bluuebunny/crossref_metadata_2025_split huggingface dataset:
An oral methionine aminopeptidase II inhibitor for high-risk non-muscle invasive bladder cancer relapsed after intravesical therapies: Update of a phase II trial.
Authors: Ye Dingwei , Yao Xudong , Wang Gongxian , Pu Jinxian , Yao Xin , Zhou Fangjian , Qi Jun , Ye Zhangqun , Xie Liping , Chen Jimin , Xie Keji , Zhao Xiaokun , Xu Zhihui , Guo Hongqian , Yang Yong , Cao Dalong , Yang Bin , Zhang Cheng , Lu Yong , Du Jun 
Published: March 2017

303 Background: In 2016, we reported the preliminary results of APL-1202, an oral MetAP2 inhibitor, in the first 18 patients enrolled in the phase II trial. The purpose of the present study is to update the results of efficacy, safety, pharmacokinetics at steady state and translational studies in 41 patients. Methods: This is an open-label, single-arm phase II trial conducted in 15 hospitals in China. High-risk in recurrence is defined according to EORTC recurrence score and probability tables in EAU 2012 Guidelines on NMIBC. The primary end point is the recurrence-free survival rate at 1 year. Plasma and urine samples at steady state were collected for pharmacokinetic studies, and separate plasma samples were collected for translational studies. Results: From May 2014, a total of 41 patients have been enrolled in this study, including 39 relapsed after intravesical chemotherapies only (chemo-failed subgroup), and 2 after both chemo and BCG treatments (BCG-failed subgroup). All of patients had TaT1 papillary tumors, and 3 with concurrent carcinoma in situ . APL-1202 did not cause any drug-related SAEs. By the time of this abstract submission, the 1-year recurrence-free rate is 54.3% (37.2-73.2%, 95% Confidence Interval) with a median recurrence-free survival of 14.7 months. APL-1202’s plasma exposure at steady state appears to increase proportionally to the increase of doses. Conclusions: APL-1202 is safe and well tolerated at a daily dose up to 750mg, TID, for 12 weeks followed by 3 months on-and-off in patients with recurred high-risk NMIBC. According to the EAU 2012 Guidelines on NMIBC, naïve high-risk NMIBC patients treated by intravesical chemotherapies have a 1-year recurrence-free rate of 39% (33-45%, 95% CI) with a median recurrence-free survival of 9 months. Our results support the concept that oral MetAP2 inhibitor APL-1202 as a second-line therapy has the potential to achieve at least similar efficacy with the first-line intravesical chemotherapies, and warrant a randomized trial alone or in combination with other therapies in NMIBC patients. Clinical trial information: CTR20131716.
18F-FDG-PET/CT imaging to assess response to treatment with cabozantinib at 4 weeks versus 8 weeks of therapy in patients (pts) with metastatic urothelial carcinoma (mUC).
Authors: Davarpanah Nicole N. , Lindenberg Liza , Paul Dereck W , Steinberg Seth M. , Francis Deneise C , Berniger Marilise Anne , Weaver Juanita , McKinney Yolanda , Parnes Howard L. , Choyke Peter L. , Apolo Andrea B. 
Published: March 2017

317 Background: This study investigates whether changes in 18F-FDG-PET/CT correlate with response to cabozantinib at an early time point (4 wks) versus the conventional time point of restaging (8 wks) in pts with mUC, using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Methods: 68 pts with mUC in a single arm phase II clinical trial of cabozantinib underwent FDG-PET/CT scans at baseline, 4 and 8 wks. Up to 5 lesions with the highest Standard Uptake Value (SUV) were designated as target lesions. Response was determined using 2 versions of PERCIST (1 lesion vs top 5 lesions with highest FDG uptake) for FDG-PET/CT at 4 and 8 wks. PERCIST response classifications were compared to RECIST v1.1 at 8 wks. Results: 54 pts had evaluable disease. The single lesion 4 wk response by PERCIST showed 40% partial metabolic response (PMR), 33% stable metabolic disease (SMD), and 27% progressive metabolic disease (PMD). The single lesion 8 wk response by PERCIST showed 31% PMR, 31% SMD, and 38% PMD. The single lesion analysis coincided with multiple lesion PERCIST analysis in 86% of pts at 4 wks and 89% at 8 wks. The 4 wk PET/CT was predictive of the 8 wk PET/CT in 75% of single lesion and 76% of multiple lesion analyses. In lesion-based analysis, the 4 wk PET/CT was predictive of the 8 wk PET/CT in 74% of bone, 89% of lung, 77% of lymph node, 74% of soft tissue, and 58% of liver lesions. Only 42% of the 8 wk PERCIST and RECIST classifications coincided. At 8 wks, 40% showed response in FDG PET-CT restaging vs 7% complete/partial response by RECIST. Conclusions: The 4 wk PET/CT scan predicts the therapy response at the 8 wk PET/CT scan however the 4 wk scan overestimates the 8 wk response. The single lesion analysis by PERCIST correlates with the multiple lesion analysis and may have more clinical utility. In the lesion-based analysis, the 4 wk PET/CT scan is predictive of the 8 wk PET/CT for bone, lung, lymph node and soft tissue but not for liver lesions. Response classifications by PERCIST are not in agreement with response classifications by RECIST. Although the methods may be complementary, they are not interchangeable. Further studies are required to validate these findings. Clinical trial information: NCT01688999.
Cross-sectional evaluation of long-term bowel issues after radical cystectomy.
Authors: Hupe Marie C , Vahlensieck Winfried , Hennig Martin Jp , Ozimek Tomasz , Struck Julian , Tezval Hossein , Merseburger Axel Stuart , Kuczyk Markus A , Kramer Mario W 
Published: March 2017

318 Background: We had previously shown that a significant number of patients after radical cystectomy (RC) suffer from changes in bowel habits and defecation. Reports addressing long-term bowel disorders following RC are rare. This cross sectional study evaluates long-term bowel issues in a large cohort with the help of an issue-tailored questionnaire. Methods: For this purpose a questionnaire assessing changes in bowel function and its impact on daily life was developed and distributed among members of the German bladder cancer self-help group. A total of 431 patients after RC were evaluated. Symptoms such as diarrhea, constipation, urge to defecate, sensation of incomplete defecation, flatulence, and impact on quality of life (QoL) were assessed. Results: A total of 324 patients were followed ≥1 year, 43% patients of those reported current bowel disorders, 40% life restriction and 60% dissatisfaction. Most frequent bowel symptoms were flatulence (49%), followed by diarrhea (30%) and the sensation of incomplete defecation (23%). The highest prevalence rate of diarrhea is reported in year 3 after surgery: <3 months after surgery 14%, 3-11 months 21%, 12-23 months 18%, 24-35 months 44%, 36-59 months 36%, ≥60 months 27% (p<0.01). Also flatulence is a long-term bowel symptom with a prevalence of 50% ≥1 year vs 37% <1 year after surgery (p=0.0334), while the prevalence of other bowel symptoms did not change over time. After 12 months, diarrhea significantly correlated with flatulence, uncontrolled stool loss, urge to defecate, younger age at time of surgery, and the size of bowel segment for urinary diversion (all p<0.01). Patients suffering from diarrhea report a higher defecation frequency, a lower QoL, a higher dissatisfaction level, a lower energy level (all p<0.01), and a lower health state (p=0.0488). Conclusions: Diarrhea is a prominent long-term bowel symptom after RC. A better understanding of long-term bowel symptoms might lead to optimized surgical procedures, post-operative medication and patient education.
Can index lesion tumor volume on T2 weighted MRI predict biochemical recurrence following radical prostatectomy?
Authors: Sugano Dordaneh , Sidana Abhinav , Calio Brian P. , Gaur Sonia , Maruf Mahir , Jain Amit L , Merino Maria J , Choyke Peter L. , Turkbey Baris , Wood Bradford J. , Pinto Peter A. 
Published: March 2017

32 Background: Several studies have demonstrated an association in prostate cancer patients between the tumor volume of the index lesion calculated from whole mount pathology after radical prostatectomy and biochemical recurrence (BCR). We aimed to evaluate whether the index lesion tumor volume (ILTV) measured on MRI would have similar predictive ability. Methods: Clinical and pathologic data from a prospectively maintained, single-institution database was analyzed for 501 patients who underwent RARP (without prior therapy) between 2007 and 2016. Patients were excluded if they were found to have metastatic disease on pathology or if postoperative PSA ≥ 0.2ng/ml after RARP. ILTV was calculated from T2W MRI by multiplying length by width by depth by 0.52. Tumor volume was stratified into two categories based on the cutoff of 2cm3. BCR was defined as 2 PSA values ≥ 0.2 ng/ml, 1 PSA value ≥ 0.4 ng/ml, or receipt of radiation therapy/hormonal therapy after RARP. Cox proportional hazard regression was used to assess associations of clinical, imaging, and histopathological variables with BCR. Results: The median age of our cohort was 60 years (IQR 10) and median PSA was 6.20 ng/ml (IQR 6). Of the 493 patients who met our inclusion criteria, 55 (11.2%) experienced BCR. Patients with ILTV > 2cc had a higher incidence of BCR compared to those with ILTV < 2cc (18.0% vs 8.8%, p = 0.008). On univariate analysis, age (HR 0.96, p = 0.026), PSA (HR 1.04, p < 0.001), black race (HR 1.816, p = 0.047), Gleason 8-10 on biopsy (HR 3.725, p < 0.001), and ILTV (HR 2.496, p = 0.002) were significant for prediction of BCR. Although age (HR 0.955, p = 0.021), PSA (HR 1.029, p = 0.013), and Gleason 8-10 on biopsy (HR3.367, p < 0.001) were found to be independent predictors of BCR, tumor volume was not found to be an independent predictor (HR 0.960, p = 0.642). Conclusions: Although ILTV alone was predictive of BCR, ILTV was not found to be an independent predictor of BCR, indicating that at this time, MRI cannot yet measure ILTV with enough accuracy to predict oncologic outcomes. As imaging technology improves, ILVT may provide additional prognostic information.
A genome-wide query of somatic copy number alterations to predict lymph node metastases and survival in patients with muscle-invasive bladder cancer.
Authors: Lindquist Karla , Sanford Thomas , Friedlander Terence W. , Paris Pamela , Porten Sima P. 
Published: March 2017

325 Background: Patients with muscle-invasive bladder cancer (MIBC) have a poor prognosis if the cancer has metastasized to surrounding lymph nodes (LN). Adding tumor-based genomic tests that improve prediction of LN status and prognosis over clinical variables alone would be useful to clinicians in making treatment decisions, potentially improving outcomes for these patients. Methods: We performed a genome-wide query of copy number alterations (CNAs) in MIBC tumors from 237 patients in The Cancer Genome Atlas who had radical cystectomy and lymphadenectomy ( ≥ 10 nodes) without neoadjuvant treatment. We independently analyzed pathology reports and copy number data to confirm LN status and gene-level CNAs. Using elastic net and logistic regression models, we sought to identify a set of genes with CNAs that predict LN status. We also tested for association between CNAs and survival. Results: We identified 26 genes with CNAs that predicted LN status. Those located on chr3p25 and chr11p11 had gains associated with LN positivity after adjusting for age, gender, race, pathological tumor stage, histology, and number of nodes examined (p = 0.03). CNAs at these loci were also associated with one-year survival in the cohort overall (p < 0.01), as well as in LN-positive patients after adjusting for node stage, LN density, and extracapsular extension (p < 0.01). Conclusions: We have identified a small set of genes with CNAs in MIBC tumors that robustly predict LN status and one-year survival. A simple copy number-based test based on these genes could potentially improve preoperative LN status determination and help inform adjuvant treatment decisions to improve outcomes in MIBC patients.
Prostate cancer in 671 hypogonadal men with and without long-term testosterone treatment: Results from a controlled registry study.
Authors: Haider Ahmad , Haider Karim Sultan 
Published: March 2017

33 Background: Despite persisting concerns, there is no evidence that TTh in men with hypogonadism increases PCa incidence or severity. Rather, a Canadian group recently found that long-term TTh decreased the risk of PCa diagnosis (Wallis et al., Lancet Diab Endocrinol 2016; 4:498). We assessed incidence and severity of PCa in hypogonadal men on long-term TTh (T-group) in comparison to an untreated hypogonadal control group (CTRL). Methods: 375 men (age range: 33-70) with testosterone ≤ 350 ng/dL and symptoms received testosterone undecanoate 1000 mg every 3 months for up to 10 years. 296 hypogonadal men (57-74) opted against TTh. Median follow-up: 7 years. Prostate volume (PV), PSA, weight and C-reactive protein (CRP) were measured and digital rectal examination/transrectal ultrasound performed before treatment initiation and then regularly every 3-6 months. Biopsies were performed when indicated according to EAU guidelines. Results: In the T-group, PV increased slightly but significantly by 2.41 mL (p < 0.0001), PSA by 0.22 (NS). In CTRL, PV decreased slightly but significantly by -1.20 mL (p < 0.005), PSA by -0.38 (p < 0.0001). Weight dropped by 18.23% in the T-group and increased by 1.78% in CTRL, CRP decreased significantly in the T-group and remained unchanged in CTRL. In the T-group, 8 men (2.1%) were diagnosed with PCa. In CTRL, 12 (4.1%) were diagnosed with PCa. The incidence per 10,000 years was 32 in the T-group and 64 in CTRL. The mean baseline age of PCa patients was 65 years in both groups. Prostatectomy was performed in all men. In the T-group, all patients had a Gleason score ≤ 6 and a predominant Gleason score of 3. Tumor grade was G2 in all 8 (100%), tumor stage T2a in 6 (75%) and T2b in 2 (25%) patients. In CTRL, Gleason score was > 6 in all 12 patients. Three men had a predominant Gleason score of 3, 8 had 4, and 1 had 5. Tumor grade was G2 in 5 (41.7%) and G3 in 7 (58.3%) patients, tumor stage T2b in 1 (8.3%), T2c in 1 (8.3%), T3b in 4 (33.3%) and T3c in 6 (50%) patients. Conclusions: TTh in hypogonadal men regularly monitored may decrease incidence of PCa compared to hypogonadal CTRL. PCa was less severe in the T-group. Weight loss and reduced inflammation by TTh may have contributed to our findings.
Avelumab in patients with metastatic urothelial carcinoma: Pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial.
Authors: Patel Manish R. , Ellerton John Allan , Infante Jeffrey R. , Agrawal Manish , Gordon Michael S. , Aljumaliy Raid , Britten Carolyn D. , Dirix Luc , Lee Keun-Wook , Taylor Matthew H. , Schöffski Patrick , Wang Ding , Ravaud Alain , Gelb Arnold , Xiong Junyuan , Rosen Galit , Apolo Andrea B. 
Published: March 2017

330 Background: Avelumab is a fully human anti‒PD-L1 IgG1 antibody with promising efficacy and safety in patients (pts) with metastatic urothelial carcinoma (mUC). To further characterize the clinical activity of avelumab in mUC, we report a planned interim pooled analysis of 2 cohorts from a large phase 1b trial (NCT01772004). Methods: Pts with mUC progressed after platinum-based therapy or cisplatin-ineligible, and unselected for tumor PD-L1 expression, received avelumab 10 mg/kg (1 h IV) Q2W. Response was assessed every 6 wks by independent review per RECIST v1.1. Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression (clone 73-10). Results: As of Mar 19, 2016, 241 pts received avelumab for a median of 8 wks (range 2-80); median follow-up was 7.3 mos (range 0-18.2). Primary tumor sites were upper tract (renal pelvis/ureter [23.7%]) and lower tract (bladder/urethra [76.3%]). 95.4% of pts had progressed on prior platinum therapy, and 63.4% had received ≥ 2 prior lines for advanced disease (range 0-6). In 153 pts with ≥ 6 mos follow-up, confirmed ORR was 17.6% (95% CI 12.0-24.6) with 9 complete responses and 18 partial responses; 24/27 (88.9%) were ongoing. Median DOR was not reached, and the 24-wk DOR rate was 92.0% (95% CI 71.6, 97.9). 36 pts had stable disease as best response (disease control rate 41.2%). Median PFS was 6.4 wks (95% CI 6.1-11.4), and median OS was 7.0 mos (95% CI 5.6-11.1). Based on a ≥ 5% PD-L1 staining cutoff in evaluable pts with PD-L1+ (n = 56) and PD-L1– (n = 75) tumors, ORR was 25.0% (95% CI 14.4-38.4) vs 14.7% (95% CI 7.6-24.7; p = 0.178). Treatment-related adverse events (TRAE) of any grade occurring in ≥ 10% of pts were infusion-related reaction (22.8%) and fatigue (12.0%). 7.5% had a grade ≥ 3 TRAE; fatigue (1.2%)/asthenia (0.8%) occurred in > 1 pt. 28 pts (11.6%) had an immune-related TRAE (grade ≥ 3 in 2.5%). There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab is well tolerated and shows promising clinical activity, including durable responses, in pts with mUC, regardless of tumor PD-L1 expression status. Follow-up is ongoing. Clinical trial information: NCT01772004.
A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma.
Authors: Petrylak Daniel Peter , Arkenau Hendrik-Tobias , Perez-Gracia Jose Luis , Krebs Matthew , Santana-Davila Rafael , Yang Jing , Rege Jessicca , Mi Gu , Ferry David , Herbst Roy S. 
Published: March 2017

349 Background: Hallmarks of tumor growth include immunosuppression and angiogenesis. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the urothelial tumor microenvironment. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02443324) enrolled patients (pts) with histologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with prior progression on platinum-based systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. Eligible pts received R at 10 mg/kg on Day 1 given with P 200 mg on Day 1 q3W. PD-L1 was classified as positive (≥1%) or negative using the DAKO PD-L1 22C3 IHC pharmDx assay. Tumor response was assessed every 6 wks (RECIST v1.1). The primary objective was to assess safety and tolerability of adding R to P and preliminary efficacy will be assessed as a secondary objective. Results: As of 23-June-2016, 24 pts have been treated. The median age was 63 years, 58% were male, 50% had ECOG PS 0, 50% were PD-L1 positive and 67% received study treatment as third or subsequent regimen. Median duration of treatment was 2.14 mo and 2.37 mo for R and P, respectively. All grades treatment-related AEs (TRAE) occurred in 13 (54%) pts; TRAEs occurring in ≥10% of pts were fatigue (21%), nausea (17%), pyrexia (13%), elevated alanine aminotransferase (13%) and elevated aspartate aminotransferase (13%). Three (13%) pts had grade 3 TRAEs (hypertension, colitis, pulmonary embolism; n=1 each). No treatment-related grade 4 or 5 events occurred. Preliminary efficacy data showed two (8%) PD-L1 positive pts had confirmed partial response, 10 (42%) pts had stable disease, and 10 (42%) had progressive disease as their best response. Two (8%) pts were not evaluable for response at the time of analysis. Median duration of response has not been reached (>2.92 mo). Median PFS was 1.87 mo (95% CI, 1.28 to 3.38). Five (21%) pts remain on treatment. Conclusions: R plus P generated no new safety signals and demonstrated antitumor activity in pts with previously treated advanced urothelial carcinoma. Clinical trial information: NCT02443324.
Assessment of blood and tissue myeloid derived suppressor cells (MDSC), clinicopathologic factors, and treatment response in urothelial carcinoma (UC) patients (pts) undergoing surgery.
Authors: Ornstein Moshe Chaim , Diaz-Montero C. Marcela , Rayman Patricia A. , Elson Paul , Haywood Samuel , Kim Jin Sub , Pavicic Paul G , Finke James , Rini Brian I. , Stephenson Andrew J. , Lamenza Marcelo , Dann Priscilla , Brey Nicole DiBiase , Devonshire Sarah , Ko Jennifer S , Fergany Amr Farouk , Ernstoff Marc S. , Hoimes Christopher J. , Garcia Jorge A. , Grivas Petros 
Published: March 2017

362 Background: MDSC are heterogeneous immunosuppressive cells with potential predictive/prognostic role in cancer. The association between MDSC, clinicopathologic factors and pathologic response in pts with UC merits evaluation. Methods: Peripheral blood and/or tissue was collected from 120 pts. MDSC were measured in fresh unfractionated whole blood (WB), in peripheral blood mononuclear cells (PBMC) and fresh tumor tissue. MDSCs were identified by flow cytometry in WB and defined as LinloCD33+/HLADR- ((T)otal MDSC). MDSC subsets were defined as LinloCD33+/HLADR- and (G)ranulocytic (CD15+CD14-), (M)onocytic (CD15-CD14+), (I)mmature (CD15-CD14-, CD11b+ ). MDSC populations were presented as % of live nucleated blood cells and as absolute numbers from WB. Spearman correlations (r) and Wilcoxon rank sum test were used to assess correlations between MDSC populations, clinicopathologic factors and pT0N0%. Results: Of 120 pts, 82 were non-metastatic: 58 had only blood, 23 had blood & tissue, 1 had only tissue available for analysis. Of these 82 non-metastatic pts, 70 were men, median age 68; 81 pts had primary UC histology, 1 small cell cancer, 24 had mixed UC histology; 24 had prior intravesical therapy, 34 had neoadjuvant therapy (79% cisplatin-based, 21% unknown), 4 pts had post-op recurrence. At cystectomy: 15/82 pT0, 22/82 pT3/4; 37/82 CIS; 8/78 pN+. Significant associations were seen between MDSC blood levels and mixed histology, CIS, pN+, and lower pT0N0% (Table). Tumor M-MDSCs were associated with pN+ (p=0.05). There was significant correlation between tumor and WB % M-MDSC (r=0.55, p=0.007), and tumor and WB % G-MDSC (r=0.46, p=0.03). Conclusions: Blood MDSC levels correlate with several clinicopathologic factors and may predict pathological complete response (pT0N0). Assessment of association between MDSC levels, outcome and immunotherapy response is ongoing including in metastatic pts. [Table: see text]