bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin (carbo) AUC dosing and crude relapse rate (RelR) in stage I seminoma.
Authors: Decatris Marios P. , Charalambous Charis , Michaelides Ioannis , Zouvani Ioanna , Kitsios Petros 
Published: March 2020

e15030 Background: Single-dose carbo is a treatment option in stage I seminoma. The MRC TE19 study update (2011) generated the hypothesis of a dose-response effect. Patients (pats) with similar creatinine clearance (CrCl) in TE19 had a higher RelR and lower relapse-free survival if treated with carbo AUC<7 than with AUC≥7. Methods: We compared the crude RelR of 40 consecutively treated pats at BoCOC, with that observed in the TE19 study cohorts and a previous large series (Dieckmann, 2000) dosing carbo in mg/m2. We determined CrCl (ml/min) with 24-hour urine collection (isotope method unavailable at our centre). Pats gave informed consent. Initially we used AUC≤7 and since 6/2008 AUC7.7. Follow-up CT scans were done annually to year 3. We compared RelR v actual mean carbo AUC between cohorts and between AUC<7 v ≥7. Results: After 3yrs median follow-up (IQR1.9-4.9), 1 pat relapsed 11months after carbo (AUC ≤7) and was salvaged with RT. Two pats were lost to follow-up at 30 and 52 months. There was a statistically significant negative correlation (Pearson coefficient) between crude RelR v actual mean carbo AUC (r2=0.91, p=0.012). The difference in frequency of relapse between cohorts treated at actual AUC<7 v AUC≥7 (24/322 v 13/370-7.5% v 3.5%) was significant (2-tailed p value for χ2 test 0.022, Fisher’s exact p=0.027). Conclusions: As the risk of relapse beyond 3yrs after carbo is very low (1/561 pats treated or 0.2% in TE19) significant number of further relapses is not expected. These results support an inverse dose-response association for carbo AUC and crude RelR. Follow-up is essential to confirm if these results are maintained. [Table: see text]
The burden of illness in metastatic renal cell carcinoma (mRCC) patients after two targeted therapies: A review of the literature.
Authors: Di Lorenzo Giuseppe , Coombs John , Casciano Roman , Stern Lee 
Published: March 2020

e15043 Background: MRCC poses a substantial burden in terms of morbidity, mortality, impaired quality of life (QoL), and costs. Despite the emergence of targeted therapies (VEGF-TKIs and mTORs) in this setting, considerable unmet medical needs remain. Methods: A comprehensive literature search was performed to systematically review available data on the burden of mRCC. Included articles focused on the efficacy, toxicity, guidelines, therapy sequencing, and overall disease burden of mRCC patients who have failed multiple targeted therapies. Of the 933 articles mRCC articles identified, 83 met the criteria for data extraction. Results: An extensive amount of literature is published on targeted therapies in the treatment of patients with mRCC. Recently approved therapies report improved outcomes in 1st and 2nd line treatment; however, there are minimal data on the efficacy and safety of treatments following failure of 2 sequential targeted therapies. Specifically, two studies report OS in 2nd line failures: one prospective study of capecitabine as 3rd line treatment (OS: 7.2 months [CI: 4.6-8.8]) and one retrospective single arm study of 3rd line sorafenib use after failure of both VEGF-TKIs and mTORs (OS: 7 months [range: 6-10]). Consequently, of the six current practice guidelines, none recommend a specific treatment for patients who fail 2 targeted therapies. As highlighted in over 20 articles on therapy sequencing, the treatment population failing 2 targeted therapies represents an extremely heterogeneous group with a variety of prior therapies, for whom data are lacking. QoL and economic data focusing on patients in this setting were not identified. However, based upon evaluations in 1st and 2nd line patients, treatment toxicity and disease progression are expected to have a negative impact on QoL while increasing costs due to the associated need for additional treatment, hospitalizations, and other management. Conclusions: Despite significant advances in the treatment options for patients with mRCC, many patients inevitably progress and are left with few options. There is substantial unmet need for safe and effective 3rd line treatment options that can provide clinical benefit.
Second-line treatment of metastatic renal cell carcinoma: The Institut Gustave Roussy experience with targeted therapies in 251 consecutive patients.
Authors: Levy Antonin , Menard Jean , Albiges Laurence , Di Palma Mario , Fizazi Karim , Escudier Bernard J. 
Published: March 2020

e15049 Background: Sequential treatment is currently the standard of care in metastatic renal cell carcinoma (mRCC). However, very little is known on how many patients (pts) can receive second line or further, and on how to predict those pts. Methods: Data from all mRCC patients treated at the IGR from 2005 to 2009 with first-line targeted therapy (sunitinib (SU), sorafenib (SO), bevacizumab (B), temsirolimus or everolimus (pooled together as mTOR)) were analyzed. Only patients with subsequent follow up have been included in this analysis. Patients were defined as “non eligible” for second treatment if: they were (i) still on first line treatment, (ii) not showing progressive (durable stable disease or partial response or complete response), or (iii) if they refused a second line treatment. Results: 251 patients, median age 60 years, median follow-up 20.2 months were treated with targeted therapy with a median OS of 25.8 months. Median OS with SU (127), SO (60) or B (61) were respectively 26.3, 16.4 and 32.5 months respectively. Only 3 patients received an mTOR inhibitor as first line. According to the eligibility criteria, the percentage of patients who received a second line was 59% (n=61/103), 52% (n=30/58) and 79% (n=38/48) for Su, So and B, respectively. MSKCC classification (p = 0.02) and first line agent (p = 0.001) were significant predictive factor for receiving a second line of treatment. Overall, patients receiving B were in better general condition, with 77% of PS = 0 compared to SO (53%) and SU (48%) (p = 0.005). Among the 131 patients who received a second line, the median OS from the start of second line treatment was 20.8 months for a TKI (n=98; 75%) and 16.6 months for an mTOR (n=32; 42%) (p = 0.12). Furthermore, the percentage of patients who received a third line was 56% (27/48), 28% (7/25) and 65% (13/20) for SU, SO and B, respectively. Conclusions: The median OS in patients treated with targeted therapies for mRCC in The Institut Gustave Roussy exceeds 2 years. The use of second line varies from 52% to 79%. Further studies are needed to validate the MSKCC groups and first line therapy as predictive factor for 2nd line treatment.
Cytogenetic changes in metastatic renal cell carcinoma: Basis for sensitivity and resistance to everolimus.
Authors: Caldwell Imogen Rose , Oei Paul , Ng Daniel , Caudwell Beth , Fong Peter C.C. , Broom Reuben James 
Published: March 2020

e15050 Background: The mTOR inhibitors have improved outcomes for pts with metastatic renal cell carcinoma (mRCC) but the duration of benefit is variable. Currently there are no predictive biomarkers for pre-selecting pts who are likely to benefit from these agents. We undertook an exploratory translational study evaluating cytogenetic changes in the context of benefit from everolimus therapy. Methods: 10 pts with clear cell mRCC treated with everolimus therapy were enrolled. 2 pts had both primary & metastatic specimens. Pre-treatment paraffin-embedded tissue specimens were analysed for cytogenetic changes using fluorescence in situ hybridisation (FISH) & clinical data including Progression-free Survival (PFS) (RECIST 1.1) were obtained. The gene probes chosen for this analysis were: VHL, FHIT, PDGFβ, PDGFRβ, FGFR1, FGFR3, EGFR, MYC, PTEN & IGH@. Results: Results are displayed in the table. The median PFS was 7.5 months (mo), including 4 pts who remain on treatment. 8 pts were treated 1st-line, one 2nd-line & one 3rd-line. The longest responder (PFS 28 mo, 3rd-line) had a normal VHL status but loss of FHIT. 2 pts with the longest PFS had gain of both PDGFβ & PDGFRβ. Changes were observed between the primary & metastatic specimens including the acquisition of gain of PDGFβ & MYC (these pts remain progression-free on treatment). Conclusions: Loss of FHIT but a normal VHL status was seen in one pt with mRCC who had an enduring response to everolimus. Concomitant gain of PDGFβ & PDGFRβ was observed in 5 pts including 2 with prolonged benefit. Acquisition of gains in gene status suggests evolution of genetic changes between primary & metastatic specimens. [Table: see text]
Primary hypertension to predict progression-free survival of target therapy in patients with metastatic renal cell carcinoma.
Authors: Chi Zhi Hong , Mao Li Li , Si Lu , Cui Chuan Liang , Sheng Xi Nan , Li Si Ming , Tang Bi Xia , Guo Jun 
Published: March 2020

e15052 Background: Primary Hypertension(PH) was identified as a risk factor for RCC(renal cell carcinoma) in previous studies, only one report showed history of hypertension predicted better survival in RCC patients. In recent years, treatment related hypertension (TRH) was found to be associated with clinical outcome of targeted therapy. However, little is known about whether primary hypertension had an effect on survival of mRCC patients treated with targeted therapy. The objective of this study was to investigate the effects of primary hypertension on treatment outcome in patients treated with targeted therapy for metastatic RCC (mRCC). Methods: We conducted follow-up on a cohort of consecutiave mRCC cases treated with sunitinib or sorafenib in our center. Baseline characters were recorded such as age, gender, blood pressure, stage, et al. 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 or older, and 47 (61%) pts received sunitinib. 28 pts(36.4%) had a history of PH and 19 pts (24.7%) developed TRH, which was more common in PH pts than pts with normal blood pressure(p=0.003). With a median follow-up time of 24 months (range: 1.5-36.2 months), 60 pts developed disease progression and 34 pts died. Patients with primary hypertension demonstrated longer median PFS than those with normal baseline blood pressure (14.0m vs 9.5m, 95%CI: 8.0-10.9m) (p=0.01). In multivariable analysis, primary hypertension was independent predictors of PFS (HR =0.51, 95% CI; 0.27-0.98). No significant differences were found between clinical outcomes and other factors such as gender, age. Conclusions: Data from this study suggested that primary hypertension may be an independent predictor of longer PFS in mRCC pts treated with targeted agents.
Allogeneic partially HLA-matched dendritic cells (DC) as a vaccine in metastatic renal cell cancer (mRCC): Final analysis of a clinical phase I/II study.
Authors: Flörcken Anne , Kopp Joachim , Movassaghi Kamran , van Lessen Antje , Takvorian Anna , Schönemann Constanze , Jöhrens Korinna , Möbs Markus , Sawitzki Birgit , Dörken Bernd , Pezzutto Antonio , Westermann Jörg 
Published: March 2020

e15053 Background: Despite novel kinase inhibitors, prognosis of metastatic RCC remains poor and new experimental approaches are warranted. Our aim was to evaluate a DC-based vaccine, which exploits alloreactivity as a means to amplify specific anti-tumor immune responses. Methods: Allogeneic, partially HLA-matched DC were generated in our GMP facility. DC were loaded with autologous tumor lysate. 8 patients with progressive mRCC were included, 7 patients were immunized repetitively with 107 DC s.c. over 20 weeks. Low-dose IL-2 (3 Mio U s.c. qd) was used concomitantly. Endpoints of the study were feasibility, safety, immunological and clinical responses. T cell responses against HLA-A2-restricted RCC-associated antigens were evaluated by proliferation assays, ELISpot and cytokine bead array (CBA). T cell repertoire was analysed by T cell receptor γ and –β PCR. Results: Vaccination was feasible and safe, no treatment-related grade 3/4 toxicity or clinically relevant autoimmunity was observed. No objective responses were observed, however, 2/7 patients showed stable disease, one a minimal clinical response. The mean TTP was 24.6 weeks (range 5 to 96). Delayed-type hypersensitivity was detected in 3/7 and HLA antibodies were induced in 3/7 patients. In 3/7 patients T cell responses against RCC-associated antigens such as TYMS, G250, vimentin, surviving and cyclin-D1 were induced by vaccination. These antigen-specific T cells showed a predominant TH1-cytokine profile. Interestingly, a clonally expanded T cell population could be detected by γ- and –β PCR in one patient with both a minimal clinical response and a T cell response. This clone is currently persisting for more than 80 months, its specificity is under investigation. Conclusions: Vaccination with allogeneic tumor-lysate-loaded DC was feasible, safe and was able to induce TH1-polarized immune responses against RCC-associated antigens. Tumor vaccination might be a promising approach in minimal residual disease, possibly in combination with antibodies against CTLA-4 or PD-1.
Safety and efficacy of everolimus in Asian patients with metastatic renal cell carcinoma (mRCC) who failed previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy: A subanalysis of REACT.
Authors: Rha Sun Young , Lee Se-Hoon , Ou Yen-Chuan , Ahn Jin-Hee , Chang Yen-Hwa , Srimuninnimit Vichien , Lim Ho Yeong , Chung Ik-Joo , Pang See-Tong , Xue Hong-Ling , Panneerselvam Ashok , Chung Jooseop , Toh Chee-Keong 
Published: March 2020

e15064 Background: Some targeted agents have shown variable safety profiles in Asian vs non-Asian patients with mRCC. A retrospective analysis of sunitinib in Korean patients with mRCC found increased incidence and severity of certain adverse events (AEs) compared with previous global trials (Hong et al. Cancer Res Treat. 2009;41:67-72). The open-label, expanded-access program REACT (RAD001 Expanded Access Clinical Trial in RCC; NCT00655252) provided everolimus, a mammalian target of rapamycin (mTOR) inhibitor, before its regulatory approval to 1367 patients with VEGFr-TKI refractory mRCC from 34 countries. Final results of REACT were recently published (Grünwald et al. Eur J Cancer. 2012;48:324-332). This analysis compared study end points in Asian patients with those in the total REACT population. Methods: The primary objective of REACT was to assess the safety of everolimus 10 mg/day, as determined by the overall occurrence of grade 3/4 AEs. Best overall tumor response was evaluated based on RECIST 1.0. Results: Baseline characteristics of Asian patients (n = 109; from South Korea, Taiwan, Thailand, and Singapore) were similar to those of the total study population. Median duration of everolimus exposure was longer in Asian patients than in the total population: 24.1 (range, 2.0-72.7) vs 14.0 (0.1-83.7) weeks. Overall incidence of grade 3/4 AEs was slightly higher in Asian patients than in the total population (70.6% vs 61.6%); common grade 3/4 AEs in Asian patients and the total population, respectively, included anemia (26.6% vs 13.4%), hyperglycemia (11.9% vs 5.5%), pneumonia (10.1% vs 4.2%), stomatitis (6.4% vs 5.4%), thrombocytopenia (3.7% vs 1.0%), and pneumonitis (3.7% vs 2.7%). More patients in the Asian population than in the total population had achieved disease control: partial response, 3.7% vs 1.7%; stable disease, 67.0% vs 51.6%. Conclusions: In this subanalysis of REACT, Asian patients treated with everolimus experienced a greater clinical benefit with a slightly higher incidence of AEs. These results are supportive of the use of everolimus in the Asian population.
The role of tumor vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFR) polymorphisms in the prediction of clinical outcome for advanced renal cell carcinoma patients receiving first-line sunitinib.
Authors: Bianconi Maristella , Scartozzi Mario , Faloppi Luca , Giampieri Riccardo , Maccaroni Elena , Bittoni Alessandro , Del Prete Michela , Loretelli Cristian , Belvederesi Laura , Conti Alessandro , Burattini Luciano , Minardi Daniele , Silva Rosa Rita , Montironi Rodolfo , Cascinu Stefano 
Published: March 2020

e15074 Background: metastatic renal cell carcinoma (mRCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic strongholds are TKIs directed against the VEGF family (sunitinib and sorafenib). The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms, in determining the clinical outcome of mRCC patients receiving first-line sunitinib Methods: 41 histologic samples (biopsies and surgical specimens) of mRCC patients were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analyzed for first line treatment. Results: VEGF A rs833061 C>T polymorphism was statistically significant in PFS (17 months for C vs 4 months for T; P = 0,0029) and OS (35,93 months for C vs 11 months for T; P = 0,0267). VEGF A rs699947 A>C was statistically significant for PFS (17 months for A vs 3,97 months for C; P = 0,0023) and OS (35,93 months for A vs 10,98 for C; P = 0,0272). VEGF A rs2010963 G>C was significant in PFS (16,98 months for G vs 4,65 for G/C vs 2,73 for C; P = 0,0188). VEGR3 rs6877011 C>G was significant in PFS (8,22 months for C vs 2,22 for C/G; P = 0,0361) and OS (35,93 months for C vs 12,08 for C/G; P = 0,0183). Conclusions: in our analysis patients with C polymorphism of rc833061, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first line therapy. VEGFR-3 role is still matter of debate but seems to be involved in vessels sprouting and architecture.
Plasma cytokines and angiogenic factors (CAFs) for evaluation of risk of recurrence and classification of patients (pts) with nonmetastatic renal cell carcinoma (RCC).
Authors: Khajavi Mehrdad , Jonasch Eric , Wang Xuemei , Wood Christopher G. , Matin Surena F. , Fiorentino Stefania , McKee Kathryn S. , Tran Hai T. , Heymach John , Zurita Amado J. 
Published: March 2020

e15075 Background: Although recent years have brought great progress into understanding the pathogenesis of RCC and multiple promising biomarkers, no tumor tissue or blood-based test has yet been established to assist in the clinical determination of prognosis. Whether CAFs can be used to classify RCC pts and the set of CAFs that is host vs. tumor-dependent remain unclear. The main objectives of this exploratory analysis were to identify CAFs predictive of recurrence, and to gain insight into coordinated regulation and tumor dependency of individual factors by comparing CAFs pre- and post-nephrectomy (Nx) in RCC pts. Methods: Plasma samples were obtained before and up to 1 year after Nx from 52 pts with sporadic, non-metastatic RCC with dominant clear cell histology. Pts were categorized based on pathologic staging (pT1/pT2 as low-risk [LR] for recurrence, n=32; pT3/pT4 as high-risk [HR], n=20). Multiplex bead suspension arrays and ELISA were used to measure concentrations of 58 CAFs including angiogenesis and invasion mediators (VEGF, VEGF-C, soluble CAIX [sCA9], HGF and TGF-b1, among others), and multiple inflammatory and/or immunomodulatory chemokines and interleukins (IL). t-test and Wilcoxon signed rank or rank-sum tests were respectively used to assess changes in CAFs between pre- and post-Nx or to compare CAFs between subgroups of pts. Results: The concentrations of IL-8 and sCA9, among others, were significantly higher in HR vs. LR RCC pts pre-Nx (P<0.01). The pre-Nx concentrations of e-selectin were lower in RCC pts with eventual disease recurrence (P=0.027). Several CAFs decreased significantly post-Nx, including sCA9 and endoglin, whereas others increased, such as stem cell factor, IL-12, IL-18 and vascular cell adhesion molecule-1. Angiogenic and hypoxia-regulated CAFs such as OPN, sCA9, HGF, endoglin and collagen type IV grouped together using unsupervised hierarchical clustering. Conclusions: Pre-Nx CAFs associated with risk for recurrence could be useful in risk stratification of non-metastatic clear cell RCC pts. Some tumor-dependent angiogenic CAFs are coordinately regulated in these pts.
Impact of race and age on surgery and outcomes of renal cell carcinoma (RCC): A population based analysis.
Authors: Preet Mohan , Brar Amarpali , Surapaneni Aparna , Khillan Ratesh , Sidhu Gurinder Singh 
Published: March 2020

e15097 Background: RCC is a surgically curable malignancy; the outcomes are typically based on tumor size/extent and histology. Partial nephrectomy (PN) is preferred as nephron sparing approach over radical nephrectomy (RN), especially in smaller tumors. Methods: We reviewed data from Surveillance, Epidemiology, and End Results (SEER) 17 Regs Research Data registry for adult patients (pts) with RCC who had data about age, race, pathology, surgery and survival outcome. Results: In all 84480 cases of pts: 31605 (37%) females (F) and 52875 (63%) males (M) were reviewed. There were 8663 (10%) African Americans (AA) and 70942 (84%) Caucasians (C). Of the AA pts, there were 3349(39%) AAF and 5314(61%) AAM. Of the C pts, there were 26412(37%) CF and 44530(63%) CM. Clear cell RCC (CRCC) was seen in 69336 (82%); AA pts with CRCC 6166 (71%) , AAF: 2588(77%) and AAM: 3578(67%). C pts with CRCC: 58936(83%) : CM 36443(82%), and CF-22493 (85%) were reviewed. In AA pts with CRCC PN was done 1282 (21%) and RN 4145 (67%)times. AA men had 818 (23%) PN and 2539 (71%) RN, where as AAF had 464 (16%) PN and 1606 (62%) RN. C pts with CRCC had PN 10402 (18%) and RN 37214 (63%) times. CM had PN 6692 (18%) and RN 23594 (65%) times; CF had PN 3710 (16%) and RN 13620 (61%) times. The median size of tumor in pts undergoing PN was 2-3 cm and independent of race or sex. In pts undergoing PN, the median survival for AAM, AAF, CM and CF was 22m, 18m, 23m and 23m respectively. In pts undergoing RN the median survival for AAM, AAF, CM and CF was 23m, 21m, 24m and 23m respectively. In pts over the age of 80, 8240 cases of CRCC were reviewed, and 3950 (48%) pts had no surgery, of pts having any surgery 376 (8%) and 2859 (68%) pts had PN and RN. Median survival of CRCC over 80 years old having no surgery, PN and RN was 5m, 27m and 29m. Race or sex made no impact on proportion of pts having no surgery. Conclusions: C pts esp. CF are more likely to have CRCC histology. The kind of surgery (PN vs. RN) and outcomes after that are similar across both ethnicities and sexes. Pts over 80 yr old are much less likely to have any surgery and have very poor outcomes, this is avoided if they have PN or RN.