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.

Seven-Year Single-Center Experience of the Efficacy and Safety of Ferric Carboxymaltose in Cancer Patients with Iron-Deficiency Anemia.

Anemia remains an essential concern affecting the quality of life and the survival of cancer patients. Although there are different approaches to treating anemia in cancer patients, the number of studies reporting the efficacy of iron replacement in cancer patients is limited. In this study, the efficacy and safety of iron carboxymaltose, a parenteral iron treatment option, in the treatment of anemia, were examined retrospectively. A total of 1102 adult patients who received IV ferric carboxymaltose treatment at Hacettepe Oncology Hospital between 2014 and 2020 were included. The mean hemoglobin change observed at the end of the 12th week was 1.8 g/dL, and the rate of patients with an increase in hemoglobin of 1 g/dL or more was 72.1%. It was observed that the treatment demonstrated effectiveness in patients receiving active cancer treatment in all tumor types. The treatment was generally safe, and no grade 3-5 side effects were observed in the patients included in the study. According to one of the most extensive series published in the literature, iron carboxymaltose is an efficient and safe alternative for cancer patients with iron-deficiency anemia.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

Sarcopenia and anthracycline cardiotoxicity in patients with cancer.

BACKGROUND: Several studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and anthracycline-related cardiotoxicity. METHODS: Patients who received anthracycline-based chemotherapy between 2014 and 2018 and had baseline abdominal CT and baseline and follow-up echocardiography after anthracycline treatment were included. European Society of Cardiology ejection fraction criteria and American Society of Echocardiography diastolic dysfunction criteria were used for definition of cardiotoxicity. Sarcopenia was defined on the basis of skeletal muscle index (SMI) and psoas muscle index (PMI) calculated on CT images at L3 and L4 vertebra levels. RESULTS: A total of 166 patients (75 men and 91 women) were included. Sarcopenia was determined in 33 patients (19.9%) according to L3-SMI, in 17 patients (10.2%) according to L4-SMI and in 45 patients (27.1%) according to PMI. 27 patients (16.3%) developed cardiotoxicity. PMI and L3-SMI were significantly associated with an increased risk of cardiotoxicity (L3-SMI: HR=3.27, 95% CI 1.32 to 8.11, p=0.01; PMI: HR=3.71, 95% CI 1.58 to 8.73, p=0.003). CONCLUSIONS: This is the first study demonstrating a significant association between CT-diagnosed sarcopenia and anthracycline-related cardiotoxicity. Routine CT scans performed for cancer staging may help clinicians identify high-risk patients in whom closer follow-up or cardioprotective measures should be considered.

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.

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.

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.

Efficacy analyses of axitinib and nivolumab in metastatic renal cell carcinoma after failure of targeted therapy: which is better?

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Lower prognostic nutritional index is associated with poorer survival in patients receiving immune checkpoint inhibitors.

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.

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.

The effect of EML4-ALK break-apart ratio on crizotinib outcomes in non-small cell lung cancer harboring EML4-ALK rearrangement.

PURPOSE: Anaplastic lymphoma kinase (ALK) gene rearrangement exists in approximately 3-7% of non-small cell lung cancer (NSCLC) and more than 15% split or isolated red signals among 50 tumor nuclei scored in the FISH analysis defines as ALK-positive. The previous studies showed that the high EGFR mutational load related to better outcomes in EGFR mutant NSCLC. Therefore, we aimed to investigate the effect of the ALK break-apart ratio on treatment outcome in metastatic ALK-positive NSCLC. METHODS: The patients (pts) who ALK-positive and treated with crizotinib were retrospectively enrolled. The 30%, 40%, 50%, 60%, and 70% break-apart ratios were determined as a threshold value, and each of these was evaluated separately. Based on the results of these analyses, we detected the optimal threshold value and also performed further investigations. RESULTS: A total of 70 patients were enrolled in the study. The most significant decrease in the risk of the progression or death was detected at the 50% threshold value and it was accepted as the optimal threshold. The median PFS was 17.9 vs. 7.06 months (mo) in the pts with high ALK rearrangement than low (HR: 0.43, 95% CI 0.24-0.76, p 0.004). The median OS was also significant longer in high ALK rearrange group (44.6 mo vs. 16.8 mo; HR: 0.37, 95% Cl 0.1883-0.7315; p 0.004). The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) DISCUSSION: In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients. Based on the results of this study, the percentage of the ALK rearrangement can be used to predict treatment outcome and to choose the optimal targeted agent in the treatment of metastatic ALK-positive NSCLC.

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.

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.

COVID-19 pandemic: changes in cancer admissions.

BACKGROUND: COVID-19 pandemic could create a collateral damage to cancer care denoting disruptions in care due to a significant burden on healthcare and resource allocations. Herein, we evaluate the early changes in the inpatient and outpatient oncology clinics to take a snapshot of this collateral damage at Hacettepe University Cancer Institute. METHODS: Patients applying the outpatient clinic and outpatient palliative care (OPC) clinic for the first time and patients admitted to inpatient wards in the first 30 days after the first case of COVID-19 in Turkey were evaluated. These data were compared with data from the same time frame in the previous 3 years. RESULTS: The mean number of daily new patient applications to the outpatient clinic (9.87±3.87 vs 6.43±4.03, p<0.001) and OPC clinic (3.87±1.49 vs 1.13±1.46, p<0.001) was significantly reduced compared with the previous years. While the number of inpatient admissions was similar for a month frame, the median duration of hospitalisation was significantly reduced. The frequency of hospitalisations for chemotherapy was higher than in previous years (p<0.001). By comparison, the rate of hospitalisations for palliative care (p=0.028) or elective interventional procedures (p=0.001) was significantly reduced. CONCLUSION: In our experience, almost all domains of care were affected during the pandemic other than patients' systemic treatments. There were significant drops in the numbers of newly diagnosed patients, patients having interventional procedures and palliative care services, and these problems should be the focus points for the risk mitigation efforts for prevention of care disruptions.

Development of de novo psoriasis during nivolumab therapy in a patient with small cell lung cancer.

INTRODUCTION: The immune checkpoint inhibitors recently entered to small cell lung cancer (SCLC) stage, firstly in the third and recently in the first lines of therapy. This efficacy comes at the expense of many toxicities including skin toxicity. This toxicity is usually in the form of rash and pruritis; however, rare reactions like psoriasis can also be seen. CASE REPORT: Herein, we report an SCLC case who developed de novo psoriasis while treated with nivolumab as the third-line treatment for SCLC. MANAGEMENT AND OUTCOME: The psoriatic plaques were regressed with the topical highly potent steroid therapy, and immunotherapy was continued without further complications. DISCUSSION: We think that rare adverse events like de novo psoriasis are important considering the expanding role of these agents; their timely recognition and treatment are important in the management of cancer patients.

Exploiting DNA repair defects in breast cancer: from chemotherapy to immunotherapy.

Introduction: Impaired DNA damage response (DDR) and subsequent genomic instability are associated with the 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. Exploiting DDR defects in breast cancer cells has been one of the main strategies in both conventional chemotherapy, targeted therapies, or immunotherapies. Areas covered: In this review, the authors first discuss DDR mechanisms in healthy cells and DDR defects in breast cancer, then focus on current therapies and developments in the treatment of DDR-deficient breast cancer. Expert opinion: Among conventional chemotherapeutics, platinum-based regimens, in particular, seem to be effective in DDR-deficient patients. PARP inhibitors represent one of the successful models of translational research in this area and clinical data showed high efficacy and reasonable toxicity with these agents in patients with breast cancer and BRCA mutation. Recent studies have underlined that some subtypes of breast cancer are highly immunogenic. Promising activity has been shown with immunotherapeutic agents, particularly in DDR-deficient breast cancers. Chemotherapeutics, DNA-repair pathway inhibitors, and immunotherapies might result in further improved outcomes in certain subsets of patients with breast cancer and DDR.

Higher Serum Endocan Level Is Associated with Alzheimer Disease.

BACKGROUND: The novel molecule endocan, which is released by endothelium and is regulated by proangiogenic and proinflammatory cytokines, may have a role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to evaluate the relationship between serum endocan levels and AD. METHODS: A total of 134 patients (47 AD, 42 amnestic mild cognitive impairment [aMCI], and 45 control patients) 65 years of age and older were recruited in this study. Cognitive status of the patients was evaluated by performing the Montreal Cognitive Assessment (MOCA) and the Mini-Mental State Examination (MMSE). Serum endocan levels were measured with an enzyme-linked immunosorbent assay kit. RESULTS: Median serum endocan level was significantly higher in AD patients (380.1 ng/mL) than in both aMCI patients (247.7 ng/mL) and controls (277.6 ng/mL; p < 0.01). Serum endocan level had a weak but significant correlation with MMSE and MOCA scores (r = -0.219 and r = -0.232; p = 0.012 and p = 0.01, respectively). Serum endocan level was detected as a factor independently associated with AD. The cutoff serum level of endocan predicting AD was >288.94 ng/mL in receiver operating characteristic curve analysis (area under the curve 0.71, 95% CI 66.7-90.9, sensitivity 80.9%, specificity 59.8%; p < 0.01). CONCLUSION: Higher serum endocan levels may be associated with the pathogenesis of AD.