bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or placebo: An exploratory post-hoc analysis of COU-AA-302 trial data.
Authors: Pilon Dominic , Behl Ajay S. , Kamstra, Rhiannon , Xiao Yongling , Lafeuille Marie-Helene , Lefebvre Patrick , Freedland Stephen J. 
Published: September 2018

e16529 Background: A post-hoc analysis of COU-AA-302 trial data showed that brief pain inventory (BPI), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bone metastases were predictors for overall survival in men with mCRPC treated with AA+P. This study aimed to identify baseline predictors of other clinical outcomes. Methods: COU-AA-302 trial data were used to develop predictive models for prostate-specific antigen (PSA) progression, Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration, and opiate use. Associations between baseline factors and outcomes were first assessed using multivariable Cox models among AA+P patients (Step 1). In Step 2, interaction testing was conducted between treatment (AA+P vs. placebo) and each potential predictor (P < 0.2) identified in Step 1. Final Cox models included predictors and any significant interactions (p < 0.05). Results: A total of 1,034 men (525 AA+P; 509 placebo) were included in the analysis. Baseline BPI, PSA, LDH, and ALP were predictors of PSA progression and opiate use regardless of AA+P or placebo with higher values indicating higher risks (all P < 0.05). Younger age, shorter time from luteinizing hormone-releasing hormone to randomization, higher Gleason score, and lower PSA at diagnosis were also associated with higher risks of opiate use: (all P < 0.05). For ECOG PS deterioration, higher baseline BPI, PSA, LDH, and Gleason score, older age, and lower baseline ECOG were associated with higher risks regardless of AA+P or placebo (all P < 0.05). Baseline ALP and site of metastasis also predicted ECOG PS deterioration but the effect varied by treatment (lower risk in AA+P versus placebo; both interactions’ P < 0.05). Conclusions: Predictors of PSA progression, ECOG PS deterioration, and opiate use were identified in AA+P and placebo-treated men with mCRPC. No predictors were associated with worse outcomes for AA+P versus placebo, while the negative impact of certain predictors on ECOG PS was favorably modified by AA+P. Further study is needed on the relationship between AA+P and prognostic factors.
Germline variants and family history in caucasian and African-American prostate cancer.
Authors: Ledet Elisa M. , Ernst Emma M. , Schiff Joshua , Lin Shuwen , Lewis Brian E. , Sartor A. Oliver 
Published: September 2018

e16548 Background: Family history (FH) is a well-documented risk factor for prostate cancer (PCa). Previously, germline pathogenic variants (PVs) have been identified in metastatic PCa. The goal of this study was to fully evaluate cancer FH and assess PVs detected in PCa patients undergoing both detailed FH ascertainment and germline genetic testing. Methods: FHs were collected from 535 PCa pts (Caucasian (Ca) n = 359, African American (AA) n = 85, Other n = 18) at Tulane from 2015-2016. Age at diagnosis, Gleasons, and the presence of metastases at any time were noted for these pts. Chi-square and the Mann-Whitney U tests were performed to identify relationships between clinical parameters and FH. 124 PCa pts including those with both localized and metastatic disease were identified with FHs that met guidelines for genetic testing. Genetic testing was done using a commercially available panel (Invitae, San Francisco, CA) of 25-79 cancer-related genes for mutations/selected exon deletions/duplications. Results: Of the 124 tested pts, 20 pts (16.1%) had ≥ 1 germline PV and 47 pts (37.9%) had ≥ 1 germline variant unknown significance. PVs included: BRCA2 (n = 4), BRCA1 (n = 3), CHEK2 (n = 3), MUTYH (n = 3), ATM (n = 2), TP53 (n = 1), MITF (n = 1), NBN (n = 1), PMS2 (n = 1), and RAD51D (n = 1). No PVs were detected in AA pts (n = 20). 435 of 535 PCa pts (81.3%) had a cancer FH with prostate (37.8%), breast (28.2%), lung (16.4%), colorectal (14.8%), and pancreatic (7.5%) cancer being most common. 281 pts (52.5%) had ≥ 2 relatives with cancer. Pts with PCa FH were more likely to be dx age ≤ 55 (p = 0.017). Median age was younger at dx for pts with PCa FH (p = 0.0005). PCa FH did not alter Gleason or metastatic rate. FH influenced age at dx for Ca men (p = 0.0009, 58 vs. 62.5 and Ca men with PCa FH) were 1.55x more likely to develop metastases (p = 0.035). In AA pts, there were no significant associations between FH, and metastases or age at dx. Conclusions: The most prevalent germline mutations in this cohort were in DNA repair pathway genes. Pts with PCa FH were younger at dx than those without PCa FH. Further studies are needed to understand the co-segregation of PCa with other cancers and genetic studies are needed to clarify the mechanisms of these trends which may differ between Ca and AA men.
The prostate clinical outlook (PCO) classifier for predicting biochemical recurrences in patients treated by stereotactic body radiation therapy.
Authors: Rho Mi Jung , Park Jihwan , Dritschilo Anatoly , Collins Sean P. , Suy Simeng , Choi In Young , Mun Seong K. 
Published: September 2018

e16552 Background: Although prostate cancer risk classifiers have been developed for predicting surgical and radiation therapy outcomes, a classifier suitable for predicting biochemical recurrence (BCR) in patients undergoing stereotactic body radiation therapy (SBRT) remains to be defined. SBRT is delivered in large fractions of highly conformal radiation therapy and such treatments are believed to be radiobiologically more effective in treating prostate cancers. The aim of this study is to develop a new classifier specifically for informing patients electing to undergo prostate cancer treatment with SBRT. Methods: We have studied outcomes of 809 patients treated with SBRT between August 2007 and November 2016 at MedStar-Georgetown University Hospital. A Cox regression to BCR was performed and the Prostate Clinical Outlook (PCO) score was calculated at diagnosis based on age at diagnosis, clinical-radiological staging, pre-treatment PSA and Gleason score. Accuracy of the PCO classifier was assessed with concordance (c)-indexes. The results were also compared to classifications by D’Amico and National Comprehensive Cancer Network (NCCN) recurrence risk groups. Results: PCO total scores range from zero to 156 points. The PCO classifier splits patients into 3 risk-groups with the following 5-year BCR-free survival: for low-risk 98%; for intermediate-risk 95%; for high-risk 86%. Our classifier outperforms D’Amico and NCCN for all of the evaluated end-points, with concordance indices of 74 % versus 64 % and 66%, respectively. Conclusions: The PCO classifier is a potential tool for employing readily available parameters to stratify prostate cancer patients and to predict probabilities of BCR after SBRT.
Moore criteria application by an Argentinean public institution on patients with advanced cervical cancer (ACC).
Authors: Caceres Maria V. , Lopez Vanesa , Albi Laura Marcela , Cagnoni Ana Lucila , Savignano Mariana , Almada Carolina , Zapata Caamano Maria Gabriela , Roganovich Gustavo , Durand Alfonso Javier , Aguilar Andrea 
Published: September 2018

e17010 Background: Moore criteria allows stratifying the risk of patients with ACC, predicting the rate of response (RR), the progression free survival (PFS) and the overall survival (OS), being an important prognostic tool being an important prognostic tool that can be used on Argentine population. Methods: Prospective, observational and descriptive analysis of 41 patients with ACC treated at Roffo Hospital in Buenos Aires, from 10/2013 to 1/2017. 35/41 (85%) patients received the planned treatment (6 cycles of Carboplatin AUC x 5 day 1, Paclitaxel 175 mg/m2 day 1) +/- Bevacizumab 15 mg/m2 day 1 every 21 days until progression. 6 patients (15%) received no treatment (2 for socioeconomic reasons and 4 due to poor performance status). 7/35 (20%) were treated without antiangiogenic (3 for the presence of a rectal-vaginal fistula and 4 due to socioeconomic reasons). These risk factors proposed by Moore were analyzed in all of the patients: performance status, previous treatment with cisplatin, pelvic disease and progression-free interval <365 days. Given the characteristics of our population, black race was not included as a prognostic factor. Results: 41 patients with ACC were analyzed: 19 (46%) were Stage IV, 5 (12%) had a persistent disease and 17 (42%) evidenced disease recurrence. Pursuant to Moore criteria, 19 patients (46%) were stratified as mid-risk, 18 (44%) as high-risk and 4 (10%) as low-risk. Treatment of mid-risk patients with Bevacizumab showed a 94% (17/18) clinical benefit rate (CBR) and the high-risk patients were 78 % (7/9) CBR. The 2 low-risk patients had partial response. Of the 7 patients treated without antiangiogenic, 2 mid-risk progressed; 1 low-risk had partial response and 4 high-risk showed 50% (2/4) partial response, and 50% (2/4) was pending at the moment this abstract was drafted. Conclusions: It is feasible to useMoore criteria to evaluate our population with ACC in order to estimate the prognosis of the disease. The percentage of low risk patients is poor in our population. Due to short follow-up time, only prognostic factors associated with CBR was assessed. Homologation of the black race factor with other socio-economical parameters related to access to healthcare is planned.
Institutional retrospective analysis of definitive chemo-radiotherapeutic treatment (QRT) in locally advanced cervical cancer.
Authors: Soule Tomas Jose , Mando Pablo , Sade Juan Pablo , Giornelli Gomez Gonzalo , Rivero Sergio Gabriel , Chacon Matias , Chacon Reinaldo D. , Orlando Mauro 
Published: September 2018

e17016 Background: Retrospective analysis of toxicity and treatment impact of gemcitabine and platinum plus radiotherapy in patients with locally advanced cervix cancer. Methods: Descriptive, retrospective and observational study of patients with locally advanced cervix cancer (EIla/IVa).The analysis included toxicity Grade III/V and it impact in treatment. Results: We analyze 56 pts, median age: 46.5, median follow up: 24 months. Patients and tumoral characteristics are described in the table below. Regarding platinum group, 2pts required dose reductions of chemotherapy, 2pts suspended a cycle due to toxicity and 4pts needed RT split. 100% pts completed chemo radiotherapy concurrent treatment. Regarding platinum+gemcitabine group: 11pts required CT dose reductions, 14pts suspended a cycle due to toxicity and 5 didn´t complete CT due to toxicity; 6 had a RT split and 18 completed RT. Grade 3-4 toxicity was more frequent in the platinum+gemcitabine group (38.9% vs 73.7%, p=0.01) In platinum group, 14 pts presented disease recurrence. In the platinum + gem group 3pts had a recurrence. Median disease free interval (DFI) was not reached in both groups, but in the univariate analysis statistical significance was achieve, favouring the combine treatment (Log rank test, p=0.03). 2 year global survival rate was 82.1% in platinum group and 91.7% in platinum+gemcitabine groups. Conclusions: This report shows that the scheme of concurrent combine chemotherapy offers higher toxicity, requiring treatment discontinuation in some patients. Nevertheless, in a univariate analysis the platinum+gemcitabine group showed better results, even in a population with more advance disease with greater risk of relapse, understanding that the retrospective evaluation may miss confounders. A correct institutional manage of toxicities may allow the use of intense treatment to obtain potential benefits. [Table: see text]
Clinical trial of biopsies in oncology: Patient-reported impact (BIOPSY).
Authors: Wilson Michelle K. , Lheureux Stephanie , Cyriac Sunu , Dhani Neesha C. , Butler Marcus O. , Gutierrez David , Mandilaras Victoria , Ethier Josee-Lyne , Colombo Ilaria , Lee Yeh Chen , Kanjanapan Yada , Bonilla Luisa , Hunt Wendy , Bowering Valerie , Oza Amit M. 
Published: September 2018

e17034 Background: Modest prospective data reports the impact of biopsies on patients (pts) with respect to adverse events (A/E) and anxiety. With increasing use of biopsies in clinical practice and trials, BIOPSY was designed to prospectively assess this. Methods: Pts undergoing a biopsy for diagnosis and/or research at Princess Margaret Cancer Centre were eligible. Surveys at 1 wk prior to biopsy and 1 wk and 1 mth post-biopsy assessed anxiety, A/E and pt experience. Anxiety was measured with a modified hospital anxiety and depression scale (HADS) score. Results: From 3/2015 to 1/2017, 51, 47 and 39 pts completed 1, 2 and 3 surveys respectively. Median age was 61 years. 40 biopsies were for research (78%) and 11 for diagnosis (22%). 46 pts were involved in a clinical trial (90%). 47 pts had a gynecological cancer (92%). 45 pts felt well-informed of the possible risks of the biopsy (88%). 23 pts noted the biopsy would not impact them directly (45%). 48 pts supported the use of tissue for future unrelated research (94%). Feelings of anxiety about the biopsy improved with time (table 1). 28 pts had pain 1 wk post-biopsy (60%) which was a moderate or major problem in 9 pts (19%). 2 pts reported reduced dignity with the biopsy (4%). 12 pts at 1 wk (26%) felt another biopsy would be a moderate-major issue. At 1 mth 3 of these pts reported a biopsy was now a mild problem. No significant A/E occurred. At baseline only 2 pts felt a biopsy would deter them from entering a clinical trial (4%). 42 pts at 1 wk (89%) and 30 pts at 1 mth (77%) felt they would consent to another biopsy for research. On univariate analysis pts with at least moderate pain post-biopsy at 1 wk or 1 mth (p=0.03) or an elevated HADS score at 1 mth (p=0.02) appeared less likely to agree to a further research biopsy but numbers were small. Conclusions: Anxiety and pain are potentially modifiable A/E that impact whether a pt will agree to a further biopsy. Overall, most pts tolerated their biopsy well, supported its use for future unspecified research and were open to further biopsies. [Table: see text]
Immunohistochemical changes in ovaries caused by chemoimmunotherapy.
Authors: Nepomnyashchaya Evgeniya M. , Nerodo Galina Andreevna , Ardzha Anna , Novikova Inna Arnoldovna , Ulianova Elena Petrovna , Zakora Galina I. 
Published: September 2018

e17038 Background: The purpose of the study was to analyze morphological and immunohistochemical changes in patients with ovarian serous carcinomas under the influence of chemoimmunotherapy. Methods: The study included patients aged 52-76 years with stage IIIC-IV ovarian cancer with ascites. The patients were divided into two groups according to the treatment received: group A – 22 patients receiving neoadjuvant chemoimmunotherapy, 500 000 IU interferon-gamma (ingaron) on the 1st day and 1 000 000 IU on days 2, 3 and 5, and chemotherapy (carboplatin AUC-6 and paclitaxel 175 mg/m2) on day 4; group B – 24 patients receiving neoadjuvant chemoimmunotherapy and the same regimen of intraperitoneal interferon-gamma. The patients in two groups were similar in terms of disease stages, health condition and age. All patients received further surgery. Immunohistochemical study was performed on paraffin sections for the standard morphological study using Ki-67 rabbit monoclonal antibodies (Thermo scientific) and P-53 mouse monoclonal antibodies (Cell Marque). UltraVision Quanto Detection System HRP DAB was used for visualization. Results: Chemoimmunotherapy plus intraperitoneal interferon-gamma resulted in grade III-IV pathomorphosis, decreased apoptosis index and proliferation activity (р53 – 19.3±2.5%; Ki-67 – 6.2±0.58%) in comparison with the group receiving intramuscular interferon-gamma (р53 –27.6±3.11%; Ki-67 – 16.2±3.09%). The group with chemotherapy and intramuscular interferon-gamma showed grade II pathomorphosis. Conclusions: The study showed that chemotherapy with intraperitoneal interferon-gamma administration, compared with intramuscular one, resulted in more enhanced morphological changes.
Ovarian cancer with peritoneal carcinomatosis: Comparing of photodynamic treatment and HIPEC.
Authors: Privalov Alexey , Vazenin Andrey , Chernova Ludmila , Taratonov Alexey , Gubaydulina Tatiana 
Published: September 2018

e17040 Background: Peritoneal carcinomatosis is a very common by ovarian cancer (OC). Usual treatment`s approaches such as systemic drugs are not very effective. 5-year survival by OC depends of stage and are 15-20% in III stage and only 5% in IV stage. Most part of this patients die with progression of peritoneal disease. Standart treatment`s approach by OC is radical surgery with adjuvant chemotherapy. But in many cases this tactic can`t control peritoneal lesions and, therefore, outcomes. Methods: In our oncology center we are performing retrospective non-randomized prospective study comparing two different treatment options by ovarian`s peritoneal carcinomatosis - photodynamic therapy (PDT) and hyperthermic intraperitoneal chemotherapy (HIPEC). There were 25 patients in PDT-group and 21 patients in HIPEC-group. Treatment in PDT-group included 2-4 cycles of neo-adjuvant chemotherapy (cyclophosphamid+cisplatinum /CP/, n=7 or paclitaxel+cisplatinum /TC/, n=18 ), after which we performed surgery+PDT and then 4-6 cycles same chemotherapy. We used iv. photolon (Russia) as photosensitizer and 630-680 nm diod laser. Time of procedure was 20 minutes. Peritoneal Carcinomatosis Index (PCI) was 4,2 an averege (1-12). Treatment in HIPEC-group included 2-4 cycles of neo-adjuvant chemotherapy (cyclophosphamid+cisplatinum /CP/, n=21), after which we performed surgery+HIPEC and then 4-6 cycles the same chemotherapy. Medium PCI was 5,6 (2-11). We used “closed” HIPEC technique, with 3 inflow and 3 outflow catheters, Performer HT device by RanD and 7 liters of saline solution with 200 mg cisplatunum or 100 mg/m2 taxans were used. Results: There were 11 recurrence in PDT-group (44%) and 10 recurrence in HIPEC-group (38%), t=1,06. Median of time to progression was 11.6 months in PDT-group and 13,5 months in HIPEC-group. Median of overall surviving was 18,4 and 24,1 months respectively. Conclusions: Using of PDT by ovarian cancer with peritoneal carcinomatosis didn`t show increasing of overall survival. We can also notice the non-statistical tendency of increasing time to progression in HIPEC-group. We run our study further and hope to collect more data for analysis.
Kinetics of HE4 and CA125 markers in metastatic ovarian cancer: The META4 study.
Authors: Lamy Pierre-Jean , Touraine Célia , Mollevi Caroline , Roques Sylvie , Viglianti Catherine , Montels Frederic , Floquet Anne , Ray-Coquard Isabelle Laure , Fabbro Michel 
Published: September 2018

e17059 Background: HE4 is a new marker that could improve the detection of ovarian cancer (OC). The objective of the present study was to compare the prognostic value of the HE4 and CA125 markers in patients (pts) with metastatic epithelial OC, considering the progression-free survival (PFS). Methods: 101 pts, treated with 2nd/3rd line of chemotherapy, were included in 3 cancer centers between 2010 and 2014. Serums were prospectively collected before the 1stchemotherapy cycle, during chemotherapy and every 3 months until disease progression. The primary endpoint was HE4 and CA125 marker level evolution under treatment. Secondary endpoints were the markers’ main kinetic parameters: initial concentration, nadir, time to nadir, time to normalisation, half-life, doubling time and time to exceed the clinical threshold (CA125≥35UI/L; HE4≥75pM) (NCT01768156). Results: 89 pts were included in the final analysis. Median age was 65 (34-83). Histological sub-types were mainly serous (88%). The median PFS was 45 weeks (95%CI: 33.4-52). At baseline, median CA125 and HE4 levels were 210UI/L (7-10310) and 184pM (31-4836), respectively. Among 12 pts (13%) CA125- (with CA125 < 35UI/L), 8 were HE4+ (with HE4≥75pM) and among 16 pts (18%) HE4-, 12 were CA125+. The median nadir was 31UI/L (3-8744) for CA125 and 75pM (20-4836) for HE4. Median time to nadir was 14 (0-130) and 12 weeks (0-52) for CA125 and HE4, respectively. The median time to normalization was 17 (3-247) and 17 weeks (2-203) for CA125 and HE4, and the median half-life was 8 (1-193) and 12 weeks (2-166), respectively. The median doubling time and the time to exceed the clinical threshold were respectively of 13.5 and 40.2 weeks for CA125, and 23 and 23.6 weeks for HE4. In multivariate analysis, the CA125 nadir ( < 35 vs ≥35: HR = 3.13; 95%CI: 1.75-5.58), CA125 time to nadir ( < 14 vs ≥14: HR = 0.46, 95%CI: 0.28-0.76), HE4 nadir ( < 75 vs ≥75: HR = 1.95; 95%CI 1.16-3.27), and HE4 time to nadir ( < 12 vs≥12: HR = 0.39; 95%CI: 0.23-0.67) were found significant prognostic factors for PFS. Conclusions: Nadir and time to nadir were significant for both HE4 and CA125 markers in multivariate analysis. Further investigations on HE4 kinetic could be helpful for monitoring pts presenting no variation of CA125. Clinical trial information: NCT01768156.
The influence of chemotherapy induced nausea and vomiting (CINV) on survival: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1213 recurrent ovarian cancer patients.
Authors: Woopen Hannah , Richter Rolf , Inci Guelhan , Chekerov Radoslav , Oskay-Oezcelik Gulten , Sehouli Jalid 
Published: September 2018

e17062 Background: Nausea and vomiting are frequent side effects of chemotherapy and are the most feared toxicities of our patients. Aim of this study is to evaluate the potential influence of chemotherapy induced nausea and vomiting (CINV) on survival. Methods: Synthesized raw data of three phase II/III studies (“Tower”, “Topotecan phase III” and “Hector”) of the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients were analyzed using logistic regression and cox regression analyses. Results: In this analysis 661 patients (54.5%) developed grade I/II and 44 patients (3.6%) grade III/IV nausea. 343 patients (28.3%) had grade I/II vomiting and 33 patients (2.7%) grade III/IV. There were no differences between severity of CINV regarding FIGO, grading, histology and amount of recurrences. Patients <65 years developed more frequently grade III/IV nausea than patients ≥ 65 years (p<0.001, OR 1.29, 95% CI 0.68-2.46). Polypharmacy was also associated with grade III/IV CINV (p<0.001 and p=0.002 respectively). Progression free survival was worse in patients with grade III/IV nausea (p=0.023, HR 1.58, 95% CI 1.14-2.20). Median overall survival (OAS) in patients without nausea was 19.0 months compared to patients with grade III/IV nausea with 11.0 months (p<0.001, HR for grade III/IV 2.35, 95% CI 1.64-3.37). Grade III/IV vomiting was also highly associated with worse OAS (median of 22.0 months in patients without vs. 5.9 months in patients with grade III/IV vomiting, p<0.001, HR for grade III/IV vomiting 3.4, 95% CI 2.32-5.00). However, dose reductions and prior discontinuation of chemotherapy were not more frequent in patients with nausea and vomiting. Conclusions: Patients with nausea and vomiting had a decreased progression and overall survival. This study underlines once again the importance of early best supportive care on survival.