A new processbased way of comprehension along with taking care of triggered seismicity

On completion of 3 years follow-up, recurrence-free survival rate of 84.31% and 86.79% and progression-free survival rate of 84.31% and 94.34% were observed for 80 and 120 mg groups, respectively; difference being statistically nonsignificant. CONCLUSION Both, 80 and 120 mg doses of Sii Onco BCG are effective and safe for prophylaxis and management of NMIBC. Despite advances in surgical technique and perioperative care pathways, complication rates following radical cystectomy for bladder cancer remain high and perioperative outcomes for elderly patients are suboptimal. UNC8153 mouse Furthermore, subjective risk assessments of patients with bladder cancer, with a high prevalence of complex comorbidity burden and risk of frailty, may result in undertreatment of patients assumed to be poor operative candidates. A critical component of preoperative patient counseling and treatment selection is accurate and objective preoperative risk appraisal. Comprehensive Geriatric Assessments are multi-domain evaluations of the medical, functional, and psychosocial aspects of health designed specifically for use in elderly patients with the objective of identifying vulnerabilities that may be targeted with interventions for improvement. While currently recommended by multiple guideline bodies for use in the preoperative evaluation of elderly patients with bladder cancer there is a paucity of data describing their use in contemporary clinical practice. Herein, then, we will describe the components of a Comprehensive Geriatric Assessments and propose strategies for their integration into the preoperative surgical workflow. INTRODUCTION AND OBJECTIVES To evaluate the prognostic role of modified Glasgow prognostic score (mGPS) for the prediction of oncological outcomes in a retrospective large multicenter cohort of upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS We retrospectively analyzed a multicenter cohort of patients treated with RNU for clinically nonmetastatic UTUC. Multivariable logistic regression analyses were performed to evaluate the ability of mGPS to predict nonorgan confined (NOC) disease and lymph-node involvement (LNI) at RNU. Multivariable Cox-regression models were performed to evaluate the preoperative and postoperative prognostic effect of mGPS on survival outcomes. RESULTS Overall, 2,492 patients were included in the study. Of these, 1,929 (77%), 530 (21%), and 33 (1%) had a mGPS of 0, 1, and 2, respectively. mGPS was associated with characteristics of tumor aggressiveness and independently predicted LNI and NOC at RNU (both P less then 0.05). On univariable and multivariable Cox-regression analyses, higher mGPS was independently associated with recurrence-free, cancer-specific, and overall survival, both in a preoperative and in a postoperative setting. The inclusion of mGPS significantly improved the discrimination of a preoperative model for the prediction of oncologic outcomes compared to standard prognosticators. CONCLUSIONS We found that mGPS is independently associated with clinicopathologic features and survival outcomes after RNU. Future studies should investigate the role of mGPS in a panel of preoperative markers for the prediction of NOC and LNI in UTUC patients, thus possibly improving the selection for perioperative systemic therapy. OBJECTIVES The purpose of this study was to evaluate both the outcomes and toxicity of second-line actinomycin D (ActD) chemotherapy in methotrexate (MTX) - resistant low-risk postmolar gestational trophoblastic neoplasia (GTN) with 5-day ActD versus pulsed ActD. METHODS This retrospective cohort study included patients with MTX-resistant low-risk postmolar GTN from 1974 to 2016. Second-line chemotherapy consisted of 5-day ActD (10-12 μg/kg per day for 5 days every 14 days) or biweekly ActD (1.25 mg/m2 every 2 weeks). Data on patient characteristics, disease presentation, treatment outcome, and toxicity were collected. RESULTS Sixty-eight MTX-resistant patients receiving ActD as second-line chemotherapy were identified (5-day ActD, 53 patients; pulsed ActD, 15 patients). No significant differences were observed in patient/disease characteristics and sustained remission (overall rate 72%) between second-line ActD regimens. Time to hCG remission was significantly faster (median 21 vs 47 days, p = .04) and required fewer treatment cycles (median 1 vs 2, p  less then  .001) with 5-day ActD. Thrombocytopenia was only observed with 5-day ActD (64.6 vs 0%, p  less then  .001). The frequency (60.4 vs 16.7%, p = .009) and severity (grade 3 37.9 vs 0%, p = .045) of oral mucositis was significantly higher with 5-day ActD. Grade 2 alopecia was significantly more frequent (70.6 vs 16.7%, p = .02) with 5-day ActD. CONCLUSIONS While 5-day ActD and pulsed ActD achieve comparable remission rates, due to its reduced toxicity, ease of administration, and patient convenience, pulsed ActD should be the treatment of choice for MTX-resistant postmolar low-risk GTN. OBJECTIVES To evaluate the safety and preliminary efficacy of demcizumab (DLL4 targeted IgG2 humanized monoclonal antibody; potent inhibitor of the Notch pathway) in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer (EOC); and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD). METHODS We conducted a 3 + 3 dose-escalation trial in patients with recurrent, platinum-resistant EOC with RECIST v. 1.1 measurable disease and ≤4 prior chemotherapy regimens. Two dosing cohorts (2.5 mg/kg and 5 mg/kg) were targeted; however, an intermediate dose level (3.5 mg/kg) was to be evaluated if the 5 mg/kg dose was not tolerable. Demcizumab was administered on days 1 and 15 and paclitaxel, weekly on days 1, 8, and 15 for each of three 28-day cycles the 3-cycle doublet could be repeated once if safe. Thereafter, paclitaxel was administered until unacceptable toxicity or disease progression. RESULTS Nineteen patients were enrolled. No dose-limiting toxicities (DLT) were observed; however, the intermediate dose level (3.5 mg/kg) was enrolled and expanded based on emerging safety data from other trials in the demcizumab program. The MTD was not reached. The most common treatment emergent adverse events (TEAE) were diarrhea (68%), fatigue (58%), peripheral edema (53%), and nausea (53%). Pulmonary hypertension, grade 2 (n = 2) and grade 1 (n = 1), was observed. Overall response rate (ORR) was 21% (95% CI 6-45%); clinical benefit rate (CBR) was 42% (95% CI 20-66%). CONCLUSIONS Demcizumab in combination with paclitaxel has a manageable toxicity profile and showed activity in patients with heavily pretreated platinum-resistant ovarian cancer.