bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a prognostic molecular signature composed of 3 genes involved in immunity in muscle-invasive bladder cancer.
Authors: LE Goux Constance , Damotte Diane , Vacher Sophie , Barry Delongchamps Nicolas , Sibony Mathilde , Terris Benoit , Zerbib Marc , Bieche Ivan , Pignot Geraldine 
Published: September 2018

e16029 Background: Immunotherapy in bladder cancer appears to be promising. The aim of this study was to evaluate the involvement of 33 genes of anti-tumor immunity in a wide range of muscle-invasive bladder cancers (MIBC) and to identify new prognostic markers. Methods: The levels of expression of 33 genes involved in anti-tumor immunity were analyzed by real-time quantitative RT-PCR on a consecutive series of 83 TVIM and 15 normal bladder samples. Tissue samples were taken on a cystectomy patch in patients operated between 2002 and 2006. All patients have signed informed consent. The results of the transcriptomic analysis were confirmed by immunohistochemistry and coupled with survival analysis. Results: Of the 33 genes studied, 24 (72.7%) were significantly overexpressed compared to normal bladder tissue. In univariate analysis, overexpression of OX40L was significantly associated with a pejorative prognosis in terms of recurrence-free survival and overall survival (p = 0.0027 and p = 0.014 respectively) while overexpression of CD8 was associated with a better prognosis (p = 0.024 and p = 0.029 respectively). A clustering analysis allowed us to identify a molecular signature composed of 3 genes ( OX40L, CD8 and TIGIT) allowing to separate the tumors into 3 distinct prognostic subgroups. In a multivariate analysis including all clinico-pathological and molecular factors significant in univariate, molecular signature was an independent prognostic factor in terms of recurrence-free survival and overall survival (p = 0.0007 and p = 0.007 respectively). Conclusions: We identified several genes involved in the immune response during bladder urothelial carcinogenesis, as well as a molecular signature composed of 3 genes ( OX40L, CD8 and TIGIT) associated with MIBC prognosis, suggesting a potential interest in Individual step.
Growing teratoma syndrome: Is it a subtype of germ-cell tumors or another entity?
Authors: Dogan Mutlu , Bal Oznur , Olcucuoglu Erkan , Algin Efnan , Zengin Nurullah 
Published: September 2018

e16040 Background: Growing teratoma syndrome(GTS ) is a process presenting with growing masses despite normal tumor marker levels(TML) after chemotherapy in non-seminomatous germ cell tumors (NSGCT). Methods: GTS patients between 2000-2016 were evaluated for clinicopathological features and survival outcomes retrospectively. Results: 17 (6,4%) of 266 NSGCT had GTS. Median follow-up was 57.7 ( 13.8-132.7) months. Median age 27 (17-51) years . Most (n = 14) of them had mixed germ-cell tumors & 12 had mature/immature teratoma in primary pathology at diagnosis. Most (n = 11) of them had stage 3 disease & 10 had high TML (S1-3). 11 GTS patients had good risk NSGCT. All (n = 17) had 4 BEP(bleomycin, etoposide, cisplatin) cycles. Recurrence occured in retroperitoneum (n = 13), lung (n = 3) & brain (n = 1). They were considered as GTS since they had normal TML despite growing masses. 5 patients were referred to surgery without salvage chemotherapy and they had teratoma on postoperative surgery. 13 had surgery after salvage chemotherapy (TIP: taxane, ifosfamide, platin) but 4 had unresectable disease and they had clinical benefit with interferone α2b. Two operated patients had diffuse necrosis on pathology whereas others had documented teratoma. Median DFS was 12.3 ( 5.7-18.8) months whereas median OS was 64.8 (15.5-158) months. 3 patients had no recurrence after surgery for GTS. 9 had salvage chemotherapy (gemcitabine/oxaliplatin, TIP) for NSGCT metastatic lesions with TML elevation and 2 of them had autolog stem cell transplantation. Conclusions: GTS is rare in NSGCT, but it should be considered in NSGCT patients with both growing masses & normal TML after primary treatment approach. GTS patients surgery with resectable masses should be referred to surgery since teratoma without viable tumor seems to have less benefit from chemotherapy and/or radiotherapy. Interferon α2b might be an option in unresectable GTS.
PSA-recurrence after radical prostatectomy for intermediate/high risk prostate cancer: A helpful parameter or just a patient stress amplifier.
Authors: Spahn Martin , Kruithof-de Julio Marianna , Boxler Silvan , Furrer Marc-Alain , Thalmann George N. , Studer Urs E. 
Published: September 2018

e16535 Background: Development of biochemical recurrence with a rising PSA level after radical prostatectomy causes significant anxiety for patients and treating oncologist. Management of these patients is controversial. Here, we characterize the natural course and pattern of disease progression and survival in men with biochemical recurrence (BCR) after radical prostatectomy (RP) for intermediate and high-risk prostate cancer (PCa) untreated until clinical failure (CF). Methods: Retrospective analysis of consecutive men with BCR after RP for intermediate/high risk PCa. All patients underwent RP+extended pelvic lymph node dissection. A PSA level > 0.2 ng/ml on two consecutive measures was considered BCR. None received neoadjuvant or adjuvant therapy prior to documented clinical failure by body imaging, which was performed at the time point of BCR or symptoms and at least once per year. Results: Of the 622 men with BCR included into the analysis, 267 (43%) had high risk PCa. Median follow-up after RP was 9.4 yrs. (IQR 4.8-15.1) and median time from RP to BCR was 1.4 yrs. (IQR 0.4-3.6). Of the patients 324 (52%) never experienced CF (Æfollow-up from BCR 5.8yr, IQR2.1-11.9); 88 (14%) had local recurrence only; 59 (9%) had lymph node metastasis +/-local recurrence and 151(24%) distant metastasis. The median times from BCR to CF were: 9.5 yrs. (IQR 5.6-13.5) for local failure; 4.9 yrs. (IQR 3.1-8.8) for lymph node failure and 5.6 yrs. (IQR 3-10.5) for distant failure. The 10-yrs cancer specific (CSS) and overall survival (OS) of the entire group from time point of BCR was 78% and 66%, respectively. 5- and 7-yrs conditional CSS from time of CF was strongly depended on recurrence pattern and ranged from 90% and 79% (local only) to 70% and 47% (lymph node+/-local) and 47% and 36% (distant mets), respectively. PSA-doubling time < 12 months and > 2 positive nodes were independent predictors of outcome in multivariate analysis. Conclusions: These data may be useful in informing men with intermediate/high risk PCa regarding the natural course of PSA recurrence and counseling the timing of additional therapies.
Relative bioavailability (BA) and bioequivalence (BE) study of abiraterone acetate (AA) fine particle (AAFP) with methylprednisolone (MP) and a reference formulation with prednisone (PN) in healthy male subjects.
Authors: Hussaini Azra , Olszanski Anthony J. , Stein Cy Aaron , Bosch Bill , Nemeth Paul 
Published: September 2018

e16538 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer when taken in combination with PN. The originator AA (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic (PK) variability. AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology™) that was designed to provide improved BA. In a prior study in healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg when given in the fasted state. In this study, AAFP was evaluated in subjects in a fasted state with steady state (SS) MP, an alternative steroid to PN. Methods: Subjects aged 18–50 years were randomized in a crossover design to receive MP (4 mg BID) or PN (5 mg BID) for 12 days in Period 1. On Day 11 of Period 1, subjects given MP received a single dose of AAFP 500 mg (test) and subjects given PN received a single dose of OAA 1000 mg (reference). After a 2-week steroid washout period, subjects received the alternate treatments in Period 2. Results: There were no statistical differences with regard to abiraterone AUC ( P≥0.38) and Cmax ( P= 0.22) between AAFP 500 mg and OAA 1000 mg (Table). Geometric mean ratio (GMR), a measure of BE, was 95.9% (90% CI: 86.0–106.9%) for AUC0-∞, 99.2% (90% CI: 88.7–110.9%) for AUC0-t, and 116.8% (90% CI: 102.2–133.4%) for Cmax. GMR of AUC0-∞ and AUC0-t, fell within the 80–125% range for BE, and Cmax 90% CI was just outside the upper limit. The coefficient of variance (CV) for both AUC and Cmaxwas smaller for AAFP compared with OAA. Both treatments were safe and well tolerated. Conclusions: AAFP 500 mg with MP gave comparable exposure to OAA 1000 mg with PN with respect to Cmaxand AUC. Less drug exposure variability was observed with AAFP compared with OAA. Reduced PK variability could improve clinical outcomes and warrants further study. [Table: see text]
SM88/SMK non-hormonal therapy in recurrent or untreated prostate cancer.
Authors: Hoffman Steve , Rothman John , Del Priore Giuseppe , Stega Jeanetta 
Published: September 2018

e16540 Background: Prostate cancer (PC) has a poor prognosis. Androgen deprivation therapy is effective but has unacceptable short and long term side effects. SM88 (modulators of mTOR, mitochondrial stress, CYP3a4 and tyrosine isomers) is a novel combination of anti-cancer therapies with previously reported favorable results yet low toxicity in a heterogeneous group of 30 patients with cancer. We now report on a PC cohort treated with SM88. Methods: Retrospective chart review. Results: Between 2012 and 2014, 6 men with PC were treated with SM88, administered 5 days/week over a 6-week treatment cycle. SM88 consisted of daily oral and subcutaneous injection of the components. The average age was 54 years (range 32-66). Five (83.3%) were Caucasian, 1 (16.7%) was Hispanic. patients with prostate cancer were treated with SM88 daily, Monday-Friday, for between 6 to 31 wks (median 11). Four patients had castrate resistant disease, two declined ADT. One had failed prior chemotherapy (see Table). All subjects were not receiving other therapy. One subject died of disease complications approximately 3 months after starting treatment but only received approximately 20 days of therapy over a 6 week cycle. Three patients had PSA nadir responses of >90% reduction over pretreatment peak levels (see table). Two others had radiographic SD for between 10-14 wks. There were no significant toxicity except cutaneous hyperpigmentation. The duration of responses ranged from 10-114 weeks. Best overall responses included 2 patients with complete biochemical response. Four subjects improved their ECOG score during treatment and 2 had no change. Conclusions: SM-88 appears to be well tolerated and to have anti-tumor activity in prostate cancer without androgen deprivation toxicity. Additional confirmatory prospective studies in prostate are ongoing and planned in other cancers. [Table: see text]
Evaluation of immunological efficacy of Japanese herbal medicine, hochu-ekki-to and keishi-bukuryo-gan, in patients with castration-resistant prostate cancer under personalized peptide vaccination.
Authors: Koga Noriko , Moriya Fukuko , Waki Kayoko , Yamada Akira , Itoh Kyogo , Noguchi Masanori 
Published: September 2018

e16584 Background: This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan, in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Methods: Seventy patients with CRPC were randomly assigned (1:1) to receive PPV plus HMs, or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 peptides derived from cancer antigens according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL), immunoglobulin G (IgG), regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (Mo-MDSC) and interleukin-6 (IL-6) responses were measured before and 8th vaccination. Clinical outcomes were also analyzed. Results: The combination therapy of PPV with HMs was well tolerated without severe adverse events but had no significant impact on antigen-specific IgG and CTL, Treg and clinical outcomes. The combination therapy of PPV with HMs stabilized the frequency of M0-MDSCs (1.91% to 1.92%, p = 0.96) and serum levels of IL-6 (19.2 pg/ml to 16.1 pg/ml, p = 0.63). On the other hand, the frequency of Mo-MDSC and levels of IL-6 in the PPV alone were significantly increased (0.91% to 1.49% for Mo-MDSC and 9.2 pg/ml to 19.4 pg/ml for IL-6, respectively). Conclusions: These results suggested that the combination usage of HMs reveals a potential to prevent the immunosuppression induced by Mo-MDSC or IL-6 during the immunotherapy. More research is needed to validate the findings of the present study. Clinical trial information: 000010290.
Vulvar cancer in Germany: Increase of incidence and change of tumor-biological characteristics in the period 1974-2013.
Authors: Barinoff Jana , Sehouli Jalid , Holleczek Bernd 
Published: September 2018

e17031 Background: Incidence of vulvar cancer in Germany is increasing. Gynecological oncologists reported to observe increasing numbers of women presenting with small tumors. The aim of the presented study is to validate this observation on a population level and to extend available incidence data. Methods: Data from the population-based Saarland Cancer Registry (CR) were used and included 1,136 female patients diagnosed with invasive vulvar cancer (ICD-10 code: C51) between 1974 and 2013. Multiple imputation methodology was used to overcome loss of precision and potential bias. Incidence trends were investigated with regard to patient and tumor characteristics. Results: During the study period, the age standardized rate of incidence increased from 1.6 to 7.9 cases per 100,000 women per year (+390%). Since 1989, the incidence of squamous cell carcinoma increased from 1.7 to 7.1 (+320%), whereas no increase was observed in other morphologic types. Simultaneously, the incidence of small vulvar tumors <= 2 cm (T1) increased from 0.8 in 1989-93 to 6.6 in 2009-13 (the proportion of T1 tumors increased from 34% to 79%, respectively). Patients aged >= 75 years suffered from more advanced disease at the time of diagnosis. Conclusions: The detailed analyses revealed that the observed increase in vulvar cancer in the past 15 years mainly resulted from newly incident squamous cell carcinomas. Furthermore, the analyses showed an almost exclusive increase of T1 tumors. An increase in vulvar cancer incidence as shown for Germany could not be observed for any other European country.
When advanced ovarian cancer is not ovarian cancer.
Authors: Dood Robert , Fleming Nicole D. , Coleman Robert L. , Westin Shannon Neville , Sood Anil 
Published: September 2018

e17066 Background:Tissue diagnosis of advanced ovarian cancer (OC) is not universally obtained prior to up-front surgery. This study sought to investigate non-OC cases discovered in the systemic laparoscopic (LSC) workup of presumed advanced OC. Methods: A prospective cohort of presumed advanced OC patients (based on elevated CA125 and/or imaging) presenting to our center without confirmed pathologic diagnosis. Patients with non-OC pathology confirmed in workup were characterized and compared to those with confirmed ovarian pathology using standard statistical tests. Results: 365 patients presented between 5/30/12 and 11/16/16. Non-OC was found in 27 cases (7.4%), including benign ovarian pathology (48%), and metastatic uterine (11%), breast (7%) and gastrointestinal (19%) cancers. A majority used diagnostic LSC or assessment at time of up-front surgery (see Table) for diagnosis. Non-OC cases were less likely to be confirmed by FNA or core biopsy, were more common in Asian patients, had better ECOG scores, and had a lower CA125. Only 1 non-OC patient (uterine sarcoma) received neo-adjuvant chemotherapy. Conclusions: A systematic LSC approach to advanced stage OC minimizes incorrect chemotherapy chemotherapy administration. Asian patients and those with low CA125 values are at highest risk of a false diagnosis of OC, but did not routinely have a diagnostic opportunity prior to systematic LSC. [Table: see text]
Characterization of differential genetic expression profiles in mesenchymal and epithelial components of uterine and ovarian carcinosarcomas.
Authors: Hernandez Blanquisett Abraham , Lopez-Reig Raquel , Romero Ignacio , Lopez-Guerrero Jose Antonio , Machado Isidro , Ballester Carmen Illueca , Ore Martin , Poveda Andres 
Published: September 2018

e17104 Background: Gynecologic carcinosarcomas (GCS) are rare tumors with poor prognosis. Reasons include a high percentage of advanced stage at diagnosis and a low response to conventional treatments. GCS constitutes a model for research in both tumoral heterogeneity and the epithelial-mesenchymal transition (EMT) process. Our aim is to define molecular expression heterogeneity in GCS distinct morphologic components. Methods: A retrospective, single institution, IRB approved study of 13 patients diagnosed with GCS was undertaken. Total RNA was extracted from representative FFPE tissue blocks of both the epithelial and mesenchymal components. The expression profile for each component (n = 26) was determined using the GeneChip WT Pico Reagent Kit and the Clariom D Array (Affymetrix Inc., Santa Clara, CA, USA). Robust multi-array normalization (RMA) and t-statistics was used for detecting differentially expressed genes between the studied conditions. Genes with a p-value < 0.05 and with an absolute fold change (FC) value > 1.5 were selected as significant. Results: A total of 13 cases representing 26 distinct samples, 9 uterine (UCS) and 4 ovarian carcinosarcoma with a median age of 68 (range: 45-81), 38% presented FIGO IIIC-IV stage at diagnosis. Among UCS, 5 women had a previous personal history of breast cancer. A total of 101 genes appeared as differentially expressed between epithelial and mesenchymal components, highlighting 5 of them: HMGA2 (FC = 2.15, p = 0.04) and ERBB4 (FC = 2.14, p = 0.005) overexpressed in epithelial component and ANX2 (FC = 1.95, p = 0.0006), SPP1 (FC = 2.15, p = 0,005) and ERRFI1 (FC = 1.95, p = 0.001) overexpressed in mesenchymal component. Conclusions: This is the first expression profiling in GCS that helps identify candidate genes that show a distinct expression in mesenchymal and epithelial components that could have a potential prognostic and predictive role.
Inhibition of CK2 by CX4945 to induce autophagy-mediated cell death through dephosphorylating acetyl-CoA carboxylase in squamous cell carcinoma of head and neck cancer.
Authors: Su Ying-Wen , Cheng Jun-Jia , Huang Wen-Yu , Chang Yi-Fang 
Published: September 2018

e17503 Background: Accumulating evidence has shown that overexpression of casein kinase 2 (CK2) in patients with squamous cell carcinoma of head and neck (SCCHN) correlates with worsened survival. Strong expression of phosphorylated acetyl CoA carboxylase (pACC) was found to be an independent prognostic marker for patients with node-positive SCCHN. Computational analysis showed that ACC was a potential substrate for CK2, and CK2 inhibition can suppress ACC phosphorylation in non-cancer cells. CX-4945, also known as silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2 and is under clinical investigation for treating malignancies. Methods: We investigated the anticancer activity of CX-4945 in 3 aggressive SCCHN cell lines. Autophagy induction and interference with cellular metabolism were characterized. Results: CX-4945 induced autophagic cell death in SCCHN cells. CX-4945 treatment caused time- and dose-dependent lipid droplet accumulation, inhibition of ACC phosphorylation, depressed cellular levels of acetyl Co-A, and severely suppressed mitochondrial respiration, without altering the expression of stress-related proteins in the endoplasmic reticulum. Conclusions: The findings demonstrated that inhibition of CK2 by CX-4945 contributed to deranged cellular energy metabolism in SCCHN cells, leading to autophagy-mediated programmed cell death. CX-4945 targeting to CK2 may be a promising therapeutic strategy against SCCHN cancer.
Patterns of HPV testing and treatment decision in patients with SCCHN.
Authors: Zanotti Giovanni , Martini Jean-Francois , Uehara Roberto , Hallworth Pamela , Byrne Katherine 
Published: September 2018

e17526 Background: Human papillomavirus (HPV) is one of the main risk factors associated with squamous cell carcinoma of the head and neck (SCCHN). Although it is a prognostic factor, SCCHN patients are not routinely tested for HPV status because it may not be informative for therapy initiation. The objective of this study was to understand the real world testing patterns, and treatment decision of SCCHN patients. Methods: Real world data was gathered using Adelphi’s Disease-Specific Programme (DSP) - a real world, cross-sectional survey conducted in the USA, France, Germany and the UK (April - September 2016). The DSP incorporated 182 physician interviews (54 US, 128 EU) covering all stages of SCCHN caseloads and treatment patterns. Physicians also provided data for 8 consecutive consulting SCCHN patients regarding treatment patterns, progression, and symptoms. Results: A total of 2193 SCCHN patient cases were captured. HPV testing was carried out in 42% of patients within the DSP data set with no particular difference across the 4 countries. Of those tested, 35% of patients were HPV positive. Testing was mainly performed at the local level (51%, onsite or local hospital) apart from Germany where central testing was higher (73%). In over half of patients cases (54%) , physicians are unaware of the type of test performed for the HPV status determination; in fact, up to 10 different types of tests were used to determine the HPV status in this real world experience. Platinum based cetuximab and fluorouracil was used in 30% of the HPV positive patients while 20% received platinum monotherapy. In 2nd line, docetaxel/paclitaxel monotherapy was used in 22% of the patients. HPV negative patients also mainly received platinum based cetuximab and fluorouracil (27%) in 1st line, while in 2ndline, docetaxel/paclitaxel monotherapy was used in 20% of the patients. Conclusions: This analysis of real world treatment patterns and outcomes among SCCHN patients shows that HPV testing is not widely carried out for either patient characterization or to guide treatment decisions within this disease. Therapy choices were generally consistent standard clinical guidelines.