bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is sarcopenia a useful prognostic indicator in patients with squamous cell carcinoma of the penis?
Authors: Christodoulidou Michelle , Burden Sorrel , Gibson Debra , Attipa Charalampos , Ramachandran Navin , Nigam Raj , Malone Peter , Mitra Anita , Lal Simon , Richards Toby , Muneer Asif 
Published: March 2017

426 Background: Sarcopenia is a decrease in skeletal muscle mass and is a quantifiable marker of frailty associated with poor oncological outcomes. Currently there are no studies using sarcopenia as a prognostic indicator for patients with penile cancer. This study investigated the association of sarcopenia with mortality and morbidity outcomes in penile cancer patients in a specialist centre. Methods: A retrospective case-controlled study was performed. Patient cohort comprised 50 patients with metastatic penile cancer ( > pN2 disease) and 50 patients with non-metastatic disease (N0) ; minimum follow-up period of 2 years. Sarcopenia was classified as a skeletal muscle index < 55cm2/m2 and was measured using software and CT imaging. Results: Sarcopenia was present in 31% of our cohort (n = 100). A univariate analysis showed a statistically significant association between the following parameters and patient mortality; sarcopenia (p = 0.005), metastatic disease (p = 0.001), tumour stage (p = 0.001), sarcomatoid squamous cell carcinoma (p = 0.009), CIS (p = 0.034), lymphovascular invasion (LVI) (p = 0.001) and perineural invasion (p = 0.002). Logistic regression analysis found an association between mortality and sarcopenia (p = 0.035) and metastatic disease (p = 0.000) and approached statistical significance with LVI (p = 0.061). Subdividing our cohort into metastatic and non-metastatic groups, showed that sarcopenia was associated with mortality in patients with metastatic disease but was not associated with post-operative complications or chemo-radiotherapy toxicity. Interestingly, sarcopenia was associated with post-operative infection in patients undergoing surgery for non-metastatic disease (p = 0.027). Additionally, for every day remaining in hospital after the 4th post-operative day, there was a 1.275 increase in the risk of death in patients with sarcopenia. Conclusions: Sarcopenia has a potential role as a novel prognostic indicator and could be used as a risk stratification tool in patients with metastatic penile cancer when deciding treatment options. By identifying this subgroup, additional nutritional support and a supervised exercise program can be implemented to improve the morbidity rate.
A phase II study of atezolizumab (atezo) with or without bevacizumab (bev) versus sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC) patients (pts).
Authors: McDermott David F. , Atkins Michael B. , Motzer Robert J. , Rini Brian I. , Escudier Bernard J. , Fong Lawrence , Joseph Richard Wayne , Pal Sumanta K. , Sznol Mario , Hainsworth John D. , Stadler Walter Michael , Hutson Thomas E. , Ravaud Alain , Bracarda Sergio , Suarez Cristina , Choueiri Toni K. , Choi YounJeong , Huseni Mahrukh A. , Fine Gregg Daniel , Powles Thomas 
Published: March 2017

431 Background: While targeting VEGF improves outcomes for mRCC pts, resistance invariably develops, often within the first year. Here, we describe the efficacy and safety of atezo (anti-PD-L1) with bev (anti-VEGF) and atezo monotherapy vs sun (TKI) in first-line mRCC. Methods: Treatment-naïve mRCC pts were enrolled in a hypothesis generating Ph II study (IMmotion150; NCT01984242) and randomized to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w, atezo alone or sun 50 mg PO QD 4 wk on/2 wk off. Crossover to atezo + bev after disease progression was allowed for pts receiving atezo or sun. PD-L1 expression was scored on tumor-infiltrating immune cells (IC, SP142 IHC assay). Coprimary endpoints were PFS (RECIST v1.1 by independent review [IRF]) in ITT pts and pts with PD-L1 expression on ≥ 1% of IC (PD-L1+). Results: Baseline characteristics were comparable across arms and between ITT and PD-L1+ pts. The majority of sun and atezo pts subsequently received atezo + bev. Median survival follow up was 20.7 mo. The PFS HR in ITT pts for atezo + bev vs sun was 1.00 and 1.19 for atezo vs sun. In PD-L1+ pts, the PFS HR for atezo + bev vs sun was 0.64 and 1.03 for atezo vs sun (table). Tx-related Gr 3-4 AEs were seen in 40%, 16% and 57% of pts in the atezo + bev, atezo and sun arms, respectively. AEs leading to death occurred in 3%, 2% and 2% of pts, respectively. Conclusion: Atezo + bev resulted in encouraging antitumor activity in the PD-L1+ subgroup of first-line RCC pts. Atezo + bev safety is consistent with the known profile of atezo and bev individually. The clinical benefit of atezo + bev vs sun will be evaluated in the ongoing Ph III study IMmotion151 (NCT02420821). Clinical trial information: NCT01984242. [Table: see text]
Comparative effectiveness of tumor response assessment methods: Standard-of-care versus computer-assisted response evaluation.
Authors: Allen Brian , Florez Edward , Sirous Reza , Lirette Seth T , Griswold Michael , Remer Erick M. , Wang Zhen J. , Bieszczad Jacob E , Cox Kelly L , Goenka Ajit H. , Howard-Claudio Candace M , Kang HyunSeon , Nandwana Sadhna B , Sanyal Rupan , Shinagare Atul B. , Henagen J. Clark , Storrs Judd , Davenport Matthew S. , Rini Brian I. , Smith Andrew Dennis 
Published: March 2017

432 Background: In clinical trials and clinical practice, tumor response assessment with computed tomography (CT) defines critical end points in patients with metastatic disease treated with systemic agents. Methods to reduce errors and improve efficiency in tumor response assessment could improve patient care. Methods: Eleven readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria using paired baseline and initial post-therapy CT studies from 20 randomly selected patients with metastatic renal cell carcinoma treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard-of-care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error-identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data/image archival. A cross-over design, patient randomization, and two-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. Results: The standard-of-care method was on average associated with one or more errors in 30.5% (6.1/20) of patients while CARE had a 0.0% (0.0/20) error rate (p<0.001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range 1-3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 vs. 13.1 minutes, p<0.001). Conclusions: Computer-assisted tumor response evaluation reduced errors and time of evaluation, indicating better overall effectiveness than manual tumor response evaluation methods that are the current standard-of-care.
Changes in tumor burden and IMDC class after active surveillance (AS) for metastatic renal cell carcinoma (mRCC).
Authors: Bimbatti Davide , Sava Teodoro , Massari Francesco , Ciccarese Chiara , Fantinel Emanuela , Dalla Volta Alberto , Artibani Walter , Tortora Giampaolo , Iacovelli Roberto 
Published: March 2017

435 Background: Targeted therapies (TT) improved survival in mRCC but treatment-related toxicities may worsen quality of life and lead to treatment discontinuation. AS is a feasible strategy in pts with indolent disease but effects on tumor burden (TB) and prognosis have not been investigated. Methods: In this retrospective study we included pts who received AS at our centre. The TB, defined as the number of sites of disease, was collected with the IMDC class, just before and after AS. The time on surveillance (ToS) was defined as the time from the start of AS to the beginning of therapy or last follow-up. The OSs were collected from the start of AS or TT. Results: 48 pts started AS from January 2007 to April 2016. After a median follow up of 37.3 months, 79.2% are still alive. At baseline the main sites of metastases were: lung (56%), nodes (25%), pancreas (14%), adrenal gland (8%), CNS (8%), and bone (6%). TB was one site in 65 %, two in 31%, and >2 sites in 4%. The IMDC prognostic class was favorable in 68,8%, intermediate in 25%, and poor in 6.3% of pts. After a median ToS of 16.7 months (95% CI 9.6-23.7), 34 patients (70.8%) started a TT, only 1/24 patient had progression as the best response. Significant difference in ToS were found where pts with good (19.9 mos) or intermediate (17.7 mos) class were compared to the poor group (5.2 months) (p<0.04). At the beginning of TT, the main sites of metastases were: lung (71%), nodes (44%), bone (15%), adrenal gland (15%), pancreas (15%), and CNS (9%). The TB was one site in 35%, two in 47%, and >2 sites in 18%; and 14 pts had new sites of disease. The IMDC class changed in four patients from good to intermediate. The median OSs was not reached from the start of surveillance and was 64.4 months from the start of TT. Conclusions: AS is an option for management of mRCC pts with good and intermediate prognosis. AS allows to delay the start of TT avoiding toxicity and worsening quality of life. Despite the fact pts in AS have increased TB and rarely a worsening of prognostic class, the survival remains longer and the effectiveness of subsequent therapy seems not to be affected.
Single-nucleotide polymorphisms (SNPs) associated with outcomes in patients with localized and metastatic renal cell carcinoma (RCC).
Authors: Garrigos Carmen , Espinosa Marta , Osman Ignacio , Ávila Rainiero , Medina Rafael , Melendez Ricardo , Salinas Ana , Perez Valderrama Begona , Duran Ignacio 
Published: March 2017

437 Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in patients (pts) with both localized and advanced RCC treated at Hospital Universitario Virgen del Rocío. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). 64 SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview, and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS), and response to treatment (RR). SPSS v16 was utilized for statistical analyses. Results: In pts with localized RCC, 6 SNPs in 3 genes involved in angiogenesis predicted for worse DFS (VEGFR2: rs10013228, rs2071559; PDGFRA: rs2228230) and shorter OS (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p<0.05). In the advanced setting, 7 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics determined inferior OS (IL8: rs2227543, NR1l2: rs3814055, NR1l3: rs2307424, PDGFA: rs9800958, PDGFRB: rs2302273) and worse RR (VEGFA: rs699947, rs3025010 p<0.01)). Additionally 3 SNPs in PDGFR-B and VEGF isoforms predicted for better RR (PDGFRB: rs17708574 (p=0.08), VEGFB: rs594942 (p=0.03), VEGFC: rs2016110 (p=0.07). Conclusions: Genetic analysis of RCC patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics seem to determine post-surgical outcomes and treatment response in our series. These results are promising. Validation of the results is ongoing.
Patients with metastatic renal cell carcinoma who have benefit from axitinib dose titration: Analysis from a randomized, double-blind, axitinib dose titration phase II study.
Authors: Tomita Yoshihiko , Uemura Hirotsugu , Oya Mototsugu , Shinohara Nobuo , Habuchi Tomonori , Fujii Yosuke , Kamei Yoichi , Umeyama Yoshiko , Bair A H. , Rini Brian I. 
Published: March 2017

438 Background: Axitinib is a potent, selective inhibitor of VEGF receptors. In a randomized, double-blind, phase II study in patients with metastatic renal cell carcinoma, median overall survival (OS) was 42.7 months who underwent axitinib titration versus (vs.) 30.4 months in placebo titration (hazard ratio [HR]: 0.785; 95% confidence interval: 0.485, 1.272). OS Kaplan-Meier curves for two arms appeared to cross over at approximately 24 months and thus we investigated baseline characteristics associated with OS benefit from axitinib titration. Methods: Patients received axitinib 5 mg twice daily (BID) for 28 days. Patients who met the dose titration criteria were randomized 1:1 to axitinib titration or placebo titration. Patients who did not meet the dose titration criteria continued axitinib 5 mg BID. Baseline characteristics were compared between patients with OS ≥ 24 and < 24 months who were randomized to axitinib titration and subsequently, multivariate analysis for baseline characteristics was conducted to investigate effect of interaction with axitinib titration. Results: Fifty-six patients underwent axitinib titration with 53 evaluable for this analysis. Thirty-three patients had an OS ≥ 24 months and had significantly fewer metastatic sites (≤2, ≥3: 52/48% vs. 10/90%), compared to the 20 patients with OS < 24 months. In addition, a lower percentage of patients with OS ≥ 24 months had lymph node metastasis (45 vs. 75%), liver metastasis (15 vs. 45%), duration from diagnosis to treatment <1 year (36 vs. 85%), and baseline hemoglobin (Hb) < LLN (lower limit of normal) (33 vs. 75%), compared to the patients with OS < 24 months. In multivariate analysis in total of 112 patients who were randomized to axitinib or placebo titration, duration from diagnosis and baseline Hb were significantly associated with favorable OS with axitinib titration (p<0.1). Conclusions: Duration from diagnosis and baseline Hb are associated with favorable OS with axitinib titration. Clinical trial information: NCT00835978.
Comparison of different prognostic scores versus physician’s subjective prognosis in patients with advanced/metastatic renal cell carcinoma treated with temsirolimus in regular clinical setting: An analysis of the STAR-TOR registry.
Authors: Boegemann Martin , Woike Michael , Gillhaus Johanna , Schrader Andres Jan 
Published: March 2017

441 Background: In treatment of metastatic renal cell carcinoma (mRCC) patients several prognostic scores are used: the MSKCC-, IMDC-, and for pts treated with Temsirolimus (TEMS) the Hudes-score. We assessed prognostic value of these scores in TEMS treated cohort and compared the results with physician’s prognosis. Methods: A German multicenter registry for pts with mRCC (NCT00700258) was established to evaluate the safety and efficacy of TEMS in clinical routine. We retrospectively analyzed the data to compare established prognostic scores with risk assessment by the treating physician and match them with survival outcomes. Results: From 02/2008-05/2015, 547 mRCC pts were treated with TEMS. Risk was calculated for 305 (MSKCC), 248 (IMDC), and 187 (Hudes) pts. Physician’s prognosis was documented for 530 pts. Multivariate survival analyses are shown in table below. Abbreviations: g (good), i (intermediate), p (poor), n-p (non-poor). Conclusions: Risk assessment by treating physician is as meaningful as objective prognostic scores. In this data set, IMDC and Hudes performed worse than the MSKCC score. Physician’s risk assessment independently discriminates better between good and intermediate risk. The MSKCC score performs better for discrimination between an intermediate and a poor prognosis. Thus, the physician seems to be able to identify a subset of patients with a good prognosis while the MSKCC score can identify pts which are falsely placed in poor risk group by the physician. [Table: see text]
Effect of benign and tumor parenchyma metabolomic profiles on compensatory renal growth in renal cell carcinoma surgical patients.
Authors: Rosenzweig Barak , Rubinstein Nimrod Daniel , Reznik Eduard , Zareba Piotr , Shingarev Roman , Juluru Krishna , Akin Oguz , Hsieh James , Jaimes Edgar A , Russo Paul , Susztak Katalin , Coleman Jonathan , Hakimi A. Ari 
Published: March 2017

446 Background: Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. Methods: Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model we identified metabolites whose abundances significantly associate with CRG. Results: We identified 13 metabolites in the benign (e.g. L-urobilin) and 163 metabolites in the malignant (e.g. 3-indoxyl-sulfate) tissues to significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with a significant positive association with CRG (e.g. p-cresol sulfate). At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, whereas in the tumor tissue significant enrichment of dipeptides (positive association) and benzoate, glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways were observed. The effect of metabolite abundances in the benign tissue on long term CRG provided further support for positive association of fatty-acid metabolism sub-pathway enrichment, where sphingolipid, monoacylglycerol, long chain fatty acids, and mid chain fatty acids were enriched for a negative association. Conclusions: These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth.
Cabozantinib (C) exposure-response (ER) modeling of safety endpoints in patients (pts) with renal cell carcinoma (RCC) in the phase III METEOR study.
Authors: Lacy Steven , Hutmacher Matthew M , Yang Bei , Motzer Robert J. , Escudier Bernard J. , Powles Thomas , Choueiri Toni K. , Nielsen Jace 
Published: March 2017

447 Background: ER models were previously developed to characterize the relationship between C exposure and efficacy endpoints in RCC pts in the phase III METEOR study (J Clin Oncol 34, 2016 [suppl; abstr 2565]). Higher C exposure correlated with decreased tumor size and improved progression-free survival and objective response rate. Model-based predictions showed that C would be effective at the 60 mg starting dose evaluated in METEOR as well as dose levels of 40 and 20 mg resulting from dose reduction. In the current study, ER models were developed to characterize the relationship between C exposure and safety endpoints in RCC pts. Methods: The ER analysis included 318 RCC pts who had received at least one C dose and had at least one measurable C concentration. Time-to-event Cox proportional hazard ER models were developed to characterize the relationship between various individual predicted C exposure measures and the likelihood of dose modification and 6 specific adverse events (AEs): fatigue/asthenia, palmar-plantar erythrodysesthesia (PPE), nausea/vomiting, diarrhea, hypertension, and stomatitis. Results: A statistically significant relationship was identified between individual predicted C clearance (CL/F) and the rate of dose modification (p <0.0001), with the risk of dose modification decreasing with increasing CL/F. An increase in average C concentration was associated with increased risk of fatigue/asthenia (Grade ≥3), PPE (Grade ≥1), hypertension (systolic blood pressure [BP] >160 mmHg or diastolic BP >100 mmHg), and diarrhea (Grade ≥3). The predicted hazard ratios for these AEs were 2.01, 2.21, 1.85, and 1.78, respectively, based on the predicted steady-stage average C concentration for a 60 mg dose relative to a 20 mg dose. Statistically significant ER relationships were not identified for nausea/vomiting (Grade ≥3) or stomatitis (Grade ≥3). Conclusions: Based on the ER analysis, higher C exposures resulting from lower C CL/F are predicted to increase the dose modification rate. Reduced C exposures resulting from dose reduction are predicted to decrease the risk of fatigue/asthenia, PPE, hypertension, and diarrhea while maintaining clinical benefit. Clinical trial information: NCT01865747.
IVOIRE: Results of a prospective multicentre cohort study in advanced renal carcinoma.
Authors: Voog Eric , Campillo-Gimenez Boris , El Kouri Claude , Priou Frank , Rolland Frederic , Laguerre Brigitte , Elhannani Chaza , Merrer Jacques , Joly Florence , Pfister Christian , Malhaire Jean-pierre , Delva Remy , Cojocarasu Oana , Cumin Isabelle , Ligeza-poisson Catherine , Schlurmann Friederike , Monpetit Erik , Deniel Lagadec Delphine , Marhuenda Fanny , Grude Francoise 
Published: March 2017

451 Background: Sequential targeted therapy is standard in patients (pts) with clear-cell renal carcinoma (CCRCC). Clinical Practice Guidelines exists only for first and second lines (ESMO recommendations). Exploratory recommendations for next treatments (ttt) have been proposed according to their MSKCSS risk. In 3rd line, pts without prior everolimus were proposed to receive it. Pts who have failed 2nd line ttt with everolimus were proposed to rechallenge Tyrosine Kinase Inhibitor only if they experimented a disease control ≤ 6 months in 1st line. For 4thline, TKI or everolimus were rechallenged according to the previously quoted criteria. Poor risk pts are not presented here. Methods: IVOIRE was a prospective multicentric study including pts treated according to these guidelines. Objectives were overall survival (OS) and for each line Best Objective Response (BOR - RECIST 1.1) and Disease Control Time (DCT: time from day 1 of ttt to the day before the next one). Results: 301 locally advanced/metastatic RCC pts have been included in 17 French centers between Sept 2011 and Sept 2014: 71% men; median age 66 years [35-90]; CCRCC: 89%; grade III-IV Führmann: 68%; tumor resection: 90%. Pts received between 2 and 8 ttt lines, including mainly TK and mTOR inhibitors, or rarely (< 5%) immunotherapies in 1st line (IFN, IL-2 and bévacizumab only). Median OS was 57 [51-70] months. Results are summarized in table. Important clinical benefit (L1: 79%; L2: 65%; L3: 59%; L4 : 38%; L5: 39%) and DCT could be observed until ttt line 5. A long DCT in 1st line was predictive of a best OS (p=0.001). Indeed, pts with short 1stline DCT (11 to 54 weeks) had a shorter median OS (32 months [23-61]] while pts with long DCT (>54 weeks) had a longer median OS: 79 months [65-100]. Conclusions: Our results confirm that clinical benefit remained important to beyond the first lines and that DCT in the first line was predictive of the global OS. Ttt sequence analysis and tolerance will be shown at the meeting. [Table: see text]