bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line mTOR inhibition in metastatic renal cell carcinoma (mRCC): An updated analysis from the International mRCC Database Consortium (IMDC).
Authors: Harshman Lauren Christine , Kroeger Nils , Rha Sun Young , Donskov Frede , Wood Lori , Tantravahi Srinivas Kiran , Vaishampayan Ulka N. , Rini Brian I. , Knox Jennifer J. , North Scott A. , MacKenzie Mary J. , Yuasa Takeshi , Srinivas Sandy , Pal Sumanta Kumar , Heng Daniel Yick Chin , Choueiri Toni K. 
Published: March 2020

e15518 Background: FDA approval of the mTOR inhibitors (mTORi) in mRCC was based on efficacy in poor risk patients (pts) in the first line setting for temsirolimus (T) and in VEGF inhibitor-refractory pts for everolimus (E). Little is known about T’s effectiveness in good and intermediate risk patients and E’s outcomes in the first line setting. Methods: We interrogated the IMDC for the outcomes of pts who received mTORi as first-line targeted therapy. Results: 127 pts received a first line mTORi; the majority received T (93 T, 34 E). The main reasons for T administration were poor risk (38%), non-clear cell histology (27%), and clinical trial (15%) whereas clinical trial (82%) and non-cc histology (6%) drove E use. Of the T and E pts, 58% and 32% were poor risk, respectively. Median age was 61 years and median KPS was 80%. 68% had prior nephrectomy (62% T vs. 82% E). Median progression-free survival (PFS) and overall survival (OS) are detailed below. In the 97 pts with response data, 5% and 53% for T and 8% and 58% for E achieved partial responses and stable disease, respectively. Progressive disease as best response occurred in 41% for T and 33% for E. Second line therapy was captured in 52 pts (41%), of whom 48 received VEGF inhibitors. Conclusions: Given the different populations in which they were administered, direct comparisons of the frontline efficacy of T vs. E cannot be made. The majority of T pts were poor risk, which their dismal PFS and OS reflect. The better outcomes in the E pts highlight that the majority were not poor risk and were healthy enough for clinical trials. While limited by small numbers, this data characterizes a real world experience of mTORi in the first line setting. [Table: see text]
Effect of cholesterol and triglyceride increases on time to progression in renal clear cell cancer patients treated with everolimus.
Authors: Pantano Francesco , Procopio Giuseppe , Silletta Marianna , Ortega Cinzia , Guida Francesco Maria , Venditti Olga , Prati Veronica , Imperatori Marco , Spoto Chiara , Verzoni Elena , Intagliata Salvatore , Vincenzi Bruno , Tonini Giuseppe , Rizzo Mimma , Santini Daniele 
Published: March 2020

e15528 Background: An increased level of cholesterolemia (C) and triglyceridemia (T) secondary to an impairment of lipidic metabolism is a well known side effect of all mTOR inhibitors including everolimus. In the phase III pivotal study of everolimus in mRCC patients, an increase of C and T was reported in 77 and 73 % of patients, respectively. Increase of C and T may represent a surrogate parameter related to mTOR pathway inhibition. On these basis, we assessed the value of C and T increase as a factor predicting the efficacy of everolimus in metastatic clear cell renal cancer. Methods: We retrospectively evaluated 46 patients ( 36 male: 10 female; mean age 61.4 years +/- 11.5) with metastatic clear cell renal cancer who received a second/third line with everolimus after at least one tyrosine-kinase inhibitor (TKI). From routinely performed blood test, we retrieved the value of total C and T the day before the first everolimus admnistration and during the entire duration of treatment. We also considered for each patient variations of glycemia, blood pressure and BMI before and after beginning of treatment, as parameters of metabolic syndrome. Time to progression (TTP) and survival were evaluated. Results: Among all the potential predictive factors considered, only the increase of cholesterol and triglyceride (> 20% compared to the baseline) within 2 months from the start of everolimus correlated with efficacy. Median TTP of the 19 patients with total early C upraising was statistically significant higher than in 27 patients without upraising (14.1 months vs 5.5 months, P= 0.009). Conversely, only a positive trend favoring patients with C upraising was recorded in median survival (24.9 months vs 16.0 months, P= 0.163 ). Both median TTP and median survival were found to be statistically significant higher in the 25 patients experiencing T upraising than in the 21 patients who did not (respectively, 13.0 months vs 4.9 months, P= 0.007 and 26.4 months vs 13.4 months, P= 0.018). Conclusions: Early C and T modifications predict everolimus efficacy in renal clear cell cancer.
Side-effect analysis of sunitinib (S) in patients treated with metastatic renal cell cancer (mRCC): Single center experience in the National Institute of Oncology, Hungary—Influence of dose reduction/modification and application schedule on the efficacy of S.
Authors: Nagyivanyi Krisztian , Biro Krisztina , Bodrogi Istvan , Gyergyay Fruzsina Eva , Kuronya Zsofia , Nemeth Hajnalka , Geczi Lajos 
Published: March 2020

e15530 Background: S, an active and relatively well tolerated treatment for mRCC, based on the result of a global phase III study. Methods: Retrospectively, 383 patient’s data with clear cell mRCC were collected, who were treated with S in our department between 01/nov/2005 and 31/dec/2012. S was used in 1st or 2 nd line setting. The first few dozen subjects were involved in a clinal trial after progression on first line INF therapy. In Hungary S became reimbursed by the public health insurence from 01/jan/2008 in second line, and from 01/feb/2010 in first line. All patients had definitely favorable or intermediate risk based on MSKCC risk group criteria. The starting dose of S was mostly 50 mg (schedule 4 weeks on followed by 2 weeks off). Results: We investigated the prevalence of necessity of dose reduction/modification or pretence to follow an out of ordinary application form. We registered the frequency and modality of the different types of side effects, we also studied the outcome of patients. Incidence of grade 3+4 side effects was nearly 60%. The most common side effects were fatigue (63%), mucositis/stomatitis (40,2%), hand-foot syndome (16,1%), diarrhea (34%), hypertension (34%), nausea (2%), anaemia (8,6%), leukopenia (4,6%), thrombopenia (20%) and hypothyreosis (20%). Objective response rate based on RECIST and progression-free survival (PFS) were also recorded. The efficacy of treatment was nearly similar to the global clinical trial results. CR was rare (4,2%), most of our patients had PR (31,1%) or SD (51,2%) as best response. In first line setting the results were even better (CR 10,5%, PR 44% and SD 57,5). Conclusions: S is effective and safe agent to treat patients with mRCC. Due to side effects, dose reduction / modification is often needed but rarely requires treatment discontinuation. The early detection and right management of side effects is crucial to maintain the patients on the treatment. Unfortunately the deviation from the standard care may bias the efficacy.
Everolimus treatment-associated interstitial lung disease (ILD) as a prognostic factor in Japanese patients with metastatic renal cell carcinoma.
Authors: Hongo Fumiya , Oishi Masakatsu , Ueda Takashi , Kimura Yasunori , Nakamura Terukazu , Naya Yoshio , Mikami Kazuya , Miki Tsuneharu 
Published: March 2020

e15531 Background: Interstitial lung disease (ILD) is one of the adverse events during treatment with everolimus for metastatic renal cell carcinoma (mRCC). Japanese study of everolimus treatment-associated ILD as a prognostic factor is rare. Methods: We retrospectively assessed the incidence and outcome of ILD in mRCC patients treated with everolimus. Between April 2010 and August 2012, 25 cases were treated with everolimus after the failure of one or two TKIs in our institute. All adverse events were graded in accordance with NCI CTCAE, version 3.0. Results: A total of 25 patients received treatment with everolimus and included 18 male and 7 female patients ranging in age from 21 to 84 years (median 62). According to MSKCC risk criteria, 6 cases were at favorable risk, 16 cases were at intermediate risk, and 3 cases were at poor risk. The median treatment term was 4 months (range 2-17 months). SD was reported in 19 cases and PD in 6 cases. Progression free survival was 3.5 months and overall survival was 12 months. ILD was found in 7 cases (28%). One was G1, five were G2, and one was G3. Corticosteroid therapy was initiated in 3 cases. In 5 of 7 ILD cases, everolimus was re-challenged. In our series, patients with ILD showed significantly better progression free survival than those without ILD (PFS was 8 months vs 3 months. Log-rank, P<0.001). There were no significant differences between the two groups in overall survival (12 months in patients with ILD vs 10 months in patients without ILD. Log-rank, NS). Conclusions: Everolimus appears to have been effective and well-tolerated in our institute. Re-challenge with everolimus was feasible after improving everolimus-induced ILD in cases of grade 1-2. To confirm these findings, the efficacy and AE profile of everolimus in Japanese patients should be investigated.
Safety and efficacy of axitinib in pretreated patients with metastatic renal cell carcinoma: A single center experience of the Medical University of Vienna, Austria.
Authors: Vogl Ursula Maria , Ponhold Lothar , Locker Gottfried J , Zielinski Christoph , Klingler Christoph , Kramer Gero , Schmidinger Manuela 
Published: March 2020

e15535 Background: Axitinib is a highly selective inhibitor of VEGFR-1, 2 and 3 and has recently been approved for second-line treatment of metastatic renal cell cancer (mRCC). We present data of 43 patients treated with axitinib in second-line and beyond. Methods: Medical records of all patients who were treated with axitinib between July 2009 and December 2012 were retrospectively reviewed. Axitinib was prescribed at a dose of 5 mg bid and escalated to 7 or 10 mg bid in the absence of hypertension and other dose-limiting toxicities. Objective response rate (ORR) was assessed by RECIST. Progression free survival (PFS) and overall survival (OS) were calculated from the first day of axitinib until progression and/or death, respectively. Results: Fourty-three patients with a median age of 65 years (range: 17-84) are currently evaluable for analysis. The majority of patients (58.1%) had an ECOG Performance status of 0 and were classified MSKC- intermediate risk (62.8%). All patients had undergone surgery for the primary tumor and 53.5% had three or more metastatic sites. Fifty-five percent of the patients received axitinib in third or fourth-line (14% and 41.9%, respectively). Prior therapies included sunitinib (86%), everolimus (35%) and pazopanib (35%) and 62.8% had progressed on sunitinib before axitinib was initiated. Objective remission and disease stabilization were observed in 14.3% and 40% of the entire population. The median PFS and OS were 6.8 months (95% CI: 5.5 – 8.0) and 17.2 months (95% CI: 10.8 – 23.6), respectively. Dose escalation to 7 or 10 mg bid was feasible in 40% of the patients. Fatigue (76.7%), hypertension (65.1%) and hypothyroidism (53.5%) were among the most commonly observed all grade toxicities. Conclusions: Axitinib showed considerable efficacy in both second-line and beyond second-line patients. Generous dose escalation based on a “treat to hypertension”-concept may have led to a longer PFS than previously reported from a purely VEGFR-TKI-refractory patient population.
The predictive value of hENT 1 molecule for gemcitabine treatment in bladder cancer.
Authors: Sener Dede Didem , Kilicaslan Aydan , Akinci Muhammed Bulent , Demirci Umut , Tahtaci Gozde , Yalcin Bulent 
Published: March 2020

e15540 Background: Human equilibrative nucleoside transporter 1 (hENT1) is the nucleoside transporter protein which plays the main role for transportation of gemcitabine into the cells. We aim to assess the predictive value of the hENT 1 molecule in bladder cancer patients treated with gemcitabine based chemoterapy. Methods: Clinically and histologically documented stage III and stage IV invazive bladder cancer patients were included in the study. The patients were assessed retrospectively. All patients were received gemsitabine-platine based chemotherapy as the first line treatment. Spesific hENT1 antibody staining was performed on the chemo-naive bladder tumor specimens immunuhistochemically. Vascular endotel and lymphocytes served as an external positive control for hENT 1 immunuhistochemistry. Staining intensity was graded as 0,absent; 1+, less intens than control tissue, 2, equally positive as control tissue; 3, more intense than control tissue. Tumor spesimens with having 3+ intensity staining in >50% of the tumor cells were accepted as showing high expression of hENT 1. Results: Fifty one patients were included in the study. The median age was 67 (range 41-85). Ninety two percent(n=52) of patients were male. Twenty six (46.4%) and 25 (44.6%) patients were stage III and stage IV disease at the beginning of the therapy, respectively. Thirty four (60.7%) patients were in neoadjuvant treatment group and 17 (30.4%) patients were in metastatic group. Tumor grades could be assessed in 33 patients; 2 (11.4%) were low grade and 31 (88%) were high grade. The median folllow up period was 13 (range 1-58) months. In neoadjuvant group 5 (14%) patients have low hENT 1 level and 21 (60%) patients have high hENT 1 level. In metastatic group 1 (5%) patients have low hENT1 level and 13 (95%) patients have high hENT 1 level. We found no statistically significant difference between hENT 1 low and hENT 1 high groups in terms of response to therapy in metastatic and neoadjuvant groups (p=0.426 and p=0.684 respectively). Conclusions: More stuides are needed to demonstrate the real role of hENT 1 molecule in terms of response to gemsitabine treatment.
Clinical prognostic factors associated with outcome in renal cell cancer (RCC) patients with prior tyrosine kinase inhibitors or immunotherapy treated with everolimus.
Authors: Amato Robert J. , Flaherty Amber Lea , Zhang Yufeng , Stepankiw Mika 
Published: March 2020

e15544 Background: Everolimus was approved for treating RCC patients who failed sunitinib or sorafenib by the Food and Drug Administration in 2009. We sought to develop a predictive clinical model predicting benefit for patients treated with everolimus as 2nd- or 3rd-line therapy for metastatic RCC. Methods: The study included 66 patients with RCC who failed immunotherapy or tyrosine kinase inhibitors to identify risk factors for progression-free survival (PFS) and overall survival (OS). Forty-one patients were updated with outcomes from the original phase II study (Amato 2009 Cancer) and an additional 25 patients were added from the expansion study. Kaplan-Meier method was used to calculate PFS and OS. Univariate and multivariate analyses were constructed using COX Proportional Hazard model and step-wise procedure. The model was validated by measuring the overall concordance index using the rms R package. Results: For the entire population, median PFS was 5.9 months (range, 0.4-34.5), and median OS was 16.1 months (range, 1.3-39.5). The univariate analysis revealed 5 factors associated with PFS and 9 factors associated with OS. From the multivariate analysis, 3 variables were kept in the final PFS model (LDH>203, no lung metastases, lymphocytes <25). Patients were assigned to 1 of 2 risk groups: ≤1 factor (favorable risk, median PFS 9.7 months) or ≥2 factors (poor risk, median PFS 2.8 months). Four variables were kept in the final OS model (lymphocytes <25, LDH >203, presence of bone metastasis, platelets ≥300). Patients were assigned to 1 of 3 groups: ≤1 factor (favorable risk, median OS 29.6 months), 2 factors (intermediate risk, median OS 14.3 months), or ≥3 factors (poor risk, median OS 7.2 months). Conclusions: A prognostic model was developed composed of 3 readily available clinical parameters for PFS and 4 clinical parameters for OS to help stratify patients into favorable, intermediate, and poor prognosis groups for the treatment of everolimus in clear cell RCC patients. These risk groups can be used by physicians to identify patients most likely to respond to everolimus. Results of the analysis will be presented.
Clinical prognostic factors associated with outcome in renal cell cancer (RCC) patients treated with modified vaccinia ankara plus tumor-associated antigen 5T4 (MVA-5T4).
Authors: Pandey Prasamsa , Xiong Youxin , Zhang Yufeng , Stepankiw Mika , Amato Robert J. 
Published: March 2020

e15545 Background: Development of MVA-5T4 as an immunotherapeutic vaccine led to studies demonstrating it is safe and highly immunogenic as a monotherapy or combination (Amato 2008 Clin Cancer Res, Amato 2008 J Immunother, Amato 2009 J Immunother). Antitumor activity has been minimal. We examined identifiable clinical factors to develop a prognostic model to select patients for vaccine immunotherapy. Methods: Clinical data from 3 phase II studies were received for a total of 50 patients treated with MVA-5T4 alone, MVA-5T4 plus interferon-α or MVA-5T4 plus interleukin-2. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analyses were constructed using COX Proportional Hazard model and step-wise procedure. The model was validated by measuring the overall concordance index. Results: For the entire population, median PFS was 3.6 months (range 0.9-42.8 months), and median OS was 12.4 months (range 1.0-45.6 months). Univariate analysis revealed 10 clinical factors associated with PFS and 9 clinical factors associated with OS. Multivariate analysis identified 5 factors associated with PFS benefit (ECOG status ≥1, lymphocytes <25, >2 metastatic sites, neutrophils ≥69, albumin <4) and 6 factors associated with OS benefit (ECOG status ≥1, >2 metastatic sites, neutrophils ≥69, platelets >300, prior treatment with tyrosine kinase inhibitors/immunotherapy, Furham grade of 3/4). The prognostic model was divided into 3 categories. Patients with 0-1 factors (favorable) had a median PFS of 9.4 months and OS of 26.2 months, patients with 2-3 factors (intermediate) had a median PFS of 3.0 months and OS of 9.1 months, and patients with 4+ factors (poor) had a median PFS of 2.0 months and OS of 2.0 months. Conclusions: This analysis identified 7 available clinical factors that can classify patients with mRCC into 3 risk groups with various outcomes. Further validation of this model will identify which patients most likely to respond to MVA-5T4 as well as other vaccines. This will allow for the appropriate application of treatment to patients most likely to benefit.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of patients with brain metastases (BM) from renal cell cancer (RCC).
Authors: Naskhletashvili David , Gorbunova Vera , Bychkov Mark , Bekyashev Ali , Karahan Vladislav , Aloshin Vladimir , Michina Zoya , Medvedev Sergey , Prozorenko Evgeny , Markovich Alla 
Published: March 2020

e15546 Background: About 2–11% of all patients (pts) with RCC develop BM, leading to a poor prognosis and a median survival of <6 months after whole brain radiotherapy. The role of targeted therapy in the management of BM is controversial. This study was designed to evaluate EGFR TKIs in RCC pts with BM. Methods: eligible pts had confirmed RCC and BM (≥1 lesion of ≥10mm diameter) aged >18 years with ECOG performanse status (PS) of 0–2. From June 2009 to January 2013, 11 pts with RCC and BM were enrolled in this study. 10 pts (91%) had extracranial metastases. 6 pts received sunitinib (50mg/day, 4 weeks, every cycle), 4 pts received sorafenib (800 mg/day) and 1 patient received pazopanib (800 mg/day) until radiologically-verified progressive disease. The primary endpoints were objective response rate (ORR) - complete and partial response in the brain and in the extracranial lesions, progressive-free survival (PFS) and overall survival. Demographics were: median age - 59 years (range 44–74 years); male/female - 10/1; PS 1/2 - 7/4; previously treated/untreated - 10/1; number of BM: ≤3/>3 - 6/5. Previous treatment: nephrectomy – 10 pts (91%), cytokines – 6 pts (54,5%), targeted therapy (before BM) – 4 pts (36,4%). Local control of BM: previous neurosurgery – 2 pts (18,2%), radiosurgery – 4 pts (36,4%), previous neurosurgery + radiosurgery – 2 pts (18,2%). Results: ORR in the brain was 27,3% (3 partial responses). All partial responses in the brain achieved in patients who received targeted therapy and radiosurgery. Stable disease in the brain was 54,5% (6 pts). 1 patient with stable in the brain received targeted therapy and radiosurgery, 5 pts received targeted therapy. ORR in the extracranial lesions was 20% (2 partial responses). Stable disease in the extracranial lesions was 50% (5 pts). The median of PFS was 6 months. The median of overall survival was 10 months. Conclusions: surgery and radiotherapy, including radiosurgery, must be considered as optimal local treatment for pts with RCC and BM. Targeted drugs have demonstrated their ability to achive a clinical and X-ray verified objective effect (as stabilization in most cases) in treating of pts with disseminated RCC and BM.
Correlation of pathologic findings after brief neoadjuvant sorafenib (neoS) with results of dynamic-contrast enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in patients (pts) with locally advanced or metastatic clear cell renal cell carcinoma (RCC).
Authors: MacVicar Gary R. , Miller Frank , Rustogi Rahul , Chen Zong-Ming , Martone Brenda K. , Kuzel Timothy 
Published: March 2020

e15554 Background: Many pts receiving tyrosine kinase inhibitors for RCC manifest stable disease as their best response by RECIST criteria. We hypothesized that tumor necrosis by DCE and DW-MRI after brief treatment with neoS may correlate with pathologic findings. We investigated in a pilot study whether these MRI changes may serve as an imaging biomarker predictive of clinical outcome. Methods: Pts with locally advanced or metastatic clear cell RCC undergoing nephrectomy or metastastectomy were treated with neoS 400mg PO bid for 28 days prior to surgery. The feasibility and safety of neoS was determined. Tumor necrosis detected by DCE and DW MRI’s pre- and post-neoS were compared and correlated with survival and pathologic findings at surgery. RECIST/WHO criteria were also compared. Results: 9 pts were enrolled, and all underwent surgery after neoS, 4 weeks (n=7) or less for toxicity (n=2). Clear cell/sarcomatoid histology was noted in 8 pts, and papillary in 1. All pts had T3 or T4 disease. 7 had M1 disease. No surgical complications occurred. 7 pts (78%) experienced Grade 3 toxicities, including hypertension (n=1), pancreatitis (n=1), hand-foot syndrome (n=1), hyponatremia (n=2), and rash (n=2). No grade 4 or 5 toxicities were observed. 4 of 8 clear cell/sarcomatoid pts (50%) have died, 3 due to progressive disease and 1 of unrelated causes. DCE and DW MRI’s with direct surgical pathological correlation were available in 7 of these pts. The mean ADC DW MRI changes in the renal lesion of 4 longer term survivors (median survival = 43 months) was +.22 vs. –0.07 in the 3 short term survivors (median survival = 13 months). RECIST/WHO criteria did not correlate with response. Evaluation of lack of enhancement on DCE MRI and increase in ADC on DW MRI were seen and correlated with necrosis on pathologic specimens. Conclusions: Four weeks of neoS is associated with significant necrosis that correlates with DCE-MRI and DW-MRI. There may be a trend in survival with greater necrosis, suggesting a role for these imaging biomarkers to assess early benefits of therapy. Clinical trial information: NCT00727532.