bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastatic prostate cancer at diagnosis: Clinical presentation in the post-PSA era
Authors: Dickstein R. J. , Kreshover J. E. , Milose J. C. , Gignac G. A. 
Published: August 2020

e16159 Background: Prostate cancer (CaP) has varying biologic behavior. Prostate-specific antigen (PSA) screening dramatically diminished the presentation of patients (pts) with metastatic CaP from 5.6% in 1990 to 1.5% in 2003 as evidenced by the CaPSURE database. Our institution has a uniquely diverse demographic and socioeconomic population and we sought to identify pts with metastatic CaP at diagnosis to evaluate contributing factors. Methods: We retrospectively reviewed all pts charts diagnosed with CaP as identified by ICD-9 code (185) between January 1st 2003 and October 31st 2008 after cross referencing with the term metastatic. Pts progressing from localized disease were excluded. Data was collected on pts initially presenting with metastases. Results: Sixty-one pts presented initially with metastatic CaP at a median age of 68 years old (45 –90) and a median PSA of 92 ng/mL (4.4 –3463). Digital rectal exam was normal in 8 pts (13%) and abnormal in 43 (70%). Median body mass index was 27.2 (16.9 –46.7) with 26 pts (42%) being smokers and 20 (32%) non-smokers. Thirty-six pts (59%) had a Charlson Comorbidity Index score of 0, 10 (16%) a score of 1, 10 (16%) a score of 2, and 5 (8%) a score of ≥ 3. Fifteen pts (24%) were Caucasian, 42 (68%) black [24 (39%) African American, 10 (16%) Caribbean, 8 (13%) African], 1 (1%) Hispanic, 1 (1%) Asian, 1 (1%) Albanian, and 1 (1%) Indian. Presenting symptoms were comprised of 32 pts (52%) with lower urinary tract symptoms including hematuria, urinary retention, and hydronephrosis, 21 (34%) with bone pain, 3 (4%) with neurologic deficits, and 17 (27%) were asymptomatic. Forty-seven pts (77%) underwent prostate biopsy of which 33 (70%) had high grade (Gleason ≥ 8) tumor. Conclusions: CaP initially presenting as metastatic disease is a rare event in the post-PSA era, but may result from lacking primary health care screening, poor patient compliance, or inherent predisposing factors of tumor biology. Our analysis identifies a predominantly non-Caucasian population of patients, contrasting the CaPSURE database, who are otherwise healthy. We plan on performing comprehensive analyses on all patients with metastatic CaP at Boston Medical Center. No significant financial relationships to disclose.
Does the day or season of operation predict biochemical recurrence after radical prostatectomy?
Authors: Hirsh A. L. , Lee D. J. , Hruby G. , Benson M. C. , McKiernan J. M. 
Published: August 2020

e16162 Background: Outcomes in hospital based medicine are associated with the experience and availability of the medical staff, as mortality and morbidity rates increase each summer with new medical graduates. Hospital staff members are thought to be more fatigued and less available towards the end of the week and on weekends. However it is not known if there is a difference of outcomes based on the season or day of the week. We sought to identify if different seasons or surgical days of the week can predict poor outcomes and biochemical recurrence (BCR) in radical prostatectomy (RP). Methods: A retrospective analysis of the Columbia Urologic Oncology database was performed. 1865 consecutive men underwent RP from 1991 to 2008 by three surgeons. Data was collected in an institutional review board approved registry, with median follow up of 36 months. BCR was defined as two consecutive PSA levels > 0.2 ng/ml. Stratified cox regression methods were used to model the relationship between surgeon, preoperative variables, season, day of the week, and BCR. Winter was defined as December through February, spring as March through May, summer as June through August, and fall as September through November. Results: The mean age of the men undergoing RP was 61.2 years (37–79), with a mean preoperative PSA of 8.12. 424 men (22.7%) had positive surgical margins, and the mean estimated blood loss (EBL) was 1119cc. Patient age (p=0.68), preoperative PSA (p=0.32), EBL (p=0.51), and positive surgical margin rate (p=0.78) were not significantly different between each day. Men undergoing RP did not have different rates of BCR according to the day of the operation (p=0.58) or season (p=0.997). The particular season and day of the operation were not significantly associated with BCR, and were not independent predictors of BCR in a multivariable model after adjusting for preoperative PSA, Gleason sum, tumor stage, and surgeon. Conclusions: Patient surgical outcomes and BCR rates after RP are not associated with the particular season or day of the week of the procedure. These findings suggest that men undergoing RP do not need to be concerned about the particular season or day when scheduling the procedure. No significant financial relationships to disclose.
Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma
Authors: Santin A. , Bellone S. , El-Sahwi K. , Buza N. , Tavassoli F. A. , Silasi D. , Azodi M. , Schwartz P. E. , Rutherford T. J. , Pecorelli S. 
Published: August 2020

e16502 Background: Uterine serous papillary carcinoma (USPC) represents a variant of endometrial cancer characterized by a highly aggressive biologic behavior and inborn resistance to chemotherapy. MT201 is a fully human monoclonal antibody recently developed against epithelial cell adhesion molecule (EpCAM). In this study we have evaluated the potential of MT201 as a novel therapeutic strategy against USPC. Methods: EpCAM expression was evaluated by real time-PCR and immunohistochemistry (IHC) in a total of 54 USPC fresh-frozen biopsies and paraffin embedded tissues. EpCAM surface expression was evaluated by flow cytometry in 6 freshly established USPC cell lines derived from advanced stage USPC patients. Sensitivity to MT201 antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) was tested in standard 4-hour chromium (51Cr) release cytotoxicity assays. Results: EpCAM transcript was significantly overexpressed in fresh frozen USPC when compared to fresh-frozen normal endometrial cells (NEC) [i.e., mean (minimum-maximum) copy number of 515.4 (31.5–1568.3) in tumor samples versus 8.1 (1.0–25.5) in flash-frozen NEC (p < 0.001)]. By IHC, EpCAM protein expression was found in 96% (26 out of 27) USPC samples and this expression was significantly higher when compared to normal endometrial cells (p < 0.01). High surface expression of EpCAM by flow cytometry was found in 83% (5 out of 6) of the primary USPC cell lines available to this study. Importantly, while primary USPC cell lines were highly resistant to natural killer dependent cytotoxicity in vitro, EpCAM positive cell lines were found highly sensitive to MT201-mediated ADCC. Human serum IgG did inhibit MT201-mediated cytotoxicity against USPC in vitro. Conclusions: These results demonstrate for the first time high EpCAM expression in uterine serous carcinoma at mRNA and protein levels and high sensitivity to MT201-mediated cytotoxicity in vitro by primary USPC cell lines. MT201 might be a novel and attractive therapeutic strategy in patients harboring advanced, recurrent or metastatic USPC refractory to standard treatment modalities. No significant financial relationships to disclose.
Population profiles of extra-ovarian and ovarian serous adenocarcinomas: Comparisons with grade stratification
Authors: Grimley P. M. , Matsuno R. , Anderson W. F. 
Published: August 2020

e16506 Background: Molecular studies of ovarian serous adenocarcinomas (OSC) have linked distinct patterns of gene expression or mutations to high or low tumor grade. This heterogeneity appears to be mirrored in two population subgroups delineated by age-specific incidence rates (ASIR) stratified by grade. We aimed to determine whether serous adenocarcinomas of the peritoneum (PSC) or fallopian tubes (FSC) comprised grade-related subgroups comparable to OSC. Methods: Data for women with invasive OSC (25,997 cases), PSC (2,157), and/or FSC (618) registered in the NCI's Surveillance, Epidemiology, and End Results program (1976–2005) were analyzed. Incidence rates (IR) stratified by grade were compared by year or age of diagnosis. Descriptive analyses were supplemented with tests for trend or age interaction by grade. Cancer-specific survival also was compared by grade (Kaplan-Meier estimator). Results: We observed trend interactions by grade for OSC, PSC, and FSC (p < 0.001); age-adjusted incidence rates rose more rapidly for high than low grade tumors over time. ASIR for OSC/PSC were higher for low than high grade tumors prior to age 40 years, after which rates became higher for high grade (p < 0.001 for age interaction by grade). ASIR were similar for FSC but interpretation was limited by small sample sizes. Unilateral carcinomas were far more common for FSC than OSC (90.9% versus 40.6%). Actuarial cancer-specific cumulative survival was worse for high than low grade tumors (all anatomic sites). Conclusions: Trend and survival analyses both were consistent with a biologically significant high/low grade stratification of OSC, PSC, and FSC. For PSC, significant correlations to ASIR by high/low grade were consistent with two population subgroups as defined for OSC; and also appeared congruent with molecular models that project dual pathways of carcinogenesis. For FSC, definitive correlations will require larger sample sizes. No significant financial relationships to disclose.
A phase II evaluation of pemetrexed (ALIMTA, LY231514, IND#40061) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group
Authors: Miller D. S. , Blessing J. A. , Krasner C. N. , Drake R. D. , Higgins R. , McMeekin D. S. , Puneky L. V. 
Published: August 2020

e16507 Background: To estimate the anti-tumor activity of pemetrexed in patients with advanced or recurrent carcinoma of the endometrium that failed on higher priority treatment protocols and to determine the nature and degree of toxicity. Methods: A multicenter phase II trial was conducted by the Gynecologic Oncology Group (GOG). Patients must have had advanced or recurrent measurable carcinoma of the endometrium and failed one prior chemotherapy regimen. Pemetrexed at a dose of 900 mg/m2 was to be administered as an IV infusion over 10 minutes every 21 days. Results: From May 1, 2006 to July 31, 2007, 27 patients were entered by ten member institutions of the GOG. A total of 101 cycles were administered with 27% of patients receiving five or more cycles. The treatment was well tolerated overall. More serious toxicities (grade 3 and 4) included anemia in 19%, leukopenia in 38%, neutropenia in 46%, and constitutional in 19%. No treatment related deaths were reported. One patient (4%) had a partial response. Twelve patients (46%) had stable disease and eleven (46%) patients had increasing disease. Median progression-free survival (PFS) was 2.7 months and overall survival (OS) was 9.4 months. Conclusions: Pemetrexed has minimal activity in the treatment of recurrent or persistent endometrial carcinoma at the dose and schedule tested. [Table: see text]
Does repeat usage of bevacizumab in patients with progressive recurrent ovarian cancer offer a survival advantage?
Authors: Richardson D. L. , Backes F. J. , Seamon L. G. , Seamon L. G. , Hurt J. D. , Cohn D. E. , Fowler J. M. , Copeland L. J. , O'Malley D. M. 
Published: August 2020

e16510 Background: Many studies show bevacizumab (BEV) has activity in the treatment of recurrent ovarian cancer, especially when combined with cytotoxic chemotherapy. However, it is uncertain whether BEV should be continued if a patient progressives on treatment which includes BEV. Therefore, our objective is to compare response rates (RR), progression-free survival (PFS), and overall survival (OS) between patients who continued on BEV after progression on BEV (BPB) versus patients who were treated with cytotoxic chemotherapy without BEV (no BPB). Methods: All patients who received treatment with BEV (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution were identified. Patients who received additional therapy after progression on BEV were included. Patients who were treated on GOG 218 or received first-line BEV or had their first BEV therapy discontinued due to side effects from BEV were excluded. RR were assessed using RECIST criteria, CA125 levels, or progressive disease symptoms. PFS was defined as the period from initiation of the treatment regimen until progression or date of last contact. OS was defined as the period from initiation of the second treatment regimen until death or date of last contact. Results: 35 patients met inclusion criteria. The median number of previous chemotherapy regimens was 4 (range 1–8). About 50% of the patients had a CR or PR prior to progressing on BEV. There were 27 patients in the BPB group, and 8 patients in the no BPB group. 13% (1/7) of patients responded to cytotoxic chemo after BEV, and 15% (4/27) of patients responded to repeat treatment with BEV, p = 1. The median PFS for patients in the no BPB group was 4.6 months (95% CI 1.6–5 mo), compared to 4.8 months (2.7–7.5 mo) for patients in the BPB group, p = 0.11. There was no difference in OS, 9.8 months (95% CI 2.73- ∞) versus 8.4 months (95% CI 5.8–15.6 months) p = 0.43 for patients in the no BPB group versus the BPB group. One patient in the BPB group died of a bowel perforation. Conclusions: We offer the first comparison of PFS and OS in patients treated with cytotoxic chemotherapy ± BEV after progression on BEV. After progressing on a BEV regimen, there was no difference in the PFS, OS or RR in those pts treated with or without BEV with an overall OS < 1 year. [Table: see text]
Gene therapy for pretreated ovarian cancer via a novel fiber modified mdr1 targeting conditionally replicating adenovirus
Authors: Beyer I. , Bauerschmitz G. J. , Breidenbach M. , Dragoi A. , Niederacher D. , Janni W. , Rein D. T. 
Published: August 2020

e16513 Background: Ovarian cancer (OC) is a leading cause of death from gynecologic malignancies. Oncolytic adenoviruses (CRAd) are a new approach for cancer treatment. In this study, we constructed a fiber-modified CRAd containing the multi drug resistance gene (mdr) 1 promoter to control viral replication (Ad5/3MDR1). Antineoplastic agents induce mdr1-gene expression triggering chemoresistance. Methods: RT-PCR was performed for expression of mdr1 in cell lines and primary patient samples. We constructed Ad5/3MDR1luc1 to determine relative activity in a variety of cell lines, patient samples, and normal control cells. Replication and oncolysis of Ad5/3MDR1 were assessed in naïve and pretreated OC cell lines. The specificity of viral replication was analyzed in co-culture of pretreated OC cell lines and human fibroid cells. A mouse model of peritoneal carcinomatosis was used to evaluate the efficacy of a combined chemo- and gene therapy for OC. Results: RT-PCR reveals a significantly (p < 0.05) increased expression of the mdr1 gene in OC cell lines and patient samples. Compared to the ubiquitous cmv promoter, mdr1 showed a high level of activity in chemoresistant OC cell lines (7.3%-11.5 %) and OC patient samples (8.8%-12.4%), whereas activity in normal fibroblasts (<1%) was low. Ad5/3MDR1 shows highly selective replication in chemoresistant OC cells in a co-culture with fibroblast cells. Cell killing of Ad5/3MDR1 was comparable to Ad5/3Δ24, a CRAD that replicates in cancer cells inactive in the Rb/p16 pathway, in chemotherapy naïve OC cells but displayed significantly (1.5 log; p < 0.05) higher oncolytic potency in pretreated OC cell lines and primary cells from pretreated OC patients. Moreover, in a therapeutic orthotopic mouse model of peritoneal carcinomatosis, dramatically enhanced survival was noted with Ad5/3MDR1. Conclusions: Ad5/3MDR1 is a promising candidate for gene therapy of metastatic chemoresistant OC with great potential for clinical testing. No significant financial relationships to disclose.
The effects of body mass index on curative radiation therapy in cervical carcinoma: An analysis of complications and survival
Authors: Thaker P. H. , Gao F. , Zighelboim I. , Powell M. A. , Rader J. S. , Mutch D. G. , Kizer N. 
Published: August 2020

e16520 Background: Recently, the rates of obese and overweight patients have increased dramatically. However, the effect of body mass index (BMI) have not been evaluated in treatment outcomes for patients with advanced stage cervical cancer receiving definitive chemotherapy and radiation therapy, and is the purpose of this study. Methods: After obtaining approval from the Washington University Human Studies Protection Office, a retrospective cohort study (n = 321) was performed on all cervical cancer patients with stage IB1 with positive lymph nodes or ≥ stage IB2 from January 1998 to January 2008. The median duration of follow up was 60 months. BMI was calculated using the National Institute of Health online BMI calculator. Main outcomes were overall survival, disease free survival, and radiation complications such as radiation enteritis/cystitis, bowel obstruction, and fistula formation. Univariate and multivariate analyses were performed, and Kaplan-Meier curves were generated. Results: Underweight patients (BMI<18.5 kg/m2) compared to normal weight (BMI = 18.5–25 kg/m2) and overweight/obese (>25 kg/m2) have a higher actuarial complication rate (p = 0.0137). Regardless of weight there is no difference in disease free survival. However, underweight patients have a significantly poorer overall survival than those patients with a higher BMI (>18.5 kg/m2) (p < 0.001). Conclusions: Underweight patients have a diminished overall survival compared to normal or obese cervical cancer patients. This is of clinical relevance when counseling underweight cervical cancer patients who will be cured of the disease with chemotherapy and radiation therapy, but have a significant risk of suffering potentially fatal complications from treatment. Further study needs to be done to elucidate this relationship further. No significant financial relationships to disclose.
Correlation between preoperative serum CA 125 and surgicopathologic prognostic factors in endometrial cancer
Authors: Espino-Strebel E. , Luna J. T. 
Published: August 2020

e16524 Background: Poor prognostic factors dictating the need for extended surgical staging among endometrial cancer patients can be accurately determined only after laparotomy. An adequate preoperative work-up is thus necessary to tailor surgical treatment individually. This prospective study was conducted to determine the correlation between preoperative serum CA125 and surgicopathologic prognostic factors in endometrial cancer. It also aimed to determine the CA125 cutoff value which best predicted the prognostic factors to which it was correlated. Methods: Endometrial cancer patients diagnosed from October 2006 to July 2008 who were eligible for primary surgical treatment were included. Serum CA125 determination was done by a chemiluminescent enzyme immunoassay prior to surgery. All patients underwent laparotomy, peritoneal fluid cytology, extrafascial/radical hysterectomy, bilateral salpingooophorectomy, bilateral pelvic lymph node dissection, and para-aortic lymph node sampling. Specimens were examined for tumor differentiation, lymphovascular space invasion, depth of myometrial invasion, cervical, adnexal, and vaginal involvement, pelvic and para-aortic lymph node metastases, and peritoneal fluid cytology. Pearson r correlation test was used to evaluate the correlation of serum CA125 with the prognostic factors. A receiver operating characteristic curve was used to determine the optimal cutoff value of preoperative CA125. Results: Ninety patients with endometrioid endometrial adenocarcinoma were included. Preoperative serum CA125 was significantly correlated with deep myometrial invasion (p = 0.02), adnexal metastasis (p = 0.01), pelvic (p < 0.01), and para-aortic node involvement (p<0.01). It was also significantly correlated with extrauterine disease (p = 0.01). A cutoff value of 55U/mL can predict extrauterine spread with 53.85% sensitivity, 84.38% specificity and 75.56% accuracy. Conclusions: Preoperative serum CA125 has a significant correlation with deep myometrial invasion, adnexal metastasis, pelvic and para-aortic lymph node involvement, and extrauterine disease at a cutoff value of 55U/mL. It is recommended that serum CA125 determination be part of the preoperative work-up of endometrial cancer patients. No significant financial relationships to disclose.
Dalteparin low molecular weight heparin (LMWH) in ovarian cancer: A phase II randomized study
Authors: Elit L. , Lee A. , Julian J. , Hoskins P. , Julian D. , Parpia S. , Levine M. 
Published: August 2020

e16529 Background: Up to 17% of women with ovarian cancer (OC) develop venous thromboembolism (VTE). LMWH reduces the risk of VTE and may have antineoplastic effects because tissue factor on OC cells stimulates tumor growth. A multicentre, open-label phase II randomized trial was undertaken to identify a potentially efficacious and safe dose of dalteparin to investigate its antineoplastic potential in OC. Methods: Women with newly diagnosed epithelial OC were randomized to receive taxane and platinum chemotherapy (CT) and one of 3 doses of dalteparin (50 IU/kg, 100 IU/kg, or 150 IU/kg) subcu daily during the first 3 cycles of CT. With each cycle of CT, patients had a CA125 and were assessed for bleeding or VTE. A response was defined as a ≥50% reduction in CA125 from baseline sustained for at least 28 days (according to GCIG criteria). To select the best LMWH group with a ≥ 80% response rate (RR) {vs. 60% with CT alone} with 90% probability, 39 patients per group were needed. Patients were followed until the end of CT. Results: 77 women were randomized and 72 of them completed follow-up. Compliance with injections was > 80%. There were no major bleeding events and 3 patients in the highest dose group had minor bleeding. There were no VTEs while on or within 7 days of finishing LMWH. There were 2 deaths attributed to the underlying OC. A 50% drop in CA125 by the start of cycle 4 was seen in 87% of the 50 IU/kg group, 92% of the100 IU/kg group, and 84% of the 150 IU/kg group, respectively. The corresponding RRs by the end of cycle 6 were 91%, 92% and 92%. Conclusions: Use of dalteparin is safe and well tolerated in women who are receiving CT for newly diagnosed OC. This therapy was effective in preventing VTE. A dose response effect on CA125 levels was not identified. [Table: see text]