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Background: Gaucher disease is a common lysosomal storage disease caused by the deficiency of the β-glucosidase enzyme, leading to sphingolipid accumulation in the reticuloendothelial system in Gaucher cells. Clinical findings are quite variable and some patients may remain asymptomatic lifelong. However, even when patients have mild symptoms, there is a significant increase in their quality of life with enzyme replacement therapy. We aimed to reveal the relationship between a rare mutation in the Glucosylceramidase Beta (GBA) gene and clinical signs and symptoms. Another aim of the study was to show the effect of enzyme replacement therapy on the quality of life, even in patients with mild symptoms. Case presentation: Here, we report a 46-year-old male diagnosed with Gaucher disease based on splenic Gaucheromas incidentally discovered in a cardiac computerized tomography scan. In GBA gene analysis, the extremely rare R87W mutation was detected in a homozygous state. In retrospect, the patient had nonspecific symptoms such as fatigue and bone pain for a long time, which were substantially ameliorated by enzyme replacement therapy. Conclusion: In patients with adult-onset Gaucher disease, the symptoms may be mild, causing significant diagnostic delay. Gaucher disease may be included in the differential diagnosis of abdominal malignancies. Early diagnosis and treatment can improve quality of life and prevent unnecessary procedures.

Aim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status. WOS:000685162800001 34397271 Q3

Purpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02–67.63) years, and the median follow-up was 12.26 (IQR 5.6–24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. 5 (p: 0.007).

OBJECTIVE: The albumin to globulin ratio (AGR) has been demonstrated to be associated with survival outcomes in various tumor types. However, the prognostic value of AGR in patients with metastatic renal carcinoma (mRCC) remains unclear. Therefore, this study aimed to investigate the impact of AGR values in predicting overall survival (OS) of patients with mRCC treated with targeted therapy. MATERIAL AND METHODS: A total of 163 patients with mRCC treated with targeted therapy between 2008 and 2019 were enrolled. The AGR value was measured as AGR: albumin/(total protein–albumin). The Kaplan-Meier method with long-rank testing and Cox proportional hazard models were used to estimate the correlation of AGR with OS. RESULTS: The receiver operating characteristic curve analysis showed that the optimal cut-off value of AGR in predicting OS was 1.11 with a sensitivity of 37.25% and specificity of 85.25% (area under curve, 0.62; 95% confidence interval [CI], 0.54–0.69; p=0.005). OS was significantly higher in patients with AGR>1.11 than in those with AGR≤1.11 (36.2 vs. 12.4 months; p

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil–lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (

BACKGROUND/AIM: Lycopene has been shown to be associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells. MATERIALS AND METHODS: HeLa cells were treated with cisplatin (1 µM) alone, lycopene (10 µM ) alone, and in combination for 72 hours. The cell viability of HeLa cells was assessed via MTS Assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-?B), B-cell associated X protein (Bax), nuclear factor erythroid 2-related factor (Nrf2), and B-cell lymphoma 2 (Bcl-2). RESULTS: We have found that lycopene acts as a synergistic agent with cisplatin in preventing the growth of HeLa cells. The rates of HeLa cells? viability were 65.6% and 71.1% with lycopene and cisplatin treatment alone compared to the control group, respectively (P < 0.001). The inhibitory effect of cisplatin was enhanced with lycopene addition by declining the cell viability to 37.4% (P < 0.0001). Lycopene treatment significantly increased Bax expression (P < 0.0001) and decreased Bcl-2 expression (P < 0.0001) in HeLa cells. Furthermore, lycopene markedly activated the Nrf2 expression (P < 0.001) and suppressed the NF-?B signaling pathway (P < 0.0001). CONCLUSION: Lycopene increases the sensitization of cervical cancer cells to cisplatin via inhibition of cell viability, up-regulation of Bax expression, and down-regulation of Bcl-2 expression. Furthermore, anticancer effect of lycopene might be also associated with suppression of NF-?B-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and the concurrent cisplatin chemotherapy might have a role to improve the treatment of cervical cancer.

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. Some of the patients in this group, which is considered to have hyperprogressive disease (HPD), have a shorter overall survival compared to progressive disease (PD). Therefore, biomarkers are needed to differentiate between HPD and PD. Here, we evaluated PILE score to differentiate HPD from PD in patients treated with ICI. Methods Ninety-five patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any type of cancer with progression according to RECIST criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system was calculated, including PIV (< median vs. ≥ median), LDH (normal and > normal), and ECOG performance status (0 vs. ≥ 1). The relationship between PILE score and HPD was examined. Results The median follow-up was 6.6 months and the median OS of all cohort were 11.18 ± 1.36 months. The patients in the HPD group had decreased OS (4.77 ± 0.89 vs. 13.94 ± 1.80 months, p

BACKGROUND: Thrombospondin type 1 domain-containing 7A (THSD7A) has emerged as a new potential molecular tool for multiple tumors since that THSD7A was detected to be expressed in various malignant tumor types including colorectal cancer (CRC). Thus, we investigated the correlation between THSD7A expression and pathologic determinants of azoxymethane (AOM)-induced CRC in a rat model. METHODS: : A total of 30 rats were included in the study (experimental group; n = 15, control group; n = 15). Azoxymethane was administered to the experimental group weekly as subcutaneous injections at a dose of 15 mg/kg bodyweight for 3 weeks. Five months later, 42 tumors were obtained in the study group and histopathologic evaluation of CRC tumors for THSD7A was performed by immunohistochemical staining. Thrombospondin type 1 domain-containing 7A expression was classified according to staining levels. RESULTS: While 28.6% of the colonic tumors were stained as negative, mild-moderate and strong staining was determined in 61.9% and 9.5% of the tumors, respectively. Thrombospondin type 1 domain-containing 7A expression levels inversely correlated with Ki-67 expression (P < .001) and tumor grade (P =.02). Receiver operating characteristic analysis showed Ki-67 staining ≥20.5% was determined as a cut-off value for negatively stained THSD7A tumors with 91% sensitivity and 69% specificity (P = .001, area under curve: 0.822). Moreover, higher Ki-67 expression was found to be associated with higher tumor grade (P < .001), presence of lymphatic invasion (P = .003), and higher T stage (P = .003). CONCLUSION: Negative staining for THSD7A seems to be linked to invasive pathologic determinants in AOM-induced CRC in rats.

The objective of the present study was to compare the efficacy of axitinib and nivolumab in metastatic renal cell carcinoma (mRCC) previously treated with targeted therapy.A total of 79 patients were enrolled (39 patients in axitinib group, 40 patients in nivolumab group). Survival outcomes of patients, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test. The associations between potential prognostic variables and OS were evaluated in univariate and multivariate Cox regression analyses.The median PFS and OS of all cohort were 8.1 and 36.6 months, respectively. Higher PFS and OS were evaluated in axitinib group than nivolumab group (PFS: 9.4 months vs 6.3 months, p=0.386; OS: 38.2 months vs 36.6 months, p=0.671, respectively). Patients treated with axitinib had numerically higher objective response rate (ORR) and disease control rate (DCR) than those treated with nivolumab (ORR: 43.6% vs 27.6%, p=0.157, DCR: 74.4% vs 62.5%, p=0.157, respectively). Multivariate analysis revealed that the independent predictors of OS were higher tumor grade (hazard ratio [HR]: 6.178, p=0.004), worse response to axitinib and nivolumab (HR:4.902, p=0.011), the presence of lung metastasis (HR:15.637, p=0.002) and the presence of liver metastasis (HR:12.010, p=0.001).Comparable survival outcomes were detected in the axitinib and nivolumab groups. However, head to head comparisons are needed to highlight the relative efficacy of these therapies in mRCC.

Purpose With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to determine the factors that would predict HPD. Methods A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results The median age was 62.28 (interquartile range (IQR) 54.02-67.63) years, and the median follow-up was 12.26 (IQR 5.6-24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were most common diagnoses. Twenty patients (16.5%) had a HPD. High LDH level (p:0.001), hypoalbuminemia (p:0.016), NLR>5 (p:0.007) and NSCLC diagnosis (0.026) are at high risk for HPD. Sex (female vs. male, p:0.114), age (>65 vs 45 vs 5 (p:0.007) and NSCLC diagnosis (0.026).

Introduction It was previously demonstrated that seasonal influenza incidence was significantly decreased during the COVID-19 pandemic, possibly due to respiratory and hygiene precautions. From this point, we hypothesized that the COVID-19 precautions could lead to a decrease in nosocomial infection rates in oncology inpatient wards. Methods We evaluated the nosocomial infection rates in an inpatient palliative oncology ward in the first 3 months of the COVID-19 pandemic in our country and compared this rate with the same time frame of the previous year in our institution. Results The percentage of nosocomial infections complicating the hospitalization episodes were significantly reduced in the first 3 months of the pandemic compared to the previous year (43 vs. 55 nosocomial infection episodes; 18.6% vs. 32.2%, p = 0.002). The decrease in the nosocomial infections was consistent in the different types of infections, namely pneumonia (4.8% vs. 7.6%), urinary tract infection (5.2% vs. 7.6%), bacteremia (5.2% vs. 7%) and intraabdominal infections (2.6% vs. 3.5%). The median monthly disinfectant use was significantly increased to 98 liters (interquartile range: 82 – 114) in 2020 compared to 72 L (interquartile range: 36 – 72) in 2019 ( p = 0.046). Conclusion The continuation of the simple and feasible hygiene and distancing measures for healthcare workers and patient relatives and adaptations for earlier discharge could be beneficial for preventing nosocomial infections in oncology wards. These measures could be implemented routinely even after the COVID-19 pandemic for patient safety, especially in settings with higher nosocomial infection rates like inpatients palliative care units.

Background The association of thrombospondin type 1 domain-containing 7A (THSD7A) expression, a novel angiogenesis-related marker, with survival outcomes of tumors including renal cell carcinoma (RCC) remains to be clarified. Therefore, we investigated the impact of THSD7A on outcomes of metastatic RCC (mRCC) patients treated with targeted therapy. Methods A total of 86 mRCC patients were included. The expression of THSD7A in nephrectomy material of the patients was assessed by immunohistochemistry and expression patterns were categorized into two groups: negative (no staining) and positive. Univariable and multivariable Cox regression models evaluated the impact of THSD7A expression on progression free survival (PFS) and overall survival (OS) of the patients. Results THSD7A expression was determined in 77.9% of the patients. Kaplan-Meier analyses showed that while the patients with THSD7A expression had significantly inferior OS times than those with negative THSD7A expression (19.9 months vs. 52.2 months, P = 0.024, respectively), there was no association between THSD7A expression and PFS. The univariate analyses demonstrated that the significant variables in predicting OS were presence of bone metastasis (P = 0.030), THSD7A expression (P = 0.028), and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (P < 0.001). However, applying multivariate analyses, the independent variables in predicting OS were THSD7A expression (HR: 2.639, P = 0.037) and IMDC scoring system (P < 0.001). Conclusion We revealed that THSD7A expression was associated with OS of mRCC patients treated with targeted therapy. There might be an important link between THSD7A expression and resistance to targeted therapy.

In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

Background: To explore the clinical significance of baseline volumetric body composition parameters evaluated with computerized tomography (CT) and their changes after 3-4 months from treatment initiation of targeted therapy in patients with metastatic renal cell carcinoma (mRCC). Method: This study included 108 Caucasian mRCC patients (Male/Female: 77/31) treated with targeted therapy. Volumetric body composition parameters including total adipose tissue index (TATI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and skeletal muscle index (SMI) values were depicted from CT images at third lumbar vertebra level through volumetric measurement software. Kaplan-Meier method and the long test were used for estimation of progression free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were done to determine the associations between clinic-pathologic variables including VBC and survival outcomes. Results: The median PFS and OS of all patients were 11 months and 46 months in patients respectively. After adjustment for the variables including international mRCC database consortium (IMDC) risk score, only a high skeletal muscle index (SMI) was associated with better PFS (HR: 0.975, P=0.015). The independent predictors for OS were VATI (HR 1.005, P=0.024), SATI (HR: 0.976, P=0.019) and TATI (HR: 0.982, P=0.035) in addition to IMDC risk score. Conclusion: Our findings revealed that while SMI was the only significant determinant parameter for PFS among VBC parameters, TATI, VATI, and SATI were determined as independent predictors for OS in addition to IMDC risk score.

Introduction Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. Methods A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. Results The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). Conclusion In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Pancreatic cancer is a deadly disease with limited therapeutic options. Several strategies are being investigated to improve disease management, including the early diagnosis of recurrences and treatment tailoring by better prognosis estimation. Circulating tumor DNA (ctDNA) could be a promising tool in this regard, although the data is limited. Therefore, we conducted a systemical review and meta-analysis of the published studies on the association of ctDNA and survival outcomes in pancreatic cancer. In the pooled analysis, positive preoperative or postoperative ctDNA was associated with lower RFS/PFS (HR: 2.27, 95 % CI: 1.59-3.24, p0.001) and OS (HR: 2.04, 95 % CI: 1.29-3.21, p = 0.002) in localized pancreatic cancer. Similarly, positive baseline ctDNA was associated with lower RFS/PFS (HR: 2.61, 95 % CI: 1.94-3.51, p0.001) and OS (HR: 2.41, 95 % CI: 1.74-3.34, p0.001) in advanced pancreatic cancer. In conclusion, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in pancreatic cancer.

We aimed to investigate the prognostic value of red cell distribution width (RDW) in metastatic renal cell carcinoma (mRCC) patients treated with targeted therapy, including sunitinib and pazopanib.A total of 104 mRCC patients were included. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), and the long-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the association between RDW and PFS and OS.The PFS and OS of all cohorts were 11.8 mo and 25.9 mo, respectively. Receiver operating characteristic analysis revealed that RDW level ≥15.4 was the optimal cutoff value for OS prediction with 73.53% sensitivity and 61.11% specificity (area under curve: 0.64,Our study revealed that high RDW level, a routinely and easily assessed marker, was significantly associated with worse survival outcomes in mRCC patients treated with targeted therapy.

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors. A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. The median age was 60 (interquartile range (IQR) 48–66) years, and the median follow-up was 10.1 (IQR 5.8–18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011–9.039, p=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk. In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.

BACKGROUND/AIM We aimed to evaluate the efficacy of fulvestrant and affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05+/-0.56 and 29.70+/-1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766

Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients.A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV ( median vs. ≥ median), lactate dehydrogenase levels (normal vs. normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis.The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2-3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450-3.700, p 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263-2.954, p = 0.002) compared to PILE low-risk group (PILE score 0-1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively.In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy.

Unplanned readmission in the first 30 days after discharge is an important medical problem, although the data on cancer patients is limited. So we planned to evaluate the rates and causes of early readmissions and the predisposing factors. Patients hospitalized in Hacettepe University Oncology services between August 2018 and July 2019 were included. The demographic features, tumor stages, regular drugs, last laboratory parameters before discharge, and readmissions in the first 30 days after discharge were recorded. The predisposing features were evaluated with univariate and multivariate analyses. A total of 562 hospitalizations were included. The mean age of the patients was 58.5 ± 14.5 years. Almost 2/3 of the hospitalizations were due to symptom palliation and infections. Eighty-three percent of the patients had advanced disease, and over 60% had an ECOG score of 2 and above. In the first 30 days after discharge, 127 patients were readmitted (22.6%). Advanced stage disease, presence of polypharmacy (5 or more regular drugs), hospitalization setting (emergency department (ED) vs. outpatient clinic), and hypoalbuminemia (< 3 gr/dL) were associated with a statistically significant increase in the risk of readmission. Among these factors, advanced-stage disease (HR: 2.847, 95% CI: 1.375–5.895), hospitalization from ED (HR: 1.832, 95% CI: 1.208–2.777), and polypharmacy (HR: 1.782, 95% CI: 1.173–2.706) remained significant in multivariate analyses. In this study, 22% of cancer patients had early readmissions. The readmission risk increased in patients with advanced disease, hospitalization from ED, and polypharmacy. The optimal post-discharge plan may reduce readmissions in all oncology patients, with priority for these patient groups.

Background/aim The prognostic values of systemic inflammatory markers, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) on overall survival (OS) of metastatic renal cell carcinoma patients (mRCC) treated with tyrosine kinase inhibitors (TKI) remain unclear. Thus, the present study aimed to investigate the prognostic impact of these markers on OS of mRCC patients. Materials and methods A total of 150 patients receiving TKIs were retrospectively analyzed. Progression-free survival and OS times were analyzed with the Kaplan–Meier method, and the log‐rank test was used for comparison. Univariable and multivariable Cox regression models evaluated the impact of NLR and PLR on OS of the patients. The receiver operating characteristic curve analysis determined that the optimal cut-off values of NL, and PLR in predicting OS were 2 and 204, respectively. Results Patient with PLR > 204 had significantly lower median OS time than those with PLR ≤ 204 (14.6 months vs. 31.6 months, P < 0.001). While the univariate analyses showed that both NLR and PLR associated with OS (NLR: P = 0.002; PLR: P < 0.001), PLR, not NLR, was an independent determinant for OS in the multivariate analyses (Hazard Ratio: 2.535, 95% CI: 1.564-4.108, P < 0.001). Additionally, the presence of brain metastases and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic scoring system were identified as independent prognostic factors for OS (brain metastases: P = 0.040; IMDC: P < 0.001). Conclusion The PLR is a readily and inexpensively obtained marker, which may predict OS in patients with mRCC treated with TKIs.

Coronavirus disease 2019 (COVID-19) is expected to significantly affect cancer patients due to adverse outcomes with COVID-19 and disruptions in cancer care. Another important point is the stress and anxiety burden of COVID-19, which could affect quality of life. Patient education is vital due to the vulnerability of the topic to disinformation. To determine the areas needing improvements in patient education, and coping with stress, the burden of the problem should be pictured. From this point, we aimed to assess the perspectives and fears of cancer patients about COVID-19 with resources of COVID-19 knowledge with a questionnaire. A total of 250 adult cancer patients applied to the outpatient chemotherapy unit of Hacettepe University Cancer Center between May 27, 2020, and June 9, 2020, invited to answer a questionnaire of 13 multiple-choice questions with a return rate of 78% (195/250). Most patients acquired their knowledge about COVID-19 from television (91.9%). Social media were the second most common source of knowledge (43.8%) with a predilection in younger patients, nonsmokers, targeted therapy- or immunotherapy-treated patients, and breast cancer patients (>65 vs.

The emergency department (ED) is a crucial encounter point in cancer care. Yet, data on the causes of ED visits are limited in patients treated with immune checkpoint inhibitors (ICI). Therefore, we evaluated ED visits in patients treated with ICIs in attempt to determine the predisposing factors. We performed a retrospective chart review on adult cancer patients treated with ICIs for any type of cancer in the Hacettepe University Cancer Center. The data on ED visits after the first dose of ICIs to 6 months after the last cycle of ICIs were collected. A total of 221 patients were included in the study. The mean age was 58.46 ± 13.87 years, and 65.6% of patients were males. Melanoma was the most common diagnosis (27.6%), followed by kidney and lung cancers. Eighty-three of these patients (37.6%) had at least one emergency department (ED) visit. Most of the ED visits were related to symptoms attributable to the disease burden itself, while immune-related adverse events comprised less than 10% of these visits. While baseline Eastern Cooperative Oncology Group performance status, age, polypharmacy, concomitant chemotherapy, eosinophilia, and lactate dehydrogenase levels did not significantly increase the risk, patients with regular opioid use and baseline neutrophilia (> 8000/mm3) had a statistically significant increased risk of visiting the ED (p = 0.001 and 0.19, respectively). These two factors remained significant in the multivariate analyses. In this study, almost 40% of ICI-treated patients had ED visits. Collaboration with other specialties like emergency medicine is vital for improving the care of patients receiving immunotherapy.

The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

BackgroundWe compared the new outpatient clinic referrals during the first 10 months of the COVID-19 pandemic with the year before.MethodsWe compared baseline characteristics of the 2208 new referrals in 2020 (n=922) and 2019 (n=1286) with Χ2 and Mann-Whitney U tests and calculated ORs with binary logistic regression. To evaluate the expected changes in the cancer survival secondary to stage migration, we used the 5-year survival data of Survival, Epidemiology and End Results (SEER) Program 2010–2016.ResultsThe percentage of patients with inoperable or metastatic disease was significantly increased during the pandemic (49.8% vs 39%, OR: 1.553, 95% CI: 1.309 to 1.843, pConclusionWe think that collaborative efforts are paramount to prevent the pandemic of late cancer diagnoses and ensure patient safety during the pandemic.

Patients with advanced or metastatic castration-resistant prostate cancer have a dismal prognosis and are therefore in urgent need for therapeutic innovations. Spleen tyrosine kinase has emerged as a new molecular target for castration-resistant prostate cancer. This study was done to test the cytotoxicity of the lead nanoformulation of a potent spleen tyrosine kinase inhibitor, C61-LNP, against the human prostatic carcinoma cell line, PC-3. PC-3 cells were treated with various concentrations of C61-LNP either alone or in combination with cisplatin (CDDP) for 24, 48 and 72 hours. The cell viability was evaluated by MTS assay. Cellular expression levels of various regulatory proteins in treated PC-3 cells were evaluated by Western blot analyses. C61-LNP exhibited dose-dependent cytotoxicity against PC-3 cells. C61-LNP, as well as C61-LNP + CDDP treatments, caused pro-apoptotic proteomic changes including an increase in cleaved fragments of caspases-3 and -9 consistent with caspase activation as well as an improvement in the anti-apoptotic Bcl2 and Bax levels. The combination of C61-LNP and CDDP changed in alterations of the cell cycle regulatory proteins p53, p21, p27, cyclin D1 and cyclin E levels. C61-LNP exhibited cytotoxicity against the castration-resistant prostate cancer cell line PC3. It also caused alterations in expression levels of regulatory proteins involved in apoptosis and cell cycle regulation and these effects were not abrogated by the standard chemotherapy drug CDDP. We are planning to further develop C61-LNP as a selective spleen tyrosine kinase inhibitor as part of a multi-modality treatment strategy for advanced/metastatic castration-resistant prostate cancer.

Introduction Immune checkpoint inhibitors and angiogenesis inhibitors are novel treatment options for renal cell carcinoma and widely used in clinical practice. They are related with adverse events that occur as a consequence of immune system activation and inhibition of angiogenesis. Herein, we report a rare case of inflammatory arthritis seen in a patient treated with an anti Programmed cell death-1 pembrolizumab and an anti-vascular endothelial growth factor pazopanib. Case report A 60-year-old Caucasian male presented to our clinic with inflammatory arthritis with pitting edema. He had been started on pembrolizumab therapy for metastatic renal cell carcinoma after enrolling in the KEYNOTE-679 study. After six cycles of treatment with pembrolizumab, metastasis had been determined in the lung. Then, the patient’s therapy was changed to pazopanib. While the patient was on pazopanib treatment, he noticed a gradual swelling of both hands. Rheumatoid factor, anti-nuclear antibody and anti-cyclic citrullinated peptide were negative. Joint ultrasonography revealed acute tenosynovitis and soft tissue swelling with pitting edema, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. Management and outcome: He was started on 10 mg prednisolone daily. His symptoms dramatically responded to corticosteroid. He continued to take pazopanib. Then, the patient was discharged with 10 mg prednisolone daily. Discussion Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with pitting edema can be among the rare rheumatic immune-related adverse events that clinicians may encounter as the immune check point inhibitors and anti-VEGF use increases. Corticosteroid therapy can relieve symptoms and cessation of therapy may not be necessary.

Background: In the new era the COVID-19 disease became a world-wide pandemic in a short time, medical practice is predicted to be affected due to the both physician and patient tendencies, and usage of limited diagnosis and treatment opportunities for the outbreak In this study we investigated the characteristics of the patients who received chemotherapy (CT) or supportive treatments at the Hacettepe University Oncology Hospital Daily Treatment Unit in the first 60 days after the first case was detected in Turkey Methods: Patients recieved any CT or any kind of supportive treatment between 11th March 2020-10th May 2020 and 11th March 2019-10th May 2019 were included to the study Demographic properties and diagnoses of the patients, number of protocols and sessions applied, and non-chemotherapy treatments were investigated retrospectively Results: Between 11 th March 2020 and 10th May 2020 the average daily chemotherapy (CT) sessions apllied decreased by 7% compared to the same period of the previous year Patients receiving treatment for the first time decreased by 50% in the COVID period comparing to the last year and decreased from 146 to 73 (p=0 03) (Table) Supportive hydration treatments applied to an average of 8 3 patients daily decreased by 55% to an average of 3 8 per day In the 2019 a total of 137 transfusions were performed while in the period of COVID-19, the number of transfusions decreased by 29% to 98 [Formula presented] Conclusions: A minimal change was observed in the total number of chemotherapy applied during the pandemic period It is imperative that treatment units continue to work because most of the treatments in oncology practice is not postponable Decrease in patients who received treatment for the first time is a parameter that should be followed closely Hesitation of the patients having symptoms to consult a doctor or prolong the diagnosis period may prevent the diagnosis of curable disease on time Similarly, delay in patients' access to supportive treatments, may lead to an increase morbidity and mortality Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Aim: Hypocalcemia is a common clinical problem in critically-ill patients and it is associated with increased morbidity and mortality. The aim of this study was to investigate serum calcium, vitamin D and parathyroid hormone (PTH) levels in surviving and non-surviving septic shock patients Method: Patients with septic shock criteria and who were older than 18 years of age were included, whereas patients with diseases influencing calcium homeostasis were excluded. Demographic and laboratory parameters were recorded prospectively. Results: 41 patients, 20 of which were male were included in the study. The median (min-max) age of study population was 67 (19-88) years. Frequency of hypocalcemia in the study population was 29.2% and 68.2% according to corrected calcium and ionized calcium, respectively. On the day septic shock was diagnosed (day 1), median vitamin D levels of survivors and non-survivors were 8.7 ng/ml (4.3-30.4) and 5.3 ng/ml (1.0-21.7), respectively (p=0.05). On the same day, median PTH levels of survivors and non-survivors were 94 ng/L (16.9-1746) and 49 ng/L (6.6-339), respectively (p=0.042). Although vitamin D levels were suppressed and PTH levels were elevated in non-survivors at day 5, this change was not statistically significant (p=0.19 and p=0.187). Conclusion: Hypocalcemia is frequent in septic shock patients, whereas vitamin D levels were low and PTH levels were high in the diagnosis day. These results suggest that vitamin D is suppressed by septic shock at non-surviving patients during course of septic shock. Parathyroid hormone may be a marker for worse outcome in critically ill patients.

Background Outpatient palliative care (OPC) offers improved symptom control, quality of life and even survival. OPC clinics may be embedded in the oncology clinic or independent. We herein present our experience with an embedded OPC clinic led by a medical oncologist, an internist and a nurse in Hacettepe University Medical Oncology Clinic. Methods Patients who were referred by their oncologist or those who had severe symptoms and applied without referral were admitted. Besides baseline history and physical exam, Edmonton Symptom Assesment Scale (ESAS), Nutritional risk screening 2002 and visual analog scale for pain were routinely assessed except for patients with acute symptoms requiring urgent intervention. Interventions and consultations were recorded for all patients. Results A total of 174 patients were seen in our clinic within the first 5 months. Demographic features are shown in the table. The chief complaints were pain (26%), nausea and vomiting (13%) and decreased feeding (9%). Besides their chief complaints, patients had a median of 4 (min 0- max 8) other severe (ESAS score of > 5) complaints. The most frequent interventions were intravenous hydration, analgesic and/or antiemetic administration and prescription (n = 66), nutritionist (n = 62) and pain specialist (n = 59) consultations. Thirty-three patients (19 %) were referred for immediate hospitalization. The overall mortality within the first 30 days after the first OPC visit was 17%. Table . 1615P Baseline characteristics of the applied patients Median Age (minimum- maximum) 60.5 (17-91) Male/Female 94 (58%)/80 (42%) Patient Stages Stage 1: 4 (2.3%) Stage 2: 7 (4%) Stage 3: 18 (10.3%) Stage 4: 157 (73.6%) ECOG Performance Status ECOG 0: 19 (10.9%) ECOG 1: 50 (28.7%) ECOG 2: 36 (20.7%) ECOG 3: 40 (23%) ECOG 4: 25 (14.4%) Tumor Sites Gastrointestinal: 53 (30.5%) Lung: 43 (24.7%) Genitourinary: 15 (8.6%) Breast: 14 (8%) Gynecologic: 11 (6.3%) Head and Neck Cancer: 9 (5.2%) Other: 29 (16.7%) Conclusions Our initial experience with the embedded OPC clinic mostly included patients with advanced disease, multiple severe symptoms and high risk of mortality. Management of these patients within the oncology clinic may address palliative care needs of these patients, provide timely therapeutic interventions, reduce unnecessary diagnostic tests and diminish emergency department applications by these patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Impaired DNA damage response (DDR) mechanisms and subsequent genomic instability is associated with carcinogenic process itself, but it also results in sensitivity of tumor cells to certain drugs and can be exploited to treat cancer by inducing deadly mutations or mitotic catastrophe. As a result, BRCA1/2 testing is recommended for a group individuals with breast/ovarian cancer. Methods In this study, we retrospectively invesitigated clinicopathologic features of 303 breast cancer patients tested for BRCA 1/2 mutation in an oncology institute. NCCN recommendations are used to select patients to be tested for BRCA mutations. Results A total of 303 patients were analysed for BRCA 1/2 mutations. Median age of the patients at diagnoses were 40 (21-65). Family history for BRCA related cancers were detected in 120 patients (39.6%). BRCA 1/2 mutations have been shown in 98 of 303 patients (32.3%). Of 98 BRCA mutated patients, 43 had pathogenic BRCA1 mutation, 39 had pathogenic BRCA2 mutation, 11 had variant of uncertain significance (VUS) BRCA2 mutation, 3 had VUS BRCA1 mutation and 2 had pathogenic BRCA1 and 2 mutations. Molecular subtypes of tumors have been shown in Table. Table . 316P Molecular subtypes of tumors BRCA Status HR(+)/ HER2(-), N(%) HR(+)/ HER2(+), N(%) HR(-)/ HER2(+), N (%) Triple(-), N (%) N/A,N(%) BRCA1 18 (41.8%) 2 (4.6%) 0 22 (51.1%) 1 (2.3%) BRCA2 25 (64.1%) 3 (7.7%) 0 6 (15.3%) 5 (12.8%) BRCA1 VUS 2 (66.7%) 0 0 1 (33.3%) 0 BRCA2 VUS 11 (100%) 0 0 0 0 BRCA1 + 2 0 1 (50%) 0 1 (50%) 0 BRCA mut (-) 126 (61.4%) 25 (12.1%) 12 (5.8%) 32 (15.6%) 10 (4.8%) TOTAL 182 (60%) 31 (10.2%) 12 (3.9%) 62 (20.4%) 16 (5.2%) Twelve of 98 BRCA mutated patients (12.2%) were de novo metastatic while 15 patients (15.3%) faced with metastatic disease during follow-up. In the BRCA mutated group there was significantly high rate of metastatic disease has been detected comparing BRCA non-mutated group (27.5% vs %16.5% respectively, p = 0.026). Metastatic BRCA mutant patients showed worse OS numerically but data is not statistically significant (P = 0.894). Nine patients were diagnosed with contralateral breast cancer, and 3 patients was diagnosed with BRCA-related cancers during follow-up. Prophylactic surgery (contralateral mastectomy and/or oophorectomy) was performed in 32 of 98 patients. Conclusions According to this retrospective study, BRCA mutant patients tend to have worse clinical and pathological features comparing age-matched controls. Legal entity responsible for the study Sercan Aksoy. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e22557 Background: Liposarcomas constitute 15% of all soft tissue sarcomas.They consist of four subtypes;well-differentiated,dedifferentiated,myxoid and pleomorphic.In this trial we assessed demographic and clinical features of patients with liposarcoma who were treated in our hospital.Methods: Patients who were diagnosed with liposarcoma in Hacettepe University Medical Oncology Department between 2005and2015(n = 119) were included. Patients’ data were collected from hospital registration system.Survival analyses were performed with Kaplan Meier analyses.Results: At the time of diagnosis, the vast majority of patients had localized and/or node positive disease(n = 98),8 patients had metastatic disease.Further analyses hold for only early stage disease:Median age was 52(min:18-max:81).105 patients(94.6%) had upfront surgery.26(23.4%) and 30 patients(27%) received perioperative chemotherapy(CT) and radiotherapy(RT),respectively.The most commonly used CT agents were ifosfamide, anthracyclines, etoposide,taxanes and gemcitabine.At a median follow-up of 45months, relapses were observed in 34 patients(30.6%) and 35 patients(31.5%) died.Median overall survival(OS) was 113.1 months and median relapse free survival (RFS) was 23.8 months.Perioperative CT and RT were not associated with improved RFS and OS.Among patients with early stage disease; median RFS of patients with well-differentiated, dedifferentiated, myxoid and pleomorphic subtypes were 31.8,34.3,28 and 5.2months,respectively(p = 0.013).Well-differentiated group had significantly higher RFS than those with pleomorphic liposarcomas(p = 0.003).The mostly used CT drugs in recurrent setting were ifosfamide+doxorubicine(42.9%) and ifosfamide+etoposide(21.4%).Conclusions: Liposarcoma prognosis varies significantly with histological subtype and the efficacy of systemic chemotherapy is limited both in early stage and advanced disease.[Table: see text]