bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of anti-PSMA designer T-cell autografting in prostate cancer
Authors: Abedi M. , Ma Q. , Bais A. , Gomes E. , Beaudoin E. , Lu L. , Davol P. , Cohen S. I. , Junghans R. 
Published: August 2020

e16132 Background: We created chimeric immunoglobulin-T cell receptors (IgTCR) specific for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” specifically kill prostate cancer cells in vitro and in vivo in animal models, with 5/9 (55%) of xenografted mice experiencing complete remissions (Ma et al. Prostate 2004:61:12–25). A Phase I clinical trial was approved by the FDA in metastatic prostate cancers. Methods: Patient T cells are retrovirally transduced and expanded ex vivo to span dose levels of 10^9 to 10^11 T cells. Adapting methods of Dudley, Rosenberg and colleagues, patients undergo prior non-myeloablative (NMA) conditioning to create a “hematologic space” into which the infused designer T cells will stably engraft for prolonged in vivo efficacy. Patients are co-administered continuous infusion IL2. Outcomes will include Phase Ia goals of safety and toxicity and Phase Ib goals of establishing an optimal biologic dose in terms of designer T cell engraftment and tumor response. Results: For the first two patients, excellent T cell modifications of 50–60% were obtained. After NMA conditioning, T cells were infused and stable engraftments of 1–5% were observed post recovery, even at this lowest 10^9 T cell dose level, thus affirming one of the study end-points. The patients had PSA reductions of 50 and 70% in the two months following treatment. Patients experienced neutropenia and lymphopenia after conditioning, but no designer T cell-related toxicities. Results with additional patients will be described in terms of safety, engraftment efficiency and tumor responses. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised. This clinical trial is funded by the US Army/DOD. No significant financial relationships to disclose.
Concomitant radical non-platinum radiochemotherapy for elderly patients with invasive bladder cancer
Authors: Rodica Maricela A. , Minea L. N. , Bacinschi X. , Isacu I. , Tarlea A. 
Published: August 2020

e16135 Background: Treatment of bladder cancer in elderly patients is a challenging problem because surgery is often not tolerable and the combination of extensive radiotherapy with chemotherapy is also difficult because of patients’ compliance and associated comorbidities. Our study evaluated concurrent radiochemotherapy in elderly patients with locally advanced bladder cancer (T2-T4) in terms of efficacy and tolerability. Methods: Between January 2005 and December 2007, we treated 34 patients with transitional carcinoma of the bladder, with or without nodal involvement, no distant metastases, and median age 79 years (range 66 - 89 years). Their performance status was 0–1-2 in 10–16–8 patients respectively. Cardiovascular comorbidities were the most common (15 patients). The treatment consisted in conformal radiotherapy (mean irradiation dose = 56.4 Gy) concomitant with biweekly Gemcitabine 200 mg/sqm starting on day 1 of radiotherapy. Results: Response was assessed at 4–6 weeks after the end of treatment by cystoscopy with biopsies and MRI. All the patients could end the intended radiation therapy but four of them could not tolerate all the chemotherapy. 13 patients achieved complete response, 12 patients - partial response and 9 patients stable disease. The most common toxicities were: diarrhea (grade 1–2 in 11 patients, grade 3–6 patients), cystitis (grade 1–2 in 5 patients), leucopenia (grade 1–2 in 12 patients, grade 3–4 in 2 patients), thrombocytopenia (grade 1–2 in 6 patients) and anemia (grade 1–2 in 4 patients). Three patient required hospitalization for dehydration and two for febrile neutropenia. After a median follow-up time of 17.4 months, there were 7 relapses and 5 distant metastases. One-year survival rate was 82.41% (28 patients). 6 patients died, 3 from their cancer and 3 from comorbidities. Conclusions: Chemoradiation is well enough tolerated even in elderly patients and also an efficient and organ sparing therapeutic alternative for patients over 65 years old. The treatment choice was based on patients’ preference considering better quality of life with bladder preservation. The use of age-specific therapy adjustments has shown that aggressive treatment for bladder cancer is associated with improved survival even in elderly patients. No significant financial relationships to disclose.
Nude mice model of primary human nonseminoma germ cell tumors to study biology and resistance to cisplatin treatment
Authors: Piulats J. M. , Nadal M. , Martinez-Iniesta M. , Puertas S. , Gonzalez S. , Vidal A. , Condom E. , Germa-Lluch J. , Garcia Del Muro X. , Villanueva A. 
Published: August 2020

e16143 Testicular germ cell tumors (TGCTs) are the most common malignancy in young men. Recently, our group has reported the development of a model of human nonseminoma (NSE) after orthotopic nude mice implantation (Piulats et al, Amer Assoc Cancer Res. 2006). Pure and mix NSE anatomies were represented and they reproduce the main histological, genetic and epigenetic characteristics of paired primary tumors. Xenografts mimic distal dissemination patterns and cisplatin (CDDP) tumor behavior responses. This model has been useful for the study of antiangiogenic therapies (Piulats et al, ASCO. 2007), furthermore we want to demonstrate it is an useful tool to study the genetic mechanisms related with CDDP adquired resitance. We have generated in vivo five tumors showing increased resistance to CDDP by exposition to repetitive cycles and increasing the dose applied through different passages (1 yolk-sac; 1 choriocarcinoma; 2 embrional carcinoma; 1 mix tumor). A shortness time elipse between pasajes was observed for each tumor through CDDP treatments. To confirm increasin resistance, a parallel assay of chemotherapy response was performed between nontreated and CDDP resistant tumors. Whole genome analysis of tour xenografted tumors and their paired CDDP resistant tumor (#3 and #5 passage) were analyzed by CGH NimbeGen arrays using 60 Kb average windows. Few differential genomic changes were identified some of them were consistent across resistant tumors including gain of 9q21.11–9q33.3, 15q23–15q24.1, and 15q26.3 regions and loss of Xp22.33. In one tumour showing strong CDDP resistance compared with its sensitive counterpart it occur in absence of new genomic changes. No changes in the MSI or mutational TP53 status were observed in resisant tumors. Our data suggest that acquisition of tumor resistance to CDDP in TGCTs may proably depend of a combination of different mechanisms, including cromosomal imbalances. No significant financial relationships to disclose.
The effects of sorafenib and sunitinib on bone turnover markers in patients with bone metastases from renal cell carcinoma
Authors: Sahi C. , Knox J. J. , Hinder V. , Deva S. , Cole D. , Clemons M. , Broom R. J. 
Published: August 2020

e16145 Background: Bone metastases (BM) from renal cell carcinoma (RCC) are common and associated with poor outcomes. While the multi-tyrosine kinase inhibitors (TKI's) sunitinib and sorafenib have advanced the treatment of metastatic RCC, their efficacy on BM is unknown. Urinary N-telopeptide (uNTX) is a marker of bone turnover measured in nmol/mmol creatinine. Elevated uNTX levels correlate with an increased risk of skeletal related events and mortality in patients receiving bisphosphonates for BM from a range of primaries. In this pilot biomarker study we sought to prospectively evaluate the effects on BM of these multi-TKI's in RCC patients. Methods: Eligible patients had advanced RCC, at least one BM evident on imaging and no bisphosphonate exposure within 4 weeks. UNTX levels (OsteoMark) were measured at; baseline and weeks-1, 4, 8 and 12 after commencing either sunitinib or sorafenib. The primary endpoint was the percentage change (Ch) in uNTX levels from baseline. Serum samples were also collected for KIT and VEGFR-2 (Quantikine). Patients also completed pain (including bone pain) and quality of life questionnaires. Results: The uNTX results on the first 9 patients are presented in the table below (7 received sunitinib and 2 sorafenib). In this group, sVEGFR-2 and sKIT levels fell by week-1 and 4 respectively and at week-12 the mean % changes (95% CI) were -34% (-0.53,-0.14) and -38% (-0.58,-0.18). Conclusions: In patients with BM from RCC and at least moderately elevated uNTX levels at baseline, these multi-TKI's show a significant trend to decrease uNTX levels, but perhaps not as effectively as bone-specific therapies (e.g. bisphosphonates) do in other malignancies. SVEGFR-2 and sKIT levels also fell across the patient group over the same period. This pilot data raises questions about the activity of the multi-TKI's in BM from RCC and further research is needed. [Table: see text] [Table: see text]
Discharge in less than 30 hours after an open radical retropubic prostatectomy. A prospective study
Authors: Café E. , Tannus M. , Nepomuceno E. , Quintiliano F. , Boente P. 
Published: August 2020

e16156 Background: Radical Retropubic Prostatectomy (RRP) is one of the most frequent surgery performed by urologists and it has been accompanied by an improvement in surgical results such as duration of hospitalization. In this study we prospectively analyzed the viability of an early discharge from hospital after an open RRP. Methods: There were 37 consecutive RRP performed by the same surgeon from March 1st to August 30th of 2007. All of the patients were informed about the possibility of discharge from hospital in less than 30 hours after the surgery. The procedures were performed using a modified Walsh technique under combined anesthesia (general anesthesia and epidural anesthesia p analgesia with morphine) through midline incision initiated approximately 5,0 centimeters below of umbilicus. Obturatory lymphadenectomy was performed in only three patients and Exclusion criteria included patients with an Body Mass Index above 30, patients who refused to participate in the study and those with prior indication to go to the intensive care unit postoperatively. Respiratory and motor physiotherapy were initiated soon after return from the surgical block. Criteria to discharge from hospital included: good acceptance of oral diet, no need for parenteral analgesics; urinary volume > 75 ml/hour; no Foley catheter obstruction; absence of gross hematuria; urine drainage < 150 ml/24 hours. Results: 32 patients (86%) had discharged from hospital in less than 30 hours after the surgery: there were 25 patients (68%) discharged in the first 24 hours after surgery and 07 patients discharged between 24 and 30 hours after surgery. There wasn't any readmission in a period of 15 days after discharge from hospital. There were only three complications (8%)on days 07, 10 and 13 and 01 patient need to wash an obstructed Foley catheter with blood clot at postoperative day four. Conclusions: By means of simple criteria it is possible to early discharge patients after an open RRP in selected patients and it may represent a significant reduction in costs. No significant financial relationships to disclose.
A review of the patterns of docetaxel use for hormone refractory prostate cancer (HRPC) at the Princess Margaret Hospital
Authors: Chin S. N. , Wang L. , Lau A. , Moore M. , Sridhar S. S. 
Published: August 2020

e16161 Background: Docetaxel is standard of care for the treatment of HRPC, based on two large randomized clinical trials. The aim of this study was to determine if docetaxel use and effectiveness in routine clinical practice was similar to that seen in the TAX 327 randomized phase III clinical trial. Methods: A retrospective chart review was undertaken to assess patterns of docetaxel use for HRPC at our institution for the 2-year period since its approval for the first-line treatment of HRPC in 2005. Results: Eighty-eight patients, median age 71 and baseline PSA 107, received docetaxel in the first line setting. Main reasons for initiating docetaxel were rising PSA (90%) and progressive symptoms (71%). Eighteen percent of patients received docetaxel for rising PSA alone. A median of 7 cycles was administered. PSA response rates were 61%, time to response 1.5 months, and response duration 6.8 months. Disease progression was the most common reason for treatment discontinuation (36%). Main toxicities were fatigue (32%) and neuropathy (22%). Kaplan Meier survival analysis showed median duration of survival was 15.9 months (95% CI 12.4–20.5) from first drug use. 1-year survival was 0.63 (95% CI 0.52–0.72). Post-docetaxel, 36 patients received second-line treatment, mostly with mitoxantrone (89%). Second-line response rates were 22%, and median duration of response was 4 months. Conclusions: In routine clinical practice, docetaxel is a well-tolerated regimen for the treatment of HRPC. Response rates and toxicity profiles were comparable to the randomized trials. However, compared with the TAX 327 clinical trial, survival was slightly shorter than expected (15.9 vs. 18.9 months), possibly due to inclusion of patients with poorer performance status and comorbidities, who may be excluded from clinical trials. Second-line response rates were also comparable with previous reports. No significant financial relationships to disclose.
Demographics, response, and overall survival of patients with advanced renal cell cancer to sunitinib in a cohort of minority patient population
Authors: Shah M. , Sreenivasappa S. , Kouz R. , Ciobanu B. , Mullane M. , Yim B. 
Published: August 2020

e16164 Background: Sunitinib is a tyrosine kinase inhibitor active in renal cell cancer (RCC). There is scanty literature of its efficacy in minority population. Methods: 21 patients (pts) with RCC who received sunitinib between February 2006-September 2007 were identified and studied as a retrospective cohort. Clinical and survival data were analyzed using fisher's test, chi square test, Kaplan Meier analyses. Results: Of the 21 patients, 11 (52%) were female and 10 (47%) male, 7 (33.3%) African American, 7 (33.3%) Hispanic, and 5 (23.8%) Caucasian. Median age at diagnosis was 59 years (32–74). 7 (33.3%) had clear cell and 3 (14.3%) sarcomatoid pathology. Mixed, poorly differentiated, papillary and unknown histology were 2 (9.5%) each. 12 (57%) pts had stage 4 disease at diagnosis, stage 3 in 3 (14.3%), stage 2 in 1 (4.8%) and 5 (23%) had missing data. 14(66.7%) pts underwent nephrectomy while 7 (33.3%) did not. 6 (28.6%) pts has good MSKCC risk score, 11 (52.4%) intermediate risk and 3 (14.3%) poor risk. Sunitinib was given at a dose of 50 mg daily for 4 wks followed by 2 wks off. Median duration of treatment was 2.5 months (0–9 mts) and median follow up was 13 mts (1–21 mts). Common grade 3–4 toxicities observed were hand foot syndrome (n = 2), hypertension (n = 2) and thrombocytopenia (n = 1). 4 pts discontinued therapy due to adverse events. 5 (23.8%) has stable disease and 13 (61.9%) had progressive disease. Response to sunitinib was not influenced by sex, race, performance status, MSKCC Score, serum calcium level, LDH and hemoglobin level. Median survival of the group was 4 mts with no difference based on gender (p = 0.8), ethnicity (p = 0.8) or histologic type (p = 0.7). Survival of pts with ECOG performance status (PS) 1 was 8 mts, PS 2 was 4 mts, PS 3 was 2 mts (p = 0.001), MSKCC good risk was 9.4 mts, intermediate score was 9.4 mts and poor risk was 2 mts (p = 0.18). Hemoglobin (p = 0.6), LDH (p = 0.6), calcium (p = 0.2) did not affect the survival. Conclusions: In this minority cohort of pts with RCC treated with sunitinib, response and median survival is much lower than the historical controls. Tolerability and side effect profile are similar to reported literature. Prospective studies are warranted in the treatment of RCC with sunitinib in ethnic minority population. No significant financial relationships to disclose.
The efficacy of systemic lymphadenectomy for overall survival in epithelial ovarian cancer: A systematic review and meta-analysis by KOGYMAG
Authors: Kim H. , Ju W. , Jee B. , Kim J. , Song Y. , Lee H. 
Published: August 2020

e16509 Background: The role of systemic lymphadenectomy remains unclear for improving overall survival in epithelial ovarian cancer (EOC) till now. To evaluate the efficacy of systemic lymphadenectomy for survival in EOC, Korean Gynecologic Meta-analysis Group (KOGYMAG) performed a meta-analysis of all studies which compared systemic lymphadenectomy versus non-systemic lymphadenectomy (not performed or lymph node sampling). Methods: Studies were retrieved by searching PubMed, Embase, and Cochrane Controlled Trials Register (CENTRAL) electronic database. The literature search was conducted between 1995 and 2008. The meta-analysis was carried out on 11 studies (2 randomized controlled and 9 retrospective studies) and a total of 30,534 patients with EOC who underwent staging laparotomy including systemic lymphadenectomy or nonsystemic lymphadenectomy. The study endpoint was overall survival, and we extracted adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival from all studies and obtained pooled estimates using an inverse-variance model. Results: In all studies, systemic lymphadenectomy was a favorable factor for overall survival as compared to non-systemic lymphadenectomy (HR, 0.76, 95% CI, 0.65 to 0.88; random-effects model). When we performed sub-analysis according to disease status, patients treated with systemic lymphadenectomy showed improved overall survival compared to those with non-systemic lymphadenectomy in 3 studies where only patients with early-stage EOC (FIGO stage I-II) were included (HR, 0.70; 95% CI, 0.63 to 0.77; fixed-effects model). Furthermore, systemic lymphadenectomy was also a significant factor for improved overall survival in 5 studies where only patients with advanced-stage EOC (FIGO stage III-IV) were enrolled (HR, 0.91; 95% CI, 0.85–0.96; fixed-effects model). Conclusions: These results support that systemic lymphadnectomy may improve overall survival in patients with EOC. However, there are some limitaions including few randomized controlled studies and the deviation of weight in this meta-analysis. Thus, large-scale randomized controlled trials are required to evaluate the efficacy of systemic lymphadenectomy in EOC. No significant financial relationships to disclose.
Regulation of the EGFR-E2F3a axis by the interferon regulatory factor (IRFs) and by promoter methylation of miR-34a in ovarian cancer
Authors: Reimer D. , Hubalek M. , Riedle S. , Skvortsov S. , Erdel M. , Mueller-Holzner E. , Marth C. , Altevogt P. , Zeimet A. G. 
Published: August 2020

e16522 Background: Although, EGFR targeting has reached “bedside” in various tumor entities, including ovarian cancer, the essential role of E2F3a in EGFR mediated proliferation remained uncovered. Recently, we outlined the clinical relevance of E2F3a in ovarian cancer. Now we were able to elucidate the pathway between EGFR activation and E2F3a induction. Methods: Promoter mapping of E2F family members was assessed using the JASPER software. E2F3a protein was assessed by immunoblot analyses in siRNA based IRF-1, IRF-2 knockdown HOC-7 cells. Cell growth was determined by MTT assays after siRNA based knockdown of E2F3a. Expression of E2F3a regulating miR-34a, miR-210 and miR-20a were assessed by RT-PCR in 130 ovarian cancer patients and methylation status of the E2F3a promoter and of miRNA promoters were estimated using Methyllight. 6p22 amplification status of patients was determined by FISH analyses. Results: Promoter mapping of E2F family members revealed that IRF-1 and IRF-2 are potential intermediate components of the herein described EGFR-E2F3a axis. As evidenced by knock-down of IRF-1, IRF-2 or both, the ratio between the two mutually antagonistic IRF-1 and IRF-2 was found to be substantial for EGF induced E2F3a up-regulation. E2F3a knock-down yielded a complete abolishment of EGF induced cancer cell proliferation. Although, activated EGFR status showed a highly significant correlation with E2F3a expression, a subgroup of patients presented high E2F3a mRNA levels without EGFR activation. Within this subgroup promoter methylation of miRNA-34a, that regulates E2F3a, was revealed to represent an alternative mechanism of E2F3a regulation in ovarian cancer, whereas promoter methylation of E2F3a itself was not relevant in E2F3a control. Unlike in prostate or bladder cancer 6p22 amplification was not found to be relevant for E2F3a up-regulation in ovarian cancer. Conclusions: Our present data point to the substantial role of the ratio between IRF-1 and IRF-2 in EGFR mediated E2F3a induction. Furthermore, in vivo regulation of E2F3a involves methylation and thereby silencing of miR-34a. Targeting of the herein described molecular pathway, downstream EGFR, could represent an appealing therapeutic approach in ovarian cancer. No significant financial relationships to disclose.
Prognostic factors in ovarian cancer patients with brain metastases: Results of a German multicenter study
Authors: El Khalfaoui K. , Oskay-Ozcelik G. , Richter R. , Pietzner K. , Harter P. , Münstedt K. , Mahner S. , Hasenburg A. , Wimberger P. , Sehouli J. 
Published: August 2020

e16527 Background: Ovarian cancer is one of the leading causes of mortality in women with gynaecological malignancies. Brain metastases from ovarian cancer are rare. Up to this point there are only few data about prognostic factors for this patient collective. Methods: Within a period between 1981 and 2008 we analyzed 4,277 women with histologically confirmed ovarian cancer from six different German hospitals. Overall 72 women with brain metastases and two cases of meningosis carcinomatosa were identified, these resulting in an incidence of 1.73%. Results: The median age at the diagnosis of central nervous system (CNS) metastases was 58 years (range, 33–83). The median interval between the time of the first diagnosis of ovarian cancer and the occurrence of CNS metastases was 28.8 months (range, 3.6 -133.1). The median overall survival time after diagnosis of CNS metastases was 6.1 months (range, 0.2 -41.5). Multiple brain metastases were observed in 58 women (78.4%). Headache (36.5%), vomiting and nausea (17.1%) were the most frequent clinical symptoms. According the multivariate analysis following clinical parameter reached statistical significance: multiple lesions (hazard ratio (HR): 4.1, 95% confidence intervaI (CI): 1.9 to 8.9), grading I und II (HR: 2.8, 95% CI: 1.6 to 5.0) were associated with a negative impact on overall survival. Platinum sensitivity (HR: 0.28, 95% CI: 0.15 to 0.52) and the application of multimodal therapy strategies (surgery, radiotherapy and chemotherapy) (HR: 0.51, 95% CI: 0.28 to 0.92) and the good performance (HR: 0.52; 95% CI: 0.25 to 1.08) showed a positive impact on overall survival. Tumour histology, ascites and age at the CNS diagnosis were not significant for the survival. Conclusions: Next to the presence of multiple brain lesions and the performance status, the sensitivity to platinum based chemotherapy has an important positive impact on overall survival. This should be considered in the conduction of multimodal therapy strategies for brain metastases from ovarian cancer. No significant financial relationships to disclose.