Search

PURPOSE To compare the prevalence of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) and assess the impact of mutations on progression to castration resistance and overall survival. METHODS Targeted sequencing of germline DNA from 704 men (221 at the time of mHSPC and 483 at the time of mCRPC) enrolled in two advanced prostate cancer registries at Mayo Clinic between 2003 and 2013 was performed for 21 predisposition genes. Frequencies of pathogenic mutations were compared in patients and reference controls to identify genes enriched in metastatic prostate cancer. Multivariable Cox proportional hazards regression was used to identify predictors of progression to mCRPC and overall survival. RESULTS Sixty-eight germline mutations in 12 genes were identified in 66 men (9.4%). Mutations in ATM, BRCA2, CHEK2, FANCM, and TP53 were significantly enriched (odds ratio greater than 2.0) in the metastatic cohorts compared with reference controls. The frequency of germline mutations was similar for patients with mHSPC and mCRPC (11.8% v 8.3%; P = .16). The median time to progression from mHSPC to mCRPC was 23.1 and 32.5 months for patients with and without mutations, respectively ( P = .96). Although older age at diagnosis, Gleason score greater than 7, elevated alkaline phosphatase level, and high volume of disease were associated with shorter duration of progression to mCRPC and poor overall survival, mutation status was not (progression to mCRPC hazard ratio, 0.81; 95% CI, 0.61 to 1.09; P = .17; overall survival hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P = .98). CONCLUSION Similarly elevated rates of germline predisposition gene mutations in mHSPC and mCRPC suggest that germline genetic testing may help to guide medical management for all patients with advanced metastatic prostate cancer. Mutation status was not associated with shorter progression to mCRPC or poor overall survival.

We examined the effects of deliberate practice training focused on immediacy (Im) for 7 doctoral student trainees. Training included an 8-hr workshop, 4 individual 50-min sessions, and 4 individual 30-min homework sessions. Qualitative results indicated that trainees found the deliberate practice training to be effective, especially in helping them become aware of and manage emotions and countertransference, which had inhibited them from using Im. In addition, there was a moderate and significant effect of training on the trainee's self-efficacy for using Im, a small and significant effect on therapist-rated working alliance, and no significant effect for client-rated working alliance. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

INTRODUCTION AND OBJECTIVES:Radical prostatectomy (RP) is a mainstay of treatment for men with clinically localized, high risk prostate cancer (CLHRPC). We assessed whether chemohormonal therapy wi...

548 Background: sTILs are a well-established prognostic and predictive biomarker in patients with operable TNBC receiving pre or postoperative systemic therapy. We1 and others2,3 have also shown that sTILs are prognostic in patients who did not receive adjuvant chemotherapy. Here, we detail the outcomes of systemically untreated patients with N0 TNBC according to sTIL score. We focused on the N0 subset as a group of patients who may be candidates for future prospective therapy de-escalation trials. Methods: From a clinically annotated cohort of 605 patients with centrally confirmed TNBC (ER/PR < 1% and HER2 negative) with long-term outcomes data, we identified 182 patients treated with locoregional therapy only (breast surgery +/- radiation therapy and no chemotherapy). The clinicopathological characteristics of this cohort have previously been published1. In this analysis, we report the 5- and 10-year invasive disease-free survival (iDFS) and overall survival (OS) rates of patients with N0 TNBC according to sTIL levels. IDFS and OS were defined as per the STEEP classification and estimated using the Kaplan–Meier method. Comparisons of the survival distributions between groups were assessed by the log-rank test. sTILs were assessed as a continuous parameter according to the International TIL Working Group guidelines. For comparisons of outcomes between groups, tumors were classified as lymphocyte-predominant TNBC (defined as containing ≥50% sTILs) vs non-lymphocyte-predominant ( < 50% sTILs). Results: Of 182 systemically untreated patients, 149 (82%) were N0 and most (78%) were post-menopausal. T stage distribution was T1: 68%, T2: 28%, T3/4: 4%. Among N0 patients, 31 (21%) had lymphocyte-predominant TNBC, and in this group the 5-year iDFS and OS were 89% (95% CI 76-100) and 96% (95% CI 89-100), while the 10-year iDFS and OS were 89% (95% CI 76-100) and 87% (95% CI 73-100), respectively. In contrast, outcomes for patients with non-lymphocyte predominant TNBC were significantly worse. For this group, 5-year iDFS and OS were 62% (95% CI 53-73) and 78% (95% CI 71-86) while the 10-year iDFS and OS were 45% (95% CI 36-58) and 66% (95% CI 68-76), respectively ( log-rank p = 0.02 for iDFS and log-rank p = 0.03 for OS). Conclusions: sTIL quantification identifies a subset of patients with early-stage N0 TNBC with an exceedingly good prognosis, even in the absence of adjuvant chemotherapy. These data provide support for the evaluation of sTILs as part of prospective investigation of systemic therapy de-escalation strategies in N0 TNBC. References:1Leon-Ferre et al, Breast Cancer Res Treat (2018) 167:89-99 2Park et al, Ann Oncol (2019) 12:1941-1949 3De Jong et al, ESMO 2020

Background: Growing data established the pivotal role of preexisting immune response in triple negative breast cancer (TNBC). Conventionally, preexisting immune response can be evaluated by quantifying tumor infiltrating lymphocytes mainly in the stroma or gene expression analysis from the whole tumor section. Due to technical challenges with these conventional methods, limited data regarding specific subtypes and spatial distribution of these immune infiltrates are currently available. Methods: NanoString IO360 gene expression analysis and Digital Spatial Profiling (DSP) were used. DSP was used to quantify 29 immune-related proteins in stromal and tumor-enriched segments from 44 TNBC samples from the FinXX trial (NCT00114816) and 335 samples from the Mayo Clinic (MC) cohort of centrally reviewed TNBC (Leon-Ferre BCRT 2018). In FinXX trial, 22 patients with recurrence and 22 patients without recurrence were included. In MC cohort, 217/335 patients received adjuvant chemotherapy while 118 patients had surgery only without adjuvant chemotherapy. Regions were segmented based on pancytokeratin staining. The general linear model was used for statistical analysis of differential expression with recurrence free survival (RFS) as a categorical variable (recur yes or no). Kaplan-Meier (KM) estimates and Cox regression models were also used for analysis. Results: In the FinXX trial, there were 12 out of 29 proteins in tumor epithelial segments (intraepithelial) which were significantly expressed at higher levels among patients who were free of recurrence. These proteins include Beta-2 microglobulin, CD11c, CD20, CD40, CD56, CD8, Granzyme B, HLA-DR, ICOS, PD-L1, PD-L2, and TGFB1. In contrast, merely 5 out of 29 proteins in stromal segments were significantly differentially expressed in these 2 groups of patients. Granzyme B, IDO1, PD-L1, and PD-L2 in stroma were significantly higher and SMA was significantly lower in patients without recurrence. Using Cox regression models, intraepithelial CD56, CD40, and HLA-DR were significantly associated with outcome. When comparing between highest and lowest intraepithelial protein expression by tertile, intraepithelial CD56 (HR 0.12, 95%CI 0.03-0.39, p < 0.001), CD40 (HR 0.13, 95%CI 0.04-0.46, p = 0.002), and HLA-DR (HR 0.24, 95%CI 0.06-0.89, p = 0.032) were significantly associated with improved outcome. However, expression of these same proteins in stroma was not associated with outcome. Using KM estimates, intraepithelial CD56 (p < 0.0001), CD40 (p = 0.0006), and HLA-DR (p = 0.013) were also significantly associated with improved outcome. Nonetheless, RNA expression of these proteins by IO360 from whole tumor sections were not significantly associated with outcome (CD56 p = 0.27, CD40 p = 0.21, HLA-DR p = 0.48). Similar findings with DSP were observed in MC TNBC cohort. Comparing between the highest and lowest quartiles, there were significantly fewer patients who developed recurrence with high protein expression of intraepithelial CD56 (p < 0.001), CD40 (p = 0.002), and HLA-DR (p = 0.006). Conclusions: Using an in-depth analysis with spatially defined context, we identify that there were numerically more intraepithelial immune-related proteins associated with outcome compared to proteins in stroma. Specifically, intraepithelial CD56, CD40, and HLA-DR were significantly associated with improved outcome in both FinXX and MC TNBC cohorts. However, neither expression of these proteins in stroma nor RNA expression from whole tumor were associated with outcome. Our study highlights the impact of spatial biology and the importance of evaluating each potential biomarker in a spatially defined manner. Support: W81XWH-15-1-0292, BCRF 19-161, P50CA116201-9, P50CA015083 Citation Format: Saranya Chumsri, Jodi M. Carter, Yaohua Ma, Douglas Hinerfeld, Heather Ann Brauer, Sarah Warren, Torsten O. Nielsen, Karama Asleh, Heikki Joensuu, Edith A. Perez, Roberto A. Leon-Ferre, David W. Hillman, Judy C. Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus J. Couch, Keith L. Knutson, Matthew P. Goetz, E. A. Thompson. Spatially defined immune-related proteins and outcome in triple negative breast cancer in the FinXX trial and Mayo Clinic cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-02.

Introduction: Stromal tumor-infiltrating lymphocytes (sTILs) have established prognostic and predictive significance in triple-negative breast cancer (TNBC). However, the roles of other immune cells in TNBC are less well-established. We performed high-plex quantitative spatial profiling in a cohort of early-stage TNBC to 1) apply spatial context to tumoral immune landscapes and 2) identify immune proteins associated with clinical outcomes, independently of TILs and other established prognostic clinicopathologic variables, in patients (pts) treated with or without adjuvant chemotherapy (CTX). Methods: The Mayo TNBC cohort comprises pts with centrally-verified, CTX-naive tumors resected from 1985-2012. Using a cohort-based TMA, with Nanostring GeoMX DSP, we quantitated 58 proteins within spatially-distinct intra-epithelial, cytokeratin-positive tumor segments and adjacent cytokeratin-negative/nuclei-positive stromal segments. Differentially-expressed (DE) proteins were identified using a negative binomial generalized linear model (SNR>2, p< 0.05) and a target DE protein set was dichotomized (80th percentile). After adjusting for prognostic clinicopathologic variables, proteins associated with recurrence-free survival (RFS, defined as time from surgery to either local, regional, and distant recurrence, or death by any cause) were identified by performing variable selection using the Akaike Information Criterion (AIC) obtained from fitting all possible Cox proportional hazards regression models (performed separately for intra-epithelial/stromal segments, and in groups +/- adjuvant CTX. Results: From the TNBC TMA, DSP data (N=250 tumors) included 169 pts who received adjuvant CTX+ and 81 who did not (CTX-). Overall, 85/250 developed recurrent disease. In the CTX+ group, intra-epithelial tumor segments from pts without recurrent disease were enriched in 10 immune proteins, including CD8, markers involved in antigen presentation/dendritic cells (CD11c, CD40, HLA-DR) or NK cells (CD56) (FC: 1.4-2.1, p Citation Format: Jodi M Carter, Saranya Chumsri, David W Hillman, David M Zahrieh, Yaohua Ma, Xue Wang, Jennifer M Kachergus, Judy C Boughey, Minetta C Liu, Krishna R Kalari, JC Villasboas, Roberto A Leon Ferre, Fergus J Couch, Matthew P Goetz, E. Aubrey Thompson. Intra-epithelial tumor immune landscapes are associated with clinical outcomes in early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-01.

When students choose where to attend college, they often stay in close proximity to home and work. Much of the college choice literature, however, does not engage with the importance of geography in shaping educational destinations. Using county and commuting zone data from various federal sources, this study finds that the number of local colleges varies along lines of race and class. Communities with large Hispanic populations and low educational attainment have the fewest alternatives nearby, while White and Asian communities tend to have more. These can result in education deserts, or places where opportunities richly available for some communities are rare (or even nonexistent) in others.

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.

In 2007, Washington adopted the Student Achievement Initiative, a statewide performance accountability system designed to improve retention rates and degree productivity among community colleges. Using difference-in-differences analysis, we found that the policy change has had little immediate effect on retention rates or associate’s degree productivity. However, community colleges produced more short-term certificates after the policy reform. These results are robust across many alternative comparison groups. Considering that certificates yield less value in the labor market than associate’s degrees but are easier for colleges to produce, we discuss the unintended consequences of rewarding colleges based on the number of credentials they produce.

510 Background: Several studies have established the critical role of preexisting immune response in triple negative breast cancer (TNBC). Most studies evaluated the tumor infiltrating lymphocytes in stroma. However, limited data are available with regards to the importance of specific subtypes and spatial distribution of these immune infiltrates. Methods: NanoString IO360 gene expression analysis and Digital Spatial Profiling (DSP) were used. DSP was used to quantify 39 immune-related proteins in stromal and tumor-enriched segments from 44 TNBC samples from the FinXX trial (NCT00114816) and 335 samples from the Mayo Clinic (MC) cohort of centrally reviewed TNBC (Leon-Ferre BCRT 2018). In FinXX trial, 22 patients with recurrence and 22 patients without recurrence were included. In MC cohort, 217/335 patients received adjuvant chemotherapy while 118 patients had surgery only without adjuvant chemotherapy. Regions were segmented based on pancytokeratin staining. The general linear model was used for statistical analysis of differential expression with recurrence free survival (RFS) as a categorical variable (recur yes or no). Kaplan-Meier estimates and Cox regression models were also used for analysis. Results: In the FinXX trial, using global gene expression analysis with IO360, there was no signature significantly associated with RFS. However, using DSP, high protein expression of CD56 in the tumor-enriched segments was associated with significant improvement in RFS (HR 0.26, 95%CI 0.09-0.78, p 0.01). Nevertheless, CD56 expression in the stroma (HR 0.66, 95%CI 0.29-1.53, p 0.33) and all segments (HR 0.53, 95%CI 0.23-1.25, p 0.14) was not significantly associated with improved outcome. We further validated these findings in the MC TNBC cohort where intratumoral CD56 expression was associated with a significant improvement in RFS (HR 0.23, p 0.002) but not stromal CD56 (p 0.79). Interestingly, when evaluating the MC TNBC cohort according to receipt of chemotherapy, intratumoral CD56 was associated with improved outcome only in patients who received chemotherapy (p 0.02 vs. 0.07). In both cohorts, higher expressions of intratumoral PD-L1, HLA-DR, and CD8 were associated with improved outcome. Conclusions: Using an in-depth analysis with spatially defined context, we identify that intratumoral CD56-positive NK cells are associated with improved outcome in TNBC. Our study highlights the potential role of NK cells in TNBC and future implications for biomarkers and therapeutic targets.Support: W81XWH-15-1-0292, P50CA116201-9, P50CA015083. Clinical trial information: NCT00114816 .

1016 Background: The ph III EMBRACE trial of E vs physician’s choice of tx led to FDA approval of E as ≥3rd-line tx for MBC pts with prior exposure to anthracyclines/taxanes. The ph III BOLD 301 trial of E vs capecitabine in advanced BC treated with anthracyclines/taxanes showed a nonsignificant trend to improved median OS for all pts; pre-planned analysis by HER2 status revealed a nominally significant benefit for HER2- pts. Methods: RU011201I is an investigator initiated ph III trial with 1:1 randomization to E (1.4 mg/m2 D1,8 q21days) vs P (90 mg/m2 D1,8,15 q28days) within strata defined by (neo)adjuvant taxanes (yes/no), HR status (+/-), and line of tx (1st/2nd). Pts had measurable or non-measurable disease by RECIST v1.1; new or progressive mets; peripheral neuropathy (PN) gr3 mos were allowed. (Neo)adjuvant taxanes were allowed if >12 mos between tx completion and disease recurrence. Radiographic studies occur q12wks. Survival data are collected q12wks after the Off-Tx Visit. Pts reported side effects weekly; post-baseline symptomatic AE rates worse than baseline were compared between arms using Fisher’s exact tests. We report clinical outcomes and the primary objective related to PRO-CTCAE use. Results: 201 pts enrolled 3/2014 - 5/2018 with 33.8 mos median f/u; 3 are on tx as of 2/20/20 (1E, 2P). Pt characteristics were the same between E vs P: median age 62 yrs (range 27-85); 42% prior taxane; 78% ER+; 70% starting 1st line tx. Baseline lesion distribution was similar except for lung mets (37E, 53P). No difference was seen between E vs P in PFS (5.7 vs 5.9 mos; P=0.72), OS (18.1 vs 16.4 mos; P=0.75), TTF (5.3 vs 4.9 mos; P=0.82), DOR (10.8 vs 12.3 mos; P=0.84), or number of metastatic events (55 vs 54). 37E and 36P pts required ≥1 dose reduction. Hematologic toxicities ≥ gr 3 were higher with E (40 vs 22%). PN events were similar: 56 vs 58 total, 4 vs 7 motor, 52 vs 51 sensory. Median duration of PN and median time to 1st PN event were 74 vs 140 and 56 vs 41 days. Worsened numbness/tingling severity and other pt-reported AE rates were similar, but worsened numbness/tingling interference (63% vs 78%, P=0.04) and vomiting frequency (35% vs 57%, P=0.005) were lower with E. Conclusions: Clinical outcomes were equivalent with E vs P as 1st/2nd line tx for HER2- advanced BC. The nature and severity of PN were similar between arms, but time of onset, duration, and interference with daily living favor E. E may be a suitable treatment option in this setting. Clinical trial information: NCT02037529 .

696 Background: A number of treatments for metastatic renal cell carcinoma (RCC) have been FDA approved since December, 2005. Trials evaluating these agents excluded non-clear cell histologies and therefore the efficacy of these treatments remains unclear in patients (pts) with metastatic non-clear cell RCC (mncRCC). Methods: This is a single arm Phase II study designed to determine the efficacy of pazopanib in mncRCC. Treatment was pazopanib 800 mg by mouth daily until progression or intolerability of treatment. Dose reductions were allowed for toxicity with dose level -1 being 600 mg daily and dose level -2, 400 mg daily. Cycles were every 28 days. Main eligibility criteria included: (1) age ³ 18 years old; (2) histologic confirmation of ncRCC; (3) ECOG Performance Status (PS) 0, 1, or 2; (4) up to one prior treatment for mncRCC (5) measurable or non-measurable metastatic disease per RECIST criteria. The primary endpoint was overall survival rate at 12 months. Secondary endpoints were best tumor response rates after two cycles, PFS, OS and toxicity. Results: 38 pts were enrolled between May 16, 2013 and February 1, 2018. 35 pts were evaluable for primary endpoint. Median age 63 years old and 22/35 (62.9%) were male. Most common histology was papillary RCC, 14/35 (40%), and most common number of metastatic sites was 1. 29/35 (82.9%) had prior nephrectomy and 30/35 (85.7%) had no prior systemic therapy. Median number of cycles was 5. 12-month OS was 65.7% (90% CI, 50.5-78.9%). Best response in first 2 cycles: PR 11%, SD 60%, PD 9%, not evaluated 20%. Median PFS was 7.5 months (90% CI, 5.0-11.0); median OS 18.9 months (90% CI, 13.0-NE). Grade 3 / 4 AEs seen in 25 pts with hypertension, transaminitis and abdominal pain being most common (seen in >10%). Conclusions: There are limited data about the efficacy of available therapies for mncRCC. This study shows that pazopanib has similar efficacy compared to historical data in clinical trials using other TKIs in mncRCC. The safety profile of pazopanib in pts with mncRCC was found to be similar to that found in prior clinical trials studying pazopanib. Our findings warrant further investigation into the utility of pazopanib in metastatic ncRCC. Clinical trial information: NCT01767636.

In this chapter we identify and describe a number of the most challenging conundrums in higher education finance and provide institutional researchers with conceptual lenses, research summaries, and data sources to help navigate these challenges. Our goal is to widen the higher education finance conversation beyond price and into other fundamental areas related to the underlying cost of delivering higher education, including a review of how taxpayers and philanthropists subsidize those costs. Institutional researchers are not expected to be financial accountants, so the purpose of this chapter is not to discuss business office functions or accounting standards used in higher education finance. Similarly, this chapter is not an overview of financial management strategies. After reading this chapter institutional researchers will be even more equipped to engage campus leaders and policymakers with strategies to respond to affordability challenges in creative and effective ways.

Background With college tuition and student loan debt rising, high school students and their families are increasingly concerned about “how to” pay for college. To address this, federal/state policy makers encourage individuals to financially prepare for college early in their child's life. Drawing from social reproduction theory, we anticipate wide inequalities in who engages in college financial preparations and savings and when they begin these activities. Purpose This study updates and extends the literature on how families financially prepare for college. Data High School Longitudinal Study of 2009 (HSLS:09), a nationally representative sample of 9th grade students who began high school in 2009. Research Design We use logistic and multinomial regression to estimate four different outcomes: (1) whether the family plans to help the student pay for college; (2) whether the family has financially prepared for college; (3) whether the family has opened a college savings account; and (4) when families financially prepare for college (kindergarten, elementary, or secondary school). Results Our results have implications for social reproduction theory as we find that socioeco-nomically privileged families have greater likelihoods of financially preparing their children for college before or soon after their children enter formal schooling. Conclusions Current policy efforts to encourage college financial preparation may disproportionately benefit already-privileged families and likely exacerbate educational inequalities.

Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies. Experimental Design: We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Coexpression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate. Results: AR-V9 was frequently coexpressed with AR-V7. Both AR variant species were found to share a common 3′ terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0; 95% confidence interval, 1.31–12.2; P = 0.02). Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC. Clin Cancer Res; 23(16); 4704–15. ©2017 AACR.

In 2000, the Pennsylvania State System of Higher Education introduced a performance-based funding model aimed at increasing degree productivity among the state’s public colleges. This study examines how the new policy affected undergraduate degree completions. Using a difference-in-differences estimation strategy, results suggest the policy has not systematically increased degree completions within the state. With limited evidence of the policy’s effect, we conclude that this was an ineffective funding model in terms of its ability to increase college completions. Although we find modest impacts when compared against colleges in neighboring states, these impacts disappear when matched against similar colleges from other states.

Some states invest relatively heavily in financial aid programs that benefit lower-income citizens, while other states concentrate their investment in programs that benefit students from higher-income backgrounds. States also vary in their levels of direct appropriations to campuses, a form of public subsidy that has long been viewed as benefitting middle-income citizens. What factors influence states to allocate higher education subsidies in a more or a less redistributive manner? This article reports on a study that examined sources of variation in state spending on need-based aid, merit-based aid, and appropriations over the period 1990–2010. Findings document relationships among spending patterns and structural and political conditions of states, indicating a “trade-off” between spending on merit- and need-based aid; as states invest more in the former, they reduce spending on the latter. We also show that the presence of a Republican governor and the strength of Republican representation in statehouses each is associated with increased state spending on need-based financial aid. Our results further show that increased wealth is positively associated with state spending on merit-based financial aid programs and state appropriations for higher education, but not need-based financial aid. We also find distinctive patterns of state support for higher education depending on the degree of centralization of a state’s governance arrangement for higher education; namely, the presence of a highly centralized structure is associated with decreased spending on merit-based aid programs and increased state appropriations to colleges and universities.

In 2004, Colorado introduced the nation’s first voucher model for financing public higher education. With state appropriations now allocated to students, rather than institutions, state officials expect this model to create cost efficiencies while also expanding college access. Using difference-in-difference regression analysis, we find limited evidence that these outcomes occurred within the 4-year sector; however, the policy increased cost efficiencies among community college and reduced college access for some underrepresented groups. The paper discusses the challenges of applying market-based reforms to public higher education.

This study updates and expands the literature on student loan default. By applying multilevel regression to the Beginning Postsecondary Students survey, four key findings emerge. First, attending proprietary institutions is strongly associated with default, even after accounting for students’ socioeconomic and academic backgrounds. Second, cumulative loan debt has a non-linear relationship to defaulting. Third, minoritized and students from low-income families default at disproportionately high rates; and fourth, unemployment and degree completion are strongly associated with greater default rates. These findings counter the argument that default is a “preexisting condition,” and the discussion is framed around implications for federal financial aid policy.

5079 Background: Neoadjuvant CHT followed by RP did not increase 3-year biochemical progression free-survival (bPFS) compared to RP alone in men with CLHRPC. However, there is evidence that bPFS and overall survival over time was improved. In the current analysis we assessed whether CHT followed by RP improved pathological specimen features compared to RP alone. Methods: CALGB 90203 (Alliance) is a Phase III study which randomly assigned, in a 1:1 fashion, men with CLHRPC [biopsy Gleason Grade Group (GGG) 4 or 5 or Kattan pre-op nomogram bPFS < 60%] to RP alone or RP plus neoadjuvant CHT [androgen deprivation plus docetaxel (75 mg/m2 every 3 weeks for 6 cycles)]. We conducted an exploratory analysis comparing histologic findings, determined at the treating center, in the RP specimens of men receiving CHT plus RP and men treated with RP alone. We used the Chi-square test, with P-values adjusted by the Holm method for multiple comparisons. Results: A total of 788 men (median age, 62; range: 32-83 years) were randomized, with 738 ultimately undergoing RP. There was no difference in pathologic GGG (Table). Men treated with neoadjuvant CHT had a lower pathologic T-stage and lower likelihood of having seminal vesicle invasion (SVI), positive pelvic lymph nodes, or positive surgical margins (SM) (Table). Conclusions: Most pathologic features in the RP specimen were improved in men receiving neoadjuvant CHT compared to RP alone. The relationship between pathologic changes and the development of metastasis and survival require further analysis. RP pathologic outcomes. Summary statistics are calculated for the number of patients with non-missing data for each characteristic. Clinical trial information: NCT00430183. [Table: see text]

5008 Background: Androgen receptor (AR) signaling is an important growth mechanism in mCRPC, providing the rationale for treatment with AR axis inhibitors such as ENZ and AAP. Targeting AR with anti-androgens such as ENZ can result in compensatory autocrine and paracrine androgenic stimulation. Therefore, using ENZ with the androgen biosynthesis inhibitor AAP to dampen these resistance mechanisms could improve clinical outcomes relative to ENZ alone. Methods: Men with progressive mCRPC by Prostate Cancer Working Group 2 criteria were eligible. Prior treatment with taxanes for mCRPC and any prior treatment with ENZ or AAP was exclusionary. Patients (pts) were randomized 1:1 to ENZ or ENZ/AAP at standard FDA-approved doses. Randomization was stratified by prior chemotherapy and Halabi prognostic three risk groups. Castrating therapy was maintained. The primary endpoint was overall survival (OS) defined as the date of randomization from date of death or last follow-up. The log-rank test had 90% power to detect a hazard ratio for OS of 0.77 with a one-sided type I error rate of 0.025. Secondary endpoints included radiographic progression free survival (rPFS) and on-treatment PSA declines. Exploratory endpoints included imaging changes, and changes in serum biomarkers such as androgens, angiokines, and circulating microRNA and RNA. The primary analysis was based on the stratified log-rank test adjusting on the stratification factors. Results: Between January 2014 and August 2016, 1311 men were randomized: 657 to ENZ and 654 to ENZ/AAP. Groups were well balanced between arms, including stratification variables. 15.6% of pts were high risk, 35.3% intermediate, and 48.1% low. Median OS was 33.6 mo (95% CI 30.5-36.4) and 32.7 mo (29.9-35.4) respectively, two-sided p = 0.53. Fifty percent PSA decline rate was 80% vs. 76.5%. Grade 3-5 adverse events (AE) (all attributions) were 55.6% and 68.8% respectively. Treatment discontinuation due to AEs occurred in 5% and 12%, pt withdrawal in 5% and 13%, and progression or death in 57% and 48% of pts respectively. Conclusions: Addition of abiraterone acetate to enzalutamide did not prolong survival in men with mCRPC. The combination resulted in more AEs than enzalutamide alone. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01949337.

This study examines the institutional factors associated with student loan default. When a college has more than 30% of its students default on their loans, then the institution faces federal sanctions that could make them ineligible from participating in the federal student loan program. Using Integrated Postsecondary Education Data System (IPEDS) data from 2008 ( N = 4,488), and applying logistic regression, this study finds for-profit colleges, those accredited by vocational education programs, and those serving diverse student bodies are most at risk of federal sanctions. It concludes that accreditation reform and improving graduation rates could be long-term solutions to addressing the default problem.

Several wealthy colleges and universities have recently begun removing all loans from low-income students’ financial aid packages. This article reports on a study that found that the introduction of “no-loan” policies has positively impacted low-income enrollments, suggesting that this aid strategy may be an effective, though limited, way of increasing economic diversity on campus.

This brief utilizes the most recent and rigorous financial aid research to inform state higher education leaders about innovative and effective financial aid practices. By simplifying aid eligibility requirements, improving the aid application process, and engaging in early awareness efforts, states could improve the effectiveness of existing aid programs. Additionally, by targeting aid in ways that encourage college completion, more students (particularly those who are most constrained by finances) will improve their chances of earning postsecondary degrees. In recent years, several states have adopted goals of greatly increasing educational attainment levels, so we argue that innovative financial aid policy reform is one of the necessary steps toward meeting these goals. This brief can inform ongoing policy negotiations between state commissioners of higher education, state education task forces, and education and workforce legislative committees. © 2013 Association for Education Finance and Policy

BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels

This study uses fixed-effects panel data techniques to estimate the elasticity of community college enrollment demand relative to local unemployment rates. The findings suggest that community college enrollment demand is counter-cyclical to changes in the labor market, as enrollments rise during periods of weak economic conditions. Using national data for the years 1990 through 2009, we find that a one percentage-point change in unemployment is associated with 1.1–3.3 % increases in enrollment demand. We disaggregate the analysis by total full-time and part-time enrollment, concluding that high levels of unemployment are also associated with greater demand for full-time attendance. Additionally, enrollments are slightly more responsive to unemployment in metropolitan (rather than micropolitan) areas. Informed by enrollment demand theory, our analysis provides an update to the “unemployment elasticity” literature and could aid in current enrollment planning, economic development, and public policy efforts to educate students on the margin between college and work.

Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54–90); the median prostate-specific antigen was 66 ng/dL (0.1–99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07–0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39–3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy.

Free human kallikrein 2 (free-hK2) and hK2 pro-form (pro-hK2) have been found to be increased in tumor tissues and serum from patients with prostate cancer. We established semiautomatic assays for free-hK2 and pro-hK2 using a research version of the Beckman Coulter ACCESS2 system. Serum samples from a cohort of 189 men undergoing radical prostatectomy for known high-risk disease were assayed for Prostate-Specific Antigen (PSA), free-PSA, free-hK2, and pro-hK2. Univariate Cox regression and multivariate models were used to predict both Gleason scores and progression-free survival (PFS). Free-hk2 levels ≥80 ng/L were predictive of both Gleason scores ≥7 ( p = 0.04) and PFS ( p = 0.03). PSA ≥8.0 µg/L also was predictive of PFS ( p = 0.02). However, neither % free-PSA nor pro-hK2, when treated as continuous or cutoff variables were associated with Gleason score or PFS. Multivariable models showed that clinical stage T1c versus T2/T3, Gleason score ≥7, and PSA ≥8.0 µg/L or clinical stage T1c versus T2/T3, Gleason scores ≥7, and free-hK2 ≥80 ng/L were among the best models predicting PFS. Both free-hK2 and PSA in conjunction with clinical stage and Gleason score are good predictors of PFS in prostate cancer.

To evaluate whether germline variations in genes involved in sex steroid biosynthesis and metabolic pathways predict time to treatment failure for patients with advanced prostate cancer undergoing androgen deprivation therapy (ADT), because there are few known clinical predictors of response.In a cohort of 304 patients with advanced prostate cancer undergoing ADT, we genotyped 746 single-nucleotide polymorphisms (SNPs) from 72 genes from germline DNA (680 tagSNPs from 58 genes and 66 candidate SNPs from 20 genes [6 genes common in both]). Association with the primary end point of time to ADT failure was assessed using proportional hazards regression models at the gene level (for genes with tagging SNPs) and at the SNP level. False discovery rates (FDRs) of 0.10 or less were considered noteworthy to account for multiple testing.At the gene level, TRMT11 showed the strongest association with time to ADT failure (P.001; FDR=0.008). Two of 4 TRMT11 tagSNPs were associated with time to ADT failure. Median time to ADT failure for rs1268121 (AG) was 3.05 years for the AA, 4.27 years for the AG, and 6.22 years for the GG genotypes (P=.002), and for rs6900796 (GA), it was 2.42 years for the GG, 3.52 years for the AG, and 4.18 years for the AA genotypes (P.001). No other gene level or SNP level tests had an FDR of 0.10 or less.Genetic variation in TRMT11 was associated with time to ADT failure. Confirmation of these preliminary findings in an independent cohort is needed.

The question of how states can best use financial policy to achieve their goals is very important for many higher education stakeholders. In this study, the authors use panel data for all 50 states over a 20-year period to examine how state appropriations, need-based grants, and merit-based grants affect student enrollment in college and whether students migrate to other states for their postsecondary education. We find that increases within states in both appropriations and merit-based grants, but not need-based grants, lead to gains in postsecondary enrollment rates, and that merit-based grants are most effective at reducing outmigration for postsecondary education.

Over the next decade, Baby Boomers will be reaching retirement age in large numbers and the U.S. will be undergoing one of the most significant demographic shifts in its history. This demographic shift has important implications for the role of higher education as a provider of lifelong learning and for the changing composition of postsecondary institutions. Using data from the 2005 National Household Education Survey, the results of this study informs the higher education community about this emerging student market segment as a way to help us better respond to older adults’ demand for formal learning in postsecondary institutions.

The 2007 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) joint guidelines defined criteria for HER2 positivity of tumors that modified those of the US Food and Drug Administration (FDA), causing some confusion and uncertainty among clinicians. Using data from the HER2-positive breast cancer adjuvant trial N9831, we compared eligibility for patients who met both criteria, and disease-free survival (DFS) was assessed by Cox proportional hazards regression. The number of patients in the N9831 trial retrospectively eligible for trastuzumab therapy was decreased when ASCO/CAP criteria vs FDA criteria were applied to immunohistochemistry and/or fluorescence in situ hybridization results (107 [3.7%] of 2904 patients with immunohistochemistry results, 37 [1.3%] of 2809 patients with fluorescence in situ hybridization results, and 47 [1.7%] of 2809 patients with both results). Improvement in DFS was similar among patients treated with trastuzumab under either set of criteria (concurrent trastuzumab and chemotherapy compared with chemotherapy alone: by ASCO/CAP criteria, hazard ratio of DFS = 0.59, 95% confidence interval = 0.48 to 0.73; by FDA criteria but not ASCO/CAP criteria, hazard ratio = 0.60, 95% confidence interval = 0.12 to 3.13; number needed to treat to prevent one additional DFS event at 5 years: 10 and 11.2 patients, respectively). Following the 2007 ASCO/CAP criteria for HER2 positivity would negate the option of potentially life-saving trastuzumab therapy for a small but meaningful group of patients. We recommend using FDA-approved HER2 criteria for therapeutic decision making.

Ecological risks of Pacific salmon (spring, summer, and fall run Chinook, coho, and sockeye salmon) and steelhead trout hatchery programs operated between 2013 and 2023 in the Upper Columbia Watershed will be assessed using Delphi and modeling approaches. Committees composed of resource managers and public utility districts identified non-target taxa of concern (i.e., taxa that are not the target of supplementation), and acceptable hatchery impacts (i.e., change in population status) to those taxa. Biologists assembled information about hatchery programs, non-target taxa, and ecological interactions and this information will be provided to expert panelists in the Delphi process to facilitate assessment of risks and also used to populate the Predation, Competition, and Disease (PCD) Risk 1 model. Delphi panelists will independently estimate the proportion of a non-target taxa population that will be affected by each individual hatchery program. Estimates from each of the two approaches will be independently averaged, a measure of dispersion calculated (e.g., standard deviation), and subsequently compared to the acceptable hatchery impact levels that were determined previously by committees of resource managers and public utility districts. Measures of dispersion will be used to estimate the scientific uncertainty associated with risk estimates. Delphi and model results will be compared to evaluate the qualities of the two approaches. Furthermore, estimates of impacts from each hatchery program will be combined together to generate an estimate of cumulative impact to each non-target taxon.

Over the past decade, institutionally-funded financial aid (or “tuition discounts”) have been the fastest-growing item within most public four-year college and university operating budgets. One explanation for this trend is due to the changing structure of public colleges’ revenue streams, as tuition and fees have replaced state appropriations as a viable and predictable source of funding. This analysis explores the extent to which expenditures on institutionally-funded financial aid generates additional revenue for public four-year colleges and universities. Using institutional data (n = 174) from 2002 to 2008, the analysis implements a generalized method of moments (GMM) technique and concludes that aid indeed can be leveraged for revenue generation. However, this relationship is only sustainable to a certain point. When unfunded tuition discount rates exceed approximately 13%, institutions may experience diminishing revenue returns to this financial aid investment.

In countries charging tuition fees, and those that are considering adopting tuition fee policies, recent economic conditions are making education less affordable and accessible for students. To combat these challenges, nations, state/regional governments, and universities are experimenting with financial aid programmes by providing non‐repayable grants and scholarships to reduce price barriers. This paper synthesizes the underlying political and ethical motivations driving these financial aid policies. Aid providers interested in pursuing market prestige may prioritize “merit‐based” aid policies that are influenced by neoliberal norms; alternatively, those interested in equalizing opportunities for price‐sensitive students may prioritize policies guided by egalitarian values related to social justice. The political economy of aiding students has profound effects on educational opportunity, so this paper offers policymakers, researchers, and practitioners a model from which to frame these cross‐cutting and...

Purpose We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. Patients and Methods All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). Results Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P < .0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P < .006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor–positive or –negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. Conclusion These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.

5038Background: To determine transcriptome based markers associated with long-term response to abiraterone acetate/prednisone (AA/P) in metastatic castration-resistant prostate cancer (mCRPC). Meth...

To comply with legal mandates, meet local management objectives, or both, many federal, state, and tribal organizations have monitoring groups that assess stream habitat at different scales. This myriad of groups has difficulty sharing data and scaling up stream habitat assessments to regional or national levels because of differences in their goals and data collection methods. To assess the performance of and potential for data sharing among monitoring groups, we compared measurements made by seven monitoring groups in 12 stream reaches in northeastern Oregon. We evaluated (1) the consistency (repeatability) of the measurements within each group, (2) the ability of the measurements to reveal environmental heterogeneity, (3) the compatibility of the measurements among monitoring groups, and (4) the relationships of the measurements to values determined from more intensive sampling (detailed measurements used as a standard for accuracy and precision in this study). Overall, we found that some stre...