Does nutritional status affect treatment tolerability, chemotherapy response and survival in metastatic gastric cancer patients? Results of a prospective multicenter study in Turkey.

BACKGROUND: The possible impact of malnutrition on the efficacy and tolerability of modern chemotherapy for metastatic gastic adenocarcinoma (mGC) patients is unclear. With this study, we aimed to represent the possible impact of malnutrition on the efficacy and tolerability of chemotherapy, and also on the overall survival of mGC patients. METHODS: In this prospective multicenter study, we collected demographic, oncological and nutritional data of our mGC patients. The nutritional status of patients were assessed with the Nutritional Risk Index (NRI), Body Mass Index (BMI) and weight loss percentage within 21-day period, between the chemotherapy cycles. All of these parameters along with toxicity assessment were evaluated after each courses of chemotherapy in order to determine inter-treatment weight loss. NRIs were calculated with a formula as follows; [1.519 × serum albumin level(g/L) + 41.7 × current weight/basic weight]. Patients were classified as having 'no malnutrition' (NRI > 97.5), 'moderate malnutrition' (97.5 ≥ NRI ≥ 83.5) or 'severe malnutrition' (NRI < 83.5). Drug-induced toxicities and treatment responses were evaluated via National Cancer Institute CTCAE version 4.0 and RECIST Criteria 1.1, respectively. RESULTS: One hundred and sixteen mGC patients were enrolled into the study. Median age was 60 years with range 32-83. Primary location of the tumor was antrum in 40% of the patients and of which 24% had undergone primary tumor resection. Ninety-eight percent of the patients had WHO performance status 0 or 1. Malnutrition was diagnosed in 67% of the patients and was severe in 31% of them. All patients received chemotherapy as first-line setting. Severe malnutrition was not associated with chemotherapy responses (p = 0.57). Moderate/severe malnutrition was associated with more cytopenia, nausea/vomiting, diarrhea, neuropathy, (p < 0.05 for all parameters). Moderate/severe malnutrition is associated with worser non-hematological toxicities (p = 0.038). Forty-one percent of patients died during the follow up period (Median: 138 days, range: 21-378). Malnutritional level was associated with significantly reduced overall survival. Severe malnutrition was associated with shorter median overall survival (74 days (95% CI, 20.7-111.0) vs. 237 (95% CI, 148.4-325.6) in none/moderate groups, p = 0.007). CONCLUSIONS: In mGC patients, moderate/severe malnutrition is associated with worse non-hematological toxicities. Severe malnutrition is also associated with reduced overall survival.

Does nutritional status affect treatment tolarability, response and survival in metastatic colorectal cancer patients? Results of a prospective multicenter study.

BACKGROUND: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. METHODS: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI (Nutritional Risk Assessment), BMI (Body Mass Index) and WL (Weight Loss) before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. NRIs were examined in 3 categories as 'no malnutrition' (NRI >97.5), 'moderate malnutrition' (97.5 ≥NRI ≥83.5) or 'severe malnutrition' (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively. RESULTS: One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p = 0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS (World Health Organization Performance Status) of 1, over the median value of CEA/CA 19-9 (carcinoembryonic antigen/carbohydate antigen 19-9) levels (p = 0.003, p = 0.03, p < 0.001, and p = 0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p < 0.001 and p < 0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p = 0.02 and p = 0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p < 0.001]. CONCLUSIONS: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.

Circulating interleukin-18 (IL-18) is a predictor of response to gemcitabine based chemotherapy in patients with pancreatic adenocarcinoma.

BACKGROUND: This study was conducted to investigate the serum levels of interleukin-18 (IL-18) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. METHODS: Thirty-three patients with PA were studied. Serum samples were obtained on first admission before any treatment. Serum IL-18 levels were analyzed using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis. RESULTS: The median age at diagnosis was 59 years, range 32-84 years; 20 (61%) patients were men and the remaining were women. The median follow-up time was 26.0 weeks (range: 1.0-184.0 weeks). The median overall survival of the whole group was 41.3 ± 8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum IL-18 levels were significantly higher in patients with PA than in the control group (p < 0.001). Serum IL-18 levels were significantly higher in the patients with high erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) (p = 0.01 and p = 0.05). Moreover, the chemotherapy-(CTx) unresponsive patients had higher serum IL-18 levels compared to CTx-responsive (p = 0.04) subjects. Conversely, serum IL-18 concentration was found to have no prognostic role on survival (p = 0.45). CONCLUSION: Serum levels of IL-18 can be a good diagnostic and predictive marker; especially for predicting the response to gemcitabine based CTx in patients with PA but it has no prognostic role.

Clinical significance of serum interleukin-17 levels in colorectal cancer patients.

PURPOSE: The proinflammatory cytokine, interleukin-17 (IL-17) plays a potent role in T-cell mediated angiogenesis and promotes tumorigenicity. The objective of this study was to determine the clinical outcomes of colorectal cancer (CRC) patients in relation to serum IL-17 levels. METHODS: Ninety-six CRC patients were enrolled in this study. Pre-treatment serum IL-17 levels were determined by enzyme- linked immunosorbent assay (ELISA). Thirty age - and sex-matched healthy controls were included in the analysis. RESULTS: The median patient age was 60 years (range: 24-84) and the most frequent localization was colon (N=59;61%). Median follow-up time was 14 months, 27 patients (28%) experienced disease progression, and 20 of the remaining patients (20%) died. The estimated and 1-year progression-free survival (PFS) and 2-year overall survival (OS) rates for the whole patient group were 26.9% (95% confidence interval [CI]=9.9-44.0) and 71% (95% CI=56.0- 85.0), respectively. The number of patients who received neoadjuvant treatment was 25. Of the patients who received palliative treatment, 11 had oxaliplatin whereas 18 and 7 had irinotecan and FU/capecitabine, chemotherapy (CTx). Twenty-four and nine of the patients who received targeted therapy had bevacizumab and cetuximab, respectively. Thirty-three percent of 36 metastatic patients who received palliative CTx were CTx-responsive. The baseline median serum IL-17 levels were significantly lower in patients with CRC than in the healthy control group (p=0.01). Moreover, known clinical variables including older age, poor grade and low albumin levels were found to be correlated with high serum IL-17 concentrations (p=0.02, p=0.02, and p=0.04, respectively). No statistically significant serum IL- 17 concentrations were noted regarding PFS and OS. CONCLUSION: Serum levels of IL-17 may be diagnostic marker in CRC patients. However, no predictive and prognostic values were determined.

Serum leptin levels may have diagnostic and predictive roles in patients with pancreatic adenocarcinoma treated with gemcitabine-based chemotherapy.

PURPOSE: Leptin is a highly pleiotropic adipokine. Pancreatic adenocarcinoma (PA) and leptin relationship is important. Our aim was to investigate the serum levels of leptin in patients with PA, the relationship of leptin with tumor progression and known prognostic parameters and its diagnostic, predictive and prognostic role. METHODS: Thirty-three patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum leptin levels were determined using enzyme-linked immunosorbent assay (ELISA). Age, sex, and body mass index (BMI) matched to 20 healthy controls were included in the analysis. RESULTS: The median patient age at diagnosis was 59 years (range 32-84) and 20 (61%) patients were men. The tumor was located in the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (N=19; 83%). The median follow-up time was 26.0 weeks (range 1.0-184.0). At the end of the observation period, 32 patients (97%) had died. The baseline serum leptin levels were significantly higher in patients with PA than in the control group (p=0.02). Thirty-nine percent of 23 metastatic patients who received palliative gemcitabine-based chemotherapy (gCTx) were gCTx-responsive. Serum leptin levels were significantly higher in the gCTx-unresponsive patients compared with gCTx -responsive (median 5.32 vs 1.16 ng/mL, p=0.004). Conversely, serum leptin concentration was found to have no prognostic role on survival (p=0.20). CONCLUSION: Serum leptin levels may be a good diagnostic and predictive tool on the response to gCTx in PA patients.

Sweet syndrome in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma: curious lymphocyte/neutrophil fluctuations.

UNLABELLED: Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) which is a relatively rare co-occurrence. CONFLICT OF INTEREST: None declared.

The effect of mutation status, pathological features and tumor location on prognosis in patients with colorectal cancer.

OBJECTIVE: Colorectal cancer is the most common malignancy of the gastrointestinal tract. It is the third most common tumor in both genders and the second reason of cancer-related deaths. In recent years, tumor location has gained importance as a prognostic indicator. In this study, we aimed to analyze if there was a prognostic effect of tumor location, the pathological features, and the mutation status of patients on survival. METHODS: Two-hundred and ten colorectal cancer patients aged 18 years and older were included into the study. One-hundred and forty-two patients had left-sided tumor and 68 patients had right-sided tumor. Patients who had other malignancies rather than squamous cell skin cancer and in situ cervical cancer were excluded. All statistical tests were carried out using two-sided process, and a p≤0.05 was considered statistically significant. RESULTS: There were 140 men and 70 women in the study. The median age of the patients was 62 years old. There was no statistically significant difference according to tumor location and survival of patients. The overall survival of patients with right-sided tumors was 60.5 months and 47.2 months for left-sided tumors. Disease-free survival of patients was 63.7 months for right-sided tumors and 46 months for left-sided ones. Perineural invasion, grade and stage were crucial prognostic parameters. Disease-free survival was longer for female colorectal cancer patients. CONCLUSION: According to our study, survival of patients was similar regardless of tumor location. This can be explained by the different sequencing of treatment strategies and divergent population genetics.

Tubular gastric adenocarcinoma: machine learning-based CT texture analysis for predicting lymphovascular and perineural invasion.

PURPOSE: Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poor prognosis in gastric cancers. In this work, we aimed to investigate the potential role of computed tomography (CT) texture analysis in predicting LVI and PNI in patients with tubular gastric adenocarcinoma (GAC) using a machine learning (ML) approach. METHODS: Sixty-eight patients who underwent total gastrectomy with curative (R0) resection and D2-lymphadenectomy were included in this retrospective study. Texture features were extracted from the portal venous phase CT images. Dimension reduction was first done with a reproducibility analysis by two radiologists. Then, a feature selection algorithm was used to further reduce the high-dimensionality of the radiomic data. Training and test splits were created with 100 random samplings. ML-based classifications were done using adaptive boosting, k-nearest neighbors, Naive Bayes, neural network, random forest, stochastic gradient descent, support vector machine, and decision tree. Predictive performance of the ML algorithms was mainly evaluated using the mean area under the curve (AUC) metric. RESULTS: Among 271 texture features, 150 features had excellent reproducibility, which were included in the further feature selection process. Dimension reduction steps yielded five texture features for LVI and five for PNI. Considering all eight ML algorithms, mean AUC and accuracy ranges for predicting LVI were 0.777-0.894 and 76%-81.5%, respectively. For predicting PNI, mean AUC and accuracy ranges were 0.482-0.754 and 54%-68.2%, respectively. The best performances for predicting LVI and PNI were achieved with the random forest and Naive Bayes algorithms, respectively. CONCLUSION: ML-based CT texture analysis has a potential for predicting LVI and PNI of the tubular GACs. Overall, the method was more successful in predicting LVI than PNI.

Serum IL-17 levels can be diagnostic for gastric cancer.

PURPOSE: Gastric cancer (GC) is one of the most common malignancies worldwide. Although it has been strongly associated with immunopathology, IL-17 also has an important role in host defense so this makes it more important in GC, which is a microorganism-related cancer. The aim of this study was to determine the clinical significance of the serum levels of IL-17 in GC patients. METHODS: A total of 76 patients with GC and 30 healthy age- and sex-matched controls were enrolled in this study. Serum IL-17 levels were determined by the enzyme-linked immunosorbent assay method (ELISA) and these values were compared between groups. RESULTS: The median age at diagnosis was 60 years (21-84). Fifty-three (70%) patients were male and cardia was the most common tumor localization (n=40, 53%). Thirty-eight patients had metastasis (n=38, 50%) at presentation and liver was the most common organ with metastasis (n=17, 22%). Mean progression free survival (PFS) and overall survival (OS) of GC patients were 4.0 ± 0.9 months (95% CI: 2 - 6 months) and 14.6 ± 1.2 months (95% CI:12-17), respectively. 1-year OS rate was 52.8% (95% CI: 40.5-65.2). The median serum IL-17 levels of GC patients were significantly higher than of controls (9.04 vs. 8.07 pg/mL, p=0.01). There was no significant difference according to known disease-related clinicopathological and most of the laboratory parameters (p>0.05) but there was a positive relationship between CA-19.9 and IL-17 levels (p=0.04). Serum IL-17 levels had no significant impact on PFS, OS (p=0.51 and p=0.33) and also on response to chemotherapy (p>0.05). CONCLUSION: While serum IL-17 levels were significantly higher in patients with GC compared to health subjects, it has no prognostic value on survival. Serum IL-17 levels may be a new candidate marker in the diagnosis of GC.

The effect of mutation status, pathological features and tumor location on prognosis in patients with colorectal cancer

SUMMARY OBJECTIVE: Colorectal cancer is the most common malignancy of the gastrointestinal tract. It is the third most common tumor in both genders and the second reason of cancer-related deaths. In recent years, tumor location has gained importance as a prognostic indicator. In this study, we aimed to analyze if there was a prognostic effect of tumor location, the pathological features, and the mutation status of patients on survival. METHODS: Two-hundred and ten colorectal cancer patients aged 18 years and older were included into the study. One-hundred and forty-two patients had left-sided tumor and 68 patients had right-sided tumor. Patients who had other malignancies rather than squamous cell skin cancer and in situ cervical cancer were excluded. All statistical tests were carried out using two-sided process, and a p≤0.05 was considered statistically significant. RESULTS: There were 140 men and 70 women in the study. The median age of the patients was 62 years old. There was no statistically significant difference according to tumor location and survival of patients. The overall survival of patients with right-sided tumors was 60.5 months and 47.2 months for left-sided tumors. Disease-free survival of patients was 63.7 months for right-sided tumors and 46 months for left-sided ones. Perineural invasion, grade and stage were crucial prognostic parameters. Disease-free survival was longer for female colorectal cancer patients. CONCLUSION: According to our study, survival of patients was similar regardless of tumor location. This can be explained by the different sequencing of treatment strategies and divergent population genetics.

Expression of fibroblast growth factor receptor 1, fibroblast growth factor 2, phosphatidyl inositol 3 phosphate kinase and their clinical and prognostic significance in early and advanced stage of squamous cell carcinoma of the lung.

AIM: Non-small cell lung carcinoma is the leading cause of cancer related to death in the world. Squamous cell lung carcinoma (SqCLC) is the second most frequent histological subtype of lung carcinomas. Recently, growth factors, growth factor receptors, and signal transduction system-related gene amplifications and mutations are extensively under investigation to estimate the prognosis and to develop individualized therapies in SqCLC. In this study, besides the signal transduction molecule phosphatidyl inositol-3-phosphate kinase (IP3K) p110α, we explored the expressions of fibroblast growth factor 2 (FGF2) and receptor-1 (FGFR1) in tumor tissue and also their clinical and prognostic significance in patients with early/advanced SqCLC. MATERIALS AND METHODS: From 2005 to 2013, 129 patients (23 early, 106 advanced disease) with a histopathological SqCLC diagnosis were selected from the hospital files of Cukurova University Medical Faculty for this study. Two independent pathologists evaluated FGFR1, FGF2, and PI3K (p110α) expressions in both tumor and stromal tissues from 99 of the patients with sufficient tissue samples, using immunohistochemistry. Considering survival analysis separately for patients with both early and advanced stage diseases, the relationship between the clinical features of the patients and expressions were evaluated by univariate and multivariate analyses. RESULTS: FGFR1 expression was found to be low in 59 (60%) patients and high in 40 (40%) patients. For FGF2; 12 (12%) patients had high, 87 (88%) patients had low expression and for IP3K; 31 (32%) patients had high and 66 (68%) patients had low expressions. In univariate analysis, overall survival (OS) was significantly associated with stage of the disease and the performance status of the patient (P<0.0001 and P<0.001). There was no significant difference in OS of the patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were separately taken into consideration, the relationship did not differ, either. Any of FGFR1, FGF2 or IP3K expressions was not found predictive for the treatment of early or advanced staged patients. On the other hand, the expressions of both FGFR1 and FGF2 were significantly different with respect to smoking, scar of tuberculosis and scar of radiotherapy (P=0.002; P=0.06 and P=0.05, respectively). DISCUSSION: There has not been identified an effective individualized treatment for SqCLC yet. Therefore, in order to be able to develop such a treatment in the future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviors and carcinogenesis of SqCLC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SqCLC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. In conclusion, we want to put some emphasis on the fact that, pulmonary fibrosis which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions.