bluuebunny/crossref_metadata_2025 huggingface dataset:
Thromboembolic (TE) complications in germ cell tumor (GCT) patients: Should use of peripherally inserted central catheters (PICC-Line) be pursued?
Authors: Francois Louis , Gross-Goupil Marine , Robert Gregoire , Ravaud Alain
Published: February 2018

571

Background: Patients with GCT receiving cisplatin-based chemotherapy are at high risk of TE events (TEE). Several risk factors have been reported previously, such as cisplatin, Lactate Deshydrogenase, body surf area (BSA)... Methods: we conducted a retrospective study of all patients (pts) with GCT, treated with platinum salts and followed at the university hospital and anticancer center of Bordeaux (June 2007 - January 2015). The following characteristics were recorded: age, performans status, BSA, histological type, site of primitive tumor, stage, prognosis (IGCCCG classification), size of retroperitoneal lymphnode, LDH, type of venous pathway (peripheral vein, implantable venous access port or PICC-Line), prophylaxis of anticoagulant or not, TEE and median time to onset. Results: 206 pts were selected. Thirty-six (17.4%) had one or more venous or arterial TEE during or within 3 months of the end of chemotherapy: 26 deep vein thromboses, 13 pulmonary embolisms and 4 arterial accidents (2 acute limb ischemia and 2 acute coronary syndromes). The median time between treatment initiation and occurrence of TEE was 38.5 days [7-248]. Among the 12 pts with PICC-line, 6 (50%) had a TEE, including 4 cases of pulmonary embolism. In addition to the presence of a PICC-line (OR 4.62 [1.28, 15.56]), factors associated with an increased TE risk in univariate analysis were the use of implantable venous access port (OR: 3.97 [1.81; 9.12]), size of retroperitoneal adenopathy ≥ 2 cm ([2-5 cm]: OR: 24.39 [4.50 - 454.39]; > 5cm : OR : 26.25 [5,00 - 484.5]), stage II (OR : 10.19 [1,9 - 188.96]), stage III (OR :27.2 [5.34 - 479.9]), prognosis group (good : OR : 11.16 [2.16 - 205.04]) ; intermediate : OR : 31.50 [4.81 – 624.20] ; unfavorable : OR : 33.35 [5.7 – 637.34]), VIP (etoposide-ifosfamide-cisplatin) protocol (OR :6.35 [1.51 – 28.15]) and high LDH level (OR :3.88 [1.63 – 10.34]). Conclusions: These results suggest a significant association between PICC-line and the occurrence of TEE in univariate analysis. PICC-line is not risk-free and should be used sparingly in pts with GCT whose treatment objective remains primarily a cure at the cost of less toxicity.
Tandem high-dose chemotherapy and autologous hematopoietic stem cell transplantation (SCT) compared to single SCT for relapsed/refractory germ cell tumors (GCT).
Authors: Kilari Deepak , Hari Parameswaran , Qayed Muna , Fraser Raphael , Davila Omar , Kumar Shaji , Mark Tomer Martin , Nieto Yago , D'Souza Anita
Published: February 2018

572

Background: Single-center observational studies have established the use of single or tandem SCT to salvage relapsed GCT but randomized trials are lacking. We analyzed outcomes and prognostic factors in 2,395 male SCT recipients for relapsed GCT between 1990 and 2015. Methods: Recipients of single or tandem SCT reported to the Center for International Blood and Marrow Transplant Research were identified. Outcomes were compared by SCT year: 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). A recent subset (n = 267, 2000-2015) with detailed disease- and transplant-related data was further analyzed with a multivariate (MVA) Cox proportional hazards model. Results: Median age at SCT was 31 (11-76) years and 49% received SCT within 12 months of diagnosis consistent with early relapse/primary refractory GCT. 26% had primary extragonadal GCT; 1,167 (49%) had intent to tandem transplant (TT). The median follow up was 51 (3-313) months. Day 100 non-relapse mortality was statistically similar at 8% in 1990-94 (vs. 4% in 2010-15) but 3-year progression-free survival (PFS) improved from 24 (18-31)% in 1990-94 to 47 (43-50)% in 2010-15 (p < 0.0001) and 3-year survival (OS) from 35 (29-40)% to 54 (50-57)% in 2010-15 (p < 0.0001). Compared with single SCT, TT recipients were younger 31 (16-62) vs 34 (13-76), with lower Hematopoietic Cell Transplantation-Comorbidity Index, more likely to undergo SCT after 1 line of chemotherapy (28% vs 9%), and within 1 year of diagnosis (51% vs 38%). TT was preferred over single SCT over time (48% of SCT were TT in 2000-04 vs. 81% in 2010-15). In MVA, non-seminoma histology, residual tumor at SCT, receipt of > 1 line of pre-SCT chemotherapy and single SCT (vs. TT), were associated with worse PFS and OS. Year of SCT was not significant when adjusted for these covariates. Conclusions: In this large longitudinal cohort, improvements in PFS and OS were observed in recent years. SCT earlier in disease course and tandem SCT were associated with superior outcomes. These data involving a large cohort reported from 225 centers confirm specialized centers’ date in a real-world setting.
Dissecting the expression landscape of genitourinary cancers.
Authors: Jeldres Claudio , Bouchard Sabrina , Richard Patrick O , Carmel Michel , Sabbagh Robert , Bisaillon Martin
Published: February 2018

573

Background: Genitourinary (GU) cancers include bladder urothelial carcinoma (BCa), prostate cancer, kidney clear cell or papillary carcinoma, uterus endometrial carcinoma, ovarian cystadenocarcinoma and testicular germ cell tumors. Clinical data show a higher prevalence of GU cancers for men than women, suggesting significant molecular differences depending on sex regarding cancer development. This project aims at dissecting the expression landscape for all GU cancers and identify significant dysregulated genes between cancer and normal tissues specific either for men and women. The resulting data will serve a clinical application consisting in targeting novel molecular biomarkers detected in urine for GU cancers early diagnosis. Methods: Based on RNAseq data provided by The Cancer Genome Atlas, gene expression fold-change for 19,123 genes from cancer tissues and normal tissues was initially compared for each GU cancer. To ensure significant gene dysregulation, only genes showing a fold-change ≤ -log2(2) or ≥ log2(2) and a p-value < 0.05 were retained. Next, a comparison in gene expression modification between men and women for each cancer was made to identify the most significant molecular differences between both sexes. Unique dysregulated genes for each cancer were then identified and their presence or absence in urine was confirmed. From the pool of genes expressing proteins in urine, non-parametric tests for paired and unpaired values were used to determine the statistical difference between cancer and normal tissues in terms of gene expression. Results: Among 2880 genes significantly dysregulated for all five GU cancers, more than half of them were unique to BCa. Among these, 129 gene products (proteins) were ultimately detected in urine of patients. Seven up-regulated and ten down-regulated genes have shown high statistical differences between cancer and normal tissues in the Mann-Whitney U test for unpaired values. CEACAM6, S100A8 and S100A9 have shown significant differences in the Wilcoxon test for paired values which make them potential biomarkers ready for validation by LC-MS/MS. Conclusions: This present study shows the relevance to pursue research in gene expression modification in cancer to improve early diagnosis.
Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis.
Authors: George Daniel J. , Martini Jean-Francois , Staehler Michael D. , Chang Yen-Hwa , Breza Jan , Patard Jean-Jacques , Motzer Robert J. , Magheli Ahmed , Carteni Giacomo , Donskov Frede , Escudier Bernard , Li Sherry , Casey Michelle , Valota Olga , Laguerre Brigitte , Pantuck Allan J. , Pandha Hardev S. , Patel Anup , Lechuga Mariajose , Ravaud Alain
Published: February 2018

576

Background: In the phase III S-TRAC trial, adjuvant sunitinib (SU) prolonged disease-free survival (DFS) vs placebo (PBO) in patients with locoregional renal cell carcinoma at high risk of recurrence after nephrectomy (median 6.8 vs 5.6 y; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59–0.98; P= 0.03). An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in angiogenesis-related genes and clinical outcomes in S-TRAC. Methods: Prospectively collected blood samples were genotyped for 10 SNPs and 1 insertion/deletion mutation with TaqMan assays. DFS was compared with a log-rank test for each SNP genotype in SU vs PBO arms and between SNP genotypes within each arm. P-values are unadjusted for multiplicity comparison. Results: Of 615 patients, 286 (142 SU; 144 PBO) were analyzed. There were generally no genotype frequency deviations from the Hardy-Weinberg equilibrium, but linkage disequilibrium was seen between VEGFA rs699947 and rs833061 on chromosome 6 (D′ = 1.000, r2 = 0.979). Longer DFS was observed with SU vs PBO for VEGFR1 rs9554320 C/C (median: not reached [NR] vs 5.56 y; HR 0.44, 95% CI 0.21–0.91; P= 0.023), VEGFR2 rs2071559 T/T (median: NR vs 4.47 y; HR 0.46, 95% CI 0.23–0.90; P= 0.020), and eNOS rs2070744 T/T (median: 7.07 vs 3.44 y; HR 0.53, 95% CI 0.30–0.94; P= 0.028), with a trend for VEGFR1 rs9582036 A/A (median: NR in both arms; P= 0.054) and SH3GL2 rs10963287 C/T (median: NR vs 5.35 y; P= 0.088). Shorter DFS was observed for VEGFR1 rs9582036 C/A vs C/C in the SU, PBO, and combined arms ( P< 0.05); for A/A vs common, the association was only seen in the SU arm ( P= 0.022). VEGFR1 rs9554320 A/C was associated with shorter DFS vs A/A in the PBO ( P= 0.038) and combined arm ( P= 0.006), with a trend in the SU arm ( P= 0.051). VEGFR2 rs1870377 T/T was associated with longer DFS vs A/A in the combined arms, but not in the PBO arm (n = 7 with A/A genotype in the SU arm precluded statistical tests). Conclusions: Correlations between common VEGFR1 and VEGFR2 SNPs and longer DFS with SU suggest germline SNPs are predictive of improved outcomes with adjuvant SU. Due to the exploratory nature of this analysis, prospective validation studies are needed to confirm these findings. Clinical trial information: NCT00375674.
Clinical validation of single nucleotide polymorphisms (SNPs) as predictive biomarkers in localized and metastatic renal cell cancer (RCC).
Authors: Garrigos Carmen , Salinas Ana , Melendez Ricardo , Espinosa Marta , Sánchez Iván , Osman Ignacio , Medina Rafael , Taron Miquel , Duran Ignacio
Published: February 2018

588

Background: SNPs predictive of survival outcomes in patients (pts) with localized and metastatic RCC have been identified previously by us [Garrigós C et al, 2017]. Fifteen SNPs in 9 genes involved in angiogenesis and metabolism of antiangiogenics were recognized as predictive/prognostic in a cohort of 102 pts. The aim of the present study is to validate these associations in an independent cohort of RCC pts Methods: Genotyping was performed in DNA isolated from paraffin-embedded tumor samples from 87 pts with localized and metastatic RCC. DNA was extracted by a commercial kit (QiAGEN) and amplified with a specific primers pool for each SNP as determined by the manufacturer (Lifetech). The 15 SNPs were individually genotyped by Real time quantitative PCR with specific primers and Taqman probes (Lifetech). The presence of the selected SNPs was correlated with clinical features such as disease free survival (DFS), progression free survival (PFS) and overall survival (OS). SPSS v24 was used for statistical analysis. Results: In the localized pts (n = 66), Fuhrman grades 3-4 and stage T3-T4 significantly associated with DFS (p = 0.025 and p = 0.004, respectively). The presence of allele C of rs307826 (FLT4 gene) correlated with a greater chance of relapse (p = 0.025) and also with a shorter DFS (21 vs 35 months, p = 0.007). For the metastatic pts (n = 21), allele C of rs307826 (FLT4 gene) and allele A of rs9800958 (PRKAR1B) were linked with a shorter PFS [(8 vs 18 months, p = 0.036) and (8 vs 17 months, p = 0.043) respectively]. In the localized cohort, allele T of rs2227543 (IL8 gene) was associated with longer OS (14 vs 3 months, p = 0.039) while allele G of rs10013228 (KDR gene) linked with worse OS (4 vs 17 months, p = 0.063). Conclusions: This analysis comes to confirm our previous observations that certain genotypes could be used as prognostic/predictive factors in RCC. This is particularly important in an era where multiple treatment options are available for this disease.
Clinical and genomic characterization of low-prostate-specific antigen, high-grade prostate cancer.
Authors: Mahal Brandon Arvin Virgil , Yang David Dewei , Wang Natalie , Alshalalfa Mohammed , Davicioni Elai , Choeurng Voleak , Spratt Daniel Eidelberg , Martin Neil E. , Mouw Kent William , Orio Peter F , Choueiri Toni K. , Trinh Quoc-Dien , Feng Felix Y , Nguyen Paul L.
Published: February 2018

59

Background: The consequences of a low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown. We sought to evaluate the clinical implications and genomic features of this entity. Methods: Clinical and transcriptomic data from 626,057 patients with N0M0 prostate cancer were collected from two national cohorts and a large transcriptome database. Multivariable Fine-Gray and Cox regressions analyzed prostate-cancer specific mortality (PCSM) and all-cause mortality, respectively. GRID data were used to analyze transcriptomic features. Results: For Gleason 8-10 disease, the distribution of PCSM was U-shaped by PSA (PSA 4.1-10.0 ng/mL = referent), with adjusted hazard ratio (AHR) 2.70 for PSA ≤2.5 ng/mL (P < 0.001) versus 1.97, 1.36, and 2.56 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively. In contrast, distribution of PCSM by PSA was linear for Gleason ≤7 with AHR 0.41 for PSA ≤2.5 ng/mL (P = 0.127) versus 1.38, 2.28, and 4.61 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively (PGleason*PSA interaction< 0.001). Gleason 8-10, PSA ≤2.5 ng/mL disease had a significantly higher PCSM than standard high and very high-risk disease with PSA > 2.5 ng/mL (AHR 2.15, P = 0.009; 47-month PCSM 13.8% versus 4.9%). Among Gleason 8-10 patients treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with a survival benefit for PSA > 2.5 ng/mL (AHR 0.87, P < 0.001) but not for ≤2.5ng/mL (AHR 1.36, P = 0.084; PADT*PSA interaction= 0.021). For Gleason 8-10 tumors, PSA ≤2.5 ng/mL was associated with a higher expression of neuroendocrine markers compared to > 2.5 ng/mL (P = 0.046), with no such relationship for Gleason ≤7. Conclusions: Low-PSA, high-grade prostate cancer appears to be a unique entity that has a very high risk for PCSM, potentially responds poorly to ADT, and is associated with neuroendocrine genomic features.
The impact of facility case volume on overall survival in patients with metastatic renal cell carcinoma in the targeted therapy era.
Authors: Chen Yu-Wei , Tullio Katherine , Ornstein Moshe Chaim , Grivas Petros , Garcia Jorge A. , Rini Brian I.
Published: February 2018

590

Background: Prognosis of metastatic renal cell carcinoma (mRCC) has significantly improved in the targeted therapy era. We aimed to investigate whether higher facility case volume (FCV) is associated with improved overall survival (OS) for mRCC. Methods: Patients diagnosed with mRCC from 2006-2012 were identified in the National Cancer Database. FCV was determined by the total cases of renal cell carcinoma (metastatic and non-metastatic) at each treating facility. Multivariable Cox regression model was used to investigate the association between FCV and OS. Covariates adjusted for were treatment modalities [targeted therapy, cytoreductive nephrectomy, and metastasectomy], tumor characteristics and patient sociodemographics. Results: There were 18,571 mRCC patients included in this study. The mean follow-up time was 13.2 months (median: 6; interquartile range: 2.3-17.9). After adjusting for baseline characteristics including treatment modalities (table), every increment of 100 FCV of the treating facility was associated with improved OS (AHR: 0.99, 95 CI: 0.98-0.99, p-value: 0.003). FCV was dichotomized at increasing percentiles (50th, 80th, 85th, 90th, and 95th). Improved OS was observed when high FCV was defined at 90th percentile (47 cases/year; AHR: 0.96, 95% CI: 0.92-0.99, p-value: 0.02) and 95th percentile (68 cases/year; AHR: 0.95, 95% CI: 0.91-0.98, p-value: 0.04) but not at 50th (8 cases/year), 80th (30 cases/year) or 85th percentile (38 cases/year). Conclusions: Our results suggest that treatment at hospitals with higher renal cell carcinoma FCV is associated with improved OS for patients diagnosed with mRCC in the targeted therapy era. Model is also adjusted for age, race, sex, insurance status, Charlson comorbidity score, tumor stage, nodal status, histology type, year of diagnosis, and zip code-level socioeconomic data (income, education level and residence type). [Table: see text]
Systemic immune inflammation index and treatment response in patients with metastatic renal cell cancer.
Authors: Bir YÃ¼cel Kadriye , Yasar Arzu , Ucar Gokhan , Utkan Gungor , Yildirim Nuriye , Urun Yuksel
Published: February 2018

591

Background: To investigate the prognostic value of the pretreatment inflammatory characteristics on treatment response and survival. Methods: We included 151 patients with metastatic renal cell carcinoma (mRCC) Patients’ charts were retrospectively analyzed for their clinical, pathological and demographic features. Systemic immune inflammation index (SII) cut off is estimated with median value. Overall survival (OS) was estimated by Kaplan-Meier method for univariate analysis and Cox-regression for multivariate analysis. Results: In high SII group (SII > 844) overall survival is 11 months and in low SII group (SII < 844) overall survival is 22 months (p = 0,008). Median OS is lower in the hypercalcemic group (7 months vs.18 months, P = 0,013). In patients with anemia and thrombocytosis, OS is lower (41 months vs. 13 months p = 0,001 and 6 months vs. 18 months p = 0,01). In multivariate analysis, anemia, SII, and ECOG performance status were able to predict OS (HR = 2,69, HR = 2,04, HR = 2,57) Conclusions: In patients with mRCC, SII may have a prognostic value and higher score may related with decreased overall survival.
Effect of epidural block on restoration of protease inhibitors in patients with local kidney cancer.
Authors: Kit Oleg Ivanovich , Rozenko Dmitry A. , Frantsiyants Elena , Kozlova Larisa S. , Bandovkina Valeria A. , Dimitriadi Sergey N , Ushakova Natalya D. , Rozenko Ludmila Ya. , Duritskiy Maksim N.
Published: February 2018

593

Background: The purpose of the study was to reveal the effect of the epidural block (EB) on the dynamics of the main universal inhibitors in the blood plasma and urine of patients with local kidney cancer. Methods: 58 patients aged 56.5±8.7 years underwent partial nephrectomy with warm ischemia for 15-20 minutes (EB – 35 patients, standard anesthesia (SA) - 23 patients). EB involved catheterization of the epidural space at Th10-L1 with the following infusion of a mixture of ropivacaine 2 mg/ml and epinephrine 2 μg/ml at 6-10 ml/hr using a syringe doser, intraoperatively and within the first three postoperative days. α2-Macroglobulin (α2M) and α1-proteinase inhibitor (α1PI) were studied by ELISA and spectrophotometry in the blood plasma and urine of patients before the surgery (b/s), 40 min after the start of the surgery (40' s/s) and on days 1 and 3 after the surgery (a/s). Results were compared to the levels in the blood plasma and urine of 29 healthy donors (N). Results: α2M and α1PI in the blood plasma and urine of all patients b/s were lower than N (p < 0.05). α2M in the blood plasma of all patients 40' s/s was similar to N. Normal α2M levels were maintained in the blood plasma in EB on days 1-3 a/s, while in SA they increased by 2.8 times on day 1 and decreased by 3.4 times on day 3, compared to the previous measurement results. α1PI in EB began to increase since 40' s/s with its normalization by the day 3 a/s; α1PI in SA was decreased in the blood plasma and urine during the whole study period. The urine/blood plasma ratio for α2M (α2Mu/α2Mb) was increased b/s in all patients, with its normalization on days 1-3 in EB and its decrease by 9.5-3.1 times on days 1 and 3 in SA. The α1PIu/α1PIb ratio was increased b/s on average by 2.1 times in all patients, with its normalization 40' s/s in EB, and remained similar to N by the day 3. Normalization was not observed in SA; α1PIu/α1PIb was decreased since 40' s/s to the day 3 by 1.8-1.4 times (p < 0.05), compared to N. The results showed that in SA, the proteolysis was not controlled in the kidney due to the inhibitor deficiency. Conclusions: The epidural block contributes to the restoration of the activity of α2M and α1PI universal endogenous inhibitors during and after surgery, in contrast to the standard anesthesia.
Treatment facility volume and survival in patients with metastatic renal cell carcinoma.
Authors: Geynisman Daniel M. , Handorf Elizabeth , Zibelman Matthew R. , Plimack Elizabeth R. , Uzzo Robert , Kutikov Alexander , Smaldone Marc C.
Published: February 2018

594

Background: Higher treatment facility (TF) volume has been linked with improved surgical and hematologic malignancy outcomes. We evaluated the association between TF volume and overall survival (OS) in pts with metastatic renal cell carcinoma (mRCC). Methods: The National Cancer Data Base was queried for all pts with mRCC and survival data available (2004 to 2013, cohort A). We defined high volume TFs as those in the top 20th percentile of mean number of mRCC pts treated per year ( > 5 pts). The effect of volume on OS was determined using unadjusted Kaplan-Meier curves and Cox regression models (MVA) adjusting for pt (age, sex, race, ethnicity, insurance type, income, Charlson-Deyo Score), facility (location, practice setting) and clinical characteristics (histology, presence or absence of liver and lung metastasis). Increasingly more stringent inclusion criteria were used to confirm the overall cohort association (cohort B = mRCC pts with active treatment; cohort C = mRCC pts with systemic therapy; cohort D = mRCC pts with systemic therapy at the reporting institution; cohort E = mRCC pts with systemic therapy at the reporting institution with liver and lung metastatic status known). Results: There were 44,109 mRCC pts treated at 1,224 TFs. The median age was 65, 66% were men and 75% had clear cell mRCC. Median TF volume was 2.4 pts/year (range 0.1-46.8). High volume TFs treated 54% of all mRCC pts. The unadjusted median overall survival of mRCC patients (cohort A) treated at high vs low volume TFs was 9.2 vs 6.4 months (P < 0.0001). This difference was maintained in all cohorts: cohort B = 13.7 vs 10.9, cohort C = 12.4 vs 10.0, cohort D = 12.5 vs 9.3, and cohort E = 13.4 vs 10.6 months (P < 0.0001 for all cohorts). MVA confirmed that facility volume was associated with all-cause mortality after adjustment: HR = 0.85, [95% CI 0.82-0.88], P < 0.001. These results were consistent regardless of inclusion criteria, e.g. for cohort E: HR = 0.839, [95% CI 0.785-0.897], P < 0.0001. Considering the definition of high volume, all thresholds > 5 pts/year showed a survival benefit, with the largest effects at ≥10 pts/year. Conclusions: Patients with mRCC treated at higher volume facilities had a longer survival compared with those treated at lower volume facilities.
Prospective evaluation of geriatric assessments as predictors of complications and functional outcome after major urologic tumor surgery in the older population.
Authors: Kahlmeyer Andreas , Losensky Wencke , Sikic Danijel , Keck Bastian , Goebell Peter J. , Wullich Bernd
Published: February 2018

597

Background: Old patients undergoing major urologic tumor surgery are at severe risk of functional deterioration. In this study we prospectively performed a comprehensive geriatric assessment to identify potential risk predictors for early functional outcome. Methods: Since January 2016, 75 patients undergoing elective cystectomy, prostatectomy or nephrectomy at the age of 70 or older have been enrolled prospectively. A selection of geriatric assessment tools was applied before surgery. Follow up data including standardized peri- and postoperative parameters were obtained at discharge and at day 30 and 180 after surgery (DRKS-ID: DRKS00009825). Results: 14.7% had radical cystectomy, 33.3% had radical prostatectomy and 52.0% had kidney surgery due to malignant tumor. The average age was 75.7 (70-88) years. Within hospital stay, 20.3% had major complications (Clavien-Dindo > = 3) and 25% showed incomplete functional recovery at day 30 after surgery. The average reduction in activities of daily living (ADL) was -34.71. Major complications were significantly associated with impaired mobility (TUG, OR 7.350, p = 0.002), frailty (FrailScale, OR 5.007, p = 0.019) and ASA-Score (ASA, OR 4.400, p = 0.015). Incomplete functional recovery was strongly associated with preoperative impaired mobility (TUG, OR 11.524, p < 0.001) but correlation with ASA-Score (ASA, OR 3.288, p = 0.070) and comorbidities (CCI, OR 3.833, p = 0.106) missed statistical significance. No correlation of functional deterioration was found with age and functional status at admission. The combination of selected assessment tools showed good prediction of early functional recovery (ErlangerIndex, OR 4.400, p = 0.019). Conclusions: Major urologic tumor surgery has a high risk of severe complications and incomplete recovery in old patients. Fast and easy-to-do preoperative assessment tools may predict functional outcome more precisely than age or preoperative functional status alone. Clinical trial information: DRKS00009825.
The combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) for prediction of treatment outcome for patients with localized renal cell carcinoma.
Authors: Komura Kazumasa , Tsujino Takuya , Ibuki Naokazu , Inamoto Teruo , Azuma Haruhito
Published: February 2018

598

Background: The combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) has been shown to provide prognostic information in several cancers. The object of the present study was to examine the preoperative prognostic value of the COP-NLR in localized RCC. Methods: The records of 268 patients were analyzed in the study. The cut-off value of platelet count and NLR were defined by receive operating characteristic (ROC) analysis and the areas under the curve (AUC). Patients with both an increased platelet count ( > 31.0×104 mm-3) and an elevated NLR ( > 3.85) were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively. Results: There were 198, 63, and 7 patients assigned to the COP-NLR of 0, 1, and 2, respectively. Five year OS rates were 93.8% in COP-NLR0, 72.2% in COP-NLR1 and 0% in COP-NLR 2, demonstrating a significant difference in their prognosis among the COP-NLR in localized RCC patients. Multivariate analysis using the 10 clinicopathological findings selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for OS (HR: 2.32, 95%CI: 1.22 to 4.26, p = 0.011) and RFS (HR: 1.91, 95%CI: 1.02 to 3.53, p = 0.044). Conclusions: The preoperative COP-NLR is an independent prognostic indicator of OS and RFS for patients with localized RCC. [Table: see text]
CASPIR trial: Using prostatic calculi as an alternative to fiducial markers for IGRT in for localized prostate cancer.
Authors: O'Neill Angela G.M , King Raymond , Osman Sarah , Jain Suneil , Hounsell Alan R , O'Sullivan Joe M.
Published: February 2018

60

Background: Image guided Radiotherapy (IGRT) for prostate cancer (PCA) frequently employs surgically implanted fiducial markers (FMs). However, it is estimated that up to 35% of prostate radiotherapy patients have prostatic calculi (PC) visible on treatment cone beam CTs (CBCT). The purpose of this clinical trial is to directly compare FMs with PCs as an aid to prostate IGRT. Methods: We report data from a single institution prospective clinical trial investigating the feasibility of using prostate calcifications as natural FMs for IGRT. Patients planned for standard prostate radical EBRT +/- brachytherapy were eligible. Prior to CT planning, 3 gold fiducial markers are inserted into the prostate by the trans-perineal route under TRUS guidance. PCs visible within the PTV were contoured. Participants were aligned to FMs for EBRT using daily CBCT image guidance on a Varian TrueBeam linac. Off-line, a single experienced user analyses CBCTs using Image Registration in Eclipse (version 13.6). Random and systematic set-up errors are determined based on FMs, PCs (where present), prostate gland (PG) and bony landmarks (BL) and CTV-PTV margins derived for each data set. Results: 30 participants with PC have been recruited. Data from the first 19 patients (365 fractions), resulted in 2555 individual image registrations (7665 individual data points). The PTV margins required based on each reference structure are summarised in Table 1. The maximum difference between the CTV-PTV(PC) margin and CTV-PTV(FM) margin is 2.2mm in the X or L/R dimension. Margins required for FM, PG and PC in the Y and Z dimensions are comparable, with a maximum difference of 0.5mm between CTV-PTV(PC) and CTV-PTV(PG). Conclusions: Preliminary results from this study demonstrate some evidence to support the use of PCs as an alternative to FMs for prostate IGRT. Future analysis will include location of PC according to the PIRADs schema and patient feedback in relation to FM implantation. Clinical trial information: NA. [Table: see text]
Treatment modification with sunitinib in first-line (1L) metastatic renal cell carcinoma (mRCC): An analysis of the STAR-TOR registry.
Authors: Boegemann Martin , Hubbe Marcus , Thomaidou Despina , Blackburn Stuart , Bent-Ennakhil Nawal , Wood Robert , Bargo Danielle
Published: February 2018

602

Background: The standard dosing schedule for administration of Sunitinib is 50mg once daily for a 4-week period followed by 2 weeks off. However, in clinical practice, many patients require schedule or dose reductions to mitigate toxicity. We aimed to assess if these treatment modifications result in improved outcomes in mRCC patients. Methods: Data were drawn from STAR-TOR, a German, multi-centre, real-world, prospective registry to report outcomes of mRCC patients who received Sunitinib in 1L. Patients were categorised into 2 treatment groups: 1) Sunitinib initiated at standard schedule/dose with subsequent schedule/dose modification (SM), 2) Sunitinib as per standard schedule/dosage (SS). Kaplan-Meier survival analysis was used to determine time on treatment (TT) of Sunitinib and progression-free survival (PFS). Differences between groups were assessed using log-rank tests. Results: In total 297 patients were identified initiating 1L Sunitinib. Schedule or dose reductions occurred in 33% of patients. Significant differences between groups at baseline are noted in Table 1. Median TT was greater in SM vs. SS (15.1 vs. 3.9 months (m), p < 0.0001). Median PFS was improved in SM vs. SS (15.1 vs. 6.0 m, p < 0.0001). Fatigue (31/14%), hand-foot syndrome (HFS) (28/10%), diarrhea (35/19%) and stomatitis (20/6%) were more frequently reported in SM vs. SS since initiation of Sunitinib. Incidence of adverse events, (excluding diarrhea) was reduced following schedule/ dose modification of sunitinib; fatigue (before SM/ after SM) (18/7%), HFS (21/8%) and stomatitis (8/4%). Conclusions: Modifying Sunitinib schedule or individualizing the dose represent therapy management strategies that are associated with improved tolerability, prolonged treatment duration and significant improvement in PFS in a real life setting. These data suggest that effective management of toxicity of Sunitinib can optimize patient outcomes. [Table: see text]
Incidence and mortality of renal cell carcinoma in the U.S.: A SEER-based study investigating trends over the last four decades.
Authors: Gad Mohamed M , Saad Anas M , Al-Huseini Muneer J , Ruhban Inas A. , Sonbol Mohamad B.
Published: February 2018

604

Background: Renal cell carcinoma (RCC) is the third most common urologic malignancy worldwide, with clear cell subtype being the most common. In this study, we sought to investigate RCC incidence and mortality trends by demographic and tumor characteristics using data from the surveillance, epidemiology and end results (SEER) database. Methods: We used SEER database to study RCC cases between 1973 and 2014. Incidence and mortality rates were calculated by sex, age, race, state, stage, size, and histological subtype of RCC. Annual percent change (APC) was calculated using joinpoint regression software. Results: A total of 96,058 RCC cases were identified, with 54,000 RCC deaths between 1973 and 2014. Overall incidence was 9.712 per 100,000 persons-years, being highest among males (13.698), blacks (11.886), and people older than 65 years (38.693). Incidence rates of localized cases (5.845) and tumors smaller than 7 cm (6.550) were higher than other tumor subgroups with distant disease incidence of 1.773 per 100,000 persons-years. Overall incidence rates increased by 2.709% (95% CI, 2.544-2.875, p < .001) per year over the study period, but rates became stable since 2007 with only an increase in the incidence of clear-cell subtype (2.538%; 95% CI, 1.300-3.791, p < .001). Overall RCC mortality rates have been declining since 2000, and distant disease mortality have been decreasing since 2008 with most profound decline in the period between 2012 and 2014 with APC of -22.635% (-37.419- -4.359, P = .019) Conclusions: Despite overall increase in rates over the last 40 years, recent years have shown stable incidence and decrease in mortality rates of RCC. The significant decline in mortality over the last 10 years since the approval of the first Vascular Endothelial Growth Factor ‘VEGF’ inhibitor highlights the impact of this class of medications along with other subsequent agents such as mTOR inhibitors and checkpoint inhibitors on the prognosis of renal cell carcinoma.
Conditional survival and landmark analysis for patients with small renal masses undergoing active surveillance at a tertiary care center.
Authors: Petros Firas G. , Venkatesan Aradhana M. , Kaya Diana , Ng Chaan S. , Fellman Bryan M. , Karam Jose A. , Wood Christopher G. , Matin Surena F.
Published: February 2018

609

Background: Conditional survival can provide guidance for patients once they have survived a period of time after diagnosis of their disease. We determine conditional survival for patients with small renal masses (SRM) undergoing active surveillance (AS). Methods: Patients were enrolled in a prospective AS registry at our institution between May 2005 and January 2016. Patients with localized SRM ≤4cm were included, with serial radiologic imaging available in-house for re-review. Overall survival (OS) was estimated using the Kaplan-Meier method and modeled via Cox proportional hazards models. The primary end points analyzed were the conditional probability of survival and tumor growth over time. Landmark analysis was used to evaluate survival outcomes. Results: A total of 272 patients were included in this analysis. Mean initial tumor size was 1.74 ± 0.77 cm and mean tumor size closest to the 2-year mark was 1.97 ± 0.83 cm. The likelihood of continued survival to 5 years improved after the 2-year landmark was reached. Patients with tumors < 3cm who survived the first 2-years on AS had a 0.84-0.85 chance of surviving to 5 years, and if they survived 3 years, the probability of surviving to 5 years improved to 0.91. Multivariable Cox proportional hazards analysis of survival revealed eGFR, Charlson comorbidity index (CCI), and tumor size of 3-4cm were significantly predictive of OS both at baseline and at 2-year mark (all p < 0.05). Patients with a tumor size 3-4 cm were at a greater risk of non-RCC death (HR > 3.5; p ≤ 0.001). A linear mixed effects model revealed slow tumor growth (beta: 0.12; p < 0.001) for tumors < 3cm. Adjusted tumor size predictions disclosed parallel growth rates for SRM of < 2cm and 2-2.99cm with insignificant difference (p = 0.969). Conclusions: Our study provides insight into the survival of patients with SRM on AS who have already survived a certain period of time. The conditional survival probability of patients with SRM < 3cm on AS improved after the initial 2 years, suggesting a role for re-counseling for those who survive to the 2-year landmark. Patient factors (renal function and CCI) were significantly associated with survival at baseline and at the 2-year landmark.
Metamodeling of late rectal bleeding in patients undergoing radiotherapy for prostate cancer.
Authors: Cicchetti Alessandro , Palorini Federica , Rancati Tiziana , Fiorino Claudio , Cozzarini Cesare , Avuzzi Barbara , Vavassori Vittorio , Fellin Giovanni , Stucchi Claudio , Procopio Giuseppe , Ebert Martin , Kennedy Angel , Denham James William , Joseph David John , Gabriele Pietro , Degli Esposti Claudio , Valdagni Riccardo
Published: February 2018

61

Background: Predictive models for late rectal bleeding (LRB) after radiotherapy (RT) for prostate cancer were established by several studies, with good performance on development population (POP). Nonetheless, they were found to be unsatisfactory in their generalization to independent validation cohorts. Aim of the study is to build a metamodel for grade 2-3 (G23) and grade 3 (G3) LRB (LENT/SOMA) starting from literature evidence and to validate it on a new POP. Methods: The metamodel was constituted by clinical/dosimetric features and by their coefficients. Available predictive models for LRB were selected by literature search. Models including rectal Equivalent Uniform Dose (EUD) with/without patient-related dose-modifying factors were retrieved. The process allowed identification of “evidence-based” clinical/dosimetric features associated to LRB. Coeff. for identified features were resolved by weighted mean of published values, using their standard deviation as weight and then inserted in a sigmoid-shaped logit-EUD model. The resulting metamodel was validated on a pooled POP of radically treated pts (3DCRT & IMRT). Performance was assessed through calibration. Results: The search identified rectal EUD, previous abdominal surgery (SURG), hormone therapy (HT) and use of cardiovascular drugs (CARDIO) as relevant features (coeff. presented in table). Validation POP included 1591 pts with 240 (15%) LRBG23 and 98 (6.2%) LRBG3 pts. Calibration was very good: LRBG23 slope = 1.4 with R2 = 0.86; LRBG3 slope = 1.1 with R2 = 0.96. Conclusions: A metamodel for prediction of LRB has been developed from literature, including all currently available information on association between LRB and clinical/dosimetric factors. The model was successfully validated on a large POP, proving to be a valuable tool for predicting LRB before RT. [Table: see text]
Efficacy of antiangiogenic renal neoplasm with bone metastasis: A mono-institutional study in France.
Authors: Sajous Christophe , Peron Julien , Boyle Helen Jane , Negrier Sylvie , Moriceau Guillaume , Blay Jean-Yves , Flechon Aude
Published: February 2018

610

Background: Although bone metastases occur frequently in metastatic renal cell carcinoma (mRCC) and represent approximatively 20-30% of the different sites of metastases, few studies have assessed the prognostic impact of these metastatic sites. In this context, the aim of our study was to evaluate the efficiency of antiangiogenic (AA) treatments in this particular site Methods: A retrospective review of patients with mRCC and bone metastases, treated with a first line of antiangiogenic therapy at the Centre Leon Berard (CLB) was conducted between January 2010 and November 2016. In order to identify a differential treatment effect according to the metastatic site, we assessed the bone progression-free survival (bPFS) defined as the time from the first day of 1st line AA to the date of bone progression or death; and extra bone PFS (ebPFS), defined as the time from the 1st day of 1st line AA to the date of extra-bone progression or death. The association between survival and potential prognosis factor, including metastases location was assessed using log-rank test for univariate analysis Results: A total of 200 patients (146 men; mean age 57,9 years; range 21-86) were analysed and the most common first line AA used was Sunitinib (147; 73,5%). Median PFS at the first AA line was 7,4 months (95% confidence interval (CI) = 6,1-9,2months). Median bPFS was higher than the median of extra bone metastasis PFS (11 months (95% CI = 9-14 months) versus 9 months (95% CI = 8 to 12 months). Other factors have a pejorative impact on the PFS such as sarcomatoid component, non clear cell RCC, Karnofsky index, and the presence of renal thrombus Conclusions: The efficacy of AA was similar on bone and extra-bone metastases, among patients with at least one bone metastasis
Clinical outcome of patients (Pts) with metastatic renal cell carcinoma (mRCC) progressing on front-line immune-oncology based combination (IO-COMBO) regimens.
Authors: Barata Pedro C. , Gomez de Liano Alfonso , Mendiratta Prateek , Crolley Valerie , Szabados Bernadett , Wood Laura S. , Zanick Beth , Allman Kimberly D , Tyler Allison Janine , Martin Allison , Gilligan Timothy D. , Grivas Petros , Ornstein Moshe Chaim , Garcia Jorge A. , Powles Thomas , Rini Brian I.
Published: February 2018

613

Background: Several IO-COMBO regimens are under investigation in front-line mRCC. The clinical outcome of pts who progress on an IO-COMBO regimen and receive subsequent systemic therapy is unknown. Methods: A retrospective analysis of all pts with clear-cell mRCC enrolled in one of seven clinical trials investigating an IO-COMBO at Cleveland Clinic Taussig Cancer Institute and Barts Cancer Institute was conducted. Clinical outcome of subsequent therapy including best objective response according to RECIST v1.1, progression-free survival (PFS) and adverse events (AEs) using CTCAE v4.0, were collected. Results: From a total of 89 pts enrolled on an IO-COMBO trial, final analysis included 32 pts with PD who received ≥1 line of subsequent therapy, median age 57 (41-77), 83% male, 72% ECOG 0, 78% IMDC fav-/intm- risk. Prior IO-COMBO included atezolizumab/bevacizumab (n = 20), ipilimumab/nivolumab (n = 10) and axitinib/avelumab (n = 2). All except 1 pt received IO-COMBO in the front-line setting. All pts received 1 subsequent therapy (axitinib n = 15; pazopanib n = 9; sunitinib n = 4; cabozantinib n = 3; nivolumab n = 1) after progression on IO-COMBO, 12 pts were treated with a second subsequent therapy and 5 pts were treated with ≥3 subsequent lines of treatment. For pts with available response (n = 26), the overall best response to first subsequent therapy was 27% PR, 50% SD and 15% PD. Median PFS for the first subsequent therapy was 7.9 months (95% CI, 4.5-11.3) with 8 pts remaining on treatment. The median PFS for pts previously treated with a combination of IO plus anti-VEGF was 7.9 months (95% CI, 3.1-12.7) and was 9.3 months (95% CI, 3.5-15.0) for pts treated with a prior IO plus IO combination (p = 0.732). The most frequent G3/G4 treatment-related AEs observed with first subsequent therapy were LFT elevation (9%) and diarrhea (7%); 2 pts discontinued subsequent treatment due to toxicity. Conclusions: VEGF-TKIs have clinical activity in mRCC refractory to IO-COMBO therapy, possibly impacted by the inclusion of an anti-VEGF agent in prior IO-COMBO therapy. Subsequent therapy was in general well tolerated.
Effect of SMARCB1 deficiency in renal medullary carcinoma (RMC) on genes associated with nucleosome assembly and telomere organization.
Authors: Msaouel Pavlos , Malouf Gabriel G. , Su Xiaoping , Yao Hui , Tripathi Durga N , Gao Jianjun , Rao Priya , He Rong , Karam Jose A. , Wood Christopher G. , Walker Cheryl Lyn , Tannir Nizar M.
Published: February 2018

614

Background: RMC is a highly aggressive tumor with close to universal fatality despite therapy. It is almost exclusively found in young African-Americans with sickle cell trait, and is characterized by complete loss of expression of SMARCB1, a major chromatin remodeler involved in regulation of gene expression. We investigated the effects of SMARCB1 loss on mutation frequency, gene expression, and cell growth in RMC. Methods: Whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed in RMC tissues from 15 and 11 patients respectively, each with matched adjacent normal kidney tissue controls. In vitro experiments were performed in a cell line (RMC2C) we established from a patient with RMC. SMARCB1 was conditionally re-expressed using a tetracycline-inducible lentivector. Gene ontology (GO) analysis was performed using DAVID. Results: WES showed that RMC harbors a low number (median of < 25/tumor sample) of non-synonymous exomic single nucleotide variants (SNVs) or small indels. GO analysis revealed that the most significant pathways upregulated in RMC compared with normal tissue were those associated with nucleosome assembly and telomere organization (p values < 0.0001). Re-expression of SMARCB1 at near-endogenous levels suppressed the growth rate of RMC2C cells. Subsequent silencing of SMARCB1 expression restored the growth rate of these cells. RNA-seq of RMC2C cells expressing SMARCB1 demonstrated that the most significant downregulated pathways compared with SMARCB1-negative RMC2C cells were those associated with nucleosome assembly and telomere organization (p values < 0.0001). Conclusions: RMC harbors a remarkably simple genome, as evidenced by our WES analysis. Therefore, consistently detected alterations, such as SMARCB1 loss, are likely to serve as drivers for this disease. Indeed, in vitro restoration of SMARCB1 expression suppressed the growth of RMC cells and repressed genes associated with nucleosome assembly and telomere organization, identifying for the first time a causal link between loss of SMARCB1 and dysregulation of these genes. These results provide the basis for future therapeutic strategies targeting SMARCB1 loss in RMC.
Differential expressions of PD-1, PD-L1, and PD-L2 between the primary and metastatic sites in renal cell carcinoma.
Authors: Zhang Xingming , Shen Pengfei , Zeng Hao
Published: February 2018

616

Background: To evaluate the differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastatic sites of renal cell carcinoma (RCC), and to find potential factors influencing expression difference. Methods: We included cases of RCC histologically diagnosed at West China Hospital between January 2009 and November 2016. Clinicopathological data were retrospectively extracted. SPPS 22.0 and GraphPad Prism 6 statistical software were used for data analysis. Kaplan-Meier was used to analyze PFS and OS. R software was used to calculate predictive accuracy (PA). Results: A total of 163 patients were included in this study. Immunohistochemistry results suggested significant differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastasis, with a higher detection rate of the primary than metastasis. Meanwhile, the concordance rate of PD-L1 between the primary and metastasis was only 32.5% (27/83), with a significant statistically difference (χ2 = 4.664, p = 0.031) and poor consistency (Kappa = 0.229, p = 0.031). PD-1 and PD-L1 were highly expressed in the lung/lymph node and PD-L2 was highly expressed in visceral metastases. Survival analysis suggested that PD-1 positive either in the primary or metastasis was a poor prognostic factor for OS (HR: 1.59, 95% CI 1.08-2.36, P = 0.0195). The expression of PD-L1 in the primary was a poor prognostic factor for OS (HR 2.55, 95% CI 1.06-6.15, P = 0.0373). Although the predictive effect of PD-L1 expression on OS was not statistically significant in TKI treated patients, the OS time was shorter in PD-L1-positive patients than those negative (median OS 19.0 vs 41.0 months). In the whole cohort, the PA value of COX regression analysis was 0.683 for PFS, and the addition of PD-1 expression in the primary increased the PA value to 0.699. Conclusions: The assessment of immunological checkpoint-related protein in primary tumor may not be able to provide adequate information for clinicians to evaluate or predict the patient's treatment-related efficacy and prognosis. Biopsy or resection of the metastases may provide a more accurate biological information for clinician's decision-making and the patient's prognosis.