| 1. |
- Ambring, Anneli, 1964, et al.
(författare)
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Treatment with sorafenib and sunitinib in renal cell cancer: a Swedish register-based study.
- 2013
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Ingår i: Medical oncology (Northwood, London, England). - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- Sorafenib and sunitinib are used for renal cell carcinoma (RCC). The objective was to study the treatment duration and time to death in Swedish RCC patients on sorafenib or sunitinib as first-line or monotherapy or as sequential therapy. Patients with an RCC diagnosis were identified in the Swedish Cancer Register. Information on treatment with sorafenib and sunitinib was collected from the Swedish Prescribed Drug Register, and time of death from the Cause of Death Register. Outcome measures were duration of treatment and time to death on sorafenib or sunitinib as first-line or monotherapy and sequential therapy (sorafenib-sunitinib versus sunitinib-sorafenib). Poisson regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). No difference was observed for sorafenib (n=123 patients) versus sunitinib (n=261 patients) in treatment duration (HR 1.00; CI 0.80-1.24) or risk for death (HR 1.30; CI 0.91-1.85) when used as first-line or monotherapy. The same applied for sequential therapy with sorafenib-sunitinib (n=43 patients) versus sunitinib-sorafenib (n=54 patients), HR 1.47 (CI 0.71-3.02) and HR 2.01 (CI 0.86-4.68), respectively. There was a difference between the two treatments in how the duration of first-line treatment influenced the duration of second-line treatment and time to death, in favor of starting with sorafenib. In conclusion, no difference was detected between sorafenib and sunitinib in the duration of treatment or time to death when used as first-line or monotherapy. The impact of the duration of first-line treatment differed between the two sequences, and the results indicated that sorafenib as first-line treatment is a favorable choice.
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| 2. |
- Arheden, A., et al.
(författare)
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Real-world data on PD-1 inhibitor therapy in metastatic melanoma
- 2019
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 58:7, s. 962-966
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Phase III studies of PD-1 inhibitors have demonstrated remarkable improvements in the survival of patients with metastatic melanoma (MM). If these results are generalizable to an unselected patient population treated in clinical routine is unknown. This study aimed to investigate and describe clinical efficacy and safety of PD-1 inhibitors in patients with MM treated in routine clinical practice. Material and methods: A retrospective descriptive study of patients with metastatic or inoperable cutaneous melanoma treated with PD-1 inhibitors at a single institution (Department of Oncology, Sahlgrenska University Hospital) from 1 September 2015 to 31 August 2017. Data were obtained from medical records. Results: A total of 116 patients were included in the analyses. The overall survival (OS) at 12-month follow-up was 70.2% and the median OS was 27.9 months. Patients with BRAF mutated tumors had increased OS, whereas ECOG PS >= 2, LDH > ULN and presence or history of brain metastases (stage M1d) were associated with impaired survival. Immune-related AEs of any grade occurred in 64 (55.2%) patients and 15 (12.9%) patients experienced immune-related AEs of grades 3 and 4. Notably, rheumatic adverse events occurred at a higher rate (15.5%) than previously reported. The occurrence of immune-related AEs was associated with a benefit in OS, while the severity of immune-related AEs did not affect survival, nor did the use of systemic corticosteroids. Conclusions: The efficacy and safety of PD1 inhibitors in routine clinical practice appear comparable to that described in clinical trials.
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| 3. |
- Augustsson, A, et al.
(författare)
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Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population.
- 1991
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 71:6, s. 518-24
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Tidskriftsartikel (refereegranskat)abstract
- Common naevi, dysplastic naevi (DN) and other phenotypic features were evaluated as melanoma risk factors in a Swedish case-control study. One-hundred and twenty-one prevalent melanoma cases and 378 randomly selected controls participated. The mean total body naevus count was 115 in the cases and 67 in the controls. Fifty-six per cent of the cases and 18% of the controls had clinical DN. The corresponding figures for histologically diagnosed DN were 40% and 8% respectively. Clinical DN was as good as histologically diagnosed DN in identifying individuals at risk for melanoma. Subjects with sun-sensitive skin, greater than or equal to 150 naevi and presence of DN have 50 times higher melanoma risk than those without these characteristics.
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| 4. |
- Augustsson, A, et al.
(författare)
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Melanocytic naevi in sun-exposed and protected skin in melanoma patients and controls.
- 1991
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 71:6, s. 512-7
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Tidskriftsartikel (refereegranskat)abstract
- The possible link between exposure to ultraviolet light and naevus development was studied in 121 melanoma patients and 310 controls by comparing the number of naevi in a sun-exposed area on the back with that in a sun-protected area on the buttocks. Both patients and controls had a four-fold increase in the number of naevi in the exposed compared with the protected area, p less than 0.001. The difference in naevus count between the exposed and the protected area was larger in patients than in controls, p less than 0.001. Subjects with dysplastic naevi, melanoma patients as well as controls, had a larger difference in the number of naevi between the two areas than subjects without dysplastic naevi, p less than 0.001. These results support the idea that sunlight plays an important role in naevus development and may explain why a high naevus count is a risk marker for malignant melanoma.
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| 5. |
- Augustsson, A, et al.
(författare)
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Prevalence of common and dysplastic naevi in a Swedish population.
- 1991
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Ingår i: The British journal of dermatology. - 0007-0963. ; 124:2, s. 152-6
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Tidskriftsartikel (refereegranskat)abstract
- The naevus profile was examined in a Swedish population that was randomly selected from a census file. The participation rate was considered high at 82%. The number of common naevi (CN) and the prevalence of dysplastic naevi (DN) were investigated in 379 subjects (aged 30-50 years). The mean total body count of CN greater than or equal to 2 mm was 67 (range 1-300). As many as 22% of the population had 100 naevi or more and only 18% had less than 25. The counts were not influenced by age or sex. DN were diagnosed clinically in 18% (CI 14-22%) of the subjects and histologically in 8% (CI 5-11%). Subjects with dysplastic naevi had a significantly larger number of common naevi and a more sun-sensitive skin type than subjects without DN, P less than 0.001.
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| 6. |
- Augustsson, A, et al.
(författare)
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Regional distribution of melanocytic naevi in relation to sun exposure, and site-specific counts predicting total number of naevi.
- 1992
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 72:2, s. 123-7
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Tidskriftsartikel (refereegranskat)abstract
- The role of exposure to ultraviolet light in the formation of melanocytic naevi was analysed by investigating the regional naevus distribution in 310 subjects (30-50 years) from a Swedish census file. The lateral aspect of the arms and the back had the largest concentration of naevi. The mean naevus count per unit surface area was higher in intermittently exposed than in rarely exposed skin (p less than 0.001), while the lowest mean count was found in chronically exposed skin. These results support the idea that intermittent exposure to ultraviolet light has a "naevogenic" effect while chronic exposure might be protective. Dysplastic naevi had a distribution pattern quite different from common naevi. Considering the distribution pattern solely, dysplastic naevi seem to develop independently of exposure to ultraviolet light. The numbers of naevi in different skin areas were tested for their power in predicting the total body naevus count. The strongest correlations were found between total counts and counts on the anterior surface of the thighs and the lateral aspect of the arms. Counts from any of these areas will provide a practical and satisfactory estimate of the total number of naevi.
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| 7. |
- Bhadury, Joydeep, et al.
(författare)
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Hypoxia-regulated gene expression explains differences between melanoma cell line-derived xenografts and patient-derived xenografts.
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:17
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Tidskriftsartikel (refereegranskat)abstract
- Cell line-derived xenografts (CDXs) are an integral part of drug efficacy testing during development of new pharmaceuticals against cancer but their accuracy in predicting clinical responses in patients have been debated. Patient-derived xenografts (PDXs) are thought to be more useful for predictive biomarker identification for targeted therapies, including in metastatic melanoma, due to their similarities to human disease. Here, tumor biopsies from fifteen patients and ten widely-used melanoma cell lines were transplanted into immunocompromised mice to generate PDXs and CDXs, respectively. Gene expression profiles generated from the tumors of these PDXs and CDXs clustered into distinct groups, despite similar mutational signatures. Hypoxia-induced gene signatures and overexpression of the hypoxia-regulated miRNA hsa-miR-210 characterized CDXs. Inhibition of hsa-miR-210 with decoys had little phenotypic effect in vitro but reduced sensitivity to MEK1/2 inhibition in vivo, suggesting down-regulation of this miRNA could result in development of resistance to MEK inhibitors.
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| 8. |
- Bouwhuis, Marna G, et al.
(författare)
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Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon.
- 2009
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:12, s. 869-77
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treatment with recurrence-free interval in two randomized trials that compared intermediate doses of IFN with observation for the treatment of melanoma patients. METHODS: Serum levels of anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined using enzyme-linked immunosorbent assays in 187 and 356 patients in the European Organization for Research and Treatment of Cancer (EORTC) 18952 and Nordic IFN trials, respectively, immediately before and up to 3 years after random assignment. The association of the presence of at least one of the three autoantibodies with risk of recurrence was assessed by three Cox models in patients negative for all three autoantibodies at baseline (125 from the EORTC 18952 trial and 230 from the Nordic IFN trial): 1) a model that considered appearance of autoantibodies as a time-independent variable, 2) one that considered a patient autoantibody positive once a positive test for an autoantibody was obtained, and 3) a model in which the status of the patient was defined by the most recent autoantibody test. All statistical tests were two-sided. RESULTS: When treated as a time-independent variable (model 1), appearance of autoantibodies was associated with improved relapse-free interval in both trials (EORTC 18952, hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.25 to 0.68, P < .001; and Nordic IFN, HR = 0.51, 95% CI = 0.34 to 0.76, P < .001). However, on correction for guarantee-time bias, the association was weaker and not statistically significant (model 2: EORTC 18952, HR = 0.81, 95% CI = 0.46 to 1.40, P = .44; and Nordic IFN, HR = 0.85, 95% CI = 0.55 to 1.30, P = .45; model 3: EORTC 18952, HR = 1.05, 95% CI = 0.59 to 1.87, P = .88; and Nordic IFN, HR = 0.78, 95% CI = 0.49 to 1.24, P = .30). CONCLUSIONS: In two randomized trials of IFN for the treatment of melanoma patients, appearance of autoantibodies was not strongly associated with improved relapse-free interval when correction was made for guarantee-time bias.
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| 9. |
- Brandberg, Y, et al.
(författare)
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Health-related quality of life in patients with high-risk melanoma randomised in the Nordic phase 3 trial with adjuvant intermediate-dose interferon alfa-2b.
- 2012
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Ingår i: European journal of cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:13, s. 2012-2019
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare health-related quality of life (HRQoL) and side-effects in patients with high-risk melanoma participating in a randomised phase III trial of adjuvant interferon alfa-2b (IFN). PATIENTS AND METHODS: A total of 855 patients with histologically verified resected cutaneous melanoma in AJCC stage IIb (T4 N0 M0) or stage III (Tx N1-3 M0) were randomised to: Arm A: observation only (n=284); Arm B: 1-year treatment: induction: IFN alfa-2b, 10 MU (flat dose), SC, 5days/week, 4weeks, maintenance: IFN alfa-2b, 10 MU (flat dose), SC, 3days/week for 12months (n=285); or Arm C: 2years of same treatment as Arm B. HRQoL was assessed using The European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) before randomisation and at 8 pre-defined time-points during 2years. IFN-related side-effects were assessed by a study-specific questionnaire. RESULTS: >80% of eligible patients returned questionnaires at the different assessment points. Statistically significant interactions between randomisation arm and time after randomisation were found for almost all EORTC QLQ-30 variables. While patients in Arm A improved or remained at baseline levels; patients in Arms B and C reported decreased functioning and quality of life, and an increase in side-effects during their treatment. Patients in Arm B improved after the 12th month assessment, when IFN treatment was scheduled to end, to the 16th month assessment (p<0.001). The same pattern of improvement was found for 5 of 7 interferon-related side-effects. CONCLUSION: A significant negative impact on HRQoL of IFN treatment was demonstrated, however the impact were reversible when treatment was stopped.
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| 10. |
- Brandberg, Yvonne, et al.
(författare)
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Role functioning before start of adjuvant treatment was an independent prognostic factor for survival and time to failure. A report from the Nordic adjuvant interferon trial for patients with high-risk melanoma.
- 2013
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 52:6, s. 1086-1093
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To investigate the role of health-related quality of life (HRQoL) at randomization as independent prognostic factors for survival and time to failure, and to explore associations between HRQoL and treatment effects. Material and methods. In the Nordic adjuvant interferon trial, a randomized trial evaluating if adjuvant therapy with intermediate-dose IFN had the same beneficial effects on overall and disease-free survival in high-risk melanoma as high-dose IFN, 855 patients in Denmark, Finland, Norway, and Sweden were included. The EORTC QLQ-C30 questionnaire was used to assess HRQoL before randomization. Results. A total of 785 (92%) agreed to participate in the HRQoL-study and provided baseline HRQoL data. Prognostic variables included in the multivariate model were age, sex, performance status, tumor thickness, stage, and number of positive lymph nodes. Univariate analyses revealed an association between prolonged survival and age, stage/ number of metastatic lymph nodes and the HRQoL variable role functioning (p ≤ 0.01). After controlling for other prognostic factors, these variables remained independently statistically significant for survival. The univariate analyses of time to failure showed significant associations with the clinical variable stage/nodes and with the HRQoL variables physical functioning and role functioning. Adjusted multivariate analyses including the same clinical conditions as above showed statistically significant relationships between time to failure and global quality of life, physical functioning, role functioning, social functioning and fatigue (p ≤ 0.01). No interactions between HRQoL variables and treatment were found, with the exception for cognitive functioning. Conclusion. Role functioning was found to be an independent prognostic factor for time to failure and survival in patients with high-risk melanoma. Thus, also in this early stage of melanoma, HRQoL variables might be useful as important prognostic factors for time to failure and overall survival.
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