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.

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.

Surgical management of traumatic cerebrospinal fluid fistulas with associated lesions.

BACKGROUND: Head trauma is associated with a significant risk of cerebrospinal fluid (CSF) fistula. METHODS: In this study, it was aimed to report twenty-two cases subjected to operative intervention for otorrhea, rhinorrhea and oculorrhea with associated traumatic lesions. Majority of the cases had moderate to severe head trauma with a Glascow Coma Scale (GCS) score under 14. The study group included eleven cases with depression fractures, 6 with epidural hematomas and 4 with tension pneumocephalus. RESULTS: Rhinorrhea was the most common presenting symptom encountered in fifteen cases; whereas, otorrhea was prominent in 7 and oculorrhea in 2 cases. Two patients having rhinorrhea also had oculorrhea and otorrhea. The patients were operated with unilateral approaches in twelve and bifrontal approaches in ten of the cases. CONCLUSION: Early surgical intervention should be performed in cases presenting with CSF fistula and associated traumatic lesions without considering conservative management to provide an effective control of associated complications due to CSF fistulas.

Assessment of maxillofacial trauma in emergency department.

INTRODUCTION: The incidence and epidemiological causes of maxillofacial (MF) trauma varies widely. The objective of this study is to point out maxillofacial trauma patients' epidemiological properties and trauma patterns with simultaneous injuries in different areas of the body that may help emergency physicians to deliver more accurate diagnosis and decisions. METHODS: In this study we analyze etiology and pattern of MF trauma and coexisting injuries if any, in patients whose maxillofacial CT scans was obtained in a three year period, retrospectively. RESULTS: 754 patients included in the study consisting of 73.7% male and 26.3% female, and the male-to-female ratio was 2.8:1. Mean age was 40.3 ± 17.2 years with a range of 18 to 97. 57.4% of the patients were between the ages of 18-39 years and predominantly male. Above 60 years of age, referrals were mostly woman. The most common cause of injuries were violence, accounting for 39.7% of the sample, followed by falls 27.9% and road traffic accidents 27.2%. The primary cause of injuries were violence between ages 20 and 49 and falls after 50. Bone fractures found in 56,0% of individuals. Of the total of 701 fractured bones in 422 patients the most frequent was maxillary bone 28,0% followed by nasal bone 25,3%, zygoma 20,2%, mandible 8,4%, frontal bone 8,1% and nasoethmoidoorbital bone 3,1%. Fractures to maxillary bone were uppermost in each age group.8, 9% of the patients had brain injury and only frontal fractures is significantly associated to TBI (p < 0.05) if coexisting facial bone fracture occurred. Male gender has statistically stronger association for suffering TBI than female (p < 0, 05). Most common cause of TBI in MF trauma patients was violence (47, 8%).158 of the 754 patients had consumed alcohol before trauma. No statistically significant data were revealed between alcohol consumption gender and presence of fracture. Violence is statistically significant (p < 0.05) in these patients. CONCLUSION: Studies subjected maxillofacial traumas yield various etiologic factors, demographic properties and fracture patterns probably due to social, cultural and governmental differences. Young males subjected to maxillofacial trauma more commonly as a result of interpersonal violence.