bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of clinical outcome in patients with bone metastases from prostate cancer
Authors: Saad F. , Coleman R. E. , Cook R. , Smith M. R. , Brown J. E. , Hei J. Y. , Chen Y. M. 
Published: March 2020

4555 Background: Bone metastases are a significant cause of morbidity in patients with prostate cancer (PC). To assess the predictive value of bone markers and fractures for clinical outcome in patients with bone metastases from PC, we conducted a retrospective analysis of patients in a large, randomized, controlled trial of zoledronic acid. Methods: Data were analyzed in patients treated with 4 mg zoledronic acid or placebo who had bone marker (n = 411) or fracture (n = 640) information. Cox regression models, adjusted for treatment group, were used to assess the association between bone markers (urinary N-telopeptide [NTX] and bone alkaline phosphatase [BALP]) or fractures (time-dependent variable) and the risk of death or of experiencing a first skeletal-related event (SRE) on study. For bone marker analyses, patients were grouped by low (< 50 nmol/mmol creatinine), moderate (50 to 99), or high (≥ 100) NTX levels and by low (< 146 U/L) or high (≥ 146) BALP. Results: Patients who experienced a fracture on study (19%) had shorter survival compared with patients who did not; the hazard ratio for death was 1.29 (95% CI = 1.01, 1.65; P = .04), suggesting 29% increased risk of death among these patients. When adjusted for previous SRE and baseline ECOG performance status ≥ 2, the risk for death associated with fractures was increased by 23% and trended toward statistical significance (P = .10). Patients with high NTX levels had significantly increased risk of SREs and disease progression (P < .001) compared with patients with low NTX. Relative to low NTX levels, high and moderate NTX levels were associated with a 5.72-fold (95% CI = 4.04, 8.11; P < .001) and 4.10-fold (95% CI = 2.81, 5.97; P < .001) increased risk of death, respectively. High BALP also significantly correlated with an increased risk of a first on-study SRE (P = .028) and bone lesion progression (P < .001). Conclusions: These analyses suggest that pathologic fractures are associated with increased risk if death and that high bone marker levels are associated with increased risk of SREs, bone lesion progression, and shorter survival in patients with PC and bone metastases. The results support appropriate treatment for the prevention of fractures and to decrease bone marker levels. [Table: see text]
CALGB 90207: Phase II trial of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma (TCC)
Authors: Rosenberg J. E. , Halabi S. , Sanford B. L. , Himelstein A. L. , Atkins J. N. , Hohl R. , Seagren S. L. , Bajorin D. F. , Small E. J. 
Published: March 2020

4582 Background: No standard 2nd-line chemotherapy exists for metastatic TCC. Response rates to 2nd-line chemotherapy for advanced TCC are low and response duration tends to be short. Bortezomib is a proteasome inhibitor with preclinical activity against TCC. Methods: Twenty-five patients with advanced TCC who had been previously treated with combination chemotherapy were enrolled in a multi-institutional single-arm trial from December 2003 through April 2005. Treatment consisted of bortezomib 1.3 mg/m2 intravenously twice weekly for two consecutive weeks, followed by a 1-week rest period. The primary endpoint was objective response rate by RECIST criteria. Secondary endpoints included safety, toxicity, progression-free survival, and overall survival. Results: The median age was 65.5 yrs (59–7-74.9) and the median number of years since diagnosis was 1.4 (0.9–3.6). 72% of patients were male. 65% of patients had visceral metastases, and 20% of patients had lymph node-only metastases. Prior chemotherapy regimens included gemcitabine/cisplatin (50%), gemcitabine/carboplatin (25%), paclitaxel/carboplatin (5%), single agent paclitaxel (5%), and other multi-agent regimens (15%). Median hemoglobin was 11.4 g/dL (inter-quartile range 10.6–12.3). No objective responses were observed. The median time to progression was 2.1 months (95% CI= 1.4–5.5). Median overall survival was 5.5 months (95% CI= 3.6–8.1). Toxicity was modest. Grade 3/4 drug-related toxicities included thrombocytopenia (6%), sensory neuropathy (6%), hyperglycemia (6%), neuropathic pain (6%), dehydration (6%) and vomiting (6%). There were no treatment-related deaths. Conclusions: Although bortezomib is well tolerated in patients with previously treated advanced TCC, it does not have anti-tumor activity as 2nd-line therapy in TCC. No significant financial relationships to disclose.
Evaluation of prognosis in relapsed germ cell tumors: Identification of patients who profit from high dose chemotherapy (HDCT)
Authors: Sammler C. , Beyer J. , Bokemeyer C. , Hartmann J. , Siegert W. , Rick O. 
Published: March 2020

4585 Background: To identify prognostic variables in patients (pts) with metastatic germ cell tumors (GCT) and relapse or progression after first-line chemotherapy (FLC). Methods: In our database of 257 GCT pts treated with HDCT, 176/257 (67.4%) pts with first relapse or progression were identified. All patients had received platinum-based FLC. As salvage treatment all pts had received 1–3 cycles of conventional-dose salvage chemotherapy (CDCT) followed by one cycle HDCT. First, pts were retrospectively classified according to a prognostic score developed for CDCT by Fossa et al. [Br J Cancer 1999,80:1392], based on variables present at the time of relapse. Thereafter, a multivariate analysis was performed to evaluate further risk factors. Results: After a median follow up of 9 years the event-free survival (EFS) and overall survival (OS) for all 176 patients was 34% and 38%, respectively. Patients with good (n= 100/176, 57%) and poor (n = 76/176, 43%) prognosis in accordance to Fossa et al. showed an EFS of 41% and 26% (p < 0.01) and an OS of 47% and 26% (p < 0.01). Thus, in contrast to the data of Fossa et al, long-term survival could be demonstrated even in the poor prognosis subset. In the multivariate analysis, the level of elevated tumor markers alfa-fetoprotein and human chorionic gonadotrophin (p < 0.01), the presence of extrapulmonal visceral metastases (p < 0.01) and refractoriness to cisplatin (p < 0.01) adversely influenced OS after HDCT significantly. Based on these latter factors three different groups with increasingly poor OS could be identified: none factor (n = 39/176, 22%) 4 year OS of 59%, one factor (n = 78/176, 44%) 6 year OS of 42% and more than one factor (n = 59/176, 34%) 4 year OS of 17%. Conclusion: In pts with first relapse or progression after platinum-based FLC high serum tumor markers, presence of extrapulmonal visceral metastases and cisplatin refractoriness proved to be independent prognostic significance for OS after salvage HDCT. However, even in the poor prognosis subset long-term survival could be demonstrated. No significant financial relationships to disclose.
Salvage chemotherapy with paclitaxel, ifosphamide and nedaplatin for cisplatin refractory germ cell tumors
Authors: Miki T. , Mizutani Y. , Nomoto T. , Nakamura T. , Kawauchi A. , Oka D. , Nishimura K. , Nonomura N. , Okuyama A. 
Published: March 2020

4587 Background: Only 20–30 % of patients with cisplatin (CDDP) refractory germ cell tumor (GST) will remain continuously disease free with salvage chemotherapy. The present study investigated the chemotherapy with paclitaxel (TXL) in combination with ifosphamide (IFM) and nedaplatin (NDP), which is a derivative of CDDP, as salvage chemotherapy for CDDP refractory GCT. Methods: Between 2000 and 2005, 33 patients with CDDP refractory GCT were enrolled. All patients were male, with median age 30 (range: 17–45). Median number of previous regimens was 2 (range: 1–4). The combination chemotherapy consisted of TXL: 200 mg/m2 on day 1, NDP: 100 mg/m2 on day 2 and IFM: 1.2 g/m2 on day 2–6 every three weeks. Results: A median of 5 cycles was administered to 33 patients. Grade 3/4 toxicity were reported as follows: neutropenia: 90%, thrombocytopenia: 70%, anemia: 70%, nausea/vomiting: 90%, diarrhea: 6%, alopecia: 97%. No treatment related death was observed. Response rate was 82% (CR: 9%, PRm−: 67%, PRm+: 6%, NC: 6%, PD: 6 %). Nineteen (58%) patients achieved a no evidence of disease status with a median duration of follow-up of 18 months (7–60 months). Six patients (18%) remain alive with disease. However, 8 patients (24%) died of the disease. Conclusions: This study demonstrates that the chemotherapy with TXL in combination with IFM and NDP showed a significant anticancer activity for patients with CDDP refractory GCT. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for CDDP refractory GCT. No significant financial relationships to disclose.
POMB-ACE therapy for patients with international germ cell cancer collaborative group (IGCCCG) poor risk germ cell tumors (GCT): The USC experience
Authors: Dorff T. B. , Rupani R. , Wei D. T. , Groshen S. , Pinski J. , Raghavan D. , Quinn D. , Aparicio A. 
Published: March 2020

4591 Background: Patients with poor-risk GCT have low rates of cure with standard therapy, with 3 year overall survival (OS) reported at 50% (IGCCCG, JCO 1997). POMB-ACE is a rapidly alternating, dose dense chemotherapy regimen developed to improve outcomes in this population, with reported 3 year OS of 75% (Bower et al, Ann Oncol 1997). We report our experience with this regimen, including analysis of acute and long-term toxicity. Methods: Subjects with poor-risk GCT, defined by IGCCCG criteria as AFP >10,000, bHCG >50,000, LDH > 10 × ULN, non-testicular primary, or non-pulmonary visceral metastases, who were diagnosed at Los Angeles County General Hospital and USC/Norris Cancer Center between 1998 and 2005 were identified using pathology and admission records. All clinical notes and laboratory data were reviewed. Results: Of 23 poor-risk GCT patients identified, 21 received POMB-ACE; 16 were treated at the county facility. 15 patients were Hispanic. 5 had primary mediastinal tumors. 16 were stage IIIC, 4 stage IIIB, and 1 stage IIIA. The median number of cycles was 8 (range 4–12), with a median interval between treatment cycles of 14 days (range 10–39). There were no treatment-related deaths. Febrile neutropenia occurred in 5.9% of treatment cycles, grade 3/4 hematologic toxicity in 19%, and other Grade 3/4 non-hematologic toxicities in 9.8%. G-CSF support was used with 24% of cycles. Nineteen patients (90%) had a partial response, of whom 8 underwent surgery for residual disease; only 1 had residual active tumor, 4 teratoma. Marker-negative status was achieved in 5 patients (23.8%). With median follow-up of 28 months, 9 subjects have recurred (43%) and 4 have died of disease progression. The estimated 2 year disease-free survival is 54%, and 3 year OS 75%. At the end of treatment, residual neuropathy persisted in 2 patients (9.5%), renal compromise in 2 (9.5%), pulmonary toxicity in 3 (14%), and otoxicity in 1 patient (4.7%). Conclusions: In our modern North American experience, POMB-ACE is feasible to administer, even in an uninsured population. This is an effective option in poor-risk GCT patients, with 3 year OS exceeding that achieved with standard therapy. Acute toxicity is modest, however persistent adverse sequelae are common. No significant financial relationships to disclose.
Observational study in patients with pulmonary metastases of renal cell carcinoma receiving inhaled recombinant interleukin-2 (rIL-2)
Authors: García A. G. , Esteban E. , Girón C. G. , Maroto P. , Andrés R. , Canelas A. , Caballido J. , Carles J. , Espinosa E. , Lacave A. J. 
Published: March 2020

4603 Background: Patients with metastatic renal cell carcinoma have a poor prognosis, including those with pulmonary metastases (PMRCC). The objective of this study was to obtain efficacy and safety data on inhaled rIL-2 used in clinical practice in PMRCC patients. Methods: Data provided from 107 PMRCC patients from 48 centres in Spain and 6 in Portugal, treated with inhaled rIL-2 between 2000 and 2005 were evaluated. Data were analyzed by ITT, considering a valuable patient when receiving the first dose of inhaled rIL-2. The treatment schedule was: 3 cycles of 36 MIU rIL-2 per day for 5 days/week for 12 weeks (with one week treatment free between cycles) in Spain and for 3 weeks (out of each 4 weeks) for 12 weeks in Portugal. Efficacy was assessed by best response following each treatment cycle and overall (WHO criteria). The Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS) that were measured from the time of administration of the first dose of inhaled rIL-2 until progression or death. Safety data were analysed using descriptive statistics, with toxicities expressed as number of weeks in which each toxicity was reported by cycle and by grade. Results: After 1902 treatment weeks administered (median 17.8), the overall objective response rate (complete and partial response,) was 12.2% (95% CI: 6.0–18.4) and a stable disease rate of 22.45% (95% CI: 14.5–30.3). Median PFS and OS were 3.72 (95% CI: 2.86–4.57) and 18.5 (12.69– 23.61) months, respectively. Non-haematological toxicities were the most notable adverse events observed, especially in terms of cough (20.4% of weeks) and fatigue (4.4%) being grade 1 or 2 in severity and reversible by removing the treatment in all cases. Conclusions: This study provides data of efficacy and mild toxicity of inhaled rIL-2. On the basis of these findings inhaled rIL-2 might be considered as an alternative to its systemic administration to treat patients with PMRCC. No significant financial relationships to disclose.
Comparative expression profiling with kinetic RT-PCR in paired fresh frozen and archived formalin-fixed, paraffin-embedded renal cell cancer and normal tissue
Authors: Hennig G. , Paus H. , Atkins D. , Störkel S. 
Published: March 2020

4606 Background: It would be a substantial progress if gene expression of tumor markers could be accurately analyzed on RNA isolated from formalin fixed paraffin-embedded (FFPE) tumor tissue which is routinely collected. To prove equivalence between fresh frozen and archived FFPE tissue RNA profiles, we quantified 12 different genes with kinetic RT-PCR in renal tumor and paired adjacent normal tissue archived for 8–14 years. Methods: We had access to a set of 32 clear cell renal cell cancers and its adjacent normal tissue (HELIOS Clinic, Wuppertal). Each sample existed as a FFPE tissue block and as paired fresh frozen tissue both stored over 8–14 years at RT or -80oC, respectively. RNA from FFPE tissue was isolated with a Bayer HealthCare internal silica bead-based isolation method. Each sample was analyzed with kinetic one-step RT-PCR for the gene expression of 3 housekeepers (RPL37A, GAPDH, CD63) and 9 candidate genes (EGFR, Her2/neu, Her3, Her4, EGF, TGFα, NRG1, HIF1α, VEGFα). Results: The comparative FFPE/fresh frozen expression data showed a good correlation over all data points (r = 0.87 for Ct values) and the tumor specific up- and down regulation of EGFR family genes and its ligands could be detected in both tissue types equally. We could clearly demonstrate the tumor specific up-regulation of EGFR (2-fold), TGFα (2-fold), VEGFα (4-fold) and down-regulation of EGF (60-fold), Her2/neu (4-fold), Her3 (2-fold) and Her4 (30-fold) in renal cell cancer for both tissue entities (fixed and fresh frozen). In addition a 3-dimensional Principal Component Analysis completely separated the renal tumor population from paired normal tissue in both tissue entities based on the differential gene expression. Conclusions: Here we demonstrate that a small set of genes from the EGFR family and their ligands is specifically up-/down-regulated in renal cell cancer tissue and therefore can be clearly distinguished from normal renal tissue. Furthermore, these data prove that the internal Bayer HealthCare isolation/kinetic RT-PCR detection protocol for RNA from FFPE tissue allows accurate retrospective expression profiling and validation of marker panels in archived tissue material stored for more than a decade. [Table: see text]
A phase II trial of docetaxel and samarium in patients with bone metastases from castration-refractory prostate cancer (CRPC) and a response or stabilization after induction docetaxel-estramustine
Authors: Laplanche A. , Beuzeboc P. , Lumbroso J. , Di Palma M. , Theodore C. , Prapotnich D. , Escudier B. , Bouzy J. , Haddad V. , Fizazi K. 
Published: March 2020

4608 Background: Most patients (pts) with disseminated CRPC have bone metastases. Samarium is a radio-isotope with a high affinity to bone. Docetaxel is currently the standard of care in CRPC. We assess the efficacy of combining docetaxel and samarium as consolidation treatment after docetaxel-estramustine in pts with CRPC. Methods: This is a prospective, bi-center phase II trial. Pts with bone metastases from CRPC received docetaxel 70 mg/m2 day 2 + estramustine 10 mg/Kg/day, day 1–5 (1 cycle every 3 weeks). Pts with a response or stabilization after 4 cycles were given consolidation therapy: docetaxel 20 mg/m2/week x 6 weeks + samarium 1 injection during week 1 (37 MBq/Kg). Zoledronic acid was routinely used and was stopped 1 month before samarium infusion. This study used a Simon two-step design with a final target of 39 pts receiving the consolidation treatment. Biological responses were defined according to the working group criteria (Bubley, J Clin Oncol 1999). The primary endpoint was progression-free survival (PFS). Results: From 01/2004 to 12/2005, 43 pts were included in the trial and the accrual is over. Of the 39 pts currently fully evaluable after induction treatment, 28 (72%), 10 (26%) and 1 (3%) achieved a PSA response, stabilization, and progression, respectively. Of 30 pts currently evaluable after consolidation treatment, 20 (65%), 5 (16%) and 5 (16%) achieved a PSA response, stabilization, and progression, respectively. A pain response (defined as a decrease in pain intensity by at least 2/10 on a pain analog visual scale in pts with a baseline pain level ≥ 2/10) was achieved in 89% (16/18) after consolidation treatment. The consolidation docetaxel-samarium regimen was feasible with most pts experiencing a mild (grade 1–2) and rapidly reversible thrombocytopenia at week 5. Data on PFS and overall survival are pending. Conclusions: Combining docetaxel and samarium is feasible and well-tolerated. It yields a high PSA response rate and a major pain improvement in pts with bone metastases from CRPC. [Table: see text]
Predictors of overall and cancer-specific survival in patients with clinically localized prostate cancer (PC) treated with primary androgen deprivation therapy (PADT): Results from the Prostate Cancer Outcomes Study
Authors: Graff J. , Mori M. , Li H. , Garzotto M. , Penson D. , Potosky A. , Beer T. M. 
Published: March 2020

4610 Background: Use of PADT as sole therapy for clinically localized PC is rapidly increasing, despite little evidence to support this approach. We examined predictors of overall survival (OS) and cancer-specific survival (CSS) using the data available from the Prostate Cancer Outcome Study (PCOS). Methods: PCOS recruited 5,672 patients between 1994 and 1995, within 6 months of PC diagnosis. Vital status was last updated in 12/02. 276 patients had clinically localized PC and received PADT. We examined the relationship between baseline demographic, socio-economic, and tumor factors and OS and CSS using Kaplan-Meier and Cox regression methods implemented in the SUDAAN software. Results: Of 276 patients, 148 patients have died, 35 from PC. The median age at diagnosis was 75 (50–88). The average follow-up of censored subjects was 7.6 yrs (1.1–8.1). 5-year OS was 66% (95% CI: 69–72), while the 5-year CSS was 91% (95% CI: 86–94). In the multivariate analysis (see Table), age, serum PSA at diagnosis, and Gleason score were the only independent predictors of OS. Abnormal DRE was marginally significant. The Gleason score (≥7) was the only independent predictor of CSS (HR 4.0, p = 0.04); PSA ≥ 20 (HR 2.38, p = 0.09) approached significance. This analysis was limited by a smaller number of deaths due to prostate cancer (n = 35). Conclusions: In an analysis that included a broad range of demographic and socio-economic factors, overall survival of patients with clinically localized prostate cancer treated with PADT was predicted by age and measures of tumor biology (Gleason score) and tumor mass (serum PSA). Thus, cancer remains an important contributor to overall mortality in these patients, particularly those with high Gleason score and high serum PSA. These data can be used to inform patients regarding their individual 5-year survival if they choose PADT for the treatment of their clinically localized prostate cancer. [Table: see text] No significant financial relationships to disclose.
Evaluating high-grade prostatic intraepithelial neoplasia as a predictor of outcome following radical prostatectomy
Authors: Pierorazio P. M. , Lambert S. M. , McCann T. R. , Katz A. E. , Olsson C. A. , Benson M. C. , McKiernan J. M. 
Published: March 2020

4612 Background: The presence of high-grade prostatic intraepithelial neoplasia (HGPIN) has been associated with future development of prostate cancer. High-grade intraepithelial neoplasia in other malignancies is associated with adverse outcome. This study examines the relationship between the presence of HGPIN in prostatectomy specimens, biochemical disease free survival (bDFS) and other cancer specific outcomes following radical retropubic prostatectomy (RRP). Methods: The Columbia University Urologic Oncology Database was reviewed and 2,522 were identified who had undergone radical prostatectomy from 1988 to 2005; 2,133 patients with or without HGPIN were included. Two-sample proportion analysis of means with 95% confidence intervals and ANOVA techniques were used to evaluate the relationship between HGPIN and pathologic stage, Gleason sum, perineural invasion, multifocality, extracapsular extension (ECE), margin status, and nodal status. Kaplan-Meier analysis with log-rank test and a multivariate Cox proportional hazard model controlling for preoperative PSA, Gleason sum and pathologic stage were used to assess differences in bDFS. Results: 1,885 of 2,133 (88.4%) patients demonstrated HGPIN. There was no significant difference in the distribution of pathologic stage or Gleason sum between the patients with and without HGPIN. The HGPIN-positive group had higher rates of perineural invasion (69.9 vs. 57.5%; p = 0.003), multifocality (63.0 vs. 38.4%; p = 0.000) and ECE (56.4% vs. 48.4%; p = 0.059). There was no statistically significant difference observed in nodal status or margin status between the two groups. Patients without HGPIN had an increased bDFS demonstrated by a predicted disease free survival of 73.6% versus 67.0% at 9 years (p = 0.045) with a median follow-up of 50 months. In the multivariate Cox hazard model HGPIN, PSA, Gleason sum and pathologic stage were validated as independent predictors of failure (p < 0.001). The risk of failure was 1.9 × greater in the HGPIN-positive group than the HGPIN-negative group (p=0.006). Conclusions: The presence of HGPIN in the radical prostatectomy specimen denotes a significantly higher rate of tumor multifocality, perineural invasion, ECE, and ultimately biochemical recurrence. No significant financial relationships to disclose.