bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multibiomarker approach to predict prostate cancer pathology outcomes.
Authors: Paris Pamela , Cooperberg Matthew R. , Cowan Janet , Lindquist Karla , Kobayashi Yasuko , Simko Jeff , Bengtsson Henrik , Singh Khushboo L , Newcomb Lisa F. , Lin Daniel W. , Carroll Peter 
Published: March 2019

58 Background: Distinguishing indolent from aggressive prostate cancer remains a key challenge for prostate cancer management decision-making. A growing number of biomarkers are now on the market to help address this need, but have rarely been examined together in the same patients to determine their relative value. Methods: We identified men with low-risk cancers defined by biopsy Gleason score ≤3+3, PSA ≤10ng/ml, and clinical stage ≤T2 who underwent immediate prostatectomy. We collected archived prostate tissue and pre-surgical plasma samples from N = 381 cases from UCSF and N = 279 cases from UW. Plasma was analyzed for TGFb1 and IL6SR, previously validated markers for prostate cancer prognosis, using ELISA. From prostate tissue, DNA and RNA were extracted and analyzed for the GEMCaP copy number variation score and the cell cycle progression (CCP) score, respectively, both well-validated and previously reported scores. Pathologic outcomes were minor (pGS 3+4 or pT3a) or major (pGS ≥4+3 or ≥pT3b) upgrading/upstaging (UGUS), and multinomial regression was performed to determine putative markers’ ability to predict these outcomes, controlling for PSA, percent of biopsy cores positive, age, and clinical site. Results: Overall, 357 men had no UGUS event at prostatectomy, 236 had a minor event, and 67 had a major event. Neither TGFb1 nor IL6SR statistically significantly predicted any UGUS or major UGUS. On the other hand, both CCP and GEMCaP were directly associated with minor UGUS on univariate analysis. On multivariable multinomial analysis including both scores, the CCP score predicted minor UGUS (OR 1.70, 95% CI 1.07-2.72, p = .03) and GEMCaP also predicted minor UGUS (OR 1.04, 95% CI 1.01-1.07, p < .01). Neither CCP nor GEMCaP predicted major UG/US, but the number of events was small. Noteworthy, both GEMCaP and the CCP score were statistically significant predictors of outcomes in the same model, suggesting they can complement each other by offering additional information. The other clinical parameters were not significant in this model. Conclusions: Biomarker signatures based on analysis of DNA and RNA significantly and independently predict adverse pathology among men with clinically low-risk prostate cancer undergoing prostatectomy.
Hypofractionated dose painting IMRT using 20 fractions for intermediate to high-risk localized prostate cancer: Two-year outcome data (BIOPROP20, NCT02125175).
Authors: Syndikus Isabel , Chan Joachim Kwok-Chiu , Rowntree Thelma , Howard Laura , Staffurth John 
Published: March 2019

59 Background: Prostate dose painting (boosting intra-prostatic tumour volumes) may improve biochemical relapse-free survival similar to whole organ dose-escalation without the associated increased toxicity. We present a pre-defined secondary endpoint of 2 year outcome for patients at one of two UK centres in a phase II trial (BIOPROP20) on dose-painting radiotherapy for intermediate to high risk patients treated with 60Gy/20# and concurrent 68Gy boost. Methods: Pinnacle software was used for VMAT planning and boost volumes were outlined by18F choline PET/CT and mpMRI. Patients with positive lymph nodes also had concurrent pelvic radiotherapy of 45Gy with boost to 50Gy. Patients were followed up until year 2 with PSA and toxicity scores. Results: Overall 56 patients were treated, 5 with pelvic radiotherapy. Median age and PSA was 67.5 years (range 50 - 77) and 10.0ng/ml (3.9 - 39.4). All patients had tumour volumes > 10mm diameter on pre-biopsy mpMRI. 13 and 43 patients had intermediate and high risk disease. Median % LN risk was 18% (15 - 40). ADT duration was 6 months, 2 years, and 3 years for 42, 5, and 9 patients. At the 2 year follow up review, no grade 3 late toxicity was observed. For prostate only dose painting, grade 2 GU and GI toxicity was noted in 6% and 2% respectively. For prostate and nodal dose painting, no grade 2 toxicity was noted. Median IPSS score was 5 and 9, and median PSA was 0.3 and 0.1, in the two groups respectively. 1 patient had biochemical and metastatic relapse at 18 months (prostate, pelvic nodes and bone metastasis) and 1 patient had died of unrelated disease. Conclusions: Prostate radiotherapy with hypofractionated dose painting schedule of 60Gy/20# with 68Gy boost to intra-prostatic lesions was well tolerated at 2 years follow up. Clinical trial information: NCT02125175. [Table: see text]
Synchronous and metachronous cases of renal cell carcinoma and hematologic malignancies in a state cancer registry.
Authors: Henegan John Clark , Mitchell Katelyn , Maher Joseph 
Published: March 2019

593 Background: A Swedish national family-cancer database reported an association between renal cell carcinoma (RCC) and hematologic malignancies within families. Our hypothesis was that a search of a state cancer registry would detect an increased incidence of observed (versus expected) synchronous and metachronous cases of RCC and select hematologic malignancies. Methods: A query of the Mississippi Cancer Registry was performed for synchronous ( < 6 months between diagnoses) and metachronous ( > 6 months) cases of RCC and select hematologic malignancies (non-Hodgkin lymphoma (NHL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia, and Hodgkin lymphoma) in the state from 2003 to 2013. The expected number of cases was calculated based on crude case numbers available from https://www.cancer-rates.info/ms/. The percentage of the population < 18 years of age was removed from the eligible population. 2x2 tables were constructed to calculate a chi-square score of expected versus observed cases. Using one degree of freedom, a p-value was calculated from this statistic. Due to privacy issues, the registry was unable to provide an exact number of observed combined cases if there were < 5 in the time period. Results: Conclusions: There is a statistically significantly increased incidence of observed (versus expected) synchronous and metachronous cases of RCC with the B-cell malignancies NHL, MM, and CLL in Mississippi between 2003 and 2013. Future research will focus on clinical characteristics of patients with synchronous or metachronous cases of RCC and these hematologic malignancies.[Table: see text]
Clinical predictors of sarcomatoid kidney cancer: The results of a UCLA and french UroCCR network collaboration.
Authors: Lebacle Cedric Michel , Pooli Aydin , Bernhard Jean-Christophe , Paparel Philippe , Bensalah Karim , Beauval Jean Baptiste , Mejean Arnaud , Dariane Charles , Bigot Pierre , Lang Herve , Bessede Thomas , De La Taille Alexandre , Roupret Morgan , Irani Jacques , Patard Jean-Jacques , Belldegrun Arie S. , Shuch Brian , Chamie Karim , Drakaki Alexandra , Pantuck Allan J. ,   French Research Network on Kidney Cancer UroCCR, Bordeaux, France
Published: March 2019

598 Background: Predisposing factors for sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) remain unknown. We highlighted the association of potential contributing medical conditions with the presence of sRCC. Methods: Patients with a renal cell carcinoma (RCC) from UCLA and the French UroCCR-45 study (only sRCC) were included in the study. Characteristics of patients with sRCC were compared with patients with RCC without sarcomatoid features (nsRCC) in univariable and multivariable logistic regression analyses. We quantified the association of age, gender, smoking status, hypertension, kidney function, and endocrine disorders: diabetes and hypothyroidism with sRCC. Results: A total of 2764 were included in the study (586 sRCC vs. 2178 nsRCC). On univariable analysis, age (OR=1.02, 95%CI [1.01-1.03], p<.0001), male gender (OR=1.35, 95%CI [1.10-1.65], p=.004), active smoking (OR=1.87, 95%CI [1.48-2.36], p<.0001), and diabetes (OR=1.32, 95%CI [1.03-1.70], p=.026) were associated with the presence of sRCC (Table 1). On multivariable analysis, age (+2.1% per year, OR=1.02, 95%CI [1.01-1.03], p<0.0001), male gender (OR=1.33, 95%CI [1.08-1.64], p=.008), and active smoking (OR=1.95, 95%CI [1.54-2.47], p<0.0001) were independently associated with the presence of sRCC. The AUC of the model was 0.61. Conclusions: In this study we found that sarcomatoid dedifferentiation was associated with age, male gender, and active smoking. Further studies are needed to confirm these findings and establish the underlying biology. Univariable logistic regression analysis of the association between potential pathogenic factors and sRCC. N=2764 [Table: see text]
Outcomes of stereotactic ablative radiotherapy for extra-cranial oligo-metastatic renal cell cancer.
Authors: Zhang Yuanyuan , Schoenhals Jonathan , Christie Alana , Wang Chiachien , Mohamad Osama , Singla Nirmish , Desai Neil , Choy Hak , Courtney Kevin Dale , Bagrodia Aditya , Margulis Vitaly , Bowman I. Alex , Timmerman Robert D. , Brugarolas James , Hannan Raquibul 
Published: March 2019

599 Background: Stereotactic ablative radiotherapy (SAbR) is a standard of care for treating renal cell cancer (RCC) cranial metastasis. We describe the effect of SAbR on oligometastatic extra-cranial RCC disease course. Methods: We retrospectively reviewed 49 patients with oligometastatic RCC with 68 extra-cranial lesions. Patients were treated with SAbR with a curative intent from 2007 to 2017. We analyzed local control, systemic therapy free survival (mPFS), and overall survival. Results: With a median follow-up of 28 months (IQR: 16.0-40.3), the 1-year and 2-year overall survival after SAbR was 93.4% (95% CI: 81.0-97.8), and 83% (95% CI: 67.4-91.5) respectively. The median overall survival was not reached. The median time to systemic therapy was 13.4 months from the first SAbR(95% CI: 8.8-27.6). Median times from the first SabR course to second and third line systemic therapy (or death) were 31.8 months and 45 months, respectively. Patients in the favorable risk group by the Heng’s criteria (HR = 8.67, p = 0.04), with nometastatic disease at diagnosis (HR = 10.38, p < 0.01) and with clear cell histology (HR = 6.15, p < 0.01) exhibited better survival, as shown by univariate analysis. Patients with no metastatic disease at diagnosis (HR = 2.56, p = 0.02) and only one metastasis treated with SAbR (HR = 2.36, p = 0.03) also exhibited better systemic therapy-free survival. SAbR had an excellent local control rate of 94% at 2 years with no reported grade 3 or higher toxicity. Conclusions: SAbR is an effective and safe treatment for oligometastatic RCC, offering excellent local control with minimal toxicity. SAbR delayed the start of systemic therapy for this RCC cohort, offering quality of life benefits for patients without adversely affecting the progression on subsequent lines of systemic therapy. These findings call for prospective verification.
Pembrolizumab (pembro) and cabozantinib (cabo) in patients (pts) with metastatic renal cell carcinoma (mRCC): Phase I results.
Authors: Keeler Molika Emmeline , Kessler Elizabeth Riley , Bernard Brandon , Weisdack Sarah , Breaker Kathryn M. , Wold Mali , Ertz Donna , Weitzenkamp David , Flaig Thomas W. , Lam Elaine Tat 
Published: March 2019

600 Background: PD-L1- and VEGF-targeted therapies have improved survival for mRCC pts and mechanisms of synergy have been reported. We conducted a phase I/II study to evaluate the safety and efficacy of pembro and cabo in mRCC pts. Phase I data are presented here. Methods: mRCC pts received pembro and cabo in a standard 3+3 dose escalation to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD), and objective response rate (ORR). Cabo was dosed at 40mg QD and 60mg QD in the first and second cohorts, respectively. Pembro was dosed at 200mg IV Q3W in all cohorts. The DLT window was 21 days. Scans were obtained every 9 weeks. Treatment beyond progression was allowed. Results: Eight pts (6M, 2F) were enrolled in the dose escalation cohort with cabo 40mg (5 pts) or 60mg (3 pts) and pembro 200mg. Two pts were not evaluable for DLT due to missing ≥25% of the planned cabo doses in C1, not related to DLT. Median age was 52.5 yrs (range 40-68). Seven pts had clear cell RCC and 1 pt had non-clear cell RCC. Seven pts had MSKCC intermediate risk and 1 pt had MSKCC poor risk. All pts had prior nephrectomy. Median number of prior therapies was one (range 1-3). No DLTs were observed. Drug-related G1 and G2 adverse effects included fatigue (87.5%), weight loss (75%), anorexia (50%), diarrhea (50%), dysgeusia (50%), and abnormal LFTs (50%). One pt had SAE of G3 reversible posterior leukoencephalopathy syndrome during C4, attributed to cabo. One pt each developed G3 hypertension, G3 anorexia, and G3 confusion, all occurring outside the DLT window. No dose reductions were needed at the 40mg cohort. One pt in the 60mg cohort required dose reduction to 40mg after C5. All patients were evaluable for response: 2 PR (at 60 mg cohort), 5 SD [median duration SD 18 wks (range 9-36+)], 1 PD; ORR 25%; clinical benefit rate 87.5%. No correlation was seen between PD-L1 status (archival tissue) and response. Conclusions: The MTD was determined to be pembro 200 mg Q3W and cabo 60 QD. Enrollment in the phase II dose expansion is ongoing and the MTD may be adjusted based on additional pt experience and long-term tolerability. There was encouraging early efficacy. This is an investigator-initiated study sponsored by Merck. Clinical trial information: NCT03149822.
Comparison of retroperitoneal and transperitoneal robotic partial nephrectomy by pentafecta perioperative and renal functional outcomes.
Authors: Choi Chang Il , Seo Seong Il 
Published: March 2019

602 Background: To compare and analyze surgical, oncological and functional outcomes of transperitoneal (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN). Methods: Out of 566 consecutive patients who underwent RAPN by a single surgeon from December 2008 to July 2017, this study included 523 patients (TRPN 310, RRPN 213) who evaluated preoperative and 1-year postoperative estimated glomerular filtration rate (eGFR). Our primary endpoint was to compare the perioperative and postoperative outcomes of both approaches by the measure of Pentafecta (negative surgical margin, no 30-day complication, warm ischemic time (WIT) ≤25 minutes, return of estimated glomerular filtration rate (eGFR) to > 90% from baseline and no upstaging of chronic kidney disease). Secondary endpoint was to find the factors associated with Pentafecta by multivariate regression analysis. Results: No significant difference was found in terms of age, BMI, laterality, history of hypertension or diabetes, ASA grade, tumor size and RENAL nephrometry score. These outcomes were lower in the RRPN group: operative time [median (IQR) 244 (202-295) vs. 273 (230-314); p < 0.001], WIT [median (IQR) 19 (15-25) vs. 21 (16-27); p < 0.008] and estimated blood loss (EBL) [median (IQR) 100 (60-200) vs. 150 (100-200); p < 0.003]. Hospital stay, baseline eGFR, 1-year postoperative eGFR, the rate of Pentafecta achievement, recurrence and complications were not different. The rate of WIT ≤ 25 minutes was solely significantly different (TRPN 69.7% vs. RRPN 77.9%, p = 0.045) in the Pentafecta criteria. Multivariate analysis revealed tumor size [OR (95% CI) 0.641 (0.536-0.767), p < 0.001) and hospital stays (OR 0.639, p < 0.001) as predictive for lack of Pentafecta. Conclusions: RRPN demonstrated less operative time, WIT and EBL than TPRN. Pentafecta achievements were equivalent in both approaches. Tumor size and hospital stays were found as predictive factors of Pentafecta.
Prognostic role of PD-L1 expression in patients with advanced renal cell carcinoma (RCC) treated with sunitinib.
Authors: Iglesias Clara , Cereceda García Rodrigo Ignacio , Rodríguez Arias Lucía , Alvarez Manceñido Felipe Jose , Blanco Lorenzo Verónica , Faez Laura , Solis-Hernandez Maria Pilar , Fernández Sara , Revuelta Alfonso , Gómez David , del Río Fernández Jorge , Valcárcel González Sena , Contreras Toledo Debora Corina , Mihic Góngora Luka , Esteban Emilio 
Published: March 2019

603 Background: the prognosis and treatment of advanced RCC has improved over the last decade due to a number of effective anti-angiogenic and immune checkpoint inhibitors (ICPI) therapies. Certain clinical factors, such as low Karnofsky status (≤ 70%); less than a one year period from diagnosis to treatment administration; low serum hemoglobin; high corrected serum calcium; high lactate dehydrogenase; elevated neutrophil count or platelet count exceeding the upper limit of the normal range, have been able to stratify patients into three distinct prognostic groups: favorable (zero risk factors), intermediate (one to two), and poor risk (more than two). Nowadays, the relationship between PD-L1 expression with treatment response and the survival rate of RCC is a current topic of interest. Methods: a retrospective analysis of 182 patients with advanced RCC who received sunitinb in a single Institution has been conducted with the aim of analyzing PD-L1 as a prognostic factor. To carry out the immunohistochemical analysis, microscopy samples have been treated with the PD-L1 IHC 22C3 pharmDx assay, which is intended to measure the percentage of PD-L1 expression in the primary tumor tissue. Results: a total of 65 patients with primary tumor tissue sampling, who were never treated with (ICPI), were analyzed. Among these, 95% were considered as intermediate or poor risk and 47% had PD-L1 expression. The results have shown that PD-L1 expression is associated with worse progression-free survival (PFS) and overall survival (OS). In patients with no expression of PD-L1, the median PFS was 16.89 months (95% confidence interval 11.0 – 40.87 months) and 12.61 months for those with some % of PD-L1 expression (4.43 – 53.09). (χ² = 1.16; Pr > χ² = 0.20). Likewise, the median OS was 42.28 months (13.76 – 68.13) for patients with no expression of PD-L1 and 24.60 months for those with some % of PD-L1 expression (13.76- not reached) ( χ ² = 0.12; Pr > χ ² = 0.73). Conclusions: patients treated with sunitinib who express PD-L1, have shown shorter PFS and OS. Its validation as an independent prognostic factor, with regard to other standard clinical parameters, must be considered in order to develop a more tailored approach to treatment decision.
Molecular and imaging correlates of exceptional pathologic response to neoadjuvant ADT plus enzalutamide.
Authors: Sowalsky Adam G. , Wilkinson Scott , Ye Huihui , Harmon Stephanie , Turkbey Baris , Carrabba Nicole , Atway Rayann , Chun Guinevere , VanderWeele David James , Karzai Fatima , Madan Ravi Amrit , Pinto Peter A. , Choyke Peter L. , Dahut William L. 
Published: March 2019

61 Background: AR directed therapies are standard of care for metastatic prostate cancer, and their use for high-risk localized disease may improve survival. Previous trials showed that suppression of AR activity resulting in greater pathologic responses improved survival rates. However, the underlying biology and molecular features of exceptionally responding tumors remain unknown. Methods: Men with locally advanced prostate cancer (median Gleason score 8, median PSA 9.58 ng/dl) received mpMRI and MRI/US-fusion targeted biopsies at baseline. Patients received 6 months of ADT plus enzalutamide, then received a second mpMRI, and underwent radical prostatectomy. RP specimens were whole mounted in the same plane as MRI. The location of each tumor on biopsy was mapped to prostatectomy specimens using pathologic and imaging hallmarks. FFPE sections of baseline and post-treatment tumor were stained, laser capture microdissected, and analyzed using whole exome sequencing. Amongst nonresponding patients (residual tumor burden > 0.05 cc) comparison of pre- and post-treatment tumor specimens identified evolutionary phylogenies over space and time representing intrinsic or clonal selection of pre-existing cells. Amongst responding patients, clonal extinction was confirmed by sequencing and immunostaining of surgical specimens. Results: Gleason score at baseline did not differentiate responding and nonresponding patients. Focal ERG staining in biopsies was absent in 100% of responders and present in 60% of responders. Intraductal carcinoma architecture was also absent in all responding tumors. Focal PTEN loss was observed in all nonresponders at baseline. Responding tumor foci were enriched for deletion of chromosome 6q. Comparison of baseline mpMRI sequences indicated a trend towards lower variance on dynamic contract enhanced (DCE) MR and lower local texture heterogeneity metrics in responding lesions. Conclusions: Response to neoadjuvant intense ADT correlates with distinctive pathologic, molecular, and imaging features that can be observed prior to treatment. Selection of patients based on these parameters may improve overall responses to treatment in subsequent clinical trials. Clinical trial information: NCT02430480.
Angiogenic and immunomodulatory biomarkers in axitinib-treated patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Rini Brian I. , Escudier Bernard , Murphy Danielle , Wang Panpan , Tarazi Jamal Christo , Motzer Robert J. 
Published: March 2019

614 Background: Axitinib (axi) is approved for 2nd-line treatment of aRCC. In AXIS trial, median progression-free survival (PFS) was significantly longer in axi- vs sorafenib (sor)-treated pts (hazard ratio [HR] 0.67, 95% CI 0.54–0.81, P<0.0001). Association between mRNA/miRNA expression and clinical outcomes in a subset of axi- or sor-treated pts from AXIS was assessed. Methods: mRNA/miRNA analyses were performed on archival tumor samples. Expression was summarized for responders (complete and partial response) vs non-responders (stable and progressive disease), and for maximum percent tumor change. PFS and overall survival (OS) were analyzed by Kaplan-Meier. Results: Pt characteristics were similar between axi (n=34) and sor (n=33) arms. Association with outcomes is shown in the Table. A correlation was observed for CD68 protein and mRNA expression in axi-treated pts (R=0.4774 P=0.0043 and R=0.3985 P=0.0196, respectively). Both CXCR4 and TLR3 showed differences between treatment arms and association with PFS. TNFSF10 <median, and CD163, CSF1R and miR-221-5p ≥median were associated with shorter OS with axi vs sor ( P<0.05). Clinical trial information: NCT00678392. Conclusions: Immune-related biomarkers were associated with clinical outcomes in axi/sor-treated aRCC pts. Lower CCR7 expression was associated with better response and OS in axi-treated pts. CXCR4 and TLR3 may be predictive of response to axi. Analysis in a larger cohort is warranted.[Table: see text]