| 1. |
- Donina, Simona, et al.
(författare)
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Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study
- 2015
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 25:5, s. 421-426
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Tidskriftsartikel (refereegranskat)abstract
- An oncolytic, nonpathogenic ECHO-7 virus adapted for melanoma that has not been genetically modified (Rigvir) is approved and registered for virotherapy, an active and specific immunotherapy, in Latvia since 2004. The present retrospective study was carried out to determine the effectiveness of Rigvir in substage IB, IIA, IIB and IIC melanoma patients on time to progression and overall survival. White patients (N=79) who had undergone surgical excision of the primary melanoma tumour were included in this study. All patients were free from disease after surgery and classified into substages IB, IIA, IIB and IIC. Circulating levels of clinical chemistry parameters were recorded. Survival was analysed by Cox regression. Rigvir significantly (P<0.05) prolonged survival in substage IB-IIC melanoma patients following surgery compared with patients who were under observation (according to current guidelines). The hazard ratio for patients under observation versus treated with Rigvir was statistically significantly different: hazard ratio 6.27 for all, 4.39 for substage IIA-IIB-IIC and 6.57 for substage IIB-IIC patients. The follow-up period was not statistically different between both treatment groups. These results indicate that the patients treated with Rigvir had a 4.39-6.57-fold lower mortality than those under observation. In this study, there was no untoward side effect or discontinuation of Rigvir treatment. Safety assessment of adverse events graded according to NCI CTCAE did not show any value above grade 2 in Rigvir-treated patients. In conclusion, Rigvir significantly prolongs survival in early-stage melanoma patients without any side effect.
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| 2. |
- Gogas, Helen J., et al.
(författare)
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The role of depression and personality traits in patients with melanoma : a South-European study
- 2017
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Ingår i: Melanoma research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0960-8931 .- 1473-5636. ; 27:6, s. 625-631
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Tidskriftsartikel (refereegranskat)abstract
- We explored the potential association of depression history and personality, evaluated through a robust questionnaire tool, namely the Eysenck Personality Scale, with disease risk and progression among Greek patients. A total of 106 melanoma patients and their 1 : 1 sex-matched controls were interviewed on the basis of a questionnaire comprising phenotypic, sociodemographic, lifestyle and medical history variables, as well as information on history of lifetime major depression. The Eysenck Personality Questionnaire, measuring the four personality dimensions (extraversion, neuroticism, psychoticism, lie), was thereafter completed. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses, whereas potential predictors of survival were explored using Cox proportional hazards models. Sun sensitivity score [OR: 1.55, 95% confidence interval (CI): 1.16-2.06] and major depression history (OR: 5.72, 95% CI: 1.38-23.73) were significantly associated with melanoma, whereas inverse associations of extraversion (OR: 0.90, 95% CI: 0.83-0.97) and psychoticism score (OR: 0.88, 95% CI: 0.78-1.00) were noted. These associations were more pronounced and remained solely among female patients; notably, decreased extraversion (OR: 0.86, 95% CI: 0.76-0.98) and psychoticism score (OR: 0.63, 95% CI: 0.43-0.91), as well as increased depression history (OR: 10.69, 95% CI: 1.43-80.03) were evident. Cox-derived hazard ratios showed nonsignificant associations of depression history and personality with disease outcome. Our data support the hypotheses that depression history and personality are associated with melanoma risk. No effect on survival after cancer diagnosis was observed. If confirmed in future studies, these associations may contribute toward better understanding the etiology of melanoma, enhancing health-related quality of life. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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| 3. |
- Johansson, Peter A., et al.
(författare)
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Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma
- 2019
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Ingår i: Melanoma Research. - 0960-8931 .- 1473-5636. ; 29:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency < 0.01) in families with multiple members affected by these cancers. Whole-genome or exome sequencing was performed on 160 CM and/or UM families from Australia, the Netherlands, Denmark and Sweden. Between one and five cases were sequenced from each family, totalling 307 individuals. Sanger sequencing was performed to validate BRCA1 and BRCA2 germline variants and to assess carrier status in other available family members. A nonsense and a frameshift mutation were identified in BRCA1, both resulting in premature truncation of the protein (the first at p.Q516 and the second at codon 91, after the introduction of seven amino acids due to a frameshift deletion). These variants co-segregated with CM in individuals who consented for testing and were present in individuals with pancreatic, prostate and breast cancer in the respective families. In addition, 33 rare missense mutations (variant allele frequency ranging from 0.00782 to 0.000001 in the aggregated ExAC data) were identified in 34 families. Examining the previously reported evidence of functional consequence of these variants revealed all had been classified as either benign or of unknown consequence. Seeking further evidence of an association between BRCA1 variants and melanoma, we examined two whole-genome/exome sequenced collections of sporadic CM patients (total N = 763). We identified one individual with a deleterious BRCA1 variant, however, this allele was lost (with the wild-type allele remaining) in the corresponding CM, indicating that defective BRCA1 was not a driver of tumorigenesis in this instance. Although this is the first time that deleterious BRCA1 mutations have been described in high-density CM families, we conclude that there is an insufficient burden of evidence to state that the increased familial CM or UM susceptibility is because of these variants. In addition, in conjunction with other studies, we conclude that the previously described association between BRCA2 mutations and UM susceptibility represents a rare source of increased risk.
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| 4. |
- Lyth, Johan, 1980-
(författare)
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Conditional recurrence-free survival in patients with primary stage I-II cutaneous malignant melanoma - a population-based study
- 2018
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Ingår i: Melanoma research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0960-8931 .- 1473-5636. ; 28:6, s. 637-640
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Tidskriftsartikel (refereegranskat)abstract
- Conditional survival in patients with localized primary cutaneous malignant melanoma (CMM) is well described. However, conditional recurrence-free survival (RFS) has not been investigated before. The aim of this study was to determine conditional RFS and test for time dependency in prognostic factors in patients with localized stage I-II CMM. This study included 1437 CMM patients registered in one region of Sweden during 1999-2012 followed up through 31 December 2012. To identify first recurrence of CMM disease, data from a care data warehouse, the pathology and radiology department registries were used. Patients were also followed through a Census Register and the National Cause of Death Register. The time-dependent risk of recurrence was analysed in a Coxs proportional hazard regression. The 5-year conditional RFS increased from 86% (95% confidence interval: 84-88) at diagnosis to 96% (95% confidence interval: 94-98) at 5 years after diagnosis. Women showed a 60% lower risk of recurrence than men and this effect was stable over time (P = 0.39). Patients aged greater than or equal to 65 years had a 40% higher risk of recurrence than patients aged less than 65 years, and this effect was stable over time (P = 0.65). Patients with tumour ulceration showed a 70% higher risk of recurrence than nonulcerated patients, but this effect disappeared after 2 years (P = 0.04). For patients with T3-T4 CMM, the hazard ratios decreased over time and were similar to hazard ratio of patients with T2 CMM after 2 years and later. The decreasing impact of tumour thickness and ulceration over time could have important implications for CMM patients in terms of counselling and follow-up. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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