| 1. |
- Antonsson, Malin, 1986, et al.
(författare)
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Post-surgical effects on language in patients with presumed low-grade glioma
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 137:5, s. 469-480
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Low-grade glioma (LGG) is a slow-growing brain tumour often situated in or near areas involved in language and/or cognitive functions. Thus, language impairments due to tumour growth or surgical resection are obvious risks. We aimed to investigate language outcome following surgery in patients with presumed LGG, using a comprehensive and sensitive language assessment. Materials and methods: Thirty-two consecutive patients with presumed LGG were assessed preoperative, early post-operative, and 3 months post-operative using sensitive tests including lexical retrieval, language comprehension and high-level language. The patients’ preoperative language ability was compared with a reference group, but also with performance at post-operative controls. Further, the association between tumour location and language performance pre-and post-operatively was explored. Results: Before surgery, the patients with presumed LGG performed worse on tests of lexical retrieval when compared to a reference group (BNT: LGG-group median 52, Reference-group median 54, P = .002; Animals: LGG-group mean 21.0, Reference-group mean 25, P = 001; Verbs: LGG-group mean 17.3, Reference-group mean 21.4, P = .001). At early post-operative assessment, we observed a decline in all language tests, whereas at 3 months there was only a decline on a single test of lexical retrieval (Animals: preoperative. median 20, post-op median 14, P = .001). The highest proportion of language impairment was found in the group with a tumour in language-eloquent areas at all time-points. Conclusions: Although many patients with a tumour in the left hemisphere deteriorated in their language function directly after surgery, their prognosis for recovery was good.
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| 2. |
- 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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| 3. |
- Carstam, Louise, et al.
(författare)
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Neurosurgical patterns of care for diffuse low-grade gliomas in Sweden between 2005 and 2015
- 2018
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 6:2, s. 124-133
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the last decade, increasing evidence has evolved for early and maximal safe resection of diffuse low-grade gliomas (LGGs) regarding survival. However, changes in clinical practice are known to occur slowly and we do not know if the scientific evidence has yet resulted in changes in neurosurgical patterns of care.Methods: The Swedish Brain Tumor Registry was used to identify all patients with a first-time histopathological diagnosis of LGG between 2005 and 2015. For analysis of surgical treatment patterns, we subdivided assessed time periods into 2005-2008, 2009-2012, and 2013-2015. Population-based data on patient and disease characteristics, surgical management, and outcomes were extracted.Results: A total of 548 patients with diffuse World Health Organization grade II gliomas were identified: 142 diagnosed during 2005-2008, 244 during 2009-2012, and 162 during 2013-2015. Resection as opposed to biopsy was performed in 64.3% during 2005-2008, 74.2% during 2009-2012, and 74.1% during 2013-2015 (P = .08). There was no difference among the 3 periods regarding overall survival (P = .11). However, post hoc analysis of data from the 4 (out of 6) centers that covered all 3 time periods demonstrated a resection rate of 64.3% during 2005-2008, 77.4% during 2009-2012, and 75.4% during 2013-2015 (P = .02) and longer survival of patients diagnosed 2009 and onward (P = .04).Conclusion: In this nationwide, population-based study we observed a shift over time in favor of LGG resection. Further, a positive correlation between the more active surgical strategy and longer survival is shown, although no causality can be claimed because of possible confounding factors.
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| 4. |
- Carstam, Louise
(författare)
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On the Surgical Management of Diffuse Low-Grade Gliomas in Adults
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diffuse low-grade gliomas (dLGG) are rare, slow-growing, yet difficult-to-treat brain tumors that typically affect young to middle-aged adults. The aim of the thesis has been to identify factors affecting management and outcome in terms of symptoms and primarily survival for patients with dLGG. Methods used have been uni- and multivariable analyses in institutional, national, and international dLGG cohorts. In study I, the potential effect of socio-economic factors of the patient on the surgical management was evaluated, showing that poor socio-economy was associated with longer waiting times to surgery. Study II assessed prognostic factors in molecularly defined dLGG patients with respect to the two major subtypes of these tumors, astrocytomas and oligodendrogliomas, demonstrating different results for the different tumor types. These findings underscore the importance of not treating these tumor types as a single entity. In study III epileptic seizures in dLGG before and after surgery was assessed in molecularly defined cohorts, showing what factors affect seizure outcome. In study IV, a multi-institutional long-term study of molecularly defined oligodendrogliomas, the median overall survival time (17.8 years) was longer than in earlier non-molecularly classified cohorts. In this study, small tumor size, young age and good patient pre-operative functional level were independent predictors for prolonged survival. Conclusion and implications: Adequate prognostication is important in the often long surviving dLGG patients and may guide treatment decisions, but prognostic factors must be obtained through subtype specific analyses.
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| 5. |
- Carstam, Louise, et al.
(författare)
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Seizures in patients with IDH-mutated lower grade gliomas.
- 2022
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Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 160, s. 403-411
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with Lower Grade Gliomas (LGG) present with epileptic seizures. Since the advent of molecular diagnostics, more homogenous sub-entities have emerged, including the isocitrate dehydrogenase-mutated (IDH-mutated) astrocytomasand 1p19q-codeleted oligodendrogliomas. We aimed to describe the occurrence of seizures in patients with molecularly defined LGG pre- and postoperatively and to analyze factors affecting seizure status postoperatively.A population-based cohort of 130 adult patients with IDH-mutated WHO grade 2 or 3 astrocytomas and oligodendrogliomas was assessed pertaining to seizure burden before and after surgery.Fifty-four (79.4%) patients with astrocytoma and 45 (72.6%) patients with oligodendroglioma had a history of seizures before surgery. At 12months postoperatively, 51/67 (76.1%) patients with astrocytoma and 47/62 (75.8%) patients with oligodendrogliomas were seizure free. In a multivariable logistic regression analysis, lower extent of resection (EOR) (OR 0.98; 95% CI 0.97-1.00, p=0.01) and insular tumor location (OR 5.02; 95% CI 1.01-24.87, p=0.048) were associated with presence of seizures within 1 year postoperatively in the entire LGG cohort. In sub-entities, EOR was in a similar manner associated with seizures postoperatively in astrocytomas (OR 0.98; 95% CI 0.96-0.99, p<0.01) but not in oligodendrogliomas (p=0.34).Our results are well in line with data published for non-molecularly defined LGG with a large proportion of patients being seizure free at 1 year postoperative. Better seizure outcome was observed with increased EOR in astrocytomas, but this association was absent in oligodendrogliomas.
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| 6. |
- Carstam, Louise, et al.
(författare)
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Socioeconomic factors affect treatment delivery for patients with low grade glioma : a Swedish population-based study
- 2020
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 146:2, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG).METHODS: In this nationwide registry-based study, patients who had undergone surgery for LGG during 2005-2015 were identified (n = 547) through the Swedish Brain Tumor Registry. We linked data to multiple national registries with individual level data on income, education and comorbidity and analyzed the association of disease characteristics, surgical management and outcome, with levels of income, education and sex.RESULTS: Patients with either low income, low education or female gender showed worse pre-operative performance status. Patients with low income or education also had more comorbidities and those with low education endured longer waiting times for surgery. Median time from radiological imaging to surgery was 51 days (Q1-3 27-191) for patients with low education, compared to 32 days (Q1-3 20-80) for patients with high education (p = 0.006). Differences in waiting time over educational levels remained significant after stratification for age, comorbidity, preoperative performance status, and tumor size. Overall survival was better for patients with high income or high education, but income- and education-related survival differences were not significant after adjustment for age and comorbidity. The type of surgical procedure or complications did not differ over socioeconomic groups or sex.CONCLUSION: The neurosurgical care for LGG in Sweden, a society with universal healthcare, displays differences that can be related to socioeconomic factors.
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| 7. |
- Carstam, Louise, et al.
(författare)
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WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas.
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and Methods: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.Results: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).Conclusion: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.
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| 8. |
- Corell, Alba, et al.
(författare)
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Age and surgical outcome of low-grade glioma in Sweden.
- 2018
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 138:4, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade gliomas (LGG) are slow-growing primary brain tumors that typically affect young adults. Advanced age is widely recognized as a poor prognostic factor in LGG. The impact of age on postoperative outcome in this patient group has not been systemically studied.We performed a nationwide register-based study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with a supratentorial LGG (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) during 2005-2015. Patient- and tumor-related characteristics, postoperative complications, and survival were compared between three different age groups (18-39years, 40-59years, and ≥60years).We identified 548 patients; 204 patients (37.2%) aged 18-39years, 227 patients (41.4%) aged 40-59years, and 117 patients (21.4%) ≥60years of age. Unfavorable preoperative prognostic factors (eg, functional status and neurological deficit) were more common with increased age (P<.001). In addition, overall survival was significantly impaired in those 60years and above (P<.001). We observed a clear dose-response for age with separation of survival curves at 50years. Biopsy was more common in patients ≥60years (P<.001). Subgroup analysis of patients with resection revealed a higher amount of postoperative neurological deficits in older patients (P=.029).In general, older patients with LGG have several unfavorable prognostic factors compared with younger patients but seem to tolerate surgery in a comparable fashion. However, more neurological deficits were observed following resections in elderly. Our data further support a cutoff at 50years rather than 40years for selection of high-risk patients.
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| 9. |
- Corell, Alba, et al.
(författare)
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The clinical significance of the T2-FLAIR mismatch sign in grade II and III gliomas: a population-based study.
- 2020
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- The T2-FLAIR mismatch sign is an imaging finding highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted (non-codel) gliomas (astrocytomas). In previous studies, it has shown excellent specificity but limited sensitivity for IDH-mut astrocytomas. Whether the mismatch sign is a marker of a clinically relevant subtype of IDH-mut astrocytomas is unknown.We included histopathologically verified supratentorial lower-grade gliomas (LGG) WHO grade II-III retrospectively during the period 2010-2016. In the period 2017-2018, patients with suspected LGG radiologically were prospectively included, and in this cohort other diagnoses than glioma could occur. Clinical, radiological and molecular data were collected. For clinical evaluation we included all patients with IDH-mut astrocytomas. In the 2010-2016 cohort DNA methylation analysis with Infinium MethylationEPIC BeadChip (Illumina) was performed for patients withan IDH-mut astrocytomawith available tissue. We aimed to examine the association of the T2-FLAIRmismatch sign with clinical factors and outcomes. Additionally, we evaluated the diagnostic reliability of the mismatch sign and its relation to methylation profiles.Out of 215 patients with LGG, 135 had known IDH-mutation and 1p19q codeletion status. Fifty patients hadan IDH-mut astrocytoma and 12 of these (24.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut detection were 26.4 and 97.6%, respectively. There were no differences between patients withan IDH-mut astrocytoma with or without mismatch sign when grouped according to T2-FLAIR mismatch sign with respect to baseline characteristics, clinical outcomes and methylation profiles. The overall interrater agreement between neuroradiologist and clinical neurosurgeons for the T2-FLAIR mismatch sign was significant when all 215 MRI examination assessed (κ=0.77, p<0.001, N=215).The T2-FLAIR mismatch sign in patients withan IDH-mut astrocytoma is not associated with clinical presentation or outcome. It seems unlikely that the IDH-mut astrocytomas with mismatch sign represent a specific subentity. Finally, we have validated that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.
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| 10. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 11. |
- Fytagoridis, Anders, et al.
(författare)
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Funktionell neurokirurgi möjlig hjälp vid svåra neurogena tillstånd
- 2023
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Ingår i: Läkartidningen. - : Sveriges Läkarforbund. - 0023-7205 .- 1652-7518. ; 120
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Forskningsöversikt (refereegranskat)abstract
- Funktionell neurokirurgi är ett samlingsnamn för en bred arsenal av neurokirurgiska metoder för att lindra besvär vid olika neurogena tillstånd. Syftet är genomgående att förbättra livskvalitet, och verksamheterna präglas av ett uttalat multidisciplinärt och tvärprofessionellt samarbete. Detta underlättar en god patientselektion, vilket är helt avgörande för att uppnå ett lyckat resultat. Med rätt urval och uppföljning erbjuder dessa ingrepp säker och effektiv lindring eller till och med bot för notoriskt svårbehandlade och ofta starkt funktionsnedsättande tillstånd.
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| 12. |
- Jakola, Asgeir Store, et al.
(författare)
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Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT) : Study protocol for a randomized controlled trial
- 2018
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Ingår i: F1000 Research. - : F1000Research. - 2046-1402. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O 6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment.Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety.Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues.Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.
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| 13. |
- Michaëlsson, Isak, et al.
(författare)
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Circulating Brain Injury Biomarkers: A Novel Method for Quantification of the Impact on the Brain After Tumor Surgery.
- 2023
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 93:4, s. 847-856
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Tidskriftsartikel (refereegranskat)abstract
- Clinical methods to quantify brain injury related to neurosurgery are scarce. Circulating brain injury biomarkers have recently gained increased interest as new ultrasensitive measurement techniques have enabled quantification of brain injury through blood sampling.To establish the time profile of the increase in the circulating brain injury biomarkers glial fibrillary acidic protein (GFAP), tau, and neurofilament light (NfL) after glioma surgery and to explore possible relationships between these biomarkers and outcome regarding volume of ischemic injury identified with postoperative MRI and new neurological deficits.In this prospective study, 34 adult patients scheduled for glioma surgery were included. Plasma concentrations of brain injury biomarkers were measured the day before surgery, immediately after surgery, and on postoperative days 1, 3, 5, and 10.Circulating brain injury biomarkers displayed a postoperative increase in the levels of GFAP ( P < .001), tau ( P < .001), and NfL ( P < .001) on Day 1 and a later, even higher, peak of NFL at Day 10 ( P = .028). We found a correlation between the increased levels of GFAP, tau, and NfL on Day 1 after surgery and the volume of ischemic brain tissue on postoperative MRI. Patients with new neurological deficits after surgery had higher levels of GFAP and NfL on Day 1 compared with those without new neurological deficits.Measuring circulating brain injury biomarkers could be a useful method for quantification of the impact on the brain after tumor surgery or neurosurgery in general.
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| 14. |
- Ny, Lars, 1967, et al.
(författare)
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Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models
- 2020
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:2, s. 266-273
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. Patients and methods: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. Results: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. Conclusions: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.
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| 15. |
- 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. ; 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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| 16. |
- 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
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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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| 17. |
- Svenjeby, Caroline, et al.
(författare)
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Changes in clinical management of diffuse IDH-mutated lower-grade gliomas: patterns of care in a 15-year period
- 2022
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 160:3, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Background: Isocitrate dehydrogenase (IDH) mutated diffuse lower-grade gliomas (dLGG) are infiltrating brain tumors and increasing evidence is in favor of early multimodal treatment. In a Scandinavian population-based setting, we wanted to study treatment patterns over the last 15 years, focusing on the short-term postoperative course to better understand the potential negative consequences of treatment. Methods: Patients ≥ 18 years with primary IDH-mutated dLGG grade 2 and 3, operated between January 2007–June 2021 were identified. Patients were divided into subgroups (2007–2011, 2012–2016, and 2017–2021) and comparisons regarding tumor- and disease characteristics, treatment, and postoperative outcome were performed. Results: We identified 202 patients (n = 61, 2007–2011; n = 72, 2012–2016; n = 69, 2017–2021), where of 193 underwent resection without change in proportion of resections over time. More patients underwent complete resections in recent times (6.1%; 15.7%; 26.1%, respectively; p = 0.016). Forty-two patients had any neurological deficit postoperatively (14.8%; 23.6%; 23.2%; p = 0.379), mostly minor and transient. Differences in oncological therapy were seen between the investigated subgroups. Early radiotherapy alone (32.8%; 7%; 2.9%; p < 0.001), concomitant chemoradiotherapy (23%; 37.5%; 17.4%; p = 0.022), sequential chemoradiotherapy (0%; 18%; 49.3%; p < 0.001), and no adjuvant treatment (42.6%; 23.6%; 18.8%; p = 0.009) shifted during the studied period. Increasingly more patients received proton radiotherapy compared to photon radiotherapy during the later time periods (p < 0.001). Conclusion: Complete resections were performed more often in later time periods without an apparent increase in surgical morbidity. Early adjuvant oncological treatment shifted towards providing chemotherapy and combined chemoradiotherapy more often in later time periods. Protons replaced photons as the radiation modality of choice.
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| 18. |
- Vecchio, Tomás Gomez, et al.
(författare)
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Global health status and fatigue score in isocitrate dehydrogenase-mutant diffuse glioma grades 2 and 3: A longitudinal population-based study from surgery to 12-month follow-up
- 2024
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Ingår i: NEURO-ONCOLOGY PRACTICE. - 2054-2577 .- 2054-2585.
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Tidskriftsartikel (refereegranskat)abstract
- Background. At the group level, health-related quality of life (HRQoL) in patients with IDH-mutant diffuse glioma grades 2 and 3 seems to remain stable over time. However, clinical experience indicates that there are patients with unfavorable outcomes on key HRQoL subdomains. The aim of this longitudinal population-based study, following patients over a period of 12 months from surgery, was to describe individual-level data on global health status and fatigue score and explore possible predictors of deterioration. Methods. All patients undergoing surgery for presumed glioma grades 2 or 3 at the Sahlgrenska University Hospital during 2017-2022, were screened for the study. Patients were invited to complete the European Organization of Research and Treatment of Cancer core questionnaires and brain module at baseline, 3 and 12 months postoperatively. Data is reported with respect to minimal clinical important difference (MCID). Results. We included 51 patients with IDH-mutant diffuse glioma grades 2 or 3. There was no difference in group-level data of either global health status or fatigue score from baseline to the 12-month follow-up (P-value > .05). Unfavorable individual changes (beyond MCID) in global health status and fatigue score were observed in 12 and in 17 patients, respectively (23.5% and 33.3%). A lower proportion of proton radiotherapy was found in patients with unfavorable changes in fatigue (10/15, 66.7%) compared to all other patients undergoing radiotherapy (22/23, 95.7%, P-value .03). Conclusions. Deterioration beyond MCID was seen in approximately one-third of patients. Changes in global health status could not be predicted, but changes in fatigue may be influenced by tumor-targeted and symptomatic treatment.
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| 19. |
- 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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