bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of imaging biomarker in a multicentric study to predict PFS in mRCC treated with TKI.
Authors: Lassau Nathalie , Koscielny Serge , Taieb Sophie , Lacroix Joelle , Aziza Richard , Joly Florence , Chevreau Christine , Negrier Sylvie , Gravis Gwenaelle , Escudier Bernard J.
Published: February 2017

526

Background: Tyrosine kinase inhibitors including sunitinib are the most effective treatments of metastatic renal cell carcinoma (mRCC). A multi-centric study of 539 patients (different tumors treated anti-angiogenic treatments) evaluating dynamic contrast-enhanced ultrasound (DCE-US), showed that a decrease of AUC (Area under the curve) correlated to the blood volume at one month is predictive of response. Our first objective was to validate the correlation between this parameter and the PFS in a sub-group of mRCC treated with Sunitinib The second objective was to study the variability of AUC. Methods: Each Patient had CT-scan every 2 months in order to evaluate the Response assessment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).DCE-US were performed at baseline and at D30. At each examination, we quantified 7 DCE-US parameters after bolus injection of contrast agent and mathematical modelization of raw linear data recorded during 3 minutes. We also estimated the variation between baseline and D30. The main endpoint was progression free survival assessed according to RECIST. We first selected the best parameters. We studied the trend between the parameter value and freedom from progression. After, the best cut-points were searched through a grid search. The best single cut-point was that with the lowest P-value for progression free survival. We performed this analysis in the sub-group of patients with mRCC treated with sunitinib. Morever, we studied the variability of AUC in 30 other patients treated with TKI . We performed in this group 2 DCE-US the same day before and after lunch. Results: A total of 81 mRCC patients treated with sunitinib were selected. All had DCE-US at baseline and one month. The median of follow-up was 18 months. For DCE-US, the decrease of 90 % of AUC at D 30 was correlated to the PFS (p =0.03). The difference of PFS between the groups defined by this cut-point was 4 months (bad responders) and 14 months (good responders). The results of variability are on-going. Conclusions: The decrease of more than 90% of AUC with DCE-US at one month is a potential predictive biomarker of response in mRCC patients treated with sunitinib. The results of variability of this parameter will be also presented. Clinical trial information: no. 912346.
Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases.
Authors: Kalra Sarathi , Atkinson Bradley J. , Matrana Marc Ryan , Matin Surena F. , Wood Christopher G. , Karam Jose A. , Tamboli Pheroze , Sircar Kanishka , Rao Priya , Corn Paul Gettys , Tannir Nizar M. , Jonasch Eric
Published: February 2017

527

Background: Pancreatic metastases are seen in a relatively small percentage of patients with renal cell carcinoma (mRCC). The prognostic impact of pancreatic metastases in patients receiving treatment for mRCC has not been extensively studied, and drivers of pancreatic metastases are not known. Methods: Retrospective review of mRCC patients in an outpatient clinic was done from January 2006 to November 2011. Patient characteristics including demographics, laboratory data, and outcomes were analyzed. Comparison of baseline characteristics was done using chi2and t-test and overall survival (OS) was estimated using Kaplan-Meier methods. Predictors of OS were analyzed using Cox regression. Results: A total of 228 patients were reviewed of which 44 (19.3%) had metastases to the pancreas and 184 (81.7%) had metastasis to sites other than the pancreas. The distribution of baseline characteristics and other factors was equal in both cohorts. 4 patients had isolated metastases to the pancreas, however, the majority of patients (68%) with pancreatic metastases had at least three different organ sites of metastases, as compared to 29% in patients without pancreatic metastases (p<0.01). Distribution of organ sites of metastases was similar (p>0.05), excluding pancreas. Median OS was 39 months (95% confidence interval [CI], 24-57) for patients with pancreatic metastases, compared to 26 months (95% CI, 21-31) for patients without pancreatic metastases (p-value <0.01). Conclusions: Despite a higher number of affected organ sites in the pancreatic metastasis cohort, mRCC behavior in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumor features associated with pancreatic metastases induce a less aggressive tumor phenotype. [Table: see text]
Changes of pulmonary function test and development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma treated with everolimus.
Authors: Park Kwon-Oh , Lee Jae-Lyun , Ahn Jin-Hee , Jeong In Gab , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuk , Ahn Hanjong
Published: February 2017

530

Background: The aim of this study was to evaluate the changes of pulmonary function test (PFT) during everolimus treatment and to assess whether the change of PFT is associated with the development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma. In addition, we tried to determine whether everolimus-associated pneumonitis could affect the efficacy of everolimus. Methods: Patients with mRCC who had received everolimus (10 mg dose once daily) after failure to VEGF-TKI treatment and underwent baseline PFT with regular PFT follow up were included in this study. The diffusing capacity divided by the alveolar volume (DLCO/VA) was used among various parameters of PFT. Repeated-measures ANOVA was used to describe changes of DLCO/VA. A Cox proportional hazard model with pneumonitis onset as a time-dependent covariate used to assess the prognostic role of pneumonitis. Results: This study included 36 patients. Nine patients (30%) developed everolimus-associated pneumonitis (pneumonitis group) and 27 were included in non-pneumonitis group. Five patients (14%) among pnemonitis group were symptomatic. The baseline DLCO/VA of patients was 90.0%. It decreased to 80.2%, 76.4%, 76.0%, and 72.1% after everolimus treatment of 6, 12, 18, and 24 weeks, respectively. DLCO/VA declined significantly as the treatment duration becomes longer (p < 0.001). There was no significant difference in change of DLCO/VA between patients with pneumonitis and those without pneumonitis (p =0.435). On time-variant Cox analysis, the decrease of DLCO/VA was not correlated with the efficacy of everolimus in terms of progression free survival (PFS, HR=1.0, p=0.94) and overall survival (OS, HR=0.98, p=0.18), while development of pneumonitis was associated with poor PFS (HR=4.60, p=0.005). Conclusions: Although the eveolimus treatment decreased DLCO/VA, the decline of DLCO/VA was not associated with the development of pneumonitis. Changes in DLCO/VA were not related with efficacy of everolimus, while the development of pneumonitis was a prognostic factor for PFS.
Liver metastases as predictors of outcome in renal cell carcinoma (RCC) patients (pts) treated with first-line sunitinib (SU) and sorafenib (SO).
Authors: Grassi Paolo , Verzoni Elena , Porcu Luca , Testa Isabella , Iacovelli Roberto , Garanzini Enrico , Salvioni Roberto , De Braud Filippo G. , Procopio Giuseppe
Published: February 2017

536

Background: The predictive role of metastatic sites in RCC pts treated with tyrosine kinase inhibitors (TKIs) is unclear. Aim of this study was to investigate whether first line SU and SO was associated to metastatic sites in terms of progression-free survival (PFS) and overall survival (OS). Methods: A retrospective cohort of consecutive metastatic RCC (mRCC) pts treated with TKIs at Istituto Nazionale Tumori of Milan was analyzed. All pts received at least one targeted therapy including: SO, SU, bevacizumab plus interferon-alfa, pazopanib or temsirolimus. The product limit method was used to estimate survival functions and Cox regression to estimate hazard ratios (HRs) and to test statistical interaction between sub-groups identified by different metastatic sites. Results: 358 mRCC pts receiving first line TKIs between January 2005 and October 2012 were evaluated. Overall 206 pts (58%) received SO while 103 pts (29%) SU. Median duration of treatment for SU and SO groups was 16 (95%CI 12.0-20.1) and 9 months (mo) respectively (95%CI 7.0-12.0). After a median follow-up of 56.1 mo (range: 1.0-93.2) median OS for SO group was 19.9 mo (95%CI 16.0-25.1) while OS for SU group was not yet defined. Noteworthy 142 pts (69%) treated with SO received SU at disease progression (PD) while 36 pts (35%) received SO at SU failure. A statistically significant interaction between first line treatment and metastatic sites was found for the liver site in terms of PFS and OS (PFS p=0.034; OS p=0.004). SU was associated with a 18% [95%CI (-37%)- 123%] higher risk of PD as compared to SO in pts with liver mets while pts without liver mets showed a 46% [95%CI (-61%)-(-24%)] decreased risk of PD as compared to SO. SU was associated with a 40% [95%CI (-32%)-187%] higher risk of death as compared to SO in pts with liver mets while pts without liver mets showed a 62% [95%CI (-76%)-(-40%)] decreased risk of death as compared to SO. The predictive role of liver mets was confirmed introducing the Motzer score (PFS p=0.084; OS p=0.009). Conclusions: mRCC pts with liver mets treated with first line SO showed a better outcome as compared to SU while pts without liver mets treated with first line SO showed a worse outcome as compared to SU.
Metformin use and renal cell cancer outcomes among patients with diabetes.
Authors: Khimani Farhad , Shah Nilay , Curley Brendan F. , Newton Michael David , Hogan Thomas F. , Monga Manish
Published: February 2017

543

Background: Renal Cell Carcinoma (RCC) is the third most prevalent urologic malignancy, and the sixth leading cause of cancer deaths in the United States. RCC is resistant to conventional treatment (chemotherapy, hormonal therapy and radiotherapy) therefore there is tremendous need for the development of new treatment strategies. Evidence indicates that metformin may reduce the risk of cancer and inhibit growth of several cancers, including prostate, breast, liver and colon. Metformin has been shown to inhibit RCC growth in in vitro and in vivo assays. Hence, it is pertinent to explore the role of metformin in RCC. Methods: At West Virginia University we performed an IRB approved retrospective chart review of all patients who were diagnosed with RCC at our institution from 2008-2012. Patients with Diabetes mellitus Type II (DM) were selected and stratified in to two cohorts based on metformin use. Statistical analysis was performed with SPSS Version 20.0. Results: A total of 290 patients with RCC were identified through the institutional tumor registry. Among patients with RCC, 25.1% (73) had DM. Of those DM patients, 60.2% (44) were on metformin therapy at diagnosis of RCC and 50.7% (37) were on metformin at last follow up. 84.9% (39) underwent radical or partial nephrectomy and 17.8% (13) patients received immunotherapy, targeted agents or chemotherapy. 26% (19) either had metastatic disease at diagnosis or developed recurrent disease. The metformin cohort had 27% (12) of patients with metastatic disease or a noted recurrence whereas in the non-metformin cohort 24.1% (7) had metastatic disease or recurrence. This was not statistically significant (p=0.76). No significant association was found between metformin use and mortality (p=0.46) or with stage of disease at diagnosis (p=0.35). Conclusions: Our limited retrospective review did not reveal any association between metformin usage and RCC outcomes, stage at diagnosis, or recurrence rates. However, in vitro and in vivo assays showing metformin inhibits RCC growth encourage further studies on larger patient populations to continue to explore this possible association. [Table: see text]
Dose-modified abiraterone acetate (AA) in men with metastatic castration-resistant prostate cancer (mCRPC): The Princess Margaret Cancer Centre (PM) experience.
Authors: Leibowitz-Amit Raya , Atenafu Eshetu G. , Seah Jo-An , Templeton Arnoud J. , Vera-Badillo Francisco Emilio , Solow Henry L. , Knox Jennifer J. , Sridhar Srikala S. , Tannock Ian , Joshua Anthony Michael
Published: February 2017

61

Background: AA prolongs survival in mCRPC and is used pre- and post-chemotherapy. In the phase I trial, AA showed anti-tumor activity at 250 or 500 mg daily (‘low doses’). In addition, pharmacokinetic analysis showed that when AA was administered with a high-fat meal vs the fasting state, drug exposure was increased by 4.4-fold [ Attard G et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563-4571.]. Based on this, at our cancer centre low-dose AA is sometimes prescribed with high-fat meals to men who otherwise cannot access the drug due to funding constraints, particularly in the pre-chemotherapy setting. Our aim was to study the association between AA dose, PSA response and progression-free survival (PFS). Methods: All men receiving AA at PM (Nov2009-Mar2013) were reviewed retrospectively. PSA response rate (PSA-RR) was defined according to PCWG2 criteria as a confirmed decrease ≥50% in PSA. PFS was defined from start of AA to PSA progression, clinical progression, drug cessation or death. Associations between dose, PSA-RR and PFS were assessed using chi-square and logrank tests, respectively, for all patients and for the sub-group of chemo-naive patients. Results: 109 men were treated with AA, 89 at a full dose of 1000 mg in the fasting state, 20 at low doses with high-fat meals. There was no significant difference in PFS between the two dose levels for all men. PSA-RR was non-significantly lower in chemo-naive men treated with low doses compared to full dose (p=0.09; table). Conclusions: Administration of low dose AA with high-fat meals is not associated with shorter PFS despite a trend to lower PSA-RR. These results are clinically relevant in resource-limited settings and warrant further prospective clinical research. [Table: see text]
Sipuleucel-T in metastatic castration-resistant prostate cancer (mCRPC) patients ≥80 years-old: Data from PROCEED.
Authors: Nabhan Chadi , Sartor A. Oliver , Cooperberg Matthew R. , Armstrong Andrew J. , Vacirca Jeffrey L. , Concepcion Raoul S. , Berry William R. , Dhawan Manish , Tutrone Ronald , Sandler Andrew , McCoy Candice , Whitmore James Boyd , Tyler Robert Claude , Higano Celestia S.
Published: February 2017

64

Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic mCRPC based on data from the pivotal phase 3 IMPACT trial that demonstrated a 22% reduction in the risk of death. Given the high prevalence of older men in the mCRPC patient (pt) population, we sought to understand disease characteristics and sipuleucel-T product parameters in pts ≥80 years (yrs). Methods: PROCEED is an ongoing phase 4 registry enrolling pts treated with sipuleucel-T within ≤6 months. Baseline pt demographics and disease characteristics were collected. Sipuleucel-T product parameters that were assessed included: total nucleated cell (TNC) count, antigen presenting cell (APC) count (large CD54+ cells), and APC activation (upregulation of CD54; a measure of product potency). Results: As of May 2013, 1254 subjects were enrolled and have completed treatment. Of these, 278 (20%) pts were ≥80 yrs-old. Disease and infused product characteristics in pts ≥80 yrs vs. <80 yrs are detailed in the table below. Product parameters appear similar between groups. Conclusions: In this large cohort of elderly pts ≥80 yrs treated prospectively with sipuleucel-T immunotherapy, we demonstrate that product parameters were similar to their younger counterparts (<80 years). This implies adequate immune up-regulation in elderly pts. Additional follow-up is needed to explore correlations between OS and various immune parameters in both groups. Clinical trial information: NCT01306890. [Table: see text]
Genomic analysis of circulating tumor cells (CTCs) from men with metastatic castration resistant prostate cancer (mCRPC) in the context of enzalutamide therapy.
Authors: Armstrong Andrew J. , Li Jing , Beaver Joshua , Bitting Rhonda Lynn , Gregory Simon
Published: February 2017

65

Background: Given the evolving treatments available in metastatic castration resistant prostate cancer (mCRPC), predictive biomarkers are desirable that maximize benefit and minimize harms and costs.The goal of this study was to determine the feasibility of DNA copy number and whole exome sequencing (WES) analysis of circulating tumor cells (CTCs) from men with mCRPC receiving enzalutamide. Methods: We collected CTCs from men with mCRPC in the context of enzalutamide therapy. CTCs were isolated from EDTA blood through red cell lysis, CD45 depletion, and flow sorting on EpCAM/CD45 expression. Whole genomic amplification and array based comparative genomic hybridization (CGH) was performed using Qiagen Repli-Gene Single Cell kit, multiple displacement amplification, and Agilent microarray analysis. CTC copy number changes were compared with patient leukocyte DNA and reference metastatic PC datasets. CTC AR amplification and PTEN loss was confirmed with FISH. WES on REPLI-g amplified CTC and leukocyte DNA was performed using GeneWiz and TruSeq Exome Capture Kit, and sequenced with Illumina HiSeq 2000 (20x). Results: A novel method for CTC array CGH was developed that reproducibly identified genomic lesions previously reported in metastatic CRPC including: AR amplification or focal deletions, deletions of CHD1, Rb, PHLLP, FGFR2, FOXA1, and NCOA2, and amplifications of EZH2 and MYC. AR amplification was noted in a man with mCRPC who subsequently responded to enzalutamide, with loss of AR amplification and gain of MYCN and c-MET amplification noted at progression. CGH analysis was feasible down to 10 to 20 cells using spiked cell lines. Interpatient tumor specific genomic heterogeneity was observed. FISH confirmed AR changes and PTEN loss heterogeneity. WES demonstrated acquired PTEN, MAGI1, SMAD4, and RB1 mutations in a patient who progressed through enzalutamide therapy, in addition to AR region deletion detected by CGH. Conclusions: Whole genome DNA copy number and exome sequencing analysis from CTCs in men with mCRPC is feasible in men with high CTCs and identified previously validated and novel genomic lesions and suggest the potential to identify predictive biomarkers of enzalutamide efficacy and resistance in the clinic.
A population-based study of expectant management utilization and its predictors for low-risk prostate cancer.
Authors: Maurice Matthew J. , Abouassaly Robert , Zhu Hui
Published: February 2017

68

Background: Expectant management (EM), including active surveillance and watchful waiting, is a strategy to minimize prostate cancer overtreatment. We sought to evaluate contemporary trends in EM utilization and to identify factors associated with its uptake. Methods: Using the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, we identified men with biopsy-proven low-risk (Gleason score 6 or lower, no Gleason pattern 4 or 5, cT1-cT2a) prostate cancer diagnosed between 2004 and 2011. We then classified men within this cohort as having undergone EM (no first-course surgery, radiation, hormone therapy, or chemotherapy) or active treatment. Patient and provider variables were analyzed using univariate and multivariate logistic regression models to determine predictors of EM selection. Results: Of 287,562 men with low-risk prostate cancer, we identified 34,132 patients (11.9%) who received EM. Beginning in 2008, we observed a significant and steady rise in EM usage with time (range, 9.8% to 18.6%). Compared to 2004, patients diagnosed in 2011 had 2.5 times the odds of receiving EM (odds ratio [OR] 2.52, confidence interval [CI] 2.39-2.64, p<0.0001). Aside from year of diagnosis, age, and Charlson score were strong predictors of EM usage (p<0.0001). Other strong predictors of EM included hospital type and insurance provider. Specifically, patients who were treated at comprehensive cancer centers or who had personal health insurance were significantly less likely to receive EM (OR 0.63, 0.60-0.66, p<0.0001 or OR 0.90, CI 0.88-0.93, p<0.0001, respectively). Patient race, income, and area of residence as well as hospital location were significantly but weakly associated with EM. Conclusions: In recent years, low-risk prostate cancer has been increasingly managed with EM, especially in older patients or patients with multiple comorbidities, who are least likely to benefit from active treatment. Unexpectedly, hospital type and insurance provider also predict EM usage, calling into question whether non-clinical factors are influencing EM selection.
A prognostic score for patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate post chemotherapy.
Authors: Templeton Arnoud J. , Omlin Aurelius Gabriel , Pezaro Carmel Jo , Kheoh Thian San , Leibowitz-Amit Raya , Vera-Badillo Francisco Emilio , Tannock Ian , Attard Gerhardt , Amir Eitan , De Bono Johann Sebastian
Published: February 2017

70

Background: We aimed to establish a simple prognostic score for men with mCRPC treated with abiraterone following docetaxel and explored incorporation of the neutrophil/lymphocyte ratio (NLR), a marker of host inflammation with prognostic value in many solid tumors. Methods: To develop the model, clinical and laboratory factors for 185 men treated at Royal Marsden were included in a univariable Cox regression analysis. Statistically significant variables were dichotomized using an optimal cut-off chosen by selecting the highest c-index among three potential cut-offs with high Hazard Ratios (HR). All significant variables in univariable analysis were analyzed using multivariable Cox analysis. One risk point was assigned for each variable with a P value of <0.05 in multivariable analysis and the risk points were used to establish three prognostic groups of similar prevalence. The validity of the model is being examined using the large data-set from the abiraterone registration trial (COU-AA-301). Results: Median age was 69 years, 41% had both bone and lymph node metastases (BLN), 15% had visceral disease. Involvement of BLN or visceral disease (HR 1.6, P=0.013), ALP >2.0 x ULN (HR 1.7, P=0.005), LDH >1.5 x ULN (HR 3.4, P<0.001), Hgb <12 g/dL (HR 2.1, P<0.001), and NLR >5 (HR 1.5, P=0.033) were associated with worse OS in the multivariable analysis. Outcomes for three risk groups using these 5 factors are presented in the table. The c-index was 0.73 (95% CI 0.65 - 0.80) for the prognostic score. Patients with NLR >5 at baseline and whose NLR was ≤5 within four weeks of treatment also had longer median survival (15.1 months) than those with NLR >5 at baseline that remained high (median OS 7.6 months, HR 0.48, 95% CI 0.25-0.93, P=0.029). Conclusions: This initial simple risk score provides good prognostic and discriminatory accuracy for men with mCRPC. Data from the validation cohort will be presented. [Table: see text]
ARMOR2: Galeterone in progressive CRPC patients who have failed oral therapy.
Authors: Taplin Mary-Ellen , Montgomery Robert B. ,   ARMOR2 Group
Published: February 2017

71

Background: Galeterone is a first-in-class multitargeted oral steroid analog; it suppresses prostate cancer by a combination of AR modulation (antagonism and degradation) and CYP17 inhibition. Safety and proof of concept of galeterone in CRPC was assessed in ARMOR1. Galeterone was reformulated by spray dry dispersion technology (SDD) to optimize PK and remove food effect. ARMOR2 (NCT 01709734) is an open label, 2-part phase 2 trial that evaluates safety and efficacy of SDD galeterone in 4 populations of CRPC patients. These results report Part 1. Methods: Objectives of Part 1: confirm dose equivalence of SDD formulation with evaluation of PK, safety and PSA response. Metastatic (M1) and non-metastatic (M0) treatment naïve CRPC pts enrolled to groups of 1,700, 2,550 or 3,400 mg PO daily. An abiraterone refractory (Abi-R) group of 3 patients opened at 2,550mg. Results: 28 were enrolled in part 1. Safety: All groups were safe by IMC assessment. There were 4 grade 3 adverse events. 2 were unrelated to study drug. 2 had transient G3 ALT elevations (did not recur with rechallenge). There was no AME: supplemental steroids were not required. G4 angioedema occurred in a pt receiving lisinopril (known association with angioedema). Efficacy: PSA response was improved compared to ARMOR1 (AACR 2012. Taplin et al abstract: CT-07). At early follow up Abi-R pts showed improvements in PSA with 1 PSA30% response, 2 with stablized PSA (decline in PSA-V from +0.44 to -0.39 ng/day). Conclusions: Galeterone in SDD formulation is tolerated at doses up to 3,400mg daily. SDD galeterone provides improved PSA response and durability vs. prior formulation. There is evidence of activity in abiraterone refractory patients. Clinical trial information: 01709734. [Table: see text]
Salvage chemotherapy with carboplatin plus weekly docetaxel in patients (pts) with castration- and docetaxel-resistant prostate cancer (DRPC): Associations of patient and disease characteristics with overall survival (OS).
Authors: Reuter Christoph W. , Morgan Michael A. , Grünwald Viktor , von Klot Christoph A. J. , Merseburger Axel S. , Ivanyi Philipp , Fenner Martin , Ganser Arnold
Published: February 2017

75

Background: Our recent data suggest that carboplatin is effective in combination with docetaxel (DC) in docetaxel-resistant prostate cancer (DRPC). Platinum(II)-complexes interfere with steroid biosynthesis lowering testosterone levels by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase (HSD3B1,2) and 17α hydroxylase/C17,20-lyase (CYP17A1). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted of at least two cycles of carboplatin AUC5 iv for 30 min on day one every 4 weeks (q4w), docetaxel 35 mg/m2 iv for one hour on days 1, 8, and 15 plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before (n=59) and during DC chemotherapy (n=52). Results: Of the 82 pts treated since February 2005, 95.1% had bone, 42.7% had lymph node, 26.8% liver, and 18.3% lung involvement. At the current analysis, the median follow-up time was 15.6 months. The objective response rate was 40.8% and the disease control rate 63.3% in the 49 pts with measureable disease. Response of prostate-specific antigen (greater than or equal to 50%) was observed in 3 out of /82 (47.6%) pts. Median progression-free survival (PFS) was 6.9 months (CI 95% 6.0, 7.8) and median OS was 18.0 months (CI 95% 12.7, 23.3). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (42.7/37.8%). Median free testosterone (fT) was 0.745 pg/ml before and less than 0.18 pg/ml during DC treatment (nadir levels, p=0.009; detection limit less than 0.18 pg/ml) and median serum androgene (T+DHT=TA) was 0.19 ng/ml and below the detection limit of less than 0.05 ng/ml (p<0.001). In multivariate analyses, lactate dehydrogenase, PSA response, and fT and TA nadir levels were associated with longer OS (p<0.05). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.
Antigen spread and survival with sipuleucel-T in patients with advanced prostate cancer.
Authors: Drake Charles G. , Fan Li-Qun , GuhaThakurta Debraj , Stewart Frances , Kantoff Philip W. , Small Eric Jay , Gardner Thomas A. , Sheikh Nadeem A. , Trager James B. , Higano Celestia S.
Published: February 2017

88

Background: Tumor cell death in response to an immunotherapy may lead to the release of secondary (i.e. non-targeted) tumor antigens that prime subsequent immune responses (antigen spread). This may contribute to tumor control and reveal post-treatment biomarkers of clinical outcome. Sipuleucel-T, approved in the U.S. for treatment of patients with asymptomatic or minimally symptomatic, metastatic castration-resistant prostate cancer (mCRPC), is designed to elicit an immune response to prostatic acid phosphatase. Here we show that sipuleucel-T also elicits humoral antigen spread that may be associated with clinical benefit. Methods: We used protein microarrays and Luminex xMAP to identify and validate post-treatment serum immunoglobulin G (IgG) responses against secondary antigens. Association between IgG responder status (≥ 2-fold IgG elevation post-treatment) and overall survival (OS) was assessed using a Cox regression model adjusted for baseline prognostic factors (prostate-specific antigen [PSA], lactate dehydrogenase [LDH], bone lesions, Gleason score) and prior bisphosphonate use. Results: In IMPACT (NCT00065442, the pivotal trial of sipuleucel-T), IgG responses against secondary antigens were consistently observed three to four months post-treatment in the sipuleucel-T arm but not in the control arm. In evaluable sera from IMPACT (sipuleucel-T n=93; control n=40), IgG responses against an array of secondary antigens, including an oncogene (K-RAS) and a prostate-specific antigen (KLK2/hK2), were confirmed by Luminex xMAP in sipuleucel-T-treated patients (Wilcoxon test, p≤10-6); responses were not observed in control patients (p>0.1). Antigen spread was also observed post-sipuleucel-T treatment in ProACT (Wilcoxon test, p≤0.01), an independent study in patients with mCRPC (NCT00715078, evaluable n=26). In IMPACT, OS was longer in sipuleucel-T-treatment patients with IgG response to greater than or equal to two secondary antigens than in those without such response (Cox model, p≤0.01, HR≤0.4). Conclusions: Sipuleucel-T treatment resulted in humoral antigen spread that was associated with improved OS in IMPACT. These results contribute to an understanding of sipuleucel-T’s mechanism of action, and may enable identification of post-treatment biomarkers of clinical outcome. Clinical trial information: NCT00065442.
A prospective randomized phase III trial comparing consolidation therapy with or without strontium-89 following induction chemotherapy in androgen-independent prostate cancer.
Authors: Wang Jennifer , Tu Shi-Ming , Pagliaro Lance C. , Weiss Matthias , Hajdenberg Julio , Tseng Jennifer , Wade James Lloyd , Belt Robert J. , Cannon Michael W. , Fisch Michael
Published: February 2017

90

Background: New therapies have shown benefit for advanced prostate cancer, but are not curative. Bone metastases cause significant prostate cancer morbidity. Preliminary studies showed that bone-targeted therapy with strontium-89 (Sr-89) with doxorubicin was feasible in patients with stable or responding metastatic castration-resistant prostate cancer (mCRPC) after KAVE (ketoconazole and doxorubicin alternating with estramustine and vinblastine) induction with promising time to progression (13.9 vs. 7.0 months) and overall survival (27.7 vs. 16.8 months). We conducted this phase III, randomized, double-blind, multicenter study to determine the effectiveness of consolidation therapy with or without Sr-89. Methods: Patients with progressive mCRPC with bone disease received induction with KAVE or docetaxel/prednisone (D) chosen by the treating physician. Patients with stable or responding disease were randomized at week 16 to receive doxorubicin with either one dose (4 mCi) or no Sr-89. Primary endpoint was overall survival (OS). Results: This study was activated in April 2002 with planned randomization of 480 patients (240 patients per study arm). The trial closed early with a total of 265 patients: median age 67; median prostate-specific antigen (PSA) 71.2; 109 received KAVE; 155 received D, 127 (47.9%) patients went on to randomization, 43 (39.4%) from the KAVE arm, and 84 (54.2%) from the D arm. Multivariate Cox proportional hazards regression was used to control for induction regimen, Eastern Cooperative Oncology Group (ECOG) status, and number of bone metastases. Median survival from times of registration and randomization in the no-Sr-89 arm were 26.5 months (95% CI: 21.1, 29.9) and 22.8 months (95% CI: 17.7, 26.1), respectively, compared to 27.9 months (95% CI: 23.6, 34.2) and 24.3 (95% CI:19.8, 29.9) months in the Sr-89 arm. OS from registration (p=0.61) and randomization (p=0.62) were not statistically significant on univariate or multivariate analyses. Conclusions: The addition of Sr-89 to consolidation chemo did not improve OS in this study. This community-based, multicenter study closed prematurely due to slow accrual, demonstrating challenges in conducting trials in the US that combine radionuclide therapy with chemotherapy. Clinical trial information: MDA 3410.
Ethnodrama: An innovative knowledge translation tool in the management of lymphedema.
Authors: Ahmed Shahid , Quinlan Elizabeth , McMullen Linda , Thomas Roanne , Fichtner Pam , Block Janice
Published: February 2017

102

Background: Lymphedema can cause significant physical impairment and quality-of-life issues. Yet there is a gap in knowledge about lymphedema among breast cancer survivors (BCS), and health care professionals (HCP). Ethnodrama is an innovative knowledge translation strategy that uses theatrical performances for dissemination of research results. We evaluated the impact of live ethnodrama on HCP’ and BCS' awareness and attitudes in relation to impact of lymphedema on BCS’ lives. Methods: Ethnodrama performances were developed by script writers and a theatre director in collaboration with the investigators and BCS using data from published research and pre-performances workshops. The 25- minute performance follows a readers’ theatre model. Six interactive live performances were given to audiences of BCS, HCP, and community members in four cities across Canada. After watching these live performances, the audiences were asked to complete a survey regarding their knowledge, attitudes and practices toward lymphedema. Results: Of 238 survey participants, 55 (23%) were BCS and 85 (37.5%) were HCP. The mean age was 46±15 years & M:F was 1:4.8. Most members rated the performances as very effective in changing their (84%) or other people's (93%) understanding of lymphedema. Only 2.7% of respondents judged the performances as not effective at all in changing their understanding of lymphedema. Following the performances about 87% of respondents (95% HCP vs. 86.2% BCS, p = 0.10) reported being moderately to extremely motivated to seek additional information on lymphedema; 76% BCS reported interest in discussing arm morbidity issues with their HCP & 72% HCP anticipated changes in their practices related to arm morbidities screening. Overall no significant differences were noted in responses to ethnodrama between BCS and HCP. Open-ended responses were supportive of the findings from the closed-ended questions. One of the performances (The New Normal: Living with Lymphedema) is available on https://www.youtube.com/channel/UCewEVF6CcTlEKYlLNcc8FWQ . Conclusions: Our results indicate that ethnodrama performances effectively convey information and positively affecting changes in HCP’ and BCS’ attitudes toward lymphedema.
Racial disparities in breast cancer mortality among the regions of California.
Authors: Parise Carol , Caggiano Vincent
Published: February 2017

106

Background: Racial/ethnic disparities in breast cancer mortality have been described. Geographic variation in breast cancer mortality has also been observed. The purpose of this study is to determine if there are racial disparities in breast cancer survival among eight regions in California, the most populous state in the U.S. Methods: Of 245,701 cases of first primary female invasive breast cancer from the California Cancer Registry (CCR) diagnosed in 2000-2011, we identified 143,184 with complete data. The regions of California were classified as North, Sacramento, San Francisco and Bay Area (SFBA), Central Valley, Tri-County, Desert Sierra, Los Angeles (LA), and San Diego/Orange. Cox Proportional Hazards was conducted to assess risk of mortality of African Americans, Hispanics, Asian/Pacific Islanders, and American Indians when compared with whites. The region X race interaction was tested. Analyses were adjusted for year of diagnosis, stage at diagnosis, grade, age, and socioeconomic status. Hazard ratios and 95% confidence intervals were reported. Results: The region X race/ethnicity interaction was statistically significant so separate models were fitted for each region. Blacks has increased mortality in SFBA (HR = 1.36; 1.20, 1.56), LA (HR = 1.37; 1.24, 1.51) and San Diego/Orange (HR = 1.31; 1.07, 1.60). American Indians had an increased risk of mortality in the Tri-County (HR = 3.90; 1.73, 8.78) and San Diego (HR = 1.93; 1.04, 3.64) regions. Hispanics had a reduced risk mortality only in the Tri County region (HR = 0.71; 0.55, 0.93). Asians had a lower risk of mortality in San Diego/Orange (HR = 0.81; 0.70. 0.94) and LA (HR = 0.78; 0.70; 0.87). Race was not a statistically significant factor for risk of mortality in the North, Sacramento, Central Valley, and Desert Sierra regions. Conclusions: Racial disparities in breast cancer mortality California vary by region and appear to be more prevalent in large urban areas.
Cancer team approach for prescreening and identifying breast cancer survivors as part of survivorship care plan implementation.
Authors: Danciu Oana Cristina , Bharadwaj Sushma , Hoskins Kent
Published: February 2017

107

Background: Recommendations from the Institute of Medicine are that cancer patients receive individualized survivorship care plan (SCP)and treatment summary.SCP includes guidelines for monitoring and maintaining health and is a communication tool shared with families and health care providers. Offering SCP and treatment summary to cancer survivors remains challenging due to time and resource limitations, inadequate reimbursement and survivor access. Methods: Survivorship starts when completing the initial treatment (surgery, chemotherapy or radiation therapy). A team of medical oncologists, nurse practitioner and patient navigator created a process of pre-screening and identifying breast cancer (BC) survivors. SCP and treatment summary were pre-populated, individualized for each patient, then finalized and discussed with the patients during their medical oncology clinic visit.Pre intervention data was retrospectively collected, including all BC cases from March 2014 to March 2015. Post intervention data was prospectively collected over eight weeks. Pre and post intervention SCP completion rates were compared with chi square analysis. Results: A baseline one year review of 1124 encounters noted 23 of 90 (25%) BC survivors received SCP. Ninety-six encounters occurred during the 8 week pilot period. Sixteen (16.6%) cases met the definition of BC survivor. During the pilot period, 15 out of 16 (93.7%) survivors received the SCP and treatment summary (p < 0.0001). Conclusions: We successfully piloted the implementation of SCP for BC survivors. Our team found that using clinic visit screening and pre-identifying patients that transition into the survivorship program resulted in improvement of compliance with survivorship measures. We plan to open a BC survivorship clinic to address survivorship issues and to review SCP and treatment summary.
St. Joseph Mercy Oakland Pink Ribbon Mammogram Program designed to address health-care disparities.
Authors: Sell Rachel Norianne , Muhleman Mitchel , Kirby Amy
Published: February 2017

11

Background: Despite ongoing national efforts to promote state-mandated health care, such as the Affordable Health Care Act, many regions still struggle with high rates of uninsured and under-insured residents. Over 500,000 people have enrolled in the Healthy Michigan Plan, but premium payments are often prohibitively higher than the penalties for failing to obtain insurance. In Oakland County, 15% of adults remain uninsured and only 66.4% receive access to mammography screening. Developed in 2009, the St Joseph Mercy Oakland Pink Ribbon Mammogram Program takes a unique approach to addressing this issue, providing free breast cancer screening for women in Oakland County. Methods: Since its inception six years ago, the SJMO Pink Ribbon Program has served 806 Oakland County uninsured and under-insured women. This was made possible through the coordination of funding from the Pink Ribbon Trailblazers, a local grass-roots organization led by a breast cancer survivor, and St Joseph Mercy Oakland Hospital. Our program is unique, as women not only receive a free screening mammogram, but also a personalized breast cancer risk assessment and a clinical breast exam by a breast surgeon. The program also covers diagnostic mammogram and ultrasound if necessary. Women who need biopsy meet with the oncology financial navigator. Most women are enrolled in either the State of Michigan Title XV program/BCCCP, or Mercy Support, a charitable financial assistance program through the hospital. Women diagnosed with breast cancer either continue in Mercy Support or are enrolled in Medicaid. Results: We have found that despite the recent Affordable Health Care Act, demand for our program continues to increase annually. There continues to be a need for local communities to address health care disparities amongst lower income populations in Oakland County and throughout the nation. Conclusions: The purpose of this article is to describe the way that a local charitable organization, physician, and the hospital can come together to fund and provide continuity of care from screening, diagnosis, to treatment for low income women.
Male breast cancer: Risk factors, treatment, and survival.
Authors: Arobelidze Salome , Haddad Abdo S. , Spiro Timothy Peter , Daw Hamed
Published: February 2017

110

Background: We conducted a retrospective study to investigate male breast cancer risk factors, treatment and survival. Methods: All patients with male breast cancer diagnosed between 1985 and 2014 at the Cleveland Clinic were retrospectively reviewed. Results: 131 patients were enrolled in the study. The median age at diagnosis was 66. Most of the tumors were invasive ductal carcinomas (85%, 111/131) and most were intermediate grade (47%, 41/87). Most patients had localized disease – stage 0-1 (45%, 48/107); stage 2 (35%, 37/107). Among the patients with data, 93% (94/101) were ER+, 73% (74/101) were PR+, 12% (10/80) were HER2 positive, and 6% were triple negative. Estimated median survival was 20.2 years (95% C.I. 19.0-29.4), and estimated 2 and 5-year survival were 96% + 2% and 87% + 3%. Grade was associated with outcome (p=.07). Conclusions: In our study only age at diagnosis was associated with overall survival. Further research is required to understand the treatment outcomes of this rare cancer. [Table: see text]
Influence of taxanes (docetaxel, paclitaxel) on response assessment in DCE MRI.
Authors: Schrading Simone , Kuhl Christiane K.
Published: February 2017

132

Background: To prospectively investigate the influence of taxane-containing (T-CTx) vs. non-taxane containing neoadjuvant chemotherapy (NT-CTx) on contrast-enhancement of breast-cancers, of benign-enhancing-lesions (BEL), and of background-parenchymal-enhancement (BPE) in DCE-MRI. Methods: Prospective study on 62 patients with invasive breast-cancer who received neoadjuvant multi-agent chemotherapy with (n = 49) or without (n = 13) taxanes between 2008 and 2011, with 3 years of follow-up. Written informed consent was obtained. Patients underwent DCE-MRI according to a standardized protocol before and 2 weeks after completing neoadjuvant-CTx. The percent reduction of enhancement of breast-cancers, of BEL and BPE was calculated for patients receiving NT-CTx vs. T-CTx. Final surgical-pathology served as standard-of-reference. Changes of mean enhancement of breast cancers, BEL and background enhancement in patients under T-CTx vs. NT-CTx were compared. Results: Similar rates of pCR were observed after T-CTx and NT-CTx (28/49; 57.2% vs. 8/13; 61.5%). T-CTx was associated with an almost complete suppression of enhancement not only of breast cancers, but also of BEL and of BPE in the same patients, with average reduction of enhancement by -89.9% ±9.3%, by -90.2%±11.8%, and by -91.2%±7.5 %, respectively. After T-CTx, cancers with partial (n = 21) or pCR (n = 28) exhibited a similar reduction of enhancement (-81.8% ± 17.5 % vs. -93.9% ± 2.3 %; p = 0.22). After NT-CTx, the reduction of enhancement of cancers was significantly less pronounced compared to T-CTx (-41.1%±22.8% versus 88.1± 13.9%; p < 0.0001), and effects on enhancement of BEL and BPE were significantly less pronounced compared to that of cancers in the same women (p < 0.0001). MRI overestimated response, i.e. was false-negative for residual disease, in 66.7% (14/21) patients after T-CTx, versus 20% (1/5) after NT-CTx. Conclusions: The reduction of enhancement observed in breast-cancers after T-CTx is, in part, unrelated to their oncological response. MRI-detectable effects of taxanes represent a combination of specific anti-mitotic, and non-specific, probably anti-angiogenic effects. This impacts the accuracy with which DCE-MRI predicts pCR to neoadjuvant T-Ctx.
Comparison of survival outcome of concurrent GnRH agonist plus tamoxifen to that of sequential adriamycin and cyclophosphamide chemotherapy plus tamoxifen in premenopausal, lymph node-negative, hormone-responsive, HER2-negative, T1-2 breast cancer patients.
Authors: Sohn Guiyun , Ahn Sei-Hyun , Kim Hee Jeong , Sohn Byung Ho , Lee jong Won , Ko Beom Seok , Yu Jong Han , Lee Yura , Lee Sae Byul , Baek Seunghee
Published: February 2017

137

Background: The purpose of this study was to compare treatment outcomes between gonadotropin-releasing hormone (GnRH) agonist plus tamoxifen and adriamycin and cyclophosphamide (AC)-containing chemotherapy plus tamoxifen in hormone-responsive, premenopausal, node-negative, breast cancer patients. Methods: Among 7278 breast cancer patients who were diagnosed as breast cancer at Asan medical center, Seoul, Korea, 994 premenopausal women with node-negative, hormone receptor-positive, HER2-negative, T1-2 breast cancers were included in this retrospective cohort study: A median follow-up was 7.4 years (range, 0.5-11.4 years). 608 patients (61.2%) were treated with GnRH agonist together with tamoxifen, and 386 patients (38.8%) were treated with AC-containing chemotherapy with tamoxifen. The propensity score matching and inverse probability weighting was applied to original cohort based on patients’ age, operation method, nuclear and histologic grade, estrogen receptor and progesterone receptor positivity, T stage, Her2 positivity, and p53 positivity. In final analysis, 260 patients for each treatment arm were included. Results: In propensity matched cohorts (n = 520), a total of 34 patients had recurrence. There were 5 cancer-specific deaths and 12 overall deaths among total 520 patients. There were no survival differences for recurrence-free survival (p= 0.306), cancer-specific survival (p= 0.212), and overall survival (p= 0.102) between the two treatment groups. After applying inverse probability weighting, there were no survival differences for recurrence-free survival (p = 0.522), cancer-specific survival (p= 0.154). However, GnRH agonist with tamoxifen arm showed better overall survival than AC chemotherapy with tamoxifen arm (p= 0.021). Conclusions: Adding GnRH agonist to tamoxifen is a reasonable alternative to adding AC chemotherapy to tamoxifen in premenopausal, hormone-responsive, HER2-negative, lymph node-negative, T1-2, breast cancer patients.