Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Evaluation of serum fibroblast growth factor-23 in patients with axial spondyloarthritis and its association with sclerostin, inflammation, and spinal damage.

The mechanisms underlying new bone formation in individuals with axial spondyloarthritis (axSpA) remain unclear; however, low levels of sclerostin (SOST) may be associated with development of syndesmophytes in those with ankylosing spondylitis (AS). Expression of fibroblast growth factor-23 (FGF-23), another osteocyte factor, is high in those with osteoporosis and chronic renal failure, but levels in those with axSpA are unknown. To evaluate serum FGF-23 and SOST levels in axSpA patients, and to assess their relationship with inflammation and structural damage. In total, 109 axSpA patients (55 with AS and 54 with non-radiographic axSpA) and 57 healthy control (HC) subjects were included in the analysis. Serum concentrations of FGF-23 and SOST were measured and correlation analysis was performed. The presence of syndesmophytes and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were used to assess structural damage. Levels of serum FGF-23 in axSpA patients were significantly higher than those in HCs [median (interquartile range-IQR) FGF-23 level, pg/ml; AxSpA = 144 (82.3-253.2), HC = 107 (63.3-192.8), p = 0.010]; however, there was no difference in SOST levels. FGF-23 levels correlated with the erythrocyte sedimentation rate (ESR) (r = 0.265, p = 0.006) and serum C-reactive protein (CRP) level (r = 0.229, p = 0.010). In the axSpA, SOST levels correlated negatively with mSASSS (r = - 0.283, p = 0.007), whereas those in the AS group correlated negatively with CRP (r = - 0.426, p = 0.001). Serum FGF-23 levels were high in axSpA patients. Increased FGF-23 was associated with inflammation, but not with SOST levels or disease activity. SOST correlated negatively with both inflammation and structural damage.

Can red cell distribution width be a marker of disease activity in ulcerative colitis?

AIM: The current study aimed to investigate the association between disease activity and red cell distribution width (RDW) levels in ulcerative colitis and to determine whether RDW can be used as a marker of disease activity in non-anemic ulcerative colitis. METHODS: The RDW levels of 310 ulcerative colitis patients who underwent colonoscopy were analyzed retrospectively. The patients were divided into two groups (active disease and remission) according to the endoscopic activity index. In addition, the accuracy of RDW in determining disease activity in non-anemic patients was assessed. The efficacy of RDW in determining disease activity was compared to that of white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate. RESULTS: Two hundred and six (66.5%) patients had active disease, and 104 (33.5%) were in remission. The mean RDW levels in patients with active ulcerative colitis and in those in remission were 16.8±2.9 and 15.5±1.4, respectively (P<0.001). Ninety-six (46.6%) patients in the active disease group and 89 (85.6%) in the remission group were non-anemic, and their respective RDW levels were 15.4±1.2 and 15.3±1.1 (P=0.267). The sensitivity and specificity of RDW in determining inflammation were 41% and 91%, respectively (AUC 0.65, P<0.001). CONCLUSIONS: This study demonstrated that RDW can be used as a marker for disease activity in ulcerative colitis, but it did not have the same efficacy in the non-anemic group.

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.

Impact of pre-angiogenic factors on the treatment effect of bevacizumab in patients with metastatic colorectal cancer.

Endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) play a major role in tumor growth and metastasis. Our aim was to determine whether there is any association between these endothelial parameters and tumor markers with the clinical outcome of bevacizumab-treated metastatic colorectal cancer (mCRC) patients in terms of response and survival. Pretreatment serum levels of ET-1, ADMA, carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were measured in 36 chemotherapy-naive mCRC patients treated with first-line bevacizumab-based therapy. Additionally, after first cycle of treatment, serum levels of these parameters were reanalyzed. Lower baseline serum ET-1 and ADMA levels were observed in patients responding to bevacizumab-based treatment (respectively, p = 0.037, p = 0.034). Median progression-free survival (PFS) (11 vs. 6 months, p = 0.012) and overall survival (OS) (28 vs 9 months; p = 0.007) were significantly shorter in patients with high pretreatment ET-1 levels. There was a significant decrease in ET-1 and CEA levels after first treatment (p = 0.020, p = 0.012), while ADMA and CA 19-9 levels were not significantly changed. Patients with decreased posttreatment ET-1 levels were shown to have inferior PFS (6 vs 11 months, p = 0.022), but no statistically significant difference was shown with respect to OS (p = 0.141). The effect of bevacizumab on endothelin axis including the biologic basis of decreasing ET-1 levels due to bevacizumab treatment and its association with inferior outcome has to be clarified in prospective trials.

Acute cardiotoxic effects of adjuvant trastuzumab treatment and its relation to oxidative stress.

Our aim was to evaluate the acute cardiac toxicity of adjuvant trastuzumab treatment and its possible relation to changes in oxidative stress. Electrocardiographic and echocardiographic tissue Doppler imaging (TDI) parameters, activity of antioxidant enzymes (superoxide dismutase; SOD), and products of oxidative stress (malondialdehyde; MDA) were analyzed in 30 patients with early-stage breast cancer who had adjuvant trastuzumab treatment. There was a significant prolongation of QT interval after trastuzumab treatment. There was also a significant decrease in left ventricular ejection fraction (LVEF), TDI-derived S' parameters, and SOD enzyme activity and increase in MDA levels after trastuzumab infusion. There was a positive correlation between changes in SOD activity and LVEF and a negative correlation between changes in MDA levels and LVEF. This study demonstrated a correlation between decreases in LVEF and increases in products of the oxidative stress in patients who had adjuvant trastuzumab treatment.