bluuebunny/crossref_metadata_2025_split huggingface dataset:
Craniocaudal retroperitoneal node length as a risk factor for relapse from clinical stage I testicular germ cell tumor.
Authors: Howard Stephanie Anne Holler , Gray Kathryn P. , O'Donnell Elizabeth , Fennessy Fiona M. , Beard Clair , Sweeney Christopher 
Published: February 2017

363 Background: To investigate if retroperitoneal craniocaudal nodal length (CCNL) or nodal volume (NV) predicts relapse risk in clinical stage I testicular cancer. Methods: This institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study retrospectively reviewed 826 patients with testicular cancer. One hundred eighteen out of 826 patients forming the analytic cohort had stage I disease and either more than or equal to 2 years surveillance or retroperitoneal lymph node dissection with no adjuvant chemotherapy. 3D NVs and CCNL were measured by two attending physicians in consensus. Association between relapse risk and CCNL/NV was evaluated using univariable/multivariable logistic regression analysis adjusted for known prognostic factors. Results: Sixty six out of 118 patients (56%) had nonseminomatous germ cell tumor (NSGCT) and 52 (44%) had seminomatous germ cell tumor (SGCT). Twenty one percent (25 out of 118) of patients relapsed: 24% (16 out of 66) for NSGCT and 17% (9 out of 52) for SGCT. Eighty percent of relapses were limited to the retroperitoneum; 90% of these were at the site of the largest lymph node. CCNL proved to be an independent risk factor in NSGCT using a multivariable logistic regression model adjusting for other potential known risk factors of embryonal predominance (EP) and lymphovascular invasion (LVI). For every 3 mm increase in CCNL, the risk of relapse increased by 52% (odds ratio [OR]=1.52; 95% CI=1.03- 2.25). For patients with SGCT, only the primary tumor size was an independent risk factor for relapse (OR=1.34; 95% CI=1.02-1.75). Conclusions: In NSGCT, CCNL was shown to be associated with increased risk of relapse independently of other known risk factors. If validated in a larger cohort, CCNL could provide important additional information used to inform management decisions in these patients.
Modern patterns of care in testicular seminoma: Results from the National Cancer database.
Authors: Gray Phillip John , Lin Chun Chieh , Paly Jonathan J. , Jemal Ahmedin , Efstathiou Jason Alexander 
Published: February 2017

368 Background: The management of testicular seminoma (TS) is evolving with guidelines supporting differential use of chemotherapy (CT) and radiotherapy (RT) depending on stage and presentation. We examined modern practice patterns in TS using the National Cancer Data Base. Methods: Data on 41,745 patients with TS treated between 1998 and 2010 were analyzed. Patients were grouped by stage based on National Comprehensive Cancer Network treatment guidelines. Multivariate generalized estimating equation models were used to assess factors associated with treatment paradigms. Results: Rates of surveillance after orchiectomy for those with stage IA/B TS increased from 21.4% during 1998-2001 to 40.4% from 2006-2010. Despite this, RT remained the most common adjuvant therapy (47.9% in 2006-2010). Use of adjuvant CT increased from 1.7% to 10.6% during this time. Patients with stage IS TS most commonly received RT; however, in 2006-2010, 32.4% of patients received surveillance and 15.6% received CT. Receipt of surveillance for those with stage IIA/B TS remained flat at ~12% while the use of CT rose (34.4% in 2006-2010 vs. 22.5% in 1998-2001). For patients with stage IA/B TS, Medicare or uninsured patients were more likely to receive surveillance vs. CT/RT (OR 1.54, p<0.0001 and OR 1.26, p<0.0001 respectively). Adjuvant CT/RT was more common at high volume centers (OR 0.63 vs. low volume, p<0.0001) and in patients with larger tumors (OR 0.80 for tumors ≥ 4 cm, p<0.0001). Among patients with stage IA/B TS who received adjuvant RT/CT, Medicaid or uninsured patients (OR 0.55, p<0.0001 and OR 0.68, p<0.0001 respectively) and those treated at NCI network cancer centers (OR 0.40 vs. community centers, p<0.0001) were less likely to receive RT vs. CT. For stage IIA/B TS patients, facility type was the strongest predictor for the receipt of RT vs. CT (OR 0.54 at NCI network centers, p<0.0001). Conclusions: Management of TS appears at least partially driven by economic concerns and facility type, especially in regards to selection of stage I patients for surveillance, the preferred management for this group. Many patients with stage IS are not managed according to published guidelines. Action is needed to ensure all patients with TS receive guideline supported care.
To what degree is there interobserver variability among pathologists for T1 penile cancer?
Authors: Luchey Adam , Espiritu Patrick , Agarwal Gautum , Protzel Chris , Dhillon Jasreman , Spiess Philippe E. 
Published: February 2017

381 Background: Molecular and genetic markers have yet to be developed to predict those patients that are at risk for lymph node metastasis. Currently, the grading of penile cancer plays a critical role in the determination of which patients receive an inguinal lymph node dissection (ILND) along with other treatment modalities. We sought out to determine the variance among genitourinary (GU) pathologists at a tertiary cancer center for penile cancer based on a European model. Methods: Nine patients that were diagnosed with stage pT1 primary penile squamous cell carcinoma were selected who underwent either a partial (8) or radical penectomy (1) from 10/2000 to 09/2009. All slides from each case were reviewed by each of the 3 reviewing pathologists, independently, who diagnosed the subtype of squamous cell carcinoma according to WHO criteria, assigned a grade, noted whether lymphovascular invasion was present or not and finally staged the tumor according to the AJCC Cancer Staging Manual, 7th edition. No access to the original, final pathological diagnosis was allowed. Interobserver variance between the 3 GU pathologists and each variable was calculated using Cohen’s kappa coefficient. Results: Complete agreement was reached in 3 cases for tumor grade and 4 cases for tumor stage out of 9. Overall, the 3 GU pathologists only displayed fair agreement at 30% for tumor grade (ê = 0.30, p = 0.018) and trended towards fair agreement at 24% (ê = 0.24, p = 0.077) and 25% (ê = 0.250, p = 0.097) for tumor stage and LVI respectively. Conclusions: The variance displayed herein demonstrates the difficulty in identifying individuals that would benefit from a diagnostic/therapeutic lymph node dissection based on pathological staging. This corroborates that of the European model and calls for novel methods to determine reproducible prognostic markers.
Integrated comprehensive high-throughput kinomics profiling and whole exome sequencing of penile squamous cell cancer (PSCC).
Authors: Mehta Amitkumar N. , Willey Christopher , Crowley Michael , Anderson Joshua , Chen Dongquan , Crossman David , Necchi Andrea , di Lorenzo Giuseppe , Eigl Bernhard J. , Lee Richard J. , Harshman Lauren Christine , Dorff Tanya B. , Galsky Matt D. , Milowsky Matthew I. , Bolger Graeme , DeShazo Mollie , Naik Gurudatta , Grizzle William E. , Sonpavde Guru 
Published: February 2017

383 Background: Molecular drivers in penile squamous cell cancer (PSCC), an orphan malignancy, remain unclear. The Cancer Genome Atlas (TCGA) is not studying PSCC and the Catalogue of Somatic Mutations in Cancer (COSMIC) investigators have reported only targeted analyses of PSCC. We report the first integrated analyses of comprehensive kinomics and whole exome sequencing (seq) in tumors from patients (pts) with PSCC . Methods: We performed integrated functional kinomics profiling and comprehensive exome-seq of two frozen tissue samples from men with PSCC with a matched normal tissue procured from the Cooperative Human Tissue Network (CHTN). Kinomic profiling was performed using the PamStation 12 high-content phospho-peptide substrate microarray system (PamGene International). The protein tyrosine kinome and serine/threonine kinome PamChips were used to measure global kinase activity by detecting phosphorylation of various peptides through FITC-labeled antibodies. Upstream kinase prediction was performed using a scoring algorithm that incorporates the phosphonet database (www.phosphonet.ca). Exome capture was performed with the Agilent SureSelect v5 kit and whole exome-seq was done on the Illumina HiSeq2000 with paired end 100bp chemistry. Results: In the single patient, paired kinomics analysis comparing the tumor sample to adjacent normal tissue, the HER family (EGFR, ERBB2, 3 and 4), AXL, TYRO3 and SYK kinases were the most active. When combining the two tumors in an unpaired analysis against the normal sample, the HER (EGFR, ERBB2, 3 and 4), MER, FRK, and FAK, kinases showed increased activity. When comparing whole exome-seq of the two PSCC samples with normal, among the affected genes were CCDC181, ZNF717, MUC4, HGC6.3, NOTCH1, STK11, SIRPB1, SKA3, PDE6B, FAT1, CACNA2D1, USP17L11, MNT, and CEP89. We are evaluating 10 PSCC tumors and matched normal tissue by kinomics and whole exome-seq and will present these complete data and analysis at the conference. Conclusions: In our preliminary analysis of pts that underwent the first reported integrated kinomics and whole exome-seq performed in PSCC, we identified multiple potential therapeutic targets in tumors.
SWITCH: A randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO)/sunitinib (SU) versus SU/SO in the treatment of metastatic renal cell cancer (mRCC).
Authors: Michel Maurice Stephan , Vervenne Walter , de Santis Maria , Fischer von Weikersthal Ludwig , Goebell Peter J. , Lerchenmueller Juergen , Zimmermann Uwe , Bos Monique M.E.M. , Freier Werner , Schirrmacher-Memmel Silke , Staehler Michael D. , Pahernik Sascha , Los Maartje , Schenck Marcus , Flörcken Anne , Van Arkel Cornelis , Hauswald Kirsten , Indorf Martin , Gottstein Dana , Eichelberg Christian 
Published: February 2017

393 Background: The sequential use of SO and SU has been investigated retrospectively in patients with mRCC. We report here results from the first randomized study to prospectively compare SO/SU versus SU/SO. Methods: Pts with mRCC unsuitable for cytokines without prior systemic therapy, ECOG PS 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion were randomized to receive open-label SO/SU (arm A) or SU/SO (arm B) in standard dosage. Primary endpoint: total PFS (T-PFS) from randomization to event during 2nd line therapy. Therapy continued until progression or intolerability. The study was powered to detect a 47% increase in T-PFS with SO/SU compared to SU/SO using log-rank testing and Cox proportional hazard regression model. ( NCT00732914 ). Results: A total of 365 pts were enrolled: 182 arm A, 183 arm B.The two arms were well balanced: median age (A/B): 64/65 yrs; prior nephrectomy: 74/65%; MSKCC intermediate: 59/51%, low: 39/45%; clear cell histology: 90/84%. At time of final T-PFS analysis 220 events had occurred (A, n=117 [64%]; B, n=103 [56%]). There was no statistically significant difference in T-PFS across arms: HR 1.01, p=0.54, arm A and arm B, respectively. Likewise, there was no statistically significant difference in OS: HR 0.997, p=0.49, nor in the first PFS across arms: HR 1.19, p=0.92. Fewer pts crossed over to receive SO in arm B (n=76) than to receive SU in arm A (n=103). Overall DCR was 72/67%. There was a marked difference in AEs leading to permanent discontinuation between the two groups (18.6/29.5%). Most frequent (>20%) side effects under 1st-line treatment SO vs SU were alopecia (29/4%), diarrhea (43/29%), dysgeusia (8/21%), fatigue (21/34%), HFSR (37/20%), hypertension (24/24%), nausea (18/24%) and rash (22/3%). AEs were generally lower during 2nd-line therapy. Conclusions: There was no significant difference in T-PFS, OS, DCR and 1st-line PFS between the two sequential treatments. Both drugs provided overall benefit regardless of sequence. Side effect profiles differ, but were generally less frequent during 2nd-line therapy. More patients reached 2nd-line in the SO/SU arm. Clinical trial information: NCT00732914.
Results of the MARS study on the management of antiangiogenics’ renovascular safety in renal cell carcinoma.
Authors: Ray-Coquard Isabelle Laure , Janus Nicolas , Goldwasser Francois , Mir Olivier , Oudard Stephane , Scotte Florian , Spano Jean-Philippe , Thery Jean Christophe , Beuzeboc Philippe , Daniel Catherine , Rey Jean-Baptiste , Jouannaud Christelle , Gligorov Joseph , Morere Jean F. , Azizi Michel , Dorent Richard , Deray Gilbert , Launay-Vacher Vincent 
Published: February 2017

394 Background: MARS is a prospective multicentric study conducted to assess the renovascular tolerance of anti-VEGF drugs (AVD) in the clinical setting in France, in a number of different tumor types. Methods: Patients (pts) from 8 centres were included when they were 1) naïve of any AVD and 2) about to start treatment with an AVD, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit during f/u. This sub-group analysis presents the results for renal cell carcinoma (RCC) pts receiving sunitinib. Results: 1,124 pts were included. 137 had RCC and 112 received sunitinib. Median age: 61.0 years. Visceral, bone and cerebral metastasis frequencies were 71.4, 42.0 and 12.5%, respectively. All except 3 pts, had at least one kind of metastasis. At inclusion, HTN prevalence was 43.8%. Baseline renal assessment retrieved: Pu 15.6%, Hu 8.1%, mean aMDRD 69.4 ml/min/1.73m2. The incidence of de novo Pu and HTN during f/u was 75.0 and 21.4% (Table). All pts with Pu at inclusion improved or remained stable. Among pts with de novo Pu, 75.8% afterwards improved/normalized. Mean aMDRD was 72.2 at the end of f/u. 0.7% had grade 3 SCr increase (no grade 4). No thrombotic micro-angiopathy (TMA) was reported. Conclusions: These results on the renovascular safety of AVD in RCC patients showed that 1) TMA is rare, 2) Pu develops in 75.0% of the pts, 3) 21.4% developed HTN, Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]
The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model as a prognostic tool in metastatic renal cell carcinoma (mRCC) patients previously treated with first-line targeted therapy (TT).
Authors: Ko Jenny J. , Xie Wanling , Heng Daniel Yick Chin , Kroeger Nils , Lee Jae-Lyun , Rini Brian I. , Knox Jennifer J. , Bjarnason Georg A. , Harshman Lauren Christine , Pal Sumanta Kumar , Yuasa Takeshi , Smoragiewicz Martin , Donskov Frede , Bamias Aristotelis , Wood Lori , Ernst D. Scott , Agarwal Neeraj , Vaishampayan Ulka N. , Rha Sun Young , Choueiri Toni K. 
Published: February 2017

398 Background: Prior prognostic models for 2nd-line systemic therapy have not been studied in the setting of contemporary sequential targeted therapy (TT). We sought to validate the IMDC prognostic model in patients with mRCC receiving next-line TT after progression on 1st-line TT. Methods: Patients who received 2nd-line TT after progressing on 1st-line TT for mRCC at 19 centres were analyzed. For the patients who had immunotherapy (22%) prior to their 1st TT, we examined their second TT (ie 3rd-line therapy). The endpoint was median overall survival (OS) since the initiation of 2nd-line therapy. Additionally, we compared the IMDC model with the 3-factor-MSKCC model (Motzer et al JCO 2004) used for previously-treated patients. Results: 1,021 patients treated with a second TT were included. Median time on 2nd-line TT was 3.9 months (range 0-76+). 871 (85%) of patients had stopped 2nd-line TT by the time of analysis. Median OS since 2nd-line TT was 12.5 months (95% CI: 11.3-14.3 months), with 369 (36.1%) of patients remaining alive. 5 out of 6 pre-defined factors in IMDC model (anemia, thrombocytosis, neutrophilia, KPS <80%, and <1 year from diagnosis to treatment) measured at the time of 2nd-line TT were independent predictors of poorer OS (HR between 1.39 and 1.58, p<0.05). Hypercalcemia was not statistically significant in multivariable analysis (p=0.3008) likely due to the low incidence of hypercalcemia (9%). The concordance index using all 6 prognostic factors was 0.70, and was 0.66 with the 3-factor-MSKCC model. When patients were divided into 3 risk categories using IMDC criteria, median OS was 35.8 months (95% CI 28.3-47.8) in the favorable risk group (n=76), 16.6 months (95% CI 14.9-17.9) in the intermediate risk group (n=529), and 5.4 months (95% CI 4.7-6.8) in the poor risk group (n=261). Conclusions: The IMDC prognostic model has been validated in and can be applied to patients previously treated with TT, in addition to previously validated populations in 1st-line TT and non-clear cell setting.
Results of a feasibility study of I-124 girentuximab in metastatic clear cell renal cell carcinoma (m ccRCC).
Authors: Keefe Stephen Michael , Rosen Mark Alan , Robinson Janelle , McGibney Karen , Marshall Amy , Mamtani Ronac , Vaughn David J. , O'Dwyer Peter J. , Haas Naomi B. , Pryma Daniel A. 
Published: February 2017

406 Background: Carbonic anhydrase IX (CAIX), a transmembrane glycoprotein with an intracellular enzymatic domain, is overexpressed in ccRCC as a result of VHL loss. Chimeric antibody girentuximab is a monoclonal antibody that binds an extracellular epitope of CAIX. Iodine radiolabeled (I-124) girentuximab can be used as a PET radiotracer and has been shown to identify ccRCC primary tumors with high sensitivity and specificity. This study was designed to test the feasibility of using I-124 girentuximab PET/CT in the m ccRCC setting and to produce preliminary data regarding the operating characteristics of these scans in m ccRCC. Methods: Patients (pts) with ccRCC refractory to standard antiangiogenic therapy were treated with brivanib (Bristol-Myers Squibb, Co.), a tyrosine kinase inhibitor of VEGFR2 and FGFR. Baseline I-124 girentuximab scans were obtained. For 1 pt, a second scan was performed after 8 weeks. Clinical outcome was measured radiographically by RECIST 1.0 and standard cross-sectional imaging. Results: 5 pts had 6 I-124 girentuximab PET/CT scans. No adverse events occurred. 17 RECIST target lesions were identified at baseline. PET showed heterogeneous expression of CAIX in all scans: overall, 9 of 17 (53%) metastatic target lesions expressed CAIX. Progressive disease occurred in 5/6 pts within 4 months on treatment, and progression occurred in all 8 of the CAIX non-avid lesions (100%) in these pts. One pt achieved a RECIST partial response (PR) with treatment – the pt for whom paired studies were obtained. For this pt, a PET PR was observed 2 cycles earlier than with conventional imaging. Conclusions: I-124 girentuximab PET/CT was safe and feasible in m ccRCC. We found that metastases were detected. More importantly, for pts with ccRCC refractory to conventional antiangiogenic therapies, CAIX expression was heterogeneous, and progression occurred in CAIX non-avid lesions. Taken together, these data suggest that CAIX expression identified with this functional imaging modality represents a biological prerequisite for continued antiangiogenic therapeutic activity, and the heterogeneous CAIX expression observed helps to explain why brivanib was not useful in this setting. Clinical trial information: NCT01253668.
Interim results of a phase 1b/2a study evaluating the nano pharmaceutical CRLX101 with bevacizumab (bev) in the treatment of patients (pts) with refractory metastatic renal cell carcinoma (mRCC).
Authors: Keefe Stephen Michael , Heitjan Daniel , Hennessey Meliessa , Robinson Janelle , Mykulowicz Kristine , Marshall Amy , Gunnarsson Orvar , Mamtani Ronac , Vaughn David J. , Hoffman-Censits Jean H. , Nathanson Katherine L. , Lal Priti , Pryma Daniel A. , Eliasof Scott , Garmey Edward Graeme , Cohen Roger B. , Haas Naomi B. 
Published: February 2017

412 Background: VHL is inactivated in most clear cell RCC (ccRCC) tumors giving rise to the HIF hypoxia response program and tumor angiogenesis. Antiangiogenic therapies are active in ccRCC, but resistance develops in all pts. Dual inhibition strategies may be needed to overcome resistance. CRLX101, a novel nano pharmaceutical formulation of camptothecin, has been shown in pre-clinical models to target HIF. We combined CRLX101 with bev in the treatment of pts with refractory mRCC in order to determine the safety and the recommended phase 2 dose (RP2D) of the combination, and to determine the therapeutic activity of treatment. Methods: Pts with mRCC refractory to conventional antiangiogenic therapies (all subtypes) were treated every 2 weeks with bev 10 mg/kg and escalating doses of CRLX101 (12 mg/m2, 15 mg/m2) in a standard 3+3 design with an expansion at the RP2D. Pts were treated until progression, death, or prohibitive toxicity. Adverse events were classified using CTCAE v 4.0. Radiographic results were assessed by RECIST v1.1. Results: 10 pts were enrolled on study – 6 clear cell, 2 papillary, 2 chromophobe. Median prior number of therapies was 2. No dose limiting toxicities were observed. CRLX101 at its single-agent RP2D (15 mg/m2) was safely combined with standard bev. 2 episodes of grade 3 non-infectious cystitis and 1 episode of grade 3 hypertension were observed. All other toxicities were grade 1 or 2. The median progression free survival (PFS) was 7.6 months which exceeded our pre-specified threshold of 16 weeks and has triggered 2nd stage accrual. 3 of 9 evaluable pts (33%) achieved a confirmed partial response (PR) including 1 patient with papillary mRCC; 4 pts (44%) displayed stable disease, and 2 had progressive disease as their best overall response. Conclusions: Our results demonstrate that CRLX101 can be safely combined with bev in pts with refractory mRCC. The RP2D is 15 mg/m2 q2w of CRLX101 with standard bev. Preliminary outcomes to date suggest that clinical benefit, manifest as prolonged PFS, is conferred to pts with all histologic subtypes of mRCC. Clinical trial information: NCT01625936.
The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease.
Authors: Keane Florence K. , Chen Ming-Hui , Zhang Danjie , Loffredo Marian J. , Kantoff Philip W. , Renshaw Andrew A. , D'Amico Anthony Victor 
Published: February 2017

42 Background: Recently men with intermediate-risk prostate cancer (PC) were classified into favorable and unfavorable categories but whether the risk of PC-specific mortality (PCSM) amongst men with high-risk PC is higher compared to men with unfavorable intermediate-risk PC is unknown. Methods: In a prospective randomized trial conducted between 1995 and 2001, 206 men with intermediate or high-risk PC were randomized to 70 Gy with or without six months of androgen suppression therapy (AST). The subgroup of 197 patients with available information on percent positive biopsies formed the study cohort. Fine and Gray’s regression was used to assess whether men with high-risk PC had a significantly higher risk of PCSM compared to men with unfavorable intermediate-risk PC, adjusting for age, treatment, and comorbidity category. Results: After a median follow-up of 14.3 years there were 127 deaths (64.5%), of which 22 (17.3%) were from PC. There were no PC deaths in the favorable intermediate-risk group. There was no significant increase in the risk of PCSM in men with high-risk compared to unfavorable intermediate-risk PC (Adjusted Hazard Ratio: 1.59; 95% Confidence Interval: 0.66 to 3.83; P= 0.30) after adjusting for age, randomized treatment arm and comorbidity. Conclusions: Given no significant difference in the risk of PCSM in unfavorable intermediate compared with high-risk PC, these patients may merit treatment with RT and long-term AST. The lack of PC deaths in the favorable intermediate-risk group suggests that adding AST may not reduce the risk of PCSM in these patients. [Table: see text]