bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-analyte assay for the noninvasive detection of bladder cancer.
Authors: Miyake Makito , Goodison Steve , Chang Myron , Dai Yunfeng , Urquidi Virginia , Rosser Charles Joel 
Published: February 2017

306 Background: Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. Methods: We performed a case-controlled validation study in which voided urines from 550 patients (220 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9,MMP-10, SDC1,CCL18, PAI-1, CD44, VEGF, ANG, CA9,A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. Results: An 3-biomarker model (CA9, PAI-1 and IL-8) achieved the most accurate BCa diagnosis (sensitivity 90%, specificity 88%). These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Conclusions: Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.
Phase I trial of zirconium 89 (Zr89) radiolabeled J591 in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Morris Michael J. , Pandit-Taskar Neeta , Carrasquillo Jorge A. , O' Donoghue Joseph A. , Humm John , Lyashchenko Serge K. , Haupt Eric C. , Bander Neil Harrison , Tagawa Scott T. , Holland Jason P. , Smith-Jones Peter M. , Lewis Jason Stuart , Solomon Stephen Barnett , Scher Howard I. , Larson Steven M. 
Published: February 2017

31 Background: Presently, there are no means of accurately and reproducibly imaging bone metastases for patients with mCRPC. We are investigating a prostate-specific imaging method that can directly visualize metastases using PSMA as a target and Zr89 radiolabeled anti-PSMA antibody J591 as a tracer. Following the FDA roadmap for biomarker development, we report the first human data on the tracer and its preliminary analytic validation. Methods: 5 mCi of Zr89-J591 was administered intravenously and 4 serial PET/CT scans were obtained within the following time intervals post-injection: 2-4 hours, 18-30 hours, 2-5 days, and 6-7 days. Pharmacokinetic (PK) sampling occurred at 5, 30, and 60 minutes post-injection, and at each PET scan. Patients underwent standard cross-sectional imaging, bone scintigraphy, and FDG PET scanning. Metastatic sites were biopsied in order of preference: Zr89-J591 and FDG positivity, then Zr89-J591 and FDG mismatch, and lastly standard imaging and any PET mismatch. Results: Ten patients were scanned, 132 Zr89-J591 positive sites were detected, and 12 lesions (5 bone, 6 node, 1 lung) in 8 patients were biopsied. Tissue correlation: 12/12 biopsies were positive for cancer. 11/12 biopsied lesions (5 bone, 5 node, 1 lung) were positive on Zr89-J591 imaging. 10/12 were positive by standard scans or FDG. 1 lesion was negative by Zr89-J591 PET, but positive by other modalities. Immunokinetics: Blood clearance T1/2α: 7 +/- 4.5 h (1.1-14 h); T1/2β: 62 +/- 13 h (51-89 h); Whole body clearance T1/2: 219 +/- 48 h (153-317 h). Dosimetry: Maximum retention in liver 8 +/- 1.5 SUV; Kidney 4.1 +/- 0.8 SUV; Tumor 8.2 +/- 6.5 SUV (mean SUV in bone 11.13 +/- 7.57 vs. soft tissue 4.31 +/- 2.59). Optimal time for patient imaging after injection, in terms of tumor to background ratios was 7 +/- 1 days. Conclusions: Zr89-J591 imaging demonstrates excellent tumor localization, pathology correlation, and can demonstrate the presence of tumor even when lesions are negative by standard imaging or FDG PET imaging. PK properties of the tracer have been defined. Use of Zr89-J591 to direct biopsies of metastases provides excellent yield. Further studies to examine reproducibility and post-treatment effects are planned. Clinical trial information: NCT01543659.
Selective organ preservation with neoadjuvant chemotherapy in the treatment of muscle invasive transitional cell carcinoma (TCC) of the bladder.
Authors: Hafeez Shaista , Huddart Robert Anthony 
Published: February 2017

310 Background: Radiotherapy has been previously associated with high treatment failure for those with muscle invasive bladder cancer. Evidence suggests modern organ sparing approaches may have favourable outcome in appropriately selected patients. We investigate whether response to neo-adjuvant chemotherapy can guide selection for bladder preservation and identify those patients likely to have greater success with radical radiotherapy treatment. Methods: Retrospective analysis of 94 patients with T2-T4aN0M0 bladder TCC treated between January 2000 and June 2011. Patients received platinum based chemotherapy following transuretheral resection of bladder tumour, with repeat cystoscopy (+biopsy) performed to guide subsequent management. Poor responders were advised to proceed with surgery. We report on the outcome of 79 individuals who received radiotherapy. Results: 56 (60%) patients achieved complete response following chemotherapy (72% with stage T2). 15 (16%) patients achieved partial pathological response. 12 patients had radiological assessment of partial response made. 11 patients had poor response. All patients achieving complete response, 22 with partial response and 1 with poor response proceeded to radical radiotherapy. Median time to disease progression following radiotherapy was 17months (range 8-91). 5 patients developed invasive recurrence, 17 developed superficial recurrence, 4 developed local nodal disease and 7 developed metastasises. After median follow-up of 36 months (range 6-114), 50 patients were alive with no disease, 24 had died (14 from metastatic bladder cancer and 10 from other causes). 5 patients were alive with active disease (4 with localized and 1 with metastatic disease). 13 required cystectomy (9 for superficial disease, 3 for invasive recurrence, and 1 for treatment related toxicity). Of those alive and disease free 84% had an intact bladder. 82% had an intact bladder at last follow-up or death. Conclusions: Neoadjuvant chemotherapy followed by radical radiotherapy allows bladder preservation in over 80% of selected patients with survival rates comparable to contemporary surgical series.
Cost analysis of adjuvant management strategies in early-stage testicular seminoma.
Authors: Cox John A. , Gajjar Shefali R. , Lanni Thomas B. , Swanson Todd A. 
Published: February 2017

320 Background: Acceptable post-orchiectomy management strategies for stage I seminoma include surveillance (SV), para-aortic (PA-RT) radiation therapy, dog-leg (DL-RT) or a single cycle of carboplatin (Carbo). The follow-up recommendations for each option were recently amended by the National Comprehensive Cancer Network (NCCN) in 2012. As such, surveillance imaging after treatment, a contributor to costs, was significantly scaled back. This was driven, in part, by the maturation of data from the MRC TE 19/EORTC 30982 study along with an effort to decrease exposure to frequent CT scans. Methods: NCCN guidelines were used to design treatment plans for each of the acceptable adjuvant treatments strategies: SV, Carbo (AUC=7), PA-RT (20 Gy), DL-RT (20 Gy) and salvage chemotherapy (bleomycin, etoposide, and cisplatin x 3 cycles). NCCN guidelines for growth factor support and anti-emetic use were incorporated into the treatments. Follow-up charges, including weighted costs for salvage for each modality, were generated for 10 years based on both the 2012 and the 2011 NCCN guidelines. According to published literature, the anticipated failure rate for SV, either DL-RT or PA-RT, or Carbo was 18%, 4%, and 5% respectively. 2012 Medicare reimbursement rates (both facility and professional charges) were used to determine the actual reimbursement for each treatment course over a 10-year period. Results: Under the current 2012 NCCN recommendations, the total Medicare reimbursement for SV, PA- RT, DL-RT, and Carbo, when factoring in the cost of salvage, were $10,643, $11,678, $9,662, and $7,870 respectively. This is compared to the reimbursement under the 2011 NCCN guidelines for SV, PA- RT, DL-RT, and Carbo of $20,986, $11,517, $9,394, and $20,365. Conclusions: Reduced imaging during SV or after adjuvant therapy has significantly narrowed the difference in reimbursement between adjuvant management options. This is driven primarily by the integration of results from the MRCTE19/EORTC 30982 outcomes and patterns of failures. We are currently in the process of using Treeage models to fine-tune treatment costs and patient variables to better assess cost-effectiveness between adjuvant treatment modalities.
Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.
Authors: El Bared Nancy , Taussky Daniel , Mehiri Selma , Patocskai Erika , Donath David 
Published: February 2017

322 Background: The use of intensity modulated radiation therapy (IMRT) has allowed for the administration high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neoadjuvant external beam radiation (EBRT) therapy using IMRT. Methods: This is a retrospective study of 21patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed according to the CTCAE v. 3 criteria. Results: The actuarial 3 and 5-year OS and LRFS was 66% and 51%, 57% and 41% respectively. Factors predictive for LRFS were microscopically negative margins (p=0.022), a median tumor diameter < 15 cm (p=0.007) and a pathology of liposarcoma (p=0.021); however, patients treated for recurrent disease fared worse (p=0.04). As for OS, grade 1 histology was a predictive factor for better outcome (p=0.05). EBRT was generally well tolerated. Acute gastrointestinal grade 1 or 2 toxicity occurred in 33% of patients and one patient had unexplained post-radiation grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented grade 1 gastrointestinal toxicity and one patient presented grade 3 small bowel stenosis not clearly due to radiation toxicity. Conclusions: Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.
Is there an intermediate risk group of nonseminoma?
Authors: Hajek Jaroslav , Cvek Jakub , Jackaninova Jana , Skacelikova Eva , Krhut Jan , Havranek Ondrej , Feltl David 
Published: February 2017

323 Background: To evaluate predictive factors of testicular nonseminoma cancer. Methods: Between 2000 and 2012, 189 patients with testicular nonseminoma cancer were evaluated. Stages according to TNM classification were I, II, and III for 84 patients (60%), 49 (26%), and 56 (30%). The median age of the patients was 31 years (range 18-77 years). Treatment was based on orchiectomy plus chemotherapy (bleomycine/etoposide/cisplatin and vinblastine/ifosfamide/cisplatin) and retroperitoneal lymphadenectomy in residual disease. Treatment protocol was updated regularly according to international standards. Overall survival (OS) was evaluated according to the stage, Karnofsky index (KI), and dose intensity of chemotherapy with the Kaplan-Meier method at 5% significance level. Results: There was a significant difference between OS in patient with the different stages (log-rank test, p=0.000), however, detailed analysis revealed that there is significantly worse survival in stage IIIC only (10-years OS for IIIC vs. IIIA+B, 35% vs. 88%, p=0.001) while the difference among IIIB and lower stages was not significant (p=0.383) and 10-years OS was 94%. Dose intensity of chemotherapy proved to be a significant predictive factor for OS in stage IIIA+B patients. Patients with no dose reduction had a significantly higher OS than those with any kind of dose reduction (10-years OS 96% vs. 0%, log-rank test, p=0,000). In stage IIIC, however, the dose intensity had no influence on OS (log-rank test, p=0.167). Unlike dose intensity, in stage III disease KI had no prognostic significance for OS (KI<80 versus KI≥80, Log-rank test, p=0,627) and this is true both for stages IIIA+B and for stage IIIC. Conclusions: Standard of care in testicular nonseminoma cancer offers excellent prognosis with no significant differences in OS for good and intermediate risk groups. On the other hand, outcomes for stage IIIC are poor and further intensification of treatment is warranted. We have found no impact of performance status on OS neither for stage IIIA+IIIB nor stage IIIC. Reduction of chemotherapy dose has a negative impact on OS in patients with stage IIIA+IIIB and should be avoided if possible.
A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT).
Authors: O'Donnell Elizabeth , Gray Kathryn P. , Ravi Praful , Sweeney Christopher 
Published: February 2017

324 Background: Around a quarter of men with metastatic nonseminatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is accepted to be the best way to manage large retroperitoneal masses, the treatment of small residual masses (≤1cm) is controversial. Both PC-RPLND and surveillance produce good outcomes for men in this situation, and we sought to review our experience of surveillance and synthesize the cumulative findings in the form of a meta-analysis. Methods: We searched PubMed and abstracts from ASCO and AUA to identify relevant, English language studies. Inclusion criteria was the presence of a subcentimeter post-chemotherapy retroperitoneal mass. The Dana-Farber Cancer Institute cohort was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND, and the total number of relapses, retroperitoneal (RP)-only relapses and overall survival in men undergoing surveillance. Results: A total of 47 men formed our surveillance cohort and three relapsed with a median follow-up of 5.4 years and median time to relapse of 12.7 months. All three were alive at a median of 4.2 years after relapse with salvage therapy. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71%, 24% and 4% respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of relapse rate was 5%, with an RP-only relapse rate of 3%. Overall, of the 15 men who suffered an RP-only relapse on surveillance, two died of disease. Conclusions: Surveillance is an alternative strategy for managing men with minimal residual RP disease after chemotherapy and avoids an RPLND in about 95% of men who are cured with chemotherapy alone.
Persistence of CD30 expression by embryonal carcinoma (EC) in the treatment time course: A retrospective series of multirelapsing germ cell tumors (GCT).
Authors: Giannatempo Patrizia , Necchi Andrea , Colecchia Maurizio , Paolini Biagio , Nicolai Nicola , Raggi Daniele , Catanzaro Mario , Biasoni Davide , Torelli Tullio , Stagni Silvia , Piva Luigi , Salvioni Roberto , Gianni Alessandro M. 
Published: February 2017

329 Background: CD30 is invariably expressed by untreated EC thus lending support to a rationale for a targeted approach. However, preliminary reports claimed an effect of chemotherapy (CT)-induced downmodulation of CD30 that might affect the potential use in relapsing disease. We aimed at evaluating the persistence of CD30-positivity in post-CT residuals. Methods: We retrieved paraffin-embedded post-CT samples yielding non-teratoma viable cells after ≥ 1 CDDP-based CT from the institutional surgical series. EC component was required and assessed by morphology and Oct-3/4 staining. The entire set was re-stained for CD30 and assessed by 2 pathologists blinded to study purpose. CD30-positivity was defined as a >80% membranous staining with a diffuse moderate-to-strong intensity. Clinical data included site of tumor primary, histology, CT regimen, and type of surgery. Results: From 12/1990 to 09/2012, a total of 246 cases with pure EC or mixed GCT residuals were treated. 49 (EC: 16; mixed GCT: 33) had both complete data and suitable tissue for study purposes. 40 pts had retroperitoneal or mediastinal nodes, 12 pts had lung metastases, 4 had either liver, bone or brain mets. 35/49 cases (70%) preserved CD30 positivity. 20/35 (57%) pts had residual disease after 1stline CT, 15/35 (43%) after multiple CTs (median 3.5, range 2-5). 2 pts (6%) had undergone high-dose CT and 4/35 (11%) were late relapses. 32/35 pts (91%) had gonadal primary, 1 had a retroperitoneal and another a mediastinal primary. The median survival of 35 CD30-positive patients was 16 mos (IQR 3.3-22.9) while it was 48.5 mos (IQR 21.7-72.6) for the 14 CD30-negative patients (p=0.0297 at Gehan-Breslow-Wilcoxon test). 5-year overall survival of CD30-positive and negative patients was 35.7% (95% CI: 18.2-53.6) and 49.7% (95% CI: 19.7-74.0), respectively. Conclusions: Our results on selected relapsing pts suggest that EC retained CD30 even in the far salvage setting, thus confirming to be a reliable target for treatment. A trend towards a poorer prognosis and shorter survival characterized CD30+ cases. A phase 2 study with the antibody-drug conjugate Brentuximab vedotin is currently in plan for GCT.
Characterization of patients who present with de novo metastatic prostate cancer: Single-institution database analysis.
Authors: Strock Jessica , Gray Kathryn P. , Nakabayashi Mari , Evan Carolyn , O'Donnell Elizabeth , Pomerantz Mark , Kantoff Philip W. , Sweeney Christopher 
Published: February 2017

33 Background: Less than 5% of men in a PSA screened population present with denovo metastatic prostate cancer. We sought to characterize the clinical characteristics and survival of this unique group of men. Methods: Retrospective analysis of an institutional data-base – Dana Farber Cancer Institute - Prostate Clinical Research Information Systems (CRIS). All men with metastatic disease as their first presentation of prostate cancer were identified. Patient and disease characteristics were summarized descriptively. The distributions of the study endpoints were estimated using the Kaplan-Meier method with median and 95%CI reported. Results: The analytic cohort has 185 patients with a median follow-up of 7.8 years (95% CI:7.5,11.1) and 94% diagnosed after 1998. Median age at diagnosis is 62 years (Range: 42-86); PSA at diagnosis: Median (Q1-Q3) - 100.2 (23.0, 346.0). Metastases: 97% bone, 2% liver, 2% lung, 8% lymph node. The median time from metastasis diagnosis to start of androgen deprivation therapy (ADT) was 26 days, 139 of those who started ADT had subsequently started treatment for castration resistant prostate cancer (CRPC) - 2nd line hormonal therapy and/or chemotherapy. The median time from ADT to subsequent therapy for CRPC is 14 months with 95% (CI:12,16). 128 patients have died and the median overall survival is 48 months (95% CI:40, 51). Conclusions: This unique cohort of patients at a referral institution tend to be younger and have an overall survival comparable to outcomes in modern day randomized hormone sensitive prostate cancer studies. Assessment of similar group in a multivariate analysis of a prospective trial is needed to confirm this observation. If confirmed, the data would suggest the responsiveness to therapy drives outcome rather than development of metastasis with or without a previously treated primary.
The development of a validated data linked tissue microarray of bladder cancer patients undergoing cystectomy.
Authors: Robinson Richard , Anderson Sarah , Ashton Gary , Womack Chris , Brown Mick D. , Clarke Noel W 
Published: February 2017

330 Background: Over the last 25-30 years there has been little or no advancement in the prognosis or treatment of high grade and muscle invasive bladder cancer, with 5 years survival rates following radical treatment of 40-50%. The aim of this project was to develop a validated, data linked tissue microarray (TMA) of cystectomy patients for the assessment putative biomarkers the provision of a developmental drug pre-screening tool. Methods: All cystectomy derived FFPE tissue blocks from The Christie tertiary cancer centre (1969-2006) were retrieved and independently reviewed. Representative 1mm tissue cores were extracted for TMA construction and associated DNA/RNA bank. The TMA quality was validated using standard H&E histopathological assessment and immunohistochemistry for pan-cytokeratin and phospho-tyrosine. Results: Of 889 cases identified between 1969-2006, tissue of sufficient quality for inclusion was available from 605 patients, comprising 535 bladder cancer cases (85% TCC) and a normal cohort of 70 cases where cystectomy was performed for a non-bladder malignancy. All cases have been linked to a clinical database complete with follow up data up to 10 years post treatment or death. TMA construction has been validated by immunohistochemistry. General immuno-reactivity across the TMA was confirmed by pan-cytokeratin staining (100%). Preservation of phosphorylation, demonstrated by phosph-tyrosine staining, was confirmed in 80%. Notably there was no correlation between sample age and staining. Conclusions: We have successfully created a validated bladder cancer TMA linked to long term follow up data, which provides a powerful research tool for collaborative research into putative biomarkers and novel drug targets.
Defining early-onset kidney cancer: Implications for genetic counseling.
Authors: Shuch Brian , Vourganti Srinivas , Middleton Lindsay , Linehan W. Marston 
Published: February 2017

342 Background: Approximately 1-4% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC genetic counseling. We evaluate how age of onset could guide referral for genetic testing. Methods: We analyzed the age distribution of RCC cases in the Surveillance and Epidemiology and End Results (SEER-17) program and from our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary syndrome. Models were established to evaluate the specific age thresholds for genetic counseling. Results: The median age of RCC in SEER-17 was 64 years old with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (p < 0.05). The bottom decile overall was 46 years of age and slightly differed by sex, race, and histology. The mean and median age of 608 cases of hereditary kidney cancer was 39.3 and 37 years old. While age varied by specific syndrome, 70% of the hereditary cases lied below the bottom age decile. Modeling demonstrated that age alone could limit the number of patients for counseling and that the 10th percentile maximized sensitivity and specificity. Conclusions: Besides associated clinical manifestations and personal/family history, early age of onset in RCC could be a sign of a hereditary kidney cancer. In the absence of clinical signs, an age of onset ≤46 should trigger referral for genetic counseling and may serve as a useful cutoff when establishing genetic testing guidelines.