bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying the interrelation between the HPV infection status and the morphological features of bladder cancer.
Authors: Zykova Tatiana A. , Shevchenko Alexey N. , Khomutenko Irina A. , Filatova Elena V. , Shevyakova Elena A. , Velikorodnaya Lilia A. , Dimitriadi Sergey N , Kit Oleg I. 
Published: May 2020

e17003 Background: The etiological role of human papillomavirus (HPV) in the development of squamous cell carcinoma of the cervix and larynx is considered proven. At the same time, there are conflicting data in the literature on the role of HPV in the development of bladder cancer (BC). The aim of the present study was to evaluate the prevalence of HPV infection in patients with BC, identifying the relationship between the status of infection and the morphological characteristics of the tumor. Methods: The study included 46 patients (10 women and 36 men) with morphologically confirmed urothelial cancer. Samples of urine, tumor tissue and a healthy bladder mucosa were examined. HPV DNA was determined by real-time PCR. Results: 28 (60.9%) patients were infected with high-risk HPV, including 6 (60.0%) women and 22 (61.1%) men. In 14 (30.4%) patients, HPV DNA was found in the tissue of the bladder mucosa: in 6 (13.0%) cases it was only in tumor tissue, in 4 (8.7%) only in healthy mucosa, in 4 (8.7%) simultaneously in healthy and tumor tissue. HPV DNA was detected in urine in 22 (47.8%) patients. The simultaneous presence of HPV DNA in the tissue of the bladder mucosa and urine was found in 8 (28.6%) HPV-positive patients. Single HPV infection was found in 20 (71.4%) patients, two types were found in 8 (28.6%). When analyzing type diversity, it was found that HPV16 infected 14 (38.9%) patients; HPV18, 31, 39 and 56 were determined in 4 (11.1%) cases each; 33, 52 and 59 types in 2 (5.6%) cases. Chronic inflammation was noted in 12 (26.1%) patients, 6 (50.0%) of them were HPV-positive. Among HPV-positive patients, invasive cancer was registered in 18 (64.3%), non-invasive cancer in 10 (35.7%) patients. Among HPV-negative patients, these rates were 14 (77.8%) and 4 (22.2%), respectively (p > 0.05). In the group of HPV-positive patients, tumors with a low degree of differentiation were found in 16 (57.1%), moderate in 6 (21.4%), high in 6 (21.4%). Among HPV-negative patients, these indicators were 4 (22.2%), 12 (66.7%) and 2 (11.1%), respectively (p > 0.05). Conclusions: HPV infection was detected in 60.9% of patients, including tumor tissue infection in 21.7% of patients. The most common HPV type was HPV16. There was no statistically significant difference between HPV-positive and negative tumors.
Combined OX40 agonist and PD-1 inhibitor immunotherapy improves the efficacy of vascular targeted photodynamic therapy in a urothelial tumor model.
Authors: Alvim Ricardo , Nogueira Lucas , Georgala Petrina M , Somma Alexander , Nagar Karan , Thomas Jasmine , Ledbai Souhil , Hudges Christopher , Scherz Avigdor Joshua , Zanganeh Saeid M , Kim Kwanghee , Coleman Jonathan 
Published: May 2020

e17004 Background: In patients with low-grade, small upper tract urothelial carcinomas (UTUC), as well as those in whom preservation of kidney function is critical, local ablative therapies such as vascular targeted photodynamic (VTP) therapy have emerged as a means of reducing treatment-related morbidity. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. Methods: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and metastasis and prolonged survival to a much greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.
Effect of neoadjuvant chemotherapy on health-related quality of life in patients with muscle invasive bladder cancer: Results from JCOG0209, a randomized phase III study.
Authors: Nishiyama Naotaka , Kitamura Hiroshi , Hinotsu Shiro , Tsukamoto Taiji , Shibata Taro , Mizusawa Junki , Kobayashi Takashi , Miyake Makito , Kojima Takahiro , Nishiyama Hiroyuki 
Published: May 2020

e17006 Background: Although neoadjuvant chemotherapy (NAC) provides survival benefits in muscle-invasive bladder cancer (MIBC), the impact of NAC on health-related quality of life (HRQoL) has not been investigated by a randomized trial. The purpose of this study is to compare HRQoL in patients with MIBC who received NAC followed by radical cystectomy (RC) or RC alone based on patient-reported outcome data. Methods: Patients were randomized to receive 2 cycles of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) followed by RC or RC alone. HRQoL was measured using the Functional Assessment of Cancer Therapy – Bladder (FACT-BL, version 4) questionnaire before the protocol treatments, after NAC, after RC, and one year after registration. Results: A total of 99 patients were analyzed. No statistically significant differences in postoperative HRQoL were found between the arms. In the NAC arm, the scores after NAC were significantly lower than the baseline scores in physical well-being, functional well-being, FACT-General total, weight loss, diarrhea, appetite, body appearance, embarrassment by ostomy appliance, and total FACT-BL. However, there was no difference in scores for these domains, except for embarrassment by ostomy appliance, between the two arms after RC and one year after registration. Conclusions: Although HRQoL declined during NAC, no negative effect of NAC on HRQoL was apparent after RC. These data support the view that NAC can be considered as a standard of care for patients with MIBC regarding HRQoL. Clinical trial information: C000000093.
Pembrolizumab and concurrent radiation is an effective regimen for muscle invasive bladder cancer.
Authors: Gupta Niraj K. , Reichard Chad A. , Large Michael , Leagre Christopher A. , Ney Kenneth , Liebross Robert H. , Ramsey John , Dugan Thomas , Tumati Vasu , Yadav Rina , Heckman Patrick , Tutterrow Rachelle , Schmidt Kristen 
Published: May 2020

e17020 Background: Neo-adjuvant chemotherapy with Gemcitabine and Cisplatin followed by radical cystectomy is the standard of care in muscle invasive bladder ca. Some patients, usually older patients or those with poor PS with bladder ca are either cisplatin in-eligble or medically unfit for radical cystectomy. We share our experience using a combination of Pembrozulimab and concurrent radiation in cisplatin in-eligible patients with muscle invasive bladder cancer. Methods: Patients with muscle invasive bladder ca underwent TURBT followed by treatment with Pembrolizumab 200 mg IV every three weeks for 4 cycles concurrent with radiation treatments. Radiation treatments were started 1 week after starting pembrolizumab. A total of 64-65 Gy was given to the bladder and pelvis. All patients underwent a cystoscopy to assess local response and imaging studies to rule out distant metastases. Results: Between June 2018 and October 2019, 9 patients with locally advanced, cT2-cT4 urothelial ca were treated. Male to female ratio 7 to 2. Median age was 76 years, range was 71-90. Reasons were not using cisplatin were, renal-insufficiency, 7 pts. and pt refusal in 2 pts. ECOG PS was 1 in 6 patients and 2 in 3 pts. All patients finished radiation treatments. All but one patient finished 4 cycles of pembrolizumab. One patient declined the last dose. Grade-3/4 I/O inhibitor AEs were seen in 2 patients, One had pneumonitis and other had elevation of LFTs. None of the patients was found to have distant mets on the scans done after 4 cycles of Pembrolizumab. A complete response, by cystoscopy (histology/cytology) was seen in 7/9 (77%) of the patients. The other 2 pts. with PR declined cystectomy and have continued on immunotherapy without any evidence of progression. Conclusions: A combination of Pembrolizumab concurrent with radiation treatments is an effective option and can be safely administered in cT2-T4 bladder cancer. It is an attractive option for cis-ineligible patients. The feasibility and efficacy of this combination needs to be further explored in larger studies
Heterogeneity of PD-L1 expression between primary and metastatic bladder cancer tumors and therapeutic implications between the immune cell score and combined positivity score.
Authors: Schulz Gerald Bastian , Todorova Rumyana , Rodler Severin , Grimm Tobias , Staehler Michael D. , Mayr Doris , Stief Christian G. , Casuscelli Jozefina 
Published: May 2020

e17041 Background: Heterogeneity of PD-L1 expression between primary and metastatic tumors has been reported for different cancer entities. In metastatic bladder cancer (BC), this might have an impact on therapeutic algorithms. For cisplatin-ineligible patients, first-line immune-checkpoint inhibitor therapy is recommended based on the PD-L1 expression assay employed, namely immune cell (IC) or combined positive score (CPS). Here, we compared the CPS and IC scores in bladder tumors (BT) and matched metastatic lymph nodes (LN). Methods: From our institutional database we identified patients with urothelial BC and lymphatic spread on pathologic examination of radical cystectomy specimens. Both CPS and IC were assessed by PD-L1 immunohistochemistry in the BT and matched LN metastases. Positive scores were in accordance to the respective cut-offs (CPS ≥10 and IC ≥2). Key clinicopathological parameters were correlated with CPS and IC scores. Differences between the two scores and between primary BT and LN metastasis were compared. CPS and IC scores both between and within the bladder tumour and LN metastasis were tested for correlation. Finally, the prognostic impact of the CPS and IC score was assessed. Pearson’s chi-squared test, Wilcoxon-test and Log-rank test were employed. Results: We included 108 patients (73.1% males, 26.9% females) with LN-positive urothelial BC. There was no correlation between age, gender, T-stage, number of positive lymph nodes and either CPS or IC scores. CPS was significantly more often positive in BT specimens (43.5%, n = 47/108) compared to LN samples (35.6%, n = 37/104) (p = 0.004). IC score was also significantly more often positive in BT specimens (28.7%, n = 31/108) compared to LN samples (21.2%, n = 22/104) (p = 0.013). There are significantly more CPS positive vs. IC positive cases when assessing PD-L1 expression in BT (p < 0.001). CPS and IC score positively correlated within both BT (r = 0.682, p < 0.001) and LN (r = 0.648, p < 0.001). CPS (r = 0.778, p < 0.001) and IC (r = 0.692, p < 0.001) positively correlated between the bladder tumour and LN. PD-L1 expression had no impact on oncological prognosis. Conclusions: PD-L1 expression measured by CPS correlates with IC scores in BC. There are, however, significant and clinically relevant differences between the BT and LN as well as between the two assays. Besides the implication for checkpoint-inhibitor therapy, PD-L1 expression does not seems to be prognostic in BC.
Patterns and predictors of referral among patients with muscle-invasive bladder cancer: A real-world study.
Authors: Clement Jessica Mary , Lu Zengqi , Pan Qi , Swede Helen , Mehta Rajni , Wang Xiaoyan 
Published: May 2020

e17051 Background: The multidisciplinary treatment of muscle-invasive bladder cancer (MIBC) has demonstrated considerable challenges in widespread clinical adoption. Despite guidelines recommending multidisciplinary, utilization of neoadjuvant chemotherapy for bladder cancer treatment remains low in the real-world settings. This study aims to examine the real-world referral patterns from urology to medical oncology and/or radiation oncology and the factors that associated with the referral following a diagnosis of MIBC. Methods: Following approval of involved IRBs, investigators followed a common protocol under the auspices of the Rapid Case Ascertainment at the Yale Cancer Center and performed manual chart review of MIBC patients diagnosed in the state of Connecticut from 2004 – 2015 and treated at investigator-affiliated hospitals. Information on medical history, radical or partial cystectomy, chemotherapy, radiation therapy, initial treating physician, and referrals to additional providers were recorded. This data set was linked to the Surveillance, Epidemiology, and End Results (SEER) database for demographic information. Logistic regression analysis adjusted with demographics (i.e. gender, race) and medical histories (i.e. prior cancers) was conducted to identify factors associated with referral. Results: Of the 665 patients whose initial treating physician was urologist, only 291 (43.8%) were referred to a medical oncologist and/or a radiation oncologist. Independent factors associated with lack of referral included: older age (OR = 0.994 for every incremental year, P-value: 0.0055), and greater Charlson comorbidity score (OR = 1.064. P-value: 0.015). Patients with kidney diseases and diabetes were less likely to be referred. Conclusions: Lack of referral to medical oncology and/or radiation oncology is a critical barrier to the use of optimal multidisciplinary therapy. Referral decision made by urologists is impacted by a patient’s age and overall health condition. [Table: see text]
Association of lymph node count and survival after primary retroperitoneal lymph node dissection (RPLND) for testicular nonseminomatous germ cell tumor (NSGCT).
Authors: Patel Hiren V. , Srivastava Arnav , Kim Sinae , Singer Eric A. , Kim Isaac Yi , Jang Thomas L 
Published: May 2020

e17052 Background: RPLND for clinical stage (CS) I & IIA/B NSGCT has both staging and therapeutic implications. Single center studies have reported on the impact of lymph node count on outcome after 1° RPLND for men with NSGCT. However, this has yet to be corroborated in a nationally representative dataset. Methods: Using the National Cancer Database, patients who received a 1° RPLND from 2004-2014 for CS I & IIA/B NSGCT were identified. The analytic cohort was stratified according to LN count (≤20, 21-40, and > 40 LNs). Sociodemographic characteristics were compared among groups. The Kaplan-Meier method was calculated and pairwise comparisons performed. Based on sensitivity analyses to determine LN cutoff that impacts survival, subsequent analysis compared patients with ≤20 and > 20 LNs resected. Multivariate analysis using stepwise regression was used to determine factors associated with receipt of an RPLND with > 20 LNs resected. Results: Of 1,376 men who received 1° RPLND for Stage I or IIA/B NSGCT, 35.6%, 27.4%, and 14% had ≤20, 21-40, and > 40 LNs resected, respectively. LN count was associated with overall survival (OS), with 95%, 97%, and 98% 8-year OS for men with LN count ≤20, 21-40, and > 40 LNs, respectively. OS in men with ≤20 vs 21-40 (p = 0.018) and > 40 LNs (p = 0.042) resected differed significantly. However, no significant difference was observed when 21-40 vs > 40 LNs were resected (p = 0.677). Therefore, subsequent analysis compared those who had ≤20 and > 20 LN resected, and OS between these two groups differed significantly (Figure). Multivariate analysis demonstrated that patients with private insurance, surgery having been performed at an academic center or in the Northeast, and those with pT2 disease were more likely to have > 20 LNs resected at the time of RPLND. Conclusions: Lymph node count after 1° RPLND for NSGCT is significantly associated with overall survival, with more favorable survival seen in those who receive an RPLND with > 20 LNs resected when compared to ≤20 LNs.
Standard-dose salvage chemotherapy in patients with refractory metastatic germ-cell tumors (mGCT) progressing after high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplant (PBSCT).
Authors: Agrawal Vaibhav , Althouse Sandra K. , Hanna Nasser H. , Einhorn Lawrence H. , Adra Nabil 
Published: May 2020

e17061 Background: About 40% of patients with relapsed GCT will progress after HDCT and PBSCT and are generally incurable with further standard dose chemotherapy. We previously evaluated standard dose cisplatin combination chemotherapy in 15 patients following progression from HDCT and observed only a single brief PR ( JCO 18(6), 1181-1186.). We report results of non-platinum standard-dose chemotherapy regimens in refractory mGCT. Methods: Pts with mGCT who progressed after HDCT+PBSCT at Indiana University from 2004-2019 were evaluated. Kaplan-Meier methods and log-rank tests were used to analyze PFS and OS for the regimen directly following HDCT. Results: 78 pts with refractory mGCT were reviewed. 64 pts. (82%) received paclitaxel+gemcitabine (TG), 10 pts. (13%) received daily oral etoposide (E), and 4 pts. (5%) received oxaliplatin-based (O) regimens (oxaliplatin+gemcitabine or oxaliplatin+bevacizumab). Median age was 29 (range, 16-57). Primary site was testis in 62, retroperitoneum in 6, mediastinum in 9. Metastatic sites included retroperitoneal LNs (62), pulmonary (58), liver (23), bone (6), and brain (21). IGCCCG risk was good in 16, intermediate in 5, and poor in 57. HDCT was utilized as 2nd line setting in 72 pts, and ≥3rd line in 6 pts. Median time from HDCT to progression was 4 months (upper limit 16.6 months). PS and OS data is shown in the table, with superior outcomes in TG compared to O and E (p < 0.001). Maintenance oral etoposide after HDCT was administered in 44% (n = 28) of all patients who later progressed and received TG. Among 12 patients (19%) with 12-month PFS on TG, the median overall PFS was 18.3 months with 2 patients alive at the time of last follow-up. The primary site was testis in 11 patients, 67% (n = 8) were platinum refractory, and 83% (n = 10) were IGCCCG poor risk. 10 patients achieved a PR to TG, and two patients achieved CR. Conclusions: Salvage standard-dose chemotherapy with paclitaxel+gemcitabine after progression on HDCT is superior to oral etoposide or oxaliplatin-based regimens and should be the preferred regimen in patients with refractory mGCT. [Table: see text]
Baseline and early change of neutrophil to lymphocyte ratio (bNLR and ΔNLR) as prognostic factors in metastatic renal cell carcinoma (mRCC) treated with Nivolumab: Final results of the Meet-URO 15 (I-BIO-REC) study.
Authors: Rebuzzi Sara Elena , Buti Sebastiano , Maruzzo Marco , De Giorgi Ugo , Sbrana Andrea , Zucali Paolo Andrea , Fantinel Emanuela , Procopio Giuseppe , Merler Sara , Fratino Lucia , Baldessari Cinzia , Ricotta Riccardo , Massari Francesco , Banna Giuseppe Luigi , Soraru' Mariella , Santoni Matteo , Cortellini Alessio , Bersanelli Melissa , Signori Alessio , Fornarini Giuseppe 
Published: May 2020

e17081 Background: Biomarkers to select mRCC patients most likely to benefit to immunotherapy are needed. The retrospective multicentre Meet-URO-15 study evaluated the prognostic role of peripheral blood cells in mRCC patients treated with Nivolumab. Methods: Complete blood count was assessed at the first four cycles of Nivolumab. The primary endpoint was median overall survival (mOS) according to bNLR. NLR was defined as neutrophil / lymphocyte (cutoff = 3) and ΔNLR the difference between NLR at 2nd cycle and bNLR (median as cutoff = 1.1). Results: From October 2015 to October 2019, 470 patients started Nivolumab as 2nd (67%), 3rd (22%) and > 3rd (11%) line. Median age was 66 years, 71% were male and 83% had clear cell histology. Baseline IMDC group was favorable in 25%, intermediate in 63% and poor in 12%. Lymph-nodes, visceral and bone metastases were present in 54%, 91% and 36%. mOS and progression-free survival (PFS) were 34.8 and 7.5 months. Overall response rate (ORR) and disease control rate (DCR) were 30% and 61%. bNLR was available in 404 patients: bNLR < 3 (54%) correlated with statistically significant longer PFS [11.4 vs 5.4 months; HR 1.69 (1.33-2.15)] and OS [46.2 vs 17.2 months; HR 2.37 (1.72-3.26)] (both p< 0.001), with similar ORR (35% vs 30%, p= 0.28) but higher DCR (71% vs 52%, p< 0.001). ΔNLR was available in 360 patients: ΔNLR < 1.1 (73%) correlated with a statistically significant improvement of PFS [11.2 vs 4.9 months; HR 1.53 (1.16-2.03), p= 0.03], OS [Not Reached vs 19.7 months; HR 1.83 (1.28-2.61), p= 0.001], ORR (37% vs 23%, p= 0.011) and DCR (68% vs 53%, p= 0.008). Multivariate analyses adjusted for IMDC group, line of therapy and metastatic sites, confirmed the statistically significant correlation of bNLR and ΔNLR with OS, PFS and DCR. Conclusions: Our study showed the statistically significant correlation of lower bNLR and early ΔNLR with longer OS, PFS and higher DCR in mRCC patients treated with Nivolumab.
Real-world safety and efficacy data of patients with synchronous metastatic renal cell carcinoma (mRCC) treated with nivolumab and ipilimumab (N+I) and the primary tumour (PT) in place.
Authors: Meerveld-Eggink Aafke , Graafland Niels , Wilgenhof Sofie , Van Thienen Johannes V. , Grant Michael , Szabados Bernadett , Abu-Ghanem Yasmin , Boleti Ekaterini , Blank Christian U. , Haanen John B. A. G. , Powles Thomas , Bex Axel 
Published: May 2020

e17083 Background: Following CARMENA and SURTIME, upfront cytoreductive nephrectomy (CN) is no longer standard of care. Intermediate and poor risk patients (pts) receive systemic therapy with the PT in place with the option to perform deferred CN in responding pts. This practice has been adopted after the recent shift to immune checkpoint inhibitor combination in frontline for mRCC. We assessed the safety and efficacy of this approach in a real-world population. Methods: A retrospective analysis of a clinical audit from 3 institutional datasets of pts treated with first-line N+I and the PT in place. Pts and tumour characteristics, International Metastatic RCC Database Consortium (IMDC) risk, overall response rate (ORR) in the PT and metastatic sites, time to response (TTR) of the PT, PT- and immune related- (ir) adverse events (AE), deferred CN rate, progression free- (PFS) and overall survival (OS) were assessed. Results: Of 41 pts treated with N+I and the PT in place, 46.3% were IMDC poor risk and 51.2% had > 3 metastatic sites. After a median follow-up of 5.9 (2-10.3) months, 29 had at least 1 CT scan from baseline. Of those, 7 (24.3% [95% confidence interval [CI] 0.10-0.43]) had a partial response (PR) of the PT with a median TTR of 5.3 (2.5-8.6) months. Mean and median PT reduction were 16.9% (+7.6 to -70.3%) and 10% from a baseline mean tumour size of 9.5 (3.8-16.1) cm. Pts with a PT reduction > median (n = 14) had a PR at metastatic sites in 86% (CI 0.57-0.98) and no progressive disease (PD). Pts with PT reduction < median (n = 14) had PR in only 21% and PD at metastatic sites in 57% (CI 0.28-0.82). None of the PT progressed. There was no complete response (CR) at metastatic sites . No CN was performed; 5 pts (12%) developed hematuria grade 1-3, requiring embolisation in 2 (4.9%). Grade 3-4 irAE were observed in 22% of pts. Median PFS and OS are 8.6 months and not reached. Conclusions: N+I with the PT in place is safe and PT reduction is associated with response at metastatic sites. Most PT responded by 6 months. No CR at metastatic sites were observed (compared to a 9% CR rate in the pivotal trial) in this real-world population with a relatively high percentage of poor-risk pts. Furthermore, no deferred CN has been performed, neither for near-CR at metastatic sites nor for PT symptoms.