Urbanization-driven soil degradation; ecological risks and human health implications.

Urban soils contaminated with heavy metals and pesticide residues are of great concern because of their adverse impact on human health. A total of 66 agricultural topsoil samples (15 cm) were collected to represent the study area and determine how anthropogenic activities adversely affect soil quality and human health. Sampling was conducted in the summer, when it was dry and hot, and in the winter, after atmospheric deposition. Seventeen potentially hazardous metals/metalloids (Ag, As, Al, B, Ba, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Mo, Pb, Se, Zn, and V) were measured in the soils. The mean concentrations of metals ranged between 0.05 and 8080 mg/kg, and their distribution was site-specific, with high pollution at the sampling sites owing to proximity to human activities. In agricultural areas, the greatest arsenic concentration was recorded at 48 mg/kg. The potential ecological risk index (PERI) and health hazard index (HI) were calculated, as well as metal contamination indices including contamination factor (Cf), geo-accumulation index (Igeo), and pollution load index (PLI). The mean PLI was calculated to be 4.89, indicating that the area is highly polluted. The potential ecological risk index showed remarkably high risks for As, Cd, and Hg, and moderate risks for Ni and Pb. The arsenic hazard index (HI) was greater than one (2.41) in children, indicating a risk of exposure through ingestion. Pesticide residue analyses were performed in areas where the metal intensity was high. Banned or restricted organochlorine pesticide (OCPs) residues, including, dieldrin, endrin ketone, endosulfan I, II, heptachlor, heptachlor epoxide, lindane (γ-HCH), PP-DDD, and methoxychlor, were detected between 0.002 and 1.45 mg/kg in the soil samples.

Global supply chains risks and COVID-19: Supply chain structure as a mitigating strategy for small and medium-sized enterprises.

After the COVID-19 pandemic, more research is needed to understand how the impacts of global events differ among alternative network structures in the presence of supply chain risks, and how relevant these potential risk mitigation strategies are for Small and Medium Enterprises(SMEs). Thus, our main motivation is to show how SMEs can configure their supply chains, and cost-effectively mitigate the risk created by major disruptions. We combined a case study with a simulation model. The results suggest the greater usefulness of certain network configuration strategies (e.g., collaboration, multi-sourcing) compared to others during catastrophic events. Our results indicate that SMEs can avoid suffering more harm than larger competitors by adopting strategies consisting of an adequate mix of proactive and reactive elements, and that an effective proactive strategy involves building flexibility by increasing the number of geographically spread supply chain partners, allowing for deeper discounts to preserve demand without hurting profits.

The relationship between clinicopathological parameters and PD-L1 expression level in advanced stage non-small cell lung cancer.

Introduction: Clinicopathological parameters related to programmed death ligand 1 (PD-L1) expression levels have been investigated in several studies. However, the results of these studies are conflicting and vary in different populations. This study aimed to investigate the relation of clinicopathological parameters with PD-L1 expression level in advanced stage non-small cell lung cancer patients. Materials and Methods: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The data of clinicopathological parameters was collected. Clinicopathological parameters in relation to PD-L1 expression levels (0%, 1-50%, and >50%) were analyzed as univariable and multivariable. Result: In total, 384 patients were enrolled. PD-L1 expression in tumor cells was between 1-50%, and >50% in 41.4%, and 23.4% of patients, respectively. There was no PD-L1 expression in 35.2% of the patients. In univariable analysis, we found that the parameters associated with PD-L1 expression levels revealed that metastatic site number, the subtype of cancer, diagnostic material type, platelet number, and LDH level were statistically significant. Adenocarcinoma frequency was higher in tumors that had PD-L1 expression >50% than in tumors that did not express PD-L1 and the difference was statistically significant (p= 0.04, coefficient= 0.3, 95% CI 0.09-0.94). Cytology as diagnostic material was significant in PD-L1 level 1-50% comparing to >50% (p= 0.02, coefficient= 2.2, 95% CI= 1.08-4.46). Conclusions: According to the results of our study, many of the clinicopathological parameters are not related to the PD-L1 level. The histological subtype and diagnostic material may affect the level of PD-L1 expression.

Efficacy and tolerability of vismodegib treatment in locally advanced and metastatic basal cell carcinoma: Retrospective real-life data.

The study aims to evaluate the vismodegib treatment in local advanced (laBCC) and metastatic (mBCC) basal cell carcinoma. The data of 29 patients were retrospectively reviewed. The clinical and histopathological features of the patients and adverse events of vismodegib were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated with Kaplan-Meier analysis. The median follow-up period was 17 months (range: 1.6-57.3), and the median age at diagnosis 73 years (range: 39-88). The most common disease location was head and neck (86.2%), and the most common non-skin sites of disease were lymph nodes (13.8%), bone (13.8%), lung (6.9%), and brain (6.9%). Three (10.3%) patients had Gorlin's syndrome. The number of metastatic patients was 5 (17.2%). With vismodegib treatment, the complete response rate was 27.6%, partial response 55.2%, and stable response 10.3%. Treatment responses were most frequently seen within 2 months from the beginning of vismodegib. The median OS was 43.3 ± 9.0 months (25.6-61.1) for all patients. The median PFS in the laBCC was 15.7 ± 1.8 months (12.2-19.3), and 12.1 ± 4.6 months (2.9-21.2) in the mBCC. In the univariable analysis for the OS, only the treatment after the vismodegib was statistically significant, showing chemotherapy was better comparing to no treatment or surgery. The most common adverse events were fatigue-58.6%, muscle spasms-48.3%, alopecia-13.8%, and weight loss-13.8%. This real-life data study shows that vismodegib treatment in locally advanced and metastatic BCC was well tolerated and effective.

Topical aloe vera for the treatment of cetuximab-related acneiform rash in colorectal cancer: A case report.

INTRODUCTION: Colorectal cancer is one of the most common cancers in the world. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor which provides survival benefit when combined with chemotherapy in RAS wild type metastatic colorectal cancer. Cutaneous toxicities associated with cetuximab have a significant impact on patient quality of life, treatment continuation and healthcare resource utilization. CASE REPORT: A 60-year-old male patient presented with fatigue, weight loss and abdominal pain. Two closely located malignant polypoid lesions were detected in the sigmoid colon, and pathological examination revealed colonic adenocarcinoma.Management and outcome: Thorax, abdominal and pelvic computed tomography showed metastases. FOLFOX chemotherapy and cetuximab were started. The patient developed acneiform rash firstly in his face, although prophylactic vitamin K1 0.1% containing cream was given. He was given mild potency topical corticosteroid and doxycycline. The lesions progressed to his front and back body. He did not want to use topical vitamin K1 cream, topical steroid and doxycycline tablets. Instead, he wanted to use aloe vera extract which he produced from the leaves of the plant. Patient's lesions were regressed significantly. DISCUSSION: The most common and earliest skin toxicity is acneiform rash which affects 60 to 80% of the patients. In this case, cetuximab-related severe acneiform rash was effectively treated by topical aloe vera. Topical aloe vera may be used in the management of cetuximab-related cutaneous toxicities without any side effect.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

Tumor-Induced Myeloid Cells Are Reduced by Gemcitabine-Loaded PAMAM Dendrimers Decorated with Anti-Flt1 Antibody.

While reshaping their microenvironment, tumors are also capable of influencing systemic processes including myeloid cell production. Therefore, the tumor-induced myeloid cells, such as myeloid-derived suppressor cells (MDSCs), which are characterized with pro-cancer properties, became another target in order to increase the success of the therapy. This study evaluated the capacity of a novel dendrimeric drug delivery platform to eliminate tumor-induced myeloid cells. As described in a previous study by our research group, the anti-Flt1 antibody-conjugated polyethylene glycol (PEG)-cored poly(amidoamine) (PAMAM) dendrimers improved the efficacy of gemcitabine against pancreatic cancer. Here, the biodistribution studies showed that these dendrimeric structures accumulated in the compartments that became rich in myeloid cells in the pancreatic tumor-bearing mice. When gemcitabine was loaded into the dendrimer complexes, the number of myeloid cells was significantly reduced while the percentage distribution of granulocytic and monocytic myeloid cells was not always significantly altered. The CD11b+Ly6G-Ly6C+ monocytes were more severely affected by the treatments than CD11b+Ly6G+Ly6C+ granulocytes. Immune infiltration levels in the tumor tissue were also altered. Myeloid cells in the spleen and F4/80+ macrophages of the liver were protected. The compartments, such as the liver and the bone marrow, which are known to have high vascular endothelial growth factor (VEGF)-Flt1 pathway activity, were particularly targeted by gemcitabine when delivered through anti-Flt1 antibody-conjugated PAMAM dendrimers. In conclusion, chemotherapeutic agents complexed with dendrimers not only improve anticancer efficacy, but they also assist in the elimination of the tumor-induced myeloid cells.

Evaluation of Jeffamine® Core PAMAM Dendrimers for Simultaneous Removal of Divalent Heavy Metal Ions from Aqueous Solutions by Polymer Assisted Ultrafiltration.

Different generations (G3-G4) of amine-terminated Jeffamine® T-403 core poly(amidoamine) PAMAM dendrimers (JCPDs) were used as new macromolecular heavy metal chelating agent templates in polymer assisted ultrafiltration (PAUF) for the investigation of their removal ability for some of the divalent metal ions: Cu, Co, Ni, Cd, and Zn from aqueous solutions under competitive conditions. The effects of pH and generation size of JCPDs were also investigated. Extent of binding (EOB) data can be appropriately expressed by a tetradentate coordination for JCPDs at pH 9 where the maximum removal of metal ions was observed. At pH 9.0, the affinity of both generations towards heavy metal ions was also observed in the decreasing order of Zn(II) > Co(II) > Ni(II) > Cu(II) > Cd(II). Results revealed that the highest total binding capacity was observed for G3-NH2 (262.79 ± 1.62 mg/g) as a little bit higher than that of G4-NH2 (257.27 ± 2.57 mg/g). EOB studies also proved the active contribution of amide groups to metal binding ability of PAMAMs. Both generations were selective towards Cu(II) ions at lower pH 5 and pH 7. From these results, it was concluded that studied JCPDs have the desired technical properties to be used for the removal of toxic metals from wastewaters.

Synthesis of surface-modified TREN-cored PAMAM dendrimers and their effects on the solubility of sulfamethoxazole (SMZ) as an analog antibiotic drug.

Sulfamethoxazole (SMZ) is a sulfonamide and used widely in the treatment of bacteriostatic and urinary tract infections with trimethoprim as an antibiotic. The problem with SMZ is its poor water solubility, therefore, low bioavailability in clinical applications. In this study, we synthesized new-generation Tris(2-aminoethyl)amine (TREN)-cored amine (NH2), Tris(hydroxymethyl)aminomethane (TRIS), and carboxyl (COOH) terminated different generations T2-T4 poly(amidoamine) PAMAM dendrimers. Synthesized PAMAMs were characterized by 1H NMR, 13C NMR, ATR-FTIR, spectroscopic titrations, and evaluated as potential solubility enhancers and drug carriers of sulfonamides by taking SMZ as a model drug. The effect of concentration, generation, and surface groups of PAMAMs on the solubility of SMZ was also investigated. Results showed that the solubility of SMZ improved significantly with an increasing generation size (T2-T4) and PAMAM dendrimer concentration (0-2 mM). The role of PAMAMs in the solubility enhancement of SMZ was in the order of T4.NH2 > T4.COOH > T3.NH2 > T4.TRIS > T2.NH2 > T3.COOH > T3.TRIS > T2.COOH > T2.TRIS, and in the ranges of 5- to 45-fold with maximum SMZ loading 7 to 61 mole/mole per PAMAM dendrimer molecule. In vitro release studies demonstrated that SMZ-PAMAM dendrimer complexes at the end of 2-h drug release (16-26%) was considerable slower than pure SMZ (38.8%).

The effect of PAMAM dendrimer concentration, generation size and surface functional group on the aqueous solubility of candesartan cilexetil.

This article investigates the aqueous solubility of the poorly soluble drug candesartan cilexetil (CC) in the presence of poly(amidoamine) (PAMAM) dendrimers. The effect of variables such as concentration, generation size (G2-G4), and surface groups (NH2, COOH and TRIS) of PAMAMs on the aqueous solubility of CC was studied. A two-factor factorial (3 × 3) ANOVA design was used to study the effect of generation size and surface functional group of the PAMAMs. The results showed that the aqueous solubility of CC in the presence of carboxyl and TRIS-terminated PAMAMs was higher than those of amine-terminated PAMAMs, and the effect of surface functional group of the PAMAMs on the aqueous solubility of CC was dependent on the generation size (p < 0.05). The sequence of the observed solubility fold enhancement due to PAMAMs was G4.COOH (8378)>G3.COOH (3456)>G4.TRIS (2362)>G2.COOH (1013)>G3.TRIS (749)>G2.TRIS (293)>G4.NH2 (91)>G3.NH2 (50)>G2.NH2 (37). The CC-PAMAM dendrimer inclusion complexes were characterized by UV-Vis, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential thermal analysis (DTA) techniques. Regarding the results of these techniques, improvement in the solubility of CC is expected primarily through the intermolecular hydrogen bonding between the drug and internal tertiary and surface functional groups of the studied PAMAMs.

Preparation of Cu Nanocomposites from EDA, DETA, and Jeffamine Cored PAMAM Dendrimers with TRIS and Carboxyl Surface Functional Groups.

This study presents the synthesis and UV-Vis characterization of Cu nanocomposites from ethylenediamine (EDA) (E), diethylenetriamine (DETA) (D), and Jeffamine® T-403 (P) cored PAMAM dendrimers (PAMAMs) with TRIS and carboxyl surface functional groups. Cu-PAMAM dendrimer encapsulated nanoparticles (Cu-DENs) were characterized by UV-Vis spectroscopy. Disappearance of the 680 nm d-d transition and 270-300 nm ligand to metal charge transfer (LMCT) peaks and the formation of monotically increasing exponential band were used as the evidence of the successful synthesis of Cu-DENs in addition to immediate color change of dendrimer-metal mixture solutions from blue to golden brown by reduction. Synthesized Cu-DENs could be facilitated as novel alternatives to the existing nanomaterials used in a wide range of applications involving bio and chemical sensors, catalysis, hydrogenations, oxidations, semiconductors, noble metals, magnetic dendrimer nanocomposites, environmental cleanup and many others.

Is Carpal Tunnel Release Necessary in High-Energy Distal Fractures of the Radius?

Purpose This study aimed to compare the clinical outcomes of patients who underwent volar plate osteosynthesis for high-energy distal radius fracture (DRFx) and carpal tunnel release (CTR) for acute or subacute carpal tunnel syndrome (CTS) with patients who did not undergo CTR. Methods This study is a retrospective evaluation of all high-energy DRFx treated with volar plate osteosynthesis in a regional hospital between January 2021 and January 2023. All adult patients (≥18 years) who underwent open reduction and internal fixation were included in the study after obtaining approval from the internal review board of our institution. Only patients who underwent plate osteosynthesis of the volar aspect through a modified Henry incision and patients who underwent CTR through a classic separate incision were included in the study. Clinical results include hand dynamometry, visual analog scale (VAS) scores, and physical examination findings of patients who underwent volar plate osteosynthesis because of high-energy DRFx and CTR due to CTS in the acute and subacute periods were retrospectively examined. Results Among the patients who underwent volar plate osteosynthesis because of high-energy DRFx, no statistically significant difference was detected between the hand grip strength and VAS scores of patients who underwent CTR because of acute CTS and subacute CTS at the sixth postoperative week (p>0.05). Conclusion Prophylactic CTR may be performed in the same session in selected cases, such as DRFx caused by a high-energy injury, to establish a scale for DRFx at a high risk of CTS and avoid delays in treatment. CTR for transient CTS detected in the subacute period during outpatient follow-up does not improve clinical outcomes.

The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

Distributions and prognostic effects of ABO/Rh blood groups in patients with HER2/neu positive gastric and gastroesophageal junction cancer.

BACKGROUND: The aim of study was to look at ABO/Rh blood types frequency and prognostic significance in patients with HER2/neu positive gastric cancer. METHODS: The study was designed retrospectively. Clinicopathological characteristics, treatment approaches, and the ABO/Rh blood groups features were noted. The ABO/Rh blood types for patients and healthy donors were compared by the Chi-square method. RESULTS: The average age was 61 years. The average survival time was 17.9 months (13.2-22.5). ABO blood types frequencies were not similar between patients (25.9% O, 6.3% AB, 57.1% A, and 10.7% B) and control group (34.9% O, 7.9% AB, 41.9% A, and 15.3% B) (P = 0.01). Patients and controls had the same Rh factor distribution (P = 0.07). CONCLUSIONS: We showed that A blood group frequency was increased in patients with HER2/neu receptor-positive gastric cancer than in a healthy population. Also, we detected that the frequency of O blood type was decreased. ABO/Rh blood types were not linked with prognosis for overall survival.

Evaluation of clinicopathological features determining treatment response in patients with ALK mutant NSCLC.

ALK (anaplastic lymphoma kinase) inhibitors may be used to treat patients with ALK mutant metastatic nonsmall cell cancer (NSCLC). This study aimed to investigate the factors affecting the patients response to treatment with ALK-positive metastatic NSCLC. Data of the patients were investigated retrospectively. Binary regression analysis was performed to evaluate response predictors of treatment. Furthermore, we determined the cut-off value of the ALK-positivity for objective response to the therapy using ROC analysis. A total of 68 patients were included in the research. The median overall survival was observed 39.2 months. The overall response rate was 66.2%. The ratio of ALK positivity (P = .02), gender (P = .04), and the total number of metastatic sites (P = .02) all were detected as predictors of the response to ALK inhibitor in binary regression analysis. ALK inhibitor type (P = .56), primary tumor location (P = .35), pathological subtype (P = .68), de-novo metastatic disease (P = .28), and age (P = .94) were not predictive indicators for response. The cut-off level of ALK positivity was found to be 33% in patients with an objective response. The real-life effectiveness of ALK inhibitors in NSCLC patients with ALK mutations was shown in this research. We determined that having less than 3 metastatic sites, having a high ALK positivity ratio, and being female were all good predictors of ALK inhibitor response.

The frequency and prognostic significance of ABO/Rh blood groups in male breast cancer patients: A multicenter study.

The study evaluated the distributions and prognostic significance of ABO and rhesus (D) groups in male breast cancer (MBC) patients. The data of 137 patients were retrospectively reviewed. Clinical, histopathological data and ABO/Rh blood groups of the patients were recorded. The ABO/Rh blood group distributions were compared to the healthy men control group (n = 120,160) by the chi-square test. Overall distributions of ABO blood groups were different between the patients (17.5% AB, 38% A, 19% B, and 25.5% O) and control group (7.88% AB, 42.06% A, 15.22% B, and 34.84% O) (P < .001). There were significant differences between the patients and control group with respect to AB vs non-AB blood group distributions (P < .001, odds ratio: 2.43, 95% CI) and O vs non-O blood group distributions (P = .016, odds ratio: 0.62, 95% CI). However, A vs non-A and B vs non-B blood group distributions were not significantly different. The distribution of the Rh factor was similar between patients and the control group (P = .93). In univariate analysis, ABO/Rh blood groups were not a prognostic factor on OS (P = .29). The frequency of the AB blood group in MBC patients is increased than in the healthy control group. AB blood group may be a risk factor for MBC, whereas O blood group may be a protective factor.

Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group.

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.

Trastuzumab ± Capecitabine Maintenance After the First-Line Treatment of HER2-Positive Advanced Gastric Cancer: Retrospective Observational Real-Life Data of Turkish Oncology Group.

PURPOSE: In the ToGA trial for HER2-positive advanced gastric cancer, cisplatin plus fluoropyrimidine was given for 6 cycles; trastuzumab was given until disease progression. However, there is a lack of real-life data about trastuzumab maintenance after 6 cycle chemotherapy. This study aims to present real-life data of trastuzumab ± capecitabine maintenance after 6 cycles of platinum, fluoropyrimidine, and trastuzumab in non-progressive patients. METHODS: This is a retrospective multicenter study of the Turkish Oncology Group. A total of 35 HER2-positive, inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma patients being non-progressive at the end of 6 cycle chemotherapy and being given trastuzumab ± capecitabine as maintenance treatment were included from sixteen oncology centers. Baseline characteristics, objective tumor responses, progression free and overall survival data, and toxicities were determined. RESULTS: About 68% of the patients were given CF, and 32% were given FOLFOX with trastuzumab as the first-line treatment. The best response in 6 cycle chemotherapy was complete 8 (22%), partial 24 (68%), and stable disease 3 (8%). All patients had trastuzumab maintenance (median cycle 13; range 7-51), and 49% of the patients had capecitabine with trastuzumab (median capecitabine cycle 6; range 2-30). The median PFS of the patients was 12.0 months (95% CI 10.3-13.7), and median OS was 17.4 months (95% CI 15.2-19.5). There were 2 patients with grade 1 cardiotoxicity. CONCLUSION: Trastuzumab maintenance ± capecitabine after 6 cycles of trastuzumab plus combined chemotherapy treatment revealed efficacy and safety in non-progressive HER2-positive advanced gastric cancer.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

PURPOSE: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. METHODS: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. RESULTS: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. CONCLUSION: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: a Turkish Oncology Group Study.

INTRODUCTION: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation. MATERIALS AND METHODS: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. CONCLUSION: Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.