bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predictive value of DRE in the modern era of prostate cancer diagnostics.
Authors: Andersson Joel Marcus , Nordström Tobias , Eklund Martin , Gronberg Henrik 
Published: March 2019

48 Background: DRE (digital rectal examination) suspicious for prostate cancer is still used as a clinical tool to diagnose prostate cancer. We aim to analyse the predictive value of DRE to diagnose prostate cancer ISUP grade group ≥2 (GG≥2) prostate cancer including the setting of STHLM3 test as a variable. Methods: The previously described STHLM3 screening-cohort included men between 50 to 70 years with ≥10% risk of prostate cancer as assessed by PSA or the Stockholm3 test and invited for transrectal biopsy (TRUSbx). All 7415 biopsied men was included for analysis. DRE status was categorized as T1-T4. We analysed sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for DRE status of T2-4 to predict GG≥2 and GG≥3 in biopsies. In a multivariate logistic regression analysis; we adjusted for PSA, age, PVol, earlier biopsy (EB) and adjusted STHLM3 model risk set to exclude DRE and prostate volume (PVol). We calculated adjusted odds ratio (OR) for different strata of adjusted STHLM3 risk. Results: Prevalence of ISUP≥2 was 16.8% (1,243/7415). 9.7% (716/7415) men had DRE suspicious for cancer (T2-4) with a Sn to detect GG≥2 of 25.2%. Sp, PPV and NPV was 93.5%, 43.7% and 86.1%, respectively. In univariate model the OR for DRE T2-4 vs. T1 to predict GG≥2 was 4.28 (95% CI 4.09–5.67). Logistic regression analysis including also age, PVol, PSA, earlier biopsies and adjusted STHLM3 risk (%) gave an OR for DRE T2-4 of 2.87 (95% CI 2.36–3.49). In the same analysis stratified PSA group 5-10 ng/ml with PSA < 3 ng/ml as baseline gave OR = 3.21. Using the same univariate model, OR for DRE T2-4 vs. T1 to predict GG≥3 was 6.68 (95% CI 5.44–8.21) and in the multivariate model OR was 3.25 (95% CI 2.54–4.17). Conclusions: As a diagnostic test DRE holds little merit on its own but in combination with other clinical factors and biomarkers in this study we could show that it contributes with value. Just under half of men with DRE suspicious for cancer has GG≥2 cancer. This study does not establish evidence to rule out DRE as a clinically valuable adjunct to PSA, other clinical parameters and new biomarkers like STHLM3.
Sarcopenia in bladder cancer patients is an unmodifiable outcomes predictor.
Authors: Barton Gregory John , Wang Jeanette , Chang Andrew , Tan Wei Phin , Fantony Joseph J , Wischmeyer Paul E , Gupta Rajan T. , Inman Brant Allen 
Published: March 2019

480 Background: Sarcopenia, a severe loss of skeletal muscle mass, predicts poor outcomes in bladder cancer (BC). But, why sarcopenia occurs in BC is unknown. Our objective was to assess if diet and physical activity were the primary factors causing sarcopenia, and thus assess if sarcopenia could be addressed by lifestyle interventions. Methods: 286 patients filled out the International Physical Activity Questionnaire Long Form (IPAQ-L) and the Diet History Questionnaire II (DHQ2), had a CT abdomen/pelvis within 6 months of questionnaire administration and met inclusion criteria. The DHQ2 was converted into Healthy Eating Index 2010 scores (HEI2010). Skeletal muscle area (SM, cm2) area was measured at the L3 level using Slice-O-Matic software and divided by height (m2) to arrive at skeletal muscle index (SMI). Sarcopenia was defined as SMI < 52.4 in men and < 38.5 in women. Three raters read the images and inter-rater reliability was measured by the intra-class correlation coefficient (ICC). Associations among patient demographics, tumor characteristics, physical activity, diet quality, and body composition were examined by stratified analyses and regression models with R 3.2.3. Results: Reliability was very high, ICC=0.97. Sarcopenia was present in 71% of males and 55% of females. Key predictors of decreasing SMI included increasing age (p < 0.001), female gender (p < 0.001), and white race (p < 0.001). When adjusted for these unmodifiable patient factors, there was no association between SMI and variables such as Elixhauser comorbidity score, AJCC stage, tumor grade, and procedure type. With respect to modifiable lifestyle factors, there was no association between SMI and average weekly MET-min of physical activity level (p = 0.99) nor the daily consumption of calories (p = 0.69), protein (p = 0.28), fat (p = 0.19), or carbohydrate (p = 0.77). The HEI2010 diet score was not associated with SMI (p = 0.66). Conclusions: The three strongest predictors of decreasing muscle mass (i.e. sarcopenia) in BC patients are age, gender, and race. Modifiable risk factors, such as diet and physical activity levels, did not affect sarcopenia. Therefore, we would not expect that targeted lifestyle interventions would affect sarcopenia and improve BC outcomes.
Comprehensive radiogenomics analysis of qualitative and quantitative features of cross-sectional imaging in the TCGA project in MIBC.
Authors: Lerner Seth P. , Duddalwar Vinay , Huang Erich , Altun Ersan , Bathala Tharakeswara , Kennish Steven , Ibarra Juan , Lucchesi Fabiano , Muglia Valdair Francisco , Thomas Stephen , Vikram Raghu , Vargas Hebert Alberto , Cen Steven Yong , Hwang Darryl , King Kevin George , Varghese Bino , Fevrier-Sullivan Brenda , Kirby Justin , Jaffe Carl , Freymann John 
Published: March 2019

482 Background: Quantitative imaging descriptors derived from CT and MRI can be integrated with genomic data that may be used as non-invasive prognostic or predictive biomarkers. We report an integrated radiogenomics project designed to develop subjective and objective parameters extracted from cross-sectional imaging of MIBC from studies archived in the TCIA and linked to the TCGA project. Methods: We reported comprehensive integrated genomic analysis of 412 tumors (Cell 2017). 7 of 33 tissue source sites submitted CT scans to the TCIA (n=106). We developed 17 features describing tumor size/location, metastases sites, and tumor morphology; 9 GU radiologists reviewed the scans in a blinded manner. EH analyzed the data independent of the radiologists. We computed kappa statistics for categorical features and coverage probabilities for quantitative features (Lin et al 2002). The tumor was segmented on an axial image and the segmented image analyzed using a radiomics panel (radiomicslab.usc.edu). Associations between individual features and subtypes were assessed (Fisher’s Exact Test) for categorical features and Kruskal-Wallis Test for quantitative features. Results: Substantial agreement (k≥ 0.6) was observed in 4 features: tumor laterality, tumor within bladder diverticulum, right and left UVJ involvement and hydroureter. We observed weak agreement (95% CI <0.4) for bladder neck, posterior bladder, dome, and trigone involvement, tumor margin, internal architecture, radiographic stage, left upper tract involvement, and metastases. The coverage probability for lesion size was 0.59 (0.544-0.638) (Figure). Tumor morphology was associated with microRNA cluster, with diffuse wall thickening having a higher tendency toward Clusters 3 and 4 (p < .001). Radiomic analysis identified statistically significant associations of mutations in FGFR3, CREBBP, CASP8 and EP300 with multiple radiomic features. Conclusions: This blinded comprehensive assessment of features extracted from CT images highlights many of the ongoing challenges in staging patients with MIBC. Preliminary analysis shows promise in analyzing associations between radiomic features and mutations.
Utilization and outcomes of adjuvant radiation therapy after cystectomy for urothelial carcinoma.
Authors: Verlage Kenneth , Isharwal Sudhir 
Published: March 2019

487 Background: Positive surgical margins with radical cystectomy for invasive urothelial cancer are associated with adverse prognosis. In non-metastatic patients, adjuvant radiation therapy (ART) is sometimes employed for patients with positive margins or locally advanced stage. However, evidence for benefit of ART in these patients to improve survival is limited. In this study, using a national database we investigate the factors associated with use of ART and its impact of the overall survival. Methods: National Cancer Database was queried for patients who underwent radical cystectomy from 2004-2013 for invasive urothelial cancer. Inclusion criteria were urothelial histology, pT2 stage with positive surgical margins or ³pT3 , and no evidence metastasis. Patients with regional or distant metastasis or patient who underwent adjuvant chemotherapy were excluded. Univariate and multivariate analysis performed to assess the factors associated with the use of ART. Overall survival was compared using log rank test. Results: In total, 18,828 patients met the inclusion criteria, of which 359 (1.91%) underwent ART. Mean duration between radical cystectomy and ART was 4.4 months. On univariable analysis, Black or Hispanic race, Medicare/Medicaid insurance status, treatment at community health center, ileal conduit diversion, advanced pathological stage (pT3/T4) were associated with higher use of ART (all p<0.005). On multivariate analysis community health facility and adequate lymph node dissection (>10 lymph nodes excision) were associated with use of ART (all p<0.05) (see table). The use of ART was not associated with improved overall survival. Conclusions: The utilization of ART after radical cystectomy for urothelial carcinoma is low. The benefit of ART on the overall survival is not clear and would need further investigation. [Table: see text]
Urologic malignancies: A comparison of outcomes after index surgery between academic and community hospitals.
Authors: Syed Jamil , Abello Alejandro , Javier-Desloges Juan , Leapman Michael , Kenney Patrick Aloysius 
Published: March 2019

489 Background: To compare the rate of hospital based outcomes in patients with urologic malignancies who underwent surgery as part of treatment in academic and community hospitals. Methods: We reviewed the Vizient Clinical Database from September 2014 to December 2017. Vizient is a member-driven health services organization that includes ~99% of academic hospitals (AH) and more than 40 community hospitals (CH). This is a comparative database comprised of administrative billing. Data include patient demographics, readmission rates, costs, LOS, case mix index (CMI) and mortality. Patients aged ≥ 18 were included and ICD-9 and ICD-10 codes were used to identify patients with urologic malignancies who underwent surgical treatment. Chi square and student t-tests were used to compare categorical and continuous variables, respectively. Results: We identified a total of 37,628 cases. There were 33,290 (88%) procedures performed in AH and 4,330 (12%) in CH. These included radical prostatectomy (RP) 18,540, radical nephrectomy (rNx) 8,059, partial nephrectomy (pNx) (5,287), radical cystectomy (4,421), radical nephroureterectomy (rNu) (1,006), and partial cystectomy (321). There were no significant differences in 30-day readmission rates or mortality for any procedure between AH and CH. LOS was significantly lower (P<0.01) for radical cystectomy (8.83 vs 11.43 days) and RP (1.63 days vs 1.77 days) in AH, and lower in CH for rNx (4.93 vs 4.51, P: 0.03). AH had a significantly lower amount of partial cystectomies performed when compared to community centers (6.2% vs 16.2% P<0.001), and a similar number of partial nephrectomies performed (39.8% vs 38.0%, P=0.2). The mean direct cost for index admission was significantly higher in AH for rNx, pNx, rNu, and RP. Case complexity using the CMI was similar between CH and AH. Conclusions: The Vizient clinical database provides a novel resource for observational data at US hospitals. Despite academic and community hospitals having similar case complexity, direct costs were lower in community hospitals without an associated increase in readmission rates or deaths. The only clinically significant difference in length of stay was shorter stays for cystectomy in academic centers.
Rectal toxicity results for patients treated with HDR brachytherapy as monotherapy versus dose-escalated external beam radiotherapy for localized prostate cancer.
Authors: Parzen Jacob Samuel , Ye Hong , Gustafson Gary S. , Martinez Alvaro , Sebastian Evelyn , Limbacher Amy , Krauss Daniel J. 
Published: March 2019

5 Background: We present a large retrospective analysis comparing rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. Methods: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. 545 (20.3%) received HDR and 2138 (79.7%) EBRT. HDR fractionation was 38 Gy/4 fractions (n=321), 24 Gy/2 (n=96), or 27 Gy/2 (n=128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). All EBRT patients underwent 3D image guidance via an off-line adaptive process. Treatment was directed to prostate only (n=780) or prostate and seminal vesicles (n=1351). No nodal therapy was given. Target volume for HDR patients included the prostate with no expansion. Acute and chronic gastrointestinal (GI) toxicity was defined as occurring ≤ 6 and > 6 months, respectively, after radiotherapy and was graded per CTCAE version 3.0. Toxicity variables were analyzed with χ2 test. Results: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 69.1% of EBRT patients received IMRT with the remainder treated using 3D conformal technique. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥ 2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p=0.001). Rates of chronic grade ≥ 2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p=0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥ 2 were 2.4% vs. 10.5% (p < 0.001) for HDR vs. EBRT, respectively. For the 1478 EBRT patients treated with IMRT, acute and chronic rates of any grade ≥ 2GI toxicity were 4.2% and 5.6%, respectively, compared to 1.5% (p=0.002) and 2.4% (p=0.002), respectively, for HDR patients. Conclusions: In appropriately selected patients with localized prostate cancer undergoing definitive radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing acute and chronic rectal toxicity.
Multi-institutional analysis of high-risk prostate cancer patients treated with stereotactic body radiotherapy.
Authors: Jiang Naomi Y , King Christopher R. , Katz Alan J. , Collins Sean P. , Aghdam Nima , Suy Simeng , Stephans Kevin L. , Reddy Chandana A. , Kaplan Irving D. , Appelbaum Limor , Dang Audrey , Yuan Ye , Nickols Nicholas George , Steinberg Michael L. , Kupelian Patrick , Kishan Amar Upadhyaya 
Published: March 2019

51 Background: Stereotactic Body Radiotherapy (SBRT) delivers ablative doses of radiation (RT) over a course of five treatments and has been increasingly used as a definitive RT option for low- and intermediate-risk prostate cancer (PCa). Ongoing prospective trials are evaluating the efficacy of SBRT for high-risk PCa, but clinical outcomes reports are limited. Methods: Patients treated for high-risk PCa between 2006-2017 at any of five institutions were included. SBRT doses ranged from 35-40 Gy in 5 fractions per institutional standards, with one institution using an integrated boost approach. The Phoenix definition was used to define biochemical failure (BCR). Physician-reported genitourinary (GU) and gastrointestinal (GI) toxicity outcomes were scored using the Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events systems. Results: In total, 182 patients were included in this study with a median follow-up time of 38.4 months (mos). The median age was 72. Most patients (72%) had Gleason 8-10 disease. Sixty-eight percent of patients received androgen deprivation therapy (ADT) for a median of 9 mos (interquartile range 6-9 mos). The rate of distant metastases was 3.8%. There were no acute Grade 3 (G3) or higher GU or GI toxicities. Three patients (1.6%) experienced a late G3 GU toxicity and one patient (0.5%) experienced a late G3 GI toxicity. The incidence of BCR was significantly higher in patients who did not receive ADT (30% vs. 15%, p = 0.02 by Chi-square). Conclusions: In this multi-institutional study, SBRT demonstrated an acceptable safety profile for the treatment of high-risk PCa. Longer term follow-up is necessary to evaluate the oncologic efficacy of this approach, but given the potentially higher incidence of BCR without ADT, ADT likely has an important oncologic role even with SBRT regimens.
Outcome of men with relapses after adjuvant BEP for clinical stage I nonseminoma.
Authors: Fischer Stefanie Christine , Tandstad Torgrim , Cohn-Cedermark Gabriella Elisabeth , Thibault Constance , Vincenzi Bruno , Klingbiel Dirk , Albany Costantine , Necchi Andrea , Terbuch Angelika , Lorch Anja , Aparicio Jorge , Heidenreich Axel , Hentrich Marcus , Wheater Matthew James , Langberg Carl Wilhelm , Stahl Olof , Beyer Joerg , Gillessen Silke 
Published: March 2019

510 Background: Clin. stage I (CSI) non-seminoma (NS) is disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant (adjuv) chemotherapy with BEP after which relapses are rare. Little is known about the outcome of patients (pts) relapsing after such treatment. Methods: Data from 51 pts with CSI NS and relapse after adjuv BEP from 18 centers/11 countries was collected and retrospectively analyzed. Primary endpoints were OS and PFS calculated from start of treatment of relapse. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results: 23 pts received one cycle adjuv BEP and 28 pts two. Median time to relapse was 13 months, with the earliest relapse two months after start of adjuv BEP and the latest relapse recorded after 26 years. According to IGCCCG, 84% of pts classified as good prognosis at relapse. With a median follow up of 50 months 5y PFS was 64% (95% CI 52-80%) and 5y OS 79% (95% CI 68-92%). Treatment upon relapse was diverse, the majority of pts received combination- chemotherapy and surgery. 10 pts (20%) had pure mature teratoma at relapse treated with surgery alone. None of these pts experienced a second relapse. If teratoma relapses were excluded, 5y PFS dropped to 58% (44-77%) and 5y OS to 76% (63-92%). Relapses later than three years after adjuv therapy occured in 15/51 pts. (29%) and were associated with a statistically significant higher risk of death from germ-cell cancer (p=0.02). 15/51 pts (29%) experienced a subsequent relapse. Excluding pts with teratoma only, subsequent relapses occured in 15 of the remaining 41 pts (37%). At last follow-up, 41/51 (80%) pts were alive and disease-free, 8/51 (16%) had died from progressive disease and one pt each had died from therapy-related or other causes. Conclusions: Outcome of pts with relapse after adjuv BEP seems to be better compared to pts with relapse after metastatic disease, but worse compared to de novo metastatic pts. There is a substantial rate of late and subsequent relapses. Pts and care-takers need to be informed about this and therapy intensification at first relapse might be considered. However, considering the low rate of relapses, OS in general for CSI NS pts receiving adjuv BEP is excellent.
Cross-trial comparison of taxane versus non-taxane combination chemotherapy regimens for advanced penile cancer (APC): A systematic review.
Authors: Al-Ezzi Esmail Mutahar , Riromar Jamila Jama Almi , Amir Eitan , Fazelzad Rouhi , Hansen Aaron Richard 
Published: March 2019

511 Background: Penile cancer is rare and there are scant data on the optimal chemotherapy regimen. The majority of trials are single arm, non-randomized studies. Here we report on a systematic review aiming to compare taxane combination chemotherapy regimens with non-taxane regimens for APC. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. Medline, Embase and Cochrane Central Register of Controlled Trials databases were searched using the following terms: penile cancer, penis, antineoplastic combined chemotherapy, taxane, docetaxel, paclitaxel, platinum, cisplatin, carboplatin. Studies were identified using preplanned eligibility criteria by 2 investigators (EA-E and JR). Data were extracted independently by EA-E and JR. Studies were weighted by study sample size and those comparing taxane-based chemotherapy were compared to non-taxane therapy using the Mann Whitney test. Results: The search identified 1929 publications and 40 were selected for further assessment. Of these, 8 met eligibility criteria (7 prospective and 1 retrospective). Three studies tested taxane combinations (docetaxel, cisplatin and 5FU [DCF] and paclitaxel, ifosfamide and cisplatin [TIP]). A total of 148 men with APC were treated with non-taxane regimens and 98 men received a taxane combination. Patient characteristics (age, ECOG status, stage, number of cycles) were comparable between the two groups. Partial response and overall response rates were significantly higher in the taxane versus the non-taxane group (35.7% vs. 24.2% p = 0.01 and 41.9% vs. 32.5% p = 0.007) respectively. Grade3/4 neutropenia was significantly higher in taxane group than non-taxane group (27.8% vs 19.4% p = 0.02). Median PFS and OS was numerically but not significantly higher in the taxane versus the non-taxane group (5.7 vs. 4.4 months, p = 0.45 and 12.1 vs 10 months, p = 0.48, respectively). Conclusions: Compared to non-taxane-based regimens, taxane combinations have higher response rates and may improve survival in APC. Hematologic toxicities are worse with taxane containing regimens. Taxane combinations should be the preferred regimen for suitable men with APC.