Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

The effect of concomitant beta-blocker use on survival in patients with metastatic renal cell carcinoma treated with a vascular endothelial growth factor receptor inhibitors in the first line.

PURPOSE: Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers. METHODS: A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them. RESULT: The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0-65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9-27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5-40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9-16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062). CONCLUSION: Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival.

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Background: Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. Objective: This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. Material and Methods: In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. Results: The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). Conclusions: We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

Is the Prognostic Nutritional Index a Prognostic Marker for the Survival of Patients with Lymph-Node Positive Stage II-III Gastric Cancer Who Receive Adjuvant Chemotherapy?

PURPOSE: The prognostic nutritional index (PNI), like other systemic inflammatory markers, has been shown to be a prognostic factor in various cancer patients. In this study, we aimed to show whether PNI calculated before adjuvant chemotherapy is a prognostic factor for overall survival (OS) and disease-free survival (DFS) in patients with lymph node-positive stage II-III gastric cancer. METHODS: The PNI was calculated using the albumin and lymphocyte count. The PNI cut-off value was found to be 39.5. They were divided into two groups as being ≤ 39.5 (PNI low group) and > 39.5 (PNI high group). RESULTS: Our study included 168 patients with lymph node-positive stage II-III gastric cancer who received adjuvant chemotherapy. Of the patients, 116 (69.0%) were 65 years or younger, and 52 (31.0%) were over 65 years old. Of the patients, 117 (69.6%) were pT3, 51 (30.4%) were pT4. Seventy-three (43.4%) patients had pN1-2 disease and 95 (56.6%) patients had pN3 disease. The number of stage II patients was 73 (43.5%) and the number of stage III patients was 95 (56.5%). There were 73 patients with PNI ≤ 39.5 and 95 patients with PNI > 39.5. The mOS of the patients with low PNI group was 39.5 months, while the OS of the patients with high PNI group was 96.8 months (p = 0.002). In the group of patients with PNI low group, mDFS 24.4 months was significantly higher than those with PNI high group was 50.7 months (p = 0.021). The PNI score was statistically significant in univariate and multivariate analyzes for both DFS and OS. CONCLUSION: PNI can be used as an independent prognostic factor for both OS and DFS in patients lymph node-positive, stage II-III gastric cancer who will receive adjuvant chemotherapy.

A multicentre, multinational study of clinical characteristics and prognosis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a significant health problem, and the associated mortality rate is increasing. Aim: We aimed to determine the clinical characteristics and prognosis for HCC in member countries of the OncoBridge Study Group. Methods: We recruited 630 patients diagnosed with HCC between 2013 and 2019 from 4 countries (Türkiye, Russia, Georgia, and Greece). Univariate and multivariate analyses were conducted to investigate clinical and laboratory prognostic factors. Receiver operating characteristic (ROC) analysis was used to determine the prognostic value of the neutrophil to lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) value. Results: The 3 most common etiological factors were hepatitis B infection (39.7%), hepatitis C virus infection (17.0%) and non-alcoholic fatty liver disease (9.0%). Median overall survival for the whole group was 25 [95% confidence interval (CI): 15.7-34.2] months. Cut-off values for AFP and NLR were accepted as 200 ng/mL and 3.45, respectively. The area under the ROC curve values for AFP, NLR and NLR+AFP were 0.625 (95% CI: 0.547-0.704), 0.589 (95% CI: 0.512-0.667) and 0.657 (95% CI: 0.583-0.731). From the multivariate analysis, advanced tumour size, lymph node involvement and metastasis (TNM) stage, presence of cirrhosis, high AFP, and high NLR values were associated with poor survival. Conclusion: AFP, NLR, advanced TNM, and presence of cirrhosis may predict prognosis in patients with HCC. Studies involving more countries are needed to corroborate these findings.

Low-dose (7.5 mg/kg) bevacizumab may be a viable option in recurrent ovarian cancer: A retrospective study.

Objective: Bevacizumab (BEV) is a humanized monoclonal antibody of vascular endothelial growth factor receptors and, as a result of clinical trials, was approved for the treatment of recurrent ovarian cancer (ROC). The aim of this study was to assess the clinical utility of BEV in patients with ROC in real-world practice beyond clinical trials. Materials and Methods: In this single-center retrospective cohort study, we evaluated the medical data of all patients with ROC who were treated with BEV between October 2013 and March 2020. Results: A total of 76 females were evaluated. Forty-nine (64.5%) patients were platinum sensitive and 27 (35.5%) patients were platinum resistant. BEV was used in combination with chemotherapy agents in all patients, and the most preferred combinations were gemcitabine/carboplatin (GC) (78.9%) and carboplatin/paclitaxel (14.5%). In all patients, the BEV dose was 7.5 mg/kg every 3 weeks. The median progression-free survival (PFS) was 11.1 months (95% confidence interval [CI]: 9.6-12.6), and the median overall survival (OS) was 22.3 months (95% CI: 17.5-27.2). In multivariate analysis, serous histological type (P = 0.01), maintenance BEV administration (P = 0.001), and combination of GC-BEV (P < 0.001) were associated with better PFS, while serous histological type (P = 0.016) and good performance status (P = 0.006) were associated with prolonged OS. Conclusions: Low-dose (7.5 mg/kg) BEV was found to be effective in the second-line treatment of patients with ROC in our real-life study. In addition, the combination of BEV with GC was shown to be a viable option, especially in the treatment selection of platinum-resistant patients.

Sunitinib-induced small bowel wall edema as a prognostic marker in metastatic renal cell carcinoma.

Aim: The aim of this study was to evaluate the presence of small bowel wall edema (SBWE) on computed tomography (CT) images in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib and to investigate the relationship between the presence of SBWE and survival. Materials and Methods: We retrospectively evaluated the presence of SBWE on CT images of 27 mRCC patients who received at least one cycle of sunitinib. Then, we analyzed the relationship between the presence of SBWE and progression-free survival (PFS) and overall survival (OS). RESULTS: All 27 patients had SBWE on at least one CT scan. The median value of SBWE thickness was 2.5 mm. SBWE thickness was ≤2.5 mm in 13 patients (group A) and >2.5 mm in 14 patients (group B). The median OS was significantly higher in group B (55 vs. 18 months, respectively, P = 0.02). Although it was not statistically significant (13 vs. 8 months, respectively, P = 0.69), the median PFS was longer in group B than in group A. CONCLUSIONS: This study showed that sunitinib treatment caused SBWE in all patients with mRCC who received the drug. Also, this study demonstrated an association between higher SBWE thickness and better survival outcomes.

The Evaluation of Dietary Antioxidant Capacity, Dietary Inflammatory Index and Serum Biomarkers in Breast Cancer: A Prospective Study.

Dietary antioxidant capacity (dTAC) and dietary inflammatory index (DII) are commonly used to assess nutrition. This prospective study examined dTAC, DII, and serum biomarkers in women with breast cancer (BC). Patients were followed-up before surgery (T1), before chemotherapy (T2), at 6th (T3) and 12th months of chemotherapy (T4). Serum tumor necrosis factor alpha, interleukin 1ß, interleukin 6, protein carbonyl, malondialdehyde, total antioxidant capacity (TAC), and total oxidant status levels were analyzed. Dietary antioxidant intake, dTAC, and DII were determined using a three-day dietary record. dTAC was calculated using vitamin C equivalent (VCE), oxygen radical absorption capacity (ORAC), trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), and ferrous ion reducing antioxidant potential (FRAP). This study included 32 women with BC and 32 controls (CG). ORAC, TEAC, TRAP, and FRAP were significantly lower in BC than in CG. During follow-up, only ORAC increased significantly at T2 compared to T1. A weak positive correlation was found between dTAC (VCE) and serum TAC levels at T2 (rho = 0.371, p = 0.036). The relationship between diet and serum biomarkers was not significant. Multicenter prospective studies on different age groups are needed to understand the association between diet and serum biomarkers levels in patients with BC.

Does red blood cell distribution width predict prognosis in metastatic renal cell carcinoma patients using first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy?

Aim: It is red cell distribution width (RDW) that has been reported to show an inflammatory response which has been studied recently. The aim of this study is to investigate whether the pre-treatment RDW in patients using first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) with the diagnosis of metastatic renal cell carcinoma (mRCC) predicts treatment response and is a prognostic factor or not. Methods: About 92 patients diagnosed with mRCC who were being treated with sunitinib or pazopanib in the first line between January 2015 and June 2021 were included in the study. The patients were divided into 2 groups, as being ≤15.3 and >15.3, according to the RDW cut-off value calculated by ROC analysis. Results: The mOS of patients with a RDW of ≤15.3% was 45.0 (30.0-59.9) months, and of 21.3 (10.4-32.2) in those with a RDW of >15.3%. This difference was statistically significant (p < 0.001). In the group of patients with a RDW of ≤15.3, median progression free survival (mPFS) (38.04 [16.3-59.7] months) was found to be significantly higher than those with a RDW of >15.3 (17.1 [11.8-22.5] months) (p = 0.04). In multivariate analysis, RDW level (≤15.3, >15.3), was determined to be prognostic markers (p = 0.022). Conclusion: In mRCC patients, the RDW value measured before first-line VEGFR TKI therapy is an independent prognostic marker.

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis.

Background: Small-cell lung cancer (SCLC) has a poor prognosis. For the last 30 years, first-line systemic treatment has remained unaltered. After the integration of immunotherapy, a new first-line gold standard, atezolizumab in combination with carboplatin plus etoposide, was approved in extensive-disease SCLC (ED-SCLC) in 2019. Materials and Methods: First-line randomized controlled studies that investigated anti-programmed cell death protein 1 (PD-1)/PD-1 ligand-1 (PD-L1) and anti-T-lymphocyte-associated protein 4 (CTLA-4) agents in combination with platinum plus etoposide (EP) were scoured. A total of six studies (two - anti-CTLA-4 and four - anti-PD1/PD-L1) were included and classic and network meta-analyses (NMAs) were performed. Results: Fixed model for overall survival (OAS) in the PD-1- or PD-L1-treated subgroup yielded a hazard ratio (HR) of 0.746 with a 95% confidence interval (CI) =0.662-0.840 and in the CTLA-4-treated subgroup a HR of 0.941 with a 95% CI = 0.816-1.084 for the immune therapy + chemotherapy versus chemotherapy comparison (CTLA-4-based versus PD-1- or PD-L1-based groups' comparison of OAS effect Q = 6.05, df = 1, P = 0.014). NMA showed that all chemotherapy + immunotherapy combinations were equally potent and more efficient than PE in terms of OAS and progression-free survival (PFS). Rank probability plots demonstrated nivolumab + EP as the most probable effective treatment modality in terms of OAS and PFS. Conclusion: The usage of anti-PD1/PD-L1 immunotherapy agents results in significant OAS advantage, and anti-PD1/PD-L1 agents are superior to anti-CTLA-4 approach in combination with platinum plus etoposide regimen in ED-SCLC.

The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers.

PURPOSE: It is known that the RAS and BRAF mutations are predictive for targeted therapies in treating metastatic colon cancer and negatively affect the prognosis of the disease. However, there are limited studies in early-stage colon cancer about the relationship of this mutational condition with the prognosis and relapse pattern of the disease. In this study, we evaluated the effects of mutational status on the clinical pattern of recurrence and survival in early-stage colon cancer in addition to classical risk factors. METHODS: Patients with early-stage colon cancer at the first time of diagnosis and developing recurrence or metastasis on following up were included in this study. Patients were divided into two groups according to the at the time of relapse RAS/BRAF mutation status: mutant or non-mutant/wild types. Then, mutation analysis was performed again from the early-stage tissue of the patients if available. The relationship between early-stage mutation status and progression-free survival (PFS), overall survival (OS), and relapse pattern was analyzed. RESULTS: The number of patients with mutant and non-mutations in the early stage was 39 and 40, respectively. Mutant and non-mutant patients with stage 3 disease were similar (69% and 70%, respectively). OS (47.27 months vs. 67.53 months; p = 0.02) and PFS (25.12 vs. 38.13 months; p = 0.049) were statistically significantly lower in mutant patients, respectively. Most patients had distant metastases on both sides at recurrence (61.5% vs. 62.5%, respectively). There was no significant difference between mutant and non-mutant patients regarding distant metastasis and local recurrence rates (p = 0.657). A discordance of 11.4% between early-stage and late-stage tissue mutation status. CONCLUSION: The presence of mutation in early-stage colon cancer is associated with shorter OS and PFS. The mutational status did not have a significant effect on the recurrence pattern. Because of the discordance of early-stage and late-stage mutational status, it is recommended to perform mutation analysis from tissue at relapse.

Are dietary and serum advanced glycation end-products related to inflammation and oxidation biomarkers in breast cancer patients: a follow-up study.

PURPOSE: This study is aimed at evaluating the relationship between dietary and serum advanced glycation end-products (AGEs) with serum inflammatory and oxidative stress biomarkers in breast cancer (BC). METHODS: A sample of BC patients was followed for 12 months (March 2020-January 2022). Three-day food consumption record and serum samples were taken before surgery (T1), before chemotherapy (T2), at the 6th month of chemotherapy (T3), and at the 12th month of chemotherapy (T4). Dietary AGE intake was represented by carboxymethyl lysine (dCML). Serum levels of CML, inflammation, and oxidation biomarkers were determined with biochemical blood tests. The results were compared according to human epidermal growth factor receptor-2 (HER2) status. RESULTS: Thirty-two women with BC and 32 age and body mass index-matched healthy women participated. No significant correlation was found between dCML and serum CML, inflammatory or oxidative stress biomarkers at T1, T2, and T4. A weak positive correlation was demonstrated between dCML and serum malondialdehyde levels (rho=0.355, p=0.046) at T3. The serum CML, inflammation, and oxidation biomarker levels of the HER2- group were significantly higher than those of the HER2+ group at T1. CONCLUSION: This study suggests that there is limited correlation between dCML and serum inflammation and oxidative stress biomarkers in BC patients. Inflammation and oxidative biomarker levels appear to decline with treatment although dietary and serum AGE levels show not a corresponding significant decline. The HER2- subtype appears to be associated with higher dietary and serum AGEs and higher inflammatory and oxidative stress biomarkers.

Prognostic biomarkers in metastatic colorectal cancer: delta prognostic nutritional index, delta neutrophil to lymphocyte ratio, and delta platelet to lymphocyte ratio.

BACKGROUND: The aim of this study is to determine the prognostic value of the prognostic nutritional index (PNI), the neutrophil to lymphocyte ratio (NLR), and the platelet to lymphocyte ratio (PLR) and their dynamic changes on survival outcomes in metastatic colorectal cancers (mCRC). METHODS: The data of 199 patients with mCRC were retrospectively analyzed. To evaluate the temporal relation between the PNI, NLR, and PLR values and survival, pre-chemotherapy PNI, NLR, and PLR levels were assessed from peripheral blood cell counts on admission; post-chemotherapy PNI, NLR, and PLR levels were assessed with follow-up blood cell counts within two weeks after chemotherapy; and the difference between pre-chemotherapy PNI, NLR, and PLR levels and post-chemotherapy PNI, NLR, and PLR levels was evaluated as delta PNI, delta NLR, and delta PLR. RESULTS: The median PNI, PLR, and NLR were 39.01, 150.2 and 2.53 before chemotherapy and 38.2, 146.6, and 3.31 after chemotherapy, respectively. The median OS was 23.7 months (95%CI:17.8-29.7) and 28.9 months (95%CI:24.8-33.08) for pre-chemotherapy PNI level < 39.01 vs. PNI level ≥ 39.01, respectively(p = 0.035) The positive delta PNI was significantly higher for OS than the negative delta PNI(p < 0.009). Delta PLR and delta NLR were not significant for OS and PFS(p > 0.05 for all). CONCLUSIONS: The results of this study clearly show that the negative delta PNI to be an independent predictor of poor OS and poor PFS in patients with colon cancer who received first line treatment. In addition, delta NLR and delta PLR were shown not to predict survival outcomes.

The effect of concomitant proton pump inhibitor use on survival outcomes of Nivolumab-treated renal cell carcinoma patients: a multicenter study.

AIM: We aimed to evaluate the effect of concomitant proton pump inhibitors (PPI) use with nivolumab on survival outcomes in metastatic renal cell carcinoma (mRCC) in second-line setting. METHODS: The study was designed as a multicenter and retrospective involving patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy. One hundred and nine patients with mRCC were divided into two groups based on whether they use PPI concomitantly with nivolumab: concomitant PPI users and non-users. Overall survival (OS) and progression-free survival (PFS) were compared between the groups with and without concurrent PPIs. RESULTS: Of 109 patients in our study, 59 were not using PPI concomitantly with nivolumab and 50 were using PPI concomitantly. The median PFS was 6.37 (5.2-7.5) months in the concomitant PPI group and 9.7 (4.5-15) months in the non-users (p = 0.03). The median OS was 14.6 (7.1-22.1) months in patients on PPI concurrently with nivolumab and 29.9 (17.1-42.7) months in the non-users (p = 0.01). Accordingly, PPI use for PFS (Non-use vs. Use = HR: 0.44, 95%Cl 0.28-0.96, p = 0.014) and PPI use for OS (Non-use vs. Use = HR: 0.68, 95%Cl 0.22-0.88, p = 0.01) were found to be as independent risk factors. CONCLUSIONS: Concomitant use of PPIs is associated with worse survival outcomes in patients with mRCC treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs in such patients.

Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study.

AIM: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). PATIENTS AND METHODS: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. RESULTS: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. CONCLUSION: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.

The prognostic role of HIF-1α and NF-κB expression in RAS wild-type metastatic colorectal cancer: A Turkish Oncology Group (TOG) study.

BACKGROUND: Not all RAS wild-type metastatic colorectal cancer (mCRC) patients experience the same benefit from anti-epidermal growth factor receptor (EGFR) treatments. Studies have shown that nuclear factor-κB (NF-κB), hypoxia-inducible factor-1α (HIF-1α), interleukin 8 (IL-8) and transforming growth factor ß (TGF-ß) may be therapeutic targets for mCRC. The aim of this study was to clarify the prognostic value of NF-κB, HIF-1α, IL-8, and TGF-ß expression in patients with left-sided mCRC receiving EGFR inhibitors. METHODS: Patients with RAS wild-type, left-sided mCRC treated with anti-EGFR on the first line between September 2013 and April 2022 were included. Immunohistochemical staining for NF-κB, HIF-1α, IL-8 and TGF-ß was performed from tumor tissues of 88 patients. Patients were divided into NF-κB, HIF-1α, IL-8 and TGF-ß expression positive and negative group, moreover, expression positive group were also divided into two group as expression intensity low and high group. The median follow-up was 25.2 months. RESULTS: Median progression-free survival (PFS) was 8.1 (6-10.2) months in the cetuximab group, 11.3 (8.5-14) months in the panitumumab group (p = 0.09). Median overall survival (OS) was 23.9 (4.3-43.4) months in the cetuximab group, 26.9 (15.9-31.9) months in the panitumumab group (p = 0.8). Cytoplasmic NF-κB expression was present in all patients. The mOS was 19.8 (11-28.6) months in NF-κB expression intensity low group and 36.5 (20.1-52.8) months in high group (p = 0.03). The mOS of the HIF-1α expression negative group was significantly longer compared with expression positive group (p = 0.014). There was no significant difference in IL-8 and TGF-ß expression status on mOS and mPFS (for all, p > 0.05). Positive expression of HIF-1α was poor prognostic for mOS in the univariate analysis (HR:2.7, 95% CI 1.18-6.52, p = 0.02) and in multivariate analysis (HR 3.69, 95% CI 1.41-9.6, p = 0.008). High cytoplasmic expression intensity of NF-κB was found to have a good prognostic value for mOS (HR 0.47, 95% CI 0.26-0.85, p = 0.01). CONCLUSION: High cytoplasmic expression intensity of NF-κB and negative expression of HIF-1α could be a good prognostic marker for mOS in RAS wild-type left-sided mCRC.

Ribociclib-induced hepatotoxicity.

INTRODUCTION: Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown a different adverse effect. In this case, persistent grade 3 hepatoxicity was observed after ribociclib. Therefore, ribociclib therapy was stopped, and then palbociclib was introduced. Transaminase levels returned to normal by switching to palbociclib therapy. CASE REPORT: 71-year-old postmenopausal female patient with luminal subtypes of metastatic breast cancer treated with ribociclib. MANAGEMENT & OUTCOME: Grade 3 hepatotoxicity secondary to ribociclib developed. She was successfully treated with palbociclib 125 mg. DISCUSSION: In our case, palbociclib was started with a full dose, to increase treatment success. Starting with a 125 mg dose was not cause any toxicity. Nevertheless, laboratory follow-up is required in terms of neutropenia and increased transaminases.

Could the concomitant use of beta blockers with bevacizumab improve survival in metastatic colon cancer?

AIM: Drug-drug interactions are sometimes neglected in oncology practice. Due to drug pharmacokinetic and pharmacodynamic interactions, clinically increased or decreased drug effects and increased or decreased adverse effects may occur. Considering that the concomitant use of these two drugs that affect vascular endothelial growth factor receptor (VEGFR) may cause pharmacological potentiation or additive interaction, we aimed to evaluate the survival outcomes of concomitant use of bevacizumab and beta blockers in patients with metastatic colorectal cancer (mCRC). METHODS: In total, 181 patients with mCRC administered with bevacizumab plus cytotoxic chemotherapy regimen in a first-line setting were divided into two groups: concomitant beta-blocker user and nonuser. RESULTS: The median overall survival (mOS) was 35.9 (95% CI: 27.9-43.9) months in the beta-blocker-using group and 29.6 (95% CI: 27.9-43.9) months in the beta-blocker-non-using group (p = 0.054). The median progression-free survival (mPFS) was 16.1 (95% CI: 12.4-19.9) months in the beta-blocker-using group and 12.8 (95% CI: 10.6-15.0) months in the beta-blocker-non-using group (p = 0.006). The multivariate analysis revealed that beta-blocker use was an independent predictor of mPFS (HR: 0.66, 95% CI: 0.46-0.93, p = 0.018) and mOS (HR: 0.57, 95% CI: 0.36-0.91, p = 0.02). CONCLUSION: This study demonstrated that concomitant usage of beta blockers improved both survival outcomes, irrespective of the kind of beta blocker.

The effect of concomitant use of proton pump inhibitors with CDK 4/6 inhibitors on survival in metastatic breast cancer.

AIM: To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC. METHODS: We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users. RESULTS: Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94-27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9 months (95% CI: 7.5-14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use (p = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib. CONCLUSION: Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib.