Iskanje po repozitoriju

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Povzetek: Background. Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy.Patients and methods. A retrospective analysis of patients with metastatic melanoma treated with immuno-therapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups.Results. Among the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE co-hort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.Conclusions. Patients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall re-sponse rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.
Ključne besede: immune related adverse events, immunotherapy, metastases, melanoma
Objavljeno v DiRROS: 22.07.2024; Ogledov: 101; Prenosov: 51
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Povzetek: . Electrochemotherapy (ECT) is a local cancer treatment based on electroporation where the electric field is used to enhance cell membrane permeability and thereby facilitating the transition of chemotherapeutic agents into the cell. For the treatment of non-melanoma skin cancer, a standard dosage of 15,000 IU/m2 bleomycin (BLM) is used. The aim of the present study was to evaluate the long-term ECT response in the group of elderly patients with non-melanoma skin cancer treated with a reduced dose of BLM in comparison to the outcome in the patients treated with the standard dose of BLM. Patients and methods. Twenty-eight patients older than 65 years, with a total of 52 non-melanoma skin lesions were included in the study. Twelve patients (24 lesions) in the experimental group received a reduced dose of BLM (10,000 IU/m2), 16 patients (28 lesions) were treated with a standard dose of BLM (15,000 IU/m2). Results. No statistically significant difference in tumor control was observed between both groups. In the experimental group, tumors recurred in 39.0% of treated lesions in a median follow-up time of 28 months. In the control group, the recurrence rate of treated lesions was 15.4% in a median follow-up time of 40 months. Conclusions. ECT with a reduced dose of BLM is a feasible treatment option for elderly patients with equal efficacy to standard dose treatment and should be considered as a treatment modality in advanced aged patients with comorbidities, where overall life expectancy is poor
Ključne besede: electrochemotherapy, bleomycin, non-melanoma skin cancer
Objavljeno v DiRROS: 12.07.2024; Ogledov: 108; Prenosov: 36
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Povzetek: Background. Sclerosing melanocytic lesions, which are characterized by either focal or diffuse sclerosis in the dermal component and atypical proliferation of predominantly nevoid melanocytes, remain poorly defined. Our aim was to analyze systematically their morphologic spectrum, especially the distinction between sclerosing melanocytic nevus and sclerosing melanoma, which has not been well documented. Patients and methods. We collected 90 sclerosing melanocytic lesions, occurring in 82 patients (49 male, 33 female; age range from 21 to 89 years). A four probe fluorescent in situ hybridization (FISH) assay was performed in 41 lesions to substantiate the diagnosis of sclerosing melanomas. Results. A prominent full-thickness pagetoid spread of melanocytes was identified in 44 (48%) lesions, and a melanoma in situ adjacent to the sclerosis in 55 (61%) lesions. In the intrasclerotic component, maturation was absent in 40 (44%) and mitotic figures were identified in 18 (20%) lesions. Of the 90 lesions, 26 (29%) were diagnosed morphologically as nevi and 64 (71%) as melanomas (Breslow thickness from 0.4 to 1.8 mm), including 45 (50%) melanomas with an adjacent nevus. A four-probe FISH assay was positive in the sclerotic component in 14 of 25 lesions diagnosed morphologically as melanomas and none of 16 nevi. A sentinel lymph node biopsy was performed for 17 lesions and was negative in all cases. Conclusions. Sclerosing melanocytic lesions form a morphologic spectrum and include both nevi and melanomas. The pathogenesis of sclerosis remains obscure but seems to be induced by melanocytes or an unusual host response in at least a subset of lesions.
Ključne besede: sclerosing melanoma, sclerosing nevus, fibrosis
Objavljeno v DiRROS: 02.07.2024; Ogledov: 160; Prenosov: 164
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Povzetek: Mitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combina-tion with vemurafenib.Patients and methods. In the prospective, observational study, patients with BRAF-mutated metastatic melanoma treated with cobimetinib in combination with vemurafenib at the Institute of Oncology Ljubljana were asked to par-ticipate. Ophthalmic examination was performed including measurement of visual acuity and intraocular pressure, slit lamp examination, funduscopy (CF), infrared-reflectance (IR) imaging and optical coherence tomography (OCT). Results. Five out of 7 patients noticed changes in vision few days after starting the therapy with cobimetinib. In all patients, small circular lesions, described as MEKAR lesions, were documented in outer retinal layers demonstrated with OCT, IR, and CF. Changes were in the center and/or scattered over the retina almost symmetrical in both eyes in 6 patients, and asymmetrical in one patient, the latter presented also with unilateral anterior uveitis and cystoid macular edema.Conclusions. Multiple bilateral foveal and extrafoveal small retinal lesions in the outer retinal layers develop in patients treated with MEK inhibitor in combination with BRAF inhibitor. Ophthalmologists and oncologists need to be aware of this common, yet relatively benign and often transient ocular side effect to avoid needless intervention, including the discontinuance of a potentially life-prolonging therapy.
Ključne besede: metastatic malignant melanoma, eye, MEK inhibitor, MEKAR
Objavljeno v DiRROS: 10.06.2024; Ogledov: 134; Prenosov: 49
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Povzetek: Introduction. Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. Patients and methods. From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. Results. Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age >/= 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. Conclusions. It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation.
Ključne besede: choroidal melanoma, therapy, brachytherapy, prognostic factors
Objavljeno v DiRROS: 09.05.2024; Ogledov: 307; Prenosov: 151
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