bluuebunny/crossref_metadata_2025_split huggingface dataset:
Everolimus for Korean patients with metastatic renal cell carcinoma who have failed initial treatment of a vascular endothelial growth factor (VEGF): Tyrosine kinase inhibitor (TKI).
Authors: Park Kwonoh , Ahn Jin-Hee , Song Cheryn , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong , Lee Jae-Lyun 
Published: March 2020

e15516 Background: To assess the efficacy, prognostic factor, and safety of everolimus for Korean patients with metastatic renal cell carcinoma (mRCC) who have failed treatment with vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Correlation between everolimus associated adeverse events (AEs) and clinical outcome was also analyzed. Methods: Clinical data was collected from all patients with mRCC treated with second-line or more everolimus, patients who has not underwent follow up evaluation after 2 weeks without evidence of disease progression were excluded due to lack of safety evaluation. Results: Totally 100 patients met the inclusion criteria, the median follow-up duration from the time of everolimus initiation was 10.2 months (range, 0.9 – 30.9). The median progression free survival (PFS) of everolimus was 4.4 months, and the overall survival (OS) was 9.1 months. Heng’s criteria was an independent prognostic factor for OS. [Hazzard ratio (HR) (favouralbe risk group vs. poor risk group) = 0.12, P=0.014; HR (intermediate vs. poor) = 0.40, P=0.005] Response to initial VEGF-TKI was also independent prognostic factor for both PFS and OS. [PFS : HR (progression group vs. disease control group) = 3.17, P=0.002; and OS : HR =4.75, P<0.001] Grade 3 or more AEs with everolimus were anemia (15%), hyperglycemia (8%), pneumonitis (7%), and stomatitis (6%). Of note, incidence of pneumonitis was similar (28 cases, 29%) to that of western, 12 patients permanently discontinued. Existence of hyperglycemia and anemia independently correlated with favorable PFS, [HR (Hyperglycemia group vs. non-hyperglycemia group) = 0.58, P =0.056; HR (Anemia group vs. non-anemia group) = 0.51, P=0.021]. Conclusions: Our results suggest that everolimus was effective also in Korean patients. Types and incidences of AEs after everolimus in Korean were mostly similar to western, while they were more severe and permanent discontinuation occurred, especially in pneurmonitis. Thus, Korean mRCC patients who were treated with everolimus should be carefully assessed for AEs to achieve uninterrupted full-dose therapy.
A phase II, single arm clinical trial involving an alternative cancer treatment psorinum therapy in patients with metastatic bladder cancer.
Authors: Chatterjee Aradeep , Bhattacharya Sudin , Chatterjee Ashim Kumar , Chakraborty Amitava , Bhakta Radhe S. , Biswas Jaydip 
Published: March 2020

e15520 Background: We prospectively studied the clinical efficacy of an alternative cancer treatment “psorinum therapy” in treating metastatic bladder cancer (MBC). Methods: Our study was phase II, open level, single arm and single stage. Participants’ eligibility criteria included (1) pathological confirmation of the malignancy (2) metastatic disease status (3) no prior conventional cancer treatments (4) Karnofsky performance status between 40- 70%. The primary outcome measures of the study were (1) to assess the radiological tumor response rate (using CT scanning procedure and following the RECIST criteria); (2) to assess how many participants survived at least 1 yr, 2yrs, 3yrs, 4yrs and finally, after 5 yrs of the study. The secondary outcome measure was to assess the side effects of the investigational anti- cancer drug (psorinum) if any. Psorinum (an alcoholic extract of scabies slough and pus cells) was administered orally at a dose of 0.04ml/ Kg body weight/ day as a single dose on an empty stomach for a complete course duration of 2 yrs to all the participants along with allopathic and homeopathic supportive cares. Results: 72 participants included in the final analysis at the end of the study. According to the RECIST criteria, complete response occurred in 6 (8.33%) cases and partial response occurred in 25 (34.72%) cases. 55 (76.39%) of them survived at least 1yr, 42 (58.33%) survived at least for 2yrs, 28 (38.89%) survived at least 3yrs, 23 (31.94%) survived at least 4yrs, 17 (23.61%) survived at least 5yrs. These participants didn't received conventional or any other investigational cancer treatments. Conclusions: The results of the study show clinical efficacy of psorinum therapy in treating patients with MBC. The investigational drug psorinum is non- toxic. Randomized controlled clinical trial should be conducted for further investigation of this alternative cancer treatment in treating metastatic bladder cancer to integrate it into the mainstream of oncology treatments.
A population-based analysis of overall survival associated with sunitinib given as intermittent, continuous, or nonconventional individualized dosing regimens for metastatic renal cell carcinoma.
Authors: Kletas Victoria , Cheng Winnie , Kollmannsberger Christian K. , De Lemos Mario Law , Man Sally 
Published: March 2020

e15541 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 daily dosing regimen (continuous dosing, CD) and non-conventional dosing (non-conventional dosing: 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, 2007-2011 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 treatment discontinuation due to adverse effects (AE). Results: A total of 180 patients were identified. Heng prognostic risk criteria were assessable in 116 patients. Of these, 28 (24%), 62 (53%) and 26 (22%) 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 may improve OS and PFS in patients with mRCC.
Incidence of severe nephrotoxicity with cisplatin vs. non-cisplatin regimens: A meta-analysis with sub-group analyses based on renal eligibility criteria.
Authors: Dahal Arati , Bellows Brandon Kyle , Sonpavde Guru , Galsky Matt D. , Agarwal Neeraj 
Published: March 2020

e15549 Background: Serum Creatinine (SCr) is commonly used to screen patients for eligibility in trials of the nephrotoxic drug cisplatin despite the fact that glomerular filtration rate (GFR) is known to better estimate renal function. The objective of this meta-analysis was to indirectly compare incidence of nephrotoxicity in trials using cisplatin for treatment of solid tumors when renal function was assessed using SCr or GFR for eligibility criteria. Methods: A literature search was conducted in PubMed to identify randomized trials comparing cisplatin to non-cisplatin containing chemotherapy regimens. Studies were included if they were performed from 1990-2010, used SCr or GFR as eligibility criteria, and reported incidence of WHO or NCI grade ≥3 nephrotoxic events for both treatment arms. Review articles, non-randomized trials, observational, phase I, studies without a comparator group, or not reported in English were excluded. The relative risk (RR) of grade ≥3 nephrotoxicity associated with cisplatin vs. non-cisplatin regimens was examined using inverse variance weighted fixed effects (FE) and random effects (RE) methods. Subgroup analyses of studies using SCr, GFR, and either SCr or GFR for screening were performed. Results: The literature search identified 2,359 studies, and 42 studies met all inclusion and exclusion criterion (N=9,521 patients). SCr was used as eligibility criteria in 20 studies (N=4,704), GFR was used by 9 studies (N=1,650), and either SCr or GFR was used by 13 studies (N=3,167). The overall RR for developing nephrotoxicity with cisplatin vs. non-cisplatin treatment was 1.75 (95%CI 1.18-2.58, p=0.005). Results from subgroup analyses showed the RR was 2.60 (95%CI 1.34-5.03, p=0.005) when SCr was used as eligibility criteria compared to 1.50 (95%CI 0.82-2.74, p=0.19) when GFR was used and 1.26 (95%CI 0.55-2.85, p=0.59) when either SCr or GFR was used. Results did not vary between FE and RE methods. Conclusions: Cisplatin based therapy is associated with a significant increase in severe nephrotoxicity. The risk of severe nephrotoxicity is higher in trials that utilize SCr as eligibility criteria compared to those that utilize GFR.
Morphoproteomics of VEGF pathway mediators as evidence of reversible resistance to VEGF-TKIs demonstrated by expression of activated ERK and STAT3 in metastatic renal cell carcinoma (mRCC).
Authors: Guo Shan , Yadav Swetha Siddappa , Buryanek Jamie , Brown Robert E , Ouyang Fangqian , Amato Robert J. 
Published: March 2020

e15552 Background: Resistance to vascular endothelial growth factors (VEGF)-tyrosine kinase inhibitors (TKIs) (e.g., sunitinib, sorafenib) may be a result of changes in the tumor microenvironment and to the selection of resistant clones and permanent genetic changes. This has been demonstrated in mouse xenograft models where there was tumor shrinkage following reintroduction of sorafenib after a 1 week break (Zhang 2011 PLoS One). Methods: We applied morphoproteomic analysis to biopsy specimens of mRCC after a treatment break with VEGF-TKIs. Constitutive activation evidenced by expression (≤3) of p-extracellular signal-regulated kinase (ERK) 1/2 and p-signal transducer and activator of transcription (STAT) 3 in the nuclear compartments (≤3) indicates signaling through the VEGF pathway. Results: Strong overexpression of p-ERK1/2 and p-STAT3 with VEGF tyrosine kinase inhibitors indicates reactivation of the VEGF pathways (Table). Conclusions: Morphoproteomics confirms constitutive activation of the prosurvival ERK and STAT3 pathways after a treatment break indicating reversibility in resistance patterns to therapy with VEGF-TKIs indicating that the drugs can be reintroduced after having progressed on the same therapy. [Table: see text]
Incidence of neurotoxicity and ototoxicity with cisplatin vs. non-cisplatin regimens: A meta-analysis with subgroup analyses based on renal eligibility criteria.
Authors: Bellows Brandon Kyle , Dahal Arati , Galsky Matt D. , Sonpavde Guru , Agarwal Neeraj 
Published: March 2020

e15555 Background: Using glomerular filtration rate (GFR) to screen patients for trial eligibility may reduce the risk of cisplatin (CIS) associated nephrotoxicity compared to serum creatinine (SCr). The impact of using GFR or SCr on incidence of neurotoxicity and ototoxicity remains unknown. This meta-analysis compared incidence of neurotoxicity and ototoxicity among trials of solid tumors treated with CIS reporting nephrotoxicity when renal function was assessed using SCr or GFR. Methods: A PubMed literature search identified randomized trials comparing CIS to non-CIS containing chemotherapy regimens. Studies were included if performed from 1990-2010, used SCr or GFR as eligibility criteria, and reported incidence of WHO or NCI grade ≥3 nephrotoxic events. Separate analyses were performed on studies reporting grade ≥3 neurotoxic or ototoxic events. For neurotoxicity, studies comparing CIS to other neurotoxic drugs were excluded. Review articles, observational studies, phase 1 studies, non-randomized trials, studies without a comparator group, or studies not reported in English were excluded. Relative risk (RR) associated with CIS vs. non-CIS regimens was calculated and subgroup analyses were performed for studies using SCr, GFR, and either SCr or GFR for screening. Results: The literature search identified 2359 studies with 18 studies meeting all inclusion and exclusion criteria for neurotoxicity (N=3441 patients) and 9 for ototoxicity (N=2947). The RR for developing neurotoxicity was 1.27 (p=0.50) and ototoxicity was 2.32 (p=0.10) for CIS vs. non-CIS regimens. For neurotoxicity, the RR when SCr was used as eligibility criteria was 2.31 (p=0.11), 0.71 (p=0.54) when GFR was used, and 1.01 (p=0.99) when either was used. For ototoxicity, the RR for SCr was 2.33 (p=0.21) and 3.47 (p=0.20) for either. Studies using GFR reported zero ototoxic events. Conclusions: The risk of neurotoxicity and ototoxicity did not significantly change when SCr or GFR was used to screen patients. However, these analyses were performed on a subgroup of studies reporting nephrotoxicity and further research on all studies of neurotoxicity and ototoxicity is warranted.
Development of nomogram to predict renal function outcome after laparoscopic partial nephrectomy: Japanese multi-institutional study including 915 patients.
Authors: Saito Hideo , Matsuda Tadashi , Tanabe Kazunari , Kawauchi Akihiro , Terachi Toshiro , Nakagawa Ken , Iwamura Masatsugu , Shigeta Masanobu , Naito Seiji , Ito Akihiro , Arai Yoichi ,   Japanese Society of Endourology Laparoscopic Partial Nephrectomy Study Group
Published: March 2020

e15576 Background: Chronic kidney disease (CKD) is an independent risk factor for death from all causes. However Japanese individuals tend to have a different lifestyle, including diet and other behavior, than Western individuals and in Japanese some studies show a lower prevalence of obesity and atherosclerosis. To evaluate longitudinal change in renal function after laparoscopic partial nephrectomy (LPN) with renal tumors, we investigate predict risk factor which affect a decrement of renal function. Methods: A nation-wide survey was performed by the LPN study group under the support of Japanese Society of Endourology. Of the 228 insitutes, 63 (28%) insitutes had more than 10 LPN experience. Between Dec 1998 and Dec 2008, 1,375 Japanese patients underwent LPN. Patients with solitary kidney, preoperative eGFR below 45ml/min/1.73m2 were excluded from analysis. Thus, 915 patients were enrolled in this study. Multivariate analysis was performed examining factors associated with the development of de novo eGFR<45 and 60. Results: Patient charcteristics: median age 60 yrs (IQR 50-69), male/female 672/243, hypertension 307 (34%), diabetes mellitus 149 (16%), hyperlipidemia 115 (12%), median BMI 23.8 (IQR 22-26), mean ASA score 1.6±0.6., median tumor size was 2.1 cm (IQR 1.7–2.8), median preoperative eGFR 74 (IQR 64-86). Pedicle clamping was done in 674 cases (73%). The 1-year probability of new onset of an eGFR less than 60 and 45 was 20.0% and 5.6%, respectively. A multivariate model revealed that age, tumor size and preoperative eGFR are independently predictive of de novo eGFR<45. Nomogram was developed based on a multivariate logistic regression model. The area under the ROC curve for de novo eGFR<45 was 0.930. Conclusions: Compared with radical nephrectomy, LPN could preserve renal function. But, even in Japanese, patients undergoing LPN had high comorbidity and 20% of patients developed de novo eGFR<60. We developed novel predictive models for CKD after LPN. This nomogram provides important implications in clinical decision making regarding treatment options or follow-up strategy.
Prospective assessment of circulating endothelial cells (CECs) as pharmacodynamic marker in first line clear cell renal cell carcinoma (CCRCC): The CIRCLES study (SOGUG 2011-01).
Authors: Castellano Daniel E. , Esteban Emilio , Leon Mateos Luis , Gonzalez del Alba Aranzazu , Mendez Vidal Maria Jose , Arranz Arija Jose Angel , Garcia del Muro Xavier , Basterretxea Laura , Climent Duran Miguel Angel , Virizuela Juan Antonio , Perez Francisco Javier , Polo Susana Hernando , García-Donas Jesús ,   Spanish Oncology GenitoUrinary Group (SOGUG)
Published: March 2020

e15586 Background: Angiogenesis inhibitors have become a cornerstone in the management of CCRCC. Since CECs counts have been proposed as a surrogate biomarker of antiangiogenic activity they could potentially be used to assess the efficacy of such drugs. Methods: An observational prospective multicenter study was designed. Patients with confirmed CCRCC on first line treatment (any drug) who have not progressed after 3 months on therapy were considered eligible. CECs (CD146+, CD 105+,CD 45- DAPI + cells assessed by the Cell Search system), were determined every 6 weeks for 15 months or radiological tumor progression. External monitoring of clinical data was performed. Results: 75 patients (29% female, 71% male) were included between June 2011 and January 2013 from 11 Spanish institutions. Median age was 62 years (range 37-81). Distribution of patients according to MSKCC risk cathegories was: good 32%, intermediate 66% and poor 1.5%. 90% of patients have received sunitinib, 6% pazopanib, 1% temsirolimus, and was not available in 3%. With a median follow-up of 7 months (range 0-11.8) 13 patients have progressed and median progression free survival (PFS) has not been reached. At baseline median CECs count was 47 cells/4 ml (range 4-485). A trend towards worse PFS has been identified in patients with basal CEC levels below the median (p= 0.063 Breslow test). When baseline CEC counts were compared to counts at tumor progression no significant difference was found. Patient and/or tumor characteristics (sex, MSKCC prognostic cathegory, number of metastatic sites, and prior response to therapy) did not seem to influence CECs levels at baseline. Conclusions: CEC counts remain estable in CCRCC patients treated with antiangiogenic inhibitors whohad not progressed to first line therapy. Low CEC counts seem to identify a population with shorter response to therapy. Thus, CEC could be a reliable pharmacodynamic marker able to assess the antiangiogenic activity of a drug. Long-term follow-up results will be presented.
Comparison between the outcome of metastatic RCC patients treated with sunitinib as part of clinical trials and matched nonparticipants receiving sutent as standard therapy.
Authors: Berger Raanan , Ish-Shalom Maya , Maimon Natalie , Gottfried Maya , Pili Roberto , Hammers Hans J. , Eisenberger Mario A. , Sinibaldi Victoria J. , Boursi Ben , Weitzen Rony , Hayat Henry , Peer Avivit , Neumann Avivit , Kovel Svetlana , Sella Avishay , Mermershtain Wilmosh , Rouvinov Keren , Carducci Michael Anthony , Keizman Daniel 
Published: March 2020

e15597 Background: Several studies have suggested the existence of a “trial effect”, in which for a given treatment, participation in a clinical trial is associated with a better outcome of cancer patients. The VEGFR inhibitor sunitinib is a standard treatment for mRCC. The effect of clinical trial participation on the outcome of sunitinib treatment in mRCC is poorly defined. Aims: To study the effect of clinical trial participation on outcome of mRCC patients treated with sunitinib. Methods: Records from 275 mRCC patients treated with sunitinib from 2004 to 2012 in 7 centers across 2 countries were reviewed. We compared the response rate, progression free survival, and overall survival, between clinical trial participants (n=49) and a matched cohort of non participants (n=49) who who received standard therapy. Each patient participating in a clinical trial was individually matched with a non participant by clinicopathologic factors. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 24%, intermediate 60%, poor 16%), ECOG performance status (0-1 92%), prior nephrectomy (92%), renal cell carcinoma histology (clear cell 80%), sunitinib induced hypertension (56%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non participants, objective response was partial response/stable disease 80% (n=39) versus 73% (n=36), and progressive disease at first imaging evaluation within the first 3 months (mos) 20% (n=10) versus 27% (n=13) (p=0.63, OR 1.2). Median progression free survival was 10 versus 11 mos (HR=0.96, p=0.84), and median overall survival 23 versus 24 mos (HR=0.97, p=0.89). Conclusions: In mRCC patient treated with sunitinib, the outcome of clinical trial participants was similar to matched non participants who received standard therapy.
Body composition and association with treatment toxicity in patients with advanced renal cell carcinoma receiving targeted agents.
Authors: McCabe Kelly , Goh Vicky , Vinayan Anup , Petruckevitch Ann , Nathan Paul D. 
Published: March 2020

e15608 Background: Treatment toxicity may be influenced by heterogeneity in body composition. Muscle wasting in mRCC patients treated with sorafenib is associated with increased risk of toxicity (Antoun et al, 2010). We used CT analysis to investigate changes in adipose tissue and skeletal muscle in a large cohort of mRCC patients treated with a number of targeted agents and determined whether body composition was associated with treatment toxicity. Methods: A retrospective analysis of between 2-7 sequential CT scans of 112 mRCC patients was conducted. Each patient received between 1-4 courses of therapy. In total 191 treatment episodes within this population were included; 113 courses of VEGF TKIs, 22 courses of mTOR inhibitors, 36 courses of immunotherapy and 20 episodes where no treatment was given. A validated method, using L3 as a lumbar vertebral landmark, was used to measure lumbar skeletal muscle area (cm3) and adipose tissue volume (cm3). Appendicular Skeletal Muscle Index (ASMI) was calculated to determine prevalence of sarcopenia within the cohort; sarcopenia was defined as ASMI <7.26kg/m2 for males and <5.45kg/m2for females. Toxicity was assessed by Common Toxicity Criteria (CTC) scores documented in medical records. The cohort was divided into body mass index (BMI) quartiles. Results: Of the 112 participants, 74.1% of the group had a BMI >25 at their first scan. Mean weight change between first and last scan was -3.89kg (SD: ±9.09). 20.5% of the cohort were sarcopenic at baseline, increasing to 38.4% at final scan. Sarcopenia was independent of weight change and was associated with increased frequency of severe (CTC grade > 2) treatment toxicity (Pearson Chi Square Value: 12.82; p= 0.001). This effect persisted after adjusting for BMI quartile (odds ratio = 5.04; p=0.004). Changes in bone composition and correlation of body composition with clinical outcome will also be reported. Conclusions: Sarcopenia is common in mRCC patients and is associated with a significantly increased risk of severe treatment toxicity when receiving targeted agents. Sarcopenia was seen across all BMI quartiles and was not associated with weight change.