bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic predictors of outcomes in children with stage I germ cell tumors: A pooled post hoc analysis of trials from the Children’s Oncology Group.
Authors: Singla Shyamli , Wong Justin , Singla Nirmish , Krailo Mark D. , Huang Li , Shaikh Furqan , Billmire Deborah F. , Rescorla Frederick J. , Ross Jonathan H. , Dicken Bryan J. , Amatruda James F. , Frazier A. Lindsay , Bagrodia Aditya 
Published: February 2020

418 Background: Patients with clinical stage I (CS I: cN0M0) germ cell tumors (GCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I GCT, we lack reliable means to predict relapse among pediatric patients. We sought to identify predictors of relapse in children with CS I GCT. Methods: We performed a pooled post hoc analysis on pediatric CS I GCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of outcomes. Results: 88 patients were identified with histologic data available. Most patients were pT1-2 stage. Yolk sac tumor was present in 75%, while 16% had embryonal carcinoma, and 9% had choriocarcinoma. When evaluable, lymphovascular invasion (LVI) was present in 36/66 (55%) of patients. Over a median follow-up of 5.0 years, no patients died and 24 patients (27%) relapsed (median relapse-free survival not reached). Predictors of relapse included presence of choriocarcinoma (HR 4.3, p=0.004), embryonal carcinoma (HR 3.8, p=0.002), pT3 stage (HR 6.9, p=0.027), and age >12 years (HR 3.1, p=0.011). LVI (HR 2.4, p=0.072), serum tumor markers, and dominant tumor size did not reach significance. Pediatric CS I GCT patients exhibit remarkable 5-year survival. Conclusions: Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and potentially inform personalized treatment for these patients.
Differential expression of melanoma-associated antigen A3/6 and associated immune molecules prior to and post treatment with immune checkpoint inhibitors (ICI) in patients with mUC.
Authors: Faiena Izak , Funt Samuel Aaron , Astrow Stephanie H. , Dorff Tanya B. , Adhikary Sabina , Gorgan Tristan , Rosenberg Jonathan E. , Elashoff David , Pantuck Allan J. , Drakaki Alexandra 
Published: February 2020

433 Background: MAGE is an attractive target for IO given its expression restricted to carcinomas and the testes. Engineered T-cell targeting MAGE A3/6 has shown promise. However, successful treatment is dependent on circumventing the potentially hostile immune microenvironment in metastatic tumors. In this study, we aim to assess the effects of ICI on the immune microenvironment in patients who progressed on ICI. Methods: We obtained FFPE tissue from 16 patients with mUC across 3 institutions. Samples from the primary or metastatic tumor prior to treatment with PD1/PD-L1 inhibitors (ICI) were paired with samples from metastatic sites post-treatment. Differential mRNA expression was assessed using NanoString PanCancerIO360 panel for the main genes of interest ( MAGEA3/6, CD274, HLADP, HLAA, B2M and PDCD1) in addition to immune profiling of the tumor samples. Also, IHC was done on the paired samples to assess DE for the genes of interest using an H-score analyzed via the paired T-test. p-values <0.05 were considered significant and FDR corrected. Results: MAGEA3/A6 mRNA expression was unchanged in the post-treatment samples. In addition, time to progression was not influenced by the mRNA DE. Similarly, IHC expression was not decreased post-treatment. The other genes of interest were also similarly expressed pre and post treatment. Immune cell localization genes CPA3,TPSAB1/B2, HDC, MS4A2 were significantly downregulated post treatment. Genes implicated in cancer cell killing ( MX1,KIT) were similarly downegulated whereas CD276, TLR1 were upregulated. Expression in the post treatment tissue of PTPN1, CES3, ACVR1C, and BAD were associated with increased progression. LY9, PTPRC, CTLA4, HLA-DMA, IL10RA, HLA-DMB, ITGAL, CD48 were associated with decreased progression. Conclusions: Prior ICI treatment does not decrease expression of MAGE A3/6, suggesting that salvage treatments targeting this antigen remain a viable strategy. Suggestion of immune microenvironment alterations were also noted. More work is necessary to understanding the tumor microenvironment in order to design rational treatment combinations and sequences.
Impact of 18FDG-PET CT in the management of invasive bladder cancer.
Authors: Bertolaso Pauline , Brouste Véronique , Cazeau Anne Laure , De Clermont-Gallerande Henri , Bladou Franck , Cabart Mathilde , Ravaud Alain , Gross-Goupil Marine 
Published: February 2020

444 Background: Guidelines do not recommend FDG-Positron Emission Tomography (PET) Computed Tomography (CT) for the staging of Muscle Invasive Bladder Cancer (MIBC), but rather CT scan for lymph node (LN) and metastatic staging, despite its low accuracy. We performed a retrospective analysis of patients (pts) with MIBC who had a FDG-PET CT for staging, indicated by multidisciplinary team, in two centers, and analyzed its utility in this setting. Methods: All pts who had a FDG-PET CT performed at the time of diagnosis of MIBC from 01/2005 to 12/2017 in Bordeaux (Bergonie Institute and University Hospital) were retrospectively reviewed. Nodal and metastatic staging on CT and FDG-PET CT were done independently according to the 8th TNM classification. The aims of the study were to evaluate the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification (neoadjuvant chemotherapy for curative intent, no surgery for metastatic disease), according to FDG-PET CT results. Results: Among the 130 pts included, with a median age of 65 years, 74% were considered free from nodal metastasis (N0) by CT whereas only 44% were N0 from FDG-PET CT. Based on CT results, 88% of pts were free from distant metastasis (M0) but only 75% were classified M0, on FDG-PET CT. Accuracy of LN staging for CT and FDG-PET CT at initial diagnosis were analyzed for 85 pts (including 70 pts treated with neoadjuvant chemotherapy) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (respectively 80.8% versus 26.9%) but the specificity was low (respectively 54.2% versus 83.1%). Youden index was better for FDG-PET CT (0.35; 0.1 for CT), being more accurate for determining LN staging of MIBC. FDG-PET CT findings allowed a treatment decision modification in 34/130 pts (26.1%): therapeutic intensification in 12 pts (9.2%), including surgery not previously indicated, modified radiotherapy; or de-escalation in 22 pts (16.9%), mostly avoiding surgery. Conclusions: FDG-PET CT is more sensitive to detect LN involvement at initial diagnosis of MIBC than standard CT scan. Moreover, in the present study, treatment decisions were modified, according to FDG-PET CT results, in a quarter of pts according to LN and distant metastatic staging.
Patient and caregiver benefit-risk preferences for treatment in advanced urothelial carcinoma.
Authors: Apolo Andrea B. , Cambron-Mellott M. Janelle , Will Oliver , Seal Brian S. , Maculaitis Martine C. , Bernstein Andrew , Epperson Megan , Jeffress Mara Lisa , Doleh Yunes 
Published: February 2020

448 Background: Checkpoint blockade therapy has demonstrated improved survival in second-line urothelial carcinoma and is also active as first-line (1L) therapy in locally advanced / metastatic urothelial carcinoma (mUC) patients (PTs) who are cisplatin-ineligible / PD-L1 high or platinum-ineligible regardless of PD-L1 level. This study quantified trade-offs between efficacy and adverse events (AEs) associated with 1L treatments for mUC that PTs and caregivers (CGs) are willing to make. Methods: PTs with mUC and CGs were recruited via advocacy groups to complete a cross-sectional online survey assessing treatment preferences with a discrete choice experiment (DCE) employing descriptive language. In a series of tasks, PTs and CGs chose their preferred option from two alternative treatment profiles varying on six select attributes: overall survival (OS), progression-free survival (PFS), and AEs including: all grades (AG) neuropathy; and G3/4 nausea/vomiting, fatigue, and diarrhea. Hierarchical Bayesian modelling estimated preference weights for each attribute level. Results: PTs (N=152) had a mean age of 60 years; 68% had Stage 4 UC. CGs (N=151) had a mean age of 53 years and cared for PTs with a mean age of 62; most CGs (67%) cared for a PT with Stage 4 UC. While attributes had the same rank order of importance for both PTs and CGs, improving OS from 10 to 22 months was 31% more important than improving PFS from 2 to 10 months for PTs, whereas OS and PFS were more similarly valued by CGs. CGs placed less importance than PTs on OS relative to the importance of G3/4 nausea/vomiting, G3/4 diarrhea, and AG neuropathy (all P<0.01). Despite these differences, OS was at least twice as important than reduction in AEs for both cohorts. To accept increases in G3/4 nausea/vomiting by 21%, G3/4 fatigue by 23%, G3/4 diarrhea by 7%, and AG neuropathy by 5%, OS would need to improve by 2.2, 2.3, 1.2, and 0.5 months (PTs) and 6.6, 5.5, 3.0, and 1.1 months (CGs), respectively. Conclusions: Trade-offs made between efficacy and specific AEs for mUC are nuanced between PTs and CGs, with CGs desiring larger OS benefits to accept higher AE risk. These findings suggest a need for deeper discussions between PTs, CGs and physicians about treatment decisions.
Intravesical irrigation to prevent early bladder recurrence in patients undergoing laparoscopic radical nephroureterectomy for upper urinary tract cancer.
Authors: Tamura Takaaki , Sakamoto Shinichi , Yamamoto Satoshi , Maimaiti Maihulan , Imamura Yusuke , Komiya Akira , Nagata Maki , Ichikawa Tomohiko 
Published: February 2020

454 Background: The bladder carcinoma recurrence rate after nephroureterectomy is known to be high. Here we studied the clinical benefit of Intravesical irrigation during laparoscopic radical nephroureterectomy in upper urinary tract cancer (UUTUC) patients. Methods: This study enrolled 197 UUTUC patients who receive laparoscopic radical nephroureterectomy at Chiba University Hospital and Yokohama Rosai Hospital between 2001 and 2019. Association between the various clinical factors and postoperative recurrence rates within two years were statistically analyzed. Intravesical irrigation was carried out only during surgery and by using distilled water or saline. Results: Bladder recurrence was confirmed for 79 of the 197 patients. Irrigation was carried out in 75 cases (distilled water, 49 cases; saline, 26 cases). Tumor grade (G1-2 vs G3; p=0.0029) and irrigation (with vs. without; p<0.0001) were related to bladder recurrence on univariate analysis. Even on multivariate analysis, both tumor grade (p=0.0094) and irrigation ( p<0.0001) remained as independent factors. Comparison between the irrigation and non-irrigation groups showed that bladder recurrence rates were significantly lower in the irrigation groups (irrigation group vs non-irrigation group: 29.3% vs 46.7%, p=0.015). There was no prognostic difference between the type of irrigation (distilled water vs saline, p=0.177). Conclusions: Intravesical irrigation prevented early bladder recurrence in patients undergoing radical nephroureterectomy for UUTUC. [Table: see text]
Cancer stage and quality of life in bladder cancer.
Authors: McCloskey Hannah , McCabe Sean , Gessner Kathryn , Filippou Pauline , Hamad Judy , Deal Allison Mary , Smith Angela , Gore John L. 
Published: February 2020

466 Background: Bladder cancer requires treatment and surveillance which varies in intensity by disease stage. Our objective was to evaluate stage-specific differences in generic and bladder cancer-specific quality of life (QOL) among a large bladder cancer cohort. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine generic and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 972 respondents self-identified as patients with bladder cancer. Among respondents, 41% were female and 97% were white. The mean age was 67.6 years (range 29 to 93 years). Patients identified as having non-muscle-invasive bladder cancer (NMIBC, n=578 [63%]), MIBC (n=270, 30%), and metastatic bladder cancer (n=63, 7%). On bivariable analysis ( Table), lower stage was significantly associated with better generic (p<0.01) and bladder-cancer specific QOL (p<0.01). This associated persisted on multivariable analysis adjusted for age, sex, race, years since diagnosis, and comorbidity (p<0.01 for generic, urinary, sexual, and bowel QOL). Conclusions: Disease stage significantly impacts generic and bladder cancer-specific QOL among bladder cancer survivors. Differential impact by stage may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Resource utilization analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (DD-MVAC) versus gemcitabine-cisplatin (GC) as neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC).
Authors: Montazeri Kamaneh , Dranitsaris George , Curran Catherine , Thomas Jonathan David , Ingham Matthew D. , Preston Mark A. , Steele Graeme S. , Kilbridge Kerry L. , Wei Xiao X. , McGregor Bradley Alexander , Mossanen Matthew , Sonpavde Guru 
Published: February 2020

474 Background: DD-MVAC and GC are commonly used NAC regimens for MIBC. While efficacy across studies appears similar, the resource utilization burdens have not been compared. Methods: We assessed the resource utilization and cost effectiveness of NAC with GC vs DD-MVAC for MIBC patients (pts) treated at Dana-Farber. Data on chemotherapy administered, supportive medications, relevant procedures, hospitalizations, clinic, infusion, and emergency room visits were collected retrospectively. Results: 147 patients were included, 51 in the DD-MVAC and 86 in the GC group. The two groups had similar baseline pt characteristics except lower mean age (59 vs 67 years, p<0.001) and higher proportion of ECOG-PS=0 (96.1% vs 60.5%, p<0.001) in the DD-MVAC group. The mean cumulative cisplatin dosages were similar (DD-MVAC=284 mg/m2, GC= 257 mg/m3). The DD-MVAC group exhibited a greater use of G-CSF analogues (100% vs 32.6%, p < 0.001), central line placement (28.6% vs 11.8%, p = 0.017), infusion visits/pt (12 vs 8), ER visits (35% vs 18%, p = 0.048), and cardiac imaging (0.98 vs 0.58/pt, p<0.001). Patients receiving GC were more likely to experience delayed chemotherapy cycles (30.2% vs 9.8%, p = 0.008) and required more frequent clinic visits (9 vs 5/pt). The frequency and duration of hospitalization (23.6% vs 13.7% and 0.88 vs 0.49 days/pt, p = 0.46) and rate of grade ≥3 toxicities (32.6% vs 45.1%, p = 0.18) were numerically but not statistically different between the GC and DD-MVAC group. Cost efficacy analysis is pending and will be presented. Conclusions: DD-MVAC and GC exhibit different characteristics in terms of resource utilization as NAC for MIBC. Importantly, excess resource utilization did not clearly favor one of the regimens, although the DD-MVAC group was younger with better ECOG-PS. Given that similar overall delivery of cumulative cisplatin dosage was feasible with both regimens, the values and costs affixed to different resources may impact the selection of DD-MVAC vs GC in different regions of the world.
Pembrolizumab with chemoradiotherapy as treatment for muscle invasive bladder cancer: A planned interim analysis of safety and efficacy of the PCR-MIB phase II clinical trial (ANZUP 1502).
Authors: Weickhardt Andrew James , Foroudi Farshad , Lawrentschuk Nathan , Galleta Laura , Seegum Amanda , Herschtal Alan , Link Emma , McJannett Margaret Mary , Liow Elizabeth Chien Hern , Grimison Peter S. , Zhang Alison Yan , Patanjali NItya , Ng Siobhan , Goodwin Robert , Tang Colin , Chen Colin , Hovey Elizabeth J. , Hruby George , Guminski Alexander David , Davis Ian D. ,   Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: February 2020

485 Background: In patients (pts) with muscle invasive bladder (MIBC) suitable for curative definitive chemoradiotherapy (CRT), we hypothesise that the addition of pembrolizumab may be safe and improve efficacy. A pre-planned safety analysis was performed after the first 10 of planned 30 pts were enrolled and completed treatment. Methods: Patients with maximally resected non-metastatic MIBC and ECOG 0-1, who desire bladder preservation or are ineligible for cystectomy were treated with 64Gy in 32 daily radiation fractions to the whole bladder alone over 6.5 weeks in combination with 6 concurrent doses of weekly cisplatin at 35mg/m2 IV. Pembrolizumab was commenced concurrently with radiation and given flat-dose 200mg IV q21 days for 7 doses. Surveillance cystoscopy, urine cytology and CT chest-abdomen-pelvis were performed 12 & 24 weeks post CRT. The primary endpoint is feasibility, defined by a satisfactory low rate of unacceptable toxicity of a) G3-4 non-urinary adverse events (AE) or b) failure of completion of planned CRT according to defined parameters. Secondary endpoints include complete cystoscopic response without metastatic disease at 12 & 24 weeks, loco-regional PFS, metastatic DFS, and overall survival. A 2-stage design was planned, with accrual to be halted if >5 of the first 10 pts experienced unacceptable toxicity up to 12 weeks post treatment. Results: All 10 pts completed the course of CRT and pembrolizumab without alteration in radiation dose or schedule. 1 patient had a dose of cisplatin withheld. 4/10 pts experienced G3-4 non-urinary adverse events within 12 weeks of completing treatment. One immune related AE interrupted pembrolizumab delivery (G2 nephritis). By week 24, 9/10 pts achieved a complete cystoscopic response to treatment post CRT and were free of distant metastatic disease. Conclusions: Interim results indicate that pembrolizumab and CRT shows satisfactory safety, and promising efficacy. There were no unexpected safety signals. Follow up of these and additional pts will better define the efficacy and safety of the combination. Enrolment is ongoing with 20 pts recruited out of a planned total of 30. Clinical trial information: NCT02662062.
Association of area social determinants of health with prostate cancer mortality.
Authors: Henegan John Clark 
Published: February 2020

49 Background: Validated clinical nomograms prognosticate survival for men with metastatic castrate resistant prostate cancer. In addition to clinical factors, significant disparities in survival in advanced prostate cancer are associated with social determinants of health (SDH). We performed a study of county-level data to evaluate SDH associated with prostate cancer mortality. Methods: County-level data regarding prostate cancer crude mortality rate (dependent variable) and crude incidence rate was extracted from the ten states with information at www.cancer-rates.info for the years 2006-2015. The 2014 Robert Wood Johnson County Health Rankings dataset was used for information regarding county demographics, clinical information, and available SDH(independent variables). A correlation analysis was performed between independent variables and only one variable was analyzed if a criterion of a correlation of ≥ 0.65 was present. All counties with ≤ 30 death in the specified time period or with incomplete independent variable information were excluded from analysis. A univariate linear regression analysis was performed. All individual independent variables with a statistically significant (p ≤ 0.05) association with the dependent variable were included in a multivariate linear regression model. Results: 275 counties were available for analysis. On multivariate analysis, independent variables statistically significantly associated with the crude rate of prostate cancer mortality included household income and the percentage of: a population ≥ 65 years of age, the population < 18 years of age, African Americans, the population classified as rural, women reporting a screening mammography, smokers, and uninsured patients. The multivariate model was associated with a R-squared of 0.62. Conclusions: In addition to differences in baseline clinical factors, prostate cancer quality metrics that evaluate survival should account SDH. Information from this study, if validated in subsequent work, could be used to develop a stepwise model to adjust for both clinical factors and SDH when measuring survival as a quality metric.
Analysis of clinical outcomes according to response status in prospective clinical trials of atezolizumab (atezo) in pretreated locally advanced/metastatic urothelial carcinoma (mUC).
Authors: Bedke Jens , Merseburger Axel Stuart , Loriot Yohann , Castellano Daniel , Choy Ernest , Duran Ignacio , Rosenberg Jonathan E. , Petrylak Daniel Peter , Dreicer Robert , Perez-Gracia Jose Luis , Hoffman-Censits Jean H. , Van Der Heijden Michiel Simon , Degaonkar Viraj , Thiebach Lars , de Ducla Sabine , Fear Simon , Powles Thomas , Sternberg Cora N. 
Published: February 2020

492 Background: Atezo is an approved therapy for mUC based on the IMvigor210 (IM210) and IMvigor211 (IM211) phase 2 and 3 trials. The single-arm phase 3b SAUL study in a broader patient (pt) population showed consistent efficacy and safety. The value of complete response to immunotherapy is well recognized, but less is known about the benefit of partial response (PR) or stable disease (SD). We performed post hoc analyses of outcomes in pts with PR/SD in atezo trials. Methods: Pts with mUC received atezo 1200 mg q3w until disease progression (PD) or unacceptable toxicity. Baseline characteristics, efficacy and safety were analyzed in pts achieving PR or SD in IM210 cohort 2 (2nd line), IM211 (atezo and chemotherapy [CT] arms analyzed separately) and SAUL. Data cutoffs were 5/5/15, 3/13/17 and 9/16/18, respectively. Results: The analysis population included 229 PR and 583 SD pts (183 and 421, respectively, treated with atezo); ~40% of pts had 0 Bellmunt risk factors. Baseline characteristics were generally similar between trials. PD-L1 IC 2/3 was more common in PR than SD pts in atezo-treated (41% vs 26%) and CT-treated (37% vs 23%) pts. Median time to best response (PR or SD) was 2.1 mo across trials and treatments. In PR pts, disease control (DC) and overall survival (OS) durations were longer with atezo than CT (Table). Durations of DC and OS were shorter in SD than PR pts; OS was numerically longer with atezo than with CT in the SD population. Presence of more Bellmunt risk factors was associated with worse OS with CT but showed only a weak (SD pts) or no (PR pts) association in atezo-treated pts. Conclusions: Pts achieving a PR or SD have meaningful OS expectancy; pts with PR on atezo have sustained DC. Clinical trial information: NCT02108652 ; NCT02302807 ; NCT02928406 . [Table: see text]