bluuebunny/crossref_metadata_2025_split huggingface dataset:
NT5E expression and the immune landscape of prostate cancer (PC): An analysis from The Cancer Genome Atlas database.
Authors: Tripathi Abhishek , Lin Edwin , Nussenzveig Roberto , Yandell Mark , Pal Sumanta K. , Agarwal Neeraj 
Published: May 2019

e16591 Background: Immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 pathway have shown modest activity in patients with advanced PC. Additional immunosuppressive mechanisms in the PC tumor microenvironment need to be investigated. Increased CD73 (encoded by NT5E) expression results in generation of immunosuppressive adenosine in the tumor microenvironment and has been associated with metastasis and poor survival in PC. Utilizing the TCGA dataset, we investigated the association of NT5E expression with the immune landscape of PC. Methods: RNA-seq data for 331 PC tumor samples and 51 normal adjacent tissue (NAT) samples was downloaded and log2 transformed. Patients were split into low, intermediate, and high expression groups based on NT5E expression (≤ -1, -1 to 1 and ≥1 standard deviation from the overall mean) in tumor and NAT. A tumor inflammation signature (TIS) reflecting an inflamed tumor phenotype was calculated based on the averaged tumor expression of 18 previously validated genes (Ayers et al, 2017). Abundance of infiltrating immune cell subsets was estimated based on expression of previously identified 782 immune metagenes (Charoentong et al, 2017). Immune cell abundance scores and TIS were compared between NT5E expression groups using the Mann-Whitney U test and the Bonferroni correction was used to control for false discovery rate. Results: NT5E expression in NAT was not associated with the TIS or expression of immune cell marker genes. In contrast, NT5E expression in tumor tissue correlated positively with TIS (P < 0.001). Compared to tumors with low NT5E expression, those in high NT5E expression group had higher expression of central memory CD4+, effector memory CD8+, type 1 helper, NK and regulatory T (Treg) cell markers. Conclusions: In our analysis, NT5E expression correlated with markers of inflamed tumor phenotype in PC. Although NT5E expression was associated with higher CD8+and CD4+ T cells, concurrent increase in Tregs could inhibit the infiltrating lymphocytes and promote tumor growth. Our findings indicate a possible role for the adenosine pathway as a mediator of immunosuppression in PC and a potential therapeutic target. AT and EL: Equal contribution
30-year extrapolations of overall survival (OS) and metastasis-free survival (MFS) from the SPCG-4 trial of radical prostatectomy (RP) versus watchful waiting (WW) in patients (pts) with early prostate cancer (ePCa).
Authors: Alrawashdh Neda , Oh Mok , Almutairi Abdulaali , Alkhatib Nimer S , Babiker Hani M. , MacDonald Karen , McBride Ali , Abraham Ivo 
Published: May 2019

e16597 Background: Bill-Axelson et al (NEJM, 2014) reported 18 year (y) mortality and metastasis (mets) data on ePCa pts randomized in the SPCG-4 trial to RP (n = 347) vs WW (n = 348) for all pts and by age < 65y (nRP= 157 nWW= 166) vs ≥65y (nRP= 190 nWW= 182). Using the 18y data, we estimated the cumulative incidence, OS and MFS curves, and absolute risk reduction (ARR) for death and mets up to 30y for all pts and pts < 65y vs ≥65y. Methods: Published 18y SPCG-4 cumulative incidence curves for death and mets were digitized and parametric regression models were tested to fit the data. From these we estimated, for death and mets, the respective 30y cumulative incidences, OS and MFS curves with 95%CI; and ARR. ARRs for < 65y and ≥65y were compared using the chi-squared test. Results: The exponential regression model fit the data best. Over the 18 to 30y period, OS in all pts decreased from .81 to .69 in RP and from .72 to .56 in WW; in pts < 65y from .81 to .69 in RP and from .67 to .49 in WW; in pts ≥65y from .83 to .72 in RP and from .78 to .64 in WW. Over the same period, MFS in all pts decreased from .81 to .69 in RP and from .73 to .56 in WW; in pts < 65y from .81 to .69 in RP and from .67 to .49 in WW; in pts ≥65y from .78 to .64 in RP and from .75 to .59 in WW. OS and MFS 95%CI curves overlapped in pts ≥65y but not in pts < 65y. ARRs for death and mets of RP over WW are shown below by 2y interval. ARRs for death and mets were statistically different in pts < 65y but not in pts ≥65y. Conclusions: Extrapolated to 30y post randomization, RP shows better gains in OS and MFS over WW. RP is associated with significant reductions of death and mets: 19 more surviving pts and 20 more metastasis free pts per 100 pts among pts < 65y but not among pts ≥65y. These data enable clinicians to provide ePCA pts considering RP vs WW with up to 30y prognostic information. This facilitates informed patient decision making, especially among those age < 65y. [Table: see text]
Physician benefit-risk preferences for non-metastatic castration-resistant prostate cancer treatment (nmCRPC).
Authors: Srinivas Sandy , Mohamed Ateesha F. , Appukkuttan Sreevalsa , Botteman Marc , Ng Xinyi , Joshi Namita , Horodniceanu Erica , Waldeck Reg , Simmons Stacey J. 
Published: May 2019

e16610 Background: Second-generation androgen receptor inhibitors (SGARIs) are now available for the management of nmCRPC based on improvements in metastasis-free survival. We used a discrete choice experiment (DCE) to explore how U.S. oncologists and urologists may balance different SGARIs’ risks (i.e., adverse events [AEs]) against survival, when treating an otherwise asymptomatic patient population. Methods: We invited oncologists and urologists treating nmCRPC patients via online panels to participate. The survey included 14 treatment choice questions, each comparing 2 hypothetical medication profiles, which varied in terms of 5 safety and 2 efficacy attributes. These attributes were selected via qualitative interviews and pre-testing with physicians, patients, and caregivers. We described safety attributes (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency and efficacy attributes (overall survival [OS] and time to pain progression) in terms of duration of effect. We used a main-effects random parameters logit model to estimate preference weights and importance scores for each attribute. Results: 74 oncologists and 75 urologists completed the survey. Among safety attributes, physicians were most concerned with cognitive problems, fractures, and fatigue. Physicians placed 36% more importance on reducing cognitive problems from severe to none compared to improving OS by 12 months instead of 3 months. On average, physicians were willing to trade off 7.1 months of OS for a reduction in fatigue severity from severe to mild/moderate and 0.8 months of OS for a reduction in fatigue from mild/moderate to none. Physicians were willing to trade off approximately 4.2 and 5.0 months of OS for reduction in fracture risk from 8% to 5%, and 5% to 0%, respectively. Conclusions: As shown in this DCE, physicians making treatment decisions for largely asymptomatic nmCRPC patients, were willing to trade substantial amounts of survival to avoid AEs. These results emphasize the importance of carefully balancing the risk-benefit profiles of SGARI therapy when treating this patient population, to ultimately optimize the overall quality of the patients’ survival.
Race as a prognostic factor in high-risk prostate cancer: An NCDB analysis.
Authors: Kodiyan Joyson , Guirguis Adel , Yanagihara Theodore , Ashamalla Hani 
Published: May 2019

e16611 Background: It is commonly held that race serves as a significant prognosticator in prostate cancer. However, it is unclear if race affects all risk groups similarly. We sought to analyze whether race, either African American (AfA) or Caucasian (C), impacted overall survival of men receiving standard of care treatment using a large national database. Materials and Methods: All data was obtained from the NCDB (National Cancer Database), a collaborative effort between the American Cancer Society and Commission on Cancer. The database initially contained 1,294,126 cases of prostate cancer diagnosed between 2004 and 2014. Those with documented race and minimum follow up of 4 years were analyzed in this study. Patients were eliminated from the study if they had metastatic or nodal disease, received chemotherapy, or had non-invasive disease. Patients were grouped into two cohorts as per NCCN criteria: favorable risk and unfavorable risk. All patients received definitive therapy appropriate for their risk group. AfA and C men were matched 1:1 within each risk cohort using propensity scores, and multivariate analysis was conducted on these matched cohorts. Results: The final analyzed cohort included 75,217 patients with median follow-up time of 5 years. 10-year OS for favorable risk and unfavorable risk cohorts were 78% and 73% respectively (log rank, p < 0.001). In the favorable risk cohort, 5,422 C cases were matched to 5,422 AfA cases. C men had superior OS compared to AfA men, 89% versus 86% at 8 years and 79% versus 79% at 10 years (HR 0.688, 95% CI 0.571-0.872, p = 0.0025). In the unfavorable risk cohort, 3,870 C cases were matched to 3,870 AfA cases. Race was not a significant prognostic factor for OS, 83% versus 83% at 8 years and 73% versus 71% at 10 years in C and AfA men, respectively (HR 0.961, 95%CI 0.837-1.103, p = 0.572). Conclusions: Race has no effect on overall survival in unfavorable disease while AfA race is a predictor for worse survival in favorable risk prostate cancer, independent of socioeconomic and demographic factors. This suggests that the biology of disease plays a significant role in favorable risk cohorts, but with more advanced higher risk disease, other factors besides race may play a more significant role.
Dynamics of the immune status in patients with cervical cancer receiving complex treatment with dendritic cell vaccine.
Authors: Menshenina Anna P. , Kit Oleg I. , Zlatnik Elena Yu. , Bondarenko Elena S. , Novikova Inna A. , Moiseenko Tatiana I. , Frantsiyants Elena M. , Verenikina Ekaterina V. , Selezneva Olga G. , Adamyan Meri L. , Cherkasova Anna A. 
Published: May 2019

e17005 Background: The purpose of the study was to determine the influence of complex treatment with dendritic cell vaccine on the dynamics of the immune status of patients with cervical cancer. Methods: 17 patients with cervical cancer (CC) T2b-4аN0-1M0-1 received chemotherapy with combined radiotherapy to the pelvic area. Between courses of cytostatic treatment, patients underwent dendritic cell vaccination (DCV) planned individually depending on the treatment effect, which was evaluated by the results of examination, US, CT and MRI. A control group included 19 patients with locally advanced CC receiving standard polychemotherapy (PCT) and radiotherapy. Immune status of patients was evaluated by flow cytometry (FACSCantoII BD) including T, B, NK cells, Tregs (CD4+CD25+CD127dim), memory T cells (Тm) and naïve T lymphocytes (Th0) was determined in the dynamics of the treatment. Results were calculated as a percentage from the total number of lymphocytes, for Tregs – in % from CD3+CD4+ cells, for Тm and Th0 – in % from CD3+CD4+ and CD3+CD8+ cells. Results: 1 to 4 cycles of PCT with DCV caused a transient increase in Tregs after the 1st cycle, with further regression to the initial levels; other studied lymphocyte subsets remained unchanged. Only after 8 or more DCV cycles, a favorable immunological dynamics developed; however, it was not observed in controls. DCV increased levels of lymphocytes with potential cytotoxicity: CD3+CD8+ (from 19.0±2.0 to 28.8±1.5%), NK cells (from 12.0±2.0 to 21.2±1.9%). During DCV courses helper-inducer Tm amount rose from 51.7±6.3 to 69.7±4.3%, while in remission – CD8+Tm grew from 28.5±2.1 to 40.4±5.3% (p < 0.05 for all cases). Repeated DCV was satisfactorily tolerated by CC patients and, when used in complex treatment, caused a pronounced clinical effect. DCV did not lead to serious adverse events. Patients in remission are still observed. Conclusions: Treatment for CC with DCV causes a positive dynamics of the immune status, with the maximal effect after 8 and more DCV cycles. Remission is apparently maintained due to an increase in the level of TmCD8+ cells.
A single-center retrospective analysis to evaluate the prognostic role of lymph node density in patients with lymph node-positive cervical cancer.
Authors: Polasik Arkadius A. , Janni Wolfgang , Scholz Christoph , De Gregorio Nikolaus , Schochter Fabienne , Friedl Thomas W. P. , Widschwendter Peter 
Published: May 2019

e17013 Background: The aim of this retrospective analysis is to evaluate the prognostic role of lymph node density (LND), i.e. the ratio of positive lymph nodes to the total number of lymph nodes removed during surgery, in nodal-positive cervical cancer patients. Methods: Out of 266 patients with cervical cancer that underwent surgery including lymphonodectomy between 2000 and 2017 at the Department for Gynecology and Obstetrics of the University Hospital Ulm, 86 patients with positive lymph nodes were included in the analysis. According to former study results, patients were divided into two groups with LND < 10% vs. ≥ 10%. Univariable and multivariable cox-regression models (adjusted for age, histological subtype, grading, body mass index, R-status, lymphangiosis, histologically confirmed FIGO-status and chemotherapy) were used to evaluate the association between LND and both overall survival (OS) and disease-free survival (DFS). Results: In the 86 patients, a median of 42 lymph nodes were removed (range 11 – 107), and a median of 2 lymph nodes (range 1 – 25) were found positive. 57 (66.3%) patients had a LND < 10% and 29 (33.7%) patients had a LND ≥ 10%. There was no significant association between LND (≥ 10% vs. < 10%) and OS in both univariable (hazard ratio[HR] 1.49, 95% CI 0.72 – 3.07, p = 0.280) and multivariable survival analysis (HR 1.46, 95% CI 0.64 – 3.32, p = 0.372), respectively. However, LND was significantly associated with DFS in univariable analysis (HR 2.11, 95% CI 1.10 – 4.03, p = 0.024) and was found to be an independent predictor for DFS in adjusted multivariable analysis (HR 2.30, 95% CI 1.08 – 4.91, p = 0.031). Conclusions: LND ≥ 10% in patients with lymph node-positive cervical cancer is associated with a worsened DFS compared to patients with a LND < 10%. Thus, LND may be used as an independent prognostic marker and/or for risk stratification in these patients.
A phase I trial evaluating the safety and efficacy of weekly paclitaxel or cisplatin with electro-hyperthermia in patients with recurrent or persistent epithelial ovarian, fallopian tubal or primary peritoneal carcinoma (KGOG 3030).
Authors: Kim Kidong , Suh Dong-Hoon , No Jae Hong , Kim Yong Beom , Kim Jae Hoon , Kim Seung Cheol , Ju Woong , Kim Yun Hwan 
Published: May 2019

e17032 Background: To evaluate the safety and efficacy of weekly paclitaxel or cisplatin with electro-hyperthermia in patients with recurrent or persistent epithelial ovarian, fallopian tubal or primary peritoneal carcinoma. Methods: This prospective trial employed ‘3+3 design’ with no dose escalation. Initially, patients were randomized to weekly paclitaxel (70mg/m2) or weekly cisplatin (40mg/m2) with electro-hyperthermia until three patients in each arm were evaluable for dose-limiting toxicities (DLTs). A cycle was 4 weeks long and paclitaxel or cisplatin was administered at day 1, 8, 15. Targeting tumor beds, electro-hyperthermia was administered semi-weekly (8 time/cycle) for 1 hour per session. DLT was defined as any adverse event possibly or probably related to therapy, that required intensive care or was not recovered to grade 2 or lower within 3 weeks. If ≤1 patient in an arm experienced DLT, additional 3 patients were enrolled to that arm. Unevaluable patients (n = 4) were replaced. Finally, 12 patients (6 in each arm) were evaluated for toxicities, response rate, progression-free survival (PFS) and overall survival (OS). Results: Nine patients had high grade serous histology. Median number of previous regimen was 2 (range 1- 5) and median treatment-free interval from previous chemotherapy was 6 months (range 0 – 27). Nine patients were platinum resistant or refractory. No DLT was observed. Four grade 3 toxicities were observed (nausea 1, hematologic 3) in cisplatin arm. Overall response rate was 42% (5/12), median PFS was 4.3 months (range 1.7 – 11.8), and median OS was over 13.8 months (range 3.9 – > 38.5). Conclusions: Both weekly paclitaxel and cisplatin with electro-hyperthermia are safe enough to be tested in further studies. Chemotherapy with electro-hyperthermia was seems to be an effective treatment strategy for recurrent or persistent epithelial ovarian, fallopian tubal or primary peritoneal carcinomas. No significant differences in oncologic outcomes and toxicities were observed between paclitaxel and cisplatin arms. Clinical trial information: NCT02344095.
Impact of a structured quality management program on survival of patients with advanced (AOC) and relapsed ovarian cancer (ROC) treated in a dedicated tertiary gynecologic-oncology (GO) center.
Authors: Harter Philipp , Heitz Florian , Ataseven Beyhan , Prader Sonia , Schneider Stefanie , Baert Thaïs , Alesina Pier , Groeben Harald , Traut Alexander , Du Bois Andreas 
Published: May 2019

e17048 Background: Treatment of AOC needs interdisciplinary and specialized skills and structures. We report the impact of a dedicated quality management program over 2 decades from learning curve and specialization process started in 1998-2004 when the surgical department was separated from a general clinic of obstetrics and gynecology. The next period from 2005-2010 covers the data after implementation of the first step of our ovarian cancer quality assurance program. In 2011, a dedicated department of GO was founded. Additionally, we investigated the role of subsequent centralized versus decentralized treatment when patients relapsed after they had primary therapy at our institution. Methods: Descriptive analysis of our prospective tumor registry including all consecutive patients with primary diagnosis of AOC FIGO IIB-IV treated from 1998-2004, 2005-2010 and 2011-2017. All patients having started any therapy outside of our center were excluded. Results: The number of patients with untreated AOC increased from 10 to 147 per year from 1998 to 2017. In total, 1,663 pts were analyzed. The annual percentage of FIGO IV increased from 14% in 1998 to 54-61% in recent years (2013-2017). The complete resection rate of upfront surgery was 50%, 67%, and 69% in the periods 1997-2004, 2005-2010, and 2011-2017, respectively. Correspondingly, median PFS increased from 19 to 21 and 26 months (p < 0.001) and median OS increased from 33 to 42 and 56 months, respectively (p < 0.001). Altogether, 893 pts (53.7%) experienced a relapse. 490/893 pts (54.9% of all ROC pts) were treated again in our center, the remaining 45.1% were treated somewhere else. Median OS calculated from first relapse was 43 months for patients re-treated in our institution versus 32 months for others (p < 0.001). Conclusions: We demonstrate a correlation between specialization and improved outcome in AOC. Focusing and implementing a quality assurance program including structural evolution from a department of general obstetrics/gynecology to a department of GO led to an improvement although systemic primary treatment standards did not change during this period.
Delay in time to adjuvant chemotherapy and its impact on outcome in completely resected advanced ovarian malignancies treated with CRS, CRS+IP and CRS +HIPEC.
Authors: Rajgopal Ashwin K , Somashekhar S.P. , C Rohit Kumar , Yethadka Ramya , Ahuja Vijay , Rauthan Amit , Patil Poonam 
Published: May 2019

e17051 Background: The relationship between initiation time of adjuvant chemotherapy in ovarian cancer and prognosis has remained controversial. This study was done to determine whether time from optimal cytoreductive surgery (CRS) to initiation of adjuvant chemotherapy impacts disease free & overall survival in advanced ovarian carcinoma. Methods: Total of 185 patients with primary advanced epithelial ovarian carcinoma (Stage IIIc or selected Stage IV), underwent optimal cytoreduction (either as upfront or interval) & adjuvant chemotherapy. The analysis of interval between day of surgery and start of adjuvant chemotherapy and its impact on outcome was done. Results: CRS with intraperitoneal (IP) chemotherapy either in the form of IP port or hyperthermic intraperitoneal chemotherapy (HIPEC) was done in 135patients (60+ 75) and CRS alone in 50 patients. The median delay in starting adjuvant chemotherapy was 35 days for the whole cohort (32 days in the CRS group, 34 days in CRS+ IP group and 41 days in CRS+ HIPEC group). Delay in chemotherapy, as defined by more than 42 days had significant impact on DFS in CRS alone group (36 months vs 17 months: p = 0.02) had some impact in patients receiving intraperitoneal chemotherapy (38 versus 28 months; p = 0.78) & no impact on CRS+HIPEC group (35 vs 32 months; p = 0.17). In comparison to HIPEC vs non HIPEC group (CRS & CRS+IP), there was a meaningful impact on DFS with reference to delay in non HIPEC group ( 38 vs 22 months p = .08 whereas in the HIPEC group delay didn’t have any impact(35vs 32 months p = 017). There was trend towards better OS (88 vs 71 months p = 0.49). Conclusions: Delay in starting adjuvant chemotherapy certainly had impact on outcome with respect to CRS & CRS + IP arm (non HIPEC group) whereas the delay didn’t have an impact in the HIPEC group owing to the fact that single dose of chemotherapy during surgery in heated environment may substitute for the delay. However well designed clinical studies needs to be designed to evaluate the impact of single dose of intraperitoneal heated therapy & its interplay in delay on starting adjuvant chemotherapy.