bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validated five-factor prognostic model for survival of patients (pts) with metastatic urothelial carcinoma (mUC) receiving different post-platinum PD-L1 inhibitors.
Authors: Sonpavde Guru , Hennessy Daniel , Manitz Juliane , Niegisch Guenter , Powles Thomas , Rosenberg Jonathan E. , Bajorin Dean F. , Apolo Andrea B. , Pond Gregory Russell 
Published: March 2019

476 Background: A prognostic model for overall survival (OS) of mUC was previously reported in the setting of post-platinum atezolizumab (Pond GR, GU ASCO 2018). This model was limited by employing only atezolizumab treated pts, small size of the validation dataset and unclear applicability to other PD-1/L1 inhibitors. Hence, we constructed a robust prognostic model utilizing the combined atezolizumab cohort as the discovery dataset and used a validation dataset comprised of post-platinum avelumab-treated pts. Methods: The discovery dataset consisted of pt level data from 2 phase I/II trials (IMvigor210 and PCD4989g) evaluating atezolizumab (n = 405). Pts enrolled on a phase I/II trial that received post-platinum avelumab (n = 242) comprised the validation dataset (EMR 100070-001). Cox regression analyses evaluated the association of candidate prognostic factors with OS. Factors were dichotomized and laboratory values were normalized by logarithmic transformation. Stepwise selection was employed to propose an optimal model using the discovery dataset. Discrimination (via c-statistic) and calibration were assessed in the avelumab dataset following the validation procedure by Royston and Altman (2013). Results: The 5 factors included in the optimal prognostic model in the discovery dataset were ECOG-PS (1 vs. 0; HR 1.80; 95% CI [1.36-2.36]), presence/absence of liver metastasis (HR 1.55; 95% CI [1.20-2.00]), number of platelets (HR 2.22; 95% CI [1.54-3.18]), neutrophil-lymphocyte ratio (NLR; HR 1.94; 95% CI [1.57-2.40]) and lactate dehydrogenase (LDH; HR 1.60; 95% CI [1.28-1.99]). The c-statistic for prediction of survival was 0.692 and 0.671 in the discovery and validation datasets, respectively. Acceptable or good calibration of expected 1-year survival was observed. Conclusions: A 5-factor externally validated prognostic model for OS is proposed employing a large dataset of 647 pts overall in the setting of post-platinum PD-L1 inhibitors for mUC. This model may assist in prognostic stratification and interpreting nonrandomized trials of post-platinum PD1/L1 inhibitors.
National trends and pathologic outcomes of neoadjuvant chemotherapy among patients with micropapillary variant urothelial carcinoma of the bladder.
Authors: Javier-Desloges Juan , Abello Alejandro , Syed Jamil , Leapman Michael 
Published: March 2019

477 Background: Micropapillary variants of urothelial cell carcinoma (UCC) are associated with aggressive clinical behavior including an increased risk of regional and distant metastasis. Although neoadjuvant chemotherapy (NAC) improves survival for patients with UCC who achieve a complete pathologic response (pT0), less is known regarding the uptake of this practice in patients with micropapillary variant (MV) or its effect on pathologic response. Methods: We queried the National Cancer Database to identify all patients with a diagnosis of UCC including MV from 2004-2014. We restricted our analysis to patients who underwent radical cystectomy with or without NAC. We compared clinical, demographic, and pathologic characteristics and evaluated time trends associated with use of NAC. Following propensity score matching to balance covariates associated with the receipt of NAC, we used logistic regression models to study the association of NAC use and pT0 rate. Dual analyses were performed among patients with clinical stage II (cT2) disease, as well as the entire cohort (all stages). Results: We identified 102,266 patients, including 101,272 (99.03%) pure UCC and 994 (0.97%) MV. Patients with MV were younger (Median 70 years vs 73 years, p < 0.001), more commonly male (79.0 vs 73.6% p < 0.001), were more commonly treated in academic centers (66.43% vs 44.77%), there was no difference between urban/rural areas. Use of NAC among patients with cT2 increased in the entire cohort from 27% on 2004 to 49.7% in 2014 for UCC, and from 50% to 58% for MV. Among patients with cT2 disease, 38.4% of UCC received NAC and 49% MV received NAC (P < 0.001). Following propensity score matching, receipt of NAC was associated with pT0 for both histological diagnoses (OR 2.13 95% CI: 1.65-2.78 p < 0.001). This effect persisted on restriction to patients with cT2 (OR 3.32, 95% CI: 2.32-4.75, p < 0.001). Conclusions: There has been increased use of NAC among patients with micropapillary variant. Patients with cT2 micropapillary variant were equally like to be achieve a pathologic complete response to NAC as were patients without histologic variants of urothelial cell carcinoma.
The nonsurgical management of upper tract urothelial carcinoma: A role for active surveillance?
Authors: Syed Jamil , Nguyen Kevin , Javier-Desloges Juan , Leapman Michael , Raman Jay D. , Shuch Brian M. 
Published: March 2019

485 Background: Approximately 7% of patients with localized upper tract urothelial cancer (UTUC) are treated without definitive therapy. Understanding outcomes and alternative therapy would aid in counseling older patients with co-morbidities. Methods: We utilized the National Cancer Database to identify patients with localized UTUC managed non-surgically between 2004 and 2013. Patient demographics, co-morbidity, tumor grade, and chemotherapy and radiation utilization were recorded. Survival analyses were performed with the Kaplan-Meier method and a cox proportional hazard regression model. Results: We identified 3,157 (10.9%) patients with localized UTUC who did not receive definitive surgery. Median age was 79 years, 55% were males, 79% had government health insurance, and 68% had a CDS of 0. Tumor grade was low (grade 1 or 2) in 632 (36.4%) and high (grade 3 or 4) in 1104 (63.6%). Median overall survival (OS) for the cohort was 2.2 years, significantly shorter for patients with greater co-morbidities. Chemotherapy or radiation was performed in 294 (9.3%) and 197 (6.3%) patients respectively. There were no OS differences for individuals receiving chemotherapy. Of patients who received radiation therapy, the median OS was 1.4 vs 2.0 years, (p<0.001) favoring no radiation. Those with high grade tumors had worse survival (1.9 vs 3.8 years (p<0.001). Significant predictors of shorter OS included older age, male gender, higher CDS, and government insurance. Conclusions: In this population-based cohort, 10.9% of patients with localized UTUC were managed non-surgically. Radiation and chemotherapy were not routinely utilized, and did not demonstrate improved survival. Median OS was significantly shorter for those with higher grade disease, increasing co-morbidity profile, male gender, and those with government insurance status.
Twenty-eight-day prophylaxis with apixaban after radical cystectomy: Early results in safety.
Authors: Anwar Taha , Raza Johar , Pokala Naveen , Hamilton Zachary , Murray Katie 
Published: March 2019

488 Background: Venous thromboembolism (VTE) after oncologic surgery is a known risk and therefore guidelines recommend extended VTE prophylaxis up to 4 weeks for these populations. This prophylaxis is often costly and cumbersome to patients, as it requires self-injections with enoxaparin. The FDA has extended the indication for apixaban to include deep venous thrombosis (DVT) and pulmonary embolism (PE) prophylaxis in adults who have undergone hip or knee replacement surgery. The objective of this study was to identify safety concerns with using this prophylaxis for an extended time after radical cystectomy for bladder cancer. Methods: Patients from two institutions who underwent radical cystectomy for bladder cancer were retrospectively reviewed. Patients were included if they were discharged from the hospital with at least 28 days of prophylactic apixaban 2.5 mg BID. Descriptive statistics are used to show patient and outcome characteristics. Results: As of October 2018, 12 patients met inclusion criteria for this study. The median age was 69.5 years (interquartile range: 64.75 to 74 years) and 11 (91.7%) of the patients were male. 3 (25%), 1 (8.3%), 2 (16.7%), 1 (8.3%) and 5 (41.7%) of the patients were pathologic stage T0, Tis, T1, T2, T3/4, respectively, and 2 (16.7%) had node positive disease. Seven (58.3%) of the patients received neoadjuvant chemotherapy prior to radical cystectomy. No patients were identified with a symptomatic or asymptomatic VTE during pre-operative work up or during post-operative stay. No major bleeding events or complications related to the anticoagulant were identified in any patient, and no patient has developed a post-operative VTE including DVT or PE to date. Conclusions: Apixaban is approved for prophylaxis in preventing VTE after major surgery in other surgical specialties. This report shows that in the early stages of investigation of post-discharge use of apixaban, no increase in complications or readmissions have been identified in patients who have undergone radical cystectomy for bladder cancer. This safety, efficacy, and potential superiority needs further investigation.
Robot-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC): Oncological outcomes in 469 patients with a mean follow-up of five years.
Authors: Faraj Kassem , Rose Kyle , Abdul-Muhsin Haidar , Navaratnam Anojan , Patton Michael , Cheney Scott , Tyson Mark D. , Castle Erik P. 
Published: March 2019

492 Background: There is scant information about intermediate and long-term comparative outcomes between RARC and ORC, with the exception of a recent, small randomized-trial. We present our experience with RARC and ORC in managing bladder cancer patients who require cystectomy. Methods: A query of all patients who underwent radical cystectomy for a primary bladder tumor between 01/2007 and 6/2017 at our institution yield 469 patients. Data was collected on patient demographics, pre-operative information, operative details, pathology, and follow-up. Most RARCs were performed by a high-volume robotic surgeon who preferentially used the robotic approach at the start of all cases. Statistical analyses were generated using SPSS 22.0. Any open conversions were analyzed in the RARC cohort. Results: In 469 total patients, 197 (42.0%) and 272 (58.0%) underwent RARC and ORC, respectively. There were 163 (82.7%) and 224 (82.4%) males in each group and the mean ages (SD) were 71.5 (8.6) and 70.2 (10.5) years. Mean follow-up (SD) was 75 (37.7) and 61 (35.7) months, respectively. There were 130 (66.0%) and 172 (63.2%) patients who presented with T2 or greater disease (p=0.605). Soft-tissue margin rates were 4.1% for RARC and 6.7% for ORC patients (p=0.232). Neoadjuvant chemotherapy was used in 56.9% of RARC and 45.9% of ORC patients with ≥ cT2 disease (p=0.058). The 5-year overall survival was 60.0% vs 57.0% and the 10-year overall survival was 40.3% vs 44.8% for RARC vs. ORC patients, respectively (p=0.283). The 5-year recurrence-free survival was survival (RFS) was 71.7% vs 65.7% and the 10-year RFS was 70.5% vs 62.3% for the RARC vs. open groups, respectively (p=0.078). Aggressive histological variants, which were associated with greater likelihood for recurrence, were more common in the ORC group (13.7 vs. 22.4% p=0.013). Atypical recurrences (i.e. peritoneal, extrapelvic nodes) occurred in 6 (3.0%) and 14 (5.1%) RARC and ORC patients, respectively (p=0.266). Conclusions: In experienced hands, intermediate and long-term outcomes of RARC appear equivalent to ORC with regards to recurrence free survival, overall survival, and risk of atypical recurrences.
Development and validation of a DNA methylation panel for the prediction of outcome in node-positive penile squamous cell carcinoma after lymphadenectomy.
Authors: Zhu Yao , Gu Weijie , Wan Fangning , Wang Beihe , Wei Yu , Ye Dingwei 
Published: March 2019

513 Background: Node-positive penile squamous cell carcinoma is lethal disease with heterogenous outcome after lymphadenectomy. Molecular prognostic factor are poorly tested in this population to individualize treatment. The aim of this study was to develop and validate the prognostic value of a DNA methylation panel in node-positive penile cancer after lymphadenectomy. Methods: Patients with node-positive penile squamous cell carcinoma, and received inguinal or ilioinguinal lymphadenectomy were eligible. The prognostic marker study had 3-stage design: first, discovery set of 23 frozen tissues was used to generate candidate CpG sites associated with overall survival; second, development set of 68 formalin-fixed and paraffin-embedded (FFPE) samples was used to construct a multivariable methylation panel for outcome stratification; third, validation set of 69 FFPE specimens from multi-center database was used to independently validate the performance of the prognostic marker. The study was approved by local ethnic committee. The primary endpoint was overall survival. The prognostic value of the DNA methylation panel value was evaluated by hazard ratio (HR), concordance index (C-index) and clinical benefit. Results: At discovery stage, 11 CpG sites were significantly associated with overall survival. In development set, we constructed a 3-CpGs-based prognostic panel for survival prediction. The HR of the panel (dichotomized using median cutoff) was 6.5 in multivariate analyses (p < 0.001). Addition of methylation panel significantly improved the C-index of N stage from 0.64 to 0.75 (incremental C = 0.11, p < 0.001). In the validation set, the methylation panel showed a HR of 7.8 in multivariate analyses. Addition of the molecular marker significantly improved the C-index of N stage from 0.69 to 0.78 (incremental C = 0.09, p < 0.001). The main limitation was retrospective design. Conclusions: We developed and validated a methylation prognostic panel for node-positive penile cancer. The prognostic maker showed remarkable improvement in risk stratification, and need further evaluation in prospective setting.
A phase II study of ribociclib in men with unresectable, incurable teratoma with recent progression.
Authors: Castellano Daniel E. , Quinn David I. , Feldman Darren R. , Fizazi Karim , Garcia del Muro Xavier , Gietema Jourik A. , Lauer Richard C. , Ising Mary Elizabeth , Aregay Mehreteab , Crystal Adam Samuel , Vaughn David J. 
Published: March 2019

517 Background: Most patients with teratoma are managed by surgery and no standard medical therapy exists for progressive and/or unresectable teratoma. Teratomas have functional expression of retinoblastoma protein and clinical activity was observed with CDK4/6 inhibition (Vaughn DJ, et al. Cancer. 2015). Here, we report results with the CDK4/6 inhibitor ribociclib (RIBO) for unresectable teratoma. Methods: This multicenter, double-blind study enrolled patients (pts) ≥ 15 years old with unresectable, progressive teratoma without malignant transformation, ECOG PS 0-1, and ≥ 1 line of prior chemotherapy. Pts were randomized (2:1) to receive RIBO (600 mg/day, 3 weeks on/1 week off) or placebo (PBO). Crossover to RIBO was permitted following progressive disease (PD) on PBO. The primary endpoint was progression-free survival (PFS). Secondary endpoints included additional efficacy measures, safety, and tolerability. Results: The trial was closed prematurely in the setting of slow accrual. Ten pts were randomized (8 to RIBO, 2 to PBO). Median age was 33 years (range, 21-53). All pts received study treatment, and both pts in the PBO arm crossed over to RIBO following PD. Median exposure was 385 days for RIBO and 166 days for PBO. The PFS rates at 24 months were 71% and 0% in the RIBO and PBO arms, respectively. All 8 pts in the RIBO arm had stable disease (SD) as best response at first evaluation. In the PBO arm, 1 pt had best response of PD and the other SD with durations of treatment of 78 and 254 days, respectively. After crossover, both pts received RIBO, with a best response of SD, and durations of treatment of 943 and 133 days, respectively; the former entered a rollover protocol and the latter discontinued treatment due to an adverse event. The most common reason for discontinuation in both groups was PD. Grade ≥ 3 adverse events in the RIBO group included neutropenia and non-cardiac chest pain in 2 pts, and headache, decreased appetite, asthenia, fatigue, vomiting, and increased blood creatinine in 1 pt each; all but non-cardiac chest pain were suspected to be drug related. Conclusions: In this rare clinical setting, with a limited small sample size, RIBO prolonged PFS as compared to PBO and no new safety signals emerged. Clinical trial information: NCT02300987.
Persistence of platinum in semen of cisplatin-treated survivors of advanced testicular cancer.
Authors: Malone Eoghan Ruadh , Lewin Jeremy Howard , Lau Susan , Hamilton Robert James , Hansen Aaron Richard , Jarvi Keith , Zhang Wenjiang , Chen Eric Xueyu , Bedard Philippe L. 
Published: March 2019

519 Background: Even in patients (pts) with widely metastatic germ cell tumors cure rates are high with cisplatin based chemotherapy. Survivors of testicular cancer often have impaired gonadal function possibly related to chemotherapy. Most pts develop temporary azoospermia with recovery in about 50% after 2 years and 80% after 5 years. Platinum persists in blood in these pts, however, it is not known whether platinum also persists in semen. Methods: Pts who completed cisplatin > 3 months previously were enrolled. Age, total cisplatin dose and date of completion of treatment were collected. A semen sample was collected from each patient for analysis to assess semen quality. A blood sample was collected to assess FSH/LH/testosterone/creatinine. Serum and semen platinum levels were measured using HPLC-tandem mass spectrometry. Results: Between 11/2017 and 09/2018, 9 pts (median age 32 years; range: 18-52) were enrolled to the study, all were treated with standard Bleomycin, Etoposide, Cisplatin regimen. Blood samples were collected from 7 pts, and semen samples from 4 pts. Median total cisplatin dose given was 658 mg (range: 570-780). Median serum platinum concentration was 0.395 ng/mL (range: 0.10-0.94) at a median of 10 months (range 4.5-13) post completion of treatment. Median semen platinum concentration was 1.06 ng/mL (range: 0.25-1.47) at a median of 10 months (range: 6-14) post completion of treatment. Semen platinum levels were associated with total cisplatin dose administered (Pearson correlation, r = 0.645) and time from completion of treatment (Pearson correlation, r = 0.386). In all 4 pts with matched samples, the semen platinum level was higher than the serum platinum level. Semen analysis showed 2 pts were azoospermic post treatment, 1 of these was also azoospermic prior to treatment; 1 pt had normal semen analysis post treatment and 1 had a low sperm count post treatment. Conclusions: This is the first study demonstrating that platinum persists in semen > 6 months post completion of cisplatin-containing chemotherapy. Platinum levels are higher in semen than in blood following treatment. Our preliminary findings may have important implications for reproductive health of survivors of advanced testicular cancer.
Validation of plasma miR-371a-3p expression in patients with metastatic and early stage germ cell tumor.
Authors: Nappi Lucia , Thi Marisa , Lum Amy , Huntsman David , Eigl Bernhard J. , Chi Kim N. , Martin Christopher , O Neil Brock , Maughan Benjamin Louis , So Alan , Black Peter C. , Gleave Martin , Wyatt Alexander William , Lavoie Jean-Michel , Khalaf Daniel , Daneshmand Siamak , Hamilton Robert James , Leao Ricardo Romao Nazario , Nichols Craig R. , Kollmannsberger Christian K. 
Published: March 2019

526 Background: Identification of relapsing/residual viable germ cell malignancy (GCM) is often challenging in patients with CSI on surveillance or with residual post-chemotherapy disease. The presence of a biomarker for GCM would overcome the uncertainty of the current methods and improve the quality of care of those patients. Methods: A 2-cohorts pilot study involving patients with clearcut evidence of GCM (clinical stage IS, metastatic and GCM prior orchiectomy) for the development cohort and patients with CSI with or without signs of tumor relapse and patients with metastatic GCM post-chemotherapy for the validation cohort. Blood samples collected in Streck tubes were obtained prior to chemotherapy for the development cohort and post-orchiectomy, at the time of suspicious relapse or post-chemotherapy in the validation cohort. Plasma miR-371a-3p (miR371) was analyzed by RT-PCR. Positive predictive value (PPV), sensitivity, specificity, negative predictive values (NPV) and AUC of the ROC for miR371 and standard diagnostic tools (CT scan, AFP, BHCG and LDH) were calculated correlating qualitative miR371 expression to the presence of viable GCM. Results: 132 patients were enrolled into the development (33 pts) and validation (99 pts) cohorts. Within the development cohort 31/33 pts were miR371 positive, 2/33 pts were negative. 31 true positives were found among the 31 miR371 positive patients for a PPV of 100% (31/31). Two true negatives were found among the 2 patients who had no miR371 expression identified (teratoma, lymphoma). The validation cohort was chosen to evaluate the methodology among patients with predicted lower volumes or no clinically apparent disease. 13/99 patients within the validation cohort were miR371 positive and all 13 had subsequent confirmation of viable GCM. For the overall study of 132 pts, PPV was 100% (46/46), NPV 98%, sensitivity 96% and specificity 100%, the AUC of the ROC was 0.96. Conclusions: Detectable circulating miR-371a-3p levels predict viable GCM and may represent a strategy for biological rather than radiographic assessment for surveillance of early stage and for post-treatment patients. Larger studies to validate these and like results have been planned.
The features and management of late relapse of non-seminomatous germ cell tumors: The Royal Marsden Experience.
Authors: Huddart Robert A , Mayer Erik , Jay Alexander , Pearce Adam , Reid Alison Helen , Nicol David 
Published: March 2019

529 Background: Late relapses (LR) of non-seminomatous germ cell tumours (NSGCT), defined as those occurring after a disease free interval of 2 years, are increasingly recognised. We reviewed the features of LR in NSGCT within a tertiary referral testicular cancer service. Methods: 3,064 patients (pts) were referred to the testis multi-disciplinary team (January 2005 to Dec 2017). Pts who experienced a LR where initial pathology demonstrated NSGCT were identified. Data of their original and late presentation and management was reviewed from patient electronic records. Results: Of the 3,064 pts, 101 (3.3%) had a LR, with 43 pts (43%) relapsing after 10 years. 36 were symptomatic and 39 had raised markers (AFP 29, HCG 9, both 1). Table 1 shows stage at initial presentation and time to relapse. As regards treatment before late relapse, 13 CS1 patients had received prior chemotherapy (Cht) (8 as adjuvant and 5 Cht for early relapse). 59/60 CS2/3 patients received Cht as primary treatment and 41 had a post chemotherapy retroperitoneal lymph node dissection(PC-RPLND (bilateral template in 12). 20 of these 41 men who had a PC-RPLND experienced a LR in the retroperitoneum (6 after bilateral template) Patient management at relapse is summarised in table.Time to recurrence was longer in CS2/3 patients (p<0.001). 84 surgical procedures were [performed in 82 patients; histology was TD in 43, Yolk sac 14, De-differentiated in 7 and viable GCT in 12, benign 8. To date 22 patients have died, 13 of these patients relapsed at multiple sites. Conclusions: LR of NSGCT frequently occurs after an extended interval and typically occurs earlier in CS1 disease compared to higher stages. Aggressive surgery +/- chemotherapy can cure most patients. [Table: see text]