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Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)–based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States.The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis.Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis.Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.

Example of CNA profiles obtained in LMS. Copy-number plots: x-axis represents the position on the full genome (chromosome numbers are indicated). Red dots represent normalized read count for bins of 50Kb (log R value). Y-values around 0 represent copy-number (CN) of 2 (grey line). Lower values indicate a deletion and higher values indicate a gain. The horizontal green line represents the segmented CN profiles

Significant focal events detected in leiomyosarcoma from EISAI 309 trial

Purpose:A randomized phase III study evaluated the efficacy of eribulin versus dacarbazine in patients with advanced liposarcoma and leiomyosarcoma. Improved overall survival (OS) led to approval of eribulin for liposarcoma, but not for leiomyosarcoma.Experimental Design:We explored the molecular profile of 77 archival leiomyosarcoma samples from this trial to identify potential predictive biomarkers, utilizing low-coverage whole-genome and whole-exome sequencing. Tumor molecular profiles were correlated with clinical data, and disease control was defined as complete/partial response or stable disease (RECIST v1.1).Results:Overall, 111 focal copy-number alterations were observed in leiomyosarcoma. Gain of chromosome 17q12 was the most common event, present in 43 of 77 cases (56%). In the eribulin-treated group, gains of 4q26, 20p12.2, 13q13.3, 8q22.2, and 8q13.2 and loss of 1q44 had a negative impact on progression-free survival (PFS), while loss of 2p12 correlated with better prognosis. Gains of 4q22.1 and losses of 3q14.2, 2q14.1, and 11q25 had a negative impact on OS in patients with leiomyosarcoma receiving eribulin. The most commonly mutated genes were TP53 (38%), MUC16 (32%), and ATRX (17%). The presence of ATRX mutations had a negative impact on PFS in both treatment arms; however, the correlation with worse OS was observed only in the eribulin-treated patients. TP53 mutations were associated with longer PFS on eribulin.Conclusions:Leiomyosarcoma has a complex genetic background, with multiple copy-number alterations and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of patients with leiomyosarcoma when treated with eribulin.

Purpose:A randomized phase III study evaluated the efficacy of eribulin versus dacarbazine in patients with advanced liposarcoma and leiomyosarcoma. Improved overall survival (OS) led to approval of eribulin for liposarcoma, but not for leiomyosarcoma.Experimental Design:We explored the molecular profile of 77 archival leiomyosarcoma samples from this trial to identify potential predictive biomarkers, utilizing low-coverage whole-genome and whole-exome sequencing. Tumor molecular profiles were correlated with clinical data, and disease control was defined as complete/partial response or stable disease (RECIST v1.1).Results:Overall, 111 focal copy-number alterations were observed in leiomyosarcoma. Gain of chromosome 17q12 was the most common event, present in 43 of 77 cases (56%). In the eribulin-treated group, gains of 4q26, 20p12.2, 13q13.3, 8q22.2, and 8q13.2 and loss of 1q44 had a negative impact on progression-free survival (PFS), while loss of 2p12 correlated with better prognosis. Gains of 4q22.1 and losses of 3q14.2, 2q14.1, and 11q25 had a negative impact on OS in patients with leiomyosarcoma receiving eribulin. The most commonly mutated genes were TP53 (38%), MUC16 (32%), and ATRX (17%). The presence of ATRX mutations had a negative impact on PFS in both treatment arms; however, the correlation with worse OS was observed only in the eribulin-treated patients. TP53 mutations were associated with longer PFS on eribulin.Conclusions:Leiomyosarcoma has a complex genetic background, with multiple copy-number alterations and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of patients with leiomyosarcoma when treated with eribulin.

Background Patient medication administration is one of the major responsibilities of the professional nurse. Prelicensure nursing students and new nursing graduates often lack competency to safely administer medications. Method This was a descriptive comparative design of 98 junior and 90 senior baccalaureate nursing students using the Medication Administration Safety Assessment Tool via observation during simulation. Results Independent samples t-tests comparing medication safety competency revealed 29.6% of juniors and 14.4% of seniors demonstrated competence on all eight Medication Administration Safety Assessment Tool checklist items. Seniors did not demonstrate greater medication safety competence than juniors on total scores. Conclusions Study findings can guide undergraduate curriculum planning to improve medication safety competencies in nursing students.

To examine the impact of access to and utilization of a commercially available question bank (TrueLearn) for in-training examination (ITE) preparation in Obstetrics and Gynecology (OBGYN).This was a retrospective cohort study examining the impact of TrueLearn usage on ITE examination performance outcomes. Produced by the educational arm of the American College of Obstetricians and Gynecologists, the Council on Resident Education in Obstetrics and Gynecology (CREOG) exam is a multiple-choice test given to all residents annually. Residency programs participating in this study provided residency program mean CREOG scores from the year prior (2015), and the first (2016) and second (2017) years of TrueLearn usage. Programs also contributed resident-specific CREOG scores for each resident for 2016 and 2017. This data was combined with each resident's TrueLearn usage data that was provided by TrueLearn with residency program consent. The CREOG scores consisted of the CREOG score standardized to all program years, the CREOG score standardized to the same program year (PGY) and the total percent (%) correct. TrueLearn usage data included number of practice questions completed, number of practice tests taken, average number of days between successive tests, and percent correct of answered practice questions.OBGYN Residency Training Programs.OBGYN residency programs that purchased and utilized TrueLearn for the 2016 CREOG examination were eligible for participation (n = 14). Ten residency programs participated, which consisted of 212 residents in 2016 and 218 residents in 2017.TrueLearn was used by 78.8% (167/212) of the residents in 2016 and 84.9% (185/218) of the residents in 2017. No significant difference was seen in the average CREOG scores available on a per- program level before versus after the first year of implementation either using the CREOG score standardized to all PGYs (mean difference 1.0; p = 0.58) or standardized to the same PGY (mean difference 3.1; p = 0.25). Using resident-level data, there was no significant difference in mean CREOG score standardized to all PGYs between users and non-users of TrueLearn in 2016 (mean, 199.4 vs 196.7; p = 0.41) or 2017 (mean, 198.2 vs 203.4; p = 0.19). The percent of practice questions answered correctly on TrueLearn was positively correlated with the CREOG score standardized to all PGYs (r = 0.47 for 2016 and r = 0.60 for 2017), as well as with the CREOG total percent correct (r = 0.47 for 2016 and r = 0.61 for 2017). Based on a simple linear regression, for every 500 practice questions completed, the CREOG score significantly increased for PGY-2 residents by an average (±SE) of 7.3 ± 2.8 points (p = 0.013); the average increase was 0.7 ± 2.5 (p = 0.79) for PGY-3 residents and 5.8 ± 3.3 points (p = 0.09) for PGY-4 residents.Adoption of an online question bank did not result in higher mean CREOG scores at participating institutions. However, performance on the TrueLearn questions correlated with ITE performance, supporting predictive validity and the use of this question bank as a formative assessment for resident education and exam preparation.

Background. The recent randomized phase 3 trial Eisai Study 309 evaluated efficacy of eribulin (ERI) compared to dacarbazine (DTIC) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS). Improved overall survival (OS) in ERI-treated patients led to US and EU regulatory approval of ERI for LPS, but not in LMS where DTIC has clinically relevant activity. As part of the translational effort in this trial we have now explored the molecular profile of LMS tumors from North American study sites, in order to identify potential predictive molecular factors for treatment with ERI. Material and Methods. From 82 archival primary tumor or metastatic LMS samples collected prior to study entry, 78 specimens were available for low-coverage whole genome sequencing. We analyzed copy number alterations (CNAs) and performed whole exome sequencing (WES) for mutational profiling. Forty patients received experimental treatment with ERI, while 38 were treated with DTIC. Treatment response was evaluated using RECIST v1.1; disease control was defined as complete/partial response and stable disease. Results. Overall 111 focal CNAs were observed in the entire group of LMS, including 55 gains and 56 loses. Gain of 17q12 was the most common CNA (43/78 cases; 55.1%) observed in the entire group analyzed, with 26 samples showing high level amplification. MYOCD is a suggested target of 17q12 gains in LMS, encodes myocardin which induces smooth muscle differentiation and promotes cell migration. In the ERI-treated group, gains of 4q26, 20p12.2, 13q13.3, 8q22.2, 8q13.2 and loss of 1q44 had a negative impact on progression-free survival (PFS) (p Using WES we detected an average of 266.1 (143-626) nonsynonymous substitutions and 4.7 indels (0-16) per sample, with an average of 11.5 (0-28) variants affecting Cancer Consensus Genes. The most commonly mutated genes in analyzed samples were TP53 (38%), MUC16 (31%) and ATRX (17%). In ERI-treated patients, the presence of ATRX mutations was more frequently observed in patients progressing on ERI (7/20 in patients with PD vs. 1/20 in group with disease control; p=0.0435). The presence of ATRX mutation had a negative impact on both PFS and OS. TP53 mutations were associated with longer PFS, and these mutations were more frequently observed in patients achieving disease control, although this was not statistically significant (11/20 vs. 5/20). ATRX andTP53 mutations were not linked with clinical benefit/response to DTIC. Conclusions. LMS has a complex genetic background, with multiple CNAs and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on disease control and survival of LMS patients treated with ERI. These observations require further prospective validation. Citation Format: Agnieszka Wozniak, Bram Boecks, Elodie Modave, Amy Weaver, Diether Lambrechts, Bruce A. Littlefield, Patrick Schöffski. Potential molecular biomarkers of response to eribulin in patients with leiomyosarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4280.

Background Through debriefing, students reflect on their learning and performance during a simulation and accommodate new information into their existing knowledge base. Combining a videotaped model demonstration within a debriefing session provides an opportunity to enhance students' clinical, self-confidence, and satisfaction with the learning experience. Method Students participated in a simulation followed by either the usual structured debriefing or the usual structured debriefing that included a videotaped model demonstration of the simulation scenario. Students participated in a similar simulation 1 week later followed by the usual structured debriefing. Results The use of a model demonstration during debriefing was effective in developing clinical judgment and, to a lesser degree, self-confidence. Conclusions A model demonstration of a simulation scenario can be used to develop clinical judgment and possibly self-confidence during debriefing.

doi: 10.5480/12-906.1A group of National League for Nursing (NLN) simulation lead- ers, members of the 2011-2012 NLN Simulation Leader Group, has worked on a project to organize the Annotated Bibliography section of the NLN's Simulation Innovation Resource Center (SIRC). The SIRC bibliography offers annotations of publications that report on simula- tion topics. These useful descriptions help guide faculty who are look- ing for quality simulation sources to investigate.Having used these resources when submissions were catego- rized by author only, the simulation leaders felt it would be benefi- cial to develop descriptive categories in which articles are classified, searched, and submitted. During a yearlong period, this group of seven simulation leaders organized more than 170 annotated bibliographies, identified and defined eight categories, and worked with the NLN's webmaster to ensure appropriate classification of future submissions.When the group of seven simulation leaders first met, their ini- tial objective was to make the annotated bibliography list more useful to nurse faculty, practitioners, and researchers by creating categories for the annotated bibliographies already posted on the SIRC website. Each member was assigned a group of bibliographies to review and classify according to content. More than 20 different categories were originally identified. These categories were then condensed to eight, and definitions for each category were created. The categories and descriptions are listed below.CATEGORIES AND DESCRIpTIONSReview ArticlesReview articles contain material about the current state of knowledge regarding simulation and may include literature reviews, meta-analy- sis, meta-synthesis, and integrative reviews.Curriculum IntegrationThese articles discuss the structuring of simulation activities across a program of study in order to assist students in meeting established learning outcomes. Activities covered are areas such as patient safety, standards of practice, and learning theories.InterprofessionalInterprofessional articles are about members of two or more health care professions learning simultaneously and interactively in a simu- lated setting.learning outcomesThese articles cover what learners will know or be able to do as a result of a simulated learning activity in areas such as critical thinking, clini- cal judgment, or competency testing.Faculty DevelopmentFaculty development encompasses a broad range of programs or activ- ities that help develop the use of simulation as a teaching/learning strategy; specifically, programs/activities that may enhance teaching and learning, research and scholarly activity, leadership and manage- ment, the development of new simulations, or studies of the history of simulation.SpecialtiesSpecialties are those simulations outside the adult medical-surgical setting. For example, there may be a focus on critical care, pediatrics, OB/GYN, psych-mental health, community health, geriatrics, or end- of-life care.DebriefingDebriefing covers re-examining and reflecting upon learning in order to assimilate the learning experience. These articles discuss debriefing methods, styles, quality, or the facilitator's approach.Teaching ModalitiesTeaching modalities are methods used by instructors to present mate- rials or conduct instructional activities using simulation. Examples include case studies, role-play, computer-based simulation, or stan- dardized patients.The leader group's review of annotated bibliographies has aided in identifying areas in which the current research in simulation is saturated as well as areas lacking in sufficient research. …

To determine the effect of vitamin D3 supplementation on 25-hydroxyvitamin D [25(OH)D], lipid profile and markers of insulin resistance in obese adolescents.In this double-blind, randomized, placebo-controlled trial, 58 obese adolescents (n = 58; 12-18 years of age) received either vitamin D3 (2,000 IU/day) or placebo for 12 weeks. Total 25(OH)D, fasting plasma glucose, insulin and lipid profile were measured at baseline and following supplementation.The trial was completed by 44/58 enrolled participants. At the end of the 12 weeks, total serum 25(OH)D concentrations increased to a modest degree (median 6 ng/ml) in the vitamin D-supplemented group (p0.001). Supplementation showed no detectable changes in fasting plasma glucose, insulin, homeostatic model of assessment index (HOMA-IR), lipids and highly sensitive C-reactive protein.12 weeks of vitamin D3 supplementation in obese adolescents with 2,000 IU once daily resulted in a modest increase in 25(OH)D concentration in obese adolescents, but did not affect the lipid profile and markers of insulin resistance and inflammation. Further studies with higher doses of vitamin D3 and/or longer duration of supplementation are needed to understand if vitamin D3 supplementation can impact lipid profiles and markers of insulin resistance and inflammation in obese children.

OBJECTIVES:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. RESULTS:We determined the sets of genes that were differentially altered between eribulin and paclitaxel treatment in breast, endometrial, and ovarian cancer cell line panels. Our unsupervised clustering analyses revealed that expression profiles of gene sets altered with treatments were correlated with the in vitro antiproliferative activities of the drugs. Several tubulin isotypes had significantly lower expression in cell lines treated with eribulin compared to paclitaxel. Pathway enrichment analyses of gene sets revealed that the common pathways altered between treatments in the 3 cancer panels were related to cytoskeleton remodeling and cell cycle regulation. The epithelial-mesenchymal transition (EMT) pathway was enriched in genes with significantly altered expression between the two drugs for breast and endometrial cancers, but not for ovarian cancer. Expression of genes from the EMT pathway correlated with eribulin sensitivity in breast cancer and with paclitaxel sensitivity in endometrial cancer. Alteration of expression profiles of EMT genes between sensitive and resistant cell lines allowed us to predict drug sensitivity for breast and endometrial cancers. CONCLUSION:Gene expression analysis showed that gene sets that were altered between eribulin and paclitaxel correlated with drug in vitro antiproliferative activities in breast and endometrial cancer cell line panels. Among the panels, breast cancer provided the strongest differentiation between eribulin and paclitaxel sensitivities based on gene expression. In addition, EMT genes were predictive of eribulin sensitivity in the breast and endometrial cancer panels.

Vitamin D deficiency is highly prevalent in obese children, and obese children tend to respond poorly to vitamin D supplementation. The objective of the study was to compare the response to vitamin D(3) supplementation (2,000 IU once daily for 12 weeks) between obese and non-obese Caucasian adolescents.The study design was open label non-randomized. It was carried out at a single center. Eighteen obese adolescents (aged 12-18 years) and the same number of age-, gender- and season-matched non-obese adolescents received vitamin D(3) (2,000 IU/day) orally for 12 weeks. Total serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium and phosphorus were measured at baseline and at the end of the 12-week period.The mean baseline 25(OH)D level was higher in the non-obese compared to the obese subjects (mean 28.9 vs. 25.2 ng/ml; p = 0.029). The increment in 25(OH)D levels following vitamin D supplementation was significantly lower in the obese adolescents (mean change 5.8 vs. 9.8 ng/ml; p = 0.019).Higher doses of vitamin D are required to treat vitamin D deficiency in obese adolescents compared to their non-obese peers.

An integrative review was undertaken to analyze studies published since 1998 on the use of high-fidelity patient simulation (HFPS) in undergraduate nursing education. This review found that HFPS benefits nursing students in terms of knowledge, value, realism, and learner satisfaction; findings were mixed in the areas of student confidence, knowledge transfer, and stress. Further research in these and other areas will determine whether its increased use is warranted.

This study aimed to assess (1) the relationship of systemic bone mineral density (BMD) and osteoporotic status with the surgeon's subjective assessment of local jawbone quality, and (2) whether the surgeon's subjective assessment of local jawbone quality is a predictor of implant failure.A retrospective analysis of 2,867 dental implants placed in 645 patients was accomplished. The surgeon's assessment of bone quality at the time of dental implant placement was recorded. Of those, 208 patients with 701 implants had BMD data available within 3 years. Statistical analyses were conducted to determine relationships between BMD, osteoporotic status, and local jawbone quality and to determine the relationship between local jawbone quality and implant survival.There was no association between systemic BMD and the surgeon's assessment of bone quality (p =.52) nor between osteoporotic status and the surgeon's assessment of local jawbone quality (Spearman rank correlation coefficient=0.08). Additional retrospective analysis revealed implants placed in moderate- (hazard ratio=1.67; p=.043) or poor-quality (HR=3.45, p.001) bone (surgeon's assessment) were significantly more likely to fail than implants placed in good-quality bone.Systemic BMD and osteoporotic status are not associated with local jawbone quality. Implants placed in good-quality bone, as assessed subjectively by the surgeon at the time of implant placement, have significantly better survival characteristics than implants placed in moderate-/poor-quality bone.

The bacterial endospore cortex peptidoglycan is synthesized between the double membranes of the developing forespore and is required for attainment of spore dehydration and dormancy. The Bacillus subtilis spoVB, spoVD and spoVE gene products are expressed in the mother cell compartment early during sporulation and play roles in cortex synthesis. Here we show that mutations in these genes block synthesis of cortex peptidoglycan and cause accumulation of peptidoglycan precursors, indicating a defect at the earliest steps of peptidoglycan polymerization. Loss of spoIV gene products involved in activation of later, sigma(K)-dependent mother cell gene expression results in decreased synthesis of cortex peptidoglycan, even in the presence of the SpoV proteins that were synthesized earlier, apparently due to decreased precursor production. Data show that activation of sigma(K) is required for increased synthesis of the soluble peptidoglycan precursors, and Western blot analyses show that increases in the precursor synthesis enzymes MurAA, MurB, MurC and MurF are dependent on sigma(K) activation. Overall, our results indicate that a decrease in peptidoglycan precursor synthesis during early sporulation, followed by renewed precursor synthesis upon sigma(K) activation, serves as a regulatory mechanism for the timing of spore cortex synthesis.

Tazemetostat (EPZ-6438 or E7438) is a selective small molecule inhibitor of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase (HMT). EZH2 is the catalytic subunit of the multi-protein HMT complex known as polycomb repressive complex 2 (PRC2), which is responsible for mono-, di-, and trimethylation (me3) of histone H3 lysine 27 (H3K27). An exploratory objective for the phase 1 study of tazemetostat in subjects with advanced solid tumors or B-cell lymphomas was to explore the pharmacokinetic: pharmacodynamic (PK: PD) relationships such as correlation of H3K27me3 inhibition in patient tissue with systemic drug exposure. Pre-clinical xenograft models of EZH2 inhibition have previously shown tumor regression correlating with dose-dependent H3K27me3 decreases in both tumor tissue and skin epidermis (Knutson 2014). H3K27me3 reduction in the epidermis was calculated as a change in percentage of H3K27me3 positive cell employing an immunohistochemistry (IHC) assay with subsequent image analysis. These studies and the low feasibility of obtaining matched pre- and post-treatment tumor biopsies, led to the selection of skin as a surrogate tissue for evaluation in the phase 1 study at screening and 28 days post dose and the use of IHC as a PD biomarker of target inhibition. Examination of phase 1 skin biopsies exhibited dose and exposure-dependent decreases in the percentage of H3K27me3 positive cells, however, the magnitude of reduction (60%) was less than observed in pre-clinical models (80%). Further investigation of the IHC images revealed a difference of H3K27me3 levels in distinct layers or strata of the skin. The stratum spinosum exhibited a distinct dose and exposure-dependent loss of H3K27me3 staining while the stratum basale showed a concomitant minimal loss of H3K27me3. These observations gave rise to the possibility of a stratum-specific PD response in skin to tazemetostat exposure. To fully evaluate this notion, a more sophisticated, unbiased, image analysis algorithm was employed to measure H3K27me3 levels across the strata of the epidermis. The image analysis algorithm was designed to identify three distinct regions: the full thickness epidermis, stratum basale to stratum corneum; the stratum basale alone; and the stratum spinosum. Iterative rounds of optimization were performed to identify the basale layer while excluding follicles and glands. Because skin has inherent challenges related to the chromogenic similarity between DAB and melanin, careful attention was paid to the negative control to ensure that endogenous melanin was not included in the analysis. Segregation of the stratum basale layer from the remainder of the epidermis led to a refined H3K27me3 analysis and resulted in an improved correlation of H3K27me3 inhibition with drug exposure. This analysis highlights that the zonal layers of the epidermis may require separate evaluation when analyzing skin as a surrogate tissue for proof of mechanism studies. Although more accessible for repeat biopsy, the use of skin as a surrogate tissue does not preclude the need to understand the PD effects in the target tumor tissue. To that end, optional paired tumor biopsies are being collected in the Phase 2 tazemetostat trial and will be evaluated for PD endpoints including H3K27me3 in addition to other biomarkers. Citation Format: Alice A. McDonald, Galina Kuznetsov, Namita Kumar, Amy Weaver, Trevor Do, Jeff Dzubay, Heike Keilhack, Nigel waters, Nathalie Rioux, Stephen J. Blakemore. Advanced image analysis of H3K27 trimethylation in skin from subjects dosed with the EZH2 inhibitor tazemetostat. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B6.