bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of neoadjuvant sorafenib plus cisplatin and gemcitabine (S-CG) for patients with muscle-invasive transitional cell carcinoma of the bladder (MIBC): Results at the end of first stage (NCT01222676).
Authors: Necchi Andrea , Giannatempo Patrizia , Mariani Luigi , Fina Emanuela , Nicolai Nicola , Pennati Marzia , Zaffaroni Nadia , Farè Elena , Piva Luigi , Biasoni Davide , Catanzaro Mario , Torelli Tullio , Stagni Silvia , Maffezzini Massimo , Colecchia Maurizio , Paolini Biagio , Cappelletti Vera , Daidone Maria Grazia , Gianni Alessandro M. , Salvioni Roberto 
Published: February 2017

305 Background: The small, yet significant, survival advantage with neoadjuvant chemotherapy in MIBC needs to be improved. A rationale exists for inhibiting the RAF/MEK/ERK pathway and investigating S-CG combination in an ongoing open-label, single-group, phase II trial. Methods: Patients (pts) with T2-4N0 MIBC received 4 cycles of cisplatin 70 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on day 1 and 8, every 3 weeks. Sorafenib 400 mg q12h was administered daily from day 1 to cystectomy. An optimal 2-stage Simon’s design is applied. 6 pathologic complete responses (pT0, primary endpoint) should be observed in the first stage before moving to full enrollment of 45 cases. Residual carcinoma in situ with no evidence of invasive tumor was considered as pT0. Intention-to-treat analysis was applied. Biomarker and circulating tumor cell (CTC) analysis is ongoing. Results: 23 pts were enrolled from 04/11 to 07/13. Thus far, 21 completed the treatment and are evaluable. Median age was 61yrs (IQR: 54-66). 11 had T2, 9 T3, and one a T4 disease. 6 pts had hydronephrosis at presentation. 19 pts underwent radical cystectomy. Eight pts (38.1%, 95% CI: 18.1-61.6%) had a pT0 and 2 pts a pT<2. G3-4 side effects consisted of hematologic toxicity in 8 pts (38%), hand-foot syndrome (HFS) in 3 pts, hypertension and asthenia in 2 pts each. 9 pts (42.8%) needed a temporary interruption of sorafenib, 6 a dose reduction, and 2 suspended the drug. After a median follow up of 12.6 months, 3 pts (14.3%) had a recurrence or progression and died, the remaining are disease-free. Median increase from baseline to day 8 of second cycle was observed for VEGF levels (85.8 to 119.5 pg/mL). All pts had a stepwise reduction of CTC count/5mL blood by ScreenCell (median baseline of 8 [0-40] to 2[0-6]). 3 pT0 pts starting with cT3b disease had a decrease from baseline 21, 10, and 40 cells to ≤3 cells. Increase in circulating EpCAM±Muc-1 levels by CTC was seen in accordance with disease progression (PD). Conclusions: Sorafenib seems to enhance the efficacy of CG in this setting. If confirmed, research should delineate the mechanisms behind clinical benefit and characterize PD. Clinical trial information: NCT01222676.
Impact of prior platinum agent and site of primary in patients with advanced urothelial carcinoma (UC) receiving salvage therapy.
Authors: Sonpavde Guru , Bellmunt Joaquim , Rosenberg Jonathan E. , Bajorin Dean F. , Regazzi Ashley Marie , Choueiri Toni K. , Qu Angela Q. , Niegisch Guenter , Albers Peter , Necchi Andrea , di Lorenzo Giuseppe , Fougeray Ronan , Wong Yu-Ning , Sridhar Srikala S. , Ko Yoo-Joung , Milowsky Matthew I. , Galsky Matt D. , Pond Gregory Russell 
Published: February 2017

336 Background: The prognostic impact of prior platinum agent (cisplatin vs. carboplatin) and site of primary (bladder vs. other) in the context of salvage therapy for advanced UC is unknown. Methods: We pooled 10 prospective phase II trials of ≥ second-line therapy for advanced UC with data recorded for prior platinum agent and site of primary in addition to major prognostic factors: TFPC (time from prior chemotherapy), Hb (hemoglobin), PS (performance status), and LM (liver metastasis) status. Cox proportional hazards regression was used to evaluate the association of prior platinum agent and site of primary with overall survival (OS) and progression-free survival (PFS). Trial was included as a stratification factor throughout. Kaplan-Meier method was used to estimate PFS and OS. Results: Of 731 patients overall, 559 had received one prior chemotherapy regimen, 663 were evaluable for prior platinum regimen and 512 for site of primary. The overall median PFS and OS were 2.7 and 6.8 months, respectively. The trials evaluated vinflunine (N=151), docetaxel +/- vandetanib (N=148), paclitaxel-gemcitabine (N=98), sunitinib (N=77), volasertib (N=50), nab-paclitaxel (N=48), everolimus (N=45), pazopanib (N=43), cetuximab +/-paclitaxel (N=39) and paclitaxel-cyclophosphamide (N=32). Prior platinum was cisplatin in 501 (75.6%) and carboplatin in the rest. Prior carboplatin was associated with worse OS on univariate analysis (HR 1.23 [1.00-1.52], P=0.048) but not significantly associated with either OS or PFS on multivariate analysis. Bladder was the site of primary in 388 (75.8%). The site of primary was not significantly associated with PFS and OS in either univariate or multivariate analyses. Conclusions: Neither prior platinum agent (cisplatin vs. carboplatin) nor site of primary (bladder vs. other) were independently associated with OS or PFS in patients receiving salvage therapy for advanced UC. Trials of salvage therapy may continue to utilize the previously recognized prognostic factors, and could allow patients with all sites of primary disease and regardless of the prior platinum agent. These data need external validation.
Denosumab for the prevention of symptomatic skeletal events in patients with castration-resistant advanced prostate cancer: A comparison with skeletal-related events.
Authors: Smith Matthew R. , Coleman Robert E. , Klotz Laurence , Pittman Kenneth B. , Milecki Piotr , Wei Rachel , Balakumaran Arun , Fizazi Karim 
Published: February 2017

35 Background: In a randomized controlled trial of men with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid (ZA) for reducing skeletal-related events (SRE, defined as pathological fracture, surgery or radiation to bone [including the use of radioisotopes], or spinal cord compression) (Fizazi, et al. Lancet 2011;377:813-822.). Recently, the composite endpoint of symptomatic skeletal event (SSE, defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression) was introduced as an alternative term/clinical trial endpoint to describe skeletal morbidity. Methods: Men with CRPC, ≥ 1 bone metastasis, and no prior IV bisphosphonate use received either SC denosumab 120 mg or IV ZA 4 mg (adjusted for creatinine clearance) in a blinded fashion every 4 weeks. Oral calcium and vitamin D supplements were recommended. SSEs included pathologic fractures considered symptomatic by the investigator, spinal cord compression and surgery and radiation to bone. Results: As previously reported, fewer men who received denosumab than ZA had confirmed first SREs, and experienced multiple SREs (Table). Similarly, fewer patients in the denosumab group than the ZA group had confirmed first SSE and multiple SSEs. The median (95% CI) estimate of time to first SSE (superiority analysis) for denosumab was not reached (28.8 mo, not estimable), and for ZA it was 24.2 (20.7, 30.2) mo (HR = 0.78 (0.66, 0.93) P = 0.01). Conclusions: Denosumab reduced the risk of skeletal events in men with CRPC regardless of endpoint definition as SRE or SSE. The risk of developing SSEs was reduced by up to 22% when comparing denosumab with ZA. Clinical trial information: NCT00321620. [Table: see text]
Sorafenib monotherapy in patients with inoperable/recurrent germ cell tumors (GCT) refractory to chemotherapy: Phase II study.
Authors: Skoneczna Iwona Anna , Natorska Urszula , Tacikowska Malgorzata , Kraszewska Ewa , Kotowicz Beata , Fuksiewicz Malgorzata , Rogowski Wojciech W , Federowicz Irena , Poniatowska Grazyna , Chaladaj-Kujawska Agnieszka , Michalski Wojciech 
Published: February 2017

367 Background: The phase II trial was conducted in the population of incurable patients with refractory or relapsed GCT to evaluate the activity of sorafenib, an oral multitarget inhibitor of Raf kinase and the tyrosine kinases VEGFR-2 and PDGFR-alpha. Methods: Patients with progressive metastatic GCT received sorafenib monotherapy continuosly 400mg bid until progression of disease or unacceptable toxicity. Serum tumor markers (STM) were assessed every 4 weeks and imaging was performed every 12 weeks. Responses were assessed using RECIST; STM normalization was required for complete responses and partial responses required at least STM stabilization. STM-only declines were recorded as stable disease. Descriptive analysis of efficacy and tolerance was conducted. Results: 18 male patients with nonseminoma were included between 9/2008 and 6.2010. Pts received median 3 (range 3-4) prior chemotherapy treatments, 2 had received prior high-dose therapy. Median age was 35 (range 26-48), primary site was testicular in 16 and in 2 cases retroperitoneal. All patients had STM elevation before treatment. Median treatment duration was 83 days (31, 617), 12/18 patients were treated more than 2 cycles, 8 pts experienced some degree of STM decline with prolonged SD lasted more than 350 days in 3 pts. No partial or complete responses were observed. Drug related adverse events (AEs) were mainly grade 1 and 2; 55% of patients experienced diarrhea, 44% rash, 55% HFSR, 33% hypertension, 28% fatigue. Some G3 toxicity occurred: diarrhea in one pts, hypertension in one patient, HFSR in 2/18. 31% and 22% of pts required dose interruption and reduction respectively due to AEs. Conclusions: Sorafenib monotherapy was well tolerated but did not demonstrated significant activity in patients with highly refractory GCT, although there were some prolonged SD observed. Clinical trial information: NCT00772694.
Survival analyses of adjuvant or neoadjuvant combination of a taxane plus cisplatin and 5-fluorouracil (T-PF) in patients with bulky nodal metastases from squamous cell carcinoma of the penis (PSCC): Results of a single high-volume center.
Authors: Giannatempo Patrizia , Paganoni Anna , Sangalli Laura , Colecchia Maurizio , Piva Luigi , Catanzaro Mario , Torelli Tullio , Farè Elena , Raggi Daniele , Biasoni Davide , Stagni Silvia , Pizzocaro Giorgio , Salvioni Roberto , Nicolai Nicola 
Published: February 2017

377 Background: Bulky nodal metastases (N2-N3) of PSCC represent a negative prognostic factor, yet efficacy of multimodal treatment is not defined. For these patients (pts) we explore T-PF combination in adjuvant and neo-adjuvant setting. Methods: Paclitaxel (120 mg/m2, d1) or docetaxel (75 mg/m2 d1) plus cisplatin (75-100 mg/m2 d1) and 5-fluorouracil (5FU, 750-1000 mg/m2 96h d1) were scheduled prior to or following radical inguino-pelvic dissections in N2-3 M0 pts, according to protocol indications. Primary endpoints were overall (OS) and progression-free survival (PFS); safety and response-rate represented secondary endpoints. Association of survival with treatment setting and pre-specified covariates was explored. Results: From 6/2004 to 10/2012, 47 consecutive pts received neoadjuvant (N=28) or adjuvant (N=19) T-PF. 18 (38.3%) were disease-free after a median follow-up (FU) of 22 mos (IQR 17-42). Durable remissions were more frequently observed in adjuvant (52.6%; median FU: 42 mos) than in neoadjuvant group (28.6%; median FU: 17 mos). Distribution of OS and PFS were statistically in favour of adjuvant T-PF (p=0.01 at Wilcoxon test; p=0.008 at t test). However, Kaplan-Meyer curves did not show significant differences. A model including therapy setting, N category, laterality, pelvic extent and p53 status showed that only adjuvant administration was associated with improved OS (p=0.008), while adjuvant therapy (p=0.002), pelvic extent (p=0.029) and laterality (p=0.086) were associated with PFS. In neoadjuvant group we recorded 43% responses (complete [CR] and partial) and 4 (14%) pathologic CR. Surgery was possible in 18 (64.3%) pts, independently of response. Neither OS nor PFS were associated with response. Tolerability was mild to moderate. Conclusions: Adjuvant chemotherapy was the most important favourable predictor of OS and PFS. Adjuvant T-PF results are among the best available ones. Neoadjuvant T-PF compares with other recent schedules in terms of activity and efficacy. Surgery remains the mainstay treatment for resectable nodal metastases from PSCC.
Utilization of adjuvant therapy in Medicaid and uninsured seminoma patients: Results from the National Cancer Database.
Authors: Paly Jonathan J. , Lin Chun Chieh , Gray Phillip John , Jemal Ahmedin , Efstathiou Jason Alexander 
Published: February 2017

388 Background: Seminoma is the most common testicular cancer, and cancer specific survival approaches 100% if diagnosed and treated early. Following orchiectomy, several adjuvant therapy options exist for patients with stage 1A/B and 2A/B disease. As the Affordable Care Act’s (ACA) individual insurance mandate and expansion of Medicaid coverage will begin in 2014, we sought to understand whether differences exist in receipt of adjuvant therapy between uninsured and Medicaid patients in order to predict possible treatment patterns after the ACA takes effect. Methods: Uninsured and Medicaid patients diagnosed with seminoma from 1998-2010 in the National Cancer Data Base were identified. Multivariate logistic regressions were used to assess the relationship between uninsured status vs. Medicaid and receipt of adjuvant therapy. Results: Of 41,745 seminoma patients, 5,895 (14%) patients were on Medicaid or uninsured. Compared to Medicaid patients, uninsured patients were more likely to be younger (<29 years old), Hispanic, live in the South, treated in community hospitals, reside in areas with higher education levels, and present with stage IA/B disease (66.5% vs 59.4%, p < 0.01). After controlling for sociodemographic and clinical characteristics, uninsured stage IA/B patients had a 16% decreased likelihood of receiving adjuvant radiation or chemotherapy than Medicaid patients (p<0.05). In addition, stage 1A/B patients who were Hispanic, aged 50 or more, diagnosed in 2006-2010, treated in low-volume-case facilities or had tumor size < 4cm were less likely to receive adjuvant therapy. No treatment differences by insurance were seen in stage IIA/B patients. Conclusions: Our analysis suggests a modest association between the decision to seek optional adjuvant therapy and uninsured vs. Medicaid status in patients with stage IA/B seminoma. Given that national recommendations support surveillance, it will be increasingly important to counsel newly insured patients on the benefits of post-orchiectomy surveillance for early stage disease. In addition, no difference in management was identified for CS 2A/B patients suggesting that required therapy was not modified or avoided in the uninsured.
Identification of quality improvement opportunities in kidney cancer surgery through a regional hospital-based urologic quality collaborative.
Authors: Gore John L. , Porter Michael P , Lin Daniel W. , Harper Jonathan D. , Schmidt Zeila , Flum David R ,   SCOAP-CERTAIN Collaborative
Published: February 2017

413 Background: Patient selection for radical (RN) and partial nephrectomy (PN) for suspicion of kidney cancer may depend more on provider factors than patient characteristics. Observational data suggests that patients with small renal tumors have better overall survival when managed with PN rather than RN. We prospectively evaluated perioperative processes of care for patients undergoing kidney cancer surgery at Washington State hospitals participating in a surgical collaborative to identify quality improvement opportunities in kidney cancer care. Methods: We developed a chart abstraction tool that captures potential quality concerns in kidney cancer surgical care. The abstraction tool was implemented at nine regional hospitals with data consolidated for review quarterly. A sampling of PN and RN cases was abstracted. Hospital-specific feedback reports were blinded to hospital identity; data were analyzed as aggregate rates and hospital-specific rates using descriptive statistics. Presented results were not risk-adjusted. Results: We identified 75 patients undergoing RN or PN at 9 area hospitals from 2011-2013. Staging evaluations were uncommon (preoperative chest x-ray and chest CT in 41% and 20%, respectively). 13% percent of patients had a preoperative renal mass biopsy. For renal tumors ≤ 4 cm, 16/32 (50%) underwent PN. Hospital-specific utilization of PN for small renal masses exhibited variation: in 2 hospitals, 100% of tumors ≤ 4 cm were treated with PN, while 1 hospital performed RN in all cases, and the remaining hospitals ranged from 33%-67% utilization of PN. PN was less common for tumors 4-7 cm in size (4/26 cases [15%]). Venous thromboembolic events occurred in 4% of kidney cancer surgeries. Conclusions: We identified substantial variation in selection of surgical technique and postoperative outcomes following PN and RN for kidney cancer. Patients with small renal masses appear to have variable access to PN, which could impact their long-term health outcomes. Better understanding of provider knowledge and attitudes toward management of small renal masses could inform quality improvement initiatives to address the variations in care identified.
Correlation of PDL1 tumor expression and treatment outcomes in patients with renal cell carcinoma (RCC) receiving tyrosine kinase inhibitors: COMPARZ study analysis.
Authors: Choueiri Toni K. , Figueroa David J , Liu Yuan , Gagnon Robert C. , Deen Keith C. , Carpenter Christopher , Bartlett-Pandite Arundathy N. , De Souza Paul , Powles Tom , Motzer Robert John 
Published: February 2017

416 Background: The interaction of PDL1 (B7H1) with its receptor PD-1 on activated T cells contributes to suppression of antitumor immune responses. Tumor PDL1 expression has been associated with poor outcomes in RCC but has not been investigated as a biomarker of response in RCC patients receiving standard vascular endothelial growth factor (VEGF)-targeted therapy. Methods: Formalin-fixed paraffin-embedded tumor samples were collected at baseline from consenting patients enrolled in COMPARZ—a phase lll clinical trial comparing pazopanib and sunitinib as first-line interventions for metastatic RCC (Motzer et al, NEJM 2013). PDL1 expression was evaluated using the anti-PDL1 mouseIgG1 (clone 5H1; Thompson) on the Leica automated immunohistochemistry platform. Additional dual PDL1/CD68 staining was performed on tumor associated macrophages (TAMs). Tumor PDL1 expression was quantified by an H-score (HS). PDL1+ TAMs were assessed semiquantitatively. In addition, intra-tumor CD8+ T cells were quantified morphometrically. The association between PDL1 HS, CD8+T cell counts, and survival was investigated using Kaplan-Meier analysis. Results: HS data were available from 453 of 1110 patients. 64% of patients had negative (HS = 0) PDL1 expression (HS range 0-290), but PDL1 expression was associated with tumours containing higher numbers of infiltrating macrophages. Peripheral CD8+ T cells in the invasive margin surrounding the tumor were also observed. Patients with HS >50 (n = 61, 13%) had significantly shorter overall survival (OS) in both pazopanib (19.7 vs 31.6 mo) and sunitinib (15.3 vs 27.7 mo) arms. In both arms, patients with HS >50 with intratumoral CD8+T cell counts >300 had the shortest OS. Results were similar for progression-free survival and persisted on multivariate analysis. Conclusions: This is the largest report to show that tumors’PDL1 expression and CD8+ T cell counts are associated with treatment outcome in metastatic RCC patients. Increased PDL1, or increased PDL1 plus tumor CD8+ T cell counts, were associated with shorter OS. These findings may have major implications for future trial designs that involve PD-1 inhibitors.
Survival outcomes associated with different sunitinib dosing regimens in metastatic renal cell carcinoma.
Authors: Cheng Winnie , Kletas Victoria , De Lemos Mario Law , Man Sally , Kollmannsberger Christian K. 
Published: February 2017

417 Background: Standard dosing regimen of sunitinib for metastatic renal cell carcinoma (mRCC) consists of 4 weeks treatment followed by 2-weeks rest (intermittent dosing, ID). Alternative regimens have been suggested, including continuous daily dosing (continuous dosing, CD) and non-conventional dosing (non-conventional dosing: e.g. 2 weeks on / 1-week off, ND) to provide more individualized therapy with less toxicities. It is unclear whether non-standard sunitinib dosing affects survival outcomes. Methods: mRCC patients treated with sunitinib between July 1, 2007 and July 1, 2011 were identified from the British Columbia Cancer Agency (BCCA) pharmacy database, a publicly funded cancer care organization. Medical records and dispensing data were reviewed retrospectively to categorize sunitinib dosing as ID, CD or ND. Primary outcome was to compare overall survival (OS) associated with varying regimens, with secondary outcomes of progression free survival (PFS) and incidence of treatment discontinuation due to adverse effects (AE). Results: A total of 180 patients were identified. Heng prognostic risk criteria were assessable in 162 patients. Of these, 34 (21%), 80 (49%) and 48 (30%) had low-, intermediate- and high-risk disease. Most patients received ID (120, 67%), followed by CD (32,18%) and ND (28,16%). Compared to ID, CD was associated with similar OS (median 9 vs. 13 months, HR 0.67, 95% CI 0.43-1.06, p=0.088) while ND was associated with significantly longer OS (median 9 vs. 23 months, HR 0.55, 95% CI 0.34-0.90, p=0.016). PFS was significantly better for CD (median 4 vs. 9 months, HR 0.61, 95% CI 0.40-0.94, p=0.025) and ND (median 4 vs. 10 months, HR 0.61, 95% CI 0.39-0.95, p=0.03) when compared to ID. Similar to prior sunitinib trials, a significant proportion of patients (20%) discontinued sunitinib therapy due to AE. Conclusions: In comparison to the standard ID regimen, dosing sunitinib with alternative regimens appears to be associated with improved OS and PFS in patients with mRCC. Presently, a prospective Canadian trial is underway investigating the efficacy and safety of individualized sunitinib dosing regimens.