bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent chemoradiotherapy (CRT) for bladder cancer: Practice patterns and outcomes in the general population.
Authors: Ghate Ketan , Brennan Kelly , Karim Safiya , Mackillop William J. , Booth Christopher M. 
Published: September 2018

e16025 Background: Clinical trials have shown that CRT improves survival compared to RT alone in muscle invasive bladder cancer. We describe uptake of CRT and outcomes in routine practice. Methods: Electronic treatment records were linked to the population-based Ontario Cancer Registry to identify all patients treated with curative intent RT for bladder cancer in Ontario 1999-2013. Practice patterns were described in three eras: 1999-2003, 2004-2008, 2009-2013. Modified Poisson regression was used to analyze factors associated with use of CRT. Cox model and propensity score analysis were used to explore the association between CRT and overall (OS) and cancer-specific survival (CSS). Results: 1398 patients underwent curative intent RT during 1999-2013; median age was 79 and 75% (1050/1398) were male. Use of CRT increased over time: 33% (135/409) in 1999-2003, 35% (170/482) in 2004-2008, 46% (232/507) in 2009-2013 (p < 0.001). Among the 80% (431/537) of CRT cases with available drug details, the most common regimens were single-agent Cisplatin (57%, 245/431), single-agent Carboplatin (31%, 133/431) and 5-FU/Mitomycin (4%, 19/431). Factors associated with CRT include younger age (p < 0.001), male sex (p = 0.027), and lower co-morbidity (p < 0.001). There were large regional differences in use of CRT (range 14% to 85%, p < 0.001). Five year OS, CSS, and cystectomy-free survival rates among CRT cases were 34% (95%CI 30%-39%), 45% (95%CI 40%-50%), and 30% (95%CI 26%-34%). On adjusted analyses CRT was associated with superior survival compared to RT alone (OS HR 0.68, 95%CI 0.60-0.70; CSS HR 0.64, 95%CI 0.54-0.76). These results were consistent on propensity score analysis. There was a non-significant trend towards improved survival among all treated cases in 2009-2013 compared to 1999-2003 irrespective of chemotherapy delivery (OS HR 0.86, 95%CI 0.74-1.01; CSS HR 0.82, 95%CI 0.67-1.01). Conclusions: Although there has been substantial uptake of CRT in routine practice, utilization rates vary widely by region. CRT is associated with superior survival compared to RT alone and its uptake corresponded to a temporal trend towards improved survival among all treated cases in the general population.
Targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 expressing bladder cancer using combination photoimmunotherapy (PIT).
Authors: Siddiqui Mohammad rashid , Railkar Reema S. , Sanford Thomas , Choyke Peter L. , Kobayashi Hisataka , Agarwal Piyush K. 
Published: September 2018

e16026 Background: Bladder cancer (BC) is heterogeneous, expressing various cell surface targets, such as EGFR and Her2. Photoimmunotherapy (PIT) involves antibodies (Abs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by Near infra-red light (NIR) to specifically target tumors. Our lab has previously shown that tumors expressing high levels of EGFR can be efficiently targeted with PIT. However, PIT is less effective when a tumor lacks “overwhelming” expression of a single target. Here, we present a novel, combinatorial PIT approach for such tumors expressing EGFR and Her2, using Panitumumab-IR700 (PanIR700) and Trastuzumumab-IR700 (TraIR700) antibodies, respectively. Methods: BC cell lines were analyzed for expression of EGFR and Her2 using flow cytometery. Concurrent and optimal binding of both PA-labeled Abs were determined using flow cytometery. NIR LD50 of multiple treatment regimens were determined to analyze in vitro efficacy of combination PIT. Results: The SW780 and RT112 cell lines showed low to moderate expression of EGFR and Her2. The EGFR expression was 143 fold higher in SW780 and 83 fold higher in RT112 over the isotype control. The Her2 expression was 42 fold higher in SW780 and 27 fold higher in RT112 over the isotype control. Hence, the ratio of cell surface EGFR to Her2 expression in both cell lines was about 3:1. For SW780, NIR LD50 was 28.66 J/cm2 for the combination PIT compared to 71.55 J/cm2 for the PanIR700 alone therapy. The NIR LD50 for RT112 was 14.66 J/cm2 for the combination PIT, with LD50 for PanIR700 alone therapy indeterminate from insufficient cell death. In both cases, the LD50 for TraIR700 alone therapy could not be determined from lack of sufficient cell death. Conclusions: PIT is a new targeted treatment for bladder cancer that can be effectively used either locally or for metastatic lesions accessible by the NIR light. We demonstrate a novel and promising approach to treating BC by selectively inducing cell death in BC cell lines with low to moderate expression of cell surface markers of EGFR and Her2 using combination PIT. This will be further evaluated in a xenograft model.
Potential underuse of repeat resection among patients with high-grade non-muscle invasive bladder cancer.
Authors: Check Devon , Aaronson David S. , Lee Valerie S. , Nielsen Matthew , Tang Li , Kushi Lawrence H. , Kwan Marilyn L. 
Published: September 2018

e16028 Background: For patients diagnosed with non-muscle invasive bladder cancer (NMIBC), guidelines recommend that those with high-grade (HG) T1 disease and potentially those with lower risk HG Ta disease receive a repeat resection within six weeks of initial resection. For these patients, repeat resection has diagnostic, prognostic, and therapeutic value and is critical for informing treatment decision-making, and ultimately optimizing outcomes. Current rates of repeat resection in practice are unknown. Methods: We conducted a retrospective analysis of patients diagnosed with HG T1 and HG Ta NMIBC between 1/1/2015 and 3/1/2016 using cancer registry-linked electronic medical record data. Our analysis included 118 patients with HG T1 disease and 114 patients with HG Ta disease who did not undergo a cystectomy. We used modified Poisson regression with clustered standard errors to assess the associations of patients’ clinical and socio-demographic characteristics and providers’ characteristics with patients’ receipt of repeat resection. We present adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: 40% of HG patients (55% of T1 patients; 24% of Ta patients) underwent repeat resection, with no differences in receipt by patient age, gender, race, or comorbidity burden. In addition to HG T1 (vs. HG Ta) disease (aRR: 2.20, 95% CI: 1.53-3.22), higher census-tract median household income was associated with increased likelihood of repeat resection (aRR highest vs. lowest income quartile: 1.42, 95% CI: 1.08-2.23). At the treating urologist level, more time in practice was negatively associated with likelihood of repeat resection receipt (aRR highest vs. lowest quartile of number of years in practice: 0.56, 95% CI: 0.41-0.77). Conclusions: Our data suggest that a large proportion of potentially eligible HG patients did not undergo a repeat resection, and that variation in practice is driven by patients’ social characteristics and treating urologist characteristics. Further research is needed to understand whether the variation observed reflects a quality improvement need versus patient-centered decision-making that accounts for preferences and treatment eligibility.
Systemic immune-inflammation index is prognostic in testicular germ cell tumors with PD-L1 expressing tumor infiltrating lymphocytes.
Authors: Chovanec Michal , Cierna Zuzana , Miskovska Vera , Machalekova Katarina , Kalavska Katarina , Rejlekova Katarina , Svetlovska Daniela , Macak Dusan , Spanik Stanislav , Kajo Karol , Babal Pavel , Mardiak Jozef , Mego Michal 
Published: September 2018

e16042 Background: Systemic immune-inflammation index (SII) and programmed death-ligand 1 (PD-L1) are prognostic in various types of malignancies. Recently we have shown a prognostic value of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes (TILs) in testicular germ cell tumors (GCT). This study aimed to evaluate prognostic role of SII in a GCT population of patients expressing PD-L1 on TILs. Methods: SII was calculated using platelet (P), neutrophil (N) and lymphocyte (L) counts measured prior to chemotherapy (SII = P x N/L). SII was calculated in our discovery set of 216 patients with GCT treated at National Cancer Institute and St. Elisabeths' Cancer Institute between 1999 and 2015. A model with median obtained from the discovery data was tested in an independent validation set of 181 patients that were included in a retrospective study evaluating PD-L1 on TILs in GCT. PD-L1 on TILs was detected by immunohistochemistry and scored semiquantitatively by weighted histoscore method. SII was dichotomized into low and high categories based on median value. Results: Low SII ( < 1003) was found in 133 patients (73.5%) as opposed to 48 patients (26.5%) with high SII (≥ 1003). Ten (5.5%) and 171 patients (94.5%) from the validaton set had low (HS < 150) and high (HS ≥ 160) expression of PD-L1 on TILs, respectively. Discovery group of patients with high SII had significantly shorter PFS (HR = 4.48, 95% CI 2.44 – 8.23, p = 0.0000) and OS (HR = 6.10 95% CI 3.11 – 11.95, p = 0.0000) opposite to patients with low SII. PFS from validation set confirmed shorter PFS (HR = 3.03, 95% CI 3.86 – 7.46, p = 0.0062) and OS (HR = 6.49 95% CI 2.10 – 20.03, p = 0.0001) in patients with high versus low SII. A combined prognostic value of PD-L1 TILs and SII uncovered three prognostic groups. The best prognosis was observed in patients with low SII and high PD-L1 on TILs, the worst prognosis was seen in patients with high SII and low PD-L1 on TILs. Patients with SII and PD-L1 on TILs both values high or low had intermediate prognosis. Conclusions: SII was prognostic in our patients with GCT independently of international germ cell cancer collaborative group criteria, suggesting involvement of immune mechanisms in the behavior of GCT.
Audiograms and hearing loss before and after cisplatin-based chemotherapy (CBCT) in testicular cancer survivors (TCS).
Authors: Haugnes Hege Sagstuen , Stenklev Niels Christian , Brydoy Marianne , Wilsgaard Tom , Laukli Einar , Fossa Sophie D. 
Published: September 2018

e16047 Background: 80% of TCS were reported to have a hearing loss based on post-CBCT audiograms (American Speech-Language-Hearing Association (ASHA) definition; Frisina et al, JCO 2016:34) Methods: 46 TCS treated with CBCT 1980-1994 with audiograms (0.25-8 kHz) pre chemotherapy (PRE) and at a survey (SURV) after median 10 years were included (cases). Audiograms at SURV from 46 age-matched TCS without CBCT were included as controls. Linear regression was performed to evaluate predictors for change in hearing threshold level (HTL) from PRE to SURV. Mean HTL for both ears exceeding 20 dB at any frequency 0.25-8 kHz were classified as a hearing loss (ASHA definition). We also applied the WHO definition of hearing loss, present if the average HTL threshold for the four frequencies 0.5, 1, 2 and 4 kHz exceeded 20 dB (M4 definition). At SURV, self-reported hearing loss was assessed by a questionnaire (categorized as “a little”, “quite a bit” and “very much” vs. “not at all”). Results: Age and PRE HTL was associated with change in HTL for most frequencies. Cisplatin dose was significantly associated with change in HTL for the frequencies 2 to 8 kHz, with a gradually greater change in HTL and lower p-value with increasing frequencies. For the 8 kHz frequency, each 100 mg increase in cumulative cisplatin dose was associated with a deterioration of 3.6 dB (p < .001). According to ASHA, the prevalence of a hearing loss among cases was 33% PRE, 70% at SURV, and 65% among controls at SURV (cases vs. controls, p = .66). According to M4, the prevalence of hearing loss among cases was 6.5% PRE, 13% at SURV, and 2.2% among controls at SURV (cases vs. controls, p = 0.05). Overall 29% of cases, and 33% of controls (p = .70) reported some degree of hearing impairment at SURV, of whom only 6.5% of cases reported more than “a little”. Self-reported hearing loss was not associated with hearing loss according to ASHA (p = .20), but was associated with the M4 definition (p = .02). Conclusions: Cisplatin is associated with a moderate hearing loss particularly at higher frequencies. Ageing is important for hearing loss regardless of treatment. The ASHA definition of hearing loss overestimates the hearing problem and should not be used as a clinical tool.
Activity of second line axitinib in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib: Results from SAX Italian real world trial.
Authors: Rossetti Sabrina , Romano Francesco Jacopo , D'Aniello Carmine , Cavaliere Carla , Pisconti Salvatore , Iovane Gelsomina , Berretta Massimiliano , Marchetti Paolo , Crispo Anna , Piscitelli Raffaele , Muto Paolo , Maiolino Piera , Perdonà Sisto , Botti Gerardo , Facchini Gaetano ,   SAX Study Group
Published: September 2018

e16054 Background: Axitinib, a selective tyrosine kinase inhibitor (TKI), is currently approved for the treatment of mRCC after failure of prior treatment with sunitinib or cytokine, according to AXIS trial results. The best sequence hasn’t been established: both axitinib and everolimus (a mTOR inhibitor) are viable therapeutic options, although recently immunotherapy agents entered this setting. This Italian multi-institutional retrospective analysis evaluated outcomes of Axitinib in exclusive sequence after sunitinib in second line treatment of mRCC Methods: Medical records of 148 patients treated with Axitinib from 21 Italian Oncology Centers were retrospectively assessed: PFS, OS, ORR DCR, and safety profile of axitinib were primary endpoints. Results: Median PFS and OS were 7.14 and 15.5 months, respectively. Overall, axitinib at standard schedule of 5 mg bid, was well tolerated, with no grade 4 toxicity event. Most common adverse events were hypertension (26% of the cases), fatigue (50 %), hypothyroidism (18%). At univariate analysis, when patients were stratified by Heng score, mPFS was 5.8, 7.0 and 9.0 months according to poor, intermediate and favourable risk group, respectively. When stratified by median duration of prior sunitinib therapy (≥ 13,1 mo vs < 13,1 mo), there was a statistically significant difference in PFS with 8.8 vs 6.3 months, respectively. Disease control rate (DCR) to previous sunitinib treatment was associated to longer PFS with axitinib ( 8.0 months vs4.0 months). The sequence sunitinib-axitinib was well tolerated, with a mOS of 41 months. At multivariate analysis, prognostic factors for progression were gender (p-value = 0,006), DCR to axitinib (p < 0,0001) and to previous sunitinib (p = 0,041); DCR to axitinib (p = < 0,0001), nephrectomy (p = 0,002) and Heng score (p = 0,025) independently affected overall survival. Conclusions: The preliminary SAX results in the real world population are consistent with available literature. The study confirms that Axitinib is effective and safe in routine clinical practice, and its efficacy seems to be greater in patients who most benefited from first-line sunitinib.
Can dynamic changes in prognostic markers predict survival in patients receiving VEGF-targeted therapy in clear cell renal cell carcinoma?
Authors: Shepherd Scott Thomas Colville , Hall Peter , Brown Janet Elizabeth , Larkin James M. G. , Jones Robert J. , Ralph Christy , Hawkins Robert E. , Chowdhury Simon , Boleti Ekaterini , Bahl Amit , Fife Kate , Webb Andrew , Crabb Simon J. , Geldart Thomas R. , Dunlop Joanna , McLaren Duncan , Ackerman Charlotte , Beltran Luis , Nathan Paul D. , Powles Thomas 
Published: September 2018

e16061 Background: Markers of the systemic inflammatory response have prognostic value in ccRCC prior to starting treatment. Dynamic changes during therapy and their role in predicting prognosis are not well characterised. Methods: A retrospective analysis was conducted of a randomised, double-blind phase II study evaluating cediranib vs cediranib and saracatinib in patients with relapsed metastatic ccRCC (COSAK). Haemoglobin (Hb), neutrophil count (N0) platelet count (Plt), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were recorded at randomisation, 8-weeks and progression (PD). Change in mean values at each time point were compared. Baseline prognostic values for overall survival (OS) were assessed using Cox regression. Absolute changes in parameters were calculated at 8 weeks and PD, patients were grouped around the upper or lower quartile. Prognostic value of dynamic changes was assessed at 8 weeks and PD using the Kaplan-Meier method. Results: 138 patients were assessed; median OS was 12.0 months (IQR 8.1-15.6 months). Outcomes in the combination arm were similar to single agent arm (HR 1.28 (1.00–1.63)). On multivariate analysis at baseline, MSKCC score (0/1-2/≥3) (HR 2.52 (1.60 -3.96)), CRP ( < 10/≥10mg/L) (HR 1.72 (1.04 – 2.86)) and N0 ( < 7.5/≥7.5x109) (HR 2.38 (1.43 – 3.96)) were independent predictors of OS. Mean CRP was significantly different at baseline, 8 weeks and PD (64.9, 42.3 and 85.7 mg/L respectively, p < 0.001). Mean N0 count at baseline was 5.3 x109/L and was significantly higher 6.3x 109/L at PD (p < 0.001). Mean Hb at baseline, 8 weeks and PD was 11.5, 13.0 and 12.9g/L respectively (P < 0.001). A rise in CRP or N0 at 8 weeks was predictive of poor outcome ((HR 1.62 (1.10-2.56) and (HR 1.77 (1.19-2.61) respectively). A fall in Hb was predictive of poor outcome at 8 weeks (HR 1.75 (1.18-2.60)) and PD (HR 1.80 (1.20-2.76)). Conclusions: Dynamic changes occur in prognostic markers in patients receiving VEGF-targeted therapy in ccRCC and may predict OS.
Clinical outcomes according to ethnicity in patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT).
Authors: Bosse Dominick , Xie Wanling , Wells Connor , Lalani Aly-Khan A. , Donskov Frede , Bent Alisha , Sim Hao-Wen , Beuselinck Benoit , Bamias Aristotelis , Porta Camillo , Vaishampayan Ulka N. , Pal Sumanta K. , Agarwal Neeraj , Srinivas Sandy , Rini Brian I. , Alva Ajjai Shivaram , Wood Lori , Kapoor Anil , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: September 2018

e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline characteristics and treatment outcomes in African-Americans (AA) and Hispanic patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Caucasians, AA and Hispanics with mRCC treated with 1stline VEGF-TT were identified from the IMDC. We created 2 matched cohorts: 1) AA vs. Caucasians and 2) Hispanics vs. Caucasians, both matched for age (<50; 50-59; 60-69; <70-year-old), gender, years of treatment (2003-07; 2008-12; 2013-16) and geography (Canada, USA, Europe). Weighted Cox and logistic regressions were used to compare OS, time-to-treatment failure (TTF) and best response, adjusted for nephrectomy status, IMDC risk groups, number of metastatic sites (1 v. >1) and histology (clear-cell vs. else). Results: 73 AA and 71 Hispanics met eligibility criteria and were matched with 1236 and 901 eligible Caucasians, respectively. AA had more non-clear cell histology (26% v. 11%), time from diagnosis to therapy<1 year (67% v. 55%) and anemia (75% v. 54%) vs. Caucasians. Differences were not significant for Hispanics. Clinical outcomes are presented in Table. Conclusions: Adjusted for clinical prognostic factors, Hispanics with mRCC have statistically shorter TTF and survival than Caucasians. AA had a trend toward shorter TTF (not significant) but similar survival than Caucasians. Underlying genetic/biological differences, along with potential cultural variations, may impact survival in Hispanic mRCC patients. [Table: see text]
Efficacy and safety of sunitinib and everolimus as front-line treatment for nonclear cell RCC: A pooled-analysis from randomized trials.
Authors: Messina Carlo , Messina Marco 
Published: September 2018

e16069 Background: Non-clear Renal cell carcinoma (non-ccRCC) accounts for about 25% of all RCC and generally is responsible for a poorer outcome in metastatic setting. Optimal treatment for patients with metastatic non-ccRCC has not been established yet; therefore Sunitinib and Everolimus still represent two feasible options as frontline therapy, given the results reported from single-arm trials and expanded access studies. Hence, we provided a pooled analysis from prospective randomized trials to evaluate the benefit and risks of these therapies for patients with metastatic-non-ccRCC. Methods: A systematic search of literature was carried out using Medline, Embase, ESMO and ASCO library with no data restriction up to December 2016, to identify relevant studies on this topic. Eligible studies had to fulfill the following criteria: randomized prospective trial comparing the efficacy of Sunitninb and Everolimus as first line therapy in patients with m-non-ccRCC. Studies excluded: non-randomized prospective trials, subgroup analysis data deriving from randomized prospective trials carried out on metastatic ccRCC population. No language restriction was applied. Data were pooled using RevMan 5.3 software. Results: The literature search identified 29 potential titles and abstracts of whom only 2, recruiting a total of 176 metastatic-non ccRCC patients (Sunitinib: 84, Everolimus: 92), fulfilled our eligible criteria and were included in the pooled analysis. A trend towards better outcome in terms of PFS and OS was reported among patients with non-cc RCC enrolled in Sunitinib arm. Sunitinib vs Everolimus: PFS [HR]:0,83 [0,38-1,78]; OS [HR]: 0,67 [0,37-1,21]. Moreover Sunitinib was associated with more Grade 3-4 adverse events HR: 3.06 [1,60-5,84]. Conclusions: This pooled analysis reported a trend towards favoring Sunitinib versus Everolimus for the first line treatment of patients with metastatic non-ccRCC, although statistical significance was not reached. Sutent was associated with more Grade 3-4 toxicieties. Further prospective randomized phase III trials are required to clarify the better therapeutic option for this subset of patients.