bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of expression of ERG oncoprotein with development of disease recurrence and prostate cancer-specific mortality.
Authors: Johnston Richard , Spencer Elysia Sophia , Qu Xiaoyu , Himmetoglu Ussakli Cigdem , Gordon Ryan Robert , Vakar-Lopez Funda , Lewinshtein Daniel , Lucas Jared , Dobi Albert , Mcleod David G. , Fang Min , Srivastava Shiv , Nelson Peter , Porter Christopher R. 
Published: March 2020

e15207 Background: ETS-Related Gene (ERG) protein is present in approximately half of prostate cancer (PCa) specimens and correlates with TMPRSS2-ERG rearrangement. ERG oncogenic activation is believed to be a causal genomic alteration in a significant portion of PCa, its prognostic value in disease progression remains uncertain. This study evaluated ERG levels at radical prostatectomy (RP) to determine if it was predictive of earlier relapse or prostate cancer-specific mortality (PCSM). Methods: From 1954-1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle. Recurrence was confirmed by tissue diagnosis or radiographic signs. Death certificates confirmed PCSM. Patients without tissue were excluded. 34 patients with metastases or PCSM were matched to patients without recurrence at a 1:2 ratio. Paraffin embedded tissue was stained with two anti-ERG monoclonal antibodies, clone 9FY (Furustao et al., PCPD, 2010) and clone EPR3864 (Epitomics, Burlingame, CA). A pathologist evaluated the nuclear expression intensity using a 4-point scale. Statistical analysis was performed on SAS. Results: Mean follow up was 10.26 yrs.Antibody 9FY detected ERG in 10/16 (62.5%) PCSM and 24/44 (54.6%) no recurrence patients. Cancer expression intensity was higher from patients that developed recurrent disease, 0.99 vs 1.59 (p = 0.0265) and PCSM 2.09 (p = 0.0002). Antibody EPR3864 detected ERG in 11/17 (64.7%) PCSM and 26/48 (52.1%) no recurrence patients. Cancer expression intensity was higher from patients that developed recurrent disease, 0.97 vs 1.64 (p = 0.011) and PCSM, 2.30 (p < 0.0001). The two antibodies were independent of PSA and grade and were highly correlated with each other (p < 0.0001). Conclusions: ERG expression at time of surgery was prognostic for the development of disease recurrence and PCSM. Previous studies have shown an increased lifetime risk of PCSM with ERG expression in a surveillance cohort. This is the first report linking PCSM to ERG expression in men treated with surgery. ERG scoring may be a useful metric to identify patients who would benefit from adjuvant treatment or closer follow-up, allowing more accurate individual patient treatment plans.
Oral low-dose cyclophosphamide, as a second-line agent, in patients with primary docetaxel refractory metastatic castration-resistant prostate cancer (mCRPC).
Authors: Shapiro Daniela , Symanowski James Thomas , Vogelzang Nicholas J. , Goodman Oscar B. 
Published: March 2020

e15210 Background: Docetaxel is the standard of care for treatment in mCRPC, yet docetaxel resistance is universal, presenting as primary refractoriness or developing after an initial response. While abiraterone and cabazitaxel are FDA approved after docetaxel failure, multiple other agents, including oral low dose cyclophosphamide (OLDC), have also been utilized with some clinical success. We have witnessed several remarkable responses to OLDC and sought to define clinical predictors of such responses. Methods: Twenty-one patients progressing on docetaxel were classified according to initial docetaxel response as either docetaxel non-responsive (DNR) or docetaxel responsive (DR). Patients were classified as DNR if an initial response to docetaxel by prostate specific antigen (PSA) working group-2 and RECIST criteria was absent, or if circulating tumor cells (CTC) numbers remained >5 at all assessed time points. Otherwise patients were classified as DR. All patients initiated OLDC (50-150 mg/day), and subsequent response to OLDC was determined by decrease in CTC, PSA and/or radiologically. Results: Of the DR patients 1/10(10%) responded, while for DNR patients the response rate was 7/11 (63.4%), p= 0.024 between the two groups. The median survival from the date of initial treatment with docetaxel was 84 weeks in initial responders, and 115 weeks in refractory patients (p=0.495). Conclusions: The data suggest that patients who are DNR have higher rates of response to OLDC compared DR patients and may benefit from second line OLDC. A study prospectively evaluating the role of initial response to docetaxel in predicting response to OLDC is warranted, as are additional molecular analyses of DNR patients.
Sipuleucel-T immunotherapy in clinical practice: Patient characteristics, tolerability, and survival.
Authors: O'Shaughnessy Matthew , Warlick Christopher , Ziegelmann Matthew , Konety Badrinath , Jha Gautam Gopalji 
Published: March 2020

e15211 Background: Sipuleucel-T has been shown to provide survival benefit to men with minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In the 18 months following FDA approval of sipuleucel-T, we sought to characterize patients referred for consideration of sipuleucel-T, determine the tolerability of therapy, and evaluate survival outcomes in clinical practice. Methods: We reviewed the records of patients referred to our institution for consideration of sipuleucel-T. Clinical characteristics, disease characteristics, and previous treatments were identified. Tolerability and adverse events were characterized. Results: Patients with minimally symptomatic mCRPC were offered sipuleucel-T (n=90), whereas patients with ECOG>1, progressive disease, or lack of metastases were not (n=11). Post chemotherapy patients started sipuleucel-T if their CD4 count was >400 at least 3 weeks following chemotherapy. Treatments were well tolerated, with 96% completing an entire series. Three patients did not complete treatment due to disease progression. The biggest challenge with sipuleucel-T therapy was disease control immediately before, during and post therapy. Androgen receptor blockade with nilutamide or high dose bicalutamide was used to control the disease during this time. Mean patient age was 69.8±9.7 years and all had ECOG status of 0-1. 40% of patients had minimal metastases, while 36% and 19% had moderate or extensive metastases. Median survival time (MST) for men >65 years who received sipuleucel-T was 17.6 months, whereas MST for men ≤65 years was not reached. There was no significant difference in overall survival (OS) between these groups (p=0.27). When stratified by disease burden, we found that OS of patients with extensive disease was shorter than men with mild or moderate disease burden (p=0.002 and p=0.04), with MST of 6.0 months. MST was not reached for men with mild and moderate disease burden. Conclusions: Sipuleucel-T is well tolerated in clinical practice for well-selected patients with asymptomatic or minimally symptomatic mCRPC. Patients with extensive metastatic disease, even when minimally symptomatic, did not appear to benefit from sipuleucel-T.
Salvage focal versus salvage total cryoablation for radio-recurrent prostate cancer: Seven years experience.
Authors: Ukimura Osamu , Abreu Andre Luis de Castro , Leslie Scott , Sohji Sunao , Silverman Paul , Gill Inderbir S , Bahn Duke 
Published: March 2020

e15212 Background: Salvage cryoablation (SC) of the whole prostate is a curative option for radio (RT)-recurrent prostate cancer (PCa). Focal SC has emerged as an option for minimizing morbidity. We present our 7-year experience of oncological and functional outcomes of Salvage Focal (SFC) and Salvage Total (STC) Cryoablation (CRYO) for RT-recurrent PCa. Methods: From Dec 2003 to Aug 2010, 50 men underwent SFC (n=25) or STC (n=25) for RT-recurrent PCa. SFC patients had biopsy-proven unilateral PCa and underwent a hemi-CRYO of the prostate. STC patients underwent CRYO of the whole prostate gland. All patients were evaluated to exclude metastases prior to treatment. Two freeze-thaw cycles were used to perform transperineal prostate CRYO under TRUS guidance. Follow up was assessed by PSA, TRUS, biopsy and questionnaires at 3, 6, 12, 24 and 36 mth. Results: Median (range) age, PSA and Gleason score for the SFC group were 71 y (59-81); 2.8 ng/ml (0-8.2) and 7 (6-8), while those for STC were 73 y (57-83), 3.9 ng/ml (0.1-12) and 7 (6-9), respectively. Oncological outcomes: Within one year after SC, the median percent PSA-decrease was 89% for SFC and 98% for STC. The median (range) follow up was 31 mth (4-90) for SFC and 53 mth (12-92) for STC. No patient died. One patient treated with STC developed bone metastases. Using the Phoenix criteria (PSA nadir + 2 ng/ml), 8 SFC and 3 STC patients had biochemical failure (BF), and the 5-year biochemical free survival (BFS) was 54% and 86% respectively (p=0.05). In those patients with no BF, the median PSA remained stable, ranging from 0.2 to 0.6 ng/ml for SFC and 0.1 to 0.1 ng/ml for STC during the follow up period. Follow up biopsy-proven cancer occurred in 2 patients in the SFC group (both on the untreated side), and in 1 patient in the STC group. Functional outcomes: New onset urinary incontinence occurred in none (0) of the SFC vs 3 (13%) of the STC patients. One (4%) patient in the STC group developed a recto-urethral fistula. Conclusions: Salvage Focal and Total CRYO after RT-failure are feasible and safe. Although STC had a favorable BFS compared with SFC, there was no significant difference in disease specific or overall survival between groups. SFC offered comparable cancer control to STC with lower morbidity.
Overall survival (OS) prognostic factors in metastatic castrate-resistant prostate cancer (mCRPC) patients retreated with docetaxel (D).
Authors: Shah Shilpa Rashmikant , Albany Costantine , Hahn Noah M. 
Published: March 2020

e15213 Background: Until recently, few post-D treatment options existed for mCRPC patients (pts). In pts taken off of first-line D for reasons other than progressive disease (PD), retreatment with D at the time of PD was a commonly used strategy. While several prognostic nomograms have been developed for mCRPC patients, none have exclusively examined prognostic factors in D retreated patients. In the present study, we aimed to characterize baseline clinical factors associated with OS outcomes in D retreated mCRPC pts. Methods: Between 1/2007 and 10/2010, all mCRPC pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the IRB approved biorepository protocol. Participants completed a demographic and clinical questionnaire and provided a blood sample. Only mCRPC pts retreated with D with confirmed dates for D first-line completion, D retreatment, and OS were included in this analysis. At D retreatment, patient age, Gleason Grade (GG), presence of pain, time to progression after first-line D therapy, visceral metastases, ECOG performance status, PSA, and PSA doubling time (PSAdt) were examined by Cox proportional hazards model for significant associations (p < 0.05) with OS outcomes. Results: 30 mCRPC pts retreated with D were identified. Complete data were available on 22 pts which formed the analysis cohort. Demographics included: mean age – 69.1 yrs, Caucasian/African-American – 21/1, median GG 8, 55% pain present at baseline, median time from first-line D – 8.6 mo., 30% visceral mets, ECOG 0/1/2 – 3/17/2, mean baseline PSA – 536 ng/ml, mean baseline PSAdt – 2.7 mo. By Cox proportional hazards model, baseline PSA (p = 0.006) was significantly associated with D-retreatment OS with a trend toward significance in patients with pain at baseline (p = 0.059). No other significant associations were identified. Conclusions: Baseline PSA levels were significantly associated with OS outcomes in mCRPC pts retreated with D. Validation and examination of additional clinical variables is warranted in larger datasets.
Expression and the prognostic relevance of p53, Bcl-2, Bax, and Ki-67 in uterine leiomyosarcoma.
Authors: Gagua Irina Rezo 
Published: March 2020

e15506 Background: Uterine leiomyosarcomas (LMS) are rare, aggressive gynecological malignancies of the female reproductive tract. They represent less than 2-5% of all uterine malignancies. Despite the advanced modern treatment modalities, according to our data 5 year overall and disease - free survival of patients with LMS is 48,5± 4,2% and 44.3 ± 4.3 %, respectively. One of the challenging directions in advancing the prognosis and optimization of treatment tactics in LMS is investigating the expression of molecular-biological markers in tumor tissue. So, the aim of our study was to evaluate the expression of p53, Bcl-2, Bax, and Ki-67 and their prognostic relevance. Methods: A retrospective chart review was done to 198 patients with LMS treated at the N.N. Blokhin Russian Cancer Research Center from 1971 to 2009. Immunohistochemical (IHC) staining for 20 patients was performed for p53, Bcl-2, Bax and Ki-67. Negative and positive IHC staining was scored for each marker. Survival was determined from the time of initial diagnosis to last follow-up. Results: Ten (50%) patients with LMS expressed p53. P53+ patients mostly had multiple metastases, compared to p53– patients with solitar metastases (60% against 20%) (g<0,05). Eleven (55%) patients expressed Bcl-2 and 4 (20%) expressed Bax. In Bcl-2 + patients distant metastases were observed in 45,5%, compared to Bcl-2 – patients were we observed metastatic disease in 77,8% (p=0,068). Expression of ki-67 was observed in 15 patients (75%). Conclusions: LMS patients with p53 expression had a poorer survival compared to LMS patients with negative expression (g53+ — 26,7±18,4% and g53– — 80,0±12,6%) (g<0,05). On opposite, the disease-free survivla is better in bcl-2+ patients, compared to patients, who don’t express bcl-2 (47,2±19,6% and 28,1±18,0%, respectevly (g>0,05). We didn’t observe statistical significant difference in survival depending on Bax expression. LMS patients with Ki-67 expression had a poorer survival compared to LMS patients with negative expression (34,9±13,1% and 60,0±20,7% , respectively) (g>0,05). Our study indicates that p53 expression may serve as a prognostic marker for LMS patients.
Mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy for treatment of metastatic or recurrent uterine leiomyosarcoma.
Authors: Pant Alok , Lurain John Robert , Schink Julian C. 
Published: March 2020

e15523 Background: Metastatic or recurrent uterine leiomyosarcoma is often treated with chemotherapy. There are a limited number of viable regimens that are effective and well tolerated. Our objective was to evaluate the efficacy and toxicity of the MAID chemotherapy regimen in women with advanced uterine leiomyosarcoma. Methods: We conducted a retrospective analysis of 18 patients who received MAID chemotherapy for metastatic or recurrent uterine leiomyosarcoma between 1998 and 2010. Ten patients had received prior radiation therapy (3) and/or gemcitabine-docetaxel chemotherapy (8). The MAID regimen was administered intravenously in the hospital every three weeks as follows: mesna 120 mg/m2 prior to ifosfamide day 1 and 1.2 mg/m2 infusion over 8 hours starting immediately after the ifosfamide d 1-3, doxorubicin 15 mg/m2 d 1-3, ifosfamide 1.2 gm/m2 d 1-3, and dacarbazine 200 mg/m2 d 1-3. Disease response was evaluated by physical exam and imaging studies. Toxicity was assessed using NCI Common Toxicity Criteria. Results: Response to MAID chemotherapy was observed in 7 (39%) of 18 patients: 2 (11%) complete responses and 5 (28%) partial responses. Stable disease was noted in 8 patients (44%) and disease progression occurred in 3 patients (17%). There was no difference in response rates between patients who had received prior chemotherapy (3/8, 38%) and patients who had not received prior chemotherapy (4/10, 40%). A total of 90 cycles of chemotherapy were administered with a median of 5.5 (range 1-9) cycles per patient. Grades 3 and 4 toxicity requiring dose reduction of treatment delay complicated only 4 cycles (4.4%), including only one admission for neutropenic fever. There were no reported cases of cardiac dysfunction, hemorrhagic cystitis, or encephalopathy. The median progression-free survival was 10 (range 6-152) months for responders, 7.5 (range 3-120) months for those with stable disease, and 0 months for those with progressive disease. Conclusions: This is the largest series of uterine leiomyosarcoma patients treated with MAID chemotherapy. MAID chemotherapy in the dosage schedule utilized is a well-tolerated and effective regimen.
Patient surveillance after curative-intent treatment for ovarian cancer: What motivates clinicians?
Authors: Jamaluddin Nimah , Virgo Katherine S. , Gao Feng , Mutch David Gardner , Johnson Frank E. 
Published: March 2020

e15528 Background: In the US, ovarian cancer is diagnosed in > 20,000 women and causes >13,000 deaths each year. After curative-intent initial treatment, surveillance is common. Marked variation in surveillance intensity has been documented, suggesting overuse and/or underuse of resources. We sought to determine what factors motivate gynecologic oncologists as they design their surveillance strategies. Methods: A survey about ovarian cancer surveillance after initial treatment was mailed to all 943 members of the Society of Gynecologic Oncologists. The survey included 14 questions about putative motivating factors. Responses were submitted on a 10-level Likert scale. Motivating factors were ranked by the percent of responses for each of the ten levels. Results: 323 of the 943 (34%) responded; 283 responses were evaluable. “Current literature documents significant survival benefits” was the weakest motivating factor. Conclusions: The table below is consistent with the lack of evidence that any particular surveillance strategy confers any survival benefit. This is the first empirical evidence concerning factors that may motivate gynecologic oncologists in designing their surveillance strategies. Understanding motivating factors may be useful in devising methods to diminish the marked variation in strategies. [Table: see text]
Benign cystic ovarian neoplasms and procoagulant potential.
Authors: Iqbal Omer M. , Ersahin Cagatay , Hu Zhihong , Duan Xiuzhen , Hoppensteadt Debra 
Published: March 2020

e15538 Background: Ovarian cancer is one of the leading causes of increased morbidity and mortality worldwide. The fluid content of the cystic ovarian tumors has never been thoroughly analyzed. It is hypothesized that the fluid contents of the ovarian cystic tumors have procoagulant effects. Methods: Under an institutionally approved protocol, cystic fluids from ovarian neoplasms were collected (n=28) and analyzed to determine their procoagulant potential. Assays such as Thrombelastography (TEG, Helige, Germany), Platelet aggregometry (BioData, Horsham, PA), Fibrinopeptide A (FPA, Dade Behring, Marburg, Germany), Thrombin Antithrombin Complex (TAT, Dade Behring), and Zymuphen Platelet Microparticle Activity Assay (Hyphen BioMed, Neuville-Sur-Oise, France). Cerebral Array II (Randox, Crumlin, CO) was used to determine the levels of C-reactive protein (CRP), D-Dimer, Neuron Specific Enolase (NSE), Neutrophil Gelatinase-Associated Lipocalin (NGAL), soluble Tumor Necrosis Factor Receptor I (TNFRI) and Thrombomodulin. Results: The TEG parameters such as r- time, rk-time, k-time, MA, and angle were measured to be 17 , 22 , 5 , 54 mm, 55° with clear cell carcinoma, 18 , 24 , 6 , 58 , 54° with benign serous cyst compared to saline control values of 23 , 30 , 7 , 41 mm and 48° respectively. Platelet aggregometry showed increased aggregations when cystic fluids were supplemented in donor platelet rich plasma. The levels of Fibrinopeptide A were in the range of 24.1 and 56.6 ng/ml compared to a control value of 1.8 ng/ml. The TAT complexes were in the range of 6.7- 175 µg/ml compared to a control value of 0.7 ug/ml. The platelet microparticle measurements were markedly increased and were in the range of 10-45 nM for benign and malignant cystic fluids, compared to control values in the range of 2.3-6.6 nM. The results of CRP, D-Dimer, NSE, NGAL, TNFRI and TM were 9.28 mg/m (Normal=5.03) , >2000 ng/ml (N=227.34) , >120 ng/ml (N=10.50), >1229 ng/ml (N=228.16), 3.98 ng/ml (5.91) and 13.55 ng/ml (N=13.55) respectively. Conclusions: Benign ovarian tumors have prothrombogenic activity as much as the malignant tumors. Early surgical evaluation of clinically silent benign ovarian tumors should be considered.
Estrogen receptor α phosphorylated at Ser167: Distribution and prognostic implications in endometrial cancer.
Authors: Yoshida Yoshio 
Published: March 2020

e15539 Background: Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation, which is enhanced by ligand binding. Similar to Akt, ERα is activated through phosphorylation at Ser167, resulting in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and mitogen-activated protein kinase (MAPK)/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated- (p-) ERα. The purpose of this study was to determine the importance of Ser167 phosphorylation in EEC progression. Methods: Immunohistochemical staining of primary EEC surgical specimens (n=103) was carried out using antibodies specific for p-ERα and for p-Akt, p-mTOR/S6K1 and p-MAPK/RSK. and for p-Akt, p-mTOR/S6K1 and p-MAPK/RSK. Results: Patients positive for nuclear Ser167 phosphorylation had significantly shorter relapse free survival. Althoughthe result was not significant, levels of nuclear p- tended to be higher in advanced-stage ECC patients. Nuclear p-ERα was significantly positively correlated with p-MAPK and p-S6K1. Conclusions: The amount of nuclear ERa Ser167 phosphorylation is associated with p-MAPK and p-S6K1, and may be important in EEC progression and outcome.