Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Thickness Gradient in Polymer Coating by Reactive Layer-by-Layer Assembly on Solid Substrate.

The study describes a simple yet robust methodology for forming gradients in polymer coatings with nanometer-thickness precision. The thickness gradients of 0-20 nm in the coating are obtained by a reactive layer-by-layer assembly of polyester and polyethylenimine on gold substrates. Three parameters are important in forming thickness gradients: (i) the incubation time, (ii) the incubation concentration of the polymer solutions, and (iii) the tilt angle of the gold substrate during the dipping process. After examining these parameters, the characterization of the anisotropic surface obtained under the best conditions is presented in the manuscript. The thickness profile and nanomechanical characterization of the polymer gradients are characterized by atomic force microscopy. The roughness analysis has demonstrated that the coating exhibited decreasing roughness with increasing thickness. On the other hand, Young's moduli of the thin and thick coatings are 0.50 and 1.4 MPa, respectively, which assured an increase in mechanical stability with increasing coating thickness. Angle-dependent infrared spectroscopy reveals that the C-O-C ester groups of the polyesters exhibit a perpendicular orientation to the surface, while the C≡C groups are parallel to the surface. The surface properties of the polymer gradients are explored by fluorescence microscopy, proving that the dye's fluorescence intensity increases as the coating thickness increases. The significant benefit of the suggested methodology is that it promises thickness control of gradients in the coating as a consequence of the fast reaction kinetics between layers and the reaction time.

Off-Label Uses of Ranibizumab and Aflibercept for Age-Related Macular Degeneration in Turkey.

Purpose: To evaluate the clinical and demographic aspects of off-label drug use applications for age-related macular degeneration (AMD) in Turkey. Methods: Applications for off-label drug use in the treatment of AMD to the Turkish Medicines and Medical Devices Agency (TITCK) in 2018 were retrospectively analyzed. Demographic characteristics, requested drugs, previous treatment regimens, and reasons for applications were evaluated. Results: The mean age of the patients (n = 209) was 64.9 ± 15.7 years, of which 48.8% were male and 51.2% were female. Ranibizumab (n = 113) comprised 54.1% and aflibercept (n = 96) 45.9% of off-label use applications. No application was made for bevacizumab. The most frequent reasons for application were switchback (49.3%), nonreimbursement of indicated drugs in cases under 50 years of age (24.4%), and failure to complete the loading dose (14.4%). Conclusions: Ranibizumab was the most requested off-label drug for AMD. There was no application for off-label bevacizumab since its use does not require approval from TITCK. In Turkey, new rules were established for the reimbursement of intravitreal drugs for AMD in 2019. Three doses of intravitreal bevacizumab were required initially for aflibercept and ranibizumab to be covered for reimbursement. There is not enough data in the English literature regarding the off-label use of ranibizumab and aflibercept for AMD. This study provides information about drug regulations and the off-label treatment options preferred by physicians for AMD in Turkey.

Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Biological therapy for ocular Behçet's disease with off-label drug prescription in Turkey.

OBJECTIVE: The use of biological agents in the treatment of ocular Behçet's disease has recently become more frequent. The use of two agents, infliximab (IFX) and adalimumab (ADA), for the treatment of Behçet's disease requires prior approval by the Turkish Medicines and Medical Devices Agency. We report on a review of such applications with a view to informing on how such agents are used off-label in Turkey. METHODS: Prescriptions for off-label use of IFX or ADA sent from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency in 2018 were evaluated. Demographic data, previous treatment regimens and reasons for referral were extracted from the files of the cases. RESULTS: A total of 662 patients were considered for off-label use of IFX or ADA for the treatment of ocular Behçet's disease. The mean age of the patients was 35.7±10.8 years (range 12-76); 61.5% of patients were men and 38.5% were women. Of the applications, 345 (52.1%) were for IFX and 317 (47.9%) for ADA. Among the referring hospitals, the public university hospitals ranked first, accounting for 77.9% of IFX and 88.6% of ADA prescriptions. Most applications were made after the failure of conventional therapy, which included steroids and immunosuppressive agents. CONCLUSION: IFX and ADA are rarely used as initial therapy. Stepwise treatment is still preferred in the treatment of ocular Behçet's disease in Turkey. Our report informs on the management of this difficult-to-treat condition.

Evaluation of off-label anti-vascular endothelial growth factor and steroid implant medication uses in macular edema due to retinal vein occlusion in Turkey.

WHAT IS KNOWN AND OBJECTIVE: Retinal vein occlusion (RVO) is one of the most common causes of vision loss. Anti-vascular endothelial growth factor (anti-VEGF) drugs, ranibizumab and aflibercept, and corticosteroid implants are approved treatment options for RVO-related macular edema (ME) in Turkey. To the best of our knowledge, there is no data regarding the off-label use of these drugs for RVO in English literature. We aimed to evaluate the clinical and demographic characteristics of off-label drug use applications in Turkey for RVO. METHODS: Applications made to the Turkish Medicines and Medical Devices Agency between January 1 and December 31, 2018, for the use of off-label drugs (ranibizumab, aflibercept, dexamethasone implant) for the diagnosis of RVO from hospitals across Turkey were retrospectively analysed. Data of the applications, such as demographic characteristics, previous treatment regimens, reasons for applications, applicant hospitals and their regions, were recorded. RESULTS: There were 291 approved applications for RVO. The mean age of the patients was 64.88 ± 10.78 years, 48.8% were male, and 51.2% were female. Of these applications, 44.7% were for aflibercept, 35.7% for ranibizumab and 19.6% for dexamethasone implant. No application was made for bevacizumab since it could be used without needing for an application. The most common reasons for applications were due to dose limitations, failure to complete loading doses, and glaucoma, respectively. In terms of the distribution of the applicant hospitals, public university hospitals ranked first with 72.5%, training and research hospitals ranked second with 14.7% and foundation university hospitals ranked third with 13.1% rates. WHAT IS NEW AND CONCLUSION: The practice of drug use in RVO in Turkey has changed as of the beginning of 2019. Stepwise therapy has been accepted by the drug regulatory agency Turkish Medicines and Medical Devices Agency. Utilization of licensed drugs, aflibercept, ranibizumab and dexamethasone has been allowed only after administration of 3 doses of intravitreal bevacizumab. After 3 doses of bevacizumab, the physician may continue either with bevacizumab again or a dexamethasone implant. If there is a reason such as the presence of glaucoma, the physician may skip dexamethasone and switch to aflibercept and ranibizumab, but in this case, dexamethasone cannot be administered to the patient for life. The evaluation of the off-label treatments of RVO, which is one of the most frequently followed diseases in retina clinics, not only contributes to the literature but also provides information regarding the most frequently applied treatments and the physicians' off-label drug preferences for RVO.

Spatial, temporal, and vertical variability of nutrients in the Southeastern Black Sea.

In this study, the nutrient concentrations along the coastal region of the Southeastern Black Sea were evaluated based on temporal, spatial, and vertical distributions. The water samples were collected seasonally in 2013 from 432 depths covering 55 stations. The nutrient concentrations showed significant spatial and temporal variations that declined abruptly from shore to offshore. The stations near the river discharge had the highest silicate, nitrate, and total dissolved inorganic nitrogen (DIN). The highest nitrate concentrations were determined within the oxycline layer and nitrite within the suboxic layer, while phosphate, ammonium, silicate, and DIN were within the anoxic layer. The findings of this study evinced that the Southeastern Black Sea possessed lower contents of nitrate (mean ± s.d., 0.58 ± 1.17 µM), phosphate (0.12 ± 1.00 µM), than the literature values reported for the western Black Sea, but consistent to the eastern Black Sea. However, the silicate concentrations of the study area were consistent with the western Black Sea while higher than the eastern Black Sea. The Trophic Index showed that two stations located on the coast of the Samsun and Giresun were at increased risk of eutrophication due to intensive urban and industrial inputs. This study provides detailed insights on the nutrient status of the coastal Southeastern Black Sea, which should facilitate the development of long-term monitoring programs concerning environmental aspects of marine and coastal planning.

Off-label uses of Aflibercept, Ranibizumab and Dexamethasone implant for diabetic retinopathy in Turkey.

Objective: Diabetic retinopathy (DRP) is the most common retinal vascular disease leading to blindness. There is limited data about the off-label drug use for DRP and diabetic macular edema (DME) in literature. The aim of the article was to evaluate the applications for off-label drug use in patients with DME and DRP in Turkey in terms of demographic and clinical characteristics. Methods: Applications for off-label drug use from hospitals across Turkey to the Turkish Medicines and Medical Devices Agency for DRP in 2018 were reviewed retrospectively. Results: 112 approved applications for 167 eyes were included in our study. The mean age of the cases was 61.24 ± 10.23 years, of them 57.1% were males and 42.9% were females. Of these applications, 41.1% were for aflibercept (n:46), 33.9% for ranibizumab (n:38), and 25% for dexamethasone implant (n:28). There was no application for bevacizumab. In terms of referring hospitals, public university hospitals were in the first place with a rate of 70.5%. The most common reasons for applications were drug switchback request and failure to complete loading dose, respectively. Discussions: DRP treatment can sometimes be challenging. The effectiveness of the intravitreal drugs may decrease over time and drug switching may be necessary. In Turkey, intravitreal drugs are only approved and reimbursed for DRP patients in case of macular edema. Off-label drug use may be preferred in non-approved indications and for reasons such as the need for additional drug doses to the determined limits. However, permission must be obtained from TMMDA for off-label drug use in Turkey. Conclusion: Anti-vascular endothelial growth factor drugs are the first-line treatment options for DME. TMMDA currently approves stepwise therapy for diabetic macular edema, initiated with bevacizumab. Bevacizumab administration does not require approval for off-label application. Additionally, ranibizumab, aflibercept, and dexamethasone implant are reimbursed only in case of failure to respond to 3 doses of bevacizumab injection. Our report provides information about off-label drug preferences and drug use regulations in DRP treatment in Turkey. Abbreviations:DME = diabetic macular edema, DRP = Diabetic retinopathy, FFA = fundus fluorescein angiography, TMMDA = Turkish Medicines and Medical Devices Agency, VEGF = vascular endothelial growth factor.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

The efficacy of esmolol, remifentanil and nitroglycerin in controlled hypotension for functional endoscopic sinus surgery / Eficácia do esmolol, remifentanil e nitroglicerina na hipotensão controlada para cirurgia sinusal endoscópica funcional

Abstract Introduction Controlled hypotension is a reversible procedure in which the patient's baseline mean arterial blood pressure is reduced by 30% and sustained at 60-70 mmHg during the procedure. It decreases blood loss and provides clear surgical field during the procedures. Objectives The purpose of this study was to compare the efficacy of controlled hypotension agents esmolol, remifentanil, and nitroglycerin in functional endoscopic sinus surgery, in terms of hemodynamic changes and impact on the surgical efficiency. Methods The research was carried out as a cohort study. Patients who underwent functional endoscopic sinus surgery were randomized into 3 groups. Controlled hypotension was achieved with remifentanil (Group R), esmolol (Group E) and nitroglycerin (Group N). The efficacy of the drugs was tested by comparing the length of time with the targeted mean arterial pressure, the amount of anesthetics used, surgical field bleeding score and surgeon's satisfaction. Results Between May to December 2015, 60 patients were included and randomized equally into 3 different study groups. The median of the length of time with the targeted mean arterial pressure was shorter in the Group R when compared with Group E (p = 0.01) and Group N (p = 0.14). The amount of volatile anesthetics used was 25.0 mL (15-51), 43.0 mL (21-105) and 40.0 mL (26-97) in Groups R, E and N, respectively (p < 0.001). While there was more bleeding with nitroglycerin, surgical field bleeding scores were lower in Group R when compared with esmolol (p = 0.001) and nitroglycerin (p < 0.001). The analysis of surgeon's satisfaction scores concluded that surgeons were more satisfied with the group R (100%), when compared with group E (60%) and group N (30%) (p < 0.001). Conclusion Less volatile agent, short time to achieve controlled hypotension, stable blood pressure, lower surgical field bleeding scores and larger length of time with the targeted mean arterial pressure were found as the advantages of Remifentanil. Less costly, efficiency of achieving the targeted median arterial pressure and less postoperative complications were the advantages of nitroglycerin. In functional endoscopic sinus surgery procedures, appropriate controlled hypotensive agents should be selected according to the patients' characteristics and advantages/disadvantages of the drugs.

Resumo Introdução Hipotensão controlada é um procedimento reversível no qual a pressão arterial média basal do paciente é reduzida em 30% e mantida em 60-70 mmHg durante o procedimento. Isso diminui a perda de sangue e propicia um campo cirúrgico limpo durante os procedimentos. Objetivo Comparar agentes usados para hipotensão controlada: esmolol, remifentanil e nitroglicerina em cirurgia sinusal endoscópica funcional, em termos de alterações hemodinâmicas e impactos na eficácia cirúrgica. Método O estudo foi feito como de coorte. Pacientes submetidos à cirurgia sinusal endoscópica funcional foram randomizados em 3 grupos. A hipotensão controlada foi feita com remifentanil (Grupo R), esmolol (Grupo E) e nitroglicerina (Grupo R). A eficácia dos medicamentos foi testada com a comparação do período de tempo com a pressão arterial média desejada, a quantidade de anestésicos usados, o escore de sangramento no campo cirúrgico e a satisfação do cirurgião. Resultados Entre maio e dezembro de 2015, 60 pacientes foram incluídos e randomizados igualmente nos três grupos de estudo. A mediana do período com a pressão arterial desejada foi menor no Grupo R quando comparado ao Grupo E (p = 0,01) e Grupo N (p = 0,14). A quantidade de anestésicos voláteis usados foi de 25,0 mL (15 ± 51), 43,0 mL (21 ± 105) e 40,0 mL (26 ± 97) nos Grupos R, E e N, respectivamente (p < 0,001). Houve mais sangramento com nitroglicerina e escores de sangramento no campo cirúrgico foram menores no Grupo R quando comparados com esmolol (p = 0,001) e nitroglicerina (p < 0,001). A análise dos escores da satisfação do cirurgião concluiu que os cirurgiões estavam mais satisfeitos com o grupo R (100%) quando comparados ao grupo E (60%) e o grupo N (30%) (p < 0,001). Conclusão Agente menos volátil, pouco tempo para obter a hipotensão controlada, pressão arterial estável, menor escore de sangramento no campo cirúrgico e período de pressão arterial desejada curto foram considerados como vantagens do remifentanil. Menor custo, eficácia de obtenção da pressão arterial média desejada e menos complicações pós-operatórias foram as vantagens da nitroglicerina. Nos procedimentos de cirurgia sinusal endoscópica funcional, os agentes apropriados para obtenção de hipotensão controlada devem ser selecionados de acordo com as características dos pacientes e as vantagens/desvantagens dos fármacos.

Association of illness perception with chemotherapy-induced nausea and vomiting: a Turkish Oncology Group (TOG) study.

Chemotherapy-induced nausea and vomiting (CINV) may be linked to the psychological status of cancer patients. Therefore, the authors aimed to better understand the underlying risk factors for CINV using the Brief Illness Perception Questionnaire. A total of 238 patients were recruited during three cycles of chemotherapy. Patient, disease and treatment characteristics were noted at the onset of chemotherapy. The Brief Illness Perception Questionnaire was administered face-to-face prior to chemotherapy. The relationship between illness perceptions and CINV was analyzed using Spearman's rank correlation. Positive illness perception parameters, including personal and treatment control, were negatively correlated, whereas negative illness perception parameters, including consequences, timeline, identity, concern and emotions, were positively correlated with CINV after adjusting for age, sex and emetogenic potential of chemotherapy (p < 0.001). Illness perception may be an underlying risk factor for CINV.

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.

Retrospective analysis of the effect of breast surgery on body posture in patients with early-stage breast cancer after cancer treatment (VENUS study) (Breast cancer and body posture)

Background/aim: The aim of this study was to determine whether breast surgery changes body posture in patients with early-stage breast cancer. Materials and methods: Study variables include age, side and localization of the tumor in the breast, applied breast surgery, axillary interference, pathological tumor size, axillary lymph node metastasis, body mass index, bone density, adjuvant therapies, and histological type. Thoracic kyphosis angle due to the anatomically affected primary region to detect changes in body posture and Cobb's method were used to measure this. Results: There was a statistically significant difference in the mean Cobb's angle between the follow-up times of 57 patients (P < 0.001), with a cumulative increase in the Cobb's angle from baseline to the second year. As the age of the diagnosis progressed, the Cobb's angle increased significantly at 2 years when compared to baseline (r = 0,616, P < 0,001). In terms of baseline, the higher the BMI level in the 2nd year, the higher the Cobb's angle in the 2nd year as compared to the baseline (r = 0,529, P < 0,001). Conclusion: It was concluded that the increase in thoracic kyphosis in patients with breast cancer should be examined psychosocially. The study should be supported by a larger number of patients.

The efficacy of esmolol, remifentanil and nitroglycerin in controlled hypotension for functional endoscopic sinus surgery.

INTRODUCTION: Controlled hypotension is a reversible procedure in which the patient's baseline mean arterial blood pressure is reduced by 30% and sustained at 60-70 mmHg during the procedure. It decreases blood loss and provides clear surgical field during the procedures. OBJECTIVES: The purpose of this study was to compare the efficacy of controlled hypotension agents esmolol, remifentanil, and nitroglycerin in functional endoscopic sinus surgery, in terms of hemodynamic changes and impact on the surgical efficiency. METHODS: The research was carried out as a cohort study. Patients who underwent functional endoscopic sinus surgery were randomized into 3 groups. Controlled hypotension was achieved with remifentanil (Group R), esmolol (Group E) and nitroglycerin (Group N). The efficacy of the drugs was tested by comparing the length of time with the targeted mean arterial pressure, the amount of anesthetics used, surgical field bleeding score and surgeon's satisfaction. RESULTS: Between May to December 2015, 60 patients were included and randomized equally into 3 different study groups. The median of the length of time with the targeted mean arterial pressure was shorter in the Group R when compared with Group E (p = 0.01) and Group N (p = 0.14). The amount of volatile anesthetics used was 25.0 mL (15-51), 43.0 mL (21-105) and 40.0 mL (26-97) in Groups R, E and N, respectively (p < 0.001). While there was more bleeding with nitroglycerin, surgical field bleeding scores were lower in Group R when compared with esmolol (p = 0.001) and nitroglycerin (p < 0.001). The analysis of surgeon's satisfaction scores concluded that surgeons were more satisfied with the group R (100%), when compared with group E (60%) and group N (30%) (p < 0.001). CONCLUSION: Less volatile agent, short time to achieve controlled hypotension, stable blood pressure, lower surgical field bleeding scores and larger length of time with the targeted mean arterial pressure were found as the advantages of Remifentanil. Less costly, efficiency of achieving the targeted median arterial pressure and less postoperative complications were the advantages of nitroglycerin. In functional endoscopic sinus surgery procedures, appropriate controlled hypotensive agents should be selected according to the patients' characteristics and advantages/disadvantages of the drugs.

68-months progression-free survival with crizotinib treatment in a patient with metastatic ALK positive lung adenocarcinoma and sarcoidosis: A case report.

INTRODUCTION: Lung cancer still ranks first among the most common and most lethal cancers today. The most common subtype is non-small cell lung cancer, and in this group, adenocarcinoma has the worst prognosis. EGFR, ROS1 and ALK-EML4 gene fusion mutations are common in non-small cell lung cancer. CASE REPORT: A 62-year-old non-smoker patient applied in February 2014 for purulent sputum and pain in the chest. Computed tomography revealed a 39x33 mm mass in the right hilum, multiple parenchymal nodules in the bilateral lung and mediastinal multiple enlarged lymph nodes. The patient was admitted to the lung adenocarcinoma as a result of a biopsy from the mass in the hilum, and sarcoidosis was diagnosed by mediastinal lymph node biopsy. MANAGEMENT & OUTCOME: After 4 cycles of carboplatin-pemetrexed for the first line treatment, progression was detected. The patient did not have EGFR and ROS1 mutations. The patient with positive ALK fusion mutation started crizotinib treatment in July 2014. The patient's last response assessment was in March 2020, with 68-progression-free disease with crizotinib. No toxicity was observed except for Grade 1 weakness. No dose changes were made. The patient is still being followed up without brain metastasis under the treatment of crizotinib. DISCUSSION: In this article, we wanted to share our experience of crizotinib in a 68-months progression-free survival in a 62-years old non-smoking female patient with metastatic lung adenocarcinoma who is also diagnosed with sarcoidosis.

Environmental occurrence of phthalate and organophosphate esters in sediments across the Gulf of Lion (NW Mediterranean Sea).

Seven phthalate (PAEs) and nine organophosphate esters (OPEs) were measured in surface sediments across the Gulf of Lion (NW Mediterranean Sea) at twelve stations characterized by different anthropogenic signatures. ∑PAEs and ∑OPEs concentrations ranged from 2 to 766 ng/g DW (av. 196 ng/g DW) and from 4 to 227 ng/g DW (av. 54 ng/g DW), respectively. Our analysis of the potential sources of these organic plastic additives in sediments of the Gulf of Lion suggests that the dominant factors affecting their occurrence and environmental distribution are port-based industrial activities and urban pressures. Indeed, the highest ∑PAEs and ∑OPEs concentrations were found close to the ports of Toulon and Marseille (Estaque) and at the sites impacted by the Marseille metropolitan area (i.e. at the outlets of the waste water treatment plant at Cortiou and at the mouth of the Huveaune River). The lowest levels were generally found in protected areas (e.g. Port-Cros) and at sites relatively far from the coast. DEHP was seen to be the most abundant PAE while TDCP, TEHP and TiBP were the most abundant OPEs in the area. Our results also expose the contribution of additives entering the Gulf of Lion via sedimentary material from the Rhône River, with positive correlations between the total organic carbon (TOC) content in the sediment and the ∑PAEs and ∑OPEs concentrations. However, additive concentrations decreased from shore to offshore in the Rhône River discharge area, indicating an efficient dilution of the contaminants accumulated at the river mouth area.