bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 70-gene profile and chemotherapy benefit in 1,600 breast cancer patients
Authors: Bender R. A. , Knauer M. , Rutgers E. J. , Glas A. M. , de Snoo F. A. , Linn S. C. , Van 't Veer L. J. 
Published: August 2020

512 Background: The 70-gene expression profile (MammaPrint) is validated as an independent prognostic indicator for breast cancer patients with T1–2 node-negative and positive disease regardless of estrogen receptor status. Here we present the relationship between MammaPrint outcome and chemotherapy benefit in the adjuvant setting. Methods: We performed a pooled analysis of 1,637 patients with MammaPrint outcomes (T1–2, node-negative and positive invasive breast cancer and median FU 7.1 yrs) to determine the chemotherapy benefit of patients treated with adjuvant chemotherapy in addition to endocrine therapy. Patients were collected from 7 large datasets at multiple institutions across Europe. Results: In this meta-analysis, MammaPrint assigned 772 patients (47%) to “low risk” and 865 (53%) to “high risk”. In total 349 patients were treated with endocrine therapy alone, whereas 226 were treated with both chemo- and endocrine therapy. Patients with poor prognosis MammaPrint profile had a substantial benefit from chemotherapy: At 5 years, distant disease-free survival was improved from 69% to 88% (HR 0.28 (95% CI 0.14–0.56, p<0.001) when chemotherapy was added to hormonal therapy. The results remained significant in multivariate analysis including stratification by standard clinico-pathologic prognostic factors. Patients classified by MammaPrint as good prognosis (“low risk”) had no significant benefit from chemotherapy (p=0.962). Conclusions: The 70-gene MammaPrint profile is not only a strong and independent prognostic indicator for patients with early stage breast cancer, but it may also be predictive for the benefit of chemotherapy. While MammaPrint “high risk” classified patients demonstrate a clear benefit from adjuvant chemotherapy added to hormonal therapy, patients classified by MammaPrint as “low risk” for recurrence do not appear to benefit from the addition of chemotherapy to hormonal treatment alone. [Table: see text]
Defining the role of patient navigators for men with an abnormal prostate cancer screening test result in an urban setting
Authors: Hamer S. , Nonzee N. J. , Simon M. A. , Liu D. , McKoy J. M. , Byer P. J. , Feinglass J. , Rademaker A. , Calhoun E. A. , Bennett C. L. 
Published: August 2020

5120 Background: Though several navigation programs have aimed to reduce cancer health disparities, few have evaluated the role of patients’ race/ethnicity on patient navigator activities. We report preliminary data on types of encounters and actions taken to prevent delays in prostate cancer diagnosis or treatment for 82 veterans enrolled in the NCI-funded Patient Navigation Research Program in Chicago. Methods: Male lay patient navigators and a social worker recorded encounter types, perceived or patient-identified barriers, and actions taken to prevent or resolve patient barriers to follow-up after identification of an abnormal finding for prostate cancer. Results: Of our study participants, half were African-American, 57% had an annual income of less than $30,000, 68% were unemployed, 43% were married, and the mean age was 66 years old. The most common type of patient navigator encounters included phone calls with the patient and in-person visits at the hospital, 64% and 32% respectively. Two-thirds of encounters on behalf of the patient lasted less than 15 minutes. Almost all patient navigator actions resulted from proactive case management. The most common navigator actions taken were providing support, making referrals to health providers or community resources, and verifying appointments, 32%, 29%, and 15%, respectively. There was a significant difference between African-American versus White patients with respect to type of encounter and length of encounters (p=0.002 and <0.0001, respectively) but not actions taken. Conclusions: Patient navigator activity for our study thus far largely consisted of proactive management of patient- and system-related barriers as opposed to reactive response to patient-identified barriers. Future navigation programs should consider tailoring gender- and culturally-matched interventions for their patients. [Table: see text] No significant financial relationships to disclose.
Local variation in primary treatment of localized prostate cancer
Authors: Cooperberg M. R. , Broering J. M. , Carroll P. R. 
Published: August 2020

5126 Background: We aimed to characterize and quantify variation in the primary management of localized prostate cancer at the level of clinical practice sites. Methods: Data were abstracted from patients accrued to the CaPSURE national prostate cancer registry. Patients were accrued from the 36 clinical practice sites which contributed at least 30 patients to the registry, and represented all those diagnosed since 1990 with localized disease who received radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy, active surveillance / watchful waiting (WW), or primary androgen deprivation therapy (PADT) were included. Descriptive analyses were performed, and a random effects logit hierarchical model was constructed, controlling for year of diagnosis, age, comorbidity, PSA, Gleason score, clinical T stage, and percent of biopsy cores positive, to estimate the proportion of variation in primary treatment selection explicable by practice site. Analyses were conducted for all patients and for low-risk patients (Gleason score ≤6, PSA ≤10 ng/ml, clinical stage ≤T2a). Results: 10,080 men were analyzed. The distribution among primary treatments at each clinical practice site varied widely: use of RP, for example, ranged from 12% to 95% of enrolled patients. Patterns of treatment are not reliably explained by patient risk distribution at each site. The proportion of variation attributable to clinical practice sites was 10% for PADT, 19% for WW, 21% for EBRT, 28% for RP, 37% for brachytherapy, and 75% for cryotherapy. For low-risk patients only, this proportion was higher for all treatment types except brachytherapy and cryotherapy. Only a small amount of the variation attributable to practice site can be explained by measured sociodemographic factors such as ethnicity, income, education, and geographic region. There are significant trends in treatments over time, including more use of PADT for intermediate- and high-risk patients, and more use of RP and WW for low-risk patients. Conclusions: These data do not represent a random sampling of the United States population. However, the significant variation in practice patterns across individual clinical sites suggests that factors other than patient clinical and sociodemographic factors may be driving selection of primary treatment. [Table: see text]
A randomized double blind phase I-II study to determine the tolerability/efficacy of two different doses of lenalidomide (L), CC- 5013, in biochemically relapsed (BR) prostate cancer (PC) patients (pts) (M0) after local treatment (LT)
Authors: Sinibaldi V. J. , Carducci M. A. , Moore-Cooper S. , George B. , Denmeade S. , Drake C. G. , Walczak J. , Pili R. , Zahurak M. L. , Eisenberger M. A. 
Published: August 2020

5130 Background: BR following LT is common in PC with no defined standard treatment. Lenalidomide (L) is an immunomodulatory agent with anti-angiogenic and direct antitumor effects. Methods: This trial was designed to evaluate a dose-effect relationship of L in BR PC. Pts were randomized to either 5 or 25 mg/day(d), PO, d 1–21 (28-d cycles); then stratified by PSADT (< 3, 3–8.9, ≥ 9 mos), LT and prior ADT. Eligible pts had: rising PSA (≥1 ng/mL), M0 disease, testosterone > 150 ng/mL, adequate bone marrow, renal, and hepatic function. Baseline and Q 2 mos PSA's were processed after Q 6 mos of L, along with CT and bone scan. Toxicity exams were Q mo. Primary endpoints are safety and progression after 6 mo of L (defined by a confirmed ↑ in PSA > 25% over the baseline value or mets). Secondary endpoints are changes of slopes in PSA related to pharmacokinetics (pk). A sample size of 30 pts/arm provides an 85% power to detect a PSA progression rate of 40% (compared to 80% predicted ) with a Type I error = 0.05 (Fishers exact test). Results: 59 pts were entered July 20, 2006-December 31, 2008. Pooled data from the 2 arms: median: age 64 (50–81), ECOG PS 0, baseline PSA 9.3 ng/ml (1.3–92.8 ng/ml). 16 pts had PSADT <3 mos, 26 from 3–8.9 mos, and 17 ≥ 9 mos. Median: F/U on all 59 pts is 351 + d (9 +-887+d); # cycles = 6 (1–30). Thus far, 44/59 pts completed 6 cycles of L (1 had PD, 6 stopped L due to toxicity, 8 too early). 22 /44 who completed 6 mos of L remained on L > 6 mos ( 7+-30+ mos); including 7 pts ≥ 24 mos. Of 44 pts, blinded evaluation of PSA's at 6 mos: 4 pts had ≥ 50% ↓, 22 had stable PSA,17 had PD, 1 too early . Rash was DLT. Other Gr toxicities: appendicitis, abd pain, neck pain, venous thrombolic disease, fatigue, pruritus. Conclusions: Preliminary data prior to unblinding the study treatment arms, from pooled data, suggest that L may be administered > 6 mos with acceptable toxicity, and is associated with PSA declines and long term stabilization in pts with BR. Supported by a grant from Celgene Corporation. Data coordination infrastructure is supported by the Prostate Cancer Foundation and The James Stine research fund. [Table: see text]
HLA-associated multipeptide vaccination in biochemically relapsed prostate cancer patients
Authors: Feyerabend S. , Stefanovic S. , Gouttefangeas C. , Widenmeyer M. , Wernet D. , Hennenlotter J. , Bedke J. , Dietz K. , Pascolo S. , Rammensee H. , Stenzl A. 
Published: August 2020

5134 Background: We conduct a phase I/II monocenter clinical trial using multi peptide vaccination in patients with hormone naive, biochemically relapsed prostate cancer. The synthetic peptides applied are MHC-class I (HLA-A2) and -class II binders for activating CD4+ and CD8+ T- effector cells in vivo. Study endpoints are side effects as well as PSA- and T-cell response. Methods: Patients (pts) with rising PSA after primary curative surgical treatment without metastatic imageable lesions receive 14 peptides emulsified in Montanide ISA51 subcutaneously, combined with one of four T-cell stimulatory adjuvants versus no adjuvant for 18 months (mo) or until progression. PSA doubling time (DT) and clinical performance are monitored. T-cell activity and specifity are assessed with Elispot assay, tetramer staining and intracellular cytokine stainings. Results: 25 out of 35 pts have terminated the study treatment so far. During the vaccination period, geometric mean PSA DT increased from 7.8 mo (range 1.5 - 44.8 mo, 25 pts) to 11.8 months (range 2.2 - 571.3 mo, 24pts) whereas 1 pt showed a decreasing PSA value. Overall 8/25 pts (32%) had a mean rise of PSA DT of 81.6 mo and four of them did not receive any further treatment and were evaluable for follow-up (FU) after peptide vaccination (FU median 16 mo, range 5–33). These four pts raised their mean geometric PSA DT from 8.2 mo prior study treatment to 51.9 mo at treatment end and 52.5 mo at end of FU. PSA progressed unchanged in 10 patients (40%) or increased intermittently only in 4 pts. Two pts had PSA decline or DT increase during FU but not during the treatment period. Four patients (16%) exhibited an allergic reaction CTCAE II°. All pts reacted to at least one of the tumor antigen-derived HLA-class I epitopes after the fourth vaccine injection and up to six peptides were recognized simultaneously by CD8+ T cells in some individuals. Conclusions: Multi peptide vaccination stabilized or slowed down PSA progress in 11 of 25 cases. Stimulation of specific T-cell response is observed. Rise of PSA DT delaying standard treatment up to 33 mo and thus, delaying disease specific mortality is feasible. No significant financial relationships to disclose.
A randomized, phase II study of ATN-224 in patients with biochemically relapsed, hormone-naive prostate cancer: A DOD/PCF Prostate Cancer Clinical Trials Consortium trial
Authors: Lin J. , Beer T. M. , Ryan C. J. , Mathew P. , Wilding G. , Morris M. , Callahan J. A. , Gordon G. , Reich S. , Carducci M. A. 
Published: August 2020

5135 Background: ATN-224 (choline tetrathiomolybdate) is an orally active, small molecule that has antiangiogenic and antitumor effects in prostate cancer (PCa) models. ATN-224 targets Cu2+/Zn2+superoxide dismutase 1 (SOD1) and suppress the generation of H2O2 leading to activation of a number of phosphatases, a group of negative growth regulatory enzymes. We hypothesized that ATN-224 may induce antitumor effect as an antiangiogenic (at 30 mg dose level) and possesses direct antitumor activity at higher dose (300 mg/day). Methods: PCa pts with PSA doubling time (PSADT) of < 12 months, no radiographic evidence of metastasis, no hormonal therapy within 6 months were enrolled. All pts had testosterone > 150 ng/dL at baseline. ATN-224 was administered at 2 dose levels. PSA progression was defined as at least a 50% increase in PSA and >5 ng/mL increase from baseline or post-treatment nadir and confirmed. Endpoints included the proportion of pts who did not have PSA progression for 24 weeks, change in PSA slope/PSADT, and assessment of safety and tolerability. The study was not powered to detect difference between the two groups. Results: 52 pts were enrolled at 6 centers. Fourteen of 27 (52%) in the low dose and 6/25 (24%) in the high dose cohort were PSA progression free for 24 weeks. One patient in high dose cohort showed PSA >50% decrease of 40 days duration. Pre- and on-treatment PSA kinetics are shown below. Median duration on study was 134 days in both groups. ATN-224 was well tolerated with a few reversible Grade 3/4 neutropenia and Grade 3 skin rash (both 4%). Conclusions: ATN-224 may have biologic activity in men with androgen-dependent PCa at low doses, as demonstrated by > 50% of pts being PSA progression free at 6 month and a significant decrease in mean PSA slope. The implication of this study is not clear without a comparative design and ceruloplasmin correlation which is still pending. [Table: see text] [Table: see text]
Correlation of hypoxic prostate/muscle pO2 (P/M PO2) ratio and biochemical failure in patients with localized prostate cancer: Long-term results
Authors: Turaka A. , Buyyounouski M. K. , Hanlon A. L. , Horwitz E. M. , Greenberg R. E. , Movsas B. 
Published: August 2020

5136 Background: Tumor hypoxia may confer radioresistance in prostate cancer. The purpose of this study was to correlate tumor oxygenation status with long term biochemical outcome following prostate bracytherapy. Methods: Custom made Eppendorf PO2 microelectrodes were used to obtain PO2 measurements from the prostate (P), focused on + biopsy locations, and normal muscle tissue (M), as a control, in the operating room using a sterile technique. A total of 11,516 measurements were obtained in 57 patients with localized prostate cancer immediately prior to prostate brachytherapy. The Eppendorf histograms provided the median PO2, mean PO2, and % < 5 mm Hg or < 10 mm Hg. All patients received brachytherapy implants (48 low dose rate and 9 high dose rate) and five patients had received prior hormonal therapy. Biochemical failure (BF) was defined using both the newer Phoenix (PSA nadir + 2 ng/mL) the prior ASTRO (three consecutive rises) definitions (dfn). A Cox proportional hazards regression model evaluated the influence of hypoxia on BF with P/M ratio as a continuous variable and dichotomized at 0.05, 0.10, and 0.20. Results: The median follow-up was 8 years (range: 0.8- 9.4 years). Twelve patients developed BF via ASTRO dfn and 8 via Phoenix dfn. On stepwise multivariate analysis, P/M ratio < 0.10 was a significant predictor of BF (ASTRO, p = 0.03; Phoenix p = 0.02) in a model including initial PSA, Gleason score, T-stage, perineural invasion, age, hemoglobin and use of hormonal therapy. Kaplan-Meier freedom from BF for P/M ratio < 0.10 vs. ≥ 0.10 at 8 years was 46% vs 78% (p = 0.03) for the ASTRO dfn and 66% vs 83% (p = 0.02) for the Phoenix dfn. Only one patient (in the P/M ratio < 0.10) manifested distant failure. Conclusions: Hypoxia in prostate cancer (low P/M PO2 ratio) significantly predicts for poor long term biochemical outcome on multivariate analysis, suggesting that novel hypoxic strategies should be investigated. No significant financial relationships to disclose.
Analyses of circulating tumor cell (CTC) dynamics and treatment response in prostate cancer using the CTC-chip microfluidic device
Authors: Lee R. J. , Stott S. L. , Nagrath S. , Ulkus L. E. , Dahl D. M. , Smith M. R. , Toner M. , Maheswaran S. , Haber D. A. 
Published: August 2020

5149 Background: The CTC-Chip reliably detects CTCs in patients with localized and metastatic prostate cancer. In localized disease, CTCs may be indicative of tumor invasiveness. In the metastatic setting, CTCs may be useful in monitoring response to therapy. Molecular analyses of CTCs through this minimally invasive technique may provide insights into disease behavior, whereas sampling of metastatic deposits in bone (the predominant site of prostate metastasis) is not feasible. Methods: Peripheral blood was collected from patients undergoing treatment. CTCs were captured on the CTC-Chip. Quantities were determined using cytokeratin- and PSA-based staining and enumeration. In some cases, molecular analyses for the TMPRSS2:ERG chromosomal translocation were performed using FISH in intact cells or nuclei, or RT-PCR in extracted RNA. Subgroups of patients (n) included: localized disease undergoing prostatectomy (25), and metastatic disease undergoing either androgen deprivation therapy (ADT) (12) or docetaxel chemotherapy (5). Results: PSA-stained CTCs were captured in all patients. In localized disease, CTC quantities fell to undetectable levels 7–14 days after surgery; some patients exhibited an immediate decline while others had a delayed decline (>24 hours). In patients with metastatic disease undergoing either ADT or chemotherapy, CTC quantities generally corresponded with changes in serum PSA and radiographic assessments. Approximately 50% of patients exhibited the TMPRSS2:ERG translocation. Conclusions: These studies are the first to use the highly sensitive CTC-Chip technology to assess dynamic changes in CTCs in patients undergoing prostatectomy, ADT, or chemotherapy. Ongoing larger studies will assess whether patterns of CTC changes predict recurrence or treatment response. Molecular characterization of CTCs may provide new insights into prostate cancer biology, clinical behavior, and therapeutic targets. [Table: see text]
Correlation of progression-free survival (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (CRPC) who failed first-line chemotherapy: Results from the SPARC Trial
Authors: Halabi S. , Sartor O. , Petrylak D. , Sternberg C. N. , Witjes J. A. , Noursalehi M. , McKearn T. J. , George M. J. 
Published: August 2020

5150 Background: It has been shown in chemotherapy naïve patients that PFS is a statistically significant predictor of OS. The main objectives of this analysis were to explore whether PFS at 3-months is a predictor of OS and to investigate the dependence between PFS and OS in CRPC men who failed first line chemotherapy. Methods: Data from SPARC, a multi-national, randomized, double-blind trial, comparing satraplatin + prednisone vs placebo + prednisone in 950 CRPC patients were used. For the purpose of this analysis, the two treatment groups were combined. PFS was defined as the time from date of randomization to date of first progression (bone scan progression, radiographic, soft-tissue progression, symptomatic, or skeletal related events) or death, whichever occurred first. PFS at 3-months was defined as a binary variable in the following manner: if a patient experienced any type of progression at or before 3-months then this was considered as an event. If a patient did not progress at 3 months then he was censored. Landmark analysis of PFS at 3-months predicting OS was performed. In addition, the proportional hazards model was used to assess the significance effect of PFS at 3-months in predicting OS adjusting for the stratification factors. Finally, the association between OS and PFS was investigated using a statistic that estimates Kendall's tau measure of association for bivariate time to event outcomes subject to censoring. Results: 477 (56%) men progressed at 3-months of 853 men who were alive at 3-months. The median survival times were 34.5 weeks (95% CI = 30.8–40.4) and 78.7 weeks (95% CI=70.1–83.2, p-value<0.001) respectively in men who did and did not experience progression at 3-months. Men who had progressed at 3-months were more likely to die than men who did not progress (hazard ratio = 2.16, 95% CI =1.84 -2.55, p-value < 0.001). The dependence between PFS and OS was 0.29 (95% confidence limits = 0.24–0.33, p-value < 0.00001). Conclusions: PFS at 3-months predicts OS. The results of this large retrospective analysis show moderate, but strong statistical dependence between PFS and OS. Future studies are needed to assess the clinical relevance of the distinct components of progression. [Table: see text]
Phase I trial with a combination of docetaxel and 153Sm- EDTMP in patients (pts) with castration-resistant metastatic prostate cancer (mCRPC)
Authors: Eisenberger M. A. , Lin J. , Sinibaldi V. J. , Carducci M. A. , Denmeade S. , DeWeese T. , Song D. 
Published: August 2020

5155 Background: Bone targeted therapy holds great promise for improving outcomes in mCRPC. Preclinical data strongly supported biological synergism of docetaxel (Tax) and 153Sm-EDTMP (Sm) in mCRPC. Concurrent Tax and Sm regimens were reported feasible and tolerable in phase I studies. This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles (12 wks/cycle, C) of concomitant standard dose/schedule of Sm plus Q3 wks schedule of Tax in mCRPC. Methods: mCRPC pts with progressive bone metastases were treated in 4 cohorts ( CH). Previous Tax and palliative RT to bone was admissible. Dose escalation of Tax was implemented if no DLT was observed in the preceding CH. Tax doses (on days 1, 22, per 12 wk cycle) were given as follows: CH 1- 50mg/m2 (C1 and 2); CH 2–75mg/m2 (C1) and 50mg/m2 (C2); CH3 - 75mg/m2 (C1 and 2) and CH4 ( Tax day 1, 22, 43 per 12 wk C) 75mg/m2 (C1 and 2). Sm was administered on days 2 (Q12 wks X 2) at dose of 1 mCi/kg/cycle (max. of 2 cycles). Disease status was assessed (with bone /CT scans and PSA) after every cycle. Results: Thirteen pts with progressive bone metastases were enrolled. Three had prior Tax and 3 had prior palliative radiation. Thirteen pts received total 20 cycles in 4 cohorts. Toxicity was primarily hematological. There were total 34 episodes Grade 3/4 neutropenia with a median 7 (range 7 -14) days to recovery to ≤ grade1. Tax dose was reduced to 50% in 2 CH4 pts at C2. Only 1 DLT G3 thrombocytopenia occurred on cohort 4 with duration of 9 wks. Median baseline PSA was 100.4 ng/ml (range 8.6 - 1064), 9/13 (69%) pts had PSA>50% decrease. Median time to disease progression was 147 days (range 72 days - 10 months+); 6/13 (46%) pts had stable/improved bone scans at 6 months and 8/8 (100%) symptomatic pts had improvement in pain. Conclusions: Concurrent 6-month administration of 2 and possibly 3 full dose /standard schedule of Tax with 2 full doses of Sm is feasible with reversible bone marrow suppression. The combination may provide additional clinical benefits for mCRPC pts with extensive bone metastasis. No significant financial relationships to disclose.