhesion and Calcium Signaling on the Patients' Clinical Outcome
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e98229-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The goal was to identify the functional categories (GO terms and KEGG pathways) that are consistently overrepresented in a statistically significant way in the list of genes generated from the single nucleotide polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01 were annotated to the genes by excluding or including a 20 kb up-and down-stream sequence of the genes and analyzed by six different tools. We identified eleven consistently enriched categories, the most significant ones relating to cell adhesion and calcium ion binding. Moreover, we investigated the similarity between our GWAS and the enrichment analyses of twelve published gene expression signatures for breast cancer prognosis. Five of them were commonly used and commercially available, five were based on different aspects of metastasis formation and two were developed from meta-analyses of published prognostic signatures. This comparison revealed similarities between our GWAS data and the general and the specific brain metastasis gene signatures as well as the Oncotype DX signature. As metastasis formation is a strong indicator of a patient's prognosis, this result reflects the survival aspect of the conducted GWAS and supports cell adhesion and calcium signaling as important pathways in cancer progression.
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| 9. |
- Bartek Jr., Jiri, et al.
(författare)
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Short-term outcome following surgery for rare brain tumor entities in adults : a Swedish nation-wide registry-based study and comparison with SEER database
- 2020
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Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 148:2, s. 281-290
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate outcomes after surgery for rare brain tumors using the Swedish Brain Tumor Registry (SBTR).Methods: This is a nationwide study of patient in the SBTR, validated in the Surveillance, Epidemiology, and End Results (SEER) registries. We included all adults diagnosed 2009-2015 with a rare brain tumor entity (n = 216), defined as ependymoma (EP, n = 64), subependymoma (SUBEP, n = 21), ganglioglioma (GGL, n = 54), pilocytic astrocytoma (PA, n = 56) and primitive neuroectodermal tumor (PNET, n = 21). We analyzed symptomatology, tumor characteristics and outcomes.Results: Mean age was 38.3 +/- 17.2 years in GGL, 36.2 +/- 16.9 in PA, 37.0 +/- 19.1 in PNET, 51.7 +/- 16.3 in EP and 49.8 +/- 14.3 in SUBEP. The most common symptom was focal deficit (39.6-71.4%), and this symptom was most common in GGL patients with 64.2% of GGL presenting with seizures. Most patients had no or little restriction in activity before surgery (Performance Status 0-1), although up to 15.0% of PNET patients had a performance status of 4. Gross total resection was achieved in most (> 50%) tumor categories. Incidence of new deficits was 11.1-34.4%. In terms of postoperative complications, 0-4.8% had a hematoma of any kind, 1.9-15.6% an infection, 0-7.8% a venous thromboembolism and 3.7-10.9% experienced a complication requiring reoperation. There were 3 deaths within 30-days of surgery, and a 1-year mortality of 0-14.3%.Conclusion: We have provided benchmarks for the current symptomatology, tumor characteristics and outcomes after surgery for rare brain tumors as collected by the SBTR and validated our results in an independent registry. These results may aid in clinical decision making and advising patients.
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| 10. |
- Bergstrom, Charlotta, et al.
(författare)
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Do young adults with cancer receive information about treatment- related impact on sex life? : Results from a population-based study
- 2023
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Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 12:8, s. 9893-9901
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Tidskriftsartikel (refereegranskat)abstract
- Background Sexual dysfunction is common following a cancer diagnosis in young adulthood (18-39 years) and problems related to sex life are ranked among the core concerns in this age group. Yet, few studies have investigated to what extent adults younger than 40, receive information from healthcare providers about the potential impact of cancer and its treatment on their sex life.Methods A population-based cross-sectional survey study was conducted with 1010 young adults 1.5 years after being diagnosed with cancer (response rate 67%). Patients with breast, cervical, ovarian and testicular cancer, lymphoma, and brain tumors were identified in national quality registries. Sociodemographic and clinical factors associated with receiving information were examined using multivariable binary logistic regression.Results Men to a higher extent than women reported having received information about potential cancer-related impact on their sex life (68% vs. 54%, p < 0.001). Receipt of information varied across diagnoses; in separate regression models, using lymphoma as reference, both women and men with brain tumors were less likely to receive information (women: OR 0.10, CI = 0.03-0.30; men: OR 0.37, CI = 0.16-0.85). More intensive treatment was associated with higher odds of receiving information in both women (OR 1.89; CI = 1.28-2.79) and men (OR 2.08; CI = 1.09-3.94). None of the sociodemographic factors were associated with receipt of information.Conclusions To improve sexual health communication to young adults with cancer, we recommend diagnosis-specific routines that clarify when in the disease trajectory to discuss these issues with patients and what to address in these conversations.
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