A New Scoring System for the Evaluation of Ibrutinib-Associated Arrhythmias in Chronic Lymphocytic Leukemia: The ACEF Score

Objective: Bruton tyrosine kinase inhibition in cardiac tissue causes inhibition of the PI3K-AKT signaling pathway, which is responsible for protecting cardiac tissue during stress. Therefore, there is an increase in the risk of arrhythmia. This study explores the prediction of that risk with the Age-Creatinine-Ejection Fraction (ACEF) score as a simple scoring system based on the components of age, creatinine, and ejection fraction. Materials and Methods: Patients diagnosed with chronic lymphocytic leukemia (CLL) and receiving ibrutinib treatment for at least 1 year were evaluated with echocardiography and Holter electrocardiography and the results were compared with a control group of CLL patients who had not received treatment. ACEF score was calculated with the formula age/left ventricular ejection fraction+1 (if creatinine >2.0 mg/dL). Results: When the arrhythmia development of the patients was evaluated, no statistically significant difference was found between the control and ibrutinib groups in terms of types of arrhythmias other than paroxysmal atrial fibrillation (PAF). PAF was found to occur at rates of 8% versus 22% (p=0.042) among ibrutinib non-users versus users. For patients using ibrutinib, an ACEF score of >1.21 predicted the development of PAF with 77% sensitivity and 75% specificity (area under the curve: 0.830, 95% confidence interval: 0.698-0.962, p<0.001). Conclusion: The ACEF score can be used as a risk score that predicts the development of PAF in patients diagnosed with CLL who are scheduled to start ibrutinib.

Diagnostic value of combining heart rate recovery and P-wave changes with exercise-induced changes in the ST segments for prediction of myocardial ischaemia.

BACKGROUND: In patients admitted to outpatient clinics with chest pain, changes in the ST-segments of electrocardiogram (ECG) readings are the most widely used criteria during treadmill ECG tests to determine myocardial ischaemia, despite its poor accuracy. In this study, we evaluated the benefit of combining elongation of P-wave duration (Pdur) and abnormal heart rate recovery (HRR) parameters in addition to changes in the ST-segments for the detection of myocardial ischaemia with treadmill ECG testing. METHODS: Patients (n = 369) with chest pain who underwent both a treadmill ECG test and myocardial perfusion scintigraphy (MPS) were enrolled. P-wave duration was measured at rest and at the end of the first minute of the recovery phase and elongation of the P-wave was calculated. Abnormal HRR was defined as the failure of a decreasing HR at the end of the first minute of the recovery phase >10% of the maximum HR reached during treadmill ECG testing. The sensitivity, specificity, positive and negative predictive values, diagnostic accuracy values, and likelihood ratios (LRs) of changes in the ST-segments, P-wave elongation, abnormal HRR, and the combination of these three variables for predicting myocardial ischaemia detected by MPS, were calculated separately-in patients without previous coronary artery disease (CAD) and in those with CAD. RESULTS: Elongation of Pdur by 20 ms or longer and abnormal HRR during treadmill ECG test were more common in patients with reversible perfusion defects in MPS than in those without perfusion defects (both P < 0.001). When patients were divided into two groups according to the presence or absence of a history of CAD, the addition of elongation of Pdur 20 ms and abnormal HRR to the development of significant changes in the ST-segments detected myocardial ischaemia with 46.7% sensitivity, 97.8% specificity, 67.2% negative predictive value, 88.9% positive predictive value, and 70% diagnostic accuracy in 77 patients with previous CAD. The LR+ of the combination of the three variables was 12.27. The addition of elongation of Pdur 20 ms and abnormal HRR to the development of significant changes in the ST-segments detected myocardial ischaemia with 52.7% sensitivity, 98.7% specificity, 89.9% negative predictive value, 90.6% positive predictive value, and 90% diagnostic accuracy in 292 patients without previous CAD. The LR+ of the combination of the three variables to detect myocardial ischaemia was calculated to be 41.48 in patients without a history of CAD. CONCLUSIONS: The addition of elongation of Pdur and abnormal HRR to the conventionally used criterion of changes in the ST-segments in patients with suspected myocardial ischaemia increased the specificity and positive and negative predictive values of treadmill ECG testing for detecting myocardial ischaemia, which might reduce the need for other expensive noninvasive techniques. The diagnostic utility of adding these two parameters was more obvious in patients with no history of CAD.

Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer?

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with cancer. Similarly, a study in a large series has shown that the newly defined derived NLR (dNLR; neutrophil/leukocyte-lymphocyte ratio) also has prognostic value. The present study retrospectively evaluates the prognostic significance of NLR and dNLR in breast cancer. METHODS: Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 1,527 patients diagnosed with breast cancer at Izmir Katip Celebi University Ataturk Research and Training Hospital from January 2006 to December 2011. The cut-off values were determined by calculating the NLR and dNLR of the patients. RESULTS: The cut-off values were determined as 4 and 2 for NLR and dNLR, respectively. The association between NLR and dNLR assessed by Spearman's rank correlation analysis was 0.935 (P < 0.001). There was a significant difference regarding disease free survival (DFS) and overall survival (OS) in patients with NLR <4 and NLR ≥4 (respectively, P < 0.00, P < 0.001). Similarly, there was a significant difference regarding DFS and OS in patients with dNLR <2 and dNLR ≥2 (respectively, P < 0.001, P < 0.001). Furthermore, NLR and dNLR demonstrated a significant association with the American Joint Committee on Cancer (AJCC) staging (P < 0.001). Assessment using the Cox proportional multivariate model showed that high NLR, pN, pT, luminal A-like, luminal B-like (HER2 positive), basal-like, and AJCC staging are independent prognostic factors. DISCUSSION: NLR was shown to be better than dNLR in terms of predicting prognosis in patients with breast cancer. However, large prospective studies are required to further demonstrate the prognostic significance of these two values.

Treatment of metastatic colorectal cancer with or without bevacizumab: can the neutrophil/lymphocyte ratio predict the efficiency of bevacizumab?

BACKGROUND: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. MATERIALS AND METHODS: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. RESULTS: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). CONCLUSIONS: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab- based treatments in mCRC patients.

The effects of hematological parameters and tumor-infiltrating lymphocytes on prognosis in patients with gastric cancer.

BACKGROUND: It is well known that tumor-infiltrating lymphocytes (TIL) and, to a lesser extent, peripheral hematologic parameters from patients with cancer have to effect on prognosis. The aim of this study was to evaluate the effect of hematologic parameters and TIL on prognosis of patients with gastric cancer. METHODS: 236 patients who had diagnosed as gastric adenocarcinoma. All hematologic parameters were noted at the time of diagnosis. The number of lymphocyte aggregates as well as the number of lymphocytes within these agregat was counted.The prognostic significance and correlations of high neutrophil-lymphocyte ratio (NLR) together with TIL, was evaluated by multivaried analysis. RESULTS: The cut-off values of NLR and derived NLR (dNLR) were 3.8 and 2. The NLR was independently associated with survival (P < 0.001). dNLR was not independently associated with overall survival. No significant advantages for overall survival were found for the high TIL (p: 0.372). It was not determined correlation between TIL - NLR and TIL-lymphoid aggregate density (respectivly, P: 0.104; P: 0.246). CONCLUSIONS: The results suggest that the elevated NLR predicts poor overall survival following at the time diagnosis for all stage gastric cancer. dNLR was not independently associated with overall survival. There is insufficient evidence to the assesment of TIL by a nonspesific method. Therefore further studies is required, to confirm our hypothesis in larger patient cohorts.

One-day DCF regimen in patients with metastatic gastric cancer.

BACKGROUND: Cytotoxic chemotherapy is the basic treatment for metastatic gastric cancer. The "docetaxel, cisplatin, 5-day infusion of 5-FU (DCF5)" regimen is regarded as an effective therapy. However, the poor toxicity profile of this regimen and administration by 5-day infusion are major drawbacks of this method. METHODS: Patients with measurable metastatic gastric carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, normal hematological and renal function, adequate hepatic function, and not pretreated for advanced disease with chemotherapy, received docetaxel on day 1, cisplatin on day 1, and 5-FU peripheral IV on day 1 (DCF1) every 3 weeks. The patients undergoing the DCF1 regimen could not receive the infusion regimen. This was a retrospective study about the use of DCF in 1 day in not previously treated metastatic gastric cancer. RESULTS: In total, 95 patients were treated with a median of 5 cycles per patient. Those not previously treated for advanced disease received docetaxel 75 mg/m² on day 1, cisplatin 75 mg/m² on day 1, and 5-FU peripheral IV 750 mg/m²/day on day 1, plus filgrastim or lenograstim between days 3 and 7. Grade ≥3 toxicities were neutropenia (12%), anemia (11%), thrombocytopenia (3%), fatigue (18%), mucositis (10%), diarrhea (3%), nausea/vomiting (6%), neurological (3%), and palmar-plantar (2%). Two nonfatal febrile neutropenia episodes were recorded. There were no treatment-related deaths. In all patients with measurable disease, we observed an overall response rate of 46% (40 partial responses, 4 complete responses). Thirty-one patients (33%) had stable disease. The median overall survival was 9.0 months (95% CI 7.34-10.6). CONCLUSIONS: Use of the DCF1 regimen in metastatic gastric cancer is feasible, with comparable activity to previous results achieved with epirubicin-based chemotherapy and infusion DCF in terms of overall survival. However, randomized and prospective studies need to be carried out with this regimen.