bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival benefit in bevacizumab-based therapy in sickle cell trait patients diagnosed with renal medullary carcinoma
Authors: Johnson E. D. , Tannir N. N. , Olejeme K. A. , Logothetis C. J. , Jonasch E. 
Published: August 2020

e16096 Background: Renal medullary carcinoma (RMC) is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, primarily sickle cell trait. This is a rare and highly aggressive tumor that is shown to be most resistant to chemotherapy. In an effort to evaluate treatment outcomes, we retrospectively examined those patients diagnosed with RMC who were treated with and without bevacizumab based regimens. Methods: We reviewed the genitourinary medical oncology database at M. D. Anderson Cancer Center for patient diagnosed between 1999–2008 with histology proven RMC. Vital statistics of birth and death dates were noted. In addition, detailed chemotherapy regimen as well as medical and radiological data were also obtained. Results: All patients had metastatic disease (stage IV) to at least one distant site at presentation. Distant sites included bone, liver or lungs. A sample of five black males 5/9 (53%) were treated with therapy that included a 2 or 3 drug combinations of Adriamycin, Taxol, Gemzar, cisplatin, or Gleevac. Median survival was 12.7 months (3.2–22.2) while median age was 31 year (28–59). Only 4/9 (47%) patients received bevacizumab based therapy in a 2 or 3 drug combinations with Gemzar, Xeloda, cisplatin, or Taxol. In this group, 50% were females, median age of 36 years (33–39) and median survival of 18.5 months (15.5–22.8). Conclusions: Sickle cell trait was confirmed for all in this group diagnosed with RMC. 8/9 of these patients were black and 1/9 South-Asian. The group that received bevacizumab based therapy had a median survival of 5.8 months longer. Future studies, including genetic studies on the tumor types are essential to determining the SNP profiles of renal cell carcinoma in black patients. Furthermore, a prospective multicenter trial should be developed to evaluate the efficacy of bevacizumab based regimens in renal medullary carcinoma in this population. No significant financial relationships to disclose.
Efficacy and safety of sorafenib in patients with advanced clear-cell renal cell carcinoma (RCC) with diabetes: Results from the phase III TARGET study
Authors: Oudard S. , Eisen T. , Szczylik C. , Siebels M. , Negrier S. , Chevreau C. , Cihon F. , Bukowski R. M. , Escudier B. 
Published: August 2020

e16099 Background: Results of the phase III TARGET trial, a randomized, double-blind, placebo-controlled study of sorafenib (SOR) treatment in pts with clear-cell RCC in whom 1 prior systemic therapy had failed, indicated that SOR is effective and safe for pts with advanced RCC, leading to the approval of SOR for the treatment of advanced RCC. Diabetes can be associated with increased morbidity during treatment in a variety of malignancies. Therefore, an exploratory subset analysis was performed to evaluate the efficacy and safety of SOR in pts enrolled in TARGET with or without diabetes at baseline. Methods: Pts (N=903) with advanced clear-cell RCC, ECOG PS 0–2, and low- or intermediate-risk MSKCC score were randomized 1:1 to SOR 400 mg BID or placebo (PBO). End points included OS, PFS, and safety. A planned independently-assessed formal analysis of PFS showed significant benefit for SOR over PBO; consequently, pts assigned to PBO were able to cross over to SOR. Results: Pt demographics were similar for all subsets. Pre- crossover data by subset are shown in the table . The incidence of drug-related adverse events (AEs) across subgroups was consistent with that for the overall population. In pts with vs without diabetes, treatment with SOR was not associated with increased hyperglycemia (1 pt/arm in the without diabetes subgroups only) or hypertension. Conclusions: The safety profile of SOR in pts with diabetes was comparable with that for the overall study population. SOR was well tolerated and AEs were manageable. Trends in improved PFS were observed for SOR regardless of baseline diabetes status; however, the small diabetic subset limits interpretation of a SOR OS benefit in this subpopulation. *Final PFS of overall study population based on independent review from Jan 2005; all other data from May 2005 database [Table: see text] [Table: see text]
Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer
Authors: Koie T. , Yamamoto H. , Okamoto A. , Hatakeyama S. , Momose A. , Iwabuchi I. , Yoneyama T. , Hashimoto Y. , Kamimura N. , Ohyama C. , Saijo Y. 
Published: August 2020

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.
Decreased toxicity schedule of suitinib in renal cell cancer: 2 weeks on/1 week off
Authors: Gyergyay F. , Nagyványi K. , Bodrogi I. 
Published: August 2020

e16113 Background: Sunitinib (SU) is an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET approved for treatment of metastatic renal cell cancer (mRCC). Pharmacokinetics and pharmacodynamics suggest that dose reduction might decrease the plasma concentration of SU and its major metabolite to an ineffective level. Methods: Pts with mRCC, measurable disease, ECOG PS 0–2 received SU 50 mg po daily 4 weeks on/2 weeks off. Results: Of 36 pts, median age 59.5 yrs (range 42–83), M/F (26:10), ECOG: 0 (21); 1 (9); 2 (6); prior nephrectomy (35),prior radiation therapy (28), prior cytokine therapy: IFNα (25), IL-2+IFNα (9) none (2); pts with 1 metastatic organ (24); 2 metastatic sites (7); ≥ 3 sites (5); Sites of metastases: Lung (27), Bone (11), Liver (3); MSCC risk factors: 0 (20), 1–2 (14); ≥3 (2). Objective response occurred: PR (13) 42%; CR (2) 5%; SD (9) 25%. Number of cycles (6 weeks cycles) given was: 162 (2–15).Main side effects were: fatigue 42% (Gr≥3: 17%), diarrhoea 42% (Gr≥3: 25%), nausea 31% (Gr≥3: 6%), stomatitis 10%, anorexia 10%, weight-loss 20% (Gr≥3: 11%), hand-foot syndrome 39% (Gr≥3: 17%), hypertension 28%, anemia 25%, neutropenia 8%, thrombopenia 11%, hypothyroidism 11%. Five cases of dose reduction and two cases of treatment discontinuation occurred due to toxicity. During the second part of the study if serious toxicity had been reported, instead of dose reduction, two weeks on and one week off schedule (50mg daily) had been offered to pts. 14 pts (79 cycles) were treated according to the schedule. Short term side effects decreased significantly: fatigue 28%, diarrhea 14%, nausea 14%, stomatitis 7%, anorexia 7%, weight-loss 7%, hand-foot syndrome 14%, hypertension 7%, anemia 14%, hypothyroidism 11%. Conclusions: Further prospective studies are needed to confirm the better tolerance of the SU, without decreasing the dose intensity of the treatment. No significant financial relationships to disclose.
Long-term use of sorafenib (SOR) in metastatic renal cell carcinoma (mRCC) previously treated with systemic therapy
Authors: Battaglia M. , Gernone A. 
Published: August 2020

e16123 Background: The recent development of new targeted agents for the treatment of advanced RCC has definitely changed the approach and the outcome of this disease. Among them, SOR, has proved to be highly active in the treatment of mRCC. The aim of this study was to assess the activity and the safety of SOR in pts with mRCC relapsed after prior systemic therapy. Methods: Between 2/2007 and 10/2008, 22 pts with mRCC relapsed after 1–2 prior lines of chemotherapy (gemcitabine, vinorelbine, 5-FU) have been treated with SOR orally administered at the dose of 400mg b.i.d. continuous dosing. They were18 males and 4 females, with a median age 67 years, an ECOG PS 0–2, and the majority (96%) had undergone prior nephrectomy. Patients were assessed for activity every three months (mos.) by CT. The primary endpoints were response rate (RR) evaluated by RECIST criteria and time to progression (TTP). Results: To date, 20 pts are evaluable for response: of them, 13 (59%) achieved a partial response (PR) after 3 mos. of therapy whose median duration was 13 mos. (range, 7–18), while 7 (31%) remained with stable disease (SD) with a median length of 14 mos. (range, 5–17). No complete responses have been observed. Among those who progressed (2 pts), the median time to disease progression was 7 mos. At a median length of time of 15 mos., 18 pts. are continuing the therapy with SOR and in all of them the benefit achieved remained unchanged. Two pts discontinued the treatment because of the onset of side effects, while in 4 pts dose reductions were required. Grade 3/4 toxicities were: hypertension in 3 pts (13%), hand-foot skin reactions in 5 (22%), rash/desquamation in 4 (18%), diarrhoea in 2 (9%), fatigue in 6 (27%), bleeding in 2 (9%). Conclusions: These data confirm other experiences showing the efficacy of SOR in previously treated patients with mRCC. However, notwithstanding the rather small sample size of pts., the overall clinical benefit rate (PR+SD) turned out particularly high (> 90%): chiefly, the evidence of a long lasting disease control both for patients achieving partial response and for those with stable disease makes SOR a very useful treatment for patients with mRCC. No significant financial relationships to disclose.
Use of an inhibitor of differentiation-1 (Id1) expression (exp) to discriminate good prognosis (GP) from poor prognosis (PP) prostate cancer (PCa)
Authors: Calvo A. , Ponz-Sarvisé M. , Rosell D. , Redrado M. , Nguewa P. A. , García-Foncillas J. , Abella L. , Panizo A. , Gil- Bazo I. 
Published: August 2020

e16128 Background: In the PSA era a significant proportion of PCa patients (pts) at onset have potential indolent tumors that will not impact their life expectancy or quality of life. Most of them will be radically treated and suffer its consequences. Thus, PCa overtreatment is a great concern among clinicians. Pre-treatment molecular factors may help differentiate indolent from aggressive PCa. Id1, involved in cell differentiation and angiogenesis, has recently showed to mediate lung metastasis (mts) from breast cancer. Its role in PCa endothelial (end) cells is well established but its exp and role in PCa cells is controversial. Using a new monoclonal antibody (MoAb) (195–14) for immunohistochemistry (IHC), Id1 exp is limited to some PP breast and bladder tumors. Whether Id1 exp is relevant in PCa prognosis is unknown. We tested 195–14 in PP and GP PCa samples and matched mts where available. Methods: 52 PCa pts were studied, 20 GP + 32 PP. All formalin-fixed and paraffin-embedded primary biopsies and matched mts of 16 of them were stained for tumor and end cell Id1 exp. 195–14 (1:500), (Biocheck), was used for IHC. Results: GP group: median age 65, all pts T2N0M0, median Gleason score 6 (6–9), median PSA at onset 5,5 ng/ml. After a median follow-up of 38 months (ms) 1 pt showed radiological and PSA progression (P); other PSA P. All but one remain alive. PP group: median age was 70, T3-T4 (70%), Gleason 8–10 (61%), median PSA at onset 58 ng/ml, 2 or more mts locations (79%), 94% showed P to docetaxel, median time-to- progression and overall survival after chemotherapy were 18 weeks and 7 ms. Among PP, 39% of primary PCa and 38% of mts showed Id1 tumor cell exp and 79% of primary tumors and 81% of mts showed end Id1 exp. In the GP group 0% showed Id1 tumor cell exp, and 50% showed end Id1 exp. The unexpected Id1 exp difference in tumor cells in PP compared to GP pts predicted clinical outcome. Consistently with other reports end Id1 exp is high in both groups. PP showed higher levels. Conclusions: Id1 exp discriminated GP from PP in our PCa cohort. These novel results highlight Id1 as a prognostic marker in PCa. Whether Id1 exp in the diagnostic biopsy can impact PCa therapeutic decision-making needs further investigation. No significant financial relationships to disclose.
Combined modality treatment for organ preservation in patients with invasive bladder cancer
Authors: Carrizo M. N. , Sade J. P. , Costanzo M. V. , Chacon M. , Chacon C. , Orlando M. , Chacon R. D. 
Published: August 2020

e16129 Purpose: To evaluate long term results of chemoradiation and organ preservation in invasive T2-T4a bladder carcinoma in a single institution with prolonged follow up. Methods: Sixty one patients with clinical stage II and III (T3N0) muscle invasive bladder carcinoma were treated between February 1991 and December 2007. Forty four received sequential treatment (chemo followed by radiation) and seventeen concurrent treatments. Chemotherapy was platinum based in all patients, fifth teen with Carboplatin. All underwent maximal citoreduction with TUR .First 20 patients received pelvic radiation (1991–1993),while the other 41 three-dimensional radiotherapy (median dose 60 Gy). Male/female 55/6: median age 64 (range 46–80); transitional type 58 and mixed-epidermoid 6. Grade II: 3, grade III: 48 and grade IV: 10. Clinical stage II:50 and III:11. Mean follow up 63 months. Results: The 5 year overall survival rate was 57%. Forty patients remained NED, with eight deaths due to second primary or cardiovascular disease. Twenty pts were treated more than 5 years ago, 16(80%) are alive, 14 NED,2 pts relapsed after 5 years. Of all predictive factors analyzed only clinical stage reached statistical significance for relapse (p=0.0029), and borderline significance for overall survival (p=0.064). Toxicity: Grade 3–4: 7%, with 3% of febrile neutropenia. No patient required cystectomy because of bladder morbidity. Conclusions: Trimodality treatment in selected patients offers rates of event free survival and overall survival similar to those reported for surgery with acceptable toxicity and no treatment related cystectomy. Relapse after 5 year is very uncommon. In this small group of patient results were similar with concurrent and sequential treatment. At present we treat our patients with concurrent chemoradiation with tridimensional technique. No significant financial relationships to disclose.
Pancreatic metastasis from renal cell carcinoma: Presentation, recurrence, survival, and response to antiangiogenic therapy
Authors: Albouy B. , Billemont B. , Massard C. , Gross-Goupil M. , Rixe O. , Escudier B. 
Published: August 2020

e16137 Background: Pancreas represents an uncommon site of metastasis in renal cell carcinoma (RCC). The natural history of pancreatic metastases is largely unknown, and efficacy of targeted agents has never been assessed. We examined the outcome in a series of RCC patients (pts) with pancreatic metastases, treated by either surgery or antiangiogenic therapy. Methods: We reviewed the charts of RCC pts treated for pancreatic metastases, between 2001 and 2008, in Institut Gustave Roussy and Pitié-Salpetrière Hospital. Data base was reviewed to determine presentation, clinical symptoms, pancreatic metastases treatment, use of systemic therapy, disease-free survival (DFS) or progression-free survival (PFS) and overall survival (OS) after treatment. Results: A total of 40 pts with pancreatic metastases from RCC have been analyzed. Median age was 63 years (range: 48–81), sex ratio M/F was 29/11, and metastases occurred initially (synchroneous) in 9 pts, while they were metachronous in 31 pts. Most of the metastases were asymptomatic (87%), detected on routine CT scans, while only 12% were symptomatic (pain, cholestasis). Surgical resection of pancreatic metastases was performed in 8 (20%) patients, and DFS and OS were 45 and 66 months. In patients with multiple metastatic sites (lung : 20 (50%); liver : 8 (20%); thyroid : 3(7%)), therapeutic approaches have included antiangiogenic therapies (75%): sorafenib (20 pts), sunitinib (7 pts), bevacizumab (2 pts), Torisel (1 pt). Best response was partial response in 30% of pts and stable disease in 50% of pts. Median PFS and OS were 21 months and 30 months. Conclusions: Patients with RCC pancreatic metastases seem to have a longer survival than the usual metastatic RCC pts. Surgical resection must be discussed in pauci-metastatic disease, as it can be associated with prolonged survival. Antiangiogenic therapies are active in these patients with high response rate and prolonged survival. No significant financial relationships to disclose.
Multiple primary tumors in patients with carcinosarcoma of bladder: A coincidence or an etiological association? A study of 221 carcinosarcoma of bladder cases
Authors: Wang J. , Wang F. 
Published: August 2020

e16138 Background: Carcinosarcoma of the bladder are rare; As a result, few studies of carcinosarcoma of the bladder have included sufficient number of patients to define their natural history and to determine the factors that impact survival. The objective of this study was to examine the epidemiology, natural history, and prognostic factors that affect the survival for carcinosarcoma of the bladder by using population-based registries. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program database (1973–2004) was used to identify cases of carcinosarcoma of the bladder by tumor site and histology codes. The association between clinical and demographic characteristics and survival of carcinosarcoma of the bladder was examined. Results: A total of 221 cases of histology confirmed carcinosarcoma of the bladder were identified, this account for approximately 0.11% of primary bladder tumors during same period. By using linked population files, we calculated the incidence of carcinosarcoma of the bladder as a rate 0.22 per 100,000 per year, age-adjusted to year 2000 U.S. standard population. Median age of all patients were 75 years (range 41–96). In about 40% of study population, more than one or multiple primary were also indentified. Majority of (212, 95.9 %) patients received cancer directed surgery. For survival analyses, we excluded the cases that were identified at autopsy or on the basis of death certificates only and the patients have more than one primary. Total 132 patients were included in survival analysis. The median overall survival for all cases was 9 months (range 6–12 months). In multivariate analysis, only tumor stage was found to be significant prognostic factors for disease-specific survival. Conclusions: Carcinosarcoma of the bladder are rare tumors that are challenging, the survival is poor even in patients underwent surgical resection. Better therapy is needed to improve patient's outcome. A significant fraction of carcinosarcoma patients are actually affected by multiple primary tumors, the potential association between carcinosarcoma and other neoplasms remain to be investigated. No significant financial relationships to disclose.
Unraveling the metabolome in prostate tumorigenesis: Effects by an oncogenic isopeptidase
Authors: Priolo C. , Loda M. 
Published: August 2020

e16148 Background: Cancer cells undergo fundamental changes in their metabolism, including a higher rate of glycolysis and an increase in de novo fatty acid synthesis. The high incorporation of glucose into tumor cells has already been exploited in cancer diagnostics with the generation of the FDG-PET scan technology. However, some tumors including those arising in the prostate are less prone to FDG-PET imaging and could benefit from other imaging techniques based on alternative metabolic features. We asked whether prostate epithelial cell transformation driven by specific oncogenes results in a typical metabolic profiling, whose characterization may be useful to improve diagnostics and to address new therapeutics. Methods: Normal prostate epithelial cells (RWPE-1 and PrEC) were transformed by overexpressing known oncogenes, such as the protein kinase AKT1 and the de-ubiquitinating enzyme (isopeptidase) USP2a. These cells were then subjected to mass spectrometry-based metabolomics, gene expression analysis, oxygen consumption and glucose uptake assays. Multiple bioinformatic tools were utilized for data mining and pathway visualization. Results: We integrated data from different high-throughput technologies to map metabolic changes induced during prostate tumorigenesis by genes that are often altered in prostate cancer. A different metabolic profiling was found in association to each specific oncogene. In fact, extremely significant alterations were found in the glycolytic pathways in the case of AKT-driven transformation, whereas changes in the lipid metabolism and in some aminoacids were prevalent in USP2a-overexpressing cells. Complementary assays including oxygen consumption and glucose uptake measurement confirmed the global metabolic analysis. Conclusions: These results suggest that tumors showing different genetic alterations may be characterized by a different metabolic profiling, whose assessment can potentially improve diagnostics and individualized treatment. Metabolic profiling analysis of human prostate tumors is currently ongoing. No significant financial relationships to disclose.