The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy.

BACKGROUND: The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. METHODS: We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. RESULTS: Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. CONCLUSION: Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Does systemic anti-tumor therapy increase COVID-19 risk in patients with cancer?

PURPOSE: We aimed to determine the COVID-19 infection rate and determine the factors that affect hospitalization and prognosis in patients receiving systemic chemotherapy (CT), immunotherapy (IT) and molecular-targeted therapies at our hospital within three months after the onset of COVID-19 pandemic. MATERIALS AND METHODS: The patients who received systemic treatment at chemotherapy unit with diagnosis of cancer between 11 March 2020 and 11 June 2020 were included. The clinical and demographic characteristics of patients, the systemic treatments that they received (CT, IT, targeted therapies), and the stage of disease were determined. For the parameters that affect the hospitalization of COVID-19 infected patients were also determined. RESULTS: Among 1149 patients with cancer, 84 of them were infected with COVID-19, and the median age of infected patients was 61.0 (IQR: 21-84) and 60.7% of them were male. As a subtype of cancers lung cancer was more frequent in the patients who infected with COVID compared with non-infected ones and the difference was statistically significant when the underlying malignities were compared (32.1% vs 19.0%, p = 0.031). The hospitalization rate and receiving COVID-19 treatment were more frequent in metastatic patients who were receiving palliative therapy, and the difference was statistically significant (p = 0.01, p = 0.03). In our study, infection rate was similar among patients treated with CT, IT and CT plus targeted therapy; however, fewer COVID-19 infections were seen at patients who received only targeted therapy. CONCLUSION: COVID-19 infection is more frequent in cancer patients and tends to be more severe in metastatic cancer patients receiving anticancer treatment, and the continuation of palliative cancer treatments in these patients may cause increased cancer and infection-related morbidity and mortality.

Impact of Integrating Insulin-Like Growth Factor 1 Levels into Model for End-Stage Liver Disease Score for Survival Prediction in Hepatocellular Carcinoma Patients.

BACKGROUND: Liver reserve affects survival in hepatocellular carcinoma (HCC). Model for End-Stage Liver Disease (MELD) score is used to predict overall survival (OS) and to prioritize HCC patients on the transplantation waiting list, but more accurate models are needed. We hypothesized that integrating insulin-like growth factor 1 (IGF-1) levels into MELD score (MELD-IGF-1) improves OS prediction as compared to MELD. METHODS: We measured plasma IGF-1 levels in training (n = 310) and validation (n = 155) HCC cohorts and created MELD-IGF-1 score. Cox models were used to determine the association of MELD and MELD-IGF-1 with OS. Harrell's c-index was used to compare the predictive capacity. RESULTS: IGF-1 was significantly associated with OS in both cohorts. Patients with an IGF-1 level of ≤26 ng/mL in the training cohort and in the validation cohorts had significantly higher hazard ratios than patients with the same MELD but IGF-1 >26 ng/mL. In both cohorts, MELD-IGF-1 scores had higher c-indices (0.60 and 0.66) than MELD scores (0.58 and 0.60) (p < 0.001 in both cohorts). Overall, 26% of training and 52.9% of validation cohort patients were reclassified into different risk groups by MELD-IGF-1 (p < 0.001). CONCLUSIONS: After independent validation, the MELD-IGF-1 could be used to risk-stratify patients in clinical trials and for priority assignment for patients on liver transplantation waiting list.

Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non-small cell lung cancer.

PURPOSE: The optimal chemotherapy regimen for concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) remains unclear. Cisplatin-etoposide regimen related toxicity is high, weekly regimens have been investigating. We aimed to compare the efficacy and safety of different concurrent chemotherapy regimens in the context. METHODS: A total of 225 patients with locally advanced, unresectable stage III NSCLC were included. Patients who were treated with weekly docetaxel-platin (DP), paclitaxel-platin (PP) and standard dose etoposide-platin (EP) chemotherapy regimens were selected and divided into groups for the comparison of toxicity, response rate, progression free survival (PFS), and overall survival (OS) times. RESULTS: There was a statistically significant difference between overall response rate of each treatment groups (DP: 96.1%, PP: 94% and EP: 76.7%, p < 0.001). The median PFS time of patients who were treated with DP, PP and EP was 16, 15 and 13.3 months, respectively (p = 0.435). The median OS time of patients treated with DP, PP and EP was 19.2, 29.7 and 28.3 months, respectively (p < 0.001). The rates of adverse events such as nausea, vomiting, neuropathy and anaphylaxis was similar. Grade 1-2 mucositis or esophagitis, anemia, pneumonitis were significantly higher in PP group than other groups. However, hematologic toxicities were higher in the EP group than other groups. CONCLUSIONS: Compared to the weekly chemotherapy regimens with the standard dose, our study demonstrated similar PFS, but a prolonged OS with the EP regimen. The clinical response rate of weekly regimens was better than the full-dose regimen. Adverse events and toxicity rates were different and depended on the type of chemotherapy regimen used.

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. METHODS: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. RESULTS: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32-0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20-0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67-11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88-79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40-0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7-41.3 months) and 24.1 months for nonusers (95% CI, 19.02-29.30 months; P = .008). CONCLUSION: In a case-control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.

Natural History of T1N0M0 Hepatocellular Carcinoma: Large-Scale Study in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) prognosis depends on clinicopathological features in addition to the treatment provided. We aimed to assess the natural history of TNM stage I HCC tumors which received different treatment over a period of 20 years. METHODS: Between 1992 and 2011, a total of 397 stage I HCC patients were included. Detailed information was retrieved from MD Anderson Cancer Center patients' medical records. The Kaplan-Meier method was used to calculate patients' overall survival (OS). Cox regression analysis was used to calculate the estimated hazard ratio and 95% confidence interval of different prognostic factors. RESULTS: Out of 397 patients, 67.5% were males, 42.8% had hepatitis-related HCC, and 59.7% had underlying cirrhosis. After adjustment for confounding factors, we found that all therapeutic modalities were associated with a significant mortality rate reduction with an OS of 63, 42.03, 34.3, and 22.1 months among patients treated with surgery, ablation, local, and systemic therapy, respectively. A restricted analysis of cirrhotic and noncirrhotic patients showed that ablative and local therapy were significantly associated with a longer OS compared to systemic therapy. CONCLUSION: TNM stage I HCC patients have a favorable prognosis regardless of the type of treatment. Notably, ablative and local therapy significantly improved OS compared to systemic therapy.

Comparison of prognosis and clinical features between synchronous bilateral and unilateral breast cancers.

PURPOSE: The clinical significance of synchronous bilateral breast cancer (SBBC) is unclear and its influence on prognosis is controversial. Our study objective was to determine the epidemiological features, tumor characteristics, and prognosis of SBBC in comparison with those of unilateral breast cancer (UBC). METHODS: A total of 3675 breast cancer patients diagnosed and treated between 2000 and 2014 were evaluated. Of these patients, 132 (3.6%) had bilateral breast cancer, including 55 patients (1.5%) with SBBC and 77 (2.1%) with metachronous bilateral breast cancer (MBBC). The patient demographic characteristics, including survival data and clinicopathological tumor characteristics, were obtained from medical charts and compared between the patients with SBBC and those with UBC. RESULTS: The median age in the SBBC group was 51 years (range 32-77). The mastectomy rate was higher in the SBBC group (72.7%) than in the UBC group (66.6%) (p=0.08). In both the SBBC and UBC groups, the baseline clinicopathological features and the history of treatment with radiotherapy and chemotherapy were similar. Infiltrating ductal carcinoma was the most common histology in both groups. Lobular histology was more frequent in the SBBC group (36.3%) than in the UBC group (17.1%; p<0.001). Stage IV disease at initial presentation was more frequent in the SBBC group than in the UBC group (34.5 vs 8.7%, p<0.001). The 5-year disease-free survival (DFS) rates were 90% and 82% in the SBBC and UBC groups, respectively (p=0.99). The 5-year overall survival (OS) rates were 83% and 88%, respectively (p=0.357). The multivariate Cox regression analysis, including stage, hormone receptor status, grade, and SBBC, revealed that the presence of SBBC was not associated with OS (hazard ratio 0.929; 95% confidence interval, 0.455-0.1894, p=0.839). CONCLUSION: Despite the differences in histology, initial stage, and other characteristics, the prognoses of UBC and SBBC were similar.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

Evaluation of the Relationship Between Portal Vein Diameter and Colorectal Liver Metastases on Computed Tomography.

BACKGROUND/AIM: The most common and often first metastatic site of colorectal cancer (CRC) is the liver, and radiological modalities have a critical role in the diagnosis of colorectal liver metastasis (CRLM). In this study, the possible relationship between portal vein diameter, number of metastases, and metastasis diameter was evaluated in CRLM patients who underwent computed tomography (CT) examination with intravenous contrast (IV). PATIENTS AND METHODS: Cases diagnosed with CRLM who underwent abdominal CT examination with IV contrast between December 2020 and January 2024 were retrospectively scanned. People over the age of 18 were included, and cases were divided into three subgroups according to the number of metastases: a (single), b (two), and c (three and/or more). RESULTS: There were 101 male and 74 female cases; the youngest case was 39 (male) and the oldest case was 87 (male) years old. According to the number of CRLMs, group a had 47 cases, group b had 23, and group c had 105 cases. The minimum diameter of metastasis was 0.74 cm, the maximum was 11.86 cm, and the mean diameter was 4.45±2.67 cm. There was a significant correlation between the presence of metastasis in the left lobe and the diameter of the metastases (p<0.05). CONCLUSION: The relationship between portal vein diameter and CRLM using contrast-enhanced CT scans was explored. While no significant correlation was found between portal vein diameters and metastasis size, a notable association was observed between metastasis size and their presence in the left liver lobe. These findings suggest that CRLMs in the left lobe may respond better to preoperative chemotherapy and surgical interventions. This novel insight could help develop targeted treatment strategies for CRLM, though further research with larger cohorts is needed.

A Post-International Gastrointestinal Cancers' Conference (IGICC) Position Statements.

Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40-50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient's medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

Only 32.3% of Breast Cancer Families with Pathogenic Variants in Cancer Genes Utilized Cascade Genetic Testing.

BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. METHODS: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. RESULTS: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. CONCLUSIONS: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.

The effect of exercise on disease-free survival and overall survival in patients with breast cancer.

BACKGROUND: Positive effects of exercise in cancer patients have been reported. AIM: To investigate whether intensity, duration, and timing of exercise affect disease relapse and mortality risk in patients with breast cancer (BC). METHODS: Patients with local or locally advanced stages of BC between January 2018 and January 2020 were recruited in the study. Sociodemographic and clinicopathological characteristics of patients were recorded. Exercise evaluation was performed by preparing a questionnaire and asking the patients face-to-face questions in the outpatient clinic. RESULTS: Risk of relapse was 58% lower in patients who exercised than inactive patients (p = 0.004). Patients who exercised for 2 to 5 days per week had a 63% lower relapse risk than inactive patients (p = 0.010). Risk of relapse was 66% lower in the patients who exercised for less than 1 h or 3 metabolic equivalent of task (MET)-hours per week when compared to inactive patients (p = 0.037). Similarly, relapse risk was 62% lower in patients who exercised between 1 to 3 h or 3 to 8.9 MET-hours per week than inactive patients (p = 0.026). Mortality risk was lower in patients who exercised than patients who did not (p = 0.027). A significantly decreased mortality risk was found in both groups that included patients who exercised for 1 to 5 days per week and patients who exercised for less than 3 h or 9 MET-hours per week when compared to inactive patients. CONCLUSION: Exercise was associated with decreased relapse and mortality rates in patients with BC. Therefore, exercise should be recommended to BC patients as a significant component of the treatment.

Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model.

Pazopanib is a tyrosine kinase inhibitor that is generally used for the treatment of metastatic renal cell cancer and advanced soft tissue sarcoma. It can cause various degrees of hepatotoxicity. Our study aimed to investigate the effect of taxifolin on pazopanib-induced liver toxicity. A total of 18 rats were divided into three groups: the pazopanib (PP), pazopanib plus taxifolin (TPP), and control (C) group. Taxifolin was administered to the TPP (n=6) group with a dose of 50 mg/kg. Distilled water was orally admnistered to the C (n=6) and PP (n=6) groups as a solvent. Subsequently, pazopanib 200 mg/kg was administered to the TPP and PP groups via the stomach. This procedure was repeated once a day for four weeks. Then, all rats were sacrificed, and their livers were removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), and total antioxidant status (TAS) levels were evaluated. MDA and TOS levels were higher in the PP group compared with the levels of the other parameters (P<0.001). tGSH and TAS levels were lower in the PP group than in the TPP and C groups (P<0.001), and the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were higher. Furthermore, liver tissue damage, including hemorrhage, hydropic degeneration, and necrosis was observed in the PP group. Administration of taxifolin before pazopanib significantly improved degenerative changes. Our study demonstrated that the administration of taxifolin is significantly effective in preventing pazopanib-induced hepatotoxicity in rats.

Easier and more explanatory indices by integrating leukocyte lymphocyte ratio (LLR) and prognostic nutritional index (PNI) to IPS systems in cases with classical Hodgkin lymphoma.

The aim of this study is to determine the power of he international prognostic scoring systems (IPS-7 and IPS-3) and to obtain indices by integrating leukocyte lymphocyte ratio (LLR) and prognostic nutritional index (PNI) factors as prognostic indicators in cases with classical Hodgkin lymphoma (cHL). 1012 patients with cHL were evaluated with 2 different IPS-4 scores with four parameters: stage, age, hemoglobin level, and either LLR or PNI. Statistical package SPSS v 22.0 was used. Two different Cox regression models were obtained for OS and PFS. Model 1 showed LLR ≥ 5,8 as the highest risk for OS and anemia as the highest risk for PFS. Model 2 showed PNI ≤ 45,2 as the highest risk for OS and anemia as the highest risk for PFS. IPS-4 scores obtained by integrating either LLR or PNI to IPS-3 integration of a biologic parameter either LLR or PNI need to be determined with clinical risk scoring parameters.

IPS-3 Validation in 1012 cases with classical hodgkin lymphoma.

The aim of this study is to validate the IPS-3 scoring system as a prognostic indicator in 1012 patients with advanced stage classical Hodgkin Lymphoma (cHL) treated by doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). According to the IPS-3 scoring system only 3.5 % had high risk and 50.8 % had low risk disease disease and 45.8 % of the cases had intermediate risk disease. Each factors of IPS-7 and IPS-3 scoring systems (age, sex, stage hemoglobin, albumin, lymphocyte count and white cell count) were found to be significant for overall survival (OS) and progression free survival (PFS) according to univariate analyses. Two different multivariate Cox analyses were performed for OS and PFS including the IPS-3/ IPS-7 scoring system parameters. Among 7 risk factors of IPS scoring system, gender and albumin were not found as independent risk factors for both OS and PFS according to cox regression model. But all parameters such as age, stage and hemoglobin those included in IPS-3, were found to be independent significant risk factors for both models obtained for OS and PFS. The results of the study shows that the IPS-3 scoring system can be used as a prognostic indicator in ABVD treated patients in every day practice which is more easily calculate according to the IPS-7.

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study.

INTRODUCTION: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. MATERIAL AND METHODS: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. RESULTS: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). CONCLUSIONS: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.

The Prognostic Value of Circulating VEGF-A Level in Patients With Hepatocellular Cancer.

BACKGROUND: Neovascularization plays a crucial pathogenic role in tumor development and vascular endothelial growth factor (VEGF-A) is a key signaling element that drives angiogenesis, thereby facilitating hepatocellular cancer (HCC) growth and metastasis. We aimed to define the relationship between serum VEGF-A levels and clinical outcomes in a cohort of Turkish patients with HCC. METHODS: We enrolled and prospectively followed 84 patients with HCC in our study. Serum VEGF-A levels were measured and we assessed the association between VEGF-A levels and clinical features. RESULTS: Forty-eight patients had cirrhosis while 35 patients were noncirrhotic. Serum VEGF-A levels were significantly lower in HCC patients with cirrhosis compared to non-cirrhotic HCC patients (p = 0.03).In terms of viral hepatitis subtype, 36 (%42.8) of patients were hepatitis B virus (HBV) positive and 8 (%9.5) of patients were hepatitis C virus (HCV) positive. Patients with serum VEGF-A levels ≥100 pg/mL had significantly lower OS rates than patients with serum VEGF-A level <100 pg/mL (p = 0.01). The OS rates were 5.8 and 14.2 months, respectively (p = 0.02). The median OS was 7.38 months (95% CI: 5.89-13.79 months). We observed a significant relationship between serum VEGF-A level and tumor size. Patients with tumor size ≤ 5cm had lower VEGF-A levels than patients with VEGF-A levels <5 cm. The VEGF-A levels were 132.7 and 342.1 pg/mL, respectively (p < 0.001). The median follow-up was 32 months. CONCLUSIONS: Serum VEGF-A level, a biological marker of angiogenesis, is an independent predictor of survival in patients with HCC. Serum VEGF-A levels may be utilized to predict response to treatment targeting serum VEGF-A in patients with HCC.

Prognostic value of the 2017 World Health Organization Classification System for gastric neuroendocrine tumors: A single-center experience.

BACKGROUND/AIMS: Gastric neuroendocrine tumors (G-NETs) are rare tumors, but their incidence is gradually increasing. Despite the existence of many classification systems, determining prognosis and planning treatment in patients with G-NETs remains a clinical challenge. In this study, the prognostic value of the World Health Organization (WHO) 2017 grading system and the effect of surgery on survival in low grade neuroendocrine tumors were investigated. MATERIALS AND METHODS: G-NETs who were diagnosed between January 2000 and May 2017 were included in the study. Patients' demographic characteristics, treatment details, and survival data were obtained from medical charts. Pathological samples were re-classified according to the WHO 2017 grading system. RESULTS: Of the total 94 evaluated patients, 50 (53.2%) were classified with G1 NETs, 37(39.4%) with G2 NETs, 4(4.2%) with well-differentiated G3 NETs, and the remaining 3 patients with poorly differentiated G3 neuroendocrine carcinoma (NEC). The median follow-up time was 83.2 months. There was a statistically significant difference in 5-year progression free survival (PFS) between G1 tumors (100%) and G2 tumors (76%) (p<0.001). However, there was no statistically significant deference in 5-year overall survival rate (OS) for G1 (97%) and G2 (82%) tumors (p=0.141). When G2 and G1 NETs were compared according to their surgical approach, radical surgery was more frequently performed in patients with G2 tumors (p<0.001). However, radical surgery did not improve PFS in G1 and G2 NETs. CONCLUSION: The WHO 2017 NET classification system may have low prognostic value for determining the prognosis of patients with G1 and G2 tumors. Radical surgery for G1 and G2 NETs did not improve PFS in our study.