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- Garg, G, et al.
(author)
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Patients presenting with metastases: stage IV uveal melanoma, an international study
- 2022
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In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 106:4, s. 510-517
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Journal article (peer-reviewed)abstract
- To analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.ResultsOf 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.ConclusionsThough higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.
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- Jain, P, et al.
(author)
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Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study
- 2021
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In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1358-1364
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Journal article (peer-reviewed)abstract
- To relate conjunctival melanoma characteristics to local control.MethodsRetrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system.Results288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2–8.9%), 19.3% (14.4–25.5%) and 36.9% (26.5–49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence.ConclusionThis multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.
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- Bonini, S., et al.
(author)
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Allergy and clinical immunology services in europe*
- 2006
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In: Allergy.. ; 61:10
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Journal article (peer-reviewed)abstract
- Allergology and Clinical Immunology (ACI) is an area of clinical medicine with a precise identity, relevant recent scientific achievements and well-defined educational and professional needs. In spite of the high individual and socio-economic impact of allergic diseases in Europe, the organization of ACI services is imperfect and varies among countries according to their health policies and priorities. In the firm belief of the role of ACI specialists in addressing clinical issues related to the involvement of the immune system in health and diseases-such as vaccination, immunodeficiencies, susceptibility and response to microbial agents, autoimmune and allergic diseases, immune aspects of transplantation and malignancies, in vivo and in vitro immunological tests, vaccinations, immuno-modifiers-the European Academy of Allergology and Clinical Immunology appointed an ad hoc Task Force to produce standards for ACI Services in Europe. The resulting position paper should be used as a consulting reference for National Health Services as a necessary pre-requisite for the free circulation to patients and health care professionals.
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- Fili, M, et al.
(author)
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Effect of plaque brachytherapy dose and dose rate on risk for disease-related mortality in 1238 patients with choroidal melanoma
- 2021
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In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:1, s. 57-62
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Journal article (peer-reviewed)abstract
- Episcleral brachytherapy is the most common treatment for medium-sized choroidal melanomas. Although controversial, inadequate brachytherapy dose and dose rates have at least a hypothetical implication on patient survival.MethodsAll patients who received ruthenium-106 or iodine-125 brachytherapy for choroidal melanoma at St. Erik Eye Hospital 1996 to 2016 were included (n=1238). Cox regression hazard ratios for melanoma-related mortality across deciles, quartiles and individual integers of apex radiation doses (Gy) and dose rates (Gy/hour) were calculated, adjusted for tumour size and location.ResultsThe average radiation dose at the tumour apex ranged from 73.0 Gy in the first decile to 108.6 Gy in the tenth. Decreasing apex dose by 1 Gy increments or by decile or quartile group was not associated with melanoma-related mortality (p>0.2) The average radiation dose rate at the tumour apex ranged from 0.5 Gy/hour in the first decile to 2.8 Gy/hour in the tenth. Similarly, decreasing apex dose rate by 1 Gy/hour increments or by decile or quartile groups was not associated with melanoma-related mortality (p>0.5).ConclusionThere are no increased hazards for choroidal melanoma-related mortality after brachytherapy with decreasing doses between 108.6 and 73.0 Gy, or with decreasing dose rates between 2.8 and 0.5 Gy/hour.
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| 13. |
- Fili, M, et al.
(author)
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Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of ≥5.5 mm
- 2020
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In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 104:1, s. 26-32
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Journal article (peer-reviewed)abstract
- Episcleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and β-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (<6 mm). In this study, we compare ocular and patient survival in thicker tumours treated with the respective radioisotope.MethodsAll patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups.Results317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p<0.001). Size-controlled Cox regression HRs for postbrachytherapy enucleation (125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5–7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%).ConclusionsRates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.
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| 14. |
- Gill, V, et al.
(author)
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Trends in Uveal Melanoma Presentation and Survival During Five Decades: A Nationwide Survey of 3898 Swedish Patients
- 2022
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In: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 9, s. 926034-
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Journal article (peer-reviewed)abstract
- In contrast to most other cancers, uveal melanoma (UM) is characterized by an absence of major improvements in patient survival during the last several decades. In this study, we examine changes in incidence rates, patient age and tumor size at diagnosis, treatment practices and survival for patients diagnosed in Sweden during the period 1960–2010.MethodsAll patients diagnosed with posterior UM between January 1st, 1960, and December 31st, 2009, in Sweden, were included (n = 3898). Trends in incidence, primary treatment modality, patient age and tumor size were analyzed. Disease-specific survival was plotted in Kaplan–Meier curves and the cumulative incidence of UM-related mortality was evaluated in competing risk analysis.ResultsCrude (6.5–11.6 cases/million/year) and age-standardized incidence rates (5.6–9.6 cases/million/year) varied between individual years during the study period, but both had a stable linear trend overall (p ≥ 0.12). Gradually, plaque brachytherapy with ruthenium-106 replaced enucleation as the most common primary treatment. The mean patient age at diagnosis increased from 59.8 years in 1960 to 66.0 in 2009. Conversely, the mean tumor size became gradually smaller during the period. In linear regression, the basal diameter and tumor apical thickness decreased with a slope coefficient of −0.03 mm (p = 0.012) and −0.05 mm (p = 1.2 × 10–5) per year after 1960, respectively. Patients diagnosed after 1990 had significantly better disease-specific survival than patients diagnosed before 1990 (p = 2.0 × 10–17). Similarly, the cumulative incidence of UM-related mortality was highest for patients diagnosed 1960–1969 and 1970–1979, with slightly lower incidences for patients diagnosed 1980–1989 and even lower for those diagnosed after 1990 (p = 7.1 × 10–13). The incidence of mortality from other causes than UM did not differ between periods (p = 0.16).ConclusionIn the period from 1960–2010, crude and age-standardized incidence rates of UM have remained stable in Sweden. Several other aspects have changed: Plaque brachytherapy with ruthenium-106 has replaced enucleation as the most common primary treatment modality; patients have become older and their tumors smaller at the time of diagnosis; and their survival has improved. This might indicate a beneficial survival effect of earlier diagnosis and treatment, but the potential influence from lead-time bias should be taken into consideration.
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| 15. |
- Hari-Gupta, Yukti, et al.
(author)
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Myosin VI regulates the spatial organisation of mammalian transcription initiation
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- During transcription, RNA Polymerase II (RNAPII) is spatially organised within the nucleus into clusters that correlate with transcription activity. While this is a hallmark of genome regulation in mammalian cells, the mechanisms concerning the assembly, organisation and stability remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI (MVI) in the nanoscale organisation of RNAPII. We reveal that MVI in the nucleus acts as the molecular anchor that holds RNAPII in high density clusters. Perturbation of MVI leads to the disruption of RNAPII localisation, chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of MVI in the spatial regulation of gene expression.
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| 18. |
- Stålhammar, G, et al.
(author)
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No Gender Differences in Long-Term Survival after Brachytherapy of 1,541 Patients with Uveal Melanoma
- 2019
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In: Ocular oncology and pathology. - : S. Karger AG. - 2296-4681 .- 2296-4657. ; 5:6, s. 432-439
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> In several malignancies, gender-based survival differences after specific therapeutic interventions have been demonstrated. It is not known whether such differences exist after plaque brachytherapy of uveal melanoma. <b><i>Methods:</i></b> All patients who received brachytherapy for uveal melanoma at St. Erik Eye Hospital from November 1, 1979 through November 20, 2017 were included (<i>n</i> = 1,541). Retrospective data were retrieved including baseline patient and tumor characteristics, brachytherapy nuclide (ruthenium-106 or iodine-125), radiation dose, treatment duration, tumor relapses, date of metastasis, and cause of death. <b><i>Results:</i></b> A total of 775 men and 766 women were treated with plaque brachytherapy. There were no significant differences between the genders in baseline characteristics, treatment, or follow-up. Men and women had similar rates of tumor relapses, hazard for repeated brachytherapy (men vs. women 0.8, <i>p</i> = 0.47), enucleation-free survival, and survival after detection of metastasis. Five-, 10-, and 15-year melanoma-related mortality was 14, 24, and 27% for men and 15, 26, and 32% for women, respectively. There were no significant differences in hazard for melanoma-related mortality (men vs. women 0.9, <i>p</i> = 0.32), median Kaplan-Meier disease-specific survival (men 18.2 years, women 15.5 years, <i>p</i> = 0.22), or median overall survival (men 13.5 years, women 12.6 years, <i>p</i> = 0.60). <b><i>Conclusion:</i></b> There are no relevant differences between men and women in ocular or patient survival after brachytherapy for uveal melanoma.
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