Cardiac safety of ribociclib evaluated with 24-hour rhythm Holter electrocardiogram.

OBJECTIVE: We aimed to evaluate cardiac safety profile of ribociclib with 24-h rhythm Holter ECG. MATERIAL AND METHOD: Forty-two female metastatic breast cancer patients were included in the study. Rhythm Holter ECG was performed before starting treatment with ribociclib and after 3 months of the treatment initiation. RESULTS: The mean age of the patients was 56.36 ± 12.73. 52.4% (n = 22) of the patients were using ribociclib in combination with fulvestrant and 47.6% (n = 20) with aromatase inhibitors. None of the patients developed cardiotoxicity. When the rhythm Holter results before and in third month of the treatment were compared, there was no statistically significant difference. CONCLUSION: This is the first study evaluating effects of ribociclib treatment on cardiac rhythm with Holter ECG. The findings suggested ribociclib has a low risk of causing early cardiotoxicity.

Dementia rhythms: Unveiling the EEG dynamics for MCI detection through spectral and synchrony neuromarkers.

BACKGROUND: Neurological disorders arise primarily from the dysfunction of brain cells, leading to various impairments. Electroencephalography (EEG) stands out as the most popular method in the discovery of neuromarkers indicating neurological disorders. The proposed study investigates the effectiveness of spectral and synchrony neuromarkers derived from resting state EEG in the detection of Mild Cognitive Impairment (MCI) with controls. NEW METHODS: The dataset is composed of 10 MCI and 10 HC groups. Spectral features and synchrony measures are utilized to detect slowing patterns in MCI. Efficient neuro-markers are classified by 25 classification algorithm. Independent samples t-test and Pearson's Correlation Coefficients are applied to reveal group differences for spectral markers, and repeated measures ANOVA is tested for wPLI-based markers. RESULTS: Lower peak amplitudes are prominent in MCI participants for high frequencies indicating slower physiological behavior of the demented EEG. The MCI and HC groups are correctly classified with 95 % acc. using peak amplitudes of beta band with LGBM classifier. Higher wPLI values are calculated for HC participants in high frequencies. The alpha wPLI values achieve a classification accuracy of 99 % using the LGBM algorithm for MCI detection. COMPARISON WITH EXISTING METHODS: The neuro-markers including peak amplitudes, frequencies, and wPLIs with advanced machine learning techniques showcases the innovative nature of this research. CONCLUSION: The findings suggest that peak amplitudes and wPLI in high frequency bands derived from resting state EEG are effective neuromarkers for detection of MCI. Spectral and synchrony neuro-markers hold great promise for accurate MCI detection.

Characteristic features and prognostic factors in gastric cancer patients with bone metastases: multicenter experience.

We evaluated the incidence, clinicopathological features, prognostic factors, progression-free survival (PFS) and overall survival (OS) of patients with gastric cancer and bone metastases. The medical records of 110 patients with bone metastases were retrospectively analyzed. In our study, the incidence of bone metastases was 3.2%. The median patient age was 60 years. A total of 68 (61.8%) patients exhibited synchronous metastases, and 42 (38.2%) patients developed metachronous metastases. Alkaline phosphatase (ALP) levels were high in 54 (49%) patients. At the median follow-up time of 9.8 months, median PFS and OS times were 4.7 and 6.3 months, respectively. The median interval from the diagnosis to bone metastases was 9.3 months. Univariate analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, use of zoledronic acid treatment, palliative chemotherapy post-bone metastases and radiotherapy to bone metastases were significant prognostic indicators for PFS. Additionally, ECOG PS ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, zoledronic acid treatment, palliative chemotherapy post-bone metastases, and radiotherapy to bone metastases significantly influenced OS. Moreover, in multivariate analysis, ECOG PS, time of metastases, presence of extra-bone metastases, and the use of palliative chemotherapy after bone metastases were found to be independent prognostic factors for PFS. Moreover, ECOG PS, time of metastases, and use of palliative chemotherapy after bone metastases were significantly independent prognostic indicators for OS. Our findings show that the presence of synchronous metastases, use of palliative chemotherapy, use of zoledronic acid after bone metastases, and ALP level within the normal range were significantly associated with prolonged OS in gastric cancer patients with bone metastases.

Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer.

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25-30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Prevalence and co-incidence of geriatric syndromes according to the ECOG performance status in older cancer patients.

Background: Geriatric syndromes may be more common in older cancer patients than in those without cancer. Geriatric syndromes can cause poor clinical outcomes. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is often used as a clinically reported functional status score in oncology practice. Methods: Our study was designed as a cross-sectional study and included 218 older cancer patients. This study aimed to determine the prevalence and relationship of geriatric syndromes according to the ECOG-PS in older cancer patients. Results: The mean age of 218 participants was 73.0 ± 5.6 years, with 47.7% being women and 52.3% men in our study. ECOG-PS 0, 1, and 2 groups contained 51, 39, and 10% of the patients, respectively. The mean number of geriatric syndromes in the ECOG 0, 1, and 2 groups was 2.3 ± 2.2, 4.3 ± 2.4, and 5.7 ± 2.1, respectively (p < 0.001). After adjusting for age and sex, it was determined that dynapenia was 2.9 times, probable sarcopenia was 3.5 times, frailty was 4.2 times, depression was 2.6 times, malnutrition was 3.3 times, insomnia 2 was.2 times, falls was 2.5 times, and the risk of falling (TUG) was 2.4 times more likely in those with ECOG-PS 1 compared to those with ECOG-PS 0. In addition, it was found that dynapenia was 6 times, probable sarcopenia was 6.8 times, frailty was 10.8 times, depression was 3.3 times, malnutrition was 6.3 times, the risk of falling (Tinnetti Balance) was 28 times, and the risk of falling (TUG) was 13.6 times more likely in those with ECOG-PS 2 compared to those with ECOG-PS 0. Conclusion: Our study found that the prevalence of geriatric syndromes increased as the ECOG-PS increased. Geriatric syndromes and their co-incidence were common in older cancer patients, even in normal performance status. Oncologists should incorporate geriatric syndromes into the decision-making process of cancer treatment to maximize the impact on clinical outcomes in older patients with cancer.

Deep insights into MCI diagnosis: A comparative deep learning analysis of EEG time series.

BACKGROUND: Individuals in the early stages of Alzheimer's Disease (AD) are typically diagnosed with Mild Cognitive Impairment (MCI). MCI represents a transitional phase between normal cognitive function and AD. Electroencephalography (EEG) records carry valuable insights into cerebral cortex brain activities to analyze neuronal degeneration. To enhance the precision of dementia diagnosis, automatic and intelligent methods are required for the analysis and processing of EEG signals. NEW METHODS: This paper aims to address the challenges associated with MCI diagnosis by leveraging EEG signals and deep learning techniques. The analysis in this study focuses on processing the information embedded within the sequence of raw EEG time series data. EEG recordings are collected from 10 Healthy Controls (HC) and 10 MCI participants using 19 electrodes during a 30 min eyes-closed session. EEG time series are transformed into 2 separate formats of input tensors and applied to deep neural network architectures. Convolutional Neural Network (CNN) and ResNet from scratch are performed with 2D time series with different segment lengths. Furthermore, EEGNet and DeepConvNet architectures are utilized for 1D time series. RESULTS: ResNet demonstrates superior effectiveness in detecting MCI when compared to CNN architecture. Complete discrimination is achieved using EEGNet and DeepConvNet for noisy segments. COMPARISON WITH EXISTING METHODS: ResNet has yielded a 3 % higher accuracy rate compared to CNN. None of the architectures in the literature have achieved 100 % accuracy except proposed EEGNet and DeepConvnet. CONCLUSION: Deep learning architectures hold great promise in enhancing the accuracy of early MCI detection.

Differentiation of lung and breast cancer brain metastases: Comparison of texture analysis and deep convolutional neural networks.

PURPOSE: Metastases are the most common neoplasm in the adult brain. In order to initiate the treatment, an extensive diagnostic workup is usually required. Radiomics is a discipline aimed at transforming visual data in radiological images into reliable diagnostic information. We aimed to examine the capability of deep learning methods to classify the origin of metastatic lesions in brain MRIs and compare the deep Convolutional Neural Network (CNN) methods with image texture based features. METHODS: One hundred forty three patients with 157 metastatic brain tumors were included in the study. The statistical and texture based image features were extracted from metastatic tumors after manual segmentation process. Three powerful pre-trained CNN architectures and the texture-based features on both 2D and 3D tumor images were used to differentiate lung and breast metastases. Ten-fold cross-validation was used for evaluation. Accuracy, precision, recall, and area under curve (AUC) metrics were calculated to analyze the diagnostic performance. RESULTS: The texture-based image features on 3D volumes achieved better discrimination results than 2D image features. The overall performance of CNN architectures with 3D inputs was higher than the texture-based features. Xception architecture, with 3D volumes as input, yielded the highest accuracy (0.85) while the AUC value was 0.84. The AUC values of VGG19 and the InceptionV3 architectures were 0.82 and 0.81, respectively. CONCLUSION: CNNs achieved superior diagnostic performance in differentiating brain metastases from lung and breast malignancies than texture-based image features. Differentiation using 3D volumes as input exhibited a higher success rate than 2D sagittal images.

The correlation between skeletal muscle index and anxiety in patients with lung cancer on the first day of chemotherapy.

Aim: To evaluate the relationship between anxiety and skeletal muscle index (SMI) levels in lung cancer patients on the first day of chemotherapy. Materials & methods: This cross-sectional study included 108 patients. We analyzed patient characteristics, SMI levels, pain status and predicted anxiety factors. Results: Anxiety was detected in 61% of patients. SMI levels were significantly lower in the high anxiety group than the low anxiety group (p < 0.001). A significant correlation was observed between anxiety and SMI levels (r = -0.292; p = 0.002). Anxiety levels were significantly correlated with trait anxiety (r = 0.618; p < 0.001) and visual analog scale-pain (r = 0.364; p < 0.001). SMI (odds ratio: 0.94), trait anxiety (odds ratio: 1.12) and visual analog scale pain (odds ratio: 1.28) were independent risk factors for anxiety after adjusting for sex, stage and Eastern Cooperative Oncology Group performance status. Conclusion: Our study highlighted that higher anxiety scores were significantly correlated with lower SMI levels. We found that SMI, pain and trait anxiety were independent risk factors for anxiety.

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study.

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.

Local interventions for colorectal cancer metastases to liver and lung.

BACKGROUND: Colorectal cancer is a common cause of cancer-related deaths. About 1/3 of all cases present with distant metastasis, with the liver as the leading site and the lung as the most common extra-abdominal site. AIMS: It was aimed to evaluate the clinical characteristics and the outcomes of colorectal cancer patients with liver or lung metastasis who had received local treatments. METHODS: This is a retrospective, cross-sectional, and descriptive study. The study was performed with colorectal cancer patients that referred to the medical oncology clinic of a university hospital between December 2013 and August 2021. RESULTS: A total number of 122 patients who have received local treatments were included. Radiofrequency ablation was applied in 32 patients (26.2%), metastasis was surgically resected in 84 patients (68.9%), and stereotactic body radiotherapy was preferred in six patients (4.9%). At the first follow-up control after completion of local or multimodal treatment, no residual tumor was determined with radiological assessment in 88 patients (72.1%). The median progression-free survival (16.7 months vs 9.7 months) (p = .000) and the median overall survival (37.3 months vs 25.5 months) (p = .004) of these patients were significantly better than the patients with residual disease. CONCLUSIONS: Local interventions that are applied to highly selected patients may improve the survival of metastatic colorectal cancer patients. A close follow-up after local therapies is important to diagnose recurrent disease because repeated local interventions may be possible to achieve better outcomes.

Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study.

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p=0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.

Real-life analysis of treatment approaches and the role of inflammatory markers on survival in patients with advanced biliary tract cancer.

OBJECTIVES: Advanced-stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients. METHODS: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed. RESULTS: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice (p < .001 HR:0.70 CI95% 0.55-0.9), performance status (p < .001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = .02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < .001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < .001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = .002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < .001 HR:0.55 CI 95% 0.38-0.79; p = .007 HR:0.51 CI95% 0.31-0.83, respectively). CONCLUSION: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions.

The efficacy of BNT162b2 (Pfizer-BioNTech) and CoronaVac vaccines in patients with cancer.

Although vaccination is efficacious and prevents infection in the general population, there is limited data about Coronavirus disease-19 (Covid-19) occurrence after vaccination in cancer patients. It was aimed to evaluate the efficacy of BNT162b2 (Pfizer-BioNTech) and CoronaVac vaccines against Covid-19 in patients with cancer. In this single-center, retrospective, cross-sectional, and descriptive study, the data of cancer patients referred to the medical oncology clinic of a university hospital were analyzed. The sample of the study consisted of cancer patients who had Covid-19 or were vaccinated against Covid-19. A total number of 2578 patients were included in the study. Of the patients, 2000 have never been infected with severe acute respiratory syndrome coronavirus and 578 patients have had a positive reverse-transcription polymerase chain reaction (RT-PCR) for Covid-19. It was found that 2094 patients (81.2%) were fully vaccinated, and 484 patients (18.8%) did not receive full-dose vaccination. A statistically significant difference in Covid-19 occurrence was found between the patients who had full-dose vaccination or not (p = 0.000). In in-group comparisons of full-dose vaccinated patients, while no difference was observed between two doses of BNT162b2 (Pfizer-BioNTech) and three doses of CoronaVac (p = 0.432), a statistically significant difference was observed between all other groups (p < 0.005). When the data of 578 patients who experienced Covid-19 was analyzed, a statistically significant difference was observed between the groups who were full-dose vaccinated and those who were not (p = 0.000). It is recommended that this vulnerable patient group should be prioritized in vaccination programs, and full-dose vaccination (at least two doses of vaccines) should be completed as soon as possible.

The effect of sarcopenia on erlotinib therapy in patients with metastatic lung adenocarcinoma.

Erlotinib, a tyrosine kinase inhibitor, has been shown to improve the survival of patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Sarcopenia is a status with increasing importance in lung cancer, and it may predict a poor prognosis. We aimed to evaluate the impact of sarcopenia on erlotinib therapy and prognosis in patients with EGFR-mutated (exon 19 or 21 L858R) metastatic lung adenocarcinoma. Sarcopenia was defined as skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men. The patient characteristics, inflammation parameters, clinical and survival outcomes of the erlotinib therapy were examined according to sarcopenia status. We also analyzed the erlotinib treatment-related toxicity. Seventy-two patients were included in our retrospective study, and the mean age of the patients was 63.7 years. A total of 39 (54.2%) patients were diagnosed with sarcopenia. Patients with sarcopenia had a poor prognosis and had a shorter median progression-free survival (PFS) than patients without sarcopenia (10.5 months vs. 21.8 months, p=0.002). Sarcopenia (HR 2.08) and C-reactive protein > 6.5 mg/L (HR 2.57) were determined as independent poor prognostic factors for PFS of erlotinib therapy. Treatment-related toxicity occurred in 34.7% of patients treated with erlotinib, and sarcopenia did not significantly affect treatment-related toxicity. We also found that sarcopenia significantly affected the response to erlotinib. The expected survival outcomes may be low when erlotinib therapy is used in patients with sarcopenia and metastatic lung adenocarcinoma. This study showed that survival and clinical outcomes could be better predicted by detecting sarcopenia in patients with lung cancer using erlotinib.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer in women worldwide. Ribociclib is now frequently used in the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer. CASE REPORT: A 54-year-old woman with breast cancer presented at a clinic in November 2017 with multiple lung and bone metastases. After receiving multiple lines of treatment due to disease progression, ribociclib and fulvestrant were initiated. Grade 4 toxicity was observed due to ribociclib during follow-up, and ribociclib was discontinued permanently.Management & Outcome: Given that liver transaminases and bilirubin elevation persisted despite discontinuation of the treatment, other reasons for liver toxicity were investigated. Abdominal MRI showed no liver metastases, although there was acute hepatitis. A liver biopsy was performed to determine the etiology. The pathology result was compatible with drug-induced acute fulminant toxic hepatitis. After liver biopsy, prednisolone treatment was initiated, after which the laboratory findings normalized. DISCUSSION: Although there are reported cases showing improvement in liver enzymes after ribociclib discontinuation, in our case, no recovery from hepatotoxicity was noticed. The treatment was changed to another hormonal pathway therapy option, exemestane. To the best of our knowledge, this is the first case in the literature reporting this rare side effect of ribociclib, which is a liver biopsy-proven fulminant hepatitis.

Platelet to lymphocyte ratio is associated with tumor localization and outcomes in metastatic colorectal cancer.

ABSTRACT: The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization.A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (≤196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P < .001 and P = .023 respectively).Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization.

Prognostic significance of primary tumor localization in patients with metastatic colorectal cancer: Is it beneficial to select targeted treatment? Real-life experience from Turkey.

PURPOSE: The purpose of this study was to investigate the prognostic value,and the effect of primary tumor location on targeted therapy selection in patients with metastatic colorectal cancer (mCRC). METHODS: A total of 201 patients with de novo mCRC who received first line treatment were retrospectively analyzed. Clinicopathological features, treatment outcomes, the primary tumor surgery, metastasectomies/local therapies and survivals were evaluated in terms of both RAS mutation status and primary tumor sidedness. RESULTS: Tumor localization showed 140 (69.7%) patients with left-sided and 61 (30.3%) with right-sided tumors. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with right-sided tumor than those with left-sided tumors (10.1 vs 12.9 months, p=0.005; 25 vs 44.4 months, p=0.008, respectively). In addition,the median OS interval of patients receiving anti-VEGF containing regimen was better than those treated with anti-EGFR containing regimen (50.7 vs. 26.9 months, p=0.001). Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors. CONCLUSIONS: Our results showed that primary tumor location is a prognostic factor in mCRC patients regardless of RAS status. Primary tumor location before treatment decision may be a simple indicator predicting survival and in choosing targeted agent.

Primitive Neuroectodermal Tumor of the Testis.

A 21-year male presenting with left testicular mass and retroperitoneal lymphadenopathy underwent radical orchiectomy; and his pathological examination showed a mixed germ cell tumor composed of primitive neuroectodermal tumor mixed with mature teratoma. Six cycles of IE (ifosfamide, etoposide) and VAC (vincristine, doxorubicin, cyclophosphamide) chemotherapy were given after sperm preservation. He then underwent retroperitoneal lymph node dissection (RPLND). No tumor was detected in the removed lymph nodes, and all lymph nodes were reported as showing reactive changes. Key Words: Chemotherapy, Primitive neuroectodermal tumor, Surgery, Teratom, Testis.

Complexity of EEG Dynamics for Early Diagnosis of Alzheimer's Disease Using Permutation Entropy Neuromarker.

BACKGROUND AND OBJECTIVE: Electroencephalogram (EEG) is one of the most demanded screening tools that investigates the effects of Alzheimer's Disease (AD) on human brain. Identification of AD in early stage gives rise to efficient treatment in dementia. Mild Cognitive Impairment (MCI) is considered as a conversion stage. Reducing EEG complexity can be used as a marker to detect AD. The aim of this study is to develop a 3-way diagnostic classification using EEG complexity in the detection of MCI/AD in clinical practice. This study also investigates the effects of different eyes states, i.e. eyes-open, eyes-closed on classification performance. METHODS: EEG recordings from 85 AD, 85 MCI subjects, and 85 Healthy Controls with eyes-open and eyes- closed are analyzed. Permutation Entropy (PE) values are computed from frontal, central, parietal, temporal, and occipital regions for each EEG epoch. Distribution of PE values are visualized to observe discrimination of MCI/AD with HC. Visual investigations are combined with statistical analysis using ANOVA to determine whether groups are significant or not. Multinomial Logistic Regression model is applied to feature sets in order to classify participants individually. RESULTS: Distribution of measured PE shows that EEG complexity is lower in AD and higher in HC group. MCI group is observed as an intermediate form due to heterogeneous values. Results from 3-way classification indicate that F1-scores and rates of sensitivity and specificity achieve the highest overall discrimination rates reaching up to 100% for at TP8 for eyes-closed condition; and C3, C4, T8, O2 electrodes for eyes-open condition. Classification of HC from both patient groups is achieved best. Eyes-open state increases discrimination of MCI and AD. CONCLUSIONS: This nonlinear EEG methodology study contributes to literature with high discrimination rates for identification of AD. PE is recommended as a practical diagnostic neuro-marker for AD studies. Resting state EEG at eyes-open condition can be more advantageous over eyes-closed EEG recordings for diagnosis of AD.