bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early outcome results of a phase I/II study for an IL-2/T-cell receptor fusion protein in combination with gemcitabine and cisplatin (GC) in patients with locally advanced or metastatic urothelial cancer.
Authors: Hajdenberg Julio , Landau Danny , Vaena Daniel A. , Fishman Mayer N. , Rosser Charles Joel , Milhem Mohammed M. , Weber Jeffrey S. , Rizzo Virginia , Zehr Pamela , Williams-Elson Irene , Rhode Peter , Schutt Tessa , Hernandez Liza , Huang Bee-Yau , Wong Hing C. 
Published: March 2020

e15010 Background: ALT-801 is a human IL-2/single-chain T-cell receptor fusion protein previously tested in a phase 1 in patients with advanced malignancy (Fishman 2011 CCR 17:7765) (CA097550). In various murine models, ALT-801 demonstrated potent activity against syngeneic and xenograft UC, suggesting sensitivity of this disease to IL-2 based immunotherapy (Wong, unpubl. data.). Although UC are sensitive to platinum-based chemotherapy, combinations such as gemcitabine (G) + cisplatin (C) are associated with CR rates of around 15%, and limited durability of responses with limited effects of retreatment. Methods: We report here initial efficacy results of co-administration of G (1000 mg/m2/dose, d 1 & 8), C (70 mg/m2/dose, d 1) and ALT-801 (escalating doses, d 3, 5, 8, 10) on a 21 day schedule, for 3 cycles, in patients with UC that was locally advanced, or metastatic, for whom GC chemotherapy would be considered. ALT-801 planned doses are 0.04 to 0.12 mg/kg/dose in 5 dose cohorts with a 3+3 escalation design. Subjects with at least stable disease after 3 courses may receive 4 additional weekly doses of ALT-801 alone. Results: To date, three Stage IV UC patients (1F, 2M; 59-63 yrs; 2 patients had predominantly nodal metastases and one patient liver metastases) completed treatment with 0.04 mg/kg ALT-801+GC. Two had previously undergone radical cystectomy and had then later failed following GC treatment. Grade 3/4 toxicities observed include neutropenia (2), thrombocytopenia (2), leukopenia (1), lymphopenia (1) and anemia (1), consistent with GC and ALT-801 known pharmacodynamic effects. All 3 had radiological CRs by week 13. One patient underwent radical cystectomy had a pCR. The next (0.06 mg/kg/dose) cohort has started treatment. A phase II expansion cohort is planned at the MTD. Conclusions: The early response pattern is encouraging in that ALT-801 may be a novel, active immunotherapy for UC. NCT01326871
Outcomes of small call carcinoma of bladder in elderly.
Authors: Thota Swapna , Kistangari Gaurav , Garje Rohan , Daw Hamed 
Published: March 2020

e15023 Background: Small cell carcinoma (SCCB) is an aggressive tumor and presents in an advanced stage. In this retrospective study we analyze the patterns of treatment and survival among elderly patients (age>75 years). Methods: We identified 38 patients who were diagnosed with primary SCCB at our institution and its affiliated hospitals between 1995-2010. Out of which 15 patients were above the age of 75 years. For each patient histological, demographic and clinical data were obtained by chart review. Deaths of all patients were confirmed by social security death index (SSDI). Staging of all patients were categorized as limited (T1-4N0-1M0) or extensive stage (TxNxM1 or TxN2-3M0). Results: 15 patients were identified with pure small cell carcinoma of bladder. Mean age of patients was 80 years ( ranged from 76 years to 90 years). Male to female ratio was 5:1. 86% were caucasians. Among patients with available clinical information, 5 out of 15 patients (33.3%) had extensive stage and remaining 10 had limited stage SCCB. Around 73% (11/15) of the patients underwent transurethral resection of bladder tumor (TURBT). One patient had partial cystectomy and three patients had radical cystectomy. All three pateints who underwent radical cystectomy had limited disease and had an overall median survival (OMS) of 27 months. Patients with TURBT had a OMS of 6 months. Conclusions: Prognosis for patients with SCCB remains poor. Careful selection of patients for radical cystectomy with limited disease may improve overall median survival among elderly population with SCCB.
Compliance with follow-up (f.-up) program and outcome of patients (pts) with stage I nonseminomatous germ cell tumors (NSGCT).
Authors: Fedyanin Mikhail , Tryakin Alexey , Denisova Elena , Bulanov Anatoly , Zakharova Tatiana , Matveev Vsevolod B. , Figurin Konstantin , Garin Avgust , Tjulandin Sergei 
Published: March 2020

e15025 Background: There are limited data about f.-up quality of pts with stage I NSGCT after orchiectomy (OE) management and their survival. A retrospective analysis was performed to find the impact of compliance with schedule of f.-up on outcome of relapsed pts with stage I NSGCT. Methods: We analyzed data of 261 pts with stage I GCT treated in our department from 1994 to 2010. NSGCT was revealed in 128 (49%) pts. Therapeutic options following OE comprised retroperitoneal lymph node dissection (RPLND) – in 4/128 (3%), adjuvant cisplatin-based chemotherapy (CT) - in 75/128 (58%) and surveillance - in 49/128 (39%). The following procedures were performed in our center during the f.-up: ultrasound of the abdomen and pelvis, serum AFP, HCG and LDH – bimonthly in the 1st year, quarterly in the 2nd year, biannually in the 3rd-4th years and then annually; X-Ray of the chest – thrice-yearly in the 1st year, biannually on the 2nd year and then annually. Median f.-up time was 75 (range 16 - 176) months. Results: No pts had relapse after RPLND, 4/75 (5,3%) pts had relapses after CT, 16/49 (32%) pts – in surveillance group. 17/20 (85%) relapses were revealed in the first 2 years of f.-up. During relapses, 17/20 (85%) pts had good, 2/20 (10%) - intermediate and 1 patient - poor IGCCCG prognosis. The mean number of visits in the 1st year after OE was 3, on the 2nd year -1,4, in the 3rd- 4th years - 1 per year. All relapsed pts received induction CT (EP or BEP regimen). 11/20 (55%) pts were compliant to visits, 9/20 (45%) pts were not. The 5-years overall survival was 90% and 68% (p=0,3); the median size of metastases in RPLN was 2,2 and 5,5 cm (p=0,001), respectively. All pts in intermediate and poor prognosis were in the noncompliant group, whereas all pts, who were compliant were in good prognosis (3/9 (33%) vs 0/11 (0%), p=0,07). Moreover, surgical removal of residual tumor after induction CT was more often performed in the noncompliant group (5/11 (33%) vs 5/9 (71%), р=0.6). Conclusions: Poor compliance with f.-up program in stage I NSGCT results to non significant worse long-term outcome. Also pts, who were compliant had significantly smaller size of metastases in retroperitoneal lymph nodes at relapse and had good IGCCCG prognosis in all case.
Role of an extended pathology exam in risk classification of testicular germ cell tumors (GCTs).
Authors: Marinca Mihai Vasile , Caruntu Irina Draga , Liliac Ludmila , Giusca Simona Eliza , Marinca Andreea , Miron Lucian 
Published: March 2020

e15032 Background: The 1997 IGCCCG Consensus classification provides clinicians with enough information to efficiently choose between treatment options for most GCT patients. Nevertheless, therapy is ineffective in 5-10% of cases (even more in less developed countries), and about the same numbers experience severe side effects. This exploratory study aims to assess the impact of more rigorous and detailed pathology examination on improving the assignation of these patients to prognostic groups and, consequently, making optimal therapeutic decisions. Methods: Predefined features were reviewed on histology slides from 39 GCT patients followed-up for a median of 48.28 months. We designed a uniform pathology protocol, focused on identifying potential new prognostic factors. Categorical and continuous variables were quantified using light microscopy and computer-aided morphometry and, due to the small sample size, their statistical correlation was analyzed by exact tests and Spearman’s rho, respectively. Significant (2-sided p-value <0.05, under sample size reserve) coefficient values were entered in hierarchical cluster analysis (HCA). Results: Favorable IGCCCG group, presence of seminoma, glandular tissue pattern, presence and histoarchitecture of lymphocytic infiltrate associated better survival rates and lower risk of progression. Invasion of the epididymis and spermatic cord, presence of teratoma, choriocarcinoma and yolk-sac elements, papillary pattern and cell pleomorphism predicted poorer outcomes. HCA yielded 2 significantly distinct patient groups in terms of overall survival (p=0.018) and time to progression (p=0.080), but not disease-free survival (p=0.614). Conclusions: Quantification of tumor subtypes and other histology features of GCTs (e.g. necrosis, tissue patterns, inflammation) is feasible and, if standardized, may prove useful in optimal selection of risk groups, when performed by an experienced pathologist.
Retrospective analysis of 132 patients with stage I seminoma: Observation versus adjuvant radiation or chemotherapy in a single institution.
Authors: Vega Estela , Cascales Almudena , De Velasco Guillermo , Cabeza Rodriguez Maria Angeles , Parrilla Lucia , Colmenero Maria , Manneh Ray , D'Ambrosi Rafael , Pascual Tomas , Rodriguez Garcia Sofia , Valdiviezo Natalia , Gomez Ordonez Silvia , Dorta Miriam , Guardado Sandra , Bartolome Adela , Lechuga Carmen , Perez Regadera Jose Fermin , Lanzos Gonzalez Eduardo , Cortes-Funes Hernan 
Published: March 2020

e15033 Background: Classically, radiotherapy (RT) has been the standard adjuvant treatment for stage I seminoma patients. Improvements in early relapse diagnosis have led high cure rates. Two cycles of adjuvant carboplatin present similar efficacy to radiotherapy with less toxicity have led to re-examination of the standard treatment approach. Methods: Retrospective study of 132 patients diagnosed with stage I seminoma from 1980-2010 who received whether treatment with RT, chemotherapy (Cht) or active surveillance (AS) after orchiectomy at one Universitary Hospital. The objective was to determine the relapse-free survival (RFS), overall survival (OS), and disease -specific survival (DSS). Results: Of the 132 patients, 68 were treated with prophylactic irradiation (paraaortic ± pelvic nodes, the median total dose radiation 26 Gy at 2 Gy per fraction), 33 with adjuvant chemotherapy (31 had carboplatin x 2, 2 had BEP x 2), and 31 underwent surveillance. Among the RT patients (median follow-up 121months), mean age was 40 years (range: 20-70) with mean tumor size of 5.5 cm (range: 1-14). 6% of them had rete testis involvement and 15% vascular invasion. There was 1 relapse with a median disease-free survival (DFS) of 103 months and no deaths from seminoma. RFS was 98% at 10 years. OS and DSS were 100% at 10years. Among the chemotherapy patients mean age was 30 years (range: 18-66) with mean tumor size of 6,18cm (range: 1,5-10). 9% of them had rete testis involvement and 60 % vascular invasion. With a median follow-up of 66 months, there was 1 relapse. Five-year RFS was 97%, OS and DSS were 100%. Among the observation patients (median follow-up 148 months), mean age was 35 years (range: 20-78) with mean tumor size of 3,7cm (range: 1,3-7). 6% of them had rete testis involvement and 6 % vascular invasion. There were 6 relapses with no deaths from seminoma. RFS was 80%, specific OS and DSS was 100% at 10 years. Of the patients who relapsed, all were rendered disease-free with chemotherapy; with non evidence disease at last follow-up. Conclusions: Consistent with published trials both radiotherapy, chemotherapy or active surveillance are safe and effective treatments with similar oncologic results.
Survival and prognostic factors after complete response to first-line cisplatin-based chemotherapy in patients with advanced testicular seminoma: The Instituto Nacional de Enfermedades Neoplásicas experience.
Authors: Neciosup Silvia P. , Callacondo David , Rua Oliver , Rojas Jose Ernesto , Quesada Jose , Schwarz Luis Jesus , Aguilar Marin Ivan Carlos , Más Luís , Gomez Henry , Vallejos Carlos S. 
Published: March 2020

e15036 Background: The IGCCCG classification, used to guide the management of metastatic seminomas may underestimate the predictive value of other prognostic factors. We aimed to identify prognostic factors for long term survival in patients with advanced testicular seminoma who achieved a complete response to first line cisplatin based chemotherapy. Methods: A retrospective analysis was carried out on 101 patients with advanced testicular seminoma who received induction cisplatin based chemotherapy between 1990 and 2010.Data regarding clinical and laboratory parameters that may influence the overall survival (OS) or progression free survival (PFS) were collected from clinical records. Univariate analysis was performed using the Kaplan-Meier method, while Cox regression modeling was used for multivariate analysis. Results: The mean follow up time was 8.4 years. 9 (9%) patients died and 16 (16%) developed relapse. The 10 year OS and PFS rates were 91% and 84%. In univariate analysis, a testicular tumor ≥5.5cm and a retroperitoneal metastases ≥16 cm were associated with poor OS and PFS. The prechemotherapy LDH levels ≥2.4xUNL and age ≤36 years showed a trend to shorter PFS. Multivariate analysis showed that only the retroperitoneal metastases ≥16 cm was significant independent prognostic factor for OS (p=0.04, HR 3.86; 95% CI, 1.03-14.41) and PFS (p=0.05, HR 3.17; 95% CI, 0.99-10.15). Age ≤36 years (p=0.03, HR 4.29; 95% CI, 1.12-16.34) was also an independent prognostic factor for PFS. Conclusions: The presence of a retroperitoneal metastases ≥16 cm, a testicular tumor ≥5.5cm and age ≤36 years are associated with decreased OS and/or PFS in patients who achieved a complete response to first line cisplatin based chemotherapy. The use of these factors may assist the elaboration and implementation of new prognostic models that can guide the follow-up and management of patients with advanced testicular seminomas.
Development and validation of prognostic models in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib: A Greek-French collaboration.
Authors: Karavasilis Vasilios , Tzanis Kimon , Bamia Christina , Elaidi Reza-Thierry , Kostouros Efthimios , Visvikis Antonios , Skarlos Dimosthenis-Vasilios , Linardou Helena , Razis Evangelia , Chrisofos Michael , Stravodimos Kostas , Lazaridis George , Timotheadou Eleni , Hatzimouratidis Constantinos , Oudard Stephane , Fountzilas George , Dimopoulos Meletios A. , Bamias Aristotelis 
Published: March 2020

e15040 Background: The use of tyrosine kinase inhibitors (TKIs) in mRCC has improved prognosis but the individual outcome remains largely unpredictable. The MSKCC model, used to identify risk groups, was developed in cytokine-treated patients and has not been externally validated in the TKI era. It contains 3 laboratory factors (total 5), making its application to retrospective series somewhat problematic. Subsequently, a more complicated model, using 4 laboratory factors (total 6) has been described. The Hellenic Cooperative Oncology Group recently described a simpler model with only 3 clinical factors. We are describing the application and external validation of this model. Methods: 128 Greek patients with mRCC treated with 1st line sunitinib were included. All had had nephrectomy. Previous interferon was allowed. Cox regression was used to develop a predictive model for overall survival (OS). Our model was compared to that of MSKCC and Heng’s using ROC curves and Harrell’s Concordance Index. Risk groups were defined by the calculated prognostic index and by clinical factors. External validation was done using a sample of 226 French patients. The Royston and Sauerbrei D statistic was used as a measure of discrimination of the survival model. Results: Time from diagnosis of RCC to start of sunitinib (<12), PS (>1) and number of metastatic sites (>1) were independent adverse prognostic factors in the Greek dataset. The co-efficients for each factor were: 0.51, 0.97, 0.61, respectively. The 3 risk groups were defined by the 25th and 75th percentiles of the prognostic index values (Table 1). The model was of equal prognostic value to the MSKCC (p=.272) and Heng’s (p=.075). French had better survival than Greek patients especially in the high risk group (for all models). Validation of our model in the French data showed that it was applicable (R2 D: 0.14, SE: 0.09), especially for the low/medium risk groups. Conclusions: Our model is the only one externally validated in TKI-treated patients. It may be considered as a simpler alternative to those currently applied. [Table: see text]
Partial versus radical nephrectomy in the elderly: A surgical conundrum.
Authors: Narayanan Ramkishen , O'Malley Rebecca Leigh , Brewer Katherine , Hayn Matthew H. , Mehedint Diana , Safwat Mohab W. , Kim Hyung Lae , Underwood Willie , Schwaab Thomas 
Published: March 2020

e15046 Background: Whether increased risk of complication (Cx) is balanced by the renal preserving benefits of partial nephrectomy (PN) in those with shortened lifespan is unclear. We compared Cx and renal function outcomes of PN and radical nephrectomy (RN) in the elderly. Methods: From a prospectively maintained renal tumor database, we retrospectively identified patients ≥ 75 years old who had RN or PN for a solitary, localized tumor ≤ 7cm and a normal contralateral kidney. CKD-EPI formula estimated glomerular filtration rate (eGFR). Propensity analysis was used to account for population selection bias: probability of RN was calculated by multivariate logistic regression, including variables thought to influence selection for nephrectomy type, yielding a propensity score based on quintile of RN probability. Odds ratios for any Cx, high grade Cx and postoperative stage ≥ 4 chronic kidney disease [CKD4] by nephrectomy type were recalculated using logistic regression adjusting for propensity score. Other statistical tests used were Student′s t, Wilcoxon rank-sum and Fisher′s exact. Results: 57 patients met inclusion criteria: 47% and 53% had PN and RN, respectively. Age, gender, baseline Cr, BMI and Charlson index were similar between the PN and RN groups. In both groups, surgical approach was minimally invasive in 93%. Mean tumor size with RN was larger than with PN (4.6 v. 3.6 cm, p<0.01). EBL was higher with PN (360 v. 122 mL, p=0.02), although intraoperative transfusion rate was similar (p=0.13). With similar preoperative eGFR between groups, mean postoperative eGFR was lower in the RN group (36 v. 50 ml/min/1.73m2, p<0.01). Propensity analysis showed likelihood of CKD4 was significantly higher with RN (OR 5.5, p=0.04). Cx rate was similar between PN and RN (30% v.37%, p=0.39), but most high grade Cxs were seen with PN (56% v. 23%, p=0.01). Propensity analysis supported these data in that risk of total Cxs was not increased with PN (p=0.46) but risk of high grade Cxs was significantly higher with PN (OR 9.2, p<0.01). Conclusions: Risk of significant renal dysfunction following RN was 5-fold that of PN, but risk of high grade complications with PN is 9-fold that of RN. Evaluating the clinical impact of these risks should be done on an individual patient basis.
International, expanded access program of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy (VEGFr-TKI): Subanalysis from emerging growth market (EGM) countries.
Authors: Lee Se-Hoon , Buyukberber Suleyman , Ou Yen-Chuan , Shapiro Jeremy David , Panneerselvam Ashok , Ocak Arikan Ozlem , Xue Hong-Ling , Rusakov Igor 
Published: March 2020

e15047 Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor shown to benefit patients with mRCC after failure of initial VEGFr-TKI therapy. In the phase 3 RECORD-1 trial, median progression-free survival was 4.9 months with everolimus and 1.9 months with placebo (hazard ratio, 0.33; P < .001). REACT (RAD001 Expanded Access Clinical Trial in RCC; NCT00655252) was an open-label, expanded access program that provided everolimus before commercial availability to 1367 patients with VEGFr-TKI refractory mRCC in 34 countries. Final results of REACT were recently published (Eur J Cancer. 2012;48:324-332). Methods: The primary objective of REACT was to evaluate the long-term safety of everolimus 10 mg/day as determined by the overall incidence of grades 3 and 4 adverse events (AEs). Best overall tumor response was assessed according to RECIST 1.0. This subanalysis was conducted to assess primary and secondary end points in a subgroup of patients from 11 EGM countries: Turkey, Australia, Russia, Israel, Lebanon, Jordan, Saudi Arabia, South Korea, Singapore, Taiwan, and Thailand. Results: Baseline characteristics of the EGM population (n = 243) were similar to the overall REACT population: median age, 60.0 years; clear cell histology, 95.1%; and progression on/intolerance to previous VEGFr-TKI therapy, 89.7%/16.9%. Median duration (range) of everolimus exposure was 20.4 (0.3-83.7) weeks. Clinical benefit was observed in 60.1%/53.3% of EGM patients/all patients (stable disease, 55.6%/51.6%; partial response, 4.5%/1.7%). Common grade ≥3 AEs in EGM patients/all patients included anemia (19.8%/13.4%), pneumonia (7.4%/4.2%), hyperglycemia (7.0%/5.5%), stomatitis (5.8%/5.4%), and pneumonitis (2.9%/2.7%); 13.2%/16.6% of EGM patients/all patients discontinued because of AEs. Conclusions: In patients from EGM countries, safety findings and tumor responses were consistent with the overall REACT population and with RECORD-1. Everolimus was well tolerated, with no new safety issues identified.
Association of single nucleotide polymorphisms in AGT, VEGF, and APOE genes with clinical outcome of target therapy in advanced renal cell carcinoma.
Authors: Mao Li Li , Si Lu , Chi Zhi Hong , Cui Chuan Liang , Sheng Xi Nan , Guo Jun , Tang Bi Xia , Li Si Ming 
Published: March 2020

e15051 Background: Recent evidences have indicated that hypertension and obesity predict longer PFS of targeted therapy in metastatic renal cell carcinoma (mRCC) patients, thus we suppose polymorphisms in hypertension associated genes(angiotensinogen, AGT; vascular endothelial growth factor, VEGF) and obesity associated gene (apolipoprotein E, APOE) may have an effect on treatment outcome in patients treated with targeted therapy for mRCC. Methods: A cohort of consecutive patients (pts) treated with sunitinib or sorafenib were studied. Baseline clinical characters such as age, gender, blood pressure and BMI (body mass index) were recorded. All patients were genotyped for genetic polymorphisms in rs2493137 of AGT, rs699947 of VEGF and rs8106922, rs405509 of APOE from peripheral blood. All the patients were followed up for progression free survival(PFS),overall survival (OS),objective response rate (RR). Results: We studied a cohort of 77 cases, 58 (24.7%) pts were male, 18 (23.4%) pts were ≥65 years and 47 (61%) pts received sunitinib. The distribution of all the tested SNP genotypes were in Hardy-Weinberg equilibrium (p>0·05). With a median follow-up time of 24 months (range: 1.5-36.2 months), 60 pts developed progression and 34 pts died. The rs2493137 TT genotype in the AGT gene showed a trend of prolonging PFS when compared with the CC+CT genotypes, but without statistically significance (p=0.08). No correlations were found among other genotype subgroups (rs699947, rs8106922 and rs405509) on either clinical characters or survival endpoints in this study. Conclusions: Polymorphism in the promoter of AGT gene (rs2493137) might be associated with better clinical outcome in patients treated with targeted therapy for mRCC. Further studies with a larger sample size are needed on the function of this polymorphism.