Treatment of Locally Advanced Merkel Cell Carcinoma-A Multi-Center Study.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease involves surgery and radiotherapy. To analyze real-life treatment patterns and clinical outcomes, we conducted a retrospective analysis of data from 161 MCC patients treated with curative intent in four oncological centers in Poland. The median age at diagnosis was 72 years (30-94); 49.7% were male. Lymph node (LN) involvement at diagnosis was found in 26.9% of patients. Sentinel lymph node biopsy (SLNB) was performed in 36.5% of patients (positive in 10.5%), and 51.9% of patients received perioperative treatment. The relapse rate was 38.3%. With the median follow-up of 2.3 years, the median disease-free survival (DFS) was not reached, and the 1-year rate was 65%. The negative independent risk factors for DFS were male gender, metastases in LN at diagnosis, no SLNB in patients without clinical nodal metastases, and no perioperative radiotherapy. The estimated median overall survival (OS) was 6.9 years (95% CI 4.64-9.15). The negative independent risk factors for OS were male gender, age above 70, metastases in LN at diagnosis, and no SLNB in patients without clinical nodal metastases. Our results confirm that the MCC treatment should be conducted in an experienced multidisciplinary team; however, the outcomes are still unsatisfactory.

Age as a Prognostic Factor in Patients with Ewing Sarcoma-The Polish Sarcoma Group Experience.

Ewing sarcoma (ES) is a rare and aggressive disease that requires multidisciplinary treatment with the use of chemotherapy, radiotherapy, and surgery. Our retrospective study aimed to analyze the prognostic factors and treatment results in different age groups of patients. Between 1998 and 2018, 569 patients with ES were treated in two referral centers. The patients were divided into four age groups (≤10 years; 11-18 years; 19-25, and >25). The treatment results and prognostic factors were assessed for each group. For statistical analyses, we used the Chi2 test, the Kaplan-Meier estimator with a log-rank test, and the multivariate Cox model. Five-year overall survival (OS) rate was 56%. In the age subgroups: ≤10 years, 11-18 years, 19-25 years, and >25 years, the 5-year OS rates were 75%, 58%, 41%, and 52%, respectively. Favorable prognostic factors: female gender (p = 0.024), non-axial localization (p = 0.005), VIDE regimen (p < 0.001), and surgery as a local treatment (p < 0.001) dominated in the group ≤10 years. In multivariate analysis, male (HR = 1.53), axial localization (HR = 1.46), M1 status at presentation (HR = 2.64), and age > 10 years (HR = 2.29) were associated with shorter OS. The treatment results in ES are significantly better in children aged ≤10 years; the challenge is to provide therapy for adolescents and young adults. The diagnostics and treatment of ES patients must be provided in referral centers.

Multimodal Treatment of Advanced Mucosal Melanoma in the Era of Modern Immunotherapy.

Mucosal melanoma is a rare disease epidemiologically and molecularly distinct from cutaneous melanoma developing from melanocytes located in mucosal membranes. Little is known about its therapy. In this paper, we aimed to evaluate the results of immunotherapy and radiotherapy in a group of patients with advanced mucosal melanoma, based on the experience of five high-volume centers in Poland and Italy. There were 82 patients (53 female, 29 male) included in this retrospective study. The median age in this group was 67.5 (IQR: 57.25-75.75). All patients received anti-PD1 or anti-CTLA4 antibodies in the first or second line of treatment. Twenty-three patients received radiotherapy during anti-PD1 treatment. In the first-line treatment, the median progression-free survival (PFS) reached six months in the anti-PD1 group, which was statistically better than 3.1 months in the other modalities group (p = 0.004). The median overall survival (OS) was 16.3 months (CI: 12.1-22.3) in the whole cohort. Patients who received radiotherapy (RT) during the anti-PD1 treatment had a median PFS of 8.9 months (CI: 7.4-NA), whereas patients treated with single-modality anti-PD1 therapy had a median PFS of 4.2 months (CI: 3.0-7.8); this difference was statistically significant (p = 0.047). Anti-PD1 antibodies are an effective treatment option in advanced mucosal melanoma (MM). The addition of RT may have been beneficial in the selected subgroup of mucosal melanoma patients.

The Long-Term Outcomes of Intensive Combined Therapy of Adult Patients with Localised Synovial Sarcoma.

INTRODUCTION: Synovial sarcoma (SaSy) is a high-grade, malignant soft tissue sarcoma (STS) accounting for 5-9% of STS. The aim of this study was to analyse outcomes of patients with localised SaSy treated in a single institution with a uniform neo- and adjuvant-combined therapy protocol. METHODS: 171 patients with stage II/III SaSy were treated between 1997 and 2014. Chemotherapy consisted of 4 cycles of ifosfamide 12 g/m2 and two cycles of a doxorubicin-based regimen 75 mg/m2. With the exception of patients who underwent amputation, all patients received neoadjuvant radiotherapy. RESULTS: Median age was 33 years (range 17-69). Tumours larger than 5 cm in size were found in 70% of patients. The 5-year overall survival (OS), local relapse-free survival (LRFS) and metastasis-free survival (MFS) rates were 75%, 80% and 60%, respectively. In multivariate Cox's regression, age > 35 years, male sex, larger tumour size and histology other than monophasic were associated with worse OS. CONCLUSIONS: In adult patients with localised SaSy, long-term survival can be achieved in a significant proportion of cases with intensive combined therapy. The multivariate analysis identified age, sex, disease stage and histology subtype as independent prognostic factors of OS.

Systemic Treatment for Advanced and Metastatic Malignant Peripheral Nerve Sheath Tumors-A Sarcoma Reference Center Experience.

Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate the modes and outcomes of systemic treatment of patients with diagnosed MPNST treated in a reference center. In total, 115 patients (56 female and 59 male) diagnosed with MPNST and treated due to unresectable or metastatic disease during 2000-2019 were included in the retrospective analysis. Schemes of systemic therapy and the outcomes-progression-free survival (PFS) and overall survival (OS)-were evaluated. The median PFS in the first line was 3.9 months (95% CI 2.5-5.4). Doxorubicin-based regimens were the most commonly used in the first line (50.4% of patients). There were no significant differences in PFS between chemotherapy regimens most commonly used in the first line (p = 0.111). The median OS was 15.0 months (95% CI 11.0-19.0) and the one-year OS rate was 63%. MPNST are resistant to the majority of systemic therapies, resulting in poor survival in advanced settings. Chemotherapy with doxorubicin and ifosfamide is associated with the best response and longest PFS. Future studies and the development of novel treatment options are necessary for the improvement of treatment outcomes.

Malignant peripheral nerve sheath tumors - Outcomes and prognostic factors based on the reference center experience.

INTRODUCTION: Malignant peripheral nerve sheath tumor (MPNST) accounts for about 5% of soft tissue sarcomas. It can occur as sporadic diseases or can be associated with type 1 neurofibromatosis. MPNST is usually associated with poor prognosis, mostly due to their aggressive behavior, high metastatic potential, and resistance to chemotherapy. Our study aimed to determine treatment outcomes and associated prognostic factors in a large cohort of patients with MPNSTs treated at the reference sarcoma center. METHODS: 239 consecutive patients (114 women and 125 men) diagnosed with MPNST between March 1998 and March 2018 who were treated with surgery with curative intent in the reference sarcoma center were included in the retrospective analysis. RESULTS: The mean age at diagnosis was 51 years (range 15-86). 28 (11.7%) patients had neurofibromatosis type 1 associated tumors (NF1 positive). Median OS was 126.5 months and 5-year survival rate was 61.9% in the group treated with curative intent. Median DFS, LRFS and DMFS were 91.6, 126.5 and 126.5 months, respectively. We identified tumor size, high tumor grade and positive surgical margins as independent negative predictors of DFS, LRFS, DMFS and OS. CONCLUSIONS: High-quality surgery remains a gold standard of MPNST treatment. High grade, size and quality of surgery are significant independent prognostic factors for overall survival. There is an unmet need for improvement, especially regarding the perioperative treatment and treatment of metastatic disease. Future studies on the biology of MPNST would lead to the development of novel treatment options and improvement of treatment outcomes.

The clinical prognostic factors and treatment outcomes of adult patients with Ewing sarcoma.

BACKGROUND: The data about treatment results of Ewing sarcoma in adult patients are limited. The aim of our study was to analyze prognostic factors and outcomes of therapy in this group of patients. METHODS: Between 2000 and 2018, 180 patients at the age of > 18 years old diagnosed with Ewing sarcoma were treated in referral center according to multimodal protocols. In 50 patients (28%) treatment was initiated outside our hospital, and 23 of them had started recommended therapy after 3 months since the date of biopsy/unscheduled operation. We analyzed clinical prognostic factors and overall survival (OS). RESULTS: The median age was 28 years (18-67 years), primary tumor was localized axially in 114 patients (63%), metastases at presentation were detected in 51 pts (28%). 5-year OS rate was 65% for patients with localized disease, in metastatic disease it was 15%; the presence and the number of metastases was a prognostic factor. 5-year PFS was significantly better in patients treated at referral center (or when the patients were admitted to referral center within 3 months from the date of biopsy, which was performed outside referral center), comparing to patients treated initially outside referral center; 5-year PFS rates in total population were 28 and 13%, respectively. In terms of OS, unfavorable prognostic factor showing a statistical trend (p = 0.098) was lower dose density of neoadjuvant chemotherapy due to toxicity. CONCLUSIONS: Approximately two-third of adult patients with localized Ewing sarcoma survive 5 years. In order to improve survival of this patients the multidisciplinary treatment in referral center is mandatory.

Immune checkpoint inhibitors therapy in older patients (≥ 70 years) with metastatic melanoma: a multicentre study.

INTRODUCTION: The use of immunotherapy in older patients remains challenging due to very few data on the efficacy and safety of treatment in this group. AIM: To analyse the efficacy and safety of immunotherapy with checkpoint inhibitors in older patients (≥ 70 years) with metastatic melanoma. MATERIAL AND METHODS: In the Maria Sklodowska-Curie Institute - Oncology Centre, between 2011 and 2017, 318 non-resectable or metastatic melanoma patients were treated with immune checkpoint inhibitors: anti-CTLA-4 or/and anti-PD-1. Eighty-two patients were ≥ 70 years (median age: 76 years; range: 70-90 years). Among this group 10% of patients had brain metastases, 24% of patients had BRAF mutant melanoma, and co-morbidities were present in 86% of patients (mainly hypertension, cardiovascular diseases and/or diabetes). RESULTS: Median PFS and OS were similar in patients < 70 years and ≥ 70 years. In the group of patients ≥ 70 years old, the 2-year OS rate (from the start of immunotherapy) was 27%, and in patients aged < 70 it was 28% (p = NS). Two-year progression-free survival was 13.7% in the group of patients ≥ 70 years old and in patients aged < 70 it was 13% (p = NS). Patients ≥ 70 years of age were significantly less likely to have a BRAF mutation (p = 0.020). The presence of co-morbidities was not associated with an increased risk of immunotherapy (p = 0.790). CONCLUSIONS: The survival and toxicity profile in the older patients treated with immune checkpoint inhibitors are similar to younger patients. Therefore, the age as a clinical factor should not exclude this population from the most effective therapy used nowadays in melanoma treatment.

[Leiomyosarcoma of the adrenal gland - two cases report]. / Miesniakomiesak gladkokomórkowy nadnercza ­ opis dwóch przypadków.

Primary adrenal leiomyosarcomas are very rare adrenal mesenchymal tumours, only few dozen has been reported in the English language literature so far. We present two cases of patients with primary adrenal leiomyoosarcomas. 80 year-old female admitted with left adrenal tumour with presumptive diagnosis of nonadenoma, laparoscopic adrenalectomy was performed and 85 year-old man who underwent surgical resection by laparotomy of adrenal tumour suspected for adrenal carcinoma. Native density on unenhanced CT was 30 (HU) and 28 (HU) respectively and absolute and relative contrast washout was non-characteristic. Pathologic report reviled thinly encapsulated tumours composed of neoplastic cells with strong cytoplasmic reactivity for smooth muscle actin, desmin and vimentin. Male patient 20 months after surgery was diagnosed with multiple nonresectable metastases, systemic treatment was introduced. Female patient 28 months after surgery has no signs and symptoms of recurrence. We describe the clinical course and a brief review of clinical and histological features , biologic behaviour and diagnostic and therapeutic strategies. The extremely rare occurrence of primary adrenal leiomyosarcoma and a scientific literature based on single cases present challenges in establishing any firm conclusions on management and prognosis. Obviously it's impossible to have proper diagnosis based on clinical symptoms and diagnostic imaging. Radical surgery with free margins seems to be treatment of choice.

High baseline neutrophil-to-lymphocyte ratio predicts worse outcome in patients with metastatic BRAF-positive melanoma treated with BRAF and MEK inhibitors.

Neutrophil-to-lymphocyte ratio (NLR) has been shown to be prognostic in several solid malignancies. There are limited data regarding its value during novel therapies in patients with melanoma. The aim of the study was to assess the practical utility of this ratio in patients with BRAF-mutant melanoma treated with a combination of BRAF and MEK inhibitors (BRAFi/MEKi). We included 215 patients with inoperable or metastatic melanoma who underwent BRAFi/MEKi treatment between October 2015 and June 2017. Baseline NLR and other complete blood count-derived inflammatory markers were tested for association with overall survival and progression-free survival in univariate and multivariate models. On-treatment NLR was also assessed for relationship with these outcomes using the time-dependent Cox's proportional hazard model. Prognostic model based on NLR and lactate dehydrogenase (LDH) levels was also developed. Patients with NLR values more than four had poorer progression-free survival (P<0.001, 1-year rates 51.6 vs. 26.7%) and overall survival (P<0.001, 1-year rates 77.3 vs. 53.1%). In a multivariate model adjusted for LDH levels, metastatic sites and age baseline NLR ratio and delay in starting MEKi were deemed statistically significant (hazard ratio: 1.81; 95% confidence interval: 1.16-2.85; P=0.009 and hazard ratio: 2.06; 95% confidence interval: 1.24-3.44, P=0.005 respectively). In a model based on NLR and LDH, 1-year survival rates were 57, 40 and 23%, respectively if zero, one or both factors were elevated. Our results demonstrate the usefulness of NLR and a predictive model based on combinations of NLR and LDH as a prognostic markers during BRAFi/MEKi treatment. Our real-world data confirm the efficacy of BRAFi/MEKi therapy showed in the clinical trials.

[The long-term treatment outcomes of adult osteosarcoma]. / Odlegle wyniki leczenia doroslych chorych na miesaka kosciopochodnego.

Osteosarcoma is the most common primary bone tumor. Treatment of osteosarcoma patients is based on chemotherapy as well as surgical resection of primary tumor and distant metastases. Lung metastases are the primary cause of death in this group of patients. AIM: The aim of this study is to summarize the 20 years of osteosarcoma treatment outcomes in the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw. MATERIALS AND METHODS: Our analysis included clinical data of 299 osteosarcoma patients aged between 14 and 81 years (median 32) treated in Maria Sklodowska-Curie Memorial Cancer Center between 1998 and 2016. The standard therapeutic protocol included perioperative anthracycline-based chemotherapy and surgical resection of primary tumor and distant metastases. The statistical analysis was performed using Kaplan-Meier estimator, log-rank test and Cox proportional hazards model. RESULTS: In analyzed group 38 (13%) patients had distant metastases at the diagnosis. The tumor size was greater than 8 cm in 61% of cases. In the histopathological assessment the most prevalent subtype was the conventional one (diagnosed in 76% of cases) and histological grade 3 (79%). The 5-year survival rate for patients with localized disease reached 46%. The negative prognostic factors included: distant metastases at diagnosis, axial location of primary tumor, unresectability of the primary lesion, higher histological grade, and older age of patients. CONCLUSIONS: The best results of the treatment of osteosarcoma patients are achieved with multidisciplinary treatment, and when the reference center supports other healthcare providers in management of diagnostic and treatment procedures of osteosarcoma patients.

Long-term results of therapy with sunitinib in metastatic alveolar soft part sarcoma.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare, highly vascularized soft tissue sarcoma characterized by a high frequency of metastatic disease and resistance to classical chemotherapy. The purpose of our analysis was to assess long-term sunitinib activity in the treatment of metastatic ASPS. PATIENTS AND METHODS: Between 2009 and 2015, 15 patients were diagnosed with metastatic ASPS and received therapy with sunitinib at initial continuous daily dosing of 37.5 mg. Median age was 32 years. The primary tumor sites were lower extremities (8), trunk-retroperitoneum/pelvis (2), upper extremity (3) and other (2). All patients had unresectable disease (primary or relapse in the form of metastases to the lungs ± bones). Five patients received systemic therapy before initiating sunitinib. Median follow-up from start of sunitinib was 38 months (range 5-69 months). RESULTS: At the time of analysis 4 patients continue therapy and 9 are still alive. Six patients had RECIST partial remission as best response, 8 had stable disease, and 1 had disease progression. The median progression-free survival was 19 months, with 86% of patients being free of progression at 6 months. Median overall survival was 56 months; the 5-year overall survival rate was 49%. Five patients were treated with sunitinib longer than 2 years. All patients experienced some side effects: 8 patients (53%) had CTCAE grade 3/4 toxicity, 7 patients required dose reduction. The most common toxicities were neutropenia, thrombocytopenia, hypothyroidism, arterial hypertension, and hand-foot syndrome. CONCLUSIONS: Our analysis confirms the long-term efficacy of sunitinib in patients with advanced ASPS.

The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST).

AIM OF THE STUDY: was to analyze the outcome of treatment and factors predicting results of sorafenib therapy in inoperable/metastatic CD117-positive GIST patients after failure on imatinib and sunitinib. MATERIAL AND METHODS: We identified 60 consecutive patients (40 men, 20 women) with advanced inoperable/metastatic GIST after failure on at least imatinib and sunitinib treated in one sarcoma center with sorafenib at initial dose 2 × 400 mg daily in 2007-2015 (in 56 cases it was 3rd line therapy). Median follow-up time was 39 months. RESULTS: One year progression-free survival (PFS; calculated from the date of the start of sorafenib to disease progression) rate was 23% and median PFS = 7.7 months. The median overall survival (OS) was 13.5 months calculated from sorafenib start (1-year OS rate = 57%) and 7 years from imatinib start. Three patients (5%) had objective partial responses to therapy, 31 patients (52%) had stabilization of disease > 4 months. Primary tumor mutational status was known in 43 cases (73%), but we have not identified the differences in PFS between tumors carrying different KIT/PDGFRA mutations. The most common adverse events were: diarrhoea, hand and foot syndrome, fatigue, loss of weight and skin reactions; grade 3-5 toxicity occurred in 35% of patients. 23 patients required sorafenib dose reductions due to AEs. CONCLUSIONS: We confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year.

Gene expression profiling of peripheral blood cells: new insights into Ewing sarcoma biology and clinical applications.

Ewing sarcoma (ES) is a group of highly aggressive small round cell tumors of bone or soft tissue with high metastatic potential and low cure rate. ES tumors are associated with a rapid osteolysis and necrosis. The currently accepted clinical prognostic parameters do not accurately predict survival of high-risk patients. Moreover, neither the subtype of EWS-FLI1/ERG in the tumor, nor the detection of fusion transcripts in the peripheral blood (PB) samples, has prognostic value in ES patients. We evaluated the prevalence of circulating tumor cells (CTCs) in 34 adult ES patients. Since CTCs were confirmed in only small subset of patients, we further explored the expression profiles of PB leukocytes using a panel of genes associated with immune system status and increased tumor invasiveness. Moreover, we analyzed the alterations of the routine blood tests in the examined cohort of patients and correlated our findings with the clinical outcome. A uniform decrease in ZAP70 expression in PB cells among all ES patients, as compared to healthy individuals, was observed. Monocytosis and the abnormal expression of CDH2 and CDT2 genes in the PB cells significantly correlated with poor prognosis in ES patients. Our study supports the previously proposed hypothesis of systemic nature of ES. Based on the PB cell expression profiles, we propose a mechanism by which immune system may be involved in intensification of osteoclastogenesis and disease progression in ES patients. Moreover, we demonstrate the prognostic value of molecular PB testing at the time of routine histopathological diagnosis.

Efficacy and safety of ipilimumab therapy in patients with metastatic melanoma: a retrospective multicenter analysis.

AIM OF THE STUDY: The Patient Assistance Program, a type of expanded access program, was initiated for compassionate purposes to provide ipilimumab to patients with unresectable stage III or IV melanoma with failed previous treatment. The aim of this analysis is to evaluate efficacy, safety, and tolerability of ipilimumab therapy in daily clinical practice. MATERIAL AND METHODS: We analyzed 50 patients (29 males, 21 females) aged 21 to 76 years (median: 49 years). An ipilimumab dose of 3 mg/kg was administered intravenously every 3 weeks for a total of 4 doses. Patients were assessed for response rate, progression-free survival and overall survival, and monitored for adverse events. RESULTS: The objective response (complete or partial response) rate was 12%. Median overall survival was 8 months and median progression-free survival was 3 months. In patients with ECOG-PS 0, the median overall survival was 16 months. Immune-related adverse events (irAEs) occurred in 48% of the patients, grade 3 or 4 irAEs were reported in 8% of the patients, and there were no toxic deaths. CONCLUSIONS: Ipilimumab demonstrated clinical benefit in previously treated advanced melanoma patients. Although clinical benefit is limited to a minority of the patients, there is a benefit in terms of overall survival in this group of patients.

The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study.

BACKGROUND: Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. METHODS: We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes. RESULTS: One year progression-free survival (PFS; calculated from the start of SU) rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM) was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks) in 55 patients with AH vs. 22% (median 17 weeks) in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively) than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively). We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism (OR: 10.0 p = 0.041 and OR: 10.5; p = 0.015, respectively). CONCLUSIONS: We confirmed that many advanced GIST patients benefit from SU therapy with OS > 1.5 year. Primary tumor KIT/PDGFRA genotype and SU-induced AH, as surrogate of its antiangiogenic activity are two independent factors influencing both PFS and OS.

Results of systemic treatment of cutaneous melanoma in inoperable stage III and IV.

AIM OF THE STUDY: The incidence of melanoma is increasing rapidly worldwide. Metastatic melanoma is still an incurable disease, although an era of new drugs is approaching. Current methods to predict outcomes in patients with advanced, metastatic melanoma are limited. A retrospective analysis of a contemporary large group of advanced melanomas was performed to determine clinical prognostic factors that accurately predict survival in patients with metastatic melanoma before the era of new targeted/immunological therapy. MATERIAL AND METHODS: The retrospective analysis of 427 patients with metastatic melanoma treated between 1995 and 2005 at two reference oncological centres. RESULTS: The median overall survival time (OS) was 7.1 months (95% CI: 6.7-7.9) and the 1-year, 2-year and 5-year survival rates were 32.3%; 12.5%; 3.9%, respectively. The median progression-free survival time (PFS) after the first line of treatment was 3.5 months (95% CI: 3.1-3.8). There were 19.1% objective responses (CR - 6.1%, PR - 13.0%) and SD - 45.5% after the first line of therapy. The most common adverse events were anaemia, neutropenia, thrombocytopenia, nausea and vomiting. IN MULTIVARIATE ANALYSES: PS (performance status) 0-1, normal serum levels of lactate dehydrogenase (LDH) and aspartate transaminase (AspAT), older age in women, palliative surgical treatment and palliative radiotherapy, type of the first line of therapy (DTIC), and metastatic melanoma of unknown primary site were independent positive predictors for survival. CONCLUSIONS: The survival rate of patients with metastatic melanoma has not changed significantly over the last years. We identified a set of independent positive predictors for OS treated with systemic therapy. DTIC still may be useful in treatment of patients in a good general condition and with normal serum levels of LDH. Because the results of treatment of metastatic melanoma are still not satisfactory, the majority of patients should be treated within prospective, randomized clinical trials.