bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of variant histology (VarHst) in transurethral resection of bladder tumor (TURBT) biopsies and its prognostic significance on pathologic complete response (pCR) rates to neoadjuvant chemotherapy (neo-CTx).
Authors: Pedrosa Jose Alexandre , Rice Kevin , Thomas Derek E. , Johnston Paul , Moore Marietta L. , Reed Angela D. , Cregar Dylan M. , Franklin Cindy , Koch Michael O. , Bihrle Richard , Foster Richard , Masterson Timothy A. , Gardner Thomas A. , Sundaram Chandru , Powell Charles R. , Beck Stephen , Grignon David A. , Cheng Liang , Hahn Noah M. 
Published: February 2017

295 Background: Randomized phase III clinical trial data (S8710) supports an overall survival (OS) advantage with neo-CTx for muscle-invasive urothelial carcinoma (miUC) patients (pts) prior to cystectomy. Recent S8710 subset analyses have demonstrated an OS for pts with both pure UC and VarHst. pCR to neo-CTx has been suggested as a surrogate endpoint for OS. The relationship between VarHist in TURBT specimens and pCR rates is uncertain. Methods: A retrospective review of the Indiana University Simon Cancer Center urology and medical oncology clinical databases was performed spanning the years 1991 – 2012. Subjects with miUC, pathology reports available for both TURBT and cystectomy procedures, and confirmed receipt of neo-CTx with regimen details were included in this analysis. Pts with clinically positive lymph nodes (LN+) were included provided they underwent cystectomy with curative intent and distant metastases were not present. Associations between pCR and pt baseline age, gender, race, clinical stage (T2N0 vs. T3/T4/N+), chemotherapy regimen received (cisplatin combination therapy (CisCTx) vs. non-cisplatin based), and presence of VarHst on TURBT sample were tested by multinomial logistic regression analysis with statistical significance set at p<0.05. Results: 72 miUC pts satisfying the inclusion criteria were identified. Cohort demographics included: age (median) – 59 yrs, 76% male, 93% Caucasian, 63% T2N0, 32% LN+, 81% CisCTx neo-CTx regimen, 42% VarHst on TURBT, pCR for entire cohort 18%. The presence of VarHst on TURBT sample was not associated with decreased rates of pCR (6/30 vs. 7/42) p=0.610. A trend toward significance with age over 59 was also observed. Conclusions: The presence of VarHst in TURBT specimen is not associated with decreased rates of pCR at cystectomy in miUC pts treated with neo-CTx. Further characterization of the amount of VarHst and reproducibility of its recognition in TURBT samples is warranted to determine its ultimate clinical value.
Tumor burden reduction in an orthotopic non-muscle-invasive bladder cancer model using IL-15 analogue (ALT-803) targeting T regulatory cells.
Authors: Gomes Evan , Miyake Makito , Zhang Ge , Goodison Steve , Egan Jack , Rhode Peter , Wong Hing C. , Rosser Charles Joel 
Published: February 2017

298 Background: A recent NCI review listed IL-15 as the most promising product candidate among twelve immunotherapy drugs that could potentially cure cancer. Preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL-15Rα-Fc fusion) have shown promising results for obtaining prolonged drug half-life and stimulating CD8+ T cells and NK cells. Based on these results, we hypothesized that the administration of ALT-803 will generate an immunologic response which will reduce tumor burden in a rodent carcinogen induced orthotopic non muscle invasive bladder cancer model (NMIBC). Methods: We tested intravesical ALT-803 alone and ALT-803 in combination with Bacillus Calmette-Guérin (BCG) in a rodent carcinogen induced orthotopic NMIBC model. Rats were anesthetized then a 22-gauge Teflon transurethral catheter was placed in the bladder and urine completely drained from the bladder. Next, the saline (negative control), ALT-803 (experimental agent) or BCG (positive control) therapy was delivered by transurethral instillation and allowed to dwell in the bladder for 1 hr by occlusion of the urethra with a purse string suture. The intravesical therapy was administered weekly for a total of six weeks to mimic intravesical BCG therapy in humans. Results: Herein we demonstrate that ALT-803 was safe and well tolerated alone or in combination with BCG. Furthermore, ALT-803 alone reduced tumor burden by 23% whereas BCG alone reduced tumor burden by 11% compared to control. The combination of ALT-803 and BCG reduced tumor burden by 30% compared to control. Tumoral responses of the combinational treatment were associated with 76% and 80% reduction in angiogenesis and proliferation, respectively, whereas combinational therapy was associated with a 7.7-fold increase in apoptotic index compared to control. Immune monitoring suggested that the antitumor response was linked to the activation of CD8+ cells and NK cells. Conclusions: The enhanced therapeutic index provided by ALT-803 plus BCG therefore provides a powerful justification for the development of this agent for future clinical trials in subjects with non-muscle invasive bladder cancer.
Using micro-RNA expression to predict response to neoadjuvant chemotherapy in urothelial carcinoma of the bladder.
Authors: Leibowitz-Amit Raya , Fridman Eduard , Bossel Noa , Zehavi Liron , Urban Damien , Cohen Yehudit , Dotan Zohar A. , Domany Eytan , Berger Raanan 
Published: February 2017

299 Background: Urothelial carcinoma of the bladder is among the 5 most common cancers in the US. Despite several clinical trials attempting to determine the best approach to muscle-invasive disease, the optimal treatment modalities and their sequence have not been established. Specifically, the decision to administer neo-adjuvant chemotherapy is currently based solely on clinical parameters, with no validated biomarkers. Micro-RNAs (miRNAs) are short RNA molecules that have roles in post-transcriptional gene expression regulation by binding to mRNAs. They were shown to have cardinal roles in many cancers, and their potential to serve as biomarkers is extensively studied. Our goal was to study whether miRNAs can serve as predictive biomarkers for response to neo-adjuvant chemotherapy in urothelial carcinoma. Methods: miRNAs were extracted from paraffin-embedded pre-operative muscle-invasive tumor biopsies of patients diagnosed with urothelial carcinoma, whose pathological surgical specimen was later found to either show complete or no-response to neo-adjuvant chemotherapy (termed 'responders' and 'non-responders', respectively). The expression pattern of approximately 900 miRNAs was compared using a commercial miRNA array, and the levels of candidate miRNAs was further assessed by quantitative real-time PCR (qRT-PCR). Results: The vast majority of miRNAs exhibited a similar expression pattern in the two patient groups, but two miRNAs were significantly lower in the responders (p <0.001 and q<0.1 using the false detection rate (FDR) method). Interestingly, both miRNAs can potentially target the mRNA of PTCH1 and SP5, two genes with known tumor-suppressor functions. qRT-PCR showed that high levels of one of the miRNAs correlated with lack of response to chemotherapy. Conclusions: This retrospective analysis identified two miRNAs that are differentially expressed between chemotherapy responders and non-responders. One of these miRNAs was confirmed to correlate with lack of response to neo-adjuvant chemotherapy. A prospective trial assessing the predictive values of these miRNAs is currently underway. Future research directions and potential implications will be discussed.
Paragangliomas of the urinary bladder: Experience at the National Cancer Institute.
Authors: Weintraub Michael , Siddiqui Minhaj , Vourganti Srinivas , Shuch Brian , Agarwal Piyush , Linehan W. Marston 
Published: February 2017

307 Background: Bladder paragangliomas (BP, also referred to as bladder pheochromocytomas) represent 0.06% of bladder tumors. They occur both sporadically and with familial cancer syndromes such as von Hippel-Lindau (VHL) or Succinate Dehydrogenase-B (SDH-B) deficiency. Here we describe the clinical manifestations and management of BP at our institution. Methods: A retrospective review was performed of all cases of BP treated by the Urologic Oncology Branch at the National Institutes of Health (NIH) Clinical Center from 1989 – 2012. Using an approved database, we reviewed the demographics, radiologic, pathologic, laboratory data, surgical approach, and clinical outcome of patients with BP. Results: A total of 7 patients were treated for BP. Five were part of familial syndromes (3 with VHL, 2 with SDH-B deficiency, mean tumor volume (TV): 4cc), while 2 were sporadic cases (mean TV: 43cc). There was no significant age or gender difference in sporadic versus familial patients. 6 of the 7 patients presented with at least two of the three classic symptoms of headache, palpitations, and diaphoresis. 3 patients had micturition-related symptoms. For diagnosis, urine and plasma normetanephrines and urine norephinephrine showed the greatest sensitivity (0.75, 0.75, and 0.8, respectively). MRI was performed in all patients and had a sensitivity of 100% for detection of the mass. MIBG scan was also 100% sensitive, but was only performed in 3 of the 7 patients. CT missed the lesion in one patient. 3 patients were treated with TURBT (mean TV: 2.2cc), 2 underwent partial cystectomies (mean TV: 11.6cc), and one had a radical cystectomy (TV: 63cc). 2 patients had metastatic disease detected 7 and 9 years after initial treatment. No difference was seen in outcome based on the treatment modality. Conclusions: BP in familial and sporadic cases present with similar characteristics except for size. BP is best detected with catecholamines and MIBG/MRI. Surgical management is largely dictated by the extent of disease and includes TURBT, partial, and radical cystectomy. Long-term monitoring is recommended as distant recurrences can occur.
Clinical outcomes in focal versus extensive micropapillary bladder cancer at the time of diagnostic transurethral resection.
Authors: Willis Daniel Levi , Fernandez Mario , Dickstein Rian J. , Guo Charles , Czerniak Bogdan , Parikh Sahil , Shah Jay Bakul , Pisters Louis L. , Grossman H. Barton , Dinney Colin P.N. , Kamat Ashish M. 
Published: February 2017

317 Background: It has been postulated that the outcome of patients with micropapillary bladder cancer (MPBC) is dependent on the extent of MPBC component relative to conventional urothelial carcinoma. Herein, we reviewed the clinical outcomes of patients with MPBC and evaluated the outcomes based on extent of disease in the transurethral resection (TUR) specimen. Methods: An IRB-approved institutional review of our bladder cancer database identified 255 patients with MPBC. Dedicated GU pathologists at our institution quantified MPBC as being "focal" or "extensive" in 201 patients, who form the basis of this report. Univariate analysis was performed with the chi square test and the Kaplan-Meier estimator, while multivariate analysis was performed using Cox Regression analysis. Results: Overall, 127 (63%) patients were reported as having focal MPBC and 74 (37%) patients had extensive micropapillary histology. Survival analysis demonstrated that patients with focal MPBC had a greater overall median survival of 54 mo. vs. 22 mo. for those with extensive MPBC (p=0.002). The extent of MPBC also correlated with cT stage as extensive MPBC was seen with higher stage disease (p=0.035). When stratified by cT stage, patient survival correlated with the extent of MPBC such that median survival for focal versus extensive MPBC was 122 vs. 62 mo. for cT1 (p=0.04), 54 vs. 22 mo. for cT2 (p=0.008), and 12 vs. 4 mo. for cT3 patients (p=0.017). In the cT1 cohort, patients with extensive MPBC were 2.3 times more likely to have disease progression on BCG therapy than those with focal disease (p=0.02). Extensive MPBC in the TUR specimen was also associated with higher rates of clinical lymph node metastasis (34% vs. 19%, p=0.018). The association of the extent of MPBC with overall survival remained significant after multivariate analysis with other prognostic variables including lymphovascular invasion and clinical T stage (p=0.05). Conclusions: The extent of micropapillary architecture in the TUR specimen is associated with stage of tumor at presentation. However, even when controlling for stage, patients with "extensive" MPBC on TUR specimen have independently worse outcomes compared to those with focal MPBC.
Outcome of patients with micropapillary bladder cancer treated with neoadjuvant therapy and radical cystectomy.
Authors: Willis Daniel Levi , Fernandez Mario , Dickstein Rian J. , Parikh Sahil , Siefker-Radtke Arlene O. , Guo Charles , Czerniak Bogdan , Shah Jay Bakul , Pisters Louis L. , Grossman H. Barton , Dinney Colin P.N. , Kamat Ashish M. 
Published: February 2017

318 Background: Micropapillary bladder cancer (MPBC) is an uncommon and aggressive variant of urothelial carcinoma for which the role of neoadjuvant chemotherapy (NAC) is not well-defined. Here we report a retrospective analysis of patients with MPBC undergoing radical cystectomy (RC) with and without NAC. Methods: An IRB-approved review of our radical cystectomy database demonstrated 159 patients with a preoperative diagnosis of MPBC. Of these, 131 patients presented with surgically resectable (≤cT4aN0M0) disease and form the basis of this report. Disease-specific (DSS) and overall survival (OS) were estimated using the Kaplan-Meier estimator and compared by log-rank test. Results: The clinical stage breakdown was cT1:50; cT2:66; cT3:15; and cT4a:0. NAC was administered to 61 patients (47%) with 78% receiving cisplatin-based regimens. Patients were more likely to receive NAC if they presented with cT3 disease, hydronephrosis, or lymphovascular invasion (LVI) in the transurethral resection (TUR) specimen. After a median follow-up of 44 mo., 50% of patients recurred and 41% died of disease, resulting in a 5-year estimated DSS of 58.4% for all 131 patients. Survival analysis was performed for comparable groups according to our established risk factors. For the low risk patients (i.e. cT1-T2, no hydronephrosis, and no LVI) RC upfront (n=47) resulted in a 73% 5-yr DSS compared to 83% with NAC (n=19) (p=0.47). In the high-risk group (cT3 or cT2 with LVI and/or hydronephrosis), 41 patients were treated initially with NAC and 5-yr DSS was 40%, which was similar (p=0.74) to the 31% 5-yr DSS for those treated with RC upfront (n=20). The most important overall prognostic factor was pathologic downstaging to pT0, pTa, or pTis at cystectomy (seen in 52% after NAC and 19% after TUR alone) which conferred a significant survival advantage (5-yr DSS 93% vs. 40% in those not downstaged; p<0.001). Conclusions: Despite incorporation of a multimodal treatment strategy, patients with MPBC and high risk features (LVI, hydronephrosis and/or cT3 stage) have poor outcomes. Further studies are necessary to define the optimal treatment strategy in this challenging subset of patients with urothelial cancer.
Neoadjuvant carboplatin in stage IIa and IIb seminoma.
Authors: Horwich Alan , Dearnaley David Paul , Sohaib Aslam , Pennert Kjell , Huddart Robert Anthony 
Published: February 2017

321 Background: Approaches to managing stages IIa and IIb seminoma post-orchidectomy range from combination chemotherapy (typically 3 cycles of BEP) to extended field radiotherapy (typically 36 Gy to para-aortic and ipsilateral pelvic lymph nodes. Survival rates are very good, which highlights the need to minimise toxicity risks. We report on the role of a single cycle of neoadjuvant carboplatin prior to limited field radiotherapy. Methods: In a single arm study fifty one patients were treated between May 1996 and November 2011 with a single cycle of carboplatin at an AUC of 7 mg.mins/ml followed by radiotherapy. The radiation field was reduced to just the para-aortic region and the dose to 30Gy in 39 patients. Results: After a median follow-up of 55 months (range 8-151 months) with 38 (74%) of the patients having been followed for more than 2 years, there have to date been no relapses (95% confidence limits of 5 year relapse free survival of 93-100%). Toxicity has been low with grade 3 toxicity limited to 4 patients with grade 3 haematological toxicity (with no clinical sequelae) and 1 patient with grade 3 nausea (during radiotherapy). No patients experienced grade 4 toxicity. Conclusions: The results of this pilot study suggest that a single cycle of neoadjuvant carboplatin prior to radiotherapy may reduce recurrence risk and permit a smaller radiation field, and this approach is proposed for further investigation.
Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT): Long-term efficacy and safety outcomes.
Authors: Necchi Andrea , Mariani Luigi , Nicolai Nicola , Raggi Daniele , Farè Elena , Giannatempo Patrizia , Piva Luigi , Biasoni Davide , Catanzaro Mario , Torelli Tullio , Stagni Silvia , Pizzocaro Giorgio , Gianni Alessandro M. , Salvioni Roberto 
Published: February 2017

328 Background: Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. Methods: We retrieved data of pts who received ifosfamide at 2.5 gr/m2 (with mesna) on days 1-2, etoposide and cisplatin at 100 mg/m2 and 33 mg/m2, respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. Results: From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm- were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP>1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. Conclusions: Dose-modified Italian PEI showed activity comparable with the best ones achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT.
Use of radiotherapy for seminoma patients with low-volume infradiaphragmatic nodal disease.
Authors: Sridharan Swetha , Chung Peter W. M. , Jewett Michael A. , Atenafu Eshetu , Bedard Philippe , Moore Malcolm J. , Warde Padraig Richard 
Published: February 2017

335 Background: Radiation therapy (RT) is established as standard management in testicular seminoma patients with low volume (< 5cm in maximum diameter) retroperitoneal lymphadenopathy. Increasingly multi-agent chemotherapy (CT) is being recommended as first line therapy with its attendant toxicity. To further examine this issue, we reviewed the outcomes for such patients managed at our institution. Methods: After ethics board approval, data on 106 patients identified from a prospectively maintained institutional database with low volume retroperitoneal disease (<5cm) were retrospectively reviewed. All patients were treated between 1995-2010 and had either relapsed Stage I disease on surveillance (59 pts) or Stage IIA/B at diagnosis (47 pts). Fifty eight patients had nodal disease of <2cm (57 treated with RT, 1 with CT), and 48 had disease 2-5cm (30 treated with RT, 18 with CT). Median age was 37 years (range 24-83). The preferred treatment policy was to use RT when possible (25 Gy in 20 fractions to para-aortic and pelvis with 10 Gy boost to gross disease). Reasons for using chemotherapy included multiple enlarged nodes with largest node at least 3cm (n=11), disease proximity to renal hilum (n=4), inflammatory bowel disease (n=3) and patient choice (n=1). Seventeen-patients received EP (4 cycles) chemotherapy and 2 received BEP (3 cycles). Results: With a median follow-up of 73 months, there were no disease or treatment related deaths. The 5-year overall and relapse-free survival was 100% and 91%. Of 58 patients with LN size ≤ 2 cm, 5 relapsed, all initially treated with RT. Of 48 patients with LN size 2-5cm, 4 relapsed (3/30 treated with RT, 1/18 treated with CT). Acute toxicity (CTCAE v4 >grade 1) was not observed in any patient treated with RT. In patients treated with CT, 7 developed G3/4 neutropenia, 2–grade 3 anemia, 2–grade 3 diarrhea, and 1 patient grade 3 weight loss. All relapsed patients were successfully salvaged by CT. Conclusions: A policy of routine use of RT in patients with low-volume nodal disease gives excellent results with >75% of patients avoiding CT and only 6% of patients receiving both RT and CT. Retroperitoneal RT should be strongly considered as the treatment of choice in these patients.
Survivorship care in Canadian genitourinary oncology: Toward a multidisciplinary perspective.
Authors: Richter Sue , AlMatar Ashraf , Lalani Nafisha , Bender Jackie , Wiljer David , Legere Laura , Massey Christine , Alkazaz Nour , Maganti Majula , Catton Pamela , Sridhar Srikala S. , Jewett Michael A. 
Published: February 2017

337 Background: Genitourinary (GU) cancer survivors comprise nearly 25% of cancer survivors and >50% of all male survivors. To further improve care of this patient population, we need to better understand physician specialist perceptions of survivorship care. Methods: All medical oncologists, urologists and radiation oncologists treating GU cancers in Canada were surveyed with a web−based questionnaire. A total of 27 multiple choice and Likert scale questions were developed in 5 domains: i) demographics, ii) current post cancer treatment care practices, iii) perceived barriers, iv) accessibility to survivorship resources and v) perceptions of advocacy groups. Participants were identified through their respective professional associations. Results: There were 306 responses and 260 were eligible for analysis; 45 medical oncologists, 125 urologists and 90 radiation oncologists. A total of 56% of physicians discharged GU cancer survivor follow-up care to a primary care practitioner (PCP) at some point after treatment. Compared to urologists and radiation oncologists, medical oncologists were least likely to share care with a PCP (4%). Only 47% of all physicians consistently provided a written follow up plan to the PCP and only 25% of these provided lifestyle recommendations. Lack of time and resources were the most commonly reported barriers. About half of physicians reported access to cancer rehabilitation programs as difficult and British Columbia was the most frequently cited region without access. Medical oncologists compared to other subspecialties accessed genetic counseling more easily while access to pain management programs was cited as the most difficult. In general, physicians in community hospitals had the most difficulties. Utilization of advocacy groups was limited, e.g. 23% for prostate cancer. The most underutilized advocacy group was for testis cancer (4%). Conclusions: To our knowledge this is the first study to address the challenges of GU cancer survivorship care in Canada. The barriers to care and underutilization of advocacy groups quoted in this study may be used to stimulate nationwide initiatives to further long-term strategies in GU survivorship management planning.