bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 and neutrophil to lymphocyte ratio (NLR) as predictive panel of prognosis in bladder cancer.
Authors: Qin Tao , Yu Hao , Wang Bo , Tan Cui , Hong Huangming , Hu Hai , Yao Herui 
Published: May 2020

e17040 Background: PD-1/PD-L1 blockade significantly improved survival for bladder cancer. PD-L1 expression might not be an ideal marker for patient selection in isolation. Several studies demonstrated that alternative markers such as NLR, a biomarker of systemic inflammation response to therapy, correlated with outcomes in a variety of cancers including bladder cancer, might be a predictor for patient selection and the response to immunotherapy. However, no reporters have been made combination of NLR and PD-L1 in predicting prognosis in bladder cancer. Methods: Suitable tissue of 100 FFPE blocks of bladder cancer patients treated in Sun Yat-Sen Memorial Hospital Sun Yat-sen University were stained with PD-L1 antibody. Clinicopathological data and pretreatment complete blood count were retrospectively collected. All patients were classified into high NLR group and low NLR group at cut-off 3.0. Kaplan-Meier and Cox proportional hazard models analyses were used to assessed the predictor of combined PD-L1/NLR for disease-free survival (DFS) and overall survival (OS). Results: Patients were mostly male (79%) with high grade () lymph node positive (21%), T3-4 (33%) . The positivity of PD-L1 expression was 22% (22/100) at cut-off 1%. Univariate analysis showed that PD-L1 expression was positively associated with larger tumor size, higher grade, positive lymph node metastases. Median DFS and OS were 35 months and 37 months, respectively. Both PD-L1 expression and NLR were associated with DFS and OS. COX analysis model showed that PD-L1 and NLR were independent prognostic factors for tumor prognosis. Of interest, when patients were divided in two groups based on PD-L1/NLR: patients with PD-L1+/high NLR as group 1 and other patients as group 2, group1 had significantly shorter DFS and OS (DFS, X2 = 4.146, P = 0.042; OS, X2 = 10.274, P = 0.001). COX proportional hazards regression models indicated that PD-L1+/high NLR was correlated with a significantly shorter DFS and OS (DFS, hazard ration [ HR] = 2.572, P = 0.05; OS, HR = 3.811, P = 0.003). Conclusions: The study indicated that combined use of PD-L-1/ NLR as predictive biomarker for survival. This feasible panel may be optional maker applied to select patients for immunotherapy.
Retrospective study to assess the efficacy and safety of checkpoint inhibitors in advanced urothelial carcinoma in real-world setting.
Authors: Sevillano Fernandez Elena , Puente Javier , Vidal Natalia , Pinto Alvaro , Garcia Sanchez Lourdes , Fiorini Aldo , Chara Velarde Luis Enrique , Ariza Irene Nalda , Cassinello Javier , Rodriguez Angel , Galvan Ruiz Saray , Rodriguez-Moreno Juan Francisco , Barquin Arantzazu , Ruiz Sergio , Navarro Paloma , Yagüe Monica , Grande Enrique , García-Donas Jesús 
Published: May 2020

e17043 Background: Checkpoint Inhibitors (CPI) have become a new standard of treatment in advanced urothelial carcinoma. However, little is known regarding the outcome of patients in daily practice.We aimed to assess tumor response and toxicity of CPIs in a cohort of patients treated in “real world” conditions. In parallel, a comprehensive molecular study in tumor samples from these patients, is ongoing. Methods: We designed an observational retrospective study within the “Grupo Centro” collaborative group. Adult patients diagnosed of metastasic urothelial carcinoma (mUC) and treated with CPIs between 2011-2019 in any of the 20 centers of the group, were eligible. Results: Up to date 100 patients have been included (82% males) with a median age of 74 years (48 -96). In 82% patients primary was bladder cancer. Most common metastasic sites were bone (26%) and liver (16%).With a median follow up of 10,6 months(mo) median progression free survival (mPFS) was 6,6mo (1,4-95,4 range) and median Overall Survival (mOS) was 21.3mo (3,8-121,8). 38% of patients received CPIs in first line(L): atezolizumab:27, pembrolizumab: 10, nivolumab:1. The median number of cycles was 8,2. Up to 51% received platinum-based combinations in first line. 69% (69/100) pts received 2L treatment: 68% with CPIs, 27,5% with chemotherapy and 4% with FGFR inhibitors (as part of a clinical trial). 2L mPFS was 3,5 mo (1,9-25.9). 23% (23/100) patients received 3L, of them 26% (6/23) were treated with CPIs. 3L mPFS:8,3mo(0,4-43,8). As a whole, patients treated with CPI accross different lines, achieved complete response in 8% of the cases, partial response in 18% and stable disease in 15%. Up to 44% of cases presented progressive disease as best response and evaluation was not available in 15%. Most common G1-2 AEs related to immunotherapy were: asthenia:31%,pruritus:16% and anorexia: 9%.10% pts experienced G3-4 toxicity: asthenia G3: 4, diarrhea G3: 1, erythrodysesthesia G3:1, arthromyalgia G3: 1, cardiac arrest G4:1,pneumonitis G4:1,anemia G3:1. Conclusions: This study confirms the efficacy and security of CPIs in real world. Response rates and toxicity profile were comparable to those reported in clinical trials.
Impact of concurrent angiotensin inhibitors on outcomes with PD1/L1 inhibitors for patients (pts) with metastatic urothelial carcinoma (mUC).
Authors: Curran Catherine , Pond Gregory Russell , Nuzzo Pier Vitale , Abou Alaiwi Sarah , Nassar Amin , Wei Xiao X. , Kilbridge Kerry L. , McGregor Bradley Alexander , Ravi Praful , Ravi Arvind , Sonpavde Guru 
Published: May 2020

e17044 Background: Preclinical data indicate that angiotensin inhibition may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Since (TGF)-β appears to be associated with resistance in patients with mUC receiving PD1/L1 inhibitors, we investigated whether angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) may enhance the outcomes of mUC pts receiving PD1/L1 inhibitors. Methods: Data from mUC pts who received PD1/L1 inhibitors at the Dana-Farber Cancer Institute (DFCI) was obtained. Data for ACEI and ARB administration was collected with concurrent administration defined as ongoing therapy from the time of starting PD1/L1 inhibitor treatment. A Cox logistic regression was used to investigate the impact of concurrent ACEI/ARB on any regression of tumor (ART, any decrease in size of tumor on scan) defined as any tumor regression after controlling for known prognostic factors (performance status, sites of metastasis, neutrophil/lymphocyte ratio, platelet count, hemoglobin). Results: Data was available for 178 pts with mUC who received pembrolizumab (79), atezolizumab (83), nivolumab (15), and durvalumab (1). Prior platinum chemotherapy was administered in 153 pts (86%). 33 pts (18.5%) received AECI/ARBs: 24 pts (13.5%) received ACEI and 9 pts (5.1%) received ARBs. Of 145 patients who did not receive an ACE-inhibitor nor an ARB, 49 (33.8%) patients experienced ART and their median overall survival (OS) was 9.1 months. Among/33 patients who did receive an ACEI or an ARB, 17 (51.5%) exhibited ARTand their median OS was 17.0 months. Multivariable analysis controlling for known prognostic factors revealed that patients who received ACE inhibitors or ARBs had greater ART (HR 3.0 [95% CI 1.25-7.17], p = 0.014) and improved OS, (HR 0.49 [95% CI 0.28-0.88] p = 0.016). Conclusions: In this hypothesis-generating study, concurrent angiotensin inhibitors including ACEI or ARBs were associated with significantly better outcomes in mUC pts receiving PD-1/L1 inhibitors. These results require validation in a larger mUC dataset in conjunction with probing the effect in other malignancies.
Lack of assocation of robotic radical cystectomy with increased incidence of local pelvic recurrence.
Authors: Madi Rabii 
Published: May 2020

e17045 Background: Robotic radical cystectomy (RRC) might be associated with an increased incidence of local pelvic recurrence and peritoneal seeding. We performed an institutional study evaluating the incidence and type of cancer recurrence following RRC. Methods: Between January 2012 and July 2019, 100 consecutive robotic radical cystectomies (RRC) were performed by a single surgeon RM. Pre-and Peri-operative characteristics were analyzed. Early and late, local and distant recurrences were studied, with the assumption that early local recurrences might suggest technical causative factors. Results: Median age was 63 ( IQR: 57-75). Male to female ratio is 2 to 1. Median BMI was 27.7 ( IQR: 24-32). 70% of patients were white, 27% were black, 2% were Hispanic, and 2% were Asians. Indications for cystectomy were refractory CIS in 6%, T disease in 26%, T2 disease in 52%, T3 disease in 5%, and T4 disease in 11%. Console time was 249 minutes ( IQR: 205-318). 70% of patients underwent ileal conduit, 30% underwent neobladder. 85% of patients underwent extended PLND and median blood loss was 150 ml, no patient required transfusion. Final pathology showed T0, Ta, CIS, T1, T2, T3, and T4 diseases in 2%, 5%, 10%, 10%, 21%, 36%, and 16% respectively. Median hospital stay was 6 days and 34% of patients had 30 days complications. 50% of patients had more than 36 months follow-up and overall, 24% of patients had cancer recurrences. Only 3 patients had recurrence within 3 months. Patient 1 had PT1, N1 disease with recurrences in common iliac lymph nodes and was treated by chemotherapy and is in complete remission. Patient 2 had pT3b N1 SCC with 3 months CT scans showing extensive pelvic and systemic recurrences and expired 6 months after surgery. Patient 3 had pT3a, N1 disease and had recurrence in the aorto-caval LN, received chemo-and immune therapy and has no evidence of disease. Conclusions: Our experience with robotic radical cystectomy did not show an increased incidence of early or local recurrence that could be attributed to the surgical approach. We believe that adherence to oncological principles is achievable with robotic approach.
Impact of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on overall survival or recurrence free survival in muscle-invasive bladder cancer at cystectomy.
Authors: Dawsey Scott , Sheng Iris Yeong- Fung , Ornstein Moshe Chaim , Wei Wei , Lee Byron H , Mian Omar Y. , Rini Brian I. , Garcia Jorge A. , Gilligan Timothy D. , Gupta Shilpa 
Published: May 2020

e17050 Background: The role of Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) in prognostication of MIBC is not clearly understood. There is growing evidence that, as markers of inflammation, they may have prognostic utility in MIBC at radical cystectomy (RC). Methods: We performed a retrospective analysis of MIBC patients who underwent RC at the Cleveland Clinic from 2/2015 to 1/2018. 84 patients were identified who were either diagnosed with TaN0M0 treated with Neoadjuvant Chemotherapy (NAC) or T1-T4N0M0 disease treated with or without NAC. For NAC, 27 patients received gemcitabine and cisplatin, 2 patients received gemcitabine and carboplatin, 4 patients received unknown regimen, and 3 patients received MVAC. Of the patients, there were 1 with Ta, 34 with T1, 44 with T2, 1 with T3 and 4 with T4 disease. Complete Blood Count with Differential closest to or on the day of resection was used. NLR and PLR were calculated by dividing Absolute Neutrophil Count and Platelet Count by the Absolute Lymphocyte Count, respectively. PLR and NLR were dichotomized at the median. Outcomes were analyzed via Kruskal-Wallis test. Results: Median follow up of patients was 28.8 months. Median NLR and PLR were 15.7 and 263, respectively. Mean NLR and PLR were 18.9 and 310, respectively. NLR and PLR did not correlate with overall survival, recurrence free survival, T or N stage post resection, or pathological response. Females were found to have a higher NLR than males. Conclusions: Contrary to previous reports, our study did not find any prognostic value of NLR and PLR in MIBC patients at RC. Further evaluation of PLR and NLR in MIBC and correlation with molecular features may help understand its potential prognostic role in patients undergoing surgical resection.
Response to guadecitabine (SGI-110) combined with cisplatin and gemcitabine (GCG) in platinum refractory germ cell tumors (GCTs).
Authors: Crabb Simon J. , Huddart Robert A , Brown Emma , Dunkley Denise , Downs Nichola , McDowell Cathy , Catto James WF , Griffiths Gareth Owen , Danson Sarah , Reid Alison Helen 
Published: May 2020

e17057 Background: Treatment options for platinum refractory GCTs are limited. Platinum resistance derives, in part, from tumour suppressor gene promotor methylation. In vitro, this reverses on co-administration of a DNA hypomethylating agent. Guadecitabine is a next generation hypomethylating agent. SPIRE is a phase Ib/IIa clinical trial to establish a GCG dose/schedule. Methods: We report 2 platinum refractory GCT patients (pts) treated (txd) in SPIRE with GCG (guadecitabine 20 mg/m2, SC, day (D) 1-5; cisplatin 70 mg/m2, IV, D8; gemcitabine 1000 mg/m2, IV, D8 + 15; filgrastim 300 μg, SC, D15-21; q21). Results: Pt 1: 21 yo man, testicular mixed GCT (seminoma/malignant teratoma intermediate). Prior tx: 2001, orchidectomy; 2005, 3 x BEP (bleomycin, etoposide, cisplatin) + retroperitoneal lymph node dissection. 2015, 2 x TI (paclitaxel, ifosfamide), 3 x TIP (cisplatin, ifosfamide, paclitaxel); 2016, 3 x HDCE (high dose carboplatin/ etoposide + autologous stem cell transplantation); 2017, 6 x GOP (gemcitabine, oxaliplatin, paclitaxel). In 2017, received 6 x GCG in SPIRE for CT confirmed lung metastases (mets) and rising β-hCG (human chorionic gonadotropin). Response: RECIST stable disease with metabolic CR on PET in lungs and > 90% β-hCG reduction. In Cycle 6, pt developed symptomatic brain mets, treated with WBRT (40Gy, 20#) + cyberknife to the six mets completed 2018. Since 2018, ongoing complete marker and radiologic (brain and systemic) remission (20 months). Pt 2: 44 yo man, primary mediastinal non-seminomatous GCT. Prior tx: 2008, 4 x BEP + mediastinal mass resection; 2015, 4 x TIP; 2016, 1 x HDCE. In 2017, received 5 x GCG in SPIRE for a PET avid mediastinal/pulmonary relapse and AFP (alpha-fetoprotein) rise. Response: RECIST stable and > 50% AFP reduction for 6 months (subsequent progression with intracerebral metastasis). Treatment was well tolerated. Grade 4 neutropenia/ thrombocytopenia occurred in both and febrile neutropenia in pt 1. Both required a 25% dose reduction in Cis/Gem. Conclusions: GCG produced exceptional clinical responses in both platinum refractory GCT pts. Prospective evaluation is warranted. Clinical trial information: 16332228.
Accuracy of clinical staging in stage I and IIa/b testicular nonseminomatous germ cell tumors (NSGCT) and implications on survival.
Authors: Srivastava Arnav , Patel Hiren V. , Kim Sinae , Kim Isaac , Singer Eric A. , Jang Thomas L 
Published: May 2020

e17058 Background: Clinical stage (CS) dictates treatment in men with testicular cancer and its inaccuracy may affect clinical outcome. We evaluate the accuracy of clinical staging in men with CS I and CS IIA/B NSGCT and explore the implications of inaccurate staging on overall survival. Methods: Using the National Cancer Database (NCDB), we abstracted all patients with clinical Stage I-IIB NSGCT who received a primary retroperitoneal lymph node dissection (RPLND) from 2004 to 2014. Primary RPLND was defined as RPLND performed for CS I-IIB patients without prior chemotherapy. CS was cross-tabulated with pathologic nodal staging data. Survival for patients who were accurately staged (CS I patients with pN0 disease, CS IIA patients with pN1 disease) and for CS I patients found to have pN+ disease was determined using the Kaplan Meier method. Results: 1,639 CS I-IIB patients underwent primary RPLND. Among CS I patients, 23% had upstaging of disease (pN1-3), of which 13.9%, 8%, and 1.1% were pN1, pN2, and pN3, respectively (Table). Pathologic N1-3 disease was higher in CS IB vs. CS IA patients (35.1% vs 14.2%, respectively). Of CS IIA patients, 23.1% had pN0 disease, while 44.8%, 13.4%, and 1.3% had pN1, pN2, and pN3 disease, respectively. At a median follow-up of 56.3 months, mortality rates for CS I patients who had pN1, pN2, and pN3 disease were 2.8%, 4%, and 9.1%, respectively, and < 1% for men with pN0 disease. 10-year overall survival for CS1 patients was significantly less favorable if upstaged to pN2 or pN3 disease after RPLND vs. pN0 or pN1. Conclusions: Nearly a quarter of patients with CS I NSGCT are under-staged and are found to have pN1-3 after RPLND. Nodal disease burden is associated with survival. Novel imaging techniques and biomarkers are needed to improve the sensitivity of detecting NSGCT. [Table: see text]
Effect of long-term peripheral neuropathy induced on cisplatin-based chemotherapy or radiation to the retroperitoneum in testicular germ cell tumor survivors.
Authors: Chovanec Michal , Galikova Dominika , Vasilkova Lucia , De Angelis Valentina , Rejlekova Katarina , Obertova Jana , Sycova-Mila Zuzana , Palacka Patrik , Kalavska Katarina , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Mego Michal 
Published: May 2020

e17062 Background: Treatment for testicular germ cell tumors (GCTs) results in late chemotherapy-induced peripheral neuropathy (CIPN). This study aimed to evaluate impact of curative treatments on different subtypes of self-reported peripheral nerve damage. Methods: GCT survivors (N = 186) followed-up annually at National Cancer Institute in Slovakia have prospectively completed European Organisation for Research and Treatment of Cancer (EORTC) CIPN20 questionnaire at 10 years of median follow-up (range 4-25). EORTC CIPN20 scoring allowed to obtain subscales on sensory function, motor function and autonomy function as well as an overall score. Study groups consisted of survivors treated with chemotherapy (N = 141) and radiotherapy to the retroperitoneum (N = 15). The control group consisted of survivors cured with orchiectomy alone (N = 30) Results: GCT survivors cured with chemotherapy reported higher impairment in overall peripheral neurological function compared to controls (mean score ± SEM: 24.2 ± 0.5 vs. 22.3 ± 1.1, P = 0.03). CIPN20 subscales have shown greater impairment in motor function (P = 0.04), but not in sensory/autonomy functions (both P > 0.05) in chemotherapy group versus controls. Survivors treated with BEPx3 or EPx4 reported similar CIPN in all subscales (all P > 0.05). Motor function was worse in survivors who received ³400mg/m2 of cisplatin compared to ones who received < 400mg/m2 (mean score ± SEM: 9.5 ± 0.2 vs. 8.9 ± 0.3, P = 0.04). Interestingly, patients treated with radiotherapy to the retroperitoneum (but not with chemotherapy) suffered from significantly more peripheral neuropathy in all measured domains compared to the controls (all P < 0.02) Conclusions: Evaluation of long-term perceived peripheral neuropathy after treatment for GCT has shown primarily motor function impairment after chemotherapy. Moreover, significant peripheral neuropathy in all observed CIPN20 subscales after radiotherapy to the retroperitoneum suggests this symptom is not exclusive to cisplatin-based chemotherapy.
Intrarenal renin-angiotensin system in hypertensive patients with localized kidney cancer.
Authors: Osokin Roman , Komarova Ekaterina , Aboyan Igor , Maksimov Aleksey Yu. , Ischenko Roman , Shatova Olga , Komarova Elizaveta 
Published: May 2020

e17069 Background: In the last decade, the relationship between arterial hypertension and the risk of developing kidney cancer has been pointed out. Some studies have shown that the metabolic imbalance of the components of the renal renin-angiotensin system (RAS) is associated with the development and progression of kidney cancer. Aim: To study the state of RAS in tumor and peritumoral tissues in hypertensive patients with kidney cancer. Methods: In patients with localized kidney cancer T1N0M0 and grade I-II arterial hypertension without special treatment (n = 40; KC + AH) in the samples of tumor (TT), peritumoral (PTT) and histologically unchanged tissue (HUT), the levels of angiotensin 1 and 2, 1-7 (AT1 and AT2, AT (1-7)) of angiotensin-converting enzymes (ACE and ACE2) were determined by ELISA. The comparison group consisted of patients with RC without impaired blood pressure (n = 55, KC). Results: In patients with KC, the level of AT1 is 1.5 times higher (p < 0.05), and AT2 is 1.6 times higher (p < 0.05) in TT against the background of unchanged content in PTT compared with HUT. The level of ACE is higher than HUT by 2.7 times, ACE2 - by 1.6 times (in all cases p < 0.05), and in PTT it is identical in HUT. In patients with KC + AH, the level of AT1 and AT2 in the TT is 1.8 times higher (p < 0.05) and 2.1 times (p < 0.01), respectively, the content of AT(1-7) is 1.6 times (p < 0.01). In PTT, AT1 is 1.6 times higher (p < 0.01) and AT2 is 1.9 times higher (p < 0.05), significantly lower than only AT2 in the TT (1.2 times at p < 0, 05). The level of AT(1-7) in the PTT is identical to the values in the GNT. The content of ACE and ACE2 in TT is 3.6 and 2.9 times higher, respectively, and in PTT is identical to that in TT. Correlation analysis revealed a reliable direct relationship in the studied groups for all parameters, while in the PTT of hypertensive patients, the relationship between the average blood pressure and the RAS peptide content had a higher tightness. Conclusions: An increase in the levels of angiotensin 1 and 2, angiotensin-converting enzymes ACE and ACE2 in the tumor tissues and peritumoral tissue in patients with localized kidney cancer, regardless of the presence of arterial hypertension at initially higher values in hypertensive patients, was shown. The presence of arterial hypertension in patients with KC changes the metabolism of local RAS in peritumoral tissue and is associated with an increase in the correlation between changes in the components of RAS and arterial hypertension.