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SARS-CoV-2 infection is associated with inflammation, decrease in antioxidants and oxidative damage. We aimed to investigate whether ubiquinol, reduced form of coenzyme Q10 (CoQ10), with mountain spa rehabilitation (MR) will contribute to recovering of patients with post-COVID-19 syndrome.The study included 36 patients on MR lasting 16-18 days. Twenty‑two patients were supplemented with ubiquinol 2x100 mg/day (MRQ), 14 underwent MR without supplementation. The control group consisted of 15 healthy volunteers. Concentrations of total CoQ10 (ubiquinone + ubiquinol), α- and γ-tocopherol were determined in platelets (PLT), in blood and plasma, also β-carotene was determined. Plasma concentration of thiobarbituric acid‑reactive substances (TBARS) was used as the oxidative stress marker. Clinical symptoms were evaluated by questionnaire.MRQ group showed a significant increase in CoQ10, namely in PLT by 68 %, in blood by 194 %, and in plasma by 232 %. In MR group, CoQ10 stayed unchanged. In both groups, the initially increased concentrations of tocopherols in PLT returned nearly to the control values. β-carotene levels decreased in both groups while TBARS decreased slightly in the MRQ group. More clinical symptoms disappeared in the MRQ group.Accelerated recovery of patients with post-COVID-19 syndrome was proven after mountain spa rehabilitation and ubiquinol supplementation. Increased systemic and cellular CoQ10 concentration alleviated clinical symptoms and improved antioxidant protection of the patients. We draw attention to the importance of monitoring and ensuring adequate levels of CoQ10 in post-COVID-19 syndrome (Tab. 2, Fig. 1, Ref. 45). Text in PDF www.elis.sk Keywords: COVID-19, mountain spa rehabilitation, ubiquinol, coenzyme Q10, vitamins, TBARS.

The increasing volume of the data and experience with direct oral anticoagulants (DOACS) in the primary and secondary prevention of venous thromboembolism in oncologic patients (CAVTE) has recently lead to changes in several international guidelines. We reflect these changes within the conditions in Slovak republic. In the primary prevention of CAVTE we recognise oncosurgical patients and nonsurgical patients: hospitalised and out patients. Low molecular weight heparins are still dominant in the primary prevention of CAVTE. Regarding the treatment and the secondary prevention of CAVTE, we recommend always to consider the possibility to use DOACs as they proved to be non inferior to LMWH. However, LMWH should be prefered over DOACs as well as over warfarin (VKA) in all patients who are in a clinically unstable condition with the high risk of bleeding and/or interaction with the systemic treatment. Primarily in the patients with intraluminal tumours of the upper part of the gastrointestinal tract and genitourinary tumours with the high risk of bleeding. As for the lack of data, LMWH are still preferd also in patients with primary tumours and metastatic disease of the central nervous system and in hemato oncology.

Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q10 (CoQ10) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and β-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ10 level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ10 cycle (Q-junction) to CI.

Background Germ cell tumors represent highly curable disease even in metastatic stage. However, poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Objective The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population. Design, setting, and participants This was an open-labeled, nonrandomized, single-center phase II trial to study the efficacy and toxicity of TIP in the first-line treatment of germ cell tumor patients with an unfavorable decline of STMs. Nineteen patients with a poor prognosis according to the International Germ Cell Cancer Collaboration Group classification and an unfavorable STM decline after the first cycle of chemotherapy were included in this phase II study (NCT02414685). The treatment regimen consisted of paclitaxel 250 mg/m2 on day 1, ifosfamide 1200 mg/m2 on days 1–5, and cisplatin 20 mg/m2 on days 1–5, totally for four cycles. Outcome measurements and statistical analysis The primary endpoint was complete response (CR) rate. An optimal Simon two-stage design was used with a type I error of 5% and study power of 80%. If fewer than six CRs to study therapy have been observed among the first 19 patients, the study was to be terminated. Results and limitations A CR was achieved in four (21.1%) patients; therefore, the study was terminated in the first stage. A favorable response rate (CR or partial remission with negative tumor markers) was observed in 14 (78.9%) patients. At a median follow-up period of 35.2 mo (range, 5.6–62.1 mo), ten (52.6%) patients experienced disease progression and eight patients (42.1%) died. The 2-yr progression-free and overall survival was 41.2% (95% confidence interval [CI] 16.8–65.7) and 72.7% (95% CI 48.9–96.4), respectively. TIP was well tolerated, and no unexpected toxicity was observed. No informative biomarkers, including miR-371a-3p was identified. Conclusions Treatment modification from the BEP to the TIP regimen in patients with an unfavorable STM decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population. Patient summary Poor-risk patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with an approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Treatment modification from the BEP regimen to the paclitaxel, ifosfamide, and cisplatin regimen in patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population., Take Home Message Poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population. Treatment modification from the BEP to the TIP regimen in this patient population was not associated with an improved outcome, and four cycles of BEP remain the standard treatment option in this group of patients.

BACKGROUND/AIM Systemic immune-inflammation index (SII) predicts survival of patients with various malignancies. This study explored the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects. PATIENTS AND METHODS We evaluated 181 consecutive MUC patients treated with first-line platinum-based therapy. Karnofsky performance status

BackgroundMetastatic germ cell cancer of the testis is characterized by favorable prognosis since effective treatment methods are available even in cases of extensive disease. Retroperitoneal masses frequently encroach major blood vessels requiring a vascular intervention usually performed in association with the post-chemotherapy retroperitoneal lymph node dissection (RPLND). Reported clinical case describes a successful pre-treatment endovascular surgery for abdominal aortic rupture allowing for full-dose systemic chemotherapy administration, and subsequent radical surgical intervention at primary tumor site as well as metastatic retroperitoneal lymph node dissection including the reconstruction of inferior caval vein.Case presentationPatient presented with left-sided testicular tumor and voluminous retroperitoneal mass with vascular involvement. Soon after the patient had been admitted for the first cycle of cisplatin-based chemotherapy, computed tomographic angiography (CTA) revealed a dorsal aortic wall rupture with active extravasation and irregular pseudoaneurysmatic dilatation of the aorta below the leak area. Retroperitoneal intratumoral hemorrhage associated with the bilateral iliac venous thrombosis required an endovascular repair procedure of infrarenal abdominal aorta.ConclusionsFollowing the successful endovascular aortic repair 3 cycles of BEP (bleomycin, etoposide, cisplatin) regimen were administered with subsequent delayed left radical orchiectomy and RPLND associated with vena cava inferior (VCI) resection. Reconstruction of VCI was originally not deemed necessary as collateral blood flow appeared sufficient, however, intraoperative complications resulted in the need for unilateral VCI reconstruction, using the interposed bypass between right common iliac vein and infrarenal segment of VCI. Histopathologic examination of the attained specimen detected no vital cancer structures. The patient remains disease-free 18 months after the RPLND.

European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR — mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16–18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study showed significant improvement of clinical symptoms, lungs function, and regeneration of reduced CI-linked platelet mitochondrial respiration after MR in patients with post-COVID-19 syndrome. High-altitude environment with spa rehabilitation can be recommended for the acceleration of recovery of patients with post-COVID-19 syndrome., This research was partially funded by the Comenius University in Bratislava, Faculty of Medicine and by OncoReSearch, Rovinka, Slovakia.

429 Background: Testicular cancer is the most common malignancy among young men. Vitamin D has pluripotent effects on cancer pathogenesis and plays a role in the metastatic cascade. The aim of this study is to analyze plasma vitamin D in association with clinico-pathological findings and prognosis in patients with testicular germ-cell tumours (GCTs). Methods: This study included 120 newly diagnosed and/or relapsed GCTs patients treated from April 2013 to July 2020. Blood samples were drawn at the time before 1st chemotherapy cycle as well as before the 2nd cycle. Plasma vitamin D was measured using ELISA and matched with disease characteristics and correlated with the patient outcome. For survival analysis the cohort was dichotomized to “low” and “high” based on median vitamin D. Results: Mean ± standard error of mean plasma vitamin D in GCTs patients was 15.87±0.68 mg/ml. Patients with brain metastases had significantly lower D vitamin compared to patients without brain metastases (10.9 ± 3.05 vs 15.99 ± 0.7, p=0.034). Vitamin D was not associated with other patient characteristics. Low vitamin D was associated with an unfavorable response compared to favorable responses (11.26 ± 1.84 vs 16.47± 0.74, p=0.016), with disease recurrence (16.19 vs 13.71, p=0.011) and with inferior progression-free survival but not with overall survival (HR= 3.02, 95%CI (1.36-6.71), p=0.014 for PFS and HR= 2.06, 95%CI (0.84 – 5.06), p=0.135 for OS, respectively). Conclusions: Our study suggests a prognostic value of pretreatment vitamin D concentrations in GCTs patients. Low plasma vitamin D was associated with unfavorable response to therapy and disease recurrence. However, it remains to elucidated whether the biology of the disease confirms a causative role of low vitamin D and if its supplementation affects the outcome.

417 Background: Testicular germ cell tumors (GCT) achieve exceptional cure rate with cisplatin-based chemotherapy. Survivors of GCTs represent a unique population to study post-cancer treatment physiology and late toxicities. The impact of cancer treatment on the immune-cell profile in long-term GCT survivors is unknown. In this study, we performed an immune-phenotyping in survivors of GCTs. Methods: Whole peripheral blood was obtained from GCT survivors (N = 202) at National Cancer Institute of Slovakia within the protocol of the ongoing survivorship study on a day of their annual follow-up visit. The median follow-up was 11 years (2-25). GCT survivors were distributed into treatment groups: RT – radiotherapy to the retroperitoneum (N = 18), CT - chemotherapy (N = 143), CTRT - chemotherapy + radiotherapy (N=9); and a control group: AS - active surveillance/orchiectomy only (N=32). Immuno-phenotyping of peripheral blood leukocyte populations was performed with flow-cytometry. Immune cell subpopulations were statistically assessed for associations with received treatment. Results: Survivors treated with RT vs AS had higher no of classical dendritic cells (DCs) (mean ± SEM = 82.0 ± 1.9 vs 76.5 ±1.5, p = 0.03) and non-significantly lower no of plasmacytoid DCs and CD16+ DCs (0.11 ± 0.01 vs 0.15 ± 0.01, p = 0.06 and 54.4 ± 4.1 vs 64.8 ± 3.2, p = 0.07, respectively). Survivors treated with CT vs AS had higher no of CD19+ B cells (11.9 ± 0.3 vs 10.4 ± 0.7, p = 0.04)and lower no of CD8+ T cells (26.0 ± 1.3 vs 23.7 ± 0.6, p = 0.04). Similarly, survivors treated with CTRT vs AS had higher no of CD19+ B cells (13.6 ± 1.4 vs 10.4 ± 0.7, p = 0.04) and lower no of CD8+ T cells (20.7 ± 2.4 vs 26.0 ± 1.3, p = 0.04). Survivors treated with ≥ 400mg/m2 of cisplatin-based chemotherapy vs AS had no of CD19+ B cells (12.2 ± 0.5 vs 10.4 ± 0.7, p = 0.04) and lower no of CD8+ T cells (23.4 ± 0.9 vs 26.3 ±1.3, p = 0.04). The immunoregulatory index CD4/CD8 was higher in CTRT vs AS (2.5 ± 0.3 vs 1.8 ± 0.1, p = 0.04). Conclusions: Certain subpopulations of leukocytes differ according to received treatment in survivors of GCTs. Our results may suggest that chemotherapy and/or radiotherapy may produce long-term immunomodulatory effects. Interplay between B and T cells may be a contributing mechanism of late toxicities. Further research is needed to uncover the causal relationship to the long-term health of GCT survivors.

424 Background: Germ cell tumors (GCTs) represent a highly curable malignancy; however, a small portion of patients can develop choriocarcinoma syndrome (CS) connected with acute respiratory distress syndrome (ARDS) with high mortality rate shortly after the chemotherapy start. The aim of this study was to assess the prognostic value of circulating cell-free – extracellular DNA (ecDNA) in patients with GCTs and its association with CS development and outcome. Methods: This study included 23 patients with poor-prognosis GCTs treated from November 2002 to May 2018 at the National Cancer Institute in Slovakia. Pre-treatment total ecDNA, nuclear (ncDNA) and mitochondrial DNA (mtDNA) were quantified in plasma using fluorometry and real-time PCR and analyzed in association with CS development and survival. Results: Four (17%) patients developed CS and all of them died due to ARDS shortly after the chemotherapy start. Total ecDNA, but not ncDNA or mtDNA were associated with CS development. Four out of 11 (37%) patients with high plasma ecDNA developed CS compared to 0 out of 12 (0%) patients with low plasma ecDNA (p = 0.037). In univariate analysis, higher concentration of ecDNA also positively correlated with ECOG PS ≥2, metastatic lung involvement ≥50%, weight loss ≥10%, hemoglobin ≤100 g/l, and neutrophil to lymphocyte ratio ≥ 3.3 at the time of presentation. Patients with low ecDNA had significantly better PFS (HR = 0.35, 95% CI 0.11-1.17, p = 0.043) and OS (HR = 0.26, 95% CI 0.06-1.20, p = 0.032) compared to patients with high pretreatment concentration of ecDNA. Conclusions: In this study we have proved that quantitative analysis of plasma ecDNA has prognostic value for CS development in patients treated due to GCTs. Further research focused on the biology of ecDNA may help us to understand its role as a biomarker, but also a potentially treatable pathogenic factor for choriocarcinoma syndrome development.

Testicular germ cell tumors (GCTs) are the most common solid malignancy in males aged 15-35 years. Febrile neutropenia (FN) is a serious complication of chemotherapy that frequently occurs in patients with GCTs. The present retrospective study aimed to evaluate the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in patients with GCTs. The present study included a review of the medical records of patients diagnosed with GCTs treated with first-line/adjuvant chemotherapy between January 2000 and December 2017 at the National Cancer Institute (Bratislava, Slovakia). In January 2006, a decision was made to administer G-CSF prophylaxis (filgrastim or pegfilgrastim) to patients after every cycle of chemotherapy. The present study included 385 patients, and out of these, 264 patients received primary G-CSF prophylaxis, while 121 patients did not. A total of 71 patients (18.4%) suffered from FN events. In the subgroup that did not receive primary prophylaxis, 42 patients exhibited FN, while only 29 patients with primary prophylaxis suffered from FN (34.7 vs. 11.0%; P=0.00000003). According to the subgroup analysis, FN incidence was decreased in all groups that received primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy, without affecting overall survival. Primary G-CSF prophylaxis was associated with markedly reduced FN incidence in patients treated with first-line chemotherapy for metastatic disease. Therefore, the results of the present study suggested that primary G-CSF prophylaxis should be considered in patients with GCT receiving first-line chemotherapy.

Venous thromboembolism (VTE), commonly occurring in patients with testicular germ cell tumors (GCTs), is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in patients with malignancies. The objective was to evaluate the effect of low-molecular-weight heparin (LMWH) prophylaxis on the incidence of VTE and outcome in patients with GCT treated with first-line chemotherapy. In this retrospective study, 353 chemotherapy-naive GCT patients were treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia (2000-2017). Median follow-up was 71 months. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. Exclusion criteria were LMWH use before starting chemotherapy and VTE on initial staging. We observed 14 (4.0%) VTE events. No visceral thromboses were observed. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2%, p=0.37). We observed a trend toward longer overall survival in patients without prophylaxis (hazard ratio = 0.61, 95% confidence interval = 0.32-1.13, p=0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival (hazard ratio = 0.29, 95% confidence interval = 0.08-1.12, p=0.04). This effect was most likely driven by a higher incidence of treatment-related deaths in patients with extragonadal GCT receiving LMWH (p=0.06). LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, there was a higher incidence of treatment-related deaths in patients with extragonadal tumor location. Low-molecular-weight heparin prophylaxis during hospitalization should not be used routinely in patients with testicular germ cell tumors receiving chemotherapy.

Background: Systemic immune-inflammation index (SII) predicts survival in patients with various malignancies. This study explores the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects.Methods: We evaluated 181 consecutive MUC (148 bladder, 27 upper tract) patients (135 men) treated with first-line platinum-based therapy. Karnofsky performance status Results: At median follow-up of 9.6 months (range 1.7-191.1 months), 174 patients (96.1%) experienced disease progression and 173 (95.6%) died. Subjects with low SII at baseline and at week 6 had significantly better PFS (HR 0.58; P = 0.0002 and HR 0.55; P < 0.0001) and OS (HR 0.54; P < 0.0001 and HR 0.54; P < 0.0001) compared to patients with high SII. Independent prognostic value of SII was confirmed in a multivariate analysis. Patients with low SII at baseline and at week 6 had significantly better PFS and OS compared to patients with high SII at both timepoints (P < 0.0001).Conclusion: High SII before chemotherapy that persists at week 6 negatively affects survival. SII at baseline can be used in stratification of patients within clinical trials and in clinical practice.

Testicular germ cell tumors (TGCTs) are an excellent example of chemosensitive disease. However, cisplatin-based chemotherapy has significant side effects, including myelosuppression. Previously, we found endogenous DNA damage level in peripheral blood mononuclear cells (PBMCs) to be an independent prognostic marker. In this study, we tested the hypothesis that patients with high endogenous DNA damage levels in PBMCs have an increased risk of developing hematological toxicity.One hundred twenty chemotherapy-naive TGCT patients treated in the National Cancer Institute and the St Elisabeth Cancer Institute in Bratislava, Slovakia, from 2012 to 2018 were enrolled. All patients received platinum-based chemotherapy with granulocyte colony stimulating factor support. On the day of starting treatment, we measured the DNA damage levels in PBMCs using the comet assay. We used the cutoff level of 5.25, a value previously reported to stratify patients on the basis of their prognosis. We monitored hematological toxicity during the first cycle of chemotherapy. The mean and standard error of the mean were calculated for all variables.Patients with high DNA damage levels (5.25) had more significant hematological toxicity with significantly lower nadir white blood cell count (P = .001), absolute neutrophil count (P = .013) and absolute lymphocyte count (ALC; P .001). ALCs on day 0 (P = .005) and day 22 (P = .046) were also significantly lower in patients with high DNA damage levels.This study shows that higher endogenous DNA damage levels correlate with increased risk of hematological toxicity in TGCT patients. Hence, the DNA damage levels can be used to select patients for closer monitoring because of a higher risk of acute chemotherapy-related complications.

e18774 Background: Vaccination remains the leading strategy against Covid-19 worldwide. BNT 162b2 (tozinameran) belongs among first licensed vaccines with good efficacy. However, the role of monitoring both, antibodies and cell immunity after vaccination remains unclear. Methods: We conducted a 6-month prospective study involving vaccinated workers of NCCC in Slovakia who were tested for the presence of neutralizing antibodies and cell immunity after second dose of tozinameran. SARS-CoV-2 IgG antibodies were detected by the Atellica IM sCOVG, a fully automated 2-step sandwich immunoassay using indirect chemiluminescent technology. Blood samples were tested by two IGRA tests (Quantiferon RUO and CoviFeron) to assess interferon-γ (IFN-γ) responses to SARS CoV-2 spike protein antigen and nucleocapsid protein antigen. Results were stratified by gender and body mass index. P values for categorical variables were calculated using χ2 or Fishers exact test. P values for continuous variables were calculated using T test and Wilcoxon-Mann-Whitney test. Value of statistical significance was set to 0.05. Data were analyzed using SAS 9.4 software. Results: Medical records of 94 respondents (71 females) were analyzed. Mean age was 40.2 years (23 – 62 years) and mean body mass index (BMI) ± standard error of mean (SEM) was 26.4±2.7 (21.3 – 31.7). Twenty-two (23.4 %) respondents had Covid-19 before first, 5 (5.3 %) before second, and 2 (2.15 %) after second dose of vaccine (P < 0.0001). IgG were tested 24.4±5.0, 50.2±12.1, and 187.9±12.8 days after second vaccination. IgG index progressively decline with corresponding values 126.81±40.34, 93.55±51.29, and 17.68±29.07 (P < 0.0001). Mean time from second vaccination to cell immunity testing was 157.2±101.3 days. Forty-eight (51.1 %) of respondents had negative, 6 (6.4 %) border line, and 40 (42.6 %) positive cell immunity (P < 0.0001). Conclusions: Our study confirmed the efficacy of tozinameran despite both, rapid decline of antibodies and absence of cell immunity in majority of subjects.

Chemoresistance of germ cell tumors (GCTs) represents an intensively studied property of GCTs that is the result of a complicated multifactorial process. One of the driving factors in this process is the tumor microenvironment (TME). Intensive crosstalk between the DNA damage/DNA repair pathways and the TME has already been reported. This study aimed at evaluating the interplay between the immune TME and endogenous DNA damage levels in GCT patients. A cocultivation system consisting of peripheral blood mononuclear cells (PBMCs) from healthy donors and GCT cell lines was used in an in vitro study. The patient cohort included 74 chemotherapy-naïve GCT patients. Endogenous DNA damage levels were measured by comet assay. Immunophenotyping of leukocyte subpopulations was performed using flow cytometry. Statistical analysis included data assessing immunophenotypes, DNA damage levels and clinicopathological characteristics of enrolled patients. The DNA damage level in PBMCs cocultivated with cisplatin (CDDP)-resistant GCT cell lines was significantly higher than in PBMCs cocultivated with their sensitive counterparts. In GCT patients, endogenous DNA damage levels above the cutoff value were independently associated with increased percentages of natural killer cells, CD16-positive dendritic cells and regulatory T cells. The crosstalk between the endogenous DNA damage level and specific changes in the immune TME reflected in the blood of GCT patients was revealed. The obtained data contribute to a deeper understanding of ongoing interactions in the TME of GCTs.

Introduction Rheumatoid arthritis (RA) is a chronic inflammatory autoimunne disorder affecting both small and large synovial joints, leading to their destruction. Platelet biomarkers are involved in inflammation in RA patients. Increased circulating platelet counts in RA patients may contribute to platelet hyperactivity and thrombosis. In this pilot study we evaluated platelet mitochondrial bioenergy function, CoQ10 levels and oxidative stress in RA patients. Methods Twenty-one RA patients and 19 healthy volunteers participated in the study. High resolution respirometry (HRR) was used for analysis of platelet mitochondrial bioenergetics. CoQ10 was determined by HPLC method; TBARS were detected spectrophotometrically. Results Slight dysfunction in platelet mitochondrial respiration and reduced platelet CoQ10 levels were observed in RA patients compared with normal controls. Conclusions The observed decrease in platelet CoQ10 levels may lead to platelet mitochondrial dysfunction in RA diseases. Determination of platelet mitochondrial function and platelet CoQ10 levels could be used as new diagnostic strategies for mitochondrial bioenergetics in rheumatoid diseases.

Background: Testicular germ cell tumors (GCTs) are the most common solid malignancy in men 15-35 years old. Febrile neutropenia (FN) is a grievous complication of chemotherapy, frequently occurring in GCT patients. The aim of this retrospective study was to assess the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in GCT patients. Patients and methods: This study was conducted from medical records database of GCTs patients treated with first line/adjuvant chemotherapy from January 2000 to December 2017. Starting in January 2006, patients received G-CSF prophylaxis after every cycle of chemotherapy. Results: Out of 393 patients, 265 patients received primary G-CSF prophylaxis and 128 patients did not receive prophylaxis. During the study period, 71 patients (18.1%) suffered FN events. Out of 128 patients who did not receive primary prophylaxis, 42 patients suffered FN, while only 29 patients with primary prophylaxis suffered FN (32.8% vs 10.9%, P = 0.0000001). On subgroup analysis, FN incidence decreased in all groups with primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy. Patients receiving G-CSF prophylaxis had significantly longer overall survival when compared to patients without prophylaxis. (HR = 0.44, 95% CI 0.26-0.75; P = 0.0009).Conclusions: Primary G-CSF prophylaxis was associated with significantly decreased FN incidence in patients treated with first line chemotherapy for metastatic disease. Patients receiving G-CSF prophylaxis had significantly longer overall survival. We suggest, that primary G-CSF prophylaxis should be considered in GCT patients receiving first line chemotherapy.

Since the end of 2019, a novel coronavirus (SARS-CoV-2) causing pneumonia, often progressing to rapid deterioration with acute respiratory distress syndrome (ARDS) requiring advanced life support, has been spreading worldwide The humanitarian crisis we are currently witnessing across the globe is threatening access to artificial ventilation of the lungs (AVL) for patients with respiratory failure Q-vent is a multi-way air valve system with filters and heater/humidifier module produced by 3D printer from a new composite material based on Phloxine B, Saponite, and Polylactic acid that prevents the formation of bacterial biofilms This automated device, which can be fitted with commercially available Ambu? Breathing Bags or similar, provides a high degree of controllability along with one-box complexity A built-in cough sensor warns of patient?s awakening In the case of power failure, Q-vent switches to battery reserve The developed device was tested on an intubated model (Gaumard? Scientific - UNI?) corresponding to a patient (80 kg) with lung compliance 50 ml / cm H2O to simulate ARDS for 24 hours The inspiration to expiration (I: E) ratio, tidal volume set to 8 ml/kg PBW (L-type pneumonia) and 6 ml/kg PBW (H-type Pneumonia), and frequency of inspiration were adjusted to test Q-Vent operation at a range of different conditions All functions performed reliably throughout the testing procedure Q-Vent successfully passed the Rapidly Manufactured Ventilator System (RMVS001) validation issued by MHRA and is awaiting clinical trials to determine its value in overcoming crises caused by the lack of conventional AVL

In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection.In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease.On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG.An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.

Oxidative stress plays a significant role in development and progression of cancer, including urothelial carcinomas. TBARS (Thiobarbituric acid reactive substances) represents a marker of oxidative stress increased in various diseases. In this prospective study, we tested the hypothesis of plasma TBARS concentration and correlation with survival in chemotherapy naive MUC (metastatic urothelial carcinoma) patients. Most of subjects (N = 65) were treated with gemcitabine and cisplatin (GC) chemotherapy. Performance status ECOG ≥2 had 11 patients, visceral metastases were present in 43. Based upon the mean of plasma TBARS, subjects were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared by log-rank test. At median follow-up of 9.6 months, 65 patients experienced progression and 64 died. Subjects with low TBARS had significantly better PFS (HR 0.51) and OS (HR 0.44) opposed to high TBARS. Patients with low TBARS had significantly higher rate of neutropenia G4 and less liver involvement. High TBARS correlated with BMI above 30 kg/m2. Performance status and plasma TBARS were proven to be independent predictors of PFS and OS. In this study, high TBARS in MUC patients were associated with poor survival, likely due to more aggressive disease activity as reflected in increased liver involvement. Therefore, this biomarker could be used in clinical practice for early identification of patients with worse prognosis, better patient stratification, and treatment decision making.

Background Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors. Methods GCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5–32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%). Results In univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m2 of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively). Conclusions This study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.

Background Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in patients with GCT, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in patients with malignancy. The aim of this retrospective study was to evaluate the effect of low-molecular-weight heparin (LMWH) prophylaxis on the incidence of VTE and outcome in patients with GCT treated with first-line chemotherapy. Methods Our study population included chemotherapy-naive patients with GCT treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia, from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. Patients diagnosed with VTE on initial staging exam were excluded from the study. No visceral thromboses were observed. Results Our cohort included 353 patients with GCT. LMWH prophylaxis was administered to 104 patients (29.5%), and 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% P = 0.37). We observed a trend toward longer overall survival in patients without prophylaxis (hazard ratio = 0.61, 95% confidence interval = 0.32-1.13, p = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival (hazard ratio = 0.29, 95% confidence interval = 0.08-1.12, P = 0.04). This effect was most likely driven by a higher incidence of treatment-related deaths in patients with extragonadal GCT receiving LMWH ( P = 0.06). Conclusions LMWH prophylaxis was not associated with decreased VTE incidence.Moreover, there was a higher incidence of treatment-related deaths in patients with extragonadal tumor location. LMWH prophylaxis during hospitalization should not be used routinely in patients with GCT receiving chemotherapy.

426 Background: Survivors of testicular germ cell tumors (GCT) may suffer from long-term cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis. Methods: GCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial transfer and dysbiosis (GMT) high mobility group box-1 (HMGB-1), lipopolysaccharide (LPS), d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers of GMT. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6). Results: GCT survivors with higher sCD14 had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overal cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and LPS. Survivors treated with ≥ 400mg/m2 of cisplatin based chemotherapy had higher LPS (567.8 ± 42.7 vs 462.9 ± 51.9, P = 0.03). Survivors treated with chemotherapy + radiotherapy vs orchiectomy only had non-significantly higher sCD14 (7279.9 ± 810.1 vs 5851.0 ± 481.7, P = 0.09). Conclusions: sCD14 may serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors.

Rationale: Primary diffuse leptomeningeal melanomatosis (PDLM) is a rare disease that affects melanocytes in the leptomeninges. There is very limited data on the efficacy of immunotherapy in this setting. Patient concerns: A patient (23 years old) was diagnosed with PDLM. Histologically, atypical melanocytic cells were also observed. Diagnosis: Immunohistochemistry showed positivity for S100 protein, NKiC3, and vimentin, and negativity for Melan-A and HMB-45, with a proliferation index of 30%. Extracranial disease was excluded using dermatological and other examinations, including positron emission tomography/computed tomography with 18F-fluorodeoxyglucose. Interventions: The patient was treated with whole-brain radiotherapy (10 fractions to a total dose of 30 Gy) concomitantly with pembrolizumab and then continued with immunotherapy until disease progression with a maximum effect of partial remission on magnetic resonance imaging scans. Outcomes: Progression-free survival was 6.0 months and overall survival 6.5 months. Lessons: This is one of the few case reports of an adult patient with this rare malignancy being treated with a programmed death-1 inhibitor with partial response. Immunotherapy in metastatic PDLM may be a reasonable therapeutic option.

An increased risk of venous thromboembolism (VTE) in patients with malignancy compared with the current population is determined by risk factors including the use of anticancer treatments, in particular some hormonal drugs, cytostatics, vascular endothelial growth factor (VEGF) inhibitors and epidermal receptor growth factor (EGFR) inhibitors, immunomodulators, and erythropoietins. The population of cancer patients is divided into a group of individuals with a history of malignant disease in complete remission and patients with active (locally advanced or metastatic) malignant disease in terms of approach to VTE. Venous thromboembolism negatively influences the prognosis of a patient with malignancy. Cancer associated VTE is associated with higher risk of recurrence as well as higher risk of bleeding during anticoagulation. For initial and long-term treatment, low molecular weight heparin should be preferred, for a minimum of 3-6 months. Some subgroups deserve a special approach - patients with thrombocytopenia, renal insufficiency, and patients with recurrent VTE despite anticoagulation. The treatment of an incidental pulmonary embolism is another controversial issue. The approach to a patient with cancer associated VTE should be individualized and should take into account patient´s overall prognosis and risk/benefit ratio of treatment.Key words: anticoagulation treatment - cancer - risk factors - venous thromboembolism.

Background Germ cell tumors (GCTs) are highly curable diseases; however, not all patients can be cured. Patients in their second relapse have especially poor prognoses. PD-L1 expression is significantly higher in GCTs than in normal testicular tissue, and high PD-L1 expression is associated with a poor prognosis. This study aimed to determine the efficacy and safety of avelumab, a PD-L1 inhibitor, in patients with GCTs. Methods In this phase 2 study, patients with multiple relapsed and/or refractory GCTs were treated with avelumab at a dose of 10 mg/kg administered biweekly until progression or unacceptable toxicity. The primary endpoint was 12-week progression-free survival (PFS). Fifteen evaluable patients had to be enrolled in the first cohort, and if

e17010 Background: Germ cell tumors (GCTs) represent a highly curable cancer. However, a small proportion of patients with super-high-risk characteristics can develop choriocarcinoma syndrome (CS) connected with acute respiratory distress syndrome (ARDS). CS is defined as a syndrome with hemorrhage from metastatic sites in patients with advanced GCTs with high-volume of choriocarcinoma elements, especially those with a choriogonadotropin level over 50,000 IU/l. CS typically develop shortly after the chemotherapy start with high mortality rate. Our retrospective study aimed to determine the risk factors of high-risk GCTs susceptible to CS development. Methods: Using a computerized database and a systematic chart review, we identified the records of 532 patients with GCTs treated in NCI through 2000 to 2018, and 90 eligible patients with high-risk GCTs relying on IGCCCG classification, were identified. All patients were treated with platinum-based induction chemotherapy. Clinicopathological variables were collected and analyzed in correlation to CS development. Results: Nine (10 %) of 90 patients developed CS in a median of 1 day (1- 9 days) after the chemotherapy administration. All patients died shortly after the chemotherapy start with median of 4 days (3-35 days) due to consecutive ARDS development. Predictive factors for CS development were metastatic lung involvement ≥50% of lung parenchyma, choriocarcinoma elements in histology specimen, dyspnea, cough, hemoptysis, ECOG PS ≥2, weight loss and hemoglobin ≤100 g/l at the time of presentation. In multivariate analysis, ECOG PS ≥2 and metastatic lung involvement ≥50% were independently associated with CS. All patients with these two characteristics developed CS compared to 0% with one or zero of these predictive factors (P < 0.000001). Conclusions: In our study we identified predictive factors for CS development. These factors might improve the risk stratification of the patients susceptible to CS development connected with ARDS as well as to find optimal treatment approach for them.

e18724 Background: Active immunization seems to be the most effective protection against COVID-19. The objective of this prospective study was to explore the side effects of mRNA vaccine Tozinameran and possible differences in their incidence between different categories of employees at the National Cancer Institute in Bratislava, Slovakia (NCI). Methods: Four hundred and thirteen subjects (89 men) were enrolled into this ongoing prospective study in January, 2021. Median age was 47 years (range 19-79 years). Majority were healthcare professionals (N=306), including nurses (N=125), medical-technical workers (N=89), and physicians (N=42). Presence of side effects was entered by the physicians into electronic data files and their accuracy validated for each subject by an independent investigator. Number of adverse events in the subgroups were compared with log-rank test. Results: At median follow up of 4 weeks, injection site pain (63.0%), pain in the extremity (45.5%), and fatigue (28,6%) belonged among the most common adverse events of Tozinameran. Median number of side effects was 2 (range 0-13). Adverse event incidence was significantly higher in females compare to males (median number 2 vs. 1, P < 0.00001). In a subgroup of healthcare professionals, we found a significantly higher incidence of side effects compared to non-healthcare workers (median number 2 vs. 1, P = 0.00017). Conclusions: In this study, incidence of Tozinameran adverse events was significantly higher in females vs. males and healthcare professionals vs. non-healthcare workers. All side effects were mild and no new safety signals were recognized during follow-up. Key Words: Tozinameran, Active Immunization. COVID-19. Healthcare Professionals. Adverse Events. This study was supported by National Cancer Institute in Bratislava (SK) and OncoReSearch (SK).

// Zuzana Sestakova 1, * , Katarina Kalavska 1, 2, * , Lenka Hurbanova 1 , Dana Jurkovicova 1 , Jan Gursky 1 , Michal Chovanec 3, 4 , Daniela Svetlovska 2 , Vera Miskovska 5 , Jana Obertova 3, 4 , Patrik Palacka 3, 4 , Katarina Rejlekova 3, 4 , Zuzana Sycova-Mila 4 , Silvia Cingelova 4 , Stanislav Spanik 5, 6 , Jozef Mardiak 3, 4 , Miroslav Chovanec 1, # , Michal Mego 2, 3, 4, # 1 Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia 2 Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia 3 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia 4 Department of Oncology, National Cancer Institute, Bratislava, Slovakia 5 1st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia 6 Department of Oncology, St. Elizabeth Cancer Institute, Bratislava, Slovakia * K-K and Z-S share the first authorship # M-CH and M-M share the last authorship Correspondence to: Miroslav Chovanec, email: miroslav.chovanec@savba.sk Michal Mego, email: misomego@gmail.com Keywords: DNA damage, DNA repair, cisplatin, germ cell tumors, prognostic marker Received: July 04, 2016 Accepted: September 29, 2016 Published: October 07, 2016 ABSTRACT Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naive GCT patients. PBLs isolated from 59 chemotherapy-naive GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software. The mean ± SEM (standard error of the mean) of endogenous DNA damage level was 5.25 ± 0.64. Patients with DNA damage levels lower than mean had significantly better progression free survival (hazard ratio [HR] = 0.19, 95% CI (0.04 – 0.96), P = 0.01) and overall survival (HR = 0.00, 95% CI (0.00 – 0.0), P < 0.001) compared to patients with DNA damage levels higher than mean. Moreover, there was significant correlation between the DNA damage level and presence of mediastinal lymph nodes metastases, IGCCCG (International Germ Cell Cancer Collaborative Group) risk group, and serum tumor markers level. These data suggest that DNA damage levels in PBLs of GCT patients may serve as an important prognostic marker early identifying patients with poor outcome.

Germ cell tumour (GCT) patients who fail to respond to chemotherapy or who relapse have a poor prognosis. Timely and accurately stratifying such patients could optimise their therapy. We identified endogenous DNA damage levels as a prognostic marker for progression-free (PFS) and overall (OS) survival in chemotherapy-naïve GCT patients. In the present study, we have extended our previous results and reviewed the prognostic power of DNA damage level in GCTs. Endogenous DNA damage levels were measured with the comet assay. Receiver operator characteristic analysis was applied to determine the optimal cut-off value and to evaluate its prognostic accuracy. PFS and OS were estimated by the Kaplan-Meier method and compared using the log-rank test. Hazard ratio (HR) estimates were calculated by Cox regression analysis. A cut-off value of 6.34 provided the highest sensitivity and specificity, with area under curve values of 0.813 and 0.814 for disease progression and mortality, respectively. A % DNA in tail6.34 was significantly associated with shorter PFS (HR = 9.54, 95 % confidence interval [CI]: 3.43-26.55, p 0.001) and OS (HR = 14.62, 95 % CI: 3.14-67.95, p = 0.001) by univariate analysis. The prognostic value of DNA damage measurement was confirmed by multivariate models (HR = 6.45, 95 % CI: 2.22-18.75, p = 0.001 for PFS and HR = 9.40, 95 % CI: 1.70-52.09, p = 0.010 for OS), when HR was adjusted for relevant clinical categories. The added prognostic value of DNA damage in combination with International Germ Cell Cancer Collaborative Group (IGCCCG) risk groups has been revealed. Endogenous DNA damage is an independent prognosticator for PFS and OS in GCT patients and its clinical use, particularly in combination with IGCCCG risk groups, may help in stratifying these patients.