bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 expression level in Chinese upper tract urothelial cancer (UTUC) patients and its correlation with pathological and clinical features.
Authors: Yang Kaiwei , He Qun , Li Dong , Yu Wei , Song Yi , Yang Xinyu , Hu Xiyue , Zhu Jun , Li Ting , He Zhisong 
Published: February 2020

553 Background: UTUC is a potentially lethal malignancy and PD1-1/PD-L1 antibodies have shown promising efficacy. Although it had been explored in patients of their PD-L1 expression level who were enrolled in clinical trials, most of them were not Chinese. China has a larger patient population in CKD patients, yet may cause a different level of PD-L1 expression. Methods: Patients of locally resectable disease were enrolled and tumor tissues were collected for VENTANA PD-L1 (SP263) Assay (Roch). High and Low expression levels were determined according to the interpretation guide. Clinical and pathological data were collected and statistical analyses were done by SPSS 20. Results: A total of 190 patients diagnosed with UTUC were enrolled. Forty-one (21.6%) patients were identified as high PD-L1 expression. PD-L1 expression were significantly higher in high tumor grade (p=0.001), higher T stage (≤T2 vs. >T3, p=0.002), with divergent differentiation (squamous/ glandular/ sarcomatoid vs. pure UC, p=0.005), higher neutrophil/lymphocyte ratio (NLR≤3 vs. >3, p=0.045) and higher platelet/lymphocyte ratio (PLR<150 vs.≥150, p=0.006). Notably, patients with CKD stage 3 or higher (eGFR <60ml/min/1.73m2) had comparable PD-L1 high expression population (p=0.34). The HR for metastatic free survival was 2.65 in high expression patients (95% CI 1.17~5.97, p=0.019). Conclusions: China has a large population of UTUC with CKD stage 3 or higher who are ineligible for cisplatin and call for new treatment such as PD-L1/PD1 antibody. No difference was found in different CKD groups. UTUC seems to have lower proportion of PD-L1 high expression compared to bladder cancer. Whether it is due to more N-linked glycosylation that masked the detection or there might be other reasons inlayed stilled remain further study to find out.[Table: see text]
Association of positive Ki-67 and PD-L1 expressions in post neoadjvuant chemotherapy (NAC) radical cystectomy samples with lack of tumor downstaging (TD) and shorter overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC).
Authors: Rubino Selene , Sexton Wade J. , Kim Youngchul , Zhou Junmin , Dhilon Jasreman , Spiess Philippe E. , Poch Michael Adam , Manley Brandon J , Li Roger , Pow-Sang Julio M. , Gilbert Scott Michael , Zhang Jingsong 
Published: February 2020

554 Background: Previous chart review studies have reported that adjuvant chemotherapy after NAC did not clearly increase OS in MIBC cases characterized by a lack of TD. There is an unmet need to develop biomarkers to guide adjuvant therapy for this patient population. High levels of expression of cell proliferation marker Ki-67 are associated with poor outcome in chemotherapy naïve bladder cancer. Expression of PD-L1 has been studied as a potential predictive biomarker for anti-PD1 or PD-L1 therapies in metastatic MIBC. We therefore studied Ki-67 and PD-L1 expression in post NAC radical cystectomy samples at Moffitt Cancer Center and correlate them with TD and OS. Methods: Tissue microarrays (TMAs) were constructed from 116 post NAC cystectomy samples. The expressions of Ki-67 were evaluated with immunohistochemistry (IHC) and considered positive if any of the cores per sample were stained positive for Ki-67. The Dako 22C3 assay was used for PD-L1 IHC and the combined positive score of 10 or above was considered positive for PD-L1. Results: The median survival of this cohort of 116 patients was 33.4 months (range: 1.13 -127 months). 40 patients (35%) had TD and 21 patients (18%) achieved pathological complete response. Using Cox regression for OS, positive Ki-67 expression in post NAC radical cystectomy sample was associated with poorer OS (hazard ratio=2.412, 95% CI:1.076-5.408, p=0.033), independent of the pathological N stage. Patients with Ki67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1-/Ki67+ and PD-L1+/Ki67+ tumors respectively (Log-rank test, p=0.0361). Lack of TD was significantly associated with positive Ki-67 (P<0.001) and positive PD-L1 (p=0.003) in the post NAC samples with a multi-variable logistic regression model. Conclusions: Positive Ki-67 and PD-L1 expressions in post NAC radical cystectomy samples were associated with inferior OS and absence of TD. Adjuvant anti-PD1 therapy either alone or in combination with chemotherapy would be indicated for this subset of patients.
Outcomes of advanced plasmacytoid urothelial carcinoma receiving systemic therapy.
Authors: Andrews Erik , Curran Catherine , Grivas Petros , Diamantopoulos Leonidas Nikolaos , Drakaki Alexandra , Jain Rohit K. , Tandon Ankita , Agarwal Neeraj , Tripathi Abhishek , Santos Victor Sacristan , Hussain Syed A. , Sonpavde Guru 
Published: February 2020

580 Background: Plasmacytoid urothelial carcinoma (pUC) is an aggressive variant with poor outcomes reported in small retrospective studies. Patients (pts) with plasmacytoid-predominant tumor histology have generally been excluded from clinical trials. Given the lack of systematic data regarding outcomes in metastatic pUC, we conducted a retrospective multicenter study to broadly examine outcomes. Methods: Pts who underwent any systemic therapy for metastatic pUC were eligible from collaborating institutions. Data were collected for demographics, clinical and pathological variables. Descriptive statistics were reported to examine tumor regression, time to treatment discontinuation or failure (TTF), and overall survival (OS). Results: 52 pts with metastatic pUC were evaluable from 7 institutions. The ECOG-PS ranged from 0-3 (median 1), median age was 65 (range 46 – 85), and 14 pmts (26.9%) were female. The histology consisted of predominant urothelial, predominant plasmacytoid, and pure plasmacytoid carcinoma in 35 (67.3%), 14 (26.9%) and 3 (5.8%) pts, respectively. The median OS for evaluable pts according to histology were 234 (n=21), 203 (n=11), and 12 (n=1) days (d), respectively. The sites of metastasis (mets) were liver +/- other, non-liver visceral +/- soft tissue/lymph node (ST/LN), and ST/LN only in 5 (9.6%), 36 (69.2%), and 11 (21.2%) pts, respectively. Cisplatin-based chemotherapy (cis-chemo), PD1/L1 inhibitor (i), or other non-cis-chemo was administered in 20 (41.7%), 13 (27.1%), and 15 (31.3%) pts, respectively (therapy unknown in 4 pts). Overall best response PR, CR, SD, and PD were seen in 3 (7%), 3 (7%), 7 (16.3%), and 30 (69.8%) pts, respectively. The overall median TTF and median OS were 91 and 232 d, respectively. The median TTF for cisplatin-based chemo, non-cisplatin based chemo and PD1/L1 inhibitors was 96.5, 122.5 and 73.5 d, respectively and the median OS was 236 (n=12), 221 (n=12) and 161 (n=8) d, respectively. Conclusions: The clinical outcomes of pts with metastatic pUC are dismal and appear worse than conventional UC without plasmacytoid component. Further progress will be possible only with better understanding of tumor biology and rational drug development.
A retrospective review of the effect of metformin in metastatic prostate cancer.
Authors: Lam So Yi , Lee Chung-Shien , Liu Wingsze , Sison Cristina , Miao Emily , Zhu Xinhua 
Published: February 2020

62 Background: Current treatments of metastatic prostate cancer are mainly hormone therapy and chemotherapy. The anticancer potential of metformin on metastatic prostate cancer remains obscure. In this study, we aim to investigate the significance of patients with prostate cancer taking metformin in addition to their current treatment. Methods: An IRB approved retrospective review of metastatic prostate cancer patients was conducted. Patients were categorized into metastatic castration resistant prostate cancer (mCRPC) or hormone-sensitive prostate cancer (mHSPC). Patients were further stratified to those who received metformin vs. those who did not. Progression free survival (PFS) was evaluated based on PCWG3 and RECIST criteria. 6-month (6MO) PSA response and overall survival (OS) were also evaluated in this study. Results: A total of 281 subjects were included for analysis with a mean age of 70±10. Patients were known to have either mHSPC (n = 205) or mCRPC (n = 75), and taking metformin (n = 66) or not (n = 215). There was no significant difference between metformin groups with respect to PSA response at 6MO (p < 0.73). Among those with a recorded 6MO PSA response, 70.4% (38/54) had a response in the metformin group and 72.9% (140/192) had a response in the non-metformin group. Overall median PFS was estimated to be 17 months, with no significant difference in PFS between metformin groups (16.6 vs 17.3; p < 0.88). Within the mHSPC group, metformin users had a lower risk of progression relative to non-users (HR = 0.89; 95% CI: 0.62 to 1.29). Within the mCRPC group, metformin users had a significantly higher risk of progression relative to non-users (HR = 2.65; 95% CI: 1.4 to 5.0). Median overall survival was estimated to be 81.5 months. There was a significant difference in survival time between metformin groups (148.5 vs 69.4; p < 0.02). Conclusions: No significant differences were found in 6MO PSA response or PFS. There was a significant difference in OS amongst patients who were in the metformin group and those who were not.
Does pathologic upstaging to PT3A portend a worsened prognosis when compared to non-upstaged PT3A renal cell carcinoma: Analysis of the National Cancer Database.
Authors: Patel Devin , Ghali Fady , Meagher Margaret , Bradshaw Aaron , Patel Sunil , Keiner Cathrine , Miller Nathan , Dutt Raksha , Murphy James Don , Derweesh Ithaar 
Published: February 2020

624 Background: Pathological T3a (pT3a) renal cell carcinoma (RCC) is often diagnosed at the time of final pathological analysis, though impact of lack pre-treatment detection on surgical outcomes is unclear. We sought to compare outcomes of pathologically upstaged pT3a RCC with pT3a RCC recognized clinically. Methods: We queried the National Cancer Database for incident cases of pT3a pN0/x pM0/x renal cell carcinoma (RCC) treated with radical (RN) or partial nephrectomy (PN) between 2009-2015. Tumors were staged using the AJCC staging system, 7th edition. Pathologically upstaged tumors were defined as those that had a clinical stage of T1 or T2. Non-upstaged tumors had a clinical stage of T3a. Multivariable Cox proportional hazards and Kaplan-Meier survival analysis were performed to study the impact of clinical to pathological upstaging in pT3a tumors on overall survival (OS) in patients treated with RN and PN. Results: A total of 19,538 pT3a tumors were identified of which 7,231 (37%) had concordant clinical stage (non-upstaged) and 12,307 (63%) had lower clinical stage (upstaged). Patients with upstaged tumors had longer time from diagnosis to surgery (31.5 vs. 23.8 days; p<0.001), smaller tumor size (6.7 vs. 7.4 cm; p<0.001), higher rates of treatment with partial nephrectomy (18% vs. 11%; p<0.001), and higher rates of negative margins (92% vs. 89%; p<0.001). On multivariate analysis, age (HR 1.06; p<0.001), Charlson Comorbidity Index (HR 1.51; p=0.006) and positive margin status (HR 1.55; p<0.001) were associated with worse OS. Pathological upstaging was an independent predictor of improved OS following both PN (HR 0.74; 95% CI 0.59-0.91; p=0.006) and RN (HR 0.87; 95% CI 0.82-0.93; p<0.001). Kaplan-Meier analysis showed higher OS for tumors that were upstaged following both PN (5-year OS 73 vs. 70%; p=0.0083) and RN (5-year OS 67 vs. 64%; p<0.001). Conclusions: Most pT3a RCC are pathologically upstaged. Pathological pT3a tumors that were correctly detected clinically were associated with worsened outcomes. While our findings require further confirmation, they call for consideration and refinement of risk stratification protocols in pT3a RCC.
Prospective observational study on pazopanib in patients treated for advanced/metastatic renal cell carcinoma (RCC): APOLON Study.
Authors: Barthelemy Philippe , Albiges Laurence , Escudier Bernard , Lebret Thierry , Bigot Pierre , Stein Ulrich , Dourthe Louis-Marie , De La Cruz Jeannine , Tindel Malka , Thiery-Vuillemin Antoine 
Published: February 2020

629 Background: Pazopanib (PZP), has been granted for advanced or metastatic RCC. In addition to pivotal clinical trials, real-world evidence (RWE) is required to evaluate effectiveness and safety in clinical routine practices. Methods: APOLON is a non-interventional, multicentric prospective study to assess PZP Progression-Free Survival (PFS) (8-month PFS rate as primary endpoint), Overall Survival (OS), Objective Response Rate (ORR), tolerability, subsequent post-pazopanib therapy sequences. It is conducted in France with 55 sites (hospital or private practitioners) in patients with mRCC, naïve to anti-VEGF therapy, who initiated PZP treatment. Data are collected at baseline and at 1, 2-3, 6, 9, 12, 18, 24, 30, 36 months (mo). Patients (n= 218) were recruited from Nov 2017 to Jan 2019. This interim analysis presents results 6 months after last patient was enrolled. Results: Patients were 71,1% males, with a median age of 69.6 years. They had clear-cell type RCC for 97.7% with a favourable (26.4%), intermediate (52.9%) or poor (20.7%) IMDC risk score. Comorbidities were: hypertension (75.1%), diabetes (26%), arterial disorders (20.1%), other pathologies (47.3%); 81.7% received co-medications. ECOG-PS was 0 (42.9%), 1 (40%), 2 (15.7%), Metastases were mainly located in lungs (62.8%), bones (28.9%), mediastinal (17.9%)/abdominal (17%) lymph nodes, glands (pancreas, thyroid, adrenals) (17.4%). Of them, 56% had an history of partial/total nephrectomy, 28.1% previous local treatments for metastases. Median PFS, assessed by investigator, was 11.3 mo (95%CI: 8.7-13), with an 8-mo PFS rate at 62.9%. ORR was 47.2% and 1-year OS rate was 71.2%. Treatment-related serious adverse events were reported in 17.3% of patients. No new safety signal was identified. After a median follow-up of 8.8 mo, of the 121 patients with discontinuation, 74 received post-PZP lines comprising firstly nivolumab (67.6%), cabozantinib (16.2%), sunitinib (10.8%), other (5.6%). Conclusions: APOLON study represents real-life population including elderly and frail patients with clinically meaningful ORR and PFS with PZP. Reported adverse events were consistent with known safety PZP profile.
Multicenter retrospective analysis of patients with metastatic renal cell carcinoma (mRCC) and bone metastases treated with ipilimumab and nivolumab.
Authors: Desai Kunal , Brown Landon Carter , Wei Wei , Allman Kimberly D. , Martin Allison , Wood Laura S. , Gupta Shilpa , Gilligan Timothy D. , Garcia Jorge A. , Kao Chester , Kinsey Emily Noelle , Healy Patrick , Kephart Julie , Harrison Michael Roger , Ramalingam Sundhar , Armstrong Andrew J. , George Daniel J. , Rini Brian I. , Zhang Tian , Ornstein Moshe Chaim 
Published: February 2020

648 Background: Ipilimumab & nivolumab (I+N) followed by nivolumab maintenance is approved as front-line therapy for intermediate and poor-risk metastatic renal cell carcinoma (mRCC). Bone metastases (BM) are present in up to 30% of mRCC patients (pts) and remain a clinical challenge. We present a multicenter experience of mRCC pts with BMs treated with I+N. Methods: Patients with mRCC and bone metastases treated with (I+N) at Duke Cancer Network and Cleveland Clinic were retrospectively reviewed. Patient demographics, tumor histology, IMDC risk stratification, RECIST-defined ORR and adverse events were collected. Fisher’s exact test was used to determine predictors of response (alpha 0.05). Results: Forty-eight pts with mRCC and radiographically confirmed BMs were included in the analysis: 81% male; median age 54 (range: 41-81); 77% clear cell histology; IMDC risk 17%/52%/31% favorable/intermediate/poor, respectively. I+N was used as first-line medical therapy in 63% of pts and ≥ second-line in remaining pts. Best response on I+N per RECIST criteria: objective response rate (ORR) 23% (0% CR); 23% stable disease (SD); 44% progressive disease (PD). Median duration of treatment was 64 days with 27% of pts still on I+N. PD was the most common reason for discontinuation (38%) followed by adverse events (19%). Nearly half of pts (48%) experienced at least one irAE attributed to I+N therapy. None of the factors examined above was significantly associated with response to treatment. Conclusions: I+N has clinical activity and is well tolerated in mRCC pts with bone metastases; however ORR in this population is lower than expected and 44% pts had PD as best response. Therefore, identifying prognostic factors & improving novel therapies for this cohort of patients are priorities, given overall poorer outcomes in this population.
Prognostic role of Oncological Multidimensional Prognostic Index (Onco-MPI) in elderly patients with urological cancers.
Authors: Bimbatti Davide , Maruzzo Marco , Tierno Giuseppina , Bergo Eleonora , Pierantoni Francesco , Brunello Antonella , Basso Umberto , Zagonel Vittorina 
Published: February 2020

66 Background: MPI is an effective tool for geriatric assessment in elderly patients (pts). An oncological version of MPI (Onco-MPI) has been validated by our group in pts with cancer. We evaluate here the prognostic role of Onco-MPI in pts affected by urological cancer. Methods: Pts aged ≥70 years with prostate, renal and urothelial cancer (bladder or upper urinary tract) referred to the Medical Oncology 1 Unit from Jan 2005 to Aug 2019 received a basal comprehensive geriatric assessment (CGA). Onco-MPI was calculated by a validated algorithm as a weighted linear combination of the CGA domains as previously described, identifying 3 different prognostic groups: low (scores 0.0-0.46), intermediate (scores 0.47-0.63) and high risk (scores 0.64-1.0). Results: A total of 643 pts were included; 382 with prostate, 121 renal and 140 urothelial cancer. Median age was 77 years (68-95). ECOG PS was 0 in 44%, 1 in 34.2% and >1 in 21.6%; 19.3% had stage I or II disease, 29.7% stage III and 51% stage IV. Median overall survival (OS) was 35.4 months (95% CI 29.5-41.2). Onco-MPI score (low vs medium vs high risk) was significantly associated with OS in the overall population as well as in the subgroups of patients with prostate, renal or urothelial cancer (table). In pts with prostate cancer the majority of pts were low risk (93%) and only few intermediate (7%), no one was high risk. Conclusions: Onco-MPI confirmed its prognostic role in elderly pts with prostate, renal and urothelial carcinoma. It may be therefore valuable both in clinical practice for driving decision-making, and in geriatric clinical trials thanks to its standardization.[Table: see text]
Utilization of renal mass biopsy in patients with localized renal cell carcinoma: A population-based study utilizing the National Cancer Database.
Authors: Patel Devin , Ghali Fady , Patel Sunil , Miller Nathan , Bradshaw Aaron , Meagher Margaret , Rivera-Sanfeliz Gerant , Murphy James Don , Derweesh Ithaar 
Published: February 2020

662 Background: Recent guidelines suggest an increasing role for renal mass biopsy (RMB) in the management of renal cell carcinoma (RCC) prior to ablative therapy and in patients in whom active surveillance (AS) is being considered. Methods: We queried the National Cancer Database for cases of localized (cT1-cT3N0M0) RCC between 2004-2015. Unadjusted temporal trends in receipt of RMB were characterized over the study period based on type of treatment [partial nephrectomy (PN), radical nephrectomy (RN), ablation, and surveillance], tumor size, age and Charlson Comorbidity Index and compared using analysis of variance. Multivariable logistic regression was used to test for the association between patient, tumor and treatment variables and use of RMB. Results: 338,252 patients were analyzed, with 11.9% (40,276) undergoing RMB. Use of RMB increased from 1,586 (7.6%) in 2004 to 5,629 (16.2%) in 2015 (p<0.001). On treatment strategy, use of RMB increased the greatest in association with ablation from 27% to 63% across the study period (p<0.001). On tumor size, use of RMB increased the greatest for tumors 2-4 cm from 9% to 20% (p<0.001). Conversely, utilization of RMB increased proportionally across different age (p=0.17) and comorbidity (p=0.18) groups over time. Multivariable logistic regression revealed that year of diagnosis (OR 1.06; p<0.001), black race (OR 1.04; p=0.02), higher education (OR 1.09; p<0.001) and insured status (OR 1.23; p<0.001) were associated with increased RMB. However, increasing age (p=0.23) and comorbidity (p=0.35) were not. Compared to tumors <2 cm in size, tumors 2-4 cm (OR 1.36; p<0.001), 4-7 cm (OR 1.18; p<0.001) and >7 cm (OR 1.05; p=0.03) were associated with higher RMB. Compared to treatment with RN, treatment with PN was not associated with increased RMB (p=0.92); however, treatment with ablation (OR 10.90; p<0.001) and with surveillance (OR 4.83; p<0.001) were. Conclusions: The largest increase in RMB was associated with ablation treatment. Rates of RMB for tumors <2 cm and for older, sicker patients not undergoing treatment have correspondingly increased less, indicating RMB may not be as highly used for surveillance.
Exploring motivation to pursue genomic profiling among patients with metastatic genitourinary cancers.
Authors: Philip Errol James , Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Salgia Meghan , Salgia Nicholas , Dizman Nazli , Hsu Joann , Pal Sumanta K. 
Published: February 2020

663 Background: Genomic profiling (GP) is becoming more widespread in oncologic care, yet little is known regarding patients’ motivations to pursue or accept such testing. The current study examined patients’ reasons to pursue GP in the context of advanced genitourinary disease, and their potential association with demographic characteristics and psychiatric symptoms (anxiety and depression). Methods: Patients were recruited from a single institution after receiving a standardized dialogue about GP from their oncologist. Patients were included if they had received GP in the context of routine clinical care. Patients’ reasons for pursuing GP were assessed, as well as anxiety and depression via the PROMIS measures. The Kruskal-Wallis test was used. Results: A cohort of 90 patients (median 64 years old; 76% male; 71% white) with metastatic genitourinary cancers (61% renal cell carcinoma, 22% urothelial carcinoma and 17% prostate cancer) were enrolled. Demographic characteristics and psychosocial symptoms were associated with the pursuit of GP. Older and female patients tended to report that their physician’s recommendation was a primary driver of their decision (p<0.05), while younger patients sought to avoid unnecessary treatment and side-effects (p=0.04). In addition, patients experiencing anxiety and depression reported that GP adoption was driven by a desire to predict disease outcomes (p<0.05). Conclusions: The current study provides novel insight into the motivations underlying patients’ adoption of GP. The importance of a physicians’ recommendation may be indicative of the lasting influence of a paternalistic model of care, while the desire to avoid of side-effects can help guide effective discussions concerning the role of GP in care planning. The association between anxiety/depression and the hope that GP can predict disease outcomes reinforces the importance of ensuring patients possess an accurate understanding of this testing paradigm.