Citations

The objective of this analysis of 4500 inpatients was to identify the experience and expectations of 18–35 year olds regarding chaplain visitation and to compare results with data from older adults. 71% of young adults reported wanting to be visited by a chaplain; 45.5% were visited; 68% indicated that this was important. Young adults value chaplains' role as a sign of God's care and presence (77.4%), in providing support for family (73.6%), being present during times of anxiety (66.0%), and praying/reading scripture with them (62.3%). Results were similar to older respondents, but young adults were more likely to value ethical counsel from chaplains (58.5% vs. 38.2%). This study provides clinically relevant information and suggestions for further research.

Introduction Symptomatic metastatic epidural spinal cord compression (MESCC) afflicts up to 10% of all cancer patients. MESCC is associated with shortened survival and worsened quality of life; thus, early diagnosis and management is crucial. In a multidisciplinary setting, life expectancy must be considered along with other factors, such as patient's symptoms and overall medical condition, to select the optimal patient-specific treatment plan. This study aims to identify and compare key survival prognostic factors in surgically treated symptomatic MESCC patients with a 12-month postoperative follow-up. Materials and Methods Over a 5-year period, 145 patients surgically treated for a single symptomatic MESCC lesion were enrolled in a prospective North American multicenter study. Univariate analyses, Kaplan–Meier methods, and log-rank tests were used to evaluate the prognostic value of various clinical predictors. Preoperative prognostic factors evaluated: age, gender, comorbidities, history of smoking, metastases outside the spine, site of primary tumor, previous systemic treatment for the primary tumor, MESCC location, number of vertebral body involved, previous MESCC treatment, ASIA score, motor deficits, bladder dysfunction, Oswestry Disability Index (ODI), EQ-5D, SF-36v2 mental and physical components, and ability to walk four steps. Predictors with p < 0.2 in univariate analyses were included into the final Cox proportional hazards model. Results The overall median survival was 7.7 months (235 days). Lung and breast cancer had the shortest and longest median survival, respectively (4.5 vs. 12.1 months). Nine patients (6%), whose primary cancer were lung (3), kidney (3), melanoma (1), prostate (1), and breast (1), died within 30 days after surgery; 46 (32%), 61 (42%), 74 (51%), and 86 (59%) patients died at 3, 6, 9, and 12 months, respectively. The site of primary tumor, number of vertebrae involved, ODI, EQ-5D, ASIA score, metastases outside the spine, bladder dysfunction, and ability to walk four steps were significant predictors on the univariate analyses. However, the multivariate Cox-regression analysis demonstrated that only spinal metastasis involving four or more vertebral bodies had a negative impact on survival ( p = 0.002, HR: 25). Conclusion The extent of spinal metastasis, which is regarded as an indicator of the severity of patient's metastasis burden, and the site of the primary tumor, although not statistically significant in our regression model but well recognized in the literature as an important clinical predictor, are considered as independent predictors of poor prognosis in patients with a single-level symptomatic MESCC lesion. MESCC patients are a challenging and vulnerable heterogenous population. It is essential to identify factors predicting survival, functional and clinical outcomes in this population to guide patient-centered management to optimize quality of life.

Abstract Background: The health benefits associated with maintaining adequate circulating levels of vitamin D are well known. More recently, data have emerged supporting an inverse association between vitamin D levels and risk of several human cancers. Related to this, African Americans (AAs) are at increased risk of hypovitaminosis D due to elevated levels of melanin in the skin that reduce the conversion of cholesterol to vitamin D3 (cholecalciferol). Herein, we simultaneously assess levels of awareness regarding the health benefits of vitamin D and the prevalence of hypovitaminosis D in a metropolitan African American community. Methods: From January 2012 through August 2013, we partnered with African American churches and community organizations in the metropolitan Jacksonville, FL area to provide nine education programs focused on vitamin D and the evidence linking poor vitamin D levels with increased risk of chronic disease, including cancer. Participants were offered free vitamin D testing to estimate the prevalence of vitamin D insufficiency (&lt;25 ng/mL) and deficiency (&lt; 15 ng/mL) in this population. Moreover, participants also completed surveys prior to the events to assess their awareness of issues related to vitamin D, including the emerging link with cancer risk. Results: Out of 305 attendees, 285 agreed to provide blood samples for vitamin D screening. Of these, 262 (92%) self-identified as African American (75% female, 25% male). The median age of the AA participants was 59 years. Laboratory testing for 25(OH) vit D revealed 43% of the AA participants had normal levels of vitamin D (&gt;25 ng/mL), 35% had insufficient levels (15-24 ng/mL) and 22% had deficient levels (&lt; 15 ng/mL). Of interest, despite the high level of hypovitaminosis D (insufficient + deficient) in this population, participants reported high levels of awareness regarding vitamin D prior to the education program. For example, 82% of AA respondents correctly answered that the main source of vitamin D came from sunlight and 76% correctly answered that AAs are at risk of lower levels of vitamin D because of the amount of melanin in the skin. Moreover, 83% of AA respondents answered that maintaining proper vitamin D levels could potentially decrease risk for various chronic health conditions, including certain cancers. Finally, 75% of the AA participants reported never having had a vitamin D test discussed with them by their doctor. Conclusions: We report a high prevalence of hypovitaminosis D in a large AA community in Jacksonville, FL. Moreover, we report that despite this high prevalence, awareness of the health benefits of vitamin D are high, yet regular vitamin D testing levels appear to be very low. These data provide the foundation for developing targeted interventions to raise vitamin D levels in this community. Citation Format: Alexander Parker, Monica Albertie, Nancy Diehl, Matthew Drake. Evaluation of the prevalence of hypovitaminosis D and vitamin D awareness in African Americans living in a metropolitan southern community. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B61. doi:10.1158/1538-7755.DISP13-B61

AbstractThe population pharmacokinetic model reported here was developed using data from 2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the impact of concomitant therapy with enzyme‐inducing antiepileptic drugs (EIAEDs) on irinotecan pharmacokinetics. Patients received weekly irinotecan doses of 100 to 400 mg/m2, and plasma samples were collected and analyzed for irinotecan and its APC, SN‐38, and SN‐38G metabolites. Nonlinear mixed‐effects modeling was employed for population pharmacokinetic analysis. Concomitant therapy with phenytoin, phenobarbital, or carbamazepine increased the clearances of irinotecan, SN‐38, and SN‐38G but not APC. SN‐38 clearance was 2‐fold higher with concomitant EIAED use, resulting in 40% lower SN‐38 exposure. Evaluation of additional covariates revealed no clinically relevant effects of sex or concomitant corticosteroid use. The population pharmacokinetic model suggests that a 1.7‐fold increase in irinotecan dose may compensate for decreases in SN‐38 exposure in the presence of concomitant EIAEDs. Although slightly more conservative, this dose adjustment is consistent with those recommended based on increases in the maximally tolerated dose for malignant glioma patients receiving EIAEDs and may be an appropriate starting point for further investigation when extrapolating to other cancer types or alternative regimens.

Abstract Myeloma remains a virtually incurable malignancy. The inevitable evolution of multidrug-resistant clones and widespread clonal heterogeneity limit the potential of traditional and novel therapies to eliminate minimal residual disease (MRD), a reliable harbinger of relapse. Here, we show potent anti-myeloma activity of macrophage-activating immunotherapy (αCD40+CpG) that resulted in prolongation of progression-free survival (PFS) and overall survival (OS) in an immunocompetent, preclinically validated, transplant-based model of multidrug-resistant, relapsed/refractory myeloma (t-Vκ*MYC). αCD40+CpG was effective in vivo in the absence of cytolytic natural killer, T, or B cells and resulted in expansion of M1-polarized (cytolytic/tumoricidal) macrophages in the bone marrow. Moreover, we show that concurrent loss/inhibition of Tpl2 kinase (Cot, Map3k8), a MAP3K that is recruited to activated CD40 complex and regulates macrophage activation/cytokine production, potentiated direct, ex vivo anti-myeloma tumoricidal activity of αCD40+CpG–activated macrophages, promoted production of antitumor cytokine IL12 in vitro and in vivo, and synergized with αCD40+CpG to further prolong PFS and OS in vivo. Our results support the combination of αCD40-based macrophage activation and TPL2 inhibition for myeloma immunotherapy. We propose that αCD40-mediated activation of innate antitumor immunity may be a promising approach to control/eradicate MRD following cytoreduction with traditional or novel anti-myeloma therapies. Cancer Immunol Res; 3(8); 881–90. ©2015 AACR.

Abstract Purpose: Mammographic breast density is an established and strong risk factor for breast cancer. Recently, a number of common genetic susceptibility loci have been identified as risk factors for breast cancer. We present the first report on the relative contribution of 76 validated breast cancer susceptibility loci, in the context of a polygenic risk score (PRS), to the breast density and breast cancer association. We also examine whether the PRS improves prediction of the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model above and beyond breast density and clinical factors included in the model. Methods: The study population included 1643 cases and 2397 controls from three independent epidemiologic studies: the Mayo Mammography Health Study (MMHS), the Mayo Clinic Breast Cancer Study (MCBCS), and the Bavarian Breast Cancer Cases and Control Study (BBCC). Data collected on patients in each of the studies included clinical risk factor, BI-RADS breast density [a) almost entirely fat; b) scattered fibroglandular densities; c) heterogeneously dense; and d) extremely dense] and genotypes for the 76 breast cancer susceptibility loci known at the time of the study. We formed a PRS from the reported per-SNP odds ratios (OR) for 76 known breast cancer susceptibility loci, and evaluated whether BI-RADS density and the PRS were independent risk factors for breast cancer, when adjusted for age, 1/BMI and study. We also incorporated the PRS (OR) into the BCSC 5-year risk model and estimated 5-year risk for the MMHS nested case-control study of 339 invasive cases, 765 controls. Results: BI-RADS density (p&lt;0.0001) and PRS (p&lt;0.0001) were independent risk factors for breast cancer that together showed greater discrimination of risk (AUC=0.69) than density (AUC=0.66; ΔAUC=0.029) or PRS score alone (AUC=0.68; ΔAUC=0.013; p&lt;0.001). Relative to those with scattered fibroglandular densities and average (2nd quartile) PRS, women with extremely dense breasts and in the highest PRS quartile, had a 2.7 fold (95%CI: 1.7-4.1) increased risk of breast cancer, while those with fatty breasts and in the lowest PRS quartile had a reduced risk (OR=0.30, 95%CI: 0.18-0.51). Incorporation of the PRS into the BCSC risk model improved discrimination (ΔAUC=0.031, p=0.001), for a net reclassification improvement of 20% (95%CI: 11%-28%), split equally among cases (9%) and controls (11%). Conclusion: BI-RADS density and the PRS are both important risk factors for breast cancer that can be included in breast cancer risk models to improve prediction of this disease. Using these models to identify high and low-risk risk groups will facilitate improved tailored screening and primary prevention interventions. Citation Format: Celine M. Vachon, V. Shane Pankratz, Christopher G. Scott, Lothar Haeberle, Elad Ziv, Matthew R. Jensen, Kathleen R. Brandt, Dana H. Whaley, Janet E. Olson, Katharina Heusinger, Carolin C. Hack, Sebastian M. Jud, Matthias W. Beckmann, Jeffrey A. Tice, Kristen S. Purrington, Thomas A. Sellers, Karla Kerlikowske, Peter A. Fasching, Fergus J. Couch. The contribution of common breast cancer susceptibility loci to the breast density and breast cancer association and the Breast Cancer Surveillance Consortium (BCSC) risk model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 940. doi:10.1158/1538-7445.AM2014-940

Abstract Background: Extranodal follicular dendritic cell sarcoma (FDCS) is an exceedingly rare tumor type that is limited to few cases in the literature. Given the rarity of this tumor, there is a lack of genetic understanding of this disease resulting in a non-individualized plan of care for patients with this disease. Herein, we are the first to describe extensively molecularly the DNA and RNA of this tumor. Methods: Under an IRB approved protocol, the patient's tumor and whole blood was freshly frozen for molecular analysis. We performed Next Generation Sequencing (NGS) genomic profiling including exome capture, mate pair and mRNA sequencing on this tumor. Exome and mRNA data were processed through Mayo's Bioinformatics Core standard pipelines, GENOME GPS 1.2.1 and MAPRSeq v1.2.1. Mutations and indels were prioritized depending on whether or not they belonged to known cancer associated genes. Copy number variations (CNVs) in Exome and Mate Pair data was found through PatternCNV v 1.0.1 and fusion transcripts were found using SNOWSHOES-FTD and Tophat-Fusion 2.0.6. Results: At the genomic level large scale genomic rearrangements were detected, including chr19 and chr20 trisomy, chr15q and chr17q segmental duplications result in two intra-chromosomal fusion genes, and translocations leading to four inter-chromosomal fusion genes between chr15 and chr17. Of particular interest is a stop codon gain in the CLTC1 (chr22) gene, which is involved in the mitotic spindle organization which has been associated with meningiomas and breast tumorigenesis. The new stop codon is before the site required for the recruitment of the proteins to the spindle. The large scale genomic rearrangement described above is consistent with this defective spindle assembly hypothesis. Another intriguing mutation detected in the VEGFR1 (chr13) gene leads to a 45% mis-spliced transcript. VEGFR1 is thought to modulate VEGFR2 which plays an essential role in angiogenesis, by acting as a decoy receptor. Therefore the loss of function of VEGFR1 might lead to hyper-activity of VEGFR2 pathway and a potential therapeutic strategy is to directly inhibit the VEGFR2 pathway. Furthermore missense mutations in the ATM (chr11) and TP53 (chr17) genes were found. PARP inhibitors have been used with success for cancer with defects in the ATM gene. Finally a novel fusion transcript of HDGRFP3 (chr15) and SHC4 (chr15) was identified. Such fusion results in an overexpressed SHC4 gene which has been associated with metastatic melanomas. Conclusions: In summary, genomic profiling of a rare thyroid FDCS identified drug targetable genes as well as changes related to tumor etiology. Future work is necessary to determine the functional significance of these molecular findings and whether they will predict benefit to targeted therapies. Citation Format: Jaime I. Davila, Jason Starr, Steven Attia, Chen Wang, Xue Wang, Brian Necela, Casler John, David Menke, Vivek Sarangi, Gavin Oliver, Richard Joseph, John Copland, Alexander Parker, E. Aubrey Thompson, Robert Smallridge, Yan W. Asmann. Extensive genomic profiling of a rare extranodal-follicular dendritic cell sarcoma: Implications for future individualized therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1894. doi:10.1158/1538-7445.AM2014-1894

Abstract Background: Guidelines recommend germline mutation testing of breast cancer predisposition genes in triple negative (TN) breast cancer cases with a family history of breast or ovarian cancer or when diagnosed under age 60. However, the prevalence of mutations in these genes among TN cases unselected for family history of breast or ovarian cancer is not known. Methods: To assess the frequency of mutations in 16 predisposition genes in TN cases we screened a large cohort of TN patients (n=1824) unselected for family history of breast or ovarian cancer from 12 centers and 824 study matched unaffected controls for mutations using a panel-based sequencing approach. Results: Deleterious mutations were identified in 15% of TN patients: 8.5% had BRCA1, 2.7% had BRCA2, and 3.6% had mutations in 12 other genes. Mutations in non-BRCA1/2 genes encoding proteins implicated in homologous recombination repair of DNA double strand breaks were detected at the same frequency as in breast cancer families. TN cases with mutations had high-grade tumors and were diagnosed at an earlier age than non-mutated cases. However, 10% of TN cases diagnosed at ≥60 years and 5% with no family history of cancer were also found to carry mutations. Inactivating mutations in non-BRCA1/2 predisposition genes were associated with moderate to high risks of TN breast cancer. Conclusions: National Comprehensive Cancer Network (NCCN) guidelines support clinical genetic testing of breast cancer predisposition genes in 95% of TN breast cancer patients carrying mutations in susceptibility genes. In contrast, National Institute of Health and Care Excellence (NICE) guidelines in the U.K. do not support genetic testing of a substantial proportion of TN patients with predisposing alleles. Frequency tables for inherited mutations in known predisposition genes based on age of diagnosis and family history of cancer will allow for selection of TN patients most likely to carry mutations in the predisposition genes. Citation Format: Fergus J Couch, Steven N Hart, Priyanka Sharma, Amanda Ewart Toland, Penelope Miron, Janet E Olson, Andrew Godwin, Vernon S Pankratz, Curtis Olswold, Seth Slettedahl, Lucia Guidugli, Matthias W Beckmann, Brigitte Rack, Arif B Ekici, Irene Konstantopoulou, Florentia Fostira, George Fountzilas, Liisa M Pelttari, Song Yao, Judy Garber, Angela Cox, Hiltrud Brauch, Christine Ambrosone, Heli Nevanlinna, Drakoulis Yannoukakos, Susan L Slager, Celine M Vachon, Diana M Eccles, Peter A Fasching. Triple-negative breast cancer: Frequency of inherited mutations in breast cancer susceptibility genes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-03.

Abstract Background NSABP B-36 compares 6 cycles of FEC-100 with 4 cycles of standard AC in pts with node-negative breast cancer. As reported separately, no significant differences between the two treatment arms were observed in the primary endpoint of disease-free survival or in the secondary endpoints of overall survival, recurrence-free, or distant recurrence-free intervals. Greater toxicity was reported in pts who received FEC compared to AC. We present here the results of the QOL and MH studies obtained prospectively in conjunction with the treatment study. We hypothesized that pts on FEC would experience greater treatment toxicity in the first 12 months of the study, and would have greater rates of amenorrhea at 18 months compared to pts on AC. Methods Among the 1,357 pts enrolled in the QOL study, 1,332 (675 AC, 657 FEC) submitted the baseline form and had QOL follow-up (fup) information. Pts completed: 1) the FACT-B instrument; 2) a symptom checklist; and 3) the SF-36 Vitality Scale, all at baseline, day 1 of cycle 4, and at 6, 12, 18, 24, 30, and 36 months after random assignment. FACT-B Trial Outcome Index (TOI), symptom severity, and vitality scores were compared between the two treatment arms using a mixed model for repeated measures analysis with adjustment for the baseline scores, type of surgery, and hormone receptor status, examining the first 12 months and the later time points separately. Menstrual status was collected at baseline for all enrolled pts, with subsequent assessments on day 1 of cycle 4, and at 6, 12, 18, 24, 30, and 36 months for pts with menstrual bleeding within 12 months prior to random assignment and not having had a hysterectomy and/or bilateral oophorectomy (1, 096 pts). Post-chemotherapy amenorrhea was defined as the lack of menstrual periods during the 12 months preceding the 18-month fup evaluation. Data from 921 pts (475 AC, 446 FEC) were available for analysis. Logistic regression, adjusted for type of surgery and hormone receptor status, was used to test for association of amenorrhea status and treatment. Results Both TOI and vitality scores were worse for pts on FEC compared to those on AC at 6 months (p&lt;0.01) with no significant difference at 12 months and beyond. No significant differences in symptom severity between the two treatment arms were observed. The rates of post-chemotherapy amenorrhea were significantly different between FEC and AC (66.8% vs. 58.7%, p=0.01) with positive hormone receptor status as an independent risk factor (p=0.03). Conclusions Women receiving FEC had diminished QOL at 6 months after random assignment, but no difference at 12 months or later. Premenopausal women receiving FEC experienced a higher rate of post-chemotherapy amenorrhea than women receiving AC. Support NCI grants U10-CA-12027, -37377, -69974, -69651 and -44066-26, and Pharmacia & Upjohn Company, a subsidiary of Pfizer, Inc. Citation Format: Patricia A Ganz, John W Wilson, Hanna Bandos, André Robidoux, Alexander HG Paterson, Johnathan Polikoff, Luis Baez-Diaz, Adam M Brufsky, Louis Fehrenbacher, Aroop Mangalik, Patrick J Ward, Louise Provencher, John T Hamm, Philip J Stella, Robert L Carolla, Richard G Margolese, Henry R Shibata, Edith A Perez, Norman Wolmark. Impact of treatment on quality of life (QOL) and menstrual history (MH) in the NSABP B-36: A randomized phase III trial comparing six cycles of 5-fluorouracil (5-FU), epirubicin, and cyclophosphamide (FEC) to four cycles of adriamycin and cyclophosphamide [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-01.

Abstract Recent studies have shown that associations between common genetic variation and gene expression in breast tumors provide insight into the functional mechanisms underlying breast cancer risk loci. However, the relationship between genetic variation, gene expression, and risk of triple negative (TN) breast cancer remains largely unexplored. We performed a genome-wide expression quantitative trait locus (eQTL) analysis of TN breast cancer using 668 formalin-fixed paraffin embedded TN tumors from the Triple Negative Breast Cancer Consortium (TNBCC) to identify novel genes relevant to TN breast cancer risk and to further explore the biology underlying known TN risk loci. Cis-eQTLs were defined as correlations between single nucleotide polymorphisms (SNP) and expression of genes within 1Mb, and trans-eQTLs were defined as the remainder of all SNP-gene correlations. In a genome-wide analysis, we identified 68,012 cis-eQTLs, representing correlations between 42,193 SNPs and 2,092 genes that were significant at a 10% false discovery rate (FDR). We also identified 70 trans-eQTLs across two unique genes at the same FDR threshold. Five cis-eQTLs involved SNPs previously associated with TN breast cancer risk (p&lt;5.0x10-5) in 3,700 TN cases and 4,700 controls from the TNBCC. Three of these, located on chromosomes 5p (cis-eQTL p=4.8x10-34; risk p=1.1x10-7), 7p (cis-eQTL p=6.1x10-10; risk p=1.3x10-7), and 17q (cis-eQTL p=1.8x10-15; risk p=2.9x10-7), have previously been reported in public databases of normal tissue. The remaining two TN breast cancer cis-eQTLs, located on chromosomes 8q (cis-eQTL p=6.3x10-6, risk p=8.3x10-6) and 14q (cis-eQTL p=3.1x10-6, risk p=1.2x10-5), have not been reported as eQTLs in other tissues. In addition, 12 of 25 known TN breast cancer risk loci (PEX14, MDM4, 2q31.1, ESR1, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, 19p13.1, MLK1), contained at least one significant cis-eQTL. In summary, we have identified five cis-eQTLs that may identify novel risk loci for TN breast cancer. Citation Format: Kristen S. Purrington, Drakoulis Yannoukakos, Jane Carpenter, Heli Nevanlinna, Angela Cox, Gianluca Severi, Christine Ambrosone, Amanda Ewart Toland, Andrew K. Godwin, Hiltrud Brauch, Peter A. Fasching, Penelope Miron, Jenny Chang-Claude, Nicholas G. Martin, Grant W. Montgomery, Vessela Kristensen, Hoda Anton-Culver, Paul Goodfellow, Janet E. Olson, Hugues Sicotte, Naresh Prodduturi, Daniel W. Visscher, Jeanette E. Eckel-Passow, S. Keith Anderson, Seth Slettedahl, Curtis Olswold, Xianshu Wang, V. Shane Pankratz, Susan Slager, Wei Zheng, Arto Mannermaa, Ute Hamann, Diana M. Eccles, Celine M. Vachon, Fergus J. Couch. Expression quantitative trait locus analysis of triple negative breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3266. doi:10.1158/1538-7445.AM2014-3266