bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative risk factors predicting postoperative complications in radical cystectomy for bladder cancer.
Authors: Jensen Derek , Graw Stefan , Niu Sida , Glazyrine Vassili , Koestler Devin , Lee Eugene K. 
Published: March 2017

395 Background: Radical cystectomy is an extensive operation with complications reported in up to 30.5% of patients. High complication rates contribute to increased costs, patient morbidity and mortality. Accurate prospective predictions of patients’ risk for post−surgical complications have the potential to identify at risk patients. Risk estimators have been developed but often involve an extensive number of factors or produce expansive results that are not clinically useful. Methods: 330 patients who underwent radical cystectomy for bladder cancer from January 2008 to July 2014 were included in this study. Potential preoperative risk predictors were collected from medical history, TURBT pathology, preoperative labs, proposed procedure type, and prior treatments. Postoperative complications were graded using the Clavien−Dindo scale. Multivariate logistic regression models were used to predict post−operative complications. Accuracy of prediction models was assessed using the area under the receiver operating characteristic curve. Results: Of the potential preoperative risk factors, 5, 10 and 16 unique predictors along with two way interactions were determined to have strong association with 90 day postoperative complications, yielding an AUC of 0.69, 0.79 and 0.91 respectively. Conclusions: Our findings suggest routinely collected preoperative patient−level clinical variables may be useful for determining patient risk for short−term postoperative complications. The flexibility in our prediction model for the number of predictor inputs allow users to tailor the degree of risk assessment based on a patient’s baseline heath status. A simple and accessible prediction model with selective predictors may help identify at risk patients for patient education, counseling and development of risk reduction strategies.
Combination checkpoint immunotherapy and cytotoxic chemotherapy: Pembrolizumab (Pembro) plus either docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer.
Authors: Lara Primo , Beckett Laurel , Li Yueju , Parikh Mamta , Robles Daniel , Aujla Pawandeep , Pan Chong-xian 
Published: March 2017

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, & 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), & neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 & 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.
Evaluation of the Decipher prostate cancer classifier to predict metastasis and disease-specific mortality from genomic analysis of diagnostic prostate needle biopsy specimens.
Authors: Nguyen Paul L. , Haddad Zaid , Lam Lucia L.C. , Ong Kaye , Buerki Christine , Deheshi Samineh , Yousefi Kasra , Davicioni Elai , Tosoian Jeffrey J. , Lotan Tamara L. , Feng Felix Yi-Chung , Trock Bruce J. , Ross Ashley , Klein Eric A. 
Published: March 2017

4 Background: Accurate risk stratification after diagnosis of prostate cancer (PCa) is key to optimal treatment decision-making. Decipher RP is an extensively validated genomic classifier used to determine biological potential for metastasis. Here, in a multi-institutional cohort, we aimed to evaluate its ability to predict metastasis and prostate cancer-specific mortality from analysis of PCa needle biopsy tumor tissue specimens. Methods: We identified 175 patients treated with either first-line RP or first-line radiation therapy (RT) + androgen deprivation therapy (ADT) with available genomic expression profiles generated from diagnostic biopsy specimens obtained from three tertiary referral centers: Cleveland Clinic, Brigham and Women’s Hospital and Johns Hopkins. The core with the highest grade was sampled and Decipher was calculated based on a locked random forest model. Cox univariable and multivariable (MVA) proportional hazards model and survival c-index were used to evaluate the performance of Decipher. Results: Overall, 85% of patients had NCCN intermediate and high-risk disease. Of the 175 patients, 43% and 57% were treated with first-line RP and RT+ADT, respectively. With a median follow-up of 6 years, 32 patients developed metastases and 11 of these patients died of PCa. For prediction of metastasis 5 years post biopsy, Decipher had a c-index of 0.74 (95% confidence interval [CI] 0.63-0.84) compared to 0.66 (95% CI 0.53-0.77) for CAPRA and 0.66 (95% CI 0.55-0.77) for NCCN risk group. On MVA, when modeled with CAPRA, Bx Decipher remained a significant predictor of metastasis (Decipher Bx hazard ratio [HR] 1.33 per 10% increase in score, 95% CI 1.06–1.69, P = 0.01). Decipher Bx was also a significant predictor of PCSM (Decipher Bx HR 1.57 per 10%, 95% CI 1.07–2.40, P = 0.02) Conclusions: Decipher Bx was able to predict metastasis and PCSM from diagnostic biopsy specimens in a cohort of primarily intermediate and high-risk men regardless of first line treatment. This additional genomic information provides important risk stratification to help guide therapy for men with intermediate- and high-risk disease.
Development of a novel immunotherapy for muscle invasive bladder cancer (MIBC).
Authors: Tcherepanova Irina Y. , Leibovich Bradley C. , Slagter-Jager Jacoba , Dillon Patrick , Leland Shawn Michael , Mynderse Lance A , Costello Brian Addis , Nicolette Charles A. 
Published: March 2017

402 Background: AGS-003 is an autologous tumor RNA-loaded dendritic cell-based immunotherapy being tested in advanced renal cell carcinoma (RCC) patients. The immunologic specificity for the patient’s own tumor is achieved using amplified tumor RNA electroporated into monocyte derived dendritic cells. To produce AGS-003 for RCC patients the RNA is amplified from a 100 mg primary tumor sample obtained via nephrectomy. In this non treatment study we evaluated the feasibility of RNA amplification from MIBC tissue acquired by transurethral resection of bladder tumor (TURBT). Methods: MIBC tissue was obtained via TURBT. Following draining of the irrigant used during the TURBT procedure, tissue was placed into an RNA preservative solution to prevent RNA degradation until processing. Methods developed for the amplification of RCC tumor RNA and RNA quality testing were applied to the RNA extracted from the MIBC specimens. Results: This work demonstrated that the methods developed for the amplification and testing of RNA from RCC can be successfully employed for the amplification of RNA from MIBC specimens collected by TURBT. Results demonstrated that the total RNA yields obtained from bladder tissue exceed that of similar masses of primary RCC tumors. This finding enabled the reduction in the amount of starting material from 100 mg to 50 mg of bladder tissue. The amount of amplified RNA produced from the lower bladder cancer masses were sufficient to support the production of immunotherapy at full scale (17 doses average). Conclusions: These data demonstrate the feasibility of RNA extraction and amplification from muscle invasive bladder cancer tissue and supports our planned phase II clinical study. [Table: see text]
Post-orchiectomy adjuvant therapy versus surveillance for stage IS testicular cancer.
Authors: Kamran Sophia C. , Seisen Thomas , Markt Sarah C. , Preston Mark A , Frazier A. Lindsay , Sweeney Christopher , Beard Clair 
Published: March 2017

406 Background: To assess contemporary treatment patterns and survival for stage IS testicular cancer. Methods: Using the National Cancer Data Base, we identified 1,362 patients with AJCC stage IS testicular cancer (seminoma or non-seminoma) treated between 2004-2012 with either adjuvant therapy (AT) or initial surveillance. AT was defined as the receipt of chemotherapy, radiotherapy (RT), or retroperitoneal lymph node dissection (RPLND) as part of first line treatment after orchiectomy. Annual percent change (APC) in the use of AT was calculated and multivariable logistic regression analysis was performed to identify predictors of receiving AT. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and initial surveillance groups. All analyses were stratified according to histologic type. Results: Overall, there were 581 (43%) and 781 (57%) men with seminoma and non-seminoma, respectively. Among men with seminoma, 61% received AT (RT = 45%, chemo = 16%) while 39% received initial surveillance. The use of AT decreased over the study period (APC = -2.7; 95%CI: -4.4, 1.1; P = 0.001). Predictors of receiving AT included low income (OR = 1.63; 95%CI: 1.03, 2.56; P = 0.04), while year of diagnosis (OR = 0.89; 95%CI: 0.83, 0.96; P = 0.003) predicted the opposite. The 5-year IPTW-adjusted rates of OS were 99% and 97% in the AT and initial surveillance groups, respectively (HR = 0.36; 95%CI: 0.12, 1.14; P = 0.08). Among men with non-seminoma, 47% received AT (chemo = 38%, RPLND = 9%) while 53% received initial surveillance. The use of AT remained stable over the study period (APC = +0.8; 95%CI: -0.7, +2.2; P = 0.29). Predictors of receiving AT included stage ≥ pT2 (OR = 1.78; 95%CI: 1.06, 3.00; P = 0.03), and lymphovascular invasion (OR = 2.68; 95%CI: 1.88, 3.83; P < 0.001). The 5-year IPTW-adjusted rates of OS were 97% and 95% in the AT and initial surveillance groups, respectively (HR = 0.66; 95%CI: 0.27, 1.61; P = 0.36). Conclusions: Trends in the use of AT for stage IS testicular cancer differed according to histologic type. Nonetheless, we report 5-year OS rates of ≥ 95% for seminoma and non-seminoma without any significant benefit with the use of AT.
Evaluation of patient (Pt), treatment, and prognostic factors in urinary tract adenocarcinoma.
Authors: Sadaps Meena , Zahoor Haris , Elson Paul , Emamekhoo Hamid , Schach Kim , Brey Nicole DiBiase , Kaouk Jihad , Haber Georges-Pascal , Gong Michael C. , Berglund Ryan Kent , Krishnamurthi Venkatesh , Ulchaker James , Gilligan Timothy D. , Rini Brian I. , Garcia Jorge A. , Grivas Petros 
Published: March 2017

408 Background: Adenocarcinoma is a rare histological subtype of urinary tract cancer with limited data regarding risk factors, effectiveness of treatment, and prognostic factors. Methods: To identify prognostic features, we evaluated demographics, treatment, and progression-free and overall survival (PFS, OS) in a retrospective review of 49 pts with adenocarcinoma of the bladder (n=35), ureter (n=1), or urethra (n=13) evaluated at Cleveland Clinic from January 2000 to April 2016. Uni- and multi- variable analyses (UVA, MVA) were used to identify prognostic factors. OS was measured from diagnosis to death and PFS from diagnosis to first of recurrence/progression or death. Results: 25 (51%) pts were women, median age at diagnosis was 62 (33-82), 30 pts (61%) presented with hematuria, and 13/36 (36%) had hydronephrosis. Treatment included cystectomy in 43 pts (88%), neoadjuvant chemotherapy in 3 pts (MVAC, gemcitabine/cisplatin, paclitaxel/cisplatin), adjuvant chemotherapy in 2 pts (gemcitabine), and systemic therapy for advanced or recurrent disease in 6 pts. Overall, 23 pts (47%) recurred/progressed and 31 (63%) died [12 without recurrence/progression]. Estimated median OS and PFS from diagnosis were 38.1 and 24.5 months, respectively. Pts with hydronephrosis at time of diagnosis had shorter PFS (p=0.06) and OS (p=0.007). Among the cystectomy pts, MVA identified pN stage and presence of signet-ring cells or papillary component as the only independent predictors of OS, while pN stage was the only independent predictor of PFS. Combining these factors, 3 prognostic groups for OS were identified (Table). Conclusions: pN stage and morphology are independent predictors of OS in pts with urinary tract adenocarcinoma after radical surgery and can stratify pts into distinct prognostic groups. If validated in larger cohorts, these factors could be used for prognostication, clinical decision making, and trial stratification. [Table: see text]
Validation of a 17-Gene Genomic Prostate Score (GPS) as a predictor of biochemical recurrence (BCR) in men with prostate cancer treated with radical prostatectomy (RP) in a community setting.
Authors: VanDenEeden Stephen K. , Zhang Nan , Quesenberry Charles P , Han Jeong S , Leimpeter Amethyst D , Shan Jun , Tsiatis Athanasios C. , Lawrence H. Jeffrey , Febbo Phillip G. , Presti Joseph C 
Published: March 2017

41 Background: Validated biomarkers can improve risk stratification for men with prostate cancer (PCa). A biopsy-based RT-PCR assay that provides a GPS (scale 0-100) has been validated as an independent predictor of adverse surgical pathology and BCR after RP in men with low-risk and low-volume intermediate-risk PCa. We sought to confirm that GPS is a predictor of BCR across the full spectrum of clinical risk (low, intermediate and high) in a large cohort of men with long term follow up within Kaiser Permanente Northern California (KPNC). Methods: From the KPNC clinical database of 6,184 RP treated men diagnosed with NCCN very low, low, intermediate and high-risk PCa between 1995- 2010, we performed a retrospective cohort study using stratified cohort sampling. BCR was defined as either 2 successive post-RP PSAs ≥ 0.2, or initiation of salvage therapy after a rising PSA ≥ 0.1. Archival biopsy tissue was assayed to yield a GPS. Univariable and multivariable Cox proportional hazards models were used to estimate the association, accounting for sampling weights and covariates. Results: Tissue was retrieved for 334 patients. 279 met all eligibility criteria and 259 (93%) generated a valid GPS. The cohort consisted of 117 BCR and 142 non-BCR events. GPS was strongly associated with BCR - HR/20 GPS units = 2.5; p < 0.0001 in univariable analysis, and after adjusting for PSA, clinical T stage and central biopsy Gleason Score (HR/20 units = 2.1; p = 0.002). The association between GPS and BCR was similar within different racial groups. Each of the 4 gene groups in GPS contributed to the prediction of BCR. Conclusions: GPS was associated with BCR independently of other clinical factors in surgically treated men with PCa, and may provide improved risk stratification beyond clinical risk assessment.
Laparoscopic retroperitoneal lymph node dissection (L-RPLND) as therapeutic in stage I nonseminomatous germ cell testicular tumors: Findings from a referral center.
Authors: Nicolai Nicola , Gasperoni Francesca , Biasoni Davide , Tarabelloni Nicholas , Catanzaro Mario , Stagni Silvia , Torelli Tullio , Piva Luigi , Kungulli Afrovita , Tesone Antonio , Giannatempo Patrizia , Raggi Daniele , Necchi Andrea , Salvioni Roberto , Pizzocaro Giorgio 
Published: March 2017

411 Background: Active surveillance or one course of BEP are the usual policies in stage I NSGTT. RPLND has been progressively abandoned due to morbidity and, mostly, to its low reproducibility. L-RPLND was introduced aiming at reducing morbidity, but few systematic data are available concerning its therapeutic efficacy. A long-term accrual in a referral center is presented. Methods: Analysis includes patients undergoing primary L-RPLND between 2000 and 2014, performed by 4 different surgeons. Patients underwent unilateral dissection according to a template in use since 1980. Adjuvant chemotherapy was provided in cases with a positive nodal ratio ≥ 25%. Regular follow-up was provided. Performance, safety and effectiveness measures have been analyzed. Results: Out of 225 patients, full data including clinico-pathologic variables and follow-up are available in 188 cases. Mean age is 31 yrs, vascular invasion is present in 37.2%. Left dissections are 52%. Fifteen (8%) cases have been converted to open RPLND. Median duration of RPLND is 200 min. Median number of removed nodes is 15 (IQR: 11-20). Complications of Clavien Dindo grade ≥ 3 are 9. Twenty-six patients have metastatic nodes (pN+) and 6 received adjuvant chemotherapy. After a median follow-up of 40 months (range: 24, 71), 11 relapses occurred: 6 (3.7%) of 162 pN0 and 5 of 20 pN+ not undergoing adjuvant chemotherapy. Infield recurrences are not reported. All relapsed patients have been rescued by first line chemotherapy. Presence of vascular invasion (p .073) and node ratio as continuous variable (p .097) are not associated with recurrence considering all cases, while conversion to open RPLND is significant (p .019), considering patients operated by the two surgeons with homogeneous variables. Conclusions: L-RPLND in a referral centre is a safe procedure and is apparently effective as open surgery, as there is no an excess of relapses in pN0 cases (3.6%), and the proportion of relapses in pN1 (25%) compares with the traditional figures of open surgery. Conversion to open surgery may be a marker predicting recurrence in a mature phase of experience.
Distress screening in patients with urogenital malignancies.
Authors: Paffenholz Pia , Angerer-Shpilenya Maria , Salem Johannes , Pfister David , Heidenreich Axel 
Published: March 2017

412 Background: Malignant tumors do not only have a somatic but also a psychological impact on patients. To date, only a few studies are available which evaluated the potential psychological burden of patients suffering from urogenital cancers. In this prospective, longitudinal study we examine the baseline psychological distress of patients treated for urogenital malignancies focussing on testicular cancer (TC) and prostate cancer (PCA). Methods: Psychological distress of 192 inpatients treated for urogenital malignancies was evaluated using the distress thermometer (DT), an established tool for the detection of distress, prior to any surgical or systemic therapy. The DT consists of a visual analogue scale ranging from 0 to 10 resulting in a low (0-3), moderate (4-6) or high (7-10) stress level. Furthermore, it contains a 36-item list of problems subdivided into 5 categories (practical, family, emotional, spiritual/religious, physical). Results: The mean DT score was 5 (interquartile range (IQR) 3-7) with the most common stressors being of emotional origin, namely fear (50%), worry (44%), nervousness (42%), sleep disorders (39%) and fatigue (32%). DT analysis did not reveal any difference between the tumor entities but 64% of all patients displayed a moderate to high stress level requiring psycho-oncological support. The comparison of PCA and TC demonstrated a higher distress level in PCA patients in the subgroups of metastatic disease (median 5.5, IQR 4-8 vs. median 4, IQR 2-6; p = 0.018), secondary therapy (median 6, IQR 5-8 vs. median 4.5, IQR 2.75-6; p = 0.023) and salvage treatment (median 7, IQR 4.5-9 vs. 5, IQR 2.75-6; p = 0.021). PCA patients receiving salvage treatment displayed significantly higher distress levels compared to non-salvage treated patients (median 7, IQR 4.5-9 vs. median 5, IQR 2-7; p 0.028). Conclusions: Our study shows that 64% of urological tumor patients should be offered psycho-oncological support. Especially patients suffering from advanced stage PCA seem to have a high stress level. Thus, physicians in the field of urologic oncology should be aware of their patients’ psychological distress in order to identify high-risk patients and provide them with an appropriate psycho-oncological support.
Current patterns of care for patients with stage I testicular seminoma: Survey of U.S. radiation oncologists on treatment recommendations.
Authors: Mitin Timur , Jain Aditya , Degnin Catherine , Chen Yiyi , Hung Arthur , Jaboin Jerry Jeff , Thomas Charles R. 
Published: March 2017

418 Background: Most men with Stage I testicular seminoma are cured with surgery alone, now a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (RO) is unknown. Methods: We have surveyed practicing US RO via a short online questionnaire. Respondents’ characteristics, self-rated knowledge, perceived patient (pt) compliance rates with observation protocols and expected rate of infertility with and without adjuvant treatments were analyzed for association with treatment recommendations. Results: We received 353 responses from practicing US RO, of whom 23% consider themselves experts. Recommendations are summarized in the table. 34% believe that survival is jeopardized in case of recurrence on observation, but this belief does not impact the recommendation. Over 70% of respondents rate non-compliance with observation at > = 30%. Responders with a higher perceived non-compliance rate are more likely to recommend adjuvant therapy (Fisher’s exact p < 0.01). 52% routinely advise fertility assessment and/or sperm banking for pts who elect observation or chemotherapy, and 74% advise for pts undergoing RT. Respondents are more likely to recommend fertility assessment if they perceive a higher rate of infertility (Mantel-Haenszel Chi-square p < 0.01). 45% administer adjuvant RT in pts with elevated pre-orchiectomy alpha-fetoprotein levels. Conclusions: There is a dramatic uptake of observation as the recommended approach to pts with Stage I seminoma in US RO practices, despite a significant concern among practitioners about pt compliance. Further clinical work must establish best practices to minimize the effect on fertility, as well as guidelines for pts with Stage IS testicular seminoma. [Table: see text]