bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of toxicity of gemcitabine versus platinum-based combined chemoradiation for muscle-invasive bladder cancer: The Memorial Sloan-Kettering experience.
Authors: Baliga Sujith , Pei Xin , Bajorin Dean F. , Rosenberg Jonathan E. , Bochner Bernard , Kollmeier Marisa 
Published: February 2017

313 Background: The optimal radiosensitizer for chemoradiation therapy for bladder cancer is unknown. We compared toxicities of concurrent platinum (plat) vs gemcitabine (gem) in this setting. Methods: 88 patients with muscle invasive bladder cancer (MIBC) who underwent concurrent platinum (n=26) or gemcitabine (n=62) chemotherapy with definitive external beam radiotherapy (median dose= 64.8Gy) were included in this analysis. Gem was delivered biweekly and platinum-based (cisplatin or carboplatin) chemotherapy given weekly or every 3 weeks. Treatment interruptions, cycle delays, and dose reductions were recorded. Acute (<90 days) and late (≥90 days) toxicity was graded using CTCAE v4.0. Chi-square and fisher’s exact tests were used to compare groups with respect to stage, nodal status, tumor size, baseline urinary medication and Charlson co-morbidity index (CCMI). Results: Median follow-up was 18.5 mos. Mean age was 77 years (range 35-91). Gem patients were older (76 vs 63 years; p<0.01) and had higher CCMI (p<0.01). There were no significant differences in treatment interruption (8% vs 4%; p=0.67), cycle delays (52% vs 36%; p=0.24) or dose reductions (27% vs 12%; p=0.16) in the gem vs plat cohorts respectively. Hematologic toxicity was the most common reason in both groups. Acute and late grade ≥2 GU toxicity in the gem and plat cohorts were 30% vs 8% (p=0.03) and 8% vs 8%, respectively. More gem patients were on a baseline urinary medication (21% v 8%; p=0.22). Six patients developed urinary incontinence (all in gem cohort). One patient in the plat cohort developed late grade 3 hemorrhagic cystitis. Acute and late grade ≥2 GI toxicity in the gem and plat cohorts were 16% vs 12% (p=0.75) and 4% vs 3% (p=1), respectively. 2 patients (one in each cohort) developed acute grade 3 GI toxicity. Conclusions: Chemoradiation for MIBC with gemcitabine or platinum-based chemotherapy is generally well tolerated. In our series, despite older age and higher CCMI in the gem cohort, most (>90%) completed treatment. Higher acute GU toxicity was noted in the gem cohort. Late grade 3 GU/GI toxicity was low and comparable amongst the two radiosensitizers.
Prediction of relapse in stage I nonseminomatous germ cell tumors (NSGCT) by CXCL12: Results from the MRC TE08 and TE22 clinical trials.
Authors: Gilbert Duncan Charles , Thway Khin , Chandler Ian , Al-Saadi Reem , Gabe Rhian , Stenning Sally P. , Shipley Janet , Huddart Robert Anthony 
Published: February 2017

319 Background: Stage I NSGCT harbor occult metastatic disease in up to 50% of patients and undergo surveillance with chemotherapy at relapse or adjuvant treatment with excellent survival but concern around subsequent toxicity. Better prediction of relapse would minimize exposure to unnecessary treatments. Previous data suggested CXCL12 aided assessment of relapse risk (Gilbert DC, et al. J Pathol. 2009 Jan;217:94-102). MRC TE08 (Rustin GJ, et al. J Clin Oncol. 2007 Apr 10;25:1310-1315) and TE22 (Huddart RA, et al. J Clin Oncol. 2007 Jul 20;25:3090-3095) were clinical trials incorporating surveillance in stage I NSGCT. Methods: Tumor samples from patients enrolled in TE08 and TE22 were obtained with ethical approval and subjected to immunohistochemical staining for CXCL12. These were scored and CXCL12 analysed as a prognostic factor for relapse independently of vascular invasion (VI - the only currently validated marker). Results: Samples were obtained from 182/466 eligible patients. The 2-year relapse-free rate (RFR) was 76.4%. In CXCL12 moderate/strong cases this was 80.1% (95% CI 73.4-86.8). In CXCL12 absent/weak cases (<1% cells staining moderately or strongly) this was 64.9% (49.6-80.2); hazard ratio 0.54 (95% CI 0.28-1.04). CXCL12 intensity was independently prognostic, p=0.006 (logrank test stratified by VI). Absent/weak CXCL12 expression was significantly associated with embryonal histology (p=0.001). In multivariate analysis including clinical and pathological features, only CXCL12 (HR 0.43, 95%CI 0.22-0.83) and VI (HR 4.77, 95%CI 2.49-9.13) were predictive of relapse. Conclusions: CXCL12 intensity is prognostic for relapse independently of VI. This additional prognostic information can identify groups at very low and very high risk of relapse with potential clinical utility. Acknowledgements: Supported by MRC Biomarkers Grant G0801477 and the NCRI Testis Cancer Clinical Studies Group. [Table: see text]
Postchemotherapy retroperitoneal lymph node dissection for advanced germ cell tumors at a Japanese single high-volume center.
Authors: Nakamura Terukazu , Kimura Yasunori , Ueda Takashi , Naya Yoshio , Hongo Fumiya , Miki Tsuneharu 
Published: February 2017

331 Background: Post chemotherapy lymph node dissection (PCRPLND) plays important role in the management of advanced germ cell tumors (GCTs). Guidelines recommend performing PCRPLND for advanced GCT with tumor marker normalization. The aim of this study is to assess efficacy and preserve antegrade ejaculation at Japanese single high volume center. Methods: One hundred and eleven patients who had PCRPLND at Kyoto Prefectural University of Medicine between June 1998 and August 2011 were studied. Five cases of desperation RPLND and 6 cases of laparoscopic RPLND were also included. Results: Median age was 30 years old (17-68y.o.). Seminoma was 11 cases and nonseminoma was 100 cases at primary site. Good, intermediate and poor prognosis group of International Germ Cell Cancer classification was 48, 35 and 20 cases, respectively. Seventy-four cases were treated after induction chemotherapy and 41 cases were done after salvage chemotherapy. median operation time was 590 min. and median blood loss was 1650ml. Nerve-sparing procedure were performed for 90 cases. Antegrade ejaculation was preserved in 83.5% of this cohort. Especially, antegrade ejaculation was preserved in 93.3% of the patients with bilateral nerve sparing. Necrosi/fibrosis, teratoma only and viable cancer were detected in 54.4%, 32.5% and 13.1%, respectively. Additional procedure such as nephrectomy was performed in 12 cases. Five-year overall survival was 95.1%. In the desperation group, only one case is alive without disease. Conclusions: The results of PCRPLND at high volume center could be satisfied and preservation of antegrade ejaculation could be obtained. On the other hand, indication of desperation RPLND had to be carefully considered.
Treatment patterns for patients with localized (T1-T2) penile squamous cell carcinoma in the United States.
Authors: Barbosa Brittney Diane , Hendrix Laura H. , Pearlstein Kevin Alexander , Chen Ronald C. 
Published: February 2017

332 Background: The standard treatment for patients with localized penile squamous cell carcinoma is penectomy, which is associated with high psychosocial morbidity. Organ preservation using radiation therapy is an alternative. To our knowledge, this is the first population-based patterns of care study in this disease for a modern cohort of men. Methods: Caucasian (CA, N=1,270) and African American (AA, N=139) patients diagnosed with localized cancer from 2000-2009 were included from the Surveillance, Epidemiology and End Results (SEER) database. Treatments were categorized into ablative therapies (e.g. laser, electrocautery), surgical resection, or radiation therapy (including external beam and brachytherapy). Multivariate logistic regression assessed factors associated with receipt of radiation therapy as primary treatment. Results: 57% of patients were married. The vast majority of patients receive surgical resection, with about 1% receiving primary radiation therapy (Table). Patterns of care were not significantly different among AA and CA patients (p=.95). Multivariable analysis including diagnosis year, marital status, age, race and SEER region did not show any covariate significantly associated with receipt of primary radiation treatment. Conclusions: Surgical resection is the predominant treatment for patients with localized penile cancer in the United States, with very few patients receiving primary radiation therapy. [Table: see text]
Incidence of testicular cancer in the United States from 1992 to 2009.
Authors: Nigam Manas , Aschebrook-Kilfoy Brisa , Shikanov Sergey , Eggener Scott E. 
Published: February 2017

339 Background: The incidence of testicular cancer (TC) increased in the US through 2003. However, little is known about these trends after 2003. We sought to determine trends in TC incidence based on race, ethnicity and tumor characteristics. Methods: TC incidence and tumor characteristic data from 1992-2009 were extracted from the Surveillance, Epidemiology, and End Results-13 (SEER) registry. Trends were determined using JoinPoint. Results: TC incidence in the US increased from 1992 (5.7/100,000) to 2009 (6.8/100,000) with annual percentage change (APC) of 1.1% (p < 0.001). TC rates were highest in non-Hispanic white men (1992: 7.5/100,000; 2009: 8.6/1000) followed by Hispanic men (1992: 4.0/100,000; 2009: 6.3/100,000) and lowest among non-Hispanic black men (1992: 0.7/100,000; 2009: 1.7/100,000). Significantly increasing incidence rates were observed in non-Hispanic white men (1.2%, p < 0.001) but most prominently among Hispanics, especially from 2002-2009 (5.6%, p < 0.01). A significant increase was observed for localized TC (1.21%, p < 0.001) and metastatic TC (1.43%, p < 0.01). Increased incidence occurred in localized tumors for non-Hispanic white men (1.56%, p <0.001), while Hispanic men experienced an increase in localized (2.6%, p < 0.001), regionalized (16.5% from 2002-09, p < 0.01), and distant (2.6%, p < 0.01) disease. Conclusions: Through 2009, testicular cancer incidence continues to increase in the United States, most notably among Hispanic men. [Table: see text]
Surveillance for the management of small renal masses: Utilization and outcomes in a population-based cohort.
Authors: Huang William C. , Pinheiro Laura C. , Russo Paul , Lowrance William Thomas , Elkin Elena B. 
Published: February 2017

343 Background: Small renal masses (SRM) are comprised of a heterogeneous group of tumors with some having malignant potential. Although surgery is the standard treatment for SRMs, emerging data suggests that surgery in the elderly or morbidly ill patients may be unnecessary and may adversely impact non-oncologic outcomes. We analyzed a population-based cohort of patients to identify predictors of surveillance and assess the impact of surveillance on overall survival, kidney cancer-specific survival and cardiovascular (CV) events, compared with surgery. Methods: From surveillance, epidemiology, and end results (SEER) cancer registry data linked with Medicare claims, we performed a retrospective cohort study of patients 66 years of age or older who received surgery or surveillance for SRM (< 4 cm) diagnosed between 2000 to 2007. Propensity score methods were used to control for potential confounders in multivariable analysis. Results: Of 8,317 patients, 5,706 (70%) underwent surgery and 2,611 (31%) underwent surveillance. The use of surveillance increased from 25% in 2000 to 37% in 2007 (p < 0.001). During a median follow-up of 58 months, 2,053 (25%) patients had at least one CV event and 2,078 (25%) patients died, including 277 (3%) who died of kidney cancer. Compared with surgery, surveillance was associated with a significantly lower risk of death from any cause (hazard ratio [HR], 0.84; CI, 0.75-0.94) and of suffering a CV event (HR, 0.79; CI 0.70-0.89), controlling for patient and disease characteristics. Kidney cancer-specific survival did not differ by treatment approach (HR, 0.89; CI, 0.66-1.21). Conclusions: There is increasing utilization of surveillance as an initial treatment strategy for patients with SRMs. For older patients with SRM, surveillance does not appear to adversely affect kidney cancer-specific survival, while surgery may be associated with CV complications and an increased risk of death from any cause. Surveillance should be considered an option for patients with SRM who are not otherwise acceptable candidates for surgical treatment.
Incidence and risk of infections in renal cell cancer (RCC) and non-RCC patients treated with everolimus and temsirolimus: A meta-analysis of randomized control trials.
Authors: Kaymakcalan Marina , Je Youjin , Sonpavde Guru , Galsky Matt D. , Nguyen Paul Linh , Schutz Fabio , Heng Daniel Yick Chin , Richards Christopher J. , Choueiri Toni K. 
Published: February 2017

353 Background: Everolimus and temsirolimus are mammalian target of rapamycin (mTOR) inhibitors used in a variety of malignancies including renal cell carcinoma (RCC). These targeted agents have been associated with a unique set of adverse events including infections. We performed an up-to-date meta-analysis of published clinical trials to further characterize the risk of infections in cancer patients treated with mTOR inhibitors. Methods: Pubmed and oncology conference proceedings were searched for studies from January 1966 to June 2012. Eligible studies were limited to phase II and III randomized controlled trials (RCTs) of everolimus or temsirolimus that reported on patients with cancer of any tumor type including RCC and with adequate safety profiles. Summary incidence, RR, and 95% CIs were calculated using random- or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 2,990 patients from 8 RCTs were included. The incidence of all-grade infections due to mTOR inhibitor treatment was 35.7% (95% CI, 28.8-43.3) and that of high-grade infections was 4.2% (95% CI, 2.1-8.4). The relative risk of all-grade infection due to mTOR inhibitors was 1.95 (95% CI, 1.67-2.29, p<.001) and that of high-grade infection was 1.91 (95% CI, 1.09-3.35, p=.024). Subgroup analysis found no difference in the incidence or risks of infections between everolimus and temsirolimus or between different tumor types (RCC vs. non RCC). Infections included respiratory tract (38.0%), urinary tract (17.1%), skin/soft tissue (3.6%), others (2.6%), and infection/not specified (38.7%). No evidence of publication bias was observed. Conclusions: Treatment with mTOR inhibitors, everolimus and temsirolimus, is associated with a significant increase in risk of infection in RCC and non-RCC patients.
A phase Ib clinical trial of the multitargeted kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC).
Authors: Molina Ana M. , Hutson Thomas E. , Larkin James M. G. , Gold Anne , Andresen Corina , Wood Karen , Motzer Robert John , Michaelson M. Dror 
Published: February 2017

358 Background: Lenvatinib (L) is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR 1-4, RET, KIT, and PDGFβ. Everolimus (E) is an oral mTOR inhibitor approved for RCC. This Phase (Ph) 1b/2 study investigates the combination of L plus E in RCC patients (pts) (NCT01136733). The Ph 1b component reported here assessed safety, tolerability, and maximum tolerated dose (MTD). Methods: Pts with advanced unresectable or metastatic RCC, ECOG PS 0-1, age ≥18 y, were eligible for Ph 1b. Pts received L plus E, daily, in 28-day cycles. A standard 3+3 dose-escalation design with expansion cohort was used to identify the MTD. Results: 20 pts (M/F: 14/6; median age: 59 y [range 46-72]; median of 2 prior therapeutic regimens [range 0-5]; 17/20 pts [85%] had received prior anti-VEGF treatment (tx); 7/20 pts [35%] had also received prior mTOR-targeted tx) were treated at 3 dose levels of L (12 mg [n=7]; 18 mg [n=11]; 24 mg [n=2]) in combination with E 5 mg. DLTs were observed in 4 pts: G3 nausea and vomiting (1 pt) and G2 mucositis (1 pt) with 24 mg; G3 elevated creatinine phosphokinase, G2 fatigue, and G1 reflux with 18 mg; G3 abdominal pain with 12 mg. The MTD was L 18 mg plus E 5 mg. Median duration of tx was 19 wk (range 1-68, 6/20 (30%) pts ongoing). The most common tx-related adverse events (AEs), all grades, were fatigue 50% (G3, 5%); diarrhea 40% (G3, 10%); mucosal inflammation 40%; proteinuria 40% (G3, 10%); decreased appetite 35%; nausea, vomiting each 35% (each G3 5%); hypertension 35%; rash 30%; dry skin, epistaxis, weight decreased, constipation, edema peripheral (G3 5%), each 20%. There was 1 G4 tx-related AE of hypercholesterolemia. In the MTD and lower-dose cohorts, partial response (PR) was observed in 6/18 (33%) pts; durable stable disease (SD) (≥23 wk) or PR were achieved in 11/18 (61%) pts. Median PFS was 442 days (approx. 15 mos) in MTD and lower-dose cohorts. Conclusions: Lenvatinib 18 mg in combination with everolimus 5 mg appeared to be well tolerated when administered to multiply pretreated patients with advanced RCC in this Ph1b study. The PRs observed and SD durability warrant further evaluation in this refractory population during the ongoing Ph 2 part of the study. Clinical trial information: NCT01136733.
Association of adverse health outcomes with partial and radical nephrectomy: Is it time to reassess the “gold standard” for the small renal mass?
Authors: Shuch Brian , Hanley Janet , Lai Julie , Setodji Claude Messan , Vourganti Srinivas , Chow Wong Ho , Saigal Christopher 
Published: February 2017

363 Background: Partial (PN) and radical (RN) nephrectomy are treatments for the small renal mass. PN is considered the gold standard, as it may protect against renal dysfunction compared to RN. As active surveillance is emerging as a possible strategy, it is essential to understand the adverse health outcomes associated with both interventions. Methods: A retrospective, case-controlled series was performed using the Surveillance, Epidemiology, and End Results-Medicare dataset. Individuals treated with PN or RN for ≤4 cm non-metastatic, renal cell carcinoma (RCC) were compared to two control groups (non-muscle invasive bladder cancer [BCC] and non-cancer patients [NCC]). A Greedy Algorithm matched surgical groups (1:1) to controls by demographics and comorbidity. Medical claims >30 days after treatment were examined for renal, cardiovascular, and secondary cancer events. Results: Patients undergoing PN (1,436) and RN (4,247) were matched to controls and no significant differences were noted in key variables. All cancer groups had 10-year cancer-specific survival >95%. The time to event model demonstrated an increased risk of renal events for both treatments. Compared to BCC and NCC, RN hazard ratios were 2.415 (p < 0.0001) and 6.211 (p < 0.0001), respectively, while PN hazard ratios were 1.513 (p < 0.0001) and 4.926 (p < 0.0001), respectively. Secondary cancers were increased for both PN and RN compared to both control groups (p < 0.0001). Cardiovascular events were increased for both PN and RN compared to NCC (p < 0.0001), but this failed to reach significance when either group was compared to BCC controls. Conclusions: RCC patients treated with PN and RN are at significant risk of subsequent adverse health outcomes. When compared to RN, PN may have better renal outcome; however, when compared to controls, both options significantly increase renal events. The increase in secondary cancers and cardiovascular events with PN and RN is concerning and requires further investigation. As active surveillance is an emerging strategy, it may be time to rethink our current treatment paradigm for the small renal mass.
SGN-75 in the treatment of patients with CD70-positive malignancies including metastatic renal cell carcinoma.
Authors: Thompson John A. , Forero Andres , Heath Elisabeth I. , Pal Sumanta Kumar , Ansell Stephen Maxted , Infante Jeffrey R. , De Vos Sven , Hamlin Paul A. , Whiting Nancy Cherry , Zhao Baiteng , Tannir Nizar M. 
Published: February 2017

368 Background: SGN-75 is an antibody-drug conjugate composed of a humanized anti-CD70 mAb conjugated to the microtubule-disrupting agent MMAF via a plasma-stable linker. Upon binding to CD70, SGN-75 internalizes and releases cys‑mcMMAF which binds tubulin and induces G2/M arrest and apoptosis. Methods: A phase 1, dose-escalation, multicenter study was initiated to investigate the safety, tolerability, PK, and antitumor activity of SGN-75 monotherapy in pts with CD70-positive metastatic RCC or relapsed/refractory NHL (ClinicalTrials.gov #NCT01015911). SGN-75 was administered IV in cohort-specific doses using 2 schedules [every 3 weeks (q3wk) or weekly (days 1, 8, 15 q28 days)] at doses of 0.3-4.5 mg/kg. Pts were eligible to receive treatment until PD. Results: A total of 58 pts (39 RCC/19 NHL) with a median age of 60.5 yrs (range 30-82) were treated. The MTD was 3 mg/kg q3wk; 2 pts had DLTs at 4.5 mg/kg q3wk (NHL pt had neutropenia and RCC pt had proteinuria). Weekly dosing (N=11) was terminated at the 0.6 mg/kg dose level after 2 pts with NHL developed idiopathic thrombocytopenic purpura. At the MTD, adverse events (AEs) in ≥30% of RCC pts (N=21) were fatigue (52%), dry eye (48%), nausea (38%), constipation (33%), and corneal epithelium defect (33%). AEs ≥ Grade 3 in >10% of RCC pts treated at the MTD were corneal epithelium defect (19%) and thrombocytopenia (14%). PK analysis suggested that SGN-75 exposure was approximately dose-proportional with a mean terminal half-life of 6-11 days. Among the 32 pts with RCC treated in the q3wk schedule, all had prior nephrectomy and a median of 3 prior therapies (range 1-6). All pts had clear cell RCC, with the exception of 2 pts who had papillary RCC. Most pts had high CD70 expression by central IHC analysis (2 or 3+, 80-100% of cells). The best clinical responses of RCC pts treated q3wk were 2 PR, 12 SD, 12 PD, and 6 were not evaluable. Durations of response for the 2 responding pts were 23 and 41 weeks. The median duration of disease control (PR and SD) was 46.4 weeks [95% CI (12, 46)]. Conclusions: SGN-75 monotherapy was generally well tolerated in pts with metastatic RCC. Evidence of antitumor activity was observed in heavily pretreated RCC pts and further studies of SGN-75 in RCC are warranted. Clinical trial information: NCT01015911.