Sonographic Measurements of Rectus Femoris Muscle Thickness Strongly Predict Neutropenia in Cancer Patients Receiving Chemotherapy.

The objective of this study was to explore the possible association between low skeletal muscle mass (SMM)-assessed by computed tomography (CT) and ultrasound (US)-and hematologic toxicity in cancer patients. A prospective cohort study was conducted in cancer patients who received anthracycline-based chemotherapy between 2018 and 2020 and who had baseline abdominal CT including L3 level for measuring SMM. Regional muscle measurements were carried out using US. A total of 65 patients (14 males, 51 females) were included. ROC (receiver operating characteristic) analysis identified threshold values of 18.0 mm [AUC (area under the curve) = 0.765] for females and 20.0 mm (AUC = 0.813) for males, predicting severe neutropenia. Using these cut-offs, females with low rectus femoris (RF) thickness (<18.0 mm) had a significantly higher incidence of grade ≥3 neutropenia (50.0% vs. 10.8%, p = 0.005), and males with low RF values (<20.0 mm) had a higher incidence (80.0% vs. 22.2%, p = 0.063). A regression analysis, irrespective of age, gender, and body mass index, revealed that only low RF muscle thickness increased the risk of grade 3-4 neutropenia by 9.210 times (95% CI = 2.401-35.326, p = 0.001). Utilizing US to measure RF muscle thickness aids in identifying cancer patients at an elevated risk of developing neutropenia. Needless to say, US can serve as a convenient and easily accessible tool for assessing low SMM, providing repeat point-of-care evaluations in clinical practice.

Splenic Gaucheroma Leading to Incidental Diagnosis of Gaucher Disease in a 46-Year-Old Man with a Rare GBA Mutation: A Case Report.

BACKGROUND: Gaucher disease is a common lysosomal storage disease caused by the deficiency of the ß-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.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND: We aimed to evaluate the efficacy of fulvestrant and its 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, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p = 0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p = 0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p = 0.340), disease control rate (p = 0.076), and OS (p = 0.289) and PFS (p = 0.276) were similar to overall cohort. DISCUSSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Blood Based Biomarkers as Predictive Factors for Hyperprogressive Disease.

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. <65, p: 0.772), ECOG (0 vs. 1−4, p: 0.480) and the line of treatment (1−5, p: 0.112) were not found to be associated with hyperprogression. Conclusions: In this study, we observed HPD in 16.5% of immunotherapy-treated patients and increased HPD risk in patients with a high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007).

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy.

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 (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

Everolimus and/or Nivolumab-Associated Cytomegalovirus Colitis in a Patient with Metastatic Renal Cell Carcinoma.

Everolimus-associated cytomegalovirus colitis is very rare in cancer patients. We present a case of cytomegalovirus colitis that occurred on using everolimus in a 64-year-old male with metastatic renal cell carcinoma who received pazopanib, nivolumab, and everolimus treatments, respectively. Although an increasing number of nivolumab-related cytomegalovirus colitis cases are reported recently, its mechanism of development is still unknown. Our study highlights that clinicians should remember cytomegalovirus reactivation in the presence of diarrhea or colitis in patients receiving everolimus and/or nivolumab. Further studies are needed to elucidate the relationship between immune checkpoint inhibitors and cytomegalovirus reactivation, and these will also be a guide to prevent other possible viral infections.

THSD7A expression: a novel immunohistochemical determinant in predicting overall survival of metastatic renal cell carcinoma treated with targeted therapy.

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.

Prognosis of Liposarcoma Patients in Modern ERA: Single-Center Experience.

Objective Liposarcomas are relatively rare tumors. Prognostic and predictive factors and treatment options are limited. We herein presented our 10-year experience with liposarcomas. Materials and Methods Adult patients with liposarcoma treated between 2005 and 2015 in our center were included. Demographic and clinicopathologic features of patients were retrieved from patient files. Statistical Analyses Outcomes in terms of disease-free survival (DFS) and overall survival (OS) were assessed along with potential prognostic factors using Kaplan-Meier analyses. Results A total of 88 patients were included. The median age was 52. Rates of well-differentiated (WDLS), dedifferentiated (DDLS), myxoid (MLS), and pleomorphic liposarcomas (PLS) were 42, 9.1, 37.5, and 4.5%, respectively. Only 10% of patients had high-grade tumors and 93% had localized disease. Ninety-six percent of patients ( n = 84) underwent surgery. Adjuvant chemotherapy was delivered to 16 patients. The most common regimen was ifosfamide-doxorubicin. Recurrences were observed in 30 patients, 21 had local, and 9 had distant metastasis. Five-year DFS of patients with the localized disease was 68%. All patients with PLS had relapses and those had the highest distant relapse rates among all subtypes. Multivariate analysis showed T stage and grade were associated with DFS. Five-year OS of the entire population was 68%. Five-year OS was 79, 76, 50, and 0% in WDLS, MLS, DDLS, and PLS, respectively ( p = 0.002). Conclusion Management of liposarcomas is still challenging. Surgery is the mainstay of treatment. Novel effective therapies are needed, particularly in advanced disease settings.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors.

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.

Correlation Between THSD7A Expression and Tumor Characteristics of Azoxymethane-Induced Colon Cancer Model in Rats.

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.

A systematic review and meta-analysis of the association between circulating tumor DNA (ctDNA) and prognosis in pancreatic cancer.

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, p < 0.001) 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, p < 0.001) and OS (HR: 2.41, 95 % CI: 1.74-3.34, p < 0.001) in advanced pancreatic cancer. In conclusion, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in pancreatic cancer.

Newly diagnosed cancer and the COVID-19 pandemic: tumour stage migration and higher early mortality.

BACKGROUND: We compared the new outpatient clinic referrals during the first 10 months of the COVID-19 pandemic with the year before. METHODS: We 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. RESULTS: The 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, p<0.001). We observed a significant decrease in the percentage of patients diagnosed via the screening methods (18.8% vs 28.7%, OR: 1.698, 95% CI: 1.240 to 2.325, p=0.001). The 90-day mortality after the cancer diagnosis was significantly higher during the pandemic (10.5% vs 6.6%, OR: 1.661, 95% CI: 1.225 to 2.252, p=0.001). Due to the increased advanced-stage disease rate at first referral, significant decreases in 5-year survival rates were expected for breast cancer (-8.9%), colorectal cancer (-11.1%), cervix cancer (-10.3%) and melanoma (-7%). CONCLUSION: We think that collaborative efforts are paramount to prevent the pandemic of late cancer diagnoses and ensure patient safety during the pandemic.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

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, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p=0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p=0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p=0.340), disease control rate (p=0.076), and OS (p=0.289) and PFS (p=0.276) were similar to overall cohort. CONCLUSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Impact of albumin to globulin ratio on survival outcomes of patients with metastatic renal cell carcinoma.

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<0.001). After adjustment for the number of covariates, multivariate Cox regression analysis identified a high AGR as an independent indicator of better OS (hazard ratio, 0.476; 95% CI, 0.304-0.745; p=0.001). CONCLUSION: Our results suggested that AGR value, which is an easily obtainable and cost-effective marker in routine biochemistry testing, could function as an independent predictor of OS in patients with mRCC treated with targeted therapy.

Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of early unplanned readmissions and predisposing factors in an oncology clinic.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Predictive Value of Red Blood Cell Distribution Width for Survival Outcomes of Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, P = 0.012). RDW level ≥15.4 was found as an independent prognostic parameter for OS when adjusted for the number of covariates, including the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (hazard ratio: 1.125, 95% confidence interval: 1.024-2.235, P = 0.014). CONCLUSIONS: 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.

Evaluation of emergency departments visits in patients treated with immune checkpoint inhibitors.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Lycopene sensitizes the cervical cancer cells to cisplatin via targeting nuclear factor- kappa B (NF-κB) pathway

Background/aim: Lycopene is 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 h. 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-κB), B-cell-associated X protein (Bax), nuclear factor erythroid 2-related factor (Nrf2), and B-cell lymphoma 2 (Bcl-2). Results: We 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-κB 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, the anticancer effect of lycopene might be also associated with suppression of NF-κB-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and concurrent cisplatin chemotherapy might have a role in improving the treatment of cervical cancer.

The platelet to lymphocyte ratio predicts overall survival better than the neutrophil to lymphocyte ratio in metastatic renal cell carcinoma

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 Kaplan­Meier method, and the log­rank 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.