bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor contact length used as a biomarker to predict extracapsular extension, lymph node involvement, and biochemical recurrence.
Authors: Viana Públio , Rodrigues Thiana , Mota Davi alves martins , Guglielmetti Giuliano , Bastos Diogo Assed , Fazoli Arnaldo , Nahas William Carlos , Coelho Rafael , Cordeiro Mauricio , Horvat Natally 
Published: May 2019

e16588 Background: Prostate cancer (PC) is the cancer most commonly diagnosed in men and the second leading cause of death. Multiparametric magnetic resonance imaging (mpMRI) is the benchmark imaging standard for local staging of PC. Patients with pathological extraprostatic tumor (pEPE) have a worse prognosis than those with confined organ disease with a higher risk of biochemical recurrence (BCR) after radical prostatectomy (RP). These factors, in addition to positive lymph nodes (PLN), are pivotal in the decision-making process regarding treatment. However, the subjective MRI analysis has low sensitivity in the detection of EPE and is plagued by the low interobserver agreement. Tumor contact length (TCL) is an objective parameter of mpMRI defined as the length of prostate cancer in contact with the prostate capsule, which may provide additional information about prostate cancer outcomes. We aimed to evaluate TCL as a predictor of pECE, PLN, and BCR in patients undergoing RP. Methods: In this Institutional Review Board approved single-institution prospective study, we update the follow-up of 148 patients and included 31 new patients, with prostate cancer who underwent prostate MRI before radical prostatectomy from March 2014 to november 2018. TCL was measured using T2-weighted magnetic resonance images.Postoperative prostate-specific antigen (PSA) values were obtained every 3 months in the first year, then biannually and annually thereafter. BCR was defined as PSA≥0.2ng/mL. The exclusion criterion was prior treatment. Results: The median follow-up was 44 months. 76/179 (42,4%) patients had pEPE, 12/179 (6,7%) had pLN, and 29/179 (16,2%) had BCR. TCL values were significantly higher in patients with pathological pECE ( 20,6 mm vs 9,9 mm, p < 0.001). Using a cut-off of 11,9 mm we found area under curve (AUC) of 0,71 to predict pathological ECE, with sensitivity 72,5% and specificity 67,5% . Using a cut-off of 16,5 mm we found AUC of 0,64 to predict BCR, with sensitivity 54,2% and specificity 67,8% and with a cut-off of 21,7 mm the AUC to predict PLN was 0,77, with sensitivity 66,7% and specificity 83,6%. Conclusions: We prospectively demonstrated in our population that TCL values were significantly higher in patients with pEPE , PLN and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making.
The internet bias toward nontraditional first line prostate cancer treatments.
Authors: Landau Danny , Landau Alec 
Published: May 2019

e16594 Background: Despite relegation to relapsed localized disease per National Comprehensive Cancer Guidelines, we have noticed upticks in cryotherapy and High-intensity focused ultrasound (HIFU) as initial therapy for prostate cancer in Orlando. We believe internet advertisements play a role in this. When directly questioned, patients confirm our belief. We conducted internet searches to analyze the information available to patients. Methods: Utilizing common search engines, Google and Bing, searches were conducted using the terms “cryotherapy prostate cancer” and “HIFU”. The first three pages of general results and sponsored results were broken into categories. The categories include verified information (VI) properly describing the therapies and their indications, advertisement for traditional care (TC) centers, centers that promote nontraditional care (NTC), or information that is unclassifiable/ misleading (other). A final search was done for “alternative prostate cancer treatments”. The results that mentioned HIFU or cryotherapy were counted manually. Results: Cryotherapy Google general search In total, unverified information or advertisements for centers practicing outside of traditional norms were represented in: General search combined: 26/82: 32% Sponsored searches: 54/75: 73% The general search term “alternative prostate cancer” search including HIFU or Cryotherapy General Search: 3/55 (0.05%) Sponsored Search: 8/39 (21%). Conclusions: Using general search terms, it seems that there is a wealth of information that can influence a patient’s decision making on prostate cancer treatment. While there is more information promoting HIFU/ cryotherapy on sponsored searches, general searches have potential for misunderstanding and abuse in nearly a third of cases.[Table: see text][Table: see text][Table: see text][Table: see text][Table: see text][Table: see text][Table: see text][Table: see text]
Prognostic impact of tristetraprolin (TTP) and PTEN loss and assessment of associated immune infiltrates in localized prostate cancer (PrCa).
Authors: Hamid Anis , Werner Lillian , Huang Ying , Vicier Cecile , Morel Katherine , Ellis Leigh , Sweeney Christopher 
Published: May 2019

e16601 Background: We previously showed that loss of PTEN by quantitative multiplex immunofluorescence (qIF) is associated with relapse after prostatectomy. Low expression of TTP, which modulates the NF-kB pathway and inflammation, is prognostic for lethal PrCa after surgery. We also showed, with this assay, that low CD8+ density is a poor prognostic marker. We hypothesized that co-loss of these independent cell signaling regulators leads to poorer outcomes, and low TTP is associated with a modified tumor immune microenvironment. Methods: qIF was performed on tissue microarrays from a cohort treated by radical prostatectomy (N = 128). PTEN and TTP expression intensity was measured continuously at a cell-by-cell level and summarized per patient using binary thresholds. Immune marker (CD3, CD8, PD-L1, PD-1, FOXP3) density (positive cells/area) was evaluated in glands and stroma. Median time to biochemical recurrence (BCR) and metastasis (MFS) was estimated using Kaplan Meier method and log rank test summarized associations between expression and time to event outcomes. Wilcoxon test assessed the association of biomarker status and immune marker density. Results: Of 128 patients with a median follow-up of 14.6 years, 67 (52%) had BCR. 102 had staining for PTEN, 103 for TTP and 86 for both. Key findings are detailed in Table. PTEN and TTP co-loss was associated with the shortest time to BCR and worst MFS. TTP-low tumors had an immune infiltrate deplete of CD8 (p = 0.0004) and PD-1 (p = 0.0001) expressing cells. No significant differences in immune markers were noted by PTEN status. Conclusions: Co-loss of regulators of inflammation and cell cycling is associated with incremental risk of relapse in localized PrCa. Loss of TTP is associated with a diminished effector T cell infiltrate and may be a modifier towards a ‘cold’ PrCa immune microenvironment. Table: Clinical outcomes by biomarker status [Table: see text]
Effect of pectasol-c modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in non- metastatic biochemically relapsed prostate cancer (BRPC) patients (pts): Primary outcome analysis of a prospective phase II study.
Authors: Keizman Daniel , Frenkel Moshe A. , Peer Avivit , Rosenbaum Eli , Margel David , Sarid David , Neiman Victoria , Leibovitch Ilan , Sternberg Itay Aharon , Boursi Ben , Gottfried Maya , Dresler Hadas , Eliaz Isaac 
Published: May 2019

e16609 Background: 30% of pts with localized PC will have a biochemical relapse post local tx. Their optimal tx remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long-term benefit remain undefined, and it is associated with significant toxicities. Thus, evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, known to be involved in cancer pathogenesis. Pre-clinical data suggest that P-MCP is active in PC, and in two previous smaller clinical trials in biochemically relapsed prostate cancer (BRPC) pts, a PSA response/stabilization rate of 57%-75% was noted. In the present study, we aimed to evaluate the safety and PSA dynamics of P-MCP tx in BRPC pts. Methods: non-castrate non-metastatic BRPC pts were enrolled in a prospective phase 2 study of oral P-MCP tx, at 4.8 grams X 3/day for 6 months (mos). Eligible pts had 3 consecutive rise of PSA, without any tx in the previous 3 mos, a normal level of serum testosterone, and negative scans. The primary outcome was the rate of pts without disease progression (DP) (clinically, biochemically with stabilization/decrease of PSA or improvement of PSA doubling time = PSADT, and radiologically) at 6 mos. A Sample size of ≥ 50 pts provided 85% power to assess a decrease in DP rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. Pts that did not progress at 6 mos, were treated for subsequent 12 mos (secondary outcome of long term effect). Herein we report the results of the primary outcome analysis. Results: 53 pts were enrolled. Median age was 74 years. Tx of the primary tumor consisted of surgery in 13% (n = 7), radiation in 60% (n = 32), and both in 26% (n = 14). No pt had tx related grade 3/4 toxicity. One pt withdrew his consent after 1 mos. At present, 46 pts completed 6 mos of tx, and were analyzed for the primary outcome. Among them, 20% (n = 9) had grade 1 toxicity (all gas and bloating ). The primary outcome was met in 76% (n = 35), that did not progress at 6 mos of tx. Of these, 59% (n = 27) had a stabilization/decrease of PSA, 70% (n = 32) had an improvement (increase) of PSADT, and all had no metastases on scans at 6 mos. DP at 6 mos was noted in 24% (n = 11: PSA only in 20%, n = 9; PSA and scans in 4%, n = 2). Full cohort data (additional 6 pts that will complete 6 mos of tx) will be available by June 2019. Conclusions: The present study suggests the safety and potential benefit of P-MCP tx on progression of BRPC. Clinical trial information: NCT01681823.
Influence of the new FIGO classification for cervical cancer on patients’ survival: Retrospective analysis of 265 histologically confirmed cases with FIGO stages Ia to IIb.
Authors: de Gregorio Nikolaus , De Gregorio Amelie , Ebner Florian , Schochter Fabienne , Friedl Thomas W. P. , Huober Jens Bodo , Janni Wolfgang , Widschwendter Peter 
Published: May 2019

e17006 Background: End of 2018 a new FIGO Classification for cervical cancer was published, mainly revising stage Ib and introducing a new stage IIIc, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. Methods: We retrospectively analyzed all cases of cervical cancer stage I to IIb who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome parameters according to the new stage. Results: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage Ib and from any stage to stage IIIc1. Kaplan Meier curves for new stages showed a significant difference for stages I vs. II vs. III (log rank test, p < 0.001). Overall, patients that were upstaged had a significant worse PFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive Ib or IIb tumors were upstaged to IIIc tumors. Conclusions: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.
Trends in opioid use in patients undergoing primary surgery for cervical cancer.
Authors: Tucker Katherine , Farnan Laura , Bensen Jeannette T , Doherty Irene , Gehrig Paola A. 
Published: May 2019

e17014 Background: In response to the opioid epidemic, restrictions on prescribing opioids for pain management may result in unintended consequences for patients with cancer-related pain. Factors that place women at higher risk for opioid misuse include age, insurance status, tobacco use and a diagnosis of cervical cancer. Our objective was to describe describe patterns of opioid use and prescribing practices over time. Methods: We performed a retrospective study of patients diagnosed with cervix cancer enrolled in our institution’s Health Registry/Cancer Survivorship Cohort from 5/2010-3/2017. The dataset included demographics, clinicopathologic data, reported opioid use (prior, during and after treatment) and prescription history from the EMR after IRB approval. This preliminary analysis included frequencies, cross-tabulations, and measures of distributional characteristics. Results: Of the 122 patients identified, 94 had surgery. Mean age at diagnosis was 44.7 yrs and BMI was 29.13. Eighteen (19.1%) patients had an opioid use history. Given changes in EMR documentation in 2014, 37 were excluded as assessment of opioid use and prescriptions was limited to only MD documentation. While there was no pre-defined protocol change, post-operative opioid prescribing practices changed in late 2014. From 5/2014-11/2014, 17 patients underwent surgery with 88% receiving prescriptions for 40 tablets of an opioid. From 12/2014-12/2016, 40 patients underwent surgery with 27.5% receiving prescriptions for 40 tablets of an opioid and 65% receiving 20-30 tablets. Prior to 12/2014, 1/16 patients (6.3%) required additional opioids postoperatively with no documented complication compared to 9/40 patients (22.5%) after 12/2014. In this group, most frequent prescriptions were coming from the patient’s gynecologic oncologist and/or a primary care provider. Conclusions: We saw a small increase in additional opioids after the routine number prescribed declined. However, this comprised a minority of patients. Monitoring of the opioid needs and use among women with cervix cancer will aid in the development of clinically-tailored guidelines to replace the current reactionary restrictions on treatment for all patients.
Cervical cancer outcomes after chemoradiation and brachytherapy in New York City comparing public versus private hospitals.
Authors: Berger Amnon Asher , Ishaq Omar , Curtin John Patrick , Pothuri Bhavana , Kehoe Siobhan Marie , Schiff Peter B. , Boyd Leslie R. , Lymberis Stella C. 
Published: May 2019

e17018 Background: In the US, cervical cancer (CC) disproportionately impacts minorities and women with insufficient access to care. In our department, patients (pts) with advanced CC referred from a public hospital (PbH) and a private hospital (PrH) are treated with the same integrated team of physicians. We sought to determine whether referral source affects outcome post definitive chemoradiation (CRT) and brachytherapy (BT) for CC pts. Methods: An IRB approved retrospective review was conducted for pts diagnosed with CC and treated with definitive CRT. All pts were treated with external beam RT and chemotherapy followed by intracavitary BT boost (median 7 Gy x 4 fractions) delivered via two insertions of intracavitary BT two weeks apart with image-guided CT/MR delineation. Disease free survival (DFS) and overall survival (OS) were analyzed with the Kaplan-Meier method. Multivariate Cox hazards analysis was run to identify the effects of covariates, using R v3.5.1. Results: Between 7/2009 and 9/2017, 106 pts were diagnosed with FIGO stage IA(1), IB(22), IIA(10), IIB(46), IIIA(3), IIIB(24) and IVA(2) CC. 81 (76.4%) pts were diagnosed and received chemotherapy and operative insertion at PbH, 25 (23.6%) at PrH. Median age was 54 years (y), range (28-83). At median follow-up of 32.2 months (3.8-110.2), local control was 82%. 5-y DFS and OS was 62.4% and 84.2%. 19.8% pts were diagnosed at age 65 or greater. PbH pts were diagnosed at a younger median age of 52.4y (28.1-77.7) compared to 59.8y (30-83) at PrH (P = 0.03). PbH vs PrH pts were more likely to present at earlier stages I/II (79% vs 56%), than stages III/IV (21% vs 44%), p = 0.04 and have better outcomes; PbH vs PrH DFS was 65.0% vs 54.5% (P = 0.1), while OS was 89.3% vs 54.9% (P = 0.01). In Cox multivariate analysis, only stage at diagnosis was a significant independent predictor of survival (P = 0.006). Conclusions: Our data suggests that patients referred from a public hospital do not have worse outcomes when treated by a centralized multidisciplinary team. PrH pts presented at older age, more advanced stage and had worse OS than PbH pts. Twenty percent of pts diagnosed with advanced CC were above age 65, highlighting the need for continued screening.
Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan.
Authors: Zeybek Burak , Manzano Aranzazu , Bianchi Anna , Bonazzoli Elena , Buza Natalia , Lopez Salvatore , Perrone Emanuele , Manara Paula , Bellone Stefania , Zammataro Luca , Santin Alessandro 
Published: May 2019

e17028 Background: Recurrent disseminated cervical cancer is a discouraging clinical entity with 1-year survival rates between 10-15%, and development of novel, effective treatments remains an unmet medical need. We investigated the preclinical efficacy of IMMU-132 (sacituzumab govitecan), an antibody-drug conjugate (ADC) comprised of a humanized anti-trophoblast-cell-surface-antigen (Trop-2) antibody (hRS7), conjugated with a hydrolysable linker to the active metabolite of irinotecan (SN-38), against Trop-2 positive primary cervical cancer cell lines and mouse xenografts. Methods: Trop-2 expression was evaluated in 151 cervical tumors and 5 primary tumor cell lines by immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cervical cancer cell viability against IMMU-132, non-targeting control ADC, and naked antibody (hRS7 IgG) was evaluated using flow-cytometry-based assays after 48-72 hours of incubation at a concentration of 0.05, 0.5, 1, 2, 4, and 10 nM of each agent. In vivo antitumor activity was tested in xenograft models with 3+ Trop-2 expression. Results: Out of 151 cervical tumors, 123 were squamous cell carcinoma (SCC), 26 were adenosquamous/adenocarcinoma, 1 was neuroendocrine carcinoma, and 1 was clear cell carcinoma. Strong diffuse staining was seen in 61% (75/123) of SCCs, and 92% (24/26) of adenocarcinoma/adenosquamous cancers. The neuroendocrine carcinoma was also strongly positive, while there was no staining in the clear cell carcinoma. Four out of five (80%) primary cervical cancer cell lines evaluated overexpressed Trop-2 as determined by RT-PCR and flow cytometry. Trop-2 positive cell lines showed high sensitivity to IMMU-132 in vitro, with IC50-values in the range of 0.18 to 0.26 nM ( P= 0.02). In contrast, a Trop-2 negative cervical cell line was highly resistant to the ADC with similar IC50 for IMMU-132 and control ADC. In xenografts, twice-weekly intravenous administration of IMMU-132 for three weeks demonstrated significant tumor growth inhibition compared to controls ( P≤0.001). Overall survival was significantly increased in mice treated with IMMU-132 ( P= 0.014) when compared to naked antibody and ADC-control groups. Conclusions: Sacituzumab govitecan may represent a novel class of active drugs for cervical cancers overexpressing Trop-2. Clinical trials are warranted.
Glucocorticoid receptor expression in Müllerian carcinosarcomas.
Authors: Steiner Meghan , Veneris Jennifer Taylor , Lastra Ricardo , Weroha S. John , Hou Xiaonan , Maurer Matthew John , Heinzen Ethan P. , Oberg Ann L. , Fleming Gini F. , Conzen Suzanne D. 
Published: May 2019

e17038 Background: Carcinosarcomas (CS) are aggressive gynecologic malignancies defined by a biphasic tumor histology of carcinomatous and sarcomatous components. High expression of glucocorticoid receptor (GR) is associated with aggressive tumor biology in triple-negative breast, ovarian, and endometrial cancers. GR activation results in transcriptional regulation of epithelial-mesenchymal transition (EMT) genes. Therefore, we hypothesized that the sarcomatous component of Müllerian CS may be associated with relatively higher GR expression compared to the carcinomatous portion. Methods: Müllerian CSs from the University of Chicago tissue bank diagnosed from 5/19/2009  8/25/2014 were identified and pathology confirmed (RL). In addition, we evaluated GR expression in a mouse PDX CS model. Immunohistochemical expression of nuclear estrogen (ER), progesterone (PR), androgen (AR), and GR was quantified using the H-score. Scores between the sarcomatous and carcinomatous components were compared using a paired t-test. Results: Mean GR H-score was relatively higher in the sarcomatous vs carcinomatous component, overall (144.44 vs 38.89, P = 0.0014). Mean H-score also differed between sarcomatous and carcinomatous components for ER (3.06 vs 63.06, P = 0.016), PR (1.67 vs 47.22, P = 0.004), and AR (0 vs 2.78, P = 0.056). The significantly higher sarcomatous GR expression was replicated in IHC evaluation of the mouse PDX model. Conclusions: GR expression is significantly higher in the sarcomatous than the carcinomatous component of Müllerian CS, while ER, PR, and AR expression is significantly lower. Recent data suggest that an EMT gene signature is more prominently expressed in the sarcomatous versus carcinomatous component. We hypothesize that GR expression and activity may mediate EMT gene expression and represent a therapeutic target for CS. [Table: see text]
Selective and nonselective GR antagonists in combination with chemotherapy in ovarian cancer PDX models.
Authors: Veneris Jennifer Taylor , Hou Xiaonan , Weroha S. John , Heinzen Ethan P. , Maurer Matthew John , Oberg Ann L. , Conzen Suzanne D. , Fleming Gini F. 
Published: May 2019

e17039 Background: Treatment strategies are needed for platinum-resistant recurrent ovarian cancer. Glucocorticoid receptor (GR) is associated with poor prognosis in ovarian cancer. GR signaling inhibits chemotherapy-induced cell death via transcriptional regulation of anti-apoptotic proteins. Non-selective (mifepristone) and selective GR antagonists (Relacorilant, Corcept Therapeutics) are under clinical development (eg. NCT02046421, NCT03776812). We hypothesized that GR antagonism would improve chemotherapy sensitivity in ovarian cancer patient-derived xenograft (PDX) models. Methods: Five PDX models were selected based on GR expression above median RNA seq levels. Tissues were transplanted into 300 female SCID-Bg mice at the Mayo Clinic. Once tumor diameter reached 0.2 cm, mice were randomized into treatment arms (2-25 mice per arm) and treated intraperitoneal (i.p): control (9% saline, CTL) on day 0 (D0), 1, 7, 8, 14, 15, 21, 22; mifepristone (MIF), 15 mg/kg D0, 1, 7, 8, 14, 15, 21, 22; relacorilant (134), 20 mg/kg D0, 1, 7, 8, 14, 15, 21, 22; carboplatin (CBDCA) at the MTD, 51 mg/kg D1, 8, 15, 22; CBDCA + MIF; CBDCA + 134. Tumor area was measured by ultrasound weekly (D0-D28), and the ratio calculated relative to D0. Tumor growth curves were compared between arms for each PDX via a linear mixed effects regression test of coincident curves. Time to progression was also evaluated and will be presented. Results: In 1/5 models (PH160), CBDCA + MIF significantly suppressed tumor growth compared to CBDCA alone (p < 0.05, Table 1). Addition of 134 to CBDCA did not suppress tumor growth compared to CBDCA alone in any model. In the 2 models with no difference of CBDCA versus CTL (PH160, PH454), addition of a GR antagonist to CBDCA suppressed tumor growth versus CTL. Conclusions: Addition of GR antagonists can improve response to chemotherapy. Work is ongoing to identify the GR transcriptional network, tumor, and host characteristics which predict responses to GR antagonists. [Table: see text]