Background
Programmed Cell Death-1 (PD-1) together with Programmed Death Ligand 1 (PDL-1) have crucial roles in anti-tumor immune response, cancer susceptibility and prognosis. Since PD-1 and PDL-1 ...have been considered as important genetic risk factors in cancer development and their functions can be affected by polymorphic sites, we investigated the effects of PD-1 rs2227981, rs2227982, rs36084323 and PDL-1 rs2282055, rs822336 gene polymorphisms on colorectal cancer (CRC) risk and prognosis in Turkish subjects.
Methods and results
Our study group consisted of 5-FU or Capacitabine prescribed CRC diagnosed patients and healthy controls. Genotype analyses of PD1 and PDL-1 polymorphisms were performed with Agena MassARRAY platform. rs36084323 CT genotype frequency was found to be higher in controls compared to cases (p < 0.001). rs36084323 CT genotype was highly associated with reduced CRC risk compared to CC genotype (OR 0.068, 95% CI 0.022–0.211, p < 0.001). In adjusted analysis, rs2282055 GG genotype was found to be associated with reduced CRC risk (OR 0.271, 95% CI 0.078–0.940, p = 0.040). rs2282055 TT genotype was found to be related to longer progression-free (Bonferroni corrected Log rank p = 0.013) and overall survival (Bonferroni corrected Log rank p =
0.009
) to that of GG genotypes. Patients with rs822336 GC+CC genotypes showed longer overall survival times compared to GG (Log rank p = 0.044).
Conclusions
According to our results, PD-1 rs822336 G > C polymorphism might be useful in predicting CRC prognosis. PDL-1 rs2282055 T > G polymorphism might be useful in predicting both CRC risk and prognosis. Further studies should be conducted in larger and different populations to clear the roles of PD-1 and PDL-1 polymorphisms in CRC risk and prognosis.
Hepatocellular carcinoma (HCC) with portal vein tumor thrombus is considered an advanced stage disease. Non-surgical local and systemic therapies are the only treatment options available. To analyze ...the survival and toxicity outcomes of systemic treatment concurrent with yttrium-90 transarterial radioembolization in HCC with liver-limited disease and portal vein involvement with Child–Pugh B liver reserve. The medical records of 22 patients who underwent yttrium-90 transarterial radioembolization concomitant with capecitabine chemotherapy as first-line treatment between 2014 and 2019 were retrospectively reviewed. Twenty-two patients were included in the study. Grade 3 to 4 side effects were evaluated, and hepatic encephalopathy developed in 1 patient after yttrium-90 transarterial radioembolization. In the fourth month of radiological evaluation, 11 patients had a partial response (50%), 5 patients had stable disease (22.7%), and 6 patients (27.3%) developed progressive disease. The median survival time was 21 months. Combined treatment with yttrium-90 transarterial radioembolization and capecitabine may be an effective and safe treatment option. Treatment was associated with a median overall survival of 21 months and a disease control rate of 72.7% at 4 months in patients with inoperable HCC.
Abstract Background SBAs are rarely seen tumors.Data regarding the use of chemotherapy together with bevacizumab in advanced SBA patients are lacking Materials and Methods The aim of this study is ...the evaluation of bevacizumab in advanced SBA. Twenty-eight patients from 5 centers with diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6) and FOLFIRI chemotherapy regimens were involved in the study. All patients were divided into 2 groups; ones who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and ones who did not receive bevacizumab (Chemo group) Results The median progression-free survival (PFS) and overall survival (OS) time of all population were 8.7 months and 16.9 months, respectively. Overall response rate (ORR) was 43.7% in Chemo group and 58.3% in Chemo+Bev group. Median PFSs in Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively and median OS were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of ORR, PFS and OS Conclusion Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared to chemotherapy alone and it does not cause an excess of significant toxicity.
To analyze the reliability and the effectiveness of chemotherapy and prognostic factors for survival in patients with HER2 (human epidermal growth receptor 2) negative early-stage breast cancer ...treated with adjuvant sequential anthracycline-based chemotherapy and paclitaxel.
This analysis retrospectively evaluated the medical records of 756 HER2 negative early-stage breast cancer patients who received adjuvant sequential anthracycline-based chemotherapy and weekly paclitaxel in 15 medical oncology centers in Turkey between 2008-2015. Estrogen receptor (ER), progesterone receptor (PR),HER2,age,tumor size and grade,nodal status,perineural and lymphatic invasion,disease-free survival (DFS) and overall survival (OS) were analyzed.
The median patient age was 50 years (22-82). Median follow up period was 46 months (13-82). The rates of recurrence and death detected in this period were 14.8% and 7.4%, respectively. Median OS and PFS were not reached in this period. Five-year DFS and OS rates were 87% and 89%, respectively. Age (OR:0.35,95%Cl 0.12-0.96, p=0.04), PR status (OR:0.44,95%Cl 0.18-1, p=0.05), lymphatic invasion (OR:2.6,95%Cl 0.97-7.4, p=0.05) were independent prognostic factors. Most common grade 3-4 toxicities were fatigue (6.7%), neutropenia (1.7%) and nausea (1.3%). Neutropenic fever developed in 1.8% of the patients and peripheral neuropathy in 16.9%. Dose reduction was necessary for 10% of the patients due to grade 3-4 toxicity, whereas postponement of chemotherapy was necessary for 7% of the patients.
This multicentric retrospective study confirmed that sequential adjuvant therapy with anthracycline-based chemotherapy and paclitaxel for HER2 negative breast cancer is an effective and reliable regimen.
Purpose
In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis.
Methods
Of 405 metastatic breast cancer ...patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (
n
= 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (
n
= 34).
Results
Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27–76), and median time for development of brain metastases was 11.9 months (0–69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively,
p
= 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %,
p
= 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival odds ratio (OR), 0.57;
p
= 0.02.
Discussion
Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.
We investigated the role of standardized uptake values (SUVs) of the primary tumor in small cell lung cancer (SCLC) patients.
The relationship between SUV and response to treatment was investigated ...using receiver operating characteristic (ROC) curve analysis, and the efficient cut-off value for detecting response to treatment was determined. The effects of SUV on response to treatment and survival were investigated.
90 patients with a median age of 58 years (range 39-83 years) were included. Median follow-up was 11 months. The suitable cut-off SUV for determination of response was found to be 10 in ROC analysis. The sensitivity and specificity of this value were 85.7% (95% confidence interval (95% CI) 63-96) and 61.8% (95% CI 49-73) (area under the curve 0.783; p = 0.0001), respectively. The overall objective response rate in patients with involvement above the cut-off value was 93.3% compared to 59.1% in those with involvement below the cut-off value (p < 0.0001). In uni- and multivariate analysis, favorable effects of limited-stage disease on response to treatment were established (p < 0.05). The effect of an SUV higher than the cut-off value on progression-free survival was borderline (p = 0.085).
These data may contribute to identifying prognostic disease characteristics and response to treatment.
The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients ...with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes.
The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response.
Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16).
Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.
Netrin-1 is found to be elevated and purposive as a diagnostic biomarker in many human cancers. We evaluated serum netrin-1 concentrations in patients with advanced non-small cell lung cancer ...compared with those in a healthy group. Thirty patients with advanced non-small cell lung cancer and 30 healthy people were included in the study. Serum netrin-1 concentrations were measured by quantitative ELISA method in both groups. The mean serum netrin-1 concentrations were found to be significantly higher in patients with non-small cell lung cancer than in healthy controls. The mean serum netrin-1 concentrations were found to be significantly higher in patients with non-small cell lung cancer before the beginning of chemotherapy when compared after the completion of the third cycle. Our results represented that netrin-1 concentrations elevated in advanced non-small cell lung cancer compared to a healthy control group, and netrin-1 concentrations decreased with chemotherapy.
Abstract The determination of the approximately truest value in height measurement is important in many fields, but it is difficult to perform true measurements, especially in the elderly ...individuals. We planned to investigate the following items in geriatric Turkish population: to calculate the decrease in height with advancing age by using the standing height measurement and estimated height derived from the knee height; to evaluate the significance of difference between the two measurement methods in the calculation of body mass index (BMI) and waist/height ratio (WHtR); to determine the cut-off value of WHtR according to estimated height in elderly individuals. We studied 551 cases aged between 19 and 97 years. Knee height was measured using a sliding caliper in a sitting position. Linear regression analysis was carried out to derive predictive equations for the estimation of stature with adults (≤50 years of age) according to the gender. This equation was then used to estimate height among elderly subjects. Of the cases, 60.3% were <60 years (mean: 48.75 ± 7.50); 39.7% of the cases were >60 years (mean: 69.51 ± 7.12). Estimated BMI (EBMI) measurements in the females and males >60 years were in average 1.23 kg/m2 and 0.92 kg/m2 higher than their real BMIs, respectively. EBMI measurements in the females <60 years were 0.32 kg/m2 higher than their real BMIs ( p < 0.01). There is a statistically significant difference between WHtR in the females of both age groups, and in the males >60 years, as compared to our estimated WHtR (EWHtR) measurements ( p < 0.01). The cut-off point of WHtR was 0.61 and 0.58 in the female and male cases of >60 years in our study, respectively. WHtR seemed to be a better anthropometric index that could predict most cardiometabolic risk factors in our study. EWHtR emerged to be a better cardiometabolic risk index especially in the elderly group.
Abstract EAT is a new index of cardiac and visceral obesity. Waist circumference (WC) measurement is not fully reliable in the determination of visceral adipose tissue (VAT), especially in elderly ...individuals. Studies on the reflection of the intra-abdominal fat mass by the EAT mass surrounding the heart were performed. Our purpose in this study was to determine the relation between the MS criteria and EAT in MS cases and especially to compare anthropometric measures between non-geriatric patients under the age of 65, and geriatric ones over the age of 65 years. The study was performed during the years 2008 and 2009 on 120 cases; 66.7% of them were under the age of 65 and 33.3% of the cases were 65-year old or older. All of the patients were diagnosed as MS by the International Diabetes Federation (IDF) criteria. They were randomized as per the application order and included to the study. Each subject underwent transthoracic two-dimensional (2D) guided M-mode echocardiogram. We measured epicardial fat thickness on the 1/3 section close to the ventricle basis adjacent to the free wall of right ventricle from both the parasternal long axis (LA) and parasternal short axis (SA) views. Multiple regression analysis showed that WC, systolic blood pressure (SBP) and age were the strongest independent variables correlated with EAT ( p < 0.001). We also determined a significant correlation between low-density lipoprotein-cholesterol (LDL-C) and EAT ( p < 0.05). Our data show that EAT-measurement by echocardiography is an efficient method in determination of visceral adiposity and shall be taken into consideration especially when advanced age groups are in question.
