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The gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between the response to anti-PD-1 therapy and the baseline gut microbiome in a Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy, and ten healthy subjects were recruited. The response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis and the metataxonomics of the microbiota. In the responders, the Bacteroidota to Firmicutes ratio was higher, and the richness was decreased. The abundance of Prevotellacopri and Bacteroidesuniformis was related to the response, whereas the non-responders’ gut microbiota was enriched with Faecalibacteriumprausnitzii and Desulfovibriointestinalis and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption as well as gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota along with diet were found to be associated with the response to the therapy in the population of melanoma patients.

Aim: To evaluate treatment results in advanced/metastatic melanoma patients treated with anti-PD-1 immunotherapy in routine practice in oncology centers in Poland. Methods: Multicenter retrospective analysis included 499 patients with unresectable/metastatic (stage IIIC–IV) melanoma treated with anti-PD-1 in first-line therapy. Results: Estimated median overall survival (OS) and progression-free survival (PFS) were 19.9 and 7.9 months, respectively. Multivariate analysis confirmed that ECOG 0, no brain metastases, normal lactate dehydrogenase level and occurrence of immune-related adverse events (irAEs) were statistically significantly associated with improved OS and PFS. Any irAE occurred in 24% of patients. Grade 3 or Grade 4 irAEs occurred in 6% of patients. Conclusion: Analysis revealed a slightly worse OS in real-world treatment in comparison to clinical trials (KEYNOTE-006 and CheckMate 066). Polish population treatment results are similar to other studies of real-world data. PFS and ORR are similar in our research and clinical trials.

Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three patients were aged 80-100, 218 patients were aged 65-79, and 208 patients were

Introduction. The development of a new class of drug — checkpoint inhibitors has changed the prognosis of cancer patients. A particular class of drugs are antibodies against the programmed cell death type 1 receptor/ligand of the programmed cell death type 1 receptor (nivolumab and pembrolizumab). There are, however, no trials with a random selection of the patients which directly compare nivolumab and pembrolizumab. Because of the development of immunotherapy and many new drugs registered as anti-PD-1, it is important to determine whether there are differences in respect to effectiveness and safety in using nivolumab and pembrolizumab. Material and method. 499 patients with non-resectable or metastatic melanoma treated in the years 2016–2019 in five oncological reference centers in Poland (Cracow, Gliwice, Lublin, Poznan, Wroclaw) were included in the analysis. The criterion for inclusion in the analysis was first-line treatment with anti-PD-1 (nivolumab or pembrolizumab). Results. Median OS and PFS in the whole analyzed group were 19.9 and 7.9 months, respectively. Estimated median OS and PFS were 20.1 and 18.1 months and 8.5 and 6.0 months for nivolumab and pembrolizumab, respectively. No statistically significant difference was observed in median OS and PFS in the group of patients receiving nivolumab and pembrolizumab (respectively P = 0.6291 [HR = 1.06; Cl 95% 0.8–1.4] and P = 0.0956 [HR = 1.20; Cl 95% 0.97–1.48]). The percentage of grade G3 or/and G4 irAEs was similar in both groups treated with nivolumab or pembrolizumab, 5.8 and 5.2%, respectively. Conclusions. No differences in the range of OS, PFS and ORR was observed between therapy with nivolumab and pembrolizumab in previously untreated patients with advanced/metastatic melanoma. No differences were found in the frequency of irAEs of grade G3 or G4. The treatment with a specific preparation should be based on the preferences of the patient and the clinician.

Despite considerable progress made in the treatment of patients with advanced melanoma, the majority of the patients treated with BRAF and mitogen-activated protein inhibitors (BRAFi and MEKi) experience a disease progression due to acquired resistance. Currently, ongoing studies explore the possibility to overcome or reverse this process. Our multicenter retrospective analysis included 51 patients with metastatic BRAF-mutated melanoma who had previously progressed on BRAFi/MEKi than had progressed on immunotherapy (anti-progression disease-1 or anti-cytotoxic T-lymphocyte-associated protein 4) and next were rechallenged with BRAFi/MEKi. Median age at BRAFi/MEKi rechallenge was 56 (range: 31-82 y/o). Median overall survival from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 29.7 and 9.3 months, respectively, whereas median progression-free survival was 10.5 and 5.9 months, respectively. Six-month, annual, and 2-year overall survival rates on both treatments were: 98% and 55%, 92% and 29%, and 69% and 2%, respectively. A response rate to treatment was higher in the group receiving BRAFi/MEKi for the first time as compared with the group receiving BRAFi/MEKi rechallenge and was overall response rate 72% and 27%; disease control rate 92% and 63%. Time interval between the end of the first BRAFi/MEKi treatment and the beginning of BRAFi/MEKi rechallenge did not influence median overall survival or progression-free survival. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. BRAFi/MEKi rechallenge treatment remains clinically important and is associated with the lower toxicity. BRAFi/MEKi rechallenge efficacy is higher in patients who are in good performance status, with normal lactate dehydrogenase, and without brain metastases.

Background:Head and neck squamous cell carcinoma (HNSCC) is the most common malignant cancer occurring in the head and neck area, approximately 90% of the cases. Even in the cases of primary radical treatment (surgical, concomitant chemoradiotherapy or radiotherapy alone), subsequent local recurrence or distant metastases are often observed. In patients with recurrent disease who are unable to receive radical treatment, the results of palliative chemotherapy are not satisfactory. In this review, we summarized the standard treatment options, current development of new drugs and future perspectives in the treatment of patients with recurrent locally advanced and/or metastatic HNSCC.Methods:PubMed databases with words ‘head and neck cancer treatment’, ‘immunotherapy in head and neck cancer treatment’ were searched and yielded 186512 and 2249 papers respectively. We selected the most cited articles and reports presenting new immunotherapy agents and drug combinations in HNSCC.Results:Recently, two new agents been approved in the treatment of recurrent locally advanced and/or metastatic HNSCC. These are immune-checkpoint inhibitors targeting PD1 (nivolumab and pembrolizumab) which are the most active drugs in the second line treatment of advanced HNSCC. Still, the first line ‘golden standard’ is the chemotherapy regimen (cisplatin, 5-fluorouracyl) combined with cetuximab. Many phase 3 studies are currently ongoing, evaluating the efficacy of combinational treatment-anti-CTLA4 with anti-PD1 or anti-PDL1. Very encouraging results have been shown in early phase studies evaluating the combination of immunecheckpoint inhibitors with tumor microenvironment immunosuppressive inhibitors.Conclusion:Despite the huge progress in the systemic treatment of patients with recurrent locally advanced and/or metastatic HNSCC, the disease at this stage remains incurable. Undoubtedly, further research in the field of biomarkers for effective immunotherapy is needed in order to select a group of patients whose will benefit from this therapy, as the treatment is still ineffective in most patients.

Long non-coding RNAs (lncRNA) are dysregulated in many cancer types. Abnormal baseline levels of these lncRNAs display diagnostic and prognostic potential in cancer patients. The aim of this study was to evaluate the prognostic value of plasma lncRNAs in BRAF-mutant advanced melanoma patients treated with a BRAF inhibitor. Total RNA was isolated from plasma samples collected from 58 advanced BRAF-mutant melanoma patients and 15 healthy donors. The expression levels of 90 lncRNAs were estimated using the LncProfiler qPCR Array Kit (SBI) and LightCycler 96 (Roche). LncRNA expression levels correlated with responses to the BRAF inhibitor (vemurafenib) treatment. The patients were stratified into three groups based on their lncRNA levels with various lncRNA expressions (low, medium, and high). A Cox proportional hazards regression model was used to determine the lncRNAs that were significantly associated with both progression-free and overall survivals (PFS and OS, respectively) in patients receiving vemurafenib. The expression level of 12 lncRNAs was down-regulated, while five lncRNAs were up-regulated in melanoma patients compared to healthy donors. Kaplan-Meier analysis showed that upregulation or downregulation of 11 and 16 different lncRNAs were associated with longer median PFS and OS, respectively. Further analysis demonstrated that the baseline lncRNAs for IGF2AS, anti-Peg11, MEG3, Zeb2NAT are independent prognostic factors in BRAF-mutant advanced melanoma patients treated with vemurafenib. Evaluation of plasma lncRNAs expression level for advanced melanoma diagnosis and prognosis evaluation appears to be a safe and valuable method; however, this method requires further validation in larger cohorts and randomized trials.

Simple Summary Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. Despite good knowledge of the histological and genetic background of metastases formation, there is still a lack of specific biomarkers which would allow early detection of UM progression. Due to their unique molecular cargo consisting of proteins and nucleic acids, exosomes have been widely studied as carriers of biomarkers for cancer development and progression. In this study, we analyzed the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors using multiplex immunoassay technology. We showed a significant correlation between the disease stage and the concentration of inflammation-related proteins from exosomal cargo. Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease. Abstract Background: Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. However, despite relatively good knowledge about the histological and genetic risk factors for metastasis development, there is no specific biomarker that would allow early detection of UM progression. Recently, exosomes and their molecular cargo have been widely studied in the search for potential biomarkers in several cancers. The purpose of this study was to analyze the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors. Methods: The exosomes were isolated from the serum of primary and metastatic UM patients and healthy donors. Using multiplex immunoassay technology, we analyzed the concentration of 37 inflammation-related proteins in obtained exosomes. Results: The analysis of protein cargo showed several molecules related to inflammation, such as interferon-gamma, interleukin 2, 22 and 12(p40), Pentraxin-3, TNFSF13B and TNFSF8 which were significantly enriched in metastatic UM exosomes. We showed a significant correlation between the disease stage and the concentration of these inflammation-related proteins from exosomal cargo. Conclusions: Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease.

The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.

e21544 Background: BRAF-mutated (MUT) melanoma is characterized by specific clinical features including more aggressive biological behavior than BRAF wild-type (WT) melanoma. BRAF mutations are historically known as negative prognostic factor for to shorter overall survival (OS) in patients with stage IV disease with melanoma. Methods: Consecutive patients with unresectable or metastatic melanoma started treatment with BRAF inhibitors (BRAFi), BRAFi and MEK inhibitors (MEKi) or IT (anti-PD-1 antibody) between 1/Jan/2013 and 31/Dec/2020. Clinical factors including age, gender, primary location of melanoma, ECOG performance status, baseline LDH level, and location of metastases, response to treatment were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2021. Results: In total 1456 patients were enrolled. BRAF mutation was found in 723 (49.7%) patients and 733 (50.3%) patients were BRAF WT. All BRAF WT patients received first-line IT, while BRAF MUT patient received first-line treatment with BRAFi (n = 134/723, 18%), BRAFi and MEKi (n = 426, 58%) or anty-PD-1 (n = 173, 24%). BRAF MUT patients were significantly younger (median 60 vs 69; p < 0.0001), had worse ECOG (p = 0.0008), elevated LDH (p < 0.0001), had higher number of metastatic sites (p < 0.0001) and brain metastases (p < 0.0001). The estimated median OS (mOS) in BRAF WT group was 17.3 month while in BRAF MUT - 14.8 months (p = 0.33; HR = 0.94, Cl 95% 0.8-1.1). mOS in BRAF MUT group treated with BRAFi was - 10.0, while with BRAFi and MEKi combination - 14.9. BRAF WT and BRAF MUT groups treated with IT did not differ significantly in baseline characteristics. BRAF MUT group treated with IT achieved mOS of 26.2 months, while in BRAF WT 17.3 months. Conclusions: The analysis showed no differences in the median OS between BRAF MUT and BRAF WT patients with unresectable or metastatic melanoma treated with novel therapies (BRAFi-MEKi combination or IT), despite unfavorable prognostic factors in the BRAF MUT group. Moreover mOS was significantly prolonged in the BRAF MUT patients treated with IT.

e21539 Background: The use of targeted therapies (TT) and checkpoint inhibitors (IT) significantly prolonged survival in patients with metastatic melanoma, especially in patients with BRAF mutation-positive melanoma. Optimal sequence of therapies use is still a matter of debate. The aim of this study was to evaluate real-life practice and outcomes in melanoma patients treated sequentially. Methods: Consecutive patients with BRAF mutation-positive unresectable or metastatic melanoma started treatment with TT (BRAF and MEK inhibitors) and/or IT (anti-PD1) between 1/Oct/2016 and 31/Dec/2020. Clinical factors including age, gender, ECOG performance status, baseline LDH level, and location of metastases, response to treatment and irAEs occurrence were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2021. Results: In total 585 patients were enrolled. 170 (29%) patients were treated with IT and 415 (71%) with TT in the first line. 331 patients (56%) received only one line of treatment – 247/415 (59%) patients only TT and 84/170 (49%) patients received only IT (anti-PD1). Disease progression was found in 175 (71%) patients in the only TT group and in 43 (51%) in the only IT group. 254 patients qualified for sequential treatment 168 (29%) patients received TT then IT (TT-IT), 64 (11%) IT then TT (IT-TT), and 22 (4%) IT-IT (anti-PD-1 then anti-CTLA-4). Patients with brain metastases and elevated LDH were statistically more often treated with first line TT and more patients with normal LDH level received IT-IT therapy. No other statistically significant differences in baseline characteristics was found for IT-TT, TT-IT and IT-IT groups. The estimated median OS (mOS) was not reached in patients treated with only one line of IT treatment, while for TT only it was only 11.8 months. Estimated mOS for patients treated in the first line with IT or TT was significantly different (p = 0.02; HR = 0.74, Cl 95% 0.6-0.9) and reached 25.6 and 15.3 months, respectively; although no statistically significant mOS differences was found in the subgroups without brain metastases (p = 0.56) and with normal LDH (p = 0.36). For sequential treatment groups mOS for IT-TT, TT-IT, and IT-IT was 19.6, 19.9 and 35.9 months, respectively. There was no statistically significant difference in OS between IT-TT and TT-IT treated groups (p = 0.56), and between IT-TT, TT-IT and IT-IT groups (p = 0.19). Conclusions: Patients who were treated with IT in the 1st line had better OS than patients treated TT in the 1st line in real-world data but this may be related to better prognostic factors in the IT group. Selected patients receiving IT in the first line achieve long OS, which is a result of a long-term response to IT. Novel predictive biomarkers factors of IT response should be incorporated in prospective trials.

Healthy human subjects develop spontaneous CD8+ T cell responses to melanoma associated antigens (MA) expressed by normal melanocytes, such as Tyrosinase, MAGE-A3, Melan/Mart-1, gp100, and NY-ESO-1. This natural autoimmunity directed against melanocytes might confer protection against the development of malignant melanoma (MM), where MA are present as overexpressed tumor-associated antigens. Consistent with this notion we report here that functional T cell reactivity to MA was found to be significantly diminished to MAGE-A3, Melan-A/Mart-1, and gp100 in untreated MM patients. Three lines of evidence suggest that the MA-reactive T cells present in healthy subjects undergo exhaustion once MM establishes itself. First, only the MA-specific T cell reactivity was affected in the MM patients, that to third party recall antigens was not. Second, in these patients, the residual MA-specific T cells, unlike third party antigen reactive T cells, were functionally impaired, showing a diminished per cell IFN-&gamma, productivity. Third, we show that immunization with MA restored natural CD8+ T cell autoimmunity to MA in 85% of the MM patients. The role of natural T cell autoimmunity to tumor-associated MA is discussed based on discrete levels of T cell activation thresholds.

(1) Background: BRAFi/MEKi are usually offered as a first line treatment for patients requiring rapid response; with elevated lactate dehydrogenase (LDH) activity, large tumor burden, and with brain metastases. The efficacy of second line therapies after BRAFi/MEKI failure is now well defined. (2) Methods: Patients treated with first line target BRAFi/MEKi therapy (vemurafenib plus cobimetinib, dabrafenib plus trametinib or encorafenib plus binimetinib); and for the second line treatment immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors (nivolumab or pembrolizumab) with at least one cycle of second line were analyzed for survival and prognostic biomarkers. (3) Results: There were no statistically significant differences in ORR between the treatment groups with nivolumab and pembrolizumab, as well as median progression free-survival (PSF) and overall survival (OS) since the initiation of second line therapy; on nivolumab OS was 6.6 months, and on pembrolizumab 5.0 months. The greatest clinical benefit with second line immunotherapy was observed in patients with LDH ≤ ULN and 6 months in first line (slow progression). (4) Conclusions: Second line anti-PD1 immunotherapy is effective in BRAF-mutated melanoma patients after BRAFi/MEKi therapy failure.

Background: Currently, limited data on targeted therapy and immunotherapy sequencing in patients with BRAF-mutant melanoma is available. Targeted therapy and immunotherapy are expected to be comparable in terms of overall survival (OS) when used as second-line therapies; therefore, understanding the characteristics of patients who completed sequential treatment is needed. Methods: The primary objective of this study was to analyze the efficacy of BRAFi/MEKi activity as second-line therapy in patients with advanced melanoma. We also aimed to describe the clinical characteristics of patients with advanced melanoma who were treated sequentially with immunotherapy and targeted therapy. We enrolled 97 patients treated between 1st December 2015 and 31st December 2020 with first-line immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors; and for the second-line treatment with at least one cycle of BRAFi/MEKi therapy with follow-up through 31 January 2022. Results: Median OS since first-line treatment initiation was 19.9 months and 12.8 months since initiation of BRAFi/MEKi treatment. All BRAFi/MRKi combinations were similarly effective. Median progression free survival (PFS) was 7.5 months since initiation of any BRAFi/MEKi treatment. Conclusions: BRAFi/MEKi therapy is effective in the second-line in advanced and metastatic melanoma patients. For the first time, the efficacy of all BRAFi/MEKi combinations as second-line therapy is shown.

Purpose Immunotherapy has become a standard treatment option for patients with metastatic melanoma, and the use of checkpoint inhibitors significantly improves the treatment outcomes in this group. Patients and methods A total of 116 patients with metastatic melanoma were enrolled in the study. In the first line, they were treated with an anti-PD-1 inhibitor (nivolumab or pembrolizumab), following which ipilimumab was used as the second-line therapy. Results BRAF mutation was detected in 12 patients (10%). The median progression-free survival (PFS) of ipilimumab treatment was 2.8 months, the overall survival (OS) was 5.1 months. The rate of 6-month survival was 45%, 1-year survival was 24%, and 2-year survival was 3%. The responses to treatment were: complete response in 2 cases (2%), partial response in 7 cases (6%), stable disease in 39 cases (34%). In multivariate analysis, normal levels of lactate dehydrogenase (LDH) were associated with a longer median OS and PFS (p = 0.02 and p = 0.009, respectively), while 2 or less number of metastatic locations and the presence of BRAF mutations were correlated with a longer OS (p = 0.041 and p = 0.024, respectively). Conclusions Ipilimumab could be considered after anti-PD-1 treatment. Treatment with ipilimumab following anti-PD-1 therapy showed beneficial effects in patients with normal levels of LDH, 2 or less number of metastatic locations, and BRAF-mutated melanoma. However, further studies are required to confirm our results as the study included a low number of patients with BRAF mutation-positive melanoma. No significant increase in toxicity was detected with the use of ipilimumab after anti-PD-1 therapy.

e21514 Background: Anti-programmed cell death-1 antibodies (anti-PD-1) have become a standard treatment option for melanoma patients. Currently, two anti-PD-1 antibodies are registered in the treatment of melanoma patients: nivolumab and pembrolizumab. Nivolumab is a human monoclonal antibody, while pembrolizumab is a humanized antibody. Unfortunately, there are very few clinical data comparing the efficacy and toxicity of nivolumab and pembrolizumab in routine practice. Methods: Consecutive patients treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) for unresectable or metastatic melanoma in comprehensive cancer centers between 03/2016 and 09/2020 were enrolled in the analysis. Baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level, and location of metastases) were evaluated to identify predictors of overall survival (OS). Data on response to treatment and the occurrence of irAEs were collected prospectively during anti-PD-1 treatment. OS were assessed using Kaplan–Meier and Cox models. The Chi-Square statistic was used for testing relationships between categorical variables. Median follow up for nivolumab and pembrolizumab group was 12.6 (range 0.2-52.1) and 10.7 (range 0.03-53.5) months, respectively. Results: Overall, 736 patients were included in the present analysis (443 nivolumab, 293 pembrolizumab). There were no statistically significant differences in baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level (normal vs elevated), brain metastasis and TNM stage) between the groups. Median OS for patients treated with nivolumab and pembrolizumab was 22 and was 17.3 months, respectively. There was no statistically significant difference in OS between the nivolumab and pembrolizumab groups (p = 0.12, HR = 1.2, Cl 95% 0.9-1.4). At multivariate analysis normal LDH levels, no brain metastases, and ECOG 0 or 1 were positive prognostic factors for OS both in nivolumab and pembrolizumab groups. In the nivolumab and pembrolizumab groups, 6% and 5% CR (complete response), 33% and 31% PR (partial response), 25% and 24% SD (stable disease), respectively, were observed. There was no statistical difference between the groups in the response to treatment (p = 0.65). There was no statistical difference between the groups in occurrence of the irAEs (p = 0.97) as well as in the type of irAEs. Conclusions: Our analysis in melanoma patients treated in routine practice with nivolumab or pembrolizumab confirmed no statistical differences in OS and treatment responses between these two anti-PD-1 antibodies. There were also no differences in toxicity between the two drugs. The choice of treatment should be based on the preferences of the patient and the physician.

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

Ifosfamide is a cytostatic drug commonly used in chemotherapy. One of the common adverse effects resulting from the treatment with ifosfamide is encephalopathy. This paper describes a case study of a 64-year-old patient who suffered from a full-blown encephalopathy as a result of chemotherapy administered during the treatment of fibrosarcoma of the femur. It provides a hypothesis of the mechanism behind toxic effects of ifosfamide on the central nervous system and elaborates on a number of documented ways of preventing aforementioned complications.