bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of renal cell carcinoma in patients with primary uveal melanoma.
Authors: Valsecchi Matias Emanuel , Asija Aakanksha , Sato Takami , Shields Carol L , Shields Jerry A , Richards-Yutz Jennifer , Ganguly Arupa , Mastrangelo Michael J. , Lin Jianqing 
Published: March 2020

e15563 Background: Somatic mutations of BRCA1 associated protein1 (BAP1), a tumor suppressor gene, located on chromosome 3p21.1 is found in 50% of primary uveal melanoma (UM) and has been linked to an aggressive phenotype. It is recently reported that somatic BAP1 mutation is also found in 15% of renal cell carcinomas (RCC). We hypothesize that germ line or somatic mutation of BAP1 may contribute the carcinogenesis of patients (pts) who have both UM and RCC. Methods: Retrospective chart review on patients with primary UM treated at Wills Eye Institute and Thomas Jefferson University between 1997 and 2012 revealed 15 patients with both UM and histologically proven RCC. Clinical information on these patients was analyzed. Tumor tissue and blood specimens were also collected for BAP1 gene mutation analysis. Results: Of the 15 patients, 12 (80%) were males. Median age at diagnosis of UM was 57 years old. Six of these patients developed liver metastasis on follow-up (40%). From 8 patients whose pathology data on RCC were available, 6 of them were clear cell type (75%), one was papillary type-1 and one was multilocular cystic subtype. The diagnosis of RCC proceeded the UM diagnosis in 5 of 15 patients, while the diagnoses were made concurrently in 4 patients. Six patients were diagnosed with UM first. For pts who had genetic testing on UM, chromosome 3 abnormalities are the most common abnormalities found. Peripheral blood specimens were tested for 2 patients and germ-line BAP1 mutation was not discovered. Detailed tumor tissue BAP1 mutation analysis is ongoing. Conclusions: The development of RCC is relative common for UM and the molecular mechanism is being determined. It is male dominant in sex and mostly clear cell type in histology of RCC. Further gene mutation analysis and its association with clinical data will be reported.
Increase in blood pressure with sorafenib exposure: Renal cell carcinoma (RCC) versus other solid tumors.
Authors: Shah Amishi , Motiwala Shweta , Brose Marcia S. , O'Dwyer Peter J. , Flaherty Keith , Keefe Stephen Michael 
Published: March 2020

e15564 Background: Tyrosine kinase inhibitors (TKIs) such as sorafenib are widely used in the treatment of solid tumor malignancies. Incident hypertension with angiogenesis inhibitors has been well-documented in the RCC where incident hypertension on treatment is associated with improved clinical outcome. Little has been reported about increases in (BP) with TKIs in other solid tumor malignancies. Methods: We performed a retrospective cohort study examining changes in BP with sorafenib among the 101 patients treated at the University of Pennsylvania on a randomized discontinuation trial examining sorafenib in patients with advanced solid tumor malignancies. Solid tumor diagnoses were established on the basis of tumor histology. Treatment of patients on study with sorafenib was initiated at 400 mg BID. Patients were treated for at least 12 weeks and were evaluated at least every three weeks in the clinic. BP was recorded at each visit. Sorafenib exposure was recorded by patients in a pill diary. The primary endpoint for this study was a maximal change in BP defined as the difference between baseline BP and highest subsequent recorded systolic and diastolic BPs on treatment. Results: 72% of RCC patients developed an increase in systolic BP (SBP) of at least 20 mmHg as compared to 32% of non-RCC patients. The mean increase in SBP on study for RCC patients was 30 mmHg versus 19 mmHg in non-mRCC patients. RCC patients in the top quartile of increased SBP showed a mean increase of 54 mmHg as compared to 35 mmHg for non-mRCC patients. A chi-squared test of proportions and t-tests were used to compare rates and means, respectively. Each of the aforementioned differences were found to be statistically significant with p-values <0.003. These relationships also held true for diastolic BP. There was no difference in SBP between groups in terms of age or sorafenib exposure. Differences in BP were not related to differences in glomerular filtration rate. Conclusions: In these sorafenib-treated patients, the proportion of patients with increased BP and the mean amplitude of change in BP both were significantly greater in the RCC population than in the non-RCC group.
Comparing the efficacies of neoadjuvant non-cisplatin-based and cisplatin-based chemotherapies in obtaining pathologic complete remissions in muscle-invasive bladder cancer.
Authors: Sivakumaran Praveen , Ranpura Vishal Navnitray , Perry David John 
Published: March 2020

e15577 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease and cisplatin-based neoadjvuant chemotherapy is standard therapy. Because of renal insufficiency, many patients are unfit to receive cisplatin and, instead receive carboplatin-based chemotherapy. The efficacy of carboplatin-based chemotherapy has not been studied in this setting. We performed a study comparing the efficacies of neoadjuvant carboplatin-containing and cisplatin-containing chemotherapies in achieving pathologic complete responses (pCR) in MIBC. Overall survival (OS) was also calculated. Methods: Medical records for all patients who underwent cystectomy at MedStar Washington Hospital Center between January 1, 2002 and December 31, 2011 were reviewed to determine which neoadjuvant chemotherapy was given and whether a pCR was reached at the time of cystectomy. OS was also calculated. Results: 232 patients qualified for study. 13 received neoadjuvant cisplatin-based treatment (Group 1) and 12 received neoadjuvant carboplatin-based treatment (Group 2). pCR rates were 53.8% and 41.7% in Groups 1 and 2, respectively. 5-year OS for Groups 1 and 2 were 69% and 75%, respectively. Conclusions: Given the limitations of this small retrospective analysis, carboplatin-based neoadjuvant chemotherapy prior to cystectomy for MIBC appears to be comparable in efficacy to cisplatin-based neoadjuvant chemotherapy.
Bladder cancer in African-Americans: Defining intrinsic biology and outcome.
Authors: Chism David D. , Damrauer Jeffrey S. , Gallagher Sarah A. , Milowsky Matthew I. , Kim William Y. 
Published: March 2020

e15595 Background: Matched for stage and grade, urothelial carcinoma (UC) of the bladder has a higher cancer-specific mortality in African-Americans [AAs] as compared to whites. Gene expression studies in breast cancer have identified a basal-like subtype in AAs associated with a worse prognosis. We sought to use gene expression analysis to determine if the difference in outcome in UC is related to tumor biology. Methods: RNA expression of high-grade, muscle invasive UC tumors was filtered for dynamically expressed genes, hierarchically clustered and used to define the optimal number of gene expression subclasses by the criterion of subclass stability. 2 class Significance Analysis of Microarrays (SAM) was used to define the most differentially expressed genes and this list was analyzed by DAVID and Ingenuity (IPA) pathway analysis. The 50-gene predictor (PAM50) was used to determine correlation to the basal centroid of basal-like breast cancer. Results: Using hierarchical clustering, K=3 was independently found to yield the optimal number of subclasses. 2 class SAM generated a list of approximately 1,800 genes that were most differentially expressed between each molecular subtype and the others. DAVID and Ingenuity (IPA) pathway analysis revealed basal, urothelial, and extracellular matrix (ECM)-rich subtypes based on expression of specific genes or gene pathways. Based on the PAM50 classifier, a significant fraction of the tumors from AA (8/9) were classified as basal-like (P=0.03. Chi square). Conclusions: Our preliminary data suggests that AA patients have a higher rate of basal-like UC of the bladder cancer.
A cytokine and angiogenic factor (CAF) analysis in plasma in testicular germ cell tumor patients (TGCTs).
Authors: Mardiak Jozef , Cholujova Dana , Jurisica Igor , Gronesova Paulina , Miskovska Vera , Obertova Jana , Palacka Patrik , Rajec Jan , Sycova-Mila Zuzana , Usakova Vanda , Vertakova-Krakovska Bibiana , Chovanec Michal , Svetlovska Daniela , Salek Tomas , Bujdak Peter , Spanik Stanislav , Ondrus Dalibor , Mego Michal 
Published: March 2020

e15599 Background: We investigated cytokines and angiogenic factors (CAFs) in patients with testicular germ cell tumors (TGCTs). We aimed to link the CAF profile to type of response to chemotherapy and select candidate prognostic and predictive markers for further study. Methods: In the presented study, plasma from 99 patients (pt) with TGCTs treated with first line (95 pt) or salvage (4 pt) chemotherapy was collected. The concentrations of 51 plasma CAFs were measured pre-treatment (n = 80) and on day 22 (n = 60) using multiplex bead arrays (Human Group I and II cytokine panels and TGF beta by Bio-Plex 200 system (Bio-Rad Laboratories, Hercules, CA). We used unsupervised clustering with self-organizing map (SOM) and k-means clustering to analyze CAF expression profiles. Results: Unsupervised clustering with self-organizing maps and k-means identified characteristic plasma cytokine profiles in different subgroups of patients according to response to chemotherapy and other clinical variables. Several cytokines were differentially expressed in patients with favourable and unfavorable response in serum before chemotherapy including IL-1b, IL-15, M-CSF, IL-4, IL-5, b-NGF, IL-10, MCP-3, FGF basic, IL-6, MIP-1a, GM-CSF, IL-17, IL-13, MIP1b, IL-8, SCF, IFN alfa, SCGFb, IL-2RA, IP-10, IL-16, TGFb-3. Similarly, following cytokines were differentially expressed in serum after 1st cycle of chemotherapy IL-1b, TGFb-3, LIF, TGFb-2, IL-16, IL-18, IL-2RA, MCP-3, IFN alfa, HGF, IL1a, MIF, SCF, IL-3, SCGFb, b-NGF, MIG, CTACK. Conclusions: CAF profiling with unsupervised clustering revealed clinically relevant differences in subgroups of TGCTs patients. We suggest that this platform may provide valuable insights into TGCTs biology, and could help to identify plasma cytokine signature for predicting treatment resistance.
High-dose chemotherapy and autologous stem cell transplantation in refractory/metastatic nonseminomatous germ cell-tumors: A retrospective study of the Turkish Oncology Association.
Authors: Ozturk Mustafa , Arpaci Fikret , Ozaydin Sukru , Karadurmus Nuri , Ozdemir Evren , Ataergin Selmin , Erdem Gokhan , Karaca Halit , Cakar Mustafa , Turker Turker , Ozet Ahmet , Kuzhan Okan , Kilic Selim , Komurcu Seref , Ozet Gulsum , Dagdas Simten , Ozturk Bekir , Sivgin Serdar 
Published: March 2020

e15623 Background: Testicular cancer is a chemosensitive tumor that may be curable even in relapsed disease. Those patients who do not respond to standard combination chemotherapy or relaps may be treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) as salvage therapy. Methods: Eighty five patients that received HDC and ASCT between Feb 1993 - Dec 2012 in different university clinics of Turkey were retrospectively reviewed and evaluated. Results: Median age of the patients was 24 (range: 11-54 years) and 63 patients (74,1%) had stage III, 21 (24,7%) had stage II disease at initial diagnosis. The primary tumor location was testis in 71 patients (83,5%), and 14 patients (16,5%) had extragonadal region origin. Evaluation of metastatic focuses before HDC and ASCT was as follows: Liver metastasis (n = 23, 27.05%), lung involvement (n = 23, 27.05%) and multiorgan involvement (n =14, 16.47%) and other metastatic involvements (n=4, 4.7%). ICE (ifosfamide, carboplatin, etoposide) regimen was performed as HDC in all patients. Median follow-up was 59 (range: 8-218) months. Pre-ASCT patients’ condition was complete remission (n=28, 32.9%), partial remission (n=36, 42.4%) and never in CR (n=21, 24.7%) respectively. 32 patients (37.6%) relapsed or progressed within 1 year after HDC and ASCT median relaps was time 3 months (range: 0.3 - 36.13). Transplant related mortality was %3.5 and 3 patients died within the engraftment period after HDC. Five-year overall survival rate was 59.7%. Conclusions: HDC and ASCT is an effective and safe approach for patients with metastatic and refractory germ cell testicular cancer patients that do not respond to standard combination chemotherapy.
Prostate cancer management: Racial disparities in the United States.
Authors: Al Dhaybi Omar , Silberstein Peter T. 
Published: March 2020

e16012 Background: Racial disparities in prostate cancer management have been reported. Black patients with well–differentiated disease were less likely to receive definitive therapy than whites with similar disease according to Underwood et. al., who included 142,340 patients from the Surveillance, Epidemiology and End Result (SEER) registry (J Urol, Vol. 171, 1504 – 1507, April 2004). Our objective was to identify racial disparities in the management of prostate cancer patients from the National Cancer Database. Methods: Prostate cancer treatment according to race in the USA, obtained from the National Cancer Database, was retrospectively reviewed. 1,497,540 patients with prostate cancer in 1397 US teaching and community hospitals between 2000 and 2010 were included. Chi square and Fisher tests were used for statistical analysis. Results: Black patients with stage II disease underwent radical prostatectomy significantly less than white patients (34.3% versus 43%, p<0.05). 10.9% of blacks with stage II disease did not receive any therapy, versus 6.7% of whites (p<0.05). 0.9% of whites with stage III disease didn’t receive any therapy versus 2% of blacks (p<0.05). The disparity was even more accentuated for stage IV disease, where 13.4% of blacks did not receive any form of treatment versus 10.3% of whites (p<0.05). 44% of blacks with localized disease (stage I and II) received radiation therapy, 34% received surgery. Blacks were less likely to receive radical prostatectomy for stage I and II disease compared to whites (34% versus 43%, p<0.05). Stage IV disease at presentation was more common in blacks (7.2%) than in whites (4.7%, p<0.05). Conclusions: This is the largest study which has analyzed ethnicity and prostate cancer management. Significant racial disparities exist in prostate cancer management between whites and blacks in the USA. Our study reveals that blacks are more likely to receive radiation therapy and less likely to get radical prostatectomy for stage I and II disease. A higher percentage of black patients with stage II, III or IV disease do not undergo any treatment as compared to whites. Blacks are also more likely to present with stage IV disease.
Effects of angiotensin-converting enzyme (ACE) inhibitors on the outcomes of patients receiving primary radiotherapy for prostate cancer (PC).
Authors: Ranasinghe Weranja Kalana Bodhisiri , Williams Scott G. , Sengupta Shomik , Chang Mike , Shulkes Arthur , Bolton Damien M. , Baldwin Graham , Patel Oneel 
Published: March 2020

e16016 Background: ACE inhibitors have been linked with an increased incidence of prostate, breast and lung cancer as well as increased recurrence rates in breast cancer. However the effects of ACE inhibitors on patients receiving primary radiation therapy for PC are unknown. Methods: We conducted a retrospective medication review of a prospective cohort of 1956 men who received primary radiotherapy (RT) for PC at the Peter McCallum Cancer Institute, Melbourne, Australia from 2003 -07. A competing risks model was developed for statistical analysis of the data. Results: 56% of patients who received RT also had concurrent salvage androgen deprivation therapy (sADT). A total 502 men had subsequent biochemical failure, 314 had initiated sADT and 125 had died of prostate cancer. Median follow up after RT was 71 months and 41 months after initiation of sADT. Of the 603 men who were on ACE-inhibitors, 160 received sADT. After adjusting for patient age, initial tumor stage, Gleason Score and PSA, along with planned ADT usage and ACE27 co-morbidity score, there were significant association between ACE-inhibitors and PC-specific mortality both from the time of RT and sADT (p= 0.035 and 0.01 respectively), with a strong increase in hazard (HR 1.58 [95%CI 1.03-2.42) and 2.02 [95%CI 1.16-2.90]). No significant association was seen with time to metastasis development, suggesting the impact of ACE inhibitors may be in the post-metastasis phase of the disease. Conclusions: ACE inhibitors may increase the rates of PC-specific mortality in men receiving primary RT for PC. However these results need to be further validated by randomized controlled studies and the mechanisms need to be investigated.
Role of the urologist in whether locoregional prostate cancer patients consult with a radiation oncologist.
Authors: Quek Ruben G. W. , Ward Kevin C. , Master Viraj A. , Lin Chun Chieh , Virgo Katherine S. , Portier Kenneth M. , Lipscomb Joseph 
Published: March 2020

e16029 Background: Multiple treatment options exist for prostate cancer patients, and therapeutic recommendations may differ depending on characteristics of the specialist consulted. The clinical judgment of specialists can play a critical role in the initial treatment choice, especially in cases where there is no professional consensus regarding the optimal treatment strategy. We examined the association between prostate cancer patients’ urologists’ practice affiliation with medical schools on the likelihood the patient would consult a radiation oncologist. Methods: Using the Surveillance, Epidemiology and End Results – Medicare linked database and the American Medical Association Physician Masterfile, we conducted a retrospective cohort study of 39,915 patients aged 66 years or older who were diagnosed between 2004 - 2007 with locoregional prostate cancer, and the 2,404 urologists who performed the diagnostic biopsies. Multilevel regression analysis was used to evaluate the influence of patients’ urologists’ practice affiliations with medical schools on the patients’ consultation with a radiation oncologist within 9 months of diagnosis. Results: Overall, 25,110 (62.9%) patients consulted with a radiation oncologist. After adjusting for patient, tumor and urologist characteristics, patients who saw urologists practicing within non-institutional settings were significantly more likely to consult with a radiation oncologist (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.05-1.34, p = 0.006) when compared to those who saw urologists practicing within settings with a major medical school affiliation. In addition, patients who saw urologists ≥ 58 years old were significantly more likely to consult with a radiation oncologist (OR, 1.71; 95% CI, 1.16-2.50, p = 0.006) when compared to those who saw urologists < 43 years old. Conclusions: Locoregional prostate cancer patients who received their diagnostic biopsy by urologists practicing in non-institutional settings and those who saw older urologists were significantly more likely to eventually consult with a radiation oncologist. This may have implications on which patient eventually receives radiation as initial therapy.
Clinical outcome (CO) and predictive factors (PRE) evaluation of young (≤ 60 years) castration-resistant prostate cancer (CRPC) patients, treated with docetaxel (DOC): Preliminary results of an Italian multicenter retrospective study (CYCLOP study).
Authors: Caffo Orazio , Ortega Cinzia , Di Lorenzo Giuseppe , La Russa Francesca , Burgio Salvatore Luca , Messina Caterina , Facchini Gaetano , Iacovelli Roberto , Lodde Michele , Morelli Franco , Massari Francesco , Procopio Giuseppe , Zustovich Fable , Lo Re Giovanni , Pegoraro Cristina , Gamucci Teresa , Pappagallo Giovanni L. , Veccia Antonello , Maines Francesca , Galligioni Enzo 
Published: March 2020

e16031 Background: CRPC is rare in pts ≤ 60 yrs and clinical outcomes of these pts are not clearly defined despite there is a common feeling of a worse prognosis for them. The present study is aimed to assess CO and PRE in this specific population. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all < 60 yrs CRPC pts from participating institutions, treated with DOC. We recorded the pre and post-DOC clinical history, the DOC treatment details and outcomes. We have also assessed the ability of a series of selected 18 clinical factors to predict DOC response through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: To date we have collected a consecutive series of 98 pts from 16 Italian hospitals. The median age was 57 yrs (range 41-60). The median baseline PSA was 84 ng/ml (range 2-2721); 93% of the pts had bone metastases while 49%, 9%, and 13% showed nodal, liver and lung metastases, respectively. All but 8 pts received DOC with a 3-week standard schedule: the median number of received DOC courses was 8 (range 1-14). The main grade 3-4 toxicities were anemia (4 pts), neutropenia (15 pts), febrile neutropenia (1 pt), peripheral neuropathy(1 pt). A PSA reduction > 50% was observed in 61% of the pts while 14% and 7% of the cases showed a partial and complete response, respectively. Having a Gleason score (GS) <8 [p= 0.032], a hemoglobin initial value >12 [p= 0.052], no nodal involvement [p= 0.101], resulted to be independently predictive of a PSA reduction > 50%. The median PFS and OS were 7 mos and 19 mos, while the 1-year PFS and OS rates were 17.3% and 70%, respectively. Conclusions: From these preliminary results, we failed to confirm a worse prognosis for younger CRPC since their survival outcomes are similar to those observed in the pivotal trials. Low GS, absence of nodal involvement and good hemoglobin levels are the only predictive factors.