bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors and clinical outcomes of gastric cancer identified by screening endoscopy: A case-control study.
Authors: Jung Hwoon-Yong , Gong Eun-Jeong , Ahn Ji Yong , Lim Hyun , Choi Kwi-Sook , Lee Jeong Hoon , Kim Do Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Kim Jin-Ho , Choi Son Yeong , Choe Jaewon , Kim Min-Ju 
Published: February 2017

8 Background: A customized screening program for gastric cancer would optimize the benefits of screening endoscopy. This study investigated the risk factors for gastric cancer detected during screening, and factors affecting clinical outcomes. Methods: From April 2000 to December 2010, subjects who underwent screening endoscopy at Asan Medical Center were included. To investigate risk factors, age and sex-matched control group were selected.The clinical outcomes of gastric cancer identified during screening (screening group) were compared with age, sex and date of diagnosis-matched subjects who were diagnosed with gastric cancer in the outpatient clinic (outpatient group). Results: Of 109,530 subjects, 327 were diagnosed with gastric cancer. The median age of the screening group was 63.6 years (interquartile range: 56-71 years), and the male to female ratio was 2.4:1. When comparing with the control group, H. pylori seropositivity (odds ratio [OR] 2.933, p<0.001), carcinoembryonic antigen (OR 8.633, p=0.004), family history of gastric cancer (OR 2.254, p=0.007), and drinking (OR 3.312, p<0.001) were independent positive risk factors, and the use of aspirin a negative risk factor for gastric cancer (OR 0.445, p=0.012) in multivariate analysis. Low density lipoprotein cholesterol (hazard ratio [HR] 0.987, p=0.005), cancer antigen 19-9 (HR 21.713, p<0.001), resectability (HR 59.833, p<0.001), and family history (HR 0.308, p=0.009) were independent risk factors for death. The 5-year survival rate was significantly higher in the screening group than in the outpatient group (p<0.001). Conclusions: Early detection of gastric cancer by screening endoscopy while asymptomatic enhances patient outcomes, especially in high risk groups.
Randomized, multicenter, controlled evaluation of S-1 and oxaliplatin (SOX regimen) as neoadjuvant chemotherapy for advanced gastric cancer patients (RESONANCE trial).
Authors: Li Tao , Chen Lin 
Published: February 2017

90 Background: RESONANCE trial aims to improve 3-year disease-free survival (DFS) for patients treated with neoadjuvant chemotherapy and D2 surgery with chemotherapy postoperatively. We also evaluated the postoperative complications with and without preoperative chemotherapy to reveal the safety of SOX regimen. Methods: In this phase III multicenter study, patients with American Joint Committee on Cancer(AJCC,7thed)stage II-IIII advanced gastric cancer are treated with two to four cycles of preoperative SOX chemotherapy, followed by gastrectomy with D2 lymphadenectomy, and then another four to six postoperative cycles of SOX chemotherapy. Surgical and pathological quality control is performed. The primary endpoint is 3-year DFS, secondary endpoints are 3-year OS, D2/R0 rate, and toxicity and recurrence risk. The RESONANCE trial has been registered internationally, and twenty hospitals have participated in this trial. Results: Between February 2012 and to August 2013, 128 patients were enrolled in the neoadjuvant group , 103 patients were enrolled in the adjuvant group. Seventy-four of 128 patients underwent gastrectomy with D2 lymphadenectomy after preoperative chemotherapy. In these 74 patients, 52 (70%) patients had clinical tumor response and 10 (14%) patients achieved histological response. Operative mortality was never encountered. R0 resection rate was 90.5% after neoadjuvant chemotherapy compared with 94.2% in adjuvant group (p=0.23). Postoperative complication rates in neoadjuvant and adjuvant groups were 33.8% and 37.9% respectively (p=0.58). Conclusions: Results of this study will demonstrate whether neoadjuvant chemotherapy strategy will be superior to adjuvant chemotherapy when combined with D2 surgery for AJCC stage II-III gastric cancer patients. Furthermore, it might be an important clinical evidence to verify benefit of neoadjuvant chemotherapy in advanced gastric cancer. Clinical trial information: NCT01583361.
Prognostication in esophagogastric adenocarcinoma (OGA): Factors influencing overall survival (OS) in REAL3.
Authors: Waddell Tom Samuel , Chau Ian , Peckitt Clare , Patel Bijal , Gonzalez de Castro David , Wotherspoon Andrew , Middleton Gary William , Wadsley Jonathan , Ferry David , Mansoor Wasat , Crosby Tom David Lewis , Coxon Fareeda Y. , Smith David , Waters Justin S. , Iveson Timothy , Falk Stephen , Slater Sarah , Okines Alicia Frances Clare , Cunningham David 
Published: February 2017

91 Background: The REAL3 trial evaluated the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. We previously reported that addition of panitumumab was not associated with improvement in survival endpoints. In this analysis we aimed to explore factors associated with OS in the REAL3 population. Methods: Analysis performed in ITT population (n=553). OS was evaluated in relation to the baseline characteristics displayed in the table below. Cox regression was used to obtain HRs and 95% CIs. Factors with p<0.2 were included in a forward stepwise model and factors with p<0.1 were regarded as significant in the final model. OS was also assessed using the RMH Prognostic Index score which comprises 4 adverse variables: PS 2; liver mets; peritoneal mets; ALP >100 U/L. Results: Results of the univariate analysis are shown in the table below. In multi-variate analysis, the factors which remained statistically significant for OS were: PS (p=0.080): 1 vs 0 HR 1.24 (95% CI 0.99-1.57); 2 vs 0 HR 1.57 (95%CI 0.97-2.54) Disease extent (p=0.054): Met disease vs LA HR 1.42 (95% CI 0.99-2.02) Baseline global health score (p=0.005): Low vs high HR 1.52 (95% CI 1.16-2.00); middle vs high HR 1.45 (95% CI 1.11-1.89) Patients with an RMH Prognostic Index score of 0 (good prognosis) had median OS of 13.1 mo. This compared to 9.5 mo in patients with 1-2 adverse features (intermediate prognosis) (HR 1.37, 95% CI 1.12-1.68; p=0.002) and 4.7 mo in patients with 3-4 adverse features (poor prognosis) (HR 4.02, 95% CI 1.96-8.22; p<0.001). Conclusions: Baseline global quality of life may represent a useful adjunct to clinical parameters to guide prognostication in advanced OGA. These findings also validate the RMH Prognostic Index score in the REAL3 population. Clinical trial information: 2007-005976-15.[Table: see text]
Bone and soft tissue response from a phase I/II study with ODM-201 in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Garcia Jorge A. , Kataja Vesa V , James Nicholas David , Jones Robert Hugh , Protheroe Andrew , Massard Christophe , Mattila Leena , Mustonen Mika VJ , Aspegren John , Fizazi Karim 
Published: February 2017

102^ Background: ODM-201 is a novel potent full androgen receptor (AR) inhibitor for CRPC. ODM-201 has excellent nonclinical efficacy in xenograft studies and high PSA response rate in CYP17i-naïve CRPC patients in the phase I/II ARADES study. Methods: To further analyze clinical efficacy of ODM-201 in CRPC pts we evaluated the overall response rate (ORR) in ARADES phase I/II study (Fizazi et al. Abstract #2853, ECC2013, Amsterdam 28 Sept 2013 ).Patients (pts) were enrolled into three dose levels 100mg bid, 200mg bid and 700mg bid. Results: All eligible 124 pts had progressive mCRPC; 37 pts were pre-chemo/CYP17i-naïve, 32 post-chemo/CYP17i-naïve and 55 post-CYP17i. Thirty-two (86%) pts in the pre-chemo/CYP17i-naïve group, 27 (84%) post-chemo/CYP17i-naïve and 48 (87%) post-CYP17i had bone disease at baseline. Similarly, twenty-two (29%) pts, 19 (59%) and 36 (65%), respectively had RECIST-define measurable disease. Median baseline PSA was 101ng/mL (3-1294) in pre-chemo/CYP17-i-naïve group, 94ng/mL (8-663) in post-chemo/CYP17-i-naïve group, and 139ng/mL (9-5000) in post-CYP17i group. CTC count was over 5CTCs per 7.5ml in 43% of the pts in pre-chemo/CYP17-i-naïve group, 41% in post-chemo/CYP17-i-naïve group and 44% in postCYP17i group. ORR data is presented in table below. Conclusions: Although RECIST-define responses were observed across the 3 different group of pts treated with ODM-201 the vast majority of pts had RECIST-defined SD up to 12 weeks. These data are in line with PSA data reported previously that demonstrate the clinical activity of ODM-201 in men with mCRPC. Clinical trial information: NCT01317641, NCT01429064. [Table: see text]
Anticancer activity of the selective CYP17A1 inhibitor, VT-464, in preclinical models of castrate-resistant prostate cancer.
Authors: Toren Paul , Pham Steven , Kim Soojin , Adomat Hans , Zoubeidi Amina , Moore William R , Gleave Martin Edwin 
Published: February 2017

104 Background: Castrate resistant prostate cancer (CRPC) continues to be sensitive to anti-androgen therapy as evidenced by the recent successes of abiraterone acetate (AA) and enzalutamide (ENZ). VT-464 is a novel, non-steroidal, small molecule CYP17A1 inhibitor with selectivity for the lyase activity of this dual enzyme. The objective of this study was to evaluate the anti-cancer activity of VT-464 compared to AA in CRPC in vitro models that are ENZ-responsive and ENZ-resistant and in an ENZ-resistant xenograft model. Methods: In vitro studies used the human CRPC, C4-2, and ENZ-resistant cell lines, MR49C and MR49F cells, in androgen-free media. AR transcriptional activity was assessed by probasin luciferase. AR-related and steroidogenesis pathways were assessed by western blot and/or qRT-PCR. A MR49F xenograft model in castrate mice compared oral VT-464 treatment to vehicle and AA. Steroid concentrations were measured using LC-MS chromatography. Results: VT-464 demonstrated a greater decrease in AR transactivation compared to AA in C4-2 and both ENZ-resistant cell lines. A greater decrease in AR-dependent gene transcription occurred with VT-464 treatment compared to AA in all cell lines. Prostate-specific antigen (PSA) protein levels in vitro were also lower with VT-464. Gene transcripts StAR, CYP17A1, HSD17B3 and SRD5A1 increased following treatment with VT-464 both in vitro and in vivo. A greater increase was seen with VT-464 treatment compared to AA. In vivo results demonstrated greater tumor growth inhibition and decreased serum PSA levels in mice treated with oral VT-464 compared to AA. Steroid analysis revealed lower testosterone (T) and dihydrotestosterone (DHT) concentrations in C4-2 cells with VT-464 treatment compared to AA. In vivo, the intra-tumoral DHT and T levels were significantly lower in response to VT-464 or AA compared to vehicle, with the greatest decrease seen with VT-464. Conclusions: The selective CYP17 inhibitor VT-464 demonstrated anti-cancer activity in pre-clinical models of CRPC, lowering intratumoral T and DHT concentrations significantly in castrate mice. These results suggest greater androgen suppression and inhibition of AR axis signaling by VT-464 than by AA.
The effect of pathologic T-stage and Gleason score on cancer-specific survival for specimen-confined high-risk prostate cancer.
Authors: Tosco Lorenzo , Van Poppel Hendrik , Van den Broeck Thomas , Bastian Patrick , Briganti Alberto , Chun Felix K. , Gontero Paolo , Hsu Chien Yeh , Karnes R. Jeffrey , Marchioro Giansilvio , Sanchez-Salas Rafael , Spahn Martin , Tombal Bertrand , Van Der Poel Henk , Joniau Steven 
Published: February 2017

114 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach. The indication for adjuvant therapy after surgery for HRPC patients who have specimen-confined disease (R0, pN0, <pT3b) is still difficult. The current study aims to analyze postoperative pathological features which help to predict CSS in specimen-confined HRPC and thus may aid in the decision to administer adjuvant EBRT or ADT. Methods: From a multi-institutional retrospective cohort of 5876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1391 patients with specimen-confined disease were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT<3) and final Gleason score (GS≥8 and GS<8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age was 65 years (43-84). Of all patients, 346 (24.9%) had GS≥8 and 794 (57.1%) had pT≥3 at definitive histopathology. Patients were classified into COMBO groups: C1 (478; 34.4%; GS<8,pT<3), C2 (567; 40.8%; GS<8, pT≥3), C3 (119; 8.6%; GS≥8, pT<3), C4 (227; 16.3%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 2%/2%, C2 15%/22%, C3 3%/10%, C4 18%/25%. Kaplan Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97.4%, C2 95.2%, C3 89.9% and C4 84.4% (p<0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide specimen-confined HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [Table: see text]
Current clinical presentation and treatment of localized prostate cancer in the United States.
Authors: Mahmood Usama , Levy Lawrence B. , Nguyen Paul Linh , Lee Andrew , Kuban Deborah A. , Hoffman Karen Elizabeth 
Published: February 2017

116 Background: This year, the Surveillance, Epidemiology, and End Results (SEER) database released individual patient clinical Gleason score (GS) at the time of biopsy/transurethral resection of the prostate (TURP), which, along with the previously available clinical stage and prostate-specific antigen (PSA), allows a unique opportunity to study the clinical presentation and treatment selection of prostate cancer in the US. Methods: The SEER database was used to identify men diagnosed with localized prostate cancer in 2010 who were then assigned National Comprehensive Cancer Network (NCCN) risk group based on clinical factors at diagnosis. We determined sociodemographic factors associated with having high-risk disease and analyzed the impact of NCCN risk, along with sociodemographic factors, on local treatment selection. Results: A total of 42,403 men were identified of which 16,171 (38%) had low-risk, 16,990 (40%) had intermediate-risk, and 9,242 (22%) had high-risk disease. Older, non-white, and non-married patients living in counties with higher poverty rates, were most likely to be diagnosed with high-risk disease on multivariable analysis. Of the 38,634 men for whom prostate cancer was the first malignancy, 8,832 (23%) had no local treatment, 15,421 (40%) had prostatectomy, 13,855 (36%) had radiation treatment (including external beam radiation and/or brachytherapy), and 526 (1%) had another form of local tumor destruction (predominantly cryotherapy). In total, 29% of low-risk, 16% of intermediate-risk, and 25% of high-risk patients received no local treatment (p < 0.001). On multivariable analysis, older, non-white, and non-married patients living in counties with higher poverty rates who had low-risk disease, were least likely to receive local treatment. Conclusions: Our analysis provides information regarding the current clinical presentation and treatment of localized prostate cancer in the US. We note persistent disparities in the presentation and treatment of prostate cancer according to sociodemographic factors and potential under treatment of high-risk disease.
Does tumor grade affect the relationship between preoperative prostate-specific antigen (PSA) and biochemical recurrence (BCR)?
Authors: Sankin Alexander , Kent Matthew , Sjoberg Daniel , Scardino Peter T. 
Published: February 2017

123 Background: It has been previously hypothesized that higher grade prostate tumors exhibit less predictable PSA secretion patterns as a consequence of cellular dedifferentiation. The purpose of this study is to investigate whether the relationship between PSA and BCR is different for high and low grade disease. Methods: We identified 6,616 patients who underwent radical prostatectomy (RP) from 1992-2012 for clinically localized prostate cancer without neoadjuvant treatment. We first created a Cox models to test for an interaction between PSA and both clinical and pathologic high grade cancer (Gleason grade (GG) < 8 vs. GG 8-10). We then plotted five year risk of BCR as a function of PSA for patients with negative extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI). Results: 6,125 (93%) patients in the cohort had GG < 8, and 491 (7%) had GG 8-10. In total, 780 had BCR and 165 had distant metastasis. We found a significant interaction between PSA and pathologic high grade cancer (p=0.002). The risk of BCR increases at slightly different rates for low and high grade tumors as PSA increases. For example, an increase in PSA from 10 ng/ml to 20 ng/ml increases relative recurrence risk by 38% and 8% for low and high grade cancers, respectively. This interaction remained significant when patients with PSA < 2.5 were excluded (P=0.006). There was no significant interaction between PSA and clinical high grade tumors (p=0.3). Conclusions: There appears to be a small statistically significant difference in relationship between preoperative PSA and BCR in high grade tumors when compared to lower grade tumors. This difference is not observed, however, when using biopsy GG rather than RP specimen GG.
Results of a phase II trial of abiraterone acetate (AA) combined with dutasteride (DUT) for men with metastatic castration resistant prostate cancer (mCRPC).
Authors: McKay Rana R. , Werner Lillian , Zukotynski Katherine A. , Domachevsky Liran , Elfiky Aymen , Pomerantz Mark M, , Bubley Glenn J. , Montgomery Robert B. , Kantoff Philip W. , Taplin Mary-Ellen 
Published: February 2017

126 Background: Although abiraterone acetate (AA), a CYP17 inhibitor, increases survival in men with metastatic castration resistant prostate cancer (mCRPC), tumors eventually progress on therapy. The primary purpose of this study was to identify mechanisms of resistance to AA via analysis of the androgen receptor signaling pathway in serial tumor biopsies of men receiving AA and dutasteride (DUT), a type I and II 5-α reductase inhibitor. In this analysis, we report secondary endpoints including prostate specific antigen (PSA) response, toxicity, and incidence of flare. Methods: We enrolled 40 men with mCRPC. Patients initially received AA (1,000 mg daily) and prednisone (5 mg daily). After two months (mos), DUT (3.5 mg daily) was added. Therapy was continued until radiographic progression. A flare was recorded on bone scan, CT, or both if there were worsening lesions from baseline to 3 mos, decreasing PSA more than 50% from baseline at 3 mos, and stabilization or reduction of lesions at 6 mos. Results: Median follow-up was 13 mos. At the time of analysis, nine men remain on treatment. Twenty five percent and 18% of men received prior therapy with ketoconazole and/or chemotherapy, respectively. The median PSA at baseline was 28.8 ng/mL. After 2 mos of AA, median PSA declined by 54% to 10.9 ng/mL. Median PSA nadir was 6.3 ng/mL, reached at a median of 3.2 mos from baseline. 34 men (85%) experienced some degree of PSA decline. Twenty four men (60%) had a greater than or equal to 50% PSA decline and 12 (30%) had a greater than or equal to 90% PSA decline, reached at a median of 1.4 and 2.4 mos from baseline, respectively. There were 73% grade 1, 23% grade 2, 4% grade 3, and no grade 4 adverse events (AEs).AEs of interest included fatigue (45%), hypertension (38%, n=2 grade 3), hypokalemia (15%, n=0 grade 3), liver function test increases (15%), and edema (2%, n=0 grade 3). Seventeen men had imaging available for analysis, of whom four (23%) had flare on both 3 mos CT and bone scan and four (23%) had flare on only 3 mos CT scan. Conclusions: Given time of median PSA nadir, DUT may enhance efficacy of AA, though this warrants further investigation. Therapy with AA, prednisone (5 mg daily), and DUT is well tolerated with low rates of severe mineralocorticoid toxicity. Flare is seen on imaging in 47% of patients receiving AA. Biopsy data evaluating mechanisms for resistance to AA are not yet available. Clinical trial information: NCT01393730.
Associations between uncertainty, anxiety, and quality of life in men with favorable-risk prostate cancer on active surveillance: Two-and-a-half years' follow-up.
Authors: Parker Patricia A. , Davis John W. , Latini David , Baum George , Wang Xuemei , Ward John Francis , Kuban Deborah A. , Frank Steven J. , Lee Andrew , Logothetis Christopher , Kim Jeri 
Published: February 2017

135 Background: Active surveillance (AS) has emerged as a viable option for many men with early stage prostate cancer (PC). This approach of careful monitoring with prostate-specific antigen (PSA) level, digital rectal examination, and prostate biopsy may allow men to avoid or delay the potentially debilitating side effects of such aggressive treatments as surgery or radiation; however, AS may create uncertainty and anxiety for men with PC. We examined the associations between illness uncertainty and anxiety and general and PC-specific quality of life (QOL) of 191 men with favorable-risk PC participating in the AS program at MD Anderson Cancer Center. Methods: Men completed measures of uncertainty (Mishel Uncertainty in Illness Scale), anxiety (State-Trait Anxiety Inventory), and general (SF-12, Physical Health [PCS] and Mental Health Component Score [MCS]) and disease-specific (Expanded Prostate Index Composite [EPIC]) QOL questionnaires upon study entry and every 6 months. These results are through a 2.5 year follow-up. Results: Men were primarily (86%) white and an average age of 67.2 (SD=8.9). Average baseline PSA was 3.3 ng/mL (SD=1.6), 98% had a Gleason score of 6, and 85% had cT1c disease. Both general and PC-specific QOL were relatively unchanged across the 2.5 year study period, except for statistically significant declines in the EPIC Sexual score (p<0.05). Controlling for demographic (age, ethnicity) and clinical characteristics (study entry PSA, PSA density, testosterone, BMI, baseline number of biopsies, family history of cancer, whether patients were taking a 5-alpha-reductase inhibitor, and whether the tumor was reclassified during the study), illness uncertainty was a significant predictor of all EPIC summary scores, PCS, and MCS (all, p<0.05). Anxiety was also a significant predictor of all EPIC summary scores and MCS (all, p<0.05), but not PCS (p=0.08). Conclusions: Both increased anxiety and increased illness uncertainty were associated with poorer general and disease specific QOL. Interventions that focus on reducing uncertainty and anxiety may enhance the QOL of men on AS for PC.