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.

Relationship between Fragmented QRS Complex and Aortic Stiffness in Chronic Hemodialysis Patients.

OBJECTIVE: This study aimed to evaluate the correlation between fragmented QRS complex (fQRS), aortic stiffness, and diastolic dysfunction in hemodialysis patients. SUBJECTS AND METHODS: A sample of 56 patients who received hemodialysis treatment was stratified into 2 groups according to their electrocardiography (ECG) patterns with or without fQRS. Baseline characteristics and laboratory parameters of patients were documented. Conventional echocardiographic and Doppler echocardiographic procedures were performed in all patients. The mean early (Em) diastolic and late (Am) diastolic myocardial velocities were calculated. These tests were performed before dialysis. The Student t test, Mann-Whitney U test, χ2 test, Spearman correlation, and multivariate linear regression analysis were used to analyze parameters where appropriate. RESULTS: Of the 56 patients under hemodialysis, fQRS in ECG was detected in 26 (46.4%). Echocardiographic evaluation showed that deceleration time (237.57 ± 40.10 ms; p = 0.030), isovolumic relaxation time (126.84 ± 15.62 ms; p < 0.001), early (E)/late (A) ventricular filling velocity (E/A) ratio (1.15 ± 0.40; p ≤ 0.001), and aortic stiffness index value (9.62 ± 4.53; p = 0.016) exhibited a statistical increase in hemodialysis patients with fQRS compared to patients without fQRS. E (58.23 ± 19.96 m/s; p = 0.004), and Em (5.96 ± 2.08 cm/s; p = 0.023) velocity levels were significantly lower in hemodialysis patients with fQRS than patients without fQRS. Aortic stiffness closely correlated with diastolic dysfunction (deceleration time r = 0.273, p = 0.042; isovolumic relaxation time r = 0.497, p < 0.001; E/A ratio r = -0.449, p = 0.001). On multivariate linear regression analysis, fQRS and aortic stiffness were independently associated in hemodialysis patients (ß = 0.321, p = 0.049). CONCLUSIONS: Increased aortic stiffness and left ventricular systolic dysfunction were observed more frequently in hemodialysis patients with fQRS than in patients without fQRS. fQRS is an important determinant of aortic stiffness in hemodialysis patients.

The Relationship between Breast Cancer Subtypes, Prognostic Factors, and Apparent Diffusion Coefficient Histogram Analysis.

BACKGROUND: Diffusion Magnetic Resonance Imaging (MRI) is a useful method to evaluate tumor biology and tumor microstructure. The apparent diffusion coefficient (ADC) value correlates negatively with the cellular density of the tumor. OBJECTIVE: This study aimed to investigate the effectiveness of the ADC histogram analysis in showing the relationship between breast cancer prognostic factors and ADC parameters. METHODS: This study is a retrospective observational descriptive study. ADC histogram parameters were evaluated in all tumor volumes of 67 breast cancer patients. Minimum, 5, 10, 25, 50, 75, 90, 95 percentiles, maximum, mean, median ADC values, kurtosis, and skewness were calculated. Breast MRI examinations were performed on a 3T MR scanner. We evaluated the fibroglandular tissue density of bilateral breasts, background enhancement, localization of masses, multifocality-multicentricity, shape, rim, internal contrast enhancement, and kinetic curve on breast MRI. BIRADS scoring was performed according to breast MRI. Pathologically, histologic type, histologic grade, HER 2, Ki 67, ER-, and PR status were evaluated. RESULTS: A significant correlation was found between tumor volume and ADC scores. There is a significant correlation between min ADC values (p< 0.031), max ADC (p< 0.001), and skewness (p< 0.019). A significant correlation was found between tumor kurtosis and lymph nodes (p< 0.029). There was a significant difference in ADC values depending on ER-and PRstatus. (for ER p = 0.004, p = 0.018, p = 0.010, p = 0.008, p = 0.004, p = 0.004, p = 0.02, p = 0.02 and p = 0.038, for PR p < 0.001, p = 0.028, p = 0.011, p = 0.001, p < 0.001, p =<0.001, p < 0.001, and p < 0.001, respectively; p < 0.05). These values were lower in ER-and PR-positive status than in ER-and PR-negative receptor status. According to HER2 status, there was a statistically significant difference in ADC

Pretreatment PLR Is Preferable to NLR and LMR as a Predictor in Locally Advanced and Metastatic Bladder Cancer.

Background/Aim: Advanced bladder cancer (BC) is associated with an inflammatory nature and poor prognosis Inflammatory biomarkers are potential predictors in BC. We conducted a study to assess the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in advanced bladder cancer. Patients and Methods: A total of 226-patients with muscle-invasive BC (MIBC) were included. Overall (OS) and progression-free survival were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. Univariate and multivariate Cox proportional hazard models were used to determine NLR, PLR, and LMR association with OS. Results: Our patients' median progression-free survival and OS were 12.18 and 15.54 months, respectively. Receiver operating characteristic analysis revealed cut-off values for our chosen inflammatory markers. The patients with high NLR or PLR had inferior median OS compared to their counterparts with lower ratios for both (NLR: 22.51 vs. 9.84 months, respectively, p≤0.001; PLR: 17.68 vs. 14.08 months, respectively, p=0.08). Meanwhile, patients with low LMR had inferior median OS compared to patients with higher LMR (LMR: 20.14 months vs. 10.55 months, respectively, p<0.001). The multivariate Cox regression analysis identified a high PLR as an independent predictive factor of worse OS (hazard ratio=2.774, 95% confidence interval=1.486-5.178, p=0.001) but not NLR or LMR. Conclusion: PLR, C-reactive protein-to-albumin ratio, and serum LDH levels, but not NLR and LMR, may function as independent predictors in patients with advanced BC prior to systemic treatment.

Mucinous appendiceal neoplasms and pseudomyxoma peritonei: Morphological and clinical findings, differential diagnosis, and prognosis.

Background: Low-grade appendiceal mucinous neoplasms (LAMN) of the appendix have bland cytological features and well-differentiated morphology. Despite this, they may cause a pseudomyxoma peritonei (PMP) disease characterized by mucinous deposits in the peritoneal cavity and may exhibit malignant behavior. Aims and Objectives: In this study, we evaluated the clinical course and histopathological findings of LAMN. The rate of progression to PMP, factors affecting its development, and the clinical course of cases with PMP were investigated. Materials and Methods: Twelve thousand and forty-seven cases who underwent appendectomy were reviewed, and 71 mucinous lesions cases whose slides are in our archive were included in the study. Histopathological findings were re-evaluated. Morphological findings that guide the differential diagnosis, the clinical course of the patients, and factors affecting PMP development were determined. Results: The cases were divided into group 1 non-neoplastic (9.9%), group 2 benign (18.3%), group 3 LAMN (60.6), and group 4 malignant neoplasms (11.3%). Age, gender, appendix diameter, gross appearance, epithelial characteristics, and presence of microcalcification were significantly different between the patient groups. The presence of mucin in the ileocecal region was found to be significant in the development of PMP. It was observed that the additional procedure performed after the appendectomy did not prevent a recurrence. Conclusion: LAMNs are lesions with characteristic findings and different behaviors. The only method to distinguish from the lesions included in the differential diagnosis is to interpret the histopathological findings correctly. Additional operations after appendectomy do not contribute to preventing recurrence.

Evaluation of Serum microRNA Let-7c and Let-7d as Predictive Biomarkers for Metastatic Pancreatic Cancer.

BACKGROUND: First-line treatments for metastatic pancreatic cancer are chemotherapy regimens consisting of 5-fluorouracil or gemcitabine; however, there are no biomarkers to help determine which patients might benefit from which treatment regimens. We aimed to show that microRNAs let-7c and 7d can be used as independent predictive biomarkers for metastatic pancreatic cancer. METHODS: A total of 55 patients who had first-line chemotherapy with FOLFIRINOX or gemcitabine+capecitabine were included. Patients were divided into groups based on let-7c and let-7d levels and chemotherapy treatment as let-7c-7d high FOLFIRINOX, let7c-7d high gemcitabine+capecitabine, let-7c-7d low FOLFIRINOX, and let-7c-7d low gemcitabine+capecitabine. Blood samples were taken from patients before chemotherapy for microRNA let-7c and 7d analysis. MicroRNA isolation was performed using a miRNeasy Serum/Plasma Kit and identified using spectrophotometric measurements. After isolation, microRNA was converted to cDNA using a microRNA cDNA Synthesis Kit with poly (A) polymerase tailing. The expression of microRNA was examined using quantitative real-time polymerase chain reaction. RESULTS: The overall survival of patients who received FOLFIRINOX treatment with a high let-7c-7d level was statistically significantly longer than those who received gemcitabine+capecitabine with a high let-7c-7d level. In addition, patients with low let-7c expression receiving FOLFIRINOX progressed significantly 2.104 times earlier than patients with high let-7c expression receiving FOLFIRINOX. CONCLUSION: The serum MicroRNA let-7c level was found to be an independent predictive biomarker in the FOLFIRINOX treatment group.

The Effect of Continuing Chemotherapy after Chemoradiotherapy during the Time to Surgery on Tumor Response and Survival for Local Advanced Rectal Cancer.

Aim: The current standard treatment of locally advanced rectal carcinoma is total mesorectal excision and postoperative adjuvant chemotherapy after neoadjuvant concurrent chemoradiotherapy (NCRT). Many studies have shown that pathological complete response (pCR) is an important prognostic factor for patients receiving NCRT. Many studies have therefore been conducted to increase pCR rates by changing the perioperative treatment strategies. Prolonging the chemotherapy time may be a reasonable way to increase the effectiveness of NCRT, pCR, and survival rates. We investigated whether neoadjuvant consolidation chemotherapy had an effect on tumor response and survival. Methods: The data of 163 patients diagnosed with locally advanced rectal carcinoma were evaluated. The data of 107 patients (Group 1) who were radiologically T3-T4 and/or N+ and received chemotherapy after NCRT until their operations were compared with the data of 56 patients (Group 2) who were operated after NCRT. Results: Group 1 patients had tumor and node downstaging. Their pCR was found significantly higher than in Group 2 (p = 0.005). In Group 1 patients with T3, pCR was significantly higher than for those with T4. The elapsed time between NCRT and surgery was significantly longer in patients with pCR (respectively, p = 0.012 and p = 0.008). Conclusion: Neoadjuvant consolidation chemotherapy after NCRT is a safe approach that can lead to higher pathological complete response rates. The time until surgery with neoadjuvant consolidation chemotherapy may provide the chance to follow the patient without surgery in addition to increasing pCR.

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.