bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of survival by immunohistochemical stains (IHC) in stage D2 prostate cancer patients (pts): The importance of pTEN overexpression
Authors: Kasimis B. , Chang V. , Gounder S. , Gonzalez M. , Finch-Cruz C. , Blumenfrucht M. , Srinivas S. , Cogswell J. , Morales E. , Ahmed S. 
Published: August 2020

e16019 Background: Several signal transduction pathways,important for apoptosis and angiogenesis were idendified and their expression and correlation with survival was studied by IHC in archival prostate cancer biopsies. All pts has androgen deprivation for stage D2 disease and were followed at 3 month intervals. Methods: In an IRB approved study,42 pts had adequate tissue preserved between 1992 and 2006 and their charts were reviewed retrospectively.IHC stains to detect tumor expression of S6(ribosomal),p70s6,pTEN,AKT-1,BCL-1(Cyclin D1),VEGF,c-KIT,PDGFR-alpha and PDGFR-beta were performed by US Labs(Irvine,CA).All results were independently evaluated by two pathologists.Immunoreactivity was scored using a semiquantitative system combining intensity of staining(0–3+) and percentage of cells staining positive(0–3+).The total score was obtained by adding the scores for indensity and the percentage of positive cells,then averaging the resuts obtained by each reader.For the purpose of this study, stain intensity of 0–1+ was considered negative and the intensity of 2–3+ was considered positive.A Cox regression survival model for each stain was developed with variables known to predict survival :Gleason score,Hemoglobin(Hgb),Alkaline Phosphatase(Alk Phos),Prostate Specific Antigen(PSA),Lactate Dehydrogenase(LDH) levels. Results: The median values were: age 70yrs(56–92),Gleason score 8(6–10), LDH 171 IU/L(97–350),Hgb 12.9gm/dl (6.8–16.3), PSA 188ng/ml(2–5677),Alk Phos 139U/L(60–1756),survival 851 days(163- 6102).In univariate analysis,VEGF staining was predictive of survival (p<0.037) but not in multivariate analysis.The pTEN staining correlated with survival (p<0.0367) and a hazard ratio of 0.040 in multivariate analysis. Conclusions: In this small sample of pts, overexpression of S6,p70s6,AKT-1,BCL-1,VEGF,c-KIT,PDGFR-alpha and PDGFR-beta by IHC staining did not predict survival independently.The pTEN staining,however was strong predictor of survival in the multivariate analysis. No significant financial relationships to disclose.
Phase II trial of bevacizumab (B) and oral satraplatin (S) and prednisone in docetaxel pretreated metastatic castrate resistant prostate cancer (CRPC)
Authors: Vaishampayan U. N. , Heilbrun L. K. , Heath E. I. , Smith D. W. , Dickow B. , Baranowski K. , Powell I. , Fontana J. 
Published: August 2020

e16028 Background: In metastatic CRPC, second line therapy after docetaxel, remains a currently unmet need. Based on the efficacy and tolerability of S and B in prostate cancer, and the clinical synergy noted between chemotherapy and B, a phase II trial of the combination was conducted. Methods: Metastatic CRPC patients, with prior docetaxel based chemotherapy were eligible to receive S 80 mg/m2 orally for days 1–5, and B 10 mg/kg on day 1, and 15mg/kg on day 15 of each 35 day cycle. Prednisone was administered at a dose of 5 mg twice daily. Response was assessed every 2 cycles. Toxicity was assessed weekly during cycle 1 and on days 1 and 15 of each subsequent cycle. Primary endpoint was time to progression defined as a skeletal event, new areas of metastases on bone scans or per RECIST criteria for measurable disease. Results: 19 of 28 patients have been enrolled to date; 7 African American and 12 Caucasian,, with median age of 68.5 years and median pretherapy PSA of 137.8 ng/mL (range 16.8–994 ng/mL). 7 (44%) had bone pain, Gleason score of 7 and ≥ 8 in 7 and 12 patients respectively. Measurable disease progression was noted in 5 patients, bone scan progression in 6 patients, progression of both in 3 patients, and PSA only progression in 5 patients. 76 cycles have been administered; 7 patients continued on therapy beyond 6 cycles. The only grade 4 toxicity noted was pulmonary embolism in 2 patients, after 2 and 6 cycles of therapy. Grade 3 neutropenia, gastrointestinal toxicity, and electrolyte abnormalities were noted in 1 patient each. There were no treatment related deaths. 16/19 patients are response evaluable. 7 patients had a PSA decline of which 4 patients had a ≥30% PSA decline. 3 of 6 patients had a measurable disease response. 11 of 16 patients have progressed to date after median of 6 cycles of therapy. Time to progression and survival data will be reported. Conclusions: The combination was well tolerated, and revealed preliminary evidence of clinical efficacy in docetaxel pretreated metastatic CRPC. [Table: see text]
Salvage chemotherapy with gemcitabine, paclitaxel, ifosphamide, and cisplatin (Gem-TIP) for relapsed germ cell tumours (GCT)
Authors: Wheater M. J. , Huddart R. , White J. , Rustin G. , Abab J. , Mead G. M. 
Published: August 2020

e16031 Background: Patients with relapsed metastatic GCT following treatment with cisplatin based combination chemotherapy, may be cured with further intensive chemotherapy. A Medical Research Council trial of TIP achieved 1 year progression free survival (PFS) of 38% with 65% survival (Br J Cancer. 2005;93:178). A more dose intense schedule of TIP with growth factors achieved 2-year PFS of 91% (Proc Am Soc Clin Oncol. 22:2003 [abstr 1537]). Gemcitabine has activity in the treatment of multiply relapsed disease. This study aims to investigate the feasibility of adding gem to TIP with the addition of growth factor support, while maintaining TIP dose intensity, with a view to improving the outcome from TIP alone. Methods: A phase I dose escalation study of Gem-TIP was carried out in patients at first relapse from metastatic GCT following cisplatin chemotherapy. All patients received TIP without dose reduction (paclitaxel 175 mg/m2 d1, cisplatin 20 mg/m2 d1–5, ifosphamide 1 g/m2 d2–6) with GCSF days 7–18 of a 21 day cycle for maximum 4 cycles. 3 dose levels of gem were investigated, 600 mg/m2 d1, 900 mg/m2 d1 and 1,200 mg/m2 d1. Dose limiting toxicity (DLT) was non-haematological grade 3 or 4, except nausea, vomiting and alopecia. Results: 13 patients treated, 12 male, 1 female, age 21–48 years. Baseline histology seminoma 8, non-seminoma 5. Cohort 1: 4 patients treated, 1 withdrew after 1 cycle. No DLT observed. Cohort 2: 3 patients completed treatment with no DLT. Cohort 3: 1 patient treated suffered allergic pneumonitis at cycle 1 complicated by a malignant pleural effusion. A further 5 patients were treated at this dose level. The minimum course duration was 63 days. The mean duration for each cohort was 69 days for cohort 1 and 2, 64 days for cohort 3. Grade 3/4 haematological toxicity was; neutropaenia 9 patients, thrombocytopaenia 10 patients, with 2 episodes of febrile neutropaenia but no bleeding. 10 platelet transfusions were required. 10 patients were assessable for response, 5 CR, 3 PR, 2 PD. At median follow up 18 months the median PFS is 10 months. Conclusions: Gem-TIP can be delivered with 1200mg/m2 gem with manageable toxicity in the context of growth factor support. This dose will be taken forward to a phase II study. No significant financial relationships to disclose.
Role of obesity and race in predicting recurrence rates and survival in renal cell carcinoma
Authors: Ritch C. , Lee D. J. , Desai M. , McKiernan J. M. 
Published: August 2020

e16052 Background: Two in three Americans are obese or overweight, and African-Americans are 1.4 times as likely to be obese than whites. However, the relationship between obesity, race, and renal cell carcinoma (RCC) is highly debated. We sought to explore the relationship between BMI and race, and determine the predictors for survival and recurrence after nephrectomy (Nx) for RCC. Methods: A retrospective analysis of the Columbia Urologic Oncology Database found that 1118 consecutive patients underwent partial or radical Nx for RCC between 1988 and 2008. Of these, 499 patients had BMI and race data available. 379 (76%) were white, 51 (10.2%) were black, 37 (7.4%) were Hispanic, and 32 (6.4%) were Asian. 341 (68.3%) were male compared to 158 (31.7%) females; 215 (50.3%) had partial Nx while 284 (56.9%) had a radical Nx. Overweight and obesity were defined as having a BMI > 25 kg/m2 and a BMI > 30 kg/m2, respectively. Cox proportional hazards models were used to assess the relationship between BMI, race, and recurrence- free survival (RFS). Results: The 499 patients had a median age of 63 years were followed for a mean of 25 months. Asians had significantly lower BMI than the other races (p=0.02), but the other ethnicities had similar BMI distributions. The two year cancer-specific survival was 89.6%, 92.7%, and 96.1% for normal weight, overweight, and obese patients, respectively (p=0.036). Race did not have a significant impact on predicting RFS. A multivariate Cox regression found that male sex, BMI, size of tumor removed, tumor stage, and margin were independent predictors of RFS. Overweight and obese patients were more likely to survive from RCC without recurrence than normal weight patients (p=0.04). An analysis assessing the effect of an interaction between race and BMI demonstrated that hazard ratios for increased BMI did not differ significantly by race. Conclusions: BMI is an independent predictor of RFS in patients undergoing partial or radical Nx for RCC. Recurrence free-survival did not differ significantly among the different ethnicities, and the impact of race on recurrence-free survival did not vary among different BMI classes. The importance of these findings needs to be addressed in large multi- institutional analyses. No significant financial relationships to disclose.
A phase I study of everolimus plus sorafenib in patients with metastatic renal cell carcinoma (mRCC)
Authors: Cen P. , Daleiden A. , Doshi G. , Amato R. 
Published: August 2020

e16056 Background: Everolimus, a mTOR inhibitor and Sorafenib, a Raf kinase inhibitor had shown their efficacy in RCC, as single agents. Combining these two active agents could have potential additive or synergistic effects. We conducted a phase I study to evaluate the maximum tolerated dose (MTD) of this combination in patients with progressive mRCC. Methods: Patients predominantly had clear cell RCC, and progressive measurable diseases on prior treatments including immunotherapy, TKI and/or Everolimus. Patients were evaluated weekly for toxicities and every 8 weeks for radiological response, including at least both PET/CT and CT scans at baseline and 1st staging. Patients received daily Everolimus and twice daily sorafenib both orally at escalating dose levels of 2.5mg/400mg (dose level 0), 5mg/400mg (+1), and 10mg/400mg (+2). Results: 18 patients with mRCC were enrolled and 15 patients were evaluable. 6 patients were treated on dose level 0, dose- limited toxicity (DLT) was found in 2/6 patients, one with thrombocytopenia/leukopenia, the other with pneumonitis; 6 patients were treated on dose level +1, DLT of pulmonary embolism was found in 1/6 patient; and 3 patients were treated on dose level +2, without DLT. The most common side effect was grade 1/2 hand-foot syndrome (4/15, 27%). The MTD was dose level +2. Overall response by RECIST was 27% (4/15 patients): pathological complete response (CR) was 6% (1/15); radiographic CR was 6% (1/5); surgical CR after resection was 6% (1/15). 47% (7/15) of the patients had stable disease. Decreased FDG uptake was found in 67% (10/15) of the patients. The median PFS was 5.53 months (range, 1.4–14.7), and OS was 7.9 months (range, 2.3–23). Conclusions: The MTD of combining daily Everolimus 10mg and twice daily sorafenib 400mg are safe and effective for progressive metastatic RCC. The phase II trial is planned to start in early 2009. [Table: see text]
Oncological outcomes of radical cystectomy for bladder cancer: Laparoscopy versus open surgery
Authors: Guillotreau J. , Gamé X. , Mouzin M. , Doumerc N. , Malavaud B. , Rischmann P. 
Published: August 2020

e16059 Background: To compare the oncological outcomes of laparoscopic versus open surgery in radical cystectomy for bladder cancer. Methods: A prospective non-randomized study was conducted between January 2003 and November 2008 in 52 patients, 2 women and 50 men, who underwent radical cystectomy for bladder cancer. Thirty seven cystectomies were carried out by laparoscopic surgery (LS) and 15 by open surgery (OS). Mean patient age was 67.3 ± 9.7 years. The median preoperative ASA score was 2 (1–3) in both groups. Kaplan-Meier curves were constructed to estimate the survival rate for the whole sample. Datas were compared by Log-rank test. Current followup, overall and specific deaths were used as endpoints. The survival time was defined as the time elapsed from the date of radical cystectomy to the endpoint. Results: All tumours were transitional cell carcinoma, high-grade and stage < pT3b pN0. One patient of OS group had a positive surgical margin. Eight patients (15.4%), 7 of LS group and 1 of OS group, completed 5 years of follow-up. At the last follow-up 40 patients (76.9%) were alive with no evidence of disease and 5 (9.6%) died, two patients (3.8%) from metastasis and 3 (5.7%) from different causes. No patient developed port- site metastasis. Overall survival was significantly better in LS group than in the OS group (p=0.039). No statistical difference was noted for Specific survival. Mean patient follow-up was 30.9 ± 20.3 months. Conclusions: The data suggest that LRC provides oncological outcomes comparable to contemporary series of open RC. No significant financial relationships to disclose.
Bone markers in prostate cancer (PC) patients: Biologic criteria to identify patients at risk of developing distant metastases
Authors: Ayllon J. , Banu E. , Leviel F. , Houillier P. , Medioni J. , Barrascout E. , Oudard S. , Maruani G. 
Published: August 2020

e16069 Background: Currently, there are no specific serum and/or urinary bone markers able to accurately identify PC patients with hormone-refractory disease and/or those with distant metastases. Methods: Four categories of PC patients were defined as follows: A. hormone-sensitive without distant metastases; B. hormone-sensitive with metastases; C. hormone-refractory without metastases; D. hormone-refractory with metastases. The serum bone markers investigated were osteogenesis-related [Osteocalcin (OC), procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline phosphatase (BALP)], osteolysis-related [beta collagen 1 carboxyterminal peptide (βCTX), carboxyterminal telopeptide type 1 collagen (1CTP), tartrate resistant acid phosphatase (TRAP)] or osteoclastogenesis-related [osteoprotegerin (OPG)]. Receiver Operating Characteristic (ROC) curves and the Area Under these curves were used to estimate the overall accuracy of each marker in discriminating between the four categories (A vs. BCD; B vs. ACD; C vs. ABD and D vs. ABC) with no adjustment for multiplicity. Parametric (Student's t-test) and non-parametric (Kruskal- Wallis) tests were conducted too. All statistical analyses were performed by means of SPSS v 16 (SPSS Inc). Results: Data were from 40 consecutive PC patients treated at the Georges Pompidou European Hospital in Paris, France and who were equally distributed between categories. Hormone-refractory patients with distant metastases were accurately identified by P1NP, 1CTP and TRAP. The respective areas under the ROC values were 0.76, 0.84 and 0.79 (all Pvalues less than 0.01). None of the markers identified category B of patients. Conclusions: Some bone-related serum markers may be associated with the onset of hormone-refractory status and distant metastases. They should be prospectively validated in a larger cohort of patients. No significant financial relationships to disclose.
The impact of docetaxel (D) in an older population of patients with advanced prostate cancer (PC): A simulation study using TAX327 and SEER Medicare data
Authors: Onukwugha E. , Mullins C. D. , Obeidat N. , Seal B. , Hussain A. 
Published: August 2020

e16074 Background: The survival benefit of D in treatment of hormone refractory PC (HRPC) has been established in the TAX327 trial, but it is unclear how this benefit would translate in a heterogeneous population. This study sought to simulate the survival impact of D in a population of older pts with M1 PC on androgen deprivation therapy (ADT). Methods: A combination of TAX327 trial data and SEER-Medicare (SM) data were used. In pts age 69+ and randomized to D (every 3 weeks, D3P) or mitoxantrone (M), trial data showed a survival benefit for D. Accordingly, SM pts age 69+ diagnosed with M1 PC between 1994 and 2002 and receiving only ADT were selected. Graphical plots and statistical tests were used to find best-fitting parametric survival functions for D3P, M, and SM pts. The survival benefit for D was imposed on unadjusted and covariate-adjusted SM survival curves. The simulated benefit was assessed at 12 mos and 24 mos post-diagnosis of M1 PC in SM pts. Results: There were 326 TAX327 trial pts (D3P = 159, M = 167) used in the analysis. Median survival was 15.7 mos (12.6 - 19) in the M arm and 18.9 mos [17 - 21.8] in the D3P arm (p = 0.03). There were 3,515 SM pts, based on inclusion criteria. Median survival benefit of D was 3.2 mos based on Kaplan-Meier estimates and 2.4 mos using parametric curves in the TAX327 69+ group. Following covariate-adjustment in the SM sample, at 12 mos post-diagnosis, the median survival in mos was 61.7 (CI 36.3 - 87) in the ADT group and 62 (CI 37.6 - 87.1) in the simulated ADT+D group (i.e., 0.3 mos simulated benefit of D). A 0.8 mos simulated benefit was found if D was initiated 24 mos post diagnosis (in pts more likely to have HRPC). Conclusions: The survival benefit of docetaxel from the TAX327 trial is attenuated in a heterogeneous SEER-Medicare sample, and the simulated survival benefit is larger among patients who are more likely to have hormone refractory prostate cancer. [Table: see text]
Phase II study of everolimus (E) with imatinib (IM) in patients with previously-treated renal carcinoma (RCC)
Authors: Ryan C. W. , Vuky J. , Chan J. S. , Beer T. M. , Rothkopf M. 
Published: August 2020

e16075 Background: Inhibitors of mTOR improve progression-free survival (PFS) in advanced RCC. We hypothesized that co-administration of the mTOR inhibitor E with an upstream receptor tyrosine kinase inhibitor could augment activity in advanced RCC. We chose to study IM due to its inhibition of PDGFR, a relevant target for RCC with potential activity at both the tumor cell and the pericyte. Methods: Eligible patients had metastatic or unresectable clear cell renal carcinoma, at least one prior systemic therapy, no prior mTOR inhibitor therapy, performance status 0–2, and measurable disease. Treatment consisted of E 2.5 mg p.o. daily and IM 600 mg p.o. daily, a dose determined from a phase I study in GIST. A two-stage design was employed to test for a 3-month PFS of ≥ 70% vs. ≤ 50%. Results: 19 subjects were evaluable for toxicity and 18 for response. Median age 65; number of prior systemic therapies 1:2:3+ (47%:32%:21%); prior sorafenib and/or sunitinib 89%; MSKCC prognostic categories favorable:intermediate:poor (42%:47%:11%). There were no objective responses. Best response was stable disease (67%) and progressive disease (33%). The 3-month PFS rate was 49% (95% C.I. 23%, 72%). The median PFS was 2.9 months (95% C.I. 1.9, 6.2) and the median overall survival was 14.4 months (95% C.I. 11.3, N.R.). Toxicities and lab abnormalities affecting >50% of subjects were: nausea, elevated creatinine, edema, anemia, hypocalcemia, fatigue, diarrhea, vomiting, and dyspnea, and leucopenia. Most common grade 3+ events were: fatigue (16%), pleural effusion (16%), edema (11%), and renal failure (11%). The study was closed after the first stage as the 3-month PFS did not meet continuation criteria. Conclusions: The combination of E 2.5 mg with IM 600 mg in previously-treated patients with advanced RCC did not meet the study-defined level of activity to warrant further investigation. The natural history assumptions for this pretreated RCC population may have been overly optimistic. While the observed PFS is comparable to that reported with E 10mg monotherapy, there appears to be no advantage to combination IM therapy and the incidence of adverse events is high. Further development of this regimen for RCC is not recommended. [Table: see text]
High-grade proteinuria associated with bevacizumab in patients with renal cell cancer and non-renal cell cancer
Authors: Kim C. Y. , Chu D. , Baer L. , Wu S. 
Published: August 2020

e16089 Background: Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor. It is a widely used angiogenesis inhibitor in the treatment of renal cell cancer (RCC) and other solid tumors. Proteinuria is associated with significant morbidity and treatment interruptions. The overall risk for proteinuria is unclear. This study was conducted to determine the risk of developing proteinuria among RCC and non-RCC patients receiving bevacizumab. Methods: Databases from PUBMED and Web Science from January 1966 until July 2008 and abstracts presented at ASCO from January 2000 to July 2008 were searched to identify relevant studies. Studies included randomized controlled clinical trials in which standard anti-neoplastic therapy was administered with and without bevacizumab with available data for proteinuria. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated employing fixed or random effect models based upon the heterogeneity of included studies. Results: A total of 6,702 patients from 14 randomized controlled studies were included for analysis. The incidence of all-grade proteinuria in patients receiving bevacizumab was 19.3% (95% CI: 11.9–29.6%) with 2.3% (95% CI: 1.2–4.1%) being high-grade (grade 3 or 4). Patients treated with bevacizumab had an increased risk of developing high-grade proteinuria with RR of 6.3 (95% CI: 4.0–9.9) compared with controls. Risk may vary with dose of bevacizumab; significant difference may exist in patients receiving bevacizumab at 5 mg/kg/week (RR 9.1, 95% CI: 4.3–19.6, p < 0.001) and 2.5 mg/kg/week (RR = 5.1, 95%CI: 3.0–8.8, p < 0.001). The risk of high-grade proteinuria may also depend on tumor type; the incidence of high-grade proteinuria was 10.0% (95% CI: 4.3–22.4%) with a RR 48.7 (95% CI: 9.7–244.3) among 703 RCC patients compared with an incidence of 1.7% (95% CI: 0.09–3.2%) and RR of 5.2 (95% CI: 3.3–8.4) among 5,999 non-RCC patients. Conclusions: There is a significant risk for high-grade proteinuria in patients receiving bevacizumab. The risk may vary with bevacizumab dose and tumor type. RCC patients may have higher risk than non-RCC patients. Close monitoring and management are recommended for patients at high risk. No significant financial relationships to disclose.