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Background:Immunotherapy was first introduced into the treatment of triple negative breast cancer with the approval of nab-paclitaxel + atezolizumab in patients with metastatic PD-L1-positive disease. Continued research sheds light on the utility of other immuontherapies in the metastatic setting as well as a potential role for immunotherapy in neoadjuvant disease. Given the factors impacting patient eligibility and the rationale for further exploring immunotherapy in novel settings, education can help ensure that oncologists are well-informed about available clinical trial data and ongoing research to optimize the use of immunotherapy in this subtype of breast cancer. The goal of this study was to determine if participation in an educational activity can improve the knowledge and competency of oncologists on the application of checkpoint inhibitors in the treatment of triple negative breast cancer.Methods: An online continuing education (CME) activity consisted of a 30-minute video discussion with synchronized slides between 2 panelists about the rationale and ongoing clinical trials exploring data for immunotherapy in triple negative breast cancer. Educational effect was assessed using a repeated pairs pre-assessment/post-assessment study design and compared of content-based pre- and post-assessment responses. A chi-square test was used to identify statistical differences between pre- and post-assessment responses. P values were calculated and those < 0.05 were considered statistically significant. Data from oncologist participants in the educational activity were collected between 3/22/20 through 5/19/20. Results:Participation in education resulted in statistically significant improvement and a considerable educational effect for oncologists (n=121; p Citation Format: Kinjal Parikh, Charlotte Warren, Patrick Kugel, Ann Carothers, Haleh Kadkhoda, Leisha Emens. Utilizing education to strengthen oncologist' understanding of immunotherapy in 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 PS9-15.

Background:The treatment armamentarium for patients with refractory metastatic HER2+ breast cancer was limited due to a lack of effective agents after the use of ado-trastuzumab emtansine, trastuzumab, and pertuzumab. Novel therapies such as trastuzumab deruxtecan and tucatinib provided high response rates to a patient subgroup with unmet clinical needs for having effective therapy. As data from clinical trials become available, landmark trials are published, and FDA approvals and guidelines incorporate novel therapies, continuing medical education (CME) for oncologists is necessary to facilitate the translation of evidence to their clinical practice. Methods: A series of 4 CME-certified activities were launched to educate physicians on new therapies in metastatic HER2+ breast cancer following data releases from the 2019 San Antonio Breast Cancer Symposium. Education followed adult learning principles starting with a goal of increasing awareness on novel agents and outcomes presented at national conferences and then integrating these agents into clinical practice, including adverse event management. Panel discussions were utilized to provide multiple faculty perspectives and clinical examples. Effectiveness was analyzed using 3 multiple-choice and 1 self-efficacy question measuring knowledge, competence, and confidence, presented as pre-/post-CME repeated pairs for each of the activities. Oncologists who completed both the pre- and post-CME questions were included in analysis and McNemar’s tests were conducted to assess statistical significance of the results with p < .05 being considered significant. The CME activities launched from December 2019 through March 2020 and data collected June 2020. Results:As of 6/9/2020, 6,473 global physicians had participated in the activities including 3,036 oncologists. 62% of the Oncologists identified themselves as practicing in a community setting, with 87% reporting a plan to make changes to their practice. Analyses from the activities found significant improvements in knowledge, competence, and confidence, measured as relative changes in % of correct responses or % of confident physicians from pre- to post-CME, across the various themes of learning objectives in metastatic HER2+ breast cancer:• 62% increase in knowledge of clinical trial outcomes (n = 339; pre: 53% vs. post: 86%, p < .001)•35% increase in understanding the mechanism or rationale for novel agents (n = 368; pre: 52% vs. post: 70%, p < .001) •15% increase in the ability to identify patients eligible for novel therapies (n = 210; pre: 61% vs. post: 70%, p < .05) •38% increase in managing adverse events of novel therapies (n = 158; pre: 37% vs. post: 51%, p < .001) •83% increase in the percent of oncologists who were mostly or very confident in treating metastatic HER2+ breast cancer patients (n = 368; pre: 18% vs. post: 33%, p < .001) Conclusions: This series of online, expert-led, CME-certified educational activities resulted in significant improvement in knowledge, competence, and confidence among learners regarding the use of novel anti-HER2 therapies in the management of metastatic breast cancer. These results demonstrate the effectiveness of on-demand education to translate information from data to clinical practice and directly benefit patients. Grantors:This educational initiative was supported through educational grants from Astra Zeneca Pharmaceuticals LP and Daiichi Sankyo. Citation Format: Kinjal Parikh, Nabil Dorkhom, Pan Chen, Davecia Ragoonath Cameron, Richard Caraico, Kelly Hanley, Shanu Modi. Impact of online education regarding novel HER2 therapies on translating evidence to practice [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 PS9-64.

Background:Recently, CDK4/6 inhibitors have revolutionized the care of patients with hormone receptor (HR)-positive, HER2-negative breast cancer, improving survival outcomes. Already, there are multiple CDK4/6 inhibitors available that differ in their pharmacologic features, reported outcomes, therapeutic indications, and adverse event profiles. As data from clinical trials or subgroup analyses become available, landmark trials are published, and guideline recommendations or clinical utility of these therapies change, continuing medical education (CME) for oncologists is necessary to facilitate timely and accurate translation of evidence to their clinical practice. Methods: A series of 5 CME-certified activities were launched to educate oncologists on CDK4/6 therapies in HR-positive advanced breast cancer following data releases from ESMO 2019 through SABCS 2019. Education followed adult learning principles starting with a goal of increasing awareness on novel data and then integrating these agents into clinical practice, including adverse event management. Panel discussions were utilized to provide multiple faculty perspectives and clinical anecdotes. Effectiveness was analyzed using 3 multiple-choice and 1 self-efficacy question measuring knowledge, competence, and confidence, presented as pre-/post-CME repeated pairs for each of the activities. Oncologists who completed both the pre- and post-CME questions were included in analysis and MeNemar’s tests were conducted to assess statistical significance of the results with p < .05 being considered significant. The 5 CME activities launched from September 2019 through December 2019.Results: As of 6/9/2020, 6,037 global physicians had participated in the activities including 2,511 oncologists. 64% of the oncologists identified themselves as practicing in a community setting and 82% of them intended to modify their treatment plans as a result of education. Analyses from 3 activities using data from n=356-458 oncologists found significant improvements in: •Knowledge of clinical trial safety and efficacy data with CDK4/6 inhibitors (% pre correct 65% vs. % post correct 73%; p < .001) •Competence implementing personalized CDK4/6 inhibitor for a patient (% pre correct 74% vs. % post correct 84%; p < .001) •Knowledge of adverse events with CDK4/6 inhibitors (% pre correct 63% vs. % post correct 74%; p Citation Format: Kinjal Parikh, Nabil Dorkhom, Pan Chen, Davecia Ragoonath Cameron, Mindy Tanzola, Pamela Peters, Sara Tolaney. Multiple activities improve oncologists' knowledge and competence with CDK4/6 inhibitors in HR+ breast cancer over time [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 PS9-40.

The objective of the present investigation was to formulate and characterize a novel lipid-based carrier-emulsomes loaded with triamcinolone acetonide (TA)/Nile red (NR) for non-invasive delivery to the posterior segment of the eye upon topical application. To optimize and delineate the effect of independent variables on dependent variables, Box-Behnken design (BBD) was adopted. The optimized batch was characterized for size, zeta potential, surface morphology by transmission electron microscopy, drug-excipient interaction by differential scanning calorimetry, osmolarity, pH, ex vivo transcorneal permeation, and stability studies. A short-term exposure (STE) test was performed on Statens Seruminstitut Rabbit Corneal (SIRC) cell lines to evaluate the in vitro ocular irritation. Precorneal retention study was performed in rabbit eyes. Confocal microscopy was used for ocular distribution studies in mice eye by preparing dye (Nile red)-loaded formulations. The surface response and contour plots along with ANOVA results demonstrated an interaction between the factors. The optimized batch had particle size of 131.17 ± 3.17 nm and entrapment efficiency of 71.56 ± 4.19%. TEM image showed unimodal, nano-sized emulsomes. TA-loaded emulsomes exhibited higher transcorneal permeation as compared to drug solution. In vitro irritation studies confirmed the safety of excipients for ophthalmic use. Fluorescence microscopic images obtained after ocular distribution studies showed strong fluorescence in inner and outer plexiform layers of the retina in comparison to dye solution confirming the delivery of dye to the posterior segment of mice eye after topical ocular instillation. Graphical abstract.

BACKGROUND: Nausea and vomiting are some of the most common and distressing side effects of chemotherapy according to patients. Chemotherapy-induced nausea and vomiting (CINV) places a substantial burden on patients and their loved ones, which greatly reduces the quality of life, nutritional habits, ability to work and socialize, and adhere to treatment regimens. Therefore, assessment of CINV is an essential component of care for patients receiving chemotherapy. Multiple factors influence the incidence of CINV with the chemotherapy regimen, both type and dosage, being the primary risk factor. It is generally assumed that the strongest patient-related factors are younger age and female sex. However, reports in the literature have demonstrated that using these factors clinicians underestimate the prevalence of CINV, especially delayed nausea. Thus, there is a need for risk assessment tools to accurately identify patients requiring anti-emetic regimens to improve quality of life of patients and their families. Our assay is based on the knowledge that chemotherapeutic agents cause bursts of reactive oxygen species (ROS) resulting in cellular damage and release of substances that activate receptors in the chemoreceptor trigger zone. Glutathione (GSH), a key antioxidant, is responsible for maintaining redox homeostasis by neutralizing ROS. Therefore, we hypothesized that a patient’s risk of CINV may reflect individual variations in the efficiency to scavenge and neutralize ROS after chemotherapy. METHODS: Patients enrolled in our institutional review board approved study (N= 220), were treated in the adjuvant or neoadjuvant setting with highly or moderately emetogenic chemotherapies for their breast cancer diagnosis. Blood samples were drawn from chemotherapy naïve patients and used in the predictive blood assay. The assay is based on the conversion of a bioactive probe, hydroxyethyl disulfide, into mercaptoethanol, which once normalized to red blood cell count, indicates glutathione recycling capacity. Incidence and severity of delayed nausea symptoms were collected from notes in medical records as well as anti-emetic prescription history. RESULTS: A recent second evaluation of patients treated with platinum-based therapies confirmed our previously published data, demonstrating a correlation between low glutathione recycling capacity and risk of delayed nausea for patients with lung and colon cancer (N=111; misclassification rate 0.153; AUC 0.72). In this study, we evaluated age-matched patients treated with anthracycline/cyclophosphamide (AC)(N=42), docetaxel/cyclophosphamide (TC)(N=39), docetaxel/carboplatin/trastuzumab (TCH)(N=27) or docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP)(N=25). The incidence of moderate-to-severe nausea was highest in the AC (38.1%) and TCHP (36.0%) groups. The TCH group had the lowest incidence of patients (11%) reporting delayed nausea. SAS/STAT v.14.1 classification trees demonstrated a weak association between anthracycline-induced delayed nausea and MyNauseaRisk score (misclassification rate 0.333; AUC 0.67). Similarly, patients treated with TC demonstrated a correlation between MyNauseaRisk score and severity of nausea as previously seen for platinum therapies. The algorithm determined that age stratification of patients in the TCHP group prior to applying the MyNauseaRisk score reduced the misclassification rate (0.280) and improved the AUC (0.72). CONCLUSION: The results from this exploratory prospective study suggests that a reduced ability to recycle GSH in the blood may offer an objective prediction of delayed nausea, possibly allowing for optimal anti-emetic regimen to improve the quality-of-life for breast cancer patients. Citation Format: Nicole F Laslett, Dillon D McCourt, Kinjal Parikh, John F Kennedy, Zonera A Ali, Erik L Zeger, Aarti L Shevade, Tracey L Evans, Paul B Gilman, Margaretha Wallon. MyNauseaRisk assay - Predicting chemotherapy-induced delayed nausea using a blood-based assay [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-12.

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty‐two US pediatric institutions participated in a 10‐year review (2008–2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract‐based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community deprivation were obtained. Data for 947 cases showed median age at diagnosis of 9 years; 51% and 56% identified as male and non‐White, respectively. Most (89%) had health insurance and were first diagnosed in the United States (82%). Only 13% reported travel to an endemic region before diagnosis. Although 96% of patients were prescribed secondary prophylaxis, only 58% were prescribed intramuscular benzathine penicillin G. Higher deprivation was associated with increasing disease severity (odds ratio, 1.25; 95% CI, 1.08–1.46). Conclusions The majority of recent US cases of ARF and RHD are endemic rather than the result of foreign exposure. Children who live in more deprived communities are at risk for more severe disease. This study demonstrates a need to improve guideline‐based treatment for ARF/RHD with respect to secondary prophylaxis and to increase research efforts to better understand ARF and RHD in the United States.

Graphical abstract, Highlights • The authors report successful palliation of APVS in DORV and right-dominant AVCD. • Fetal echocardiography assists in the prenatal diagnosis. • Prenatal cardiac MRI can measure lung volumes to assess bronchial compression.

Background: Chemotherapy-induced nausea and vomiting (CINV) is a distressing side effect according to patients. CINV can negatively affect nutritional habits, ability to work and motivation to follow treatment regimens. Assessment of CINV is an essential component of care for patients receiving chemotherapy. Multiple factors influence the incidence of CINV with the chemotherapy regimen, both type and dosage, being the primary risk factor. It is generally assumed that the strongest patient-related factors are younger age and female sex. However, reports in the literature have demonstrated that using these factors clinicians underestimate the prevalence of CINV, especially delayed nausea. Thus, there is a need for risk assessment tools to accurately identify patients requiring anti-emetic regimens to improve quality of life of patients and their families. Most chemotherapeutic agents cause bursts of reactive oxygen species (ROS) resulting in cellular damage and release of substances that can activate receptors in the chemoreceptor trigger zone. Glutathione (GSH), a key antioxidant, is responsible for maintaining redox homeostasis by neutralizing ROS elicited from chemotherapy. Therefore, we hypothesized that a patient's risk of CINV may reflect individual variations in the efficiency to scavenge free radicals after chemotherapy. Methods: In our Institutional Review Board approved study, we have enrolled over 300 patients and completed assessment of 133 patients. These patients were treated with highly or moderately emetogenic chemotherapies for lung, colon, or breast cancer. Blood samples were drawn from chemotherapy naïve patients and used to determine the glutathione recycling capacity. The assay detects the conversion of a bioactive probe, hydroxyethyl disulfide, into mercaptoethanol, which once normalized to red blood cell count, indicates glutathione recycling capacity (ChemoTox). Nausea severity was reported using the Rotterdam Symptom Check-List at each treatment cycle. Self-reported symptoms were compared to notes in medical records and anti-emetic prescription history. Results: We previously published the correlation between low ChemoTox and risk of delayed nausea for patients receiving platinum-based therapy for lung and colon cancer (N=64; correctly classified 88.5%; AUC 0.77). In this second evaluation, using SAS/STAT v.14.1 classification trees, we show the results from testing this prediction tool for breast cancer patients that typically are treated with anthracycline- or taxane-based chemotherapies. An early evaluation of anthracycline-based therapies (N=37) demonstrated a weak association between experienced nausea and ChemoTox (correctly classified 69.2%; AUC 0.64). In contrast, patients treated with taxane-based therapies (N=32) demonstrated a similar correlation between ChemoTox and severity of nausea as previously seen for platinum therapies. Also, a similar accuracy in identifying patients at risk of moderate-severe nausea was identified (correctly classified 77.3%; AUC 0.79). Conclusion: The results from our prospective study suggests that a reduced ability to recycle GSH in the blood may offer an objective prediction of delayed nausea, possibly allowing for optimal anti-emetic regimen to improve the quality-of-life for breast cancer patients. Citation Format: McCourt DD, Parikh K, Dadivas A, Brady AL, Kennedy J, Ali ZA, Zeger EL, Shevade A, Gilman PB, Wallon UM. Assay for personalized prediction of chemotherapy-induced delayed nausea [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-08.

Introduction: Rheumatic heart disease (RHD) tracks with other cardiovascular health inequities in the US; however, RHD mortality captures a fraction of those affected and lags behind diagnosis by decades. There is little contemporary data on children living with acute rheumatic fever (ARF) and RHD within the US. This study describes recent pediatric ARF/RHD in the US and examines the association with community deprivation. Methods: Sixty US institutions were invited to participate in a 10-year review (2008-2018). Geocoding was used to determine a census tract-based socioeconomic deprivation index (DI) ranging from 0-1 (1 being most deprived). Independent sample t-test was used to compare DI means. Odds ratios (OR) with 95% confidence intervals were obtained from multivariable logistic regression. The DI was scaled to provide ORs for a one standard deviation increase. Results: Data for 947 cases from 22 institutions showed median age at diagnosis of 9 years, with half identifying as male (51%) and non-white (52%), and three-quarters (74%) identifying as non-Hispanic. Most identified English as their primary language, had health insurance, and were first diagnosed in the US (84%, 89%, and 82%, respectively). Of the 157 (17%) with travel exposure, Pacific Islands (38%) and Africa (21%) were most commonly identified. Nearly three-quarters (73%) were diagnosed with ARF and most (98%) had an echocardiogram at diagnosis. While 96% of patients were prescribed secondary prophylaxis, only half (58%) were prescribed intramuscular Benzathine penicillin (BPG), the gold standard. The mean DI was 0.39±0.15. Higher deprivation was associated with RHD as opposed to ARF at diagnosis (DI 0.42 vs. 0.38, p Conclusions: Recent pediatric cases of ARF and RHD in the US are endemic, rather than from foreign exposure and children who live in more deprived communities are at risk for more severe disease. Additional research is needed into why intramuscular penicillin, which has superior efficacy compared to oral penicillin, is prescribed in only half of cases.

BACKGROUND Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition characterized by a wide spectrum of clinical findings. Patients with NF1 develop benign and malignant tumors along the nerves of the skin, brain, and other body parts. Due to the unique presentation of each patient, clinicians are challenged to stay current with emerging data and how best to integrate new agents into multidisciplinary treatment paradigms. The objective of this study was to assess changes in neurologists’ and pediatricians’ knowledge and confidence through participation in education regarding NF1 treatment. METHODS The educational activity consisted of a 30-minute online enduring, 1 faculty, chapterized summary of a live symposium. Educational effect was assessed with a repeated pairs pre-/post-assessment study with a 3-item, multiple choice, knowledge questionnaire and one confidence assessment question. For all questions, each participant served as his/her own control. Pre- and post-assessment scores were compared to determine relative changes in the proportion of correct responses. A chi-square test assessed statistical significance at the P < 0.05 level. The activity launched 23rd December 2019; data were collected until 2nd April 2020. RESULTS Overall, statistically significant improvements were seen after education for neurologists (N=171, P < 0.05) and pediatricians (N=260, P < 0.01). The relative improvement in correct answers was 26% for neurologists and 48% for pediatricians (percent of total correct responses pre-/post-assessment were 27%/34% and 23%/34%, respectively). Following the activity, 16% of neurologists and 22% of pediatricians had a measurable increase in confidence regarding their understanding of multidisciplinary management of NF1. CONCLUSIONS Participation in an online, 30-minute enduring CME intervention resulted in statistically significant improvements in knowledge and confidence of neurologists and pediatricians, that result in improvements in clinical care. Continued educational activities are paramount to address residual gaps and further increase clinicians’ confidence in this clinical setting.

Background Advanced melanoma treatment selection is guided by BRAF-mutation status and patient and disease-specific factors. Historically, oncologists decided between targeted therapy or immune checkpoint inhibitors (ICI). However, given the differences in onset of activity, response durability, and adverse events combination BRAF/MEK inhibitors and ICI (triplet therapy) are being evaluated to optimize outcomes. With several trials due to report, oncologists need education to stay up-to-date on the available data and contextualize this potential treatment option. Methods An online continuing education (CME) activity consisting of a multi-media 30-minute video panel discussion explored the rationale, available clinical trial data, and future directions of triplet therapy for the treatment of advanced BRAF-mutated melanoma.1 Educational effect was assessed using a repeated pairs pre-assessment/post-assessment study design and compared the pre- and post-assessment responses. A chi-square test was used to identify differences between pre- and post-assessment responses. Effect size was calculated using Cramer’s V test by determining the strength of the association between the activity and the outcomes (V = 0.16–0.26 is considerable and V > 0.26 is extensive). P values were calculated and those Results Participation in education resulted in statistically significant improvements and noticeable educational effect for oncologists (n=49; p Conclusions This online, interactive, expert-led, CME-certified educational activity resulted in significant gains in oncologist knowledge and confidence regarding triplet therapy in the management of melanoma. These results demonstrate the effectiveness of on-demand education but also highlight an ongoing need for education on this topic as further data becomes available. Acknowledgements This educational initiative was supported through educational grants from Novartis Pharmaceuticals Corporation and Genentech Reference Sullivan RJ, Salama AKS. Managing Melanoma: Emerging Concepts of Triplet Therapy. https://www.medscape.org/viewarticle/923003

Background Adjuvant therapy for patients with melanoma is currently recommended for patients with stage III disease with either immune checkpint inhibitors or combination dabrafenib/trametinib based on BRAF-status. Adjuvant treatment demonstrates improvement in recurence-free survival and overall survival. However, risk models suggesting that patients with stage IIB/IIC disease may have a higher risk of recurrence than patients with stage IIIA disease have prompted exploration into the use of adjuvant therapy in this patient subgroup as well. With several ongoing trials due to report, oncologists need education to stay up-to-date on the available data and contextualize this potential treatment option to implement therapy at the earliest point of clinical benefit to patients while also collaborating with surgical teams for optimal care planning. Methods An online continuing education (CME) activity consisted of a multi-media 30-minute video panel of a medical oncologist and surgical oncologist discussing the rationale, available clinical trial data, and future directions of adjuvant therapy for the treatment of patients with stage II melanoma.1 Educational effect was assessed using a repeated paired pre-assessment/post-assessment study design and compared the pre- and post-assessment responses. A chi-square test was used to identify differences between pre- and post-assessment responses. Effect size was calculated using Cramer’s V test by determining the strength of the association between the activity and the outcomes (V = 0.16–0.26 is considerable and V > 0.26 is extensive). P values were calculated and those Results Participation in education resulted noticeable educational effects for both oncologists (p Conclusions This online, interactive, multi-media, expert-led, CME-certified educational activity resulted in significant gains in oncologist and surgeon knowledge and competence with improvements in confidence regarding the role of adjuvant therapy in the management of high risk stage II melanoma and recommending clinical trials for eligible patients. These results demonstrate the effectiveness of education, especially in online and on-demand formats and those requiring cross-discipline collaboration, and also highlights an ongoing need to further educate on this topic. Acknowledgements This educational initiative was supported through independent educational grants from Bristol Myers Squibb. Reference Luke J, Yoon C. Adjuvant Melanoma Treatment: Can We Improve Outcomes for More Patients: https://www.medscape.org/viewarticle/932047.

The present investigation aimed to optimize the critical parameters affecting the globule size of self-emulsifying drug delivery system. Based on preliminary screening, three critical parameters, viz., amount of oil, surfactant, and co-surfactant were found to affect the globule size. I-optimal mixture design and Artificial Neural Network (ANN) were used to optimize the formulation with respect to minimum globule size. Comparative study was carried out to identify which optimization technique gave better predictability for the selected output parameter. R-value and MSE values were taken into consideration for comparison of both techniques. Using Response Surface Methodology-based I-optimal mixture design approach, the R2 value was found to be 0.9867, whereas with ANN technique, it was found to be 0.99548. The predicted size for the optimized batch by I-optimal design was 122.377 nm, whereas by ANN, it was 119.6783 nm against the actual obtained size of 118.2 ± 2.3 nm. This analysis indicated superior predictability of output for given input variables by ANN as compared to model-dependent DoE I-optimal design approach.

Present research focuses on formulation and optimization of enteric coated bilayer tablets of mesalamine to provide colon targeted delivery for the treatment of ulcerative colitis. Non-site-specific delivery of mesalamine is the major drawback of immediate release formulations, whereas sustained release formulations lack “loading dose” when the target site is reached. Hence, we prepared bilayer tablets having combined loading and maintenance doses using QbD approach. Screening of different swellable and non-swellable polymers (HPMC K4M, HPMC K15M, HPMC E15LV, Ethyl Cellulose, Eudragit® RLPO and Eudragit® RSPO) was carried out to form a sustained release layer. The immediate release layer containing the loading dose was prepared by wet granulation and compressed over the pre-compressed SR layer. Thereafter, Eudragit® S100 coating was applied to provide colon targeted drug release. The concentrations of the polymers, HPMC K4M and HPMC K15M (which were found to be most suitable during screening study), were optimized using RSM to generate a robust design space. All tablets were characterized for assay, weight variation, hardness and friability and were found to meet the pharmacopoeial standards. Results of in vivo pharmacokinetic studies in rabbits clearly revealed sustained drug release up to 24 h. Roentogenographic studies confirmed colon targeted delivery of the developed tablets.

Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5-year survival rate for men with prostate cancer who develop metastatic disease is only 29%. Current treatment options for metastatic castration-recurrent prostate cancer (mCRPC) are associated with toxicity and a limited durable response; therefore, additional lines of efficacious and minimally toxic therapy are needed. Olaparib, a poly(adenosine 5'-diphosphate) ribose polymerase (PARP) inhibitor, received a U.S. Food and Drug Administration breakthrough therapy designation in January 2016 for the treatment of patients with BRCA1/2 or ATM gene-mutated mCRPC based on results of a compelling phase II trial of olaparib in patients with advanced castration-resistant prostate cancer (TOPARP-A). This study found that men with mCRPC and genetic mutations in DNA damage repair genes had an overall response rate of nearly 90% with olaparib treatment. In this review, we describe current therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of mCRPC. Olaparib may constitute a promising treatment to prolong survival in patients with mCRPC, with an acceptable adverse effect profile. As the role of PARP inhibition in prostate cancer and other malignancies becomes further elucidated, olaparib may be shown to be beneficial for other patient populations.

Felbamate, an antiepileptic drug is administered multiple times a day to obtain proper restorative action against seizures in childhood onset epilepsy (Lennox-Gastaut syndrome), which usually result in poor therapeutic efficacy because of fluctuating plasma levels and low patient compliance. Hence, controlled release hydroxypropyl methylcellulose matrix tablets of felbamate were formulated to overcome these drawbacks. The results of pre-formulation studies such as differential scanning calorimetry and Fourier transform infrared spectroscopy showed compatibility of drug with the selected excipients. The formulation variables were optimized using D-optimal design which can elucidate the effect of all variables simultaneously during formulation optimization. In vitro drug release at the end of 2, 8 and 20 h were taken as the response parameters for the optimization study by D-optimal design. The results enabled selection of the formulation with the desired drug release pattern approaching to zero order. The optimized batch was subjected to in vivo pharmacokinetic studies in rabbits which showed extended release of drug up to 24 h. Thus, the felbamate controlled release tablets optimized by D-optimal design have potential to reduce the dose and dosing frequency, improve therapy and patient compliance.

358 Background: Treatment paradigms for bladder (UC) and kidney (RCC) cancers is evolving with the advent of novel treatment approaches, personalized medicine, and combinatorial strategies. As the medical literature in the space evolves, identifying oncologists’ (oncs) and urologists’ (uros) educational gaps is important to inform continuing medical education (CME) needs and, ultimately, to improve patient outcomes. Methods: Medscape Oncology conducted a 16 question, online, incentivized survey in June 2020 targeting genitourinary (GU) cancer physicians. Respondents’ confidentiality was maintained and responses were de-identified and aggregated for analysis. Results: Results are reported for 100 respondents (50 oncs & 50 uros): In UC: Learners identified CME as mostly/very important for: Managing treatment related adverse events (trAEs) – 84% Clinical trial outcomes – 77% Timely/appropriate biomarker testing – 68% Understanding mechanism of action (MOA) and rationale of novel agents – 66% Treatment planning CME was considered mostly/very important for: All stages: non-muscle invasive (NMIBC), muscle-invasive (MIBC), and first line (1L) metastatic – 72%, 85%, 92% respectively Determining the optimal role for immunotherapy (IO) – 82% Sequencing therapies – 72% In subgroup analyses More oncs vs. uros identified biomarker testing and treatment selection as mostly/very important (p < .01) More general oncs vs. GU oncs identified education on clinical trial outcomes and sequencing of therapies as mostly/very important (p < .05) More uros vs. oncs identified NMIBC treatment education as mostly/very important (p < .01) More low vs. high volume treaters identified education on sequencing and MIBC as mostly/very important (p < .01) Rating % very experienced: Counseling on trAEs – 41% but mitigating AEs of FGFR therapies, ADCs, or IO was only: 16%, 19%, and 26% respectively In RCC: Learners identified CME as mostly/very important for: Selecting optimal 1L therapy – 80% Clinical trial outcomes – 77% Sequencing therapies – 69% Managing trAEs – 64% Understanding MOA and rationale of novel agents – 62% In subgroup analyses More general oncs vs. GU oncs identified importance of education on clinical trial outcomes and 1L treatment selection (p < .05) More low vs. high volume treaters identified importance of education on 1L treatment selection and clinical trial outcomes (p < .05) Rating % very experienced: Counseling on trAEs – 30% but mitigating AEs of targeted therapy or IO was only: 22% and 23% respectively Determining risk score – 22% Selecting 1L therapy – 28%. Conclusions: Medscape Oncology surveys provide valuable information to guide education for oncs and uros and individualize education unique to their treatment setting, patient volume, and practice coverage.

492 Background: Immunotherapy (IO) utility in bladder cancer (UC) has expanded into multiple stages of disease. Employing IO optimally requires mastery of clinical trial data, patient eligibility criteria, and interpretation of biomarkers and determination of treatment sequencing. Given the nuanced therapeutic decision-making, education was developed in partnership between Medscape Oncology and Society for Immunotherapy of Cancer (SITC) to assist oncologists in improving their performance surrounding the management of patients with advanced UC. Methods: A virtual patient simulation (VPS) continuing medical education (CME)-certified activity depicting 2 advanced UC cases was made available to oncologist members of Medscape. The cases depicted 1) a patient with newly diagnosed metastatic UC with comorbidities and PDL1+ disease and 2) a patient with advanced UC progressing on platinum therapy with no actionable mutations. The VPS platform captures real-life decision making process of oncologists in an EHR-like format supported by an extensive database of diagnostic and treatment possibilities. Learners were able to interact with patients via video, order lab tests, assess patients, make diagnoses, and order treatments matching the scope and depth of actual practice. Tailored clinical guidance (CG) employing up-to-date evidence-based and faculty recommendations was provided after each decision point. Decisions were collected pre- and post-CG and analyzed using McNemar’s test to determine p-values. Data were collected from 4/28/20 to 7/13/20. Results: Analyses from oncologists (n = 51-66) found significant improvement in performance measured pre- to-post CG: Case 1: Ordering appropriate testing to determine patient eligibility for therapy (39% pre; 65% post; p < .001) Prescribing appropriate therapy based on patient- and disease-specific factors (38% pre; 77% post; p < .001) Providing appropriate counseling and follow-up for a patient receiving treatment (65% pre; 80% post; p < .01) Case 2: Ordering appropriate testing to determine patient eligibility for therapy (39% pre; 57% post; p < .01) Prescribing appropriate therapy based on patient- and disease-specific factors (25% pre; 41% post; p < .01) Providing appropriate counseling and follow-up for a patient receiving treatment (71% pre; 82% post; p < .05). Conclusions: This activity demonstrates the value of providing oncologists a simulation platform to practice and master clinical decision-making of the limitless possible diagnostic and therapeutic options in the management of advanced UC. Insights from rationales for each clinical decision point uncover continued gaps for oncologists on guideline recommendations, efficacy outcomes, or molecular implications. They also highlight barriers including limited experience or confidence with IO.

137 Background: The treatment armamentarium for patients with metastatic colorectal cancer (mCRC) has expanded significantly and treatment options for progressive disease remain limited. As data from clinical trials or subgroup analyses become available, landmark trials are published, and guideline recommendations or clinical utility of these therapies change, continuing medical education (CME) for oncologists is necessary to ensure that eligible patients continue to receive effective therapies. Methods: A series of 7 activities launched from 2016-2020 to reach a global oncology audience in the care of patients with mCRC. The educational activities included multi-modality approaches with didactics, cases, simulations, and panel discussions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls to measure changes in knowledge, competence, confidence, and performance. Oncologists who completed both the pre- and post-CME questions or who made relevant clinical decisions in the simulation activity were included in analysis and McNemar’s tests were conducted to assess statistical significance of the results with p < .05 being considered significant. The first activity launched on 6/8/2016 and the data reported were collected through 7/20/20. Results: As of 7/20/2020, 59,595 learners participated in the activities, including 18,634 total physician learners with 5,862 oncologists. Significant improvements in knowledge, competence, and confidence among oncologists, measured as relative % changes in correct responses or confidence from pre- to post-CME, were seen (n=60-214) [% pre, % post, p value]: 11%: knowledge regarding therapies for progressive disease in mCRC (83; 92; p < .05); 17%: knowledge of clinical trials assessing impact of patient/disease specific aspects on treatment selection (63; 74; p < .001); 11%: competence selecting therapy (55; 61; p < .05); 41%: confidence selecting therapy (34; 48; p < .001); 24%: confidence addressing communication barriers in mCRC (50; 62; p < .01). Significant improvement in performance of oncologists, measured as absolute % changes in pre- to post-CME correct responses were seen (n = 46) [% pre, % post, p value]: 28%: starting preferred treatment options (24; 52; p < .01); 18%: prescribing regorafenib (24; 43; p < .01); 9%: prescribing trifluridine + tipiracil (0; 9; p < .05). Conclusions: This series of online, expert-led, CME-certified educational activities resulted in significant improvement in knowledge, competence, confidence, and performance among learners regarding the management of patients with progressive metastatic colorectal cancer over time. These results demonstrate the effectiveness of on-demand education as new data emerge and indications expand to reinforce existing knowledge, close persistent gaps, and increase confidence in managing these patients.

248 Background: Care of patients with gastric/GEJ cancer involves multimodality treatment including various systemic and supportive approaches and collaboration of interdisciplinary team members. Optimizing care requires not only adherence to the latest evidence-based and guideline-driven recommendations but also the management of underlying comorbidities or treatment-induced conditions. This complex interplay of factors in treatment planning requires timely education for oncologists and nurses/NPs in both clinically driven topics and interdisciplinary collaboration. Methods: A series of 2 CME/CE-certified activities were launched to educate oncologists and nurses/NPs on the changing paradigms in gastric cancer as well as the interdisciplinary collaboration needed to optimize patient eligibility for treatment. Effectiveness was analyzed using 3 multiple-choice questions measuring knowledge and competence and 1 confidence question were presented as pre-/post- repeated pairs for each of the activities. Oncologists and nurses/NPs who completed both the pre- and post-CME questions were included in the analysis and McNemar’s tests were conducted to assess statistical significance of the results with p < .05 being considered significant. The CME activities launched in 2/2020 with data collected and reported as of 9/2020. Results: 8034 learners participated in the activities including 1163 oncologists and 3665 nurses/NPs. Analyses from the activities found improvement in knowledge, competence, and confidence. Data from oncologists (n = 94-302) and nurses/NPs (n = 169-510) are reported. Statistically significant changes were seen for oncologists in: Knowledge regarding the impact of nutrition and anemia can have on quality-of-life (QOL) and further treatments (50% pre, 72% post; p < .001); Competence related to implementing strategies to address nutrition and anemia to improve quality-of-life and to advance treatment (45% pre, 72% post; p < .001); Confidence regarding their ability to work together as an integrated, interdisciplinary team to enhance quality of life and treatment outcomes through a holistic treatment approach (68% pre, 83% post; p < .001). And for nurses/NPs in: Knowledge regarding the impact that nutrition and anemia can have on QOL and further treatments (34% pre, 50% post; p < .01). Conclusions: This online, interactive, expert-led, CME/CE-certified educational activity resulted in gains in oncologist and nurse/NP knowledge, competence, and confidence surrounding advanced gastric/GEJ cancer management and team collaboration. As patients with gastric cancer continue to present with poor performance status and require not only systemic interventions but also amelioration of underlying conditions, education remains essential for optimal outcomes to members of the interdisciplinary team.

478 Background: The disruption of redox balance is increasingly thought to be one of the most important underlying factors contributing to the development, progression, and metastasis of cancers in human cells. This imbalance in redox homeostasis has been shown to be induced by the generation of free radicals, predominantly reactive oxygen species (ROS). Emerging data have established ROS as a new potential therapeutic target. Understanding the mechanisms associated with tumorigenesis is important to integrate novel potential therapeutic targets and understand which tumors or patient populations may benefit from ongoing research. Shortcomings in oncologists’ knowledge and confidence can hamper the integration of new treatments into the care of patients with cancer. Methods: An online continuing education (CME) activity consisted of a multi-media 30-minute video panel of two panelists discussing the mechanism, pathophysiology, and the premises for novel anti-cancer therapies. Educational effect was assessed using a repeated paired pre-/post-assessment study design. A McNemar’s test was used to identify differences between pre- and post-assessment responses. Effect size was calculated using Cohen’s d test by determining the strength of the association between the activity and the outcomes (d < .20 is modest and d ≥ .80 is large). P values were calculated and those < .05 were considered statistically significant. The activity launched 5/14/2020 and data are represented through 8/6/2020. Results: A total of 1,033 learners, of which there are 656 physicians, participated in the activity. Participating in education resulted in statistically significant improvements and noticeable educational effect and data for oncologists that answered all pre- and post-assessment questions are represented below (n = 45, p < .001, Cohen’s d = .454). Percentages represent relative rates of improvement The role of ROS on cancer cell proliferation, cancer cell toxicity, and the tumor microenvironment (67%, p < .05) The interplay of antioxidants to aid in the development of therapies to induce DNA-damaged cell death (100%; p < .001) The potential biomarkers to aid in the development of therapies to induce DNA-damaged cell death (34%; p < .05). Conclusions: This online, interactive, expert-led, CME-certified educational activity resulted in significant gains in oncologist knowledge and confidence regarding the ROS pathway and associated clinical pipeline developments Upon completion of the initiative, only 11% of oncologists were able to answer all 3 matched pre/post questions correctly, signifying the need for further education The novelty of the information to many learners demonstrate the need to continue highlighting clinical advances and molecular pathways that may have potential implications in cancer therapy progress.

347 Background: Chemotherapy is a mainstay treatment modality for patients with advanced cholangiocarcinoma (CCA). Recent developments and new approvals have led to changing paradigms, incorporating the use of targeted therapies for patients with progressive disease. Given the need for a greater understanding of the molecular alterations, varying targets, and available and emerging therapies, education is needed to assess knowledge regarding these recent advances in unresectable CCA. The goal of this activity was to increase the knowledge of self-assess the learning needs of oncologists in treating patients with unresectable CCA. Methods: The education included 25 multiple choice questions in a continuing medical education (CME)-certified clinical practice assessment to assess practice gaps. The questions were designed to measure knowledge, competence, confidence, and attitudes of oncologists regarding clinical evidence, role of molecular testing, and place in the treatment paradigm for targeted therapies in unresectable CCA. The self-assessment was made available online to physicians as a learning tool to gain foundational knowledge, as well as receive feedback about their performance as compared to other test-takers, to improve self-awareness of their own personal educational gaps. The activity launched 6/24/20, and data are reported through 8/31/20. Results: A total of 1,009 learners, including 758 physicians, participated in the activity. Of the 104 oncologists that participated, a majority practiced in the community setting, saw patients with a range of cancers, and were not confident about using targeted therapies or recognizing targets for biomarker testing. Oncologists demonstrated the following gaps related to: NGS sequencing and biomarkers: 21% do not use; 32% use upon progressive disease; 35% did not realize that not all panels detect FGFR2 fusions; 20% do not test for biomarkers; 29% and 56% test for IDH or FGFR, respectively; 60% recognize the incidence of IDH1 mutations; Clinical trial (FIGHT202 and ClarIDHy): 45% were able to identify biomarker eligibility for pemigatinib; 9% were able to identify pemigatinib OS outcomes; 30% were able to recognize most common grade 3 AE of pemigatinib; 51% recognized the PFS endpoint with ivosidenib; 34% were able to identify eligibility for ivosidenib; 55% recognized most common AEs of ivosidenib. Conclusions: This CME-certified clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and use of targeted therapies and emerging data in patients with unresectable CCA. As new data emerges and the number of targets and targeted therapies expand, continued education remains important to continue to optimize patient care.

479 Background: Gastrointestinal (GI) cancers are a heterogeneous group of cancers with varying underlying pathophysiology and distinct treatment paradigms. Immunotherapy (IO) is unique in each of the subtypes and biomarkers utility varies. With the expansion of IO in each cancer subtypes, education remains essential to optimize patient outcomes through integration of the latest evidence-based data at point of care. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, 2 educational activities were designed to increase the knowledge and competence of oncologists surrounding the role of IO in patients with advanced GI cancers. Methods: The 2 educational activities included a text based online activity with 3 chapters focused on gastroesophageal cancers, colorectal cancers, and hepatocellular carcinoma (HCC) and a 30-minute online, video discussion with 3 faculty and synchronized slides on HCC. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. A chi-square test was used to identify statistical significance in proportion of correct responses. The first activity launched 11/27/2019 and the second activity launched on 5/8/20. Data were collected and reported through 8/25/2020. Results: A total of 8433 learners, including 1543 oncologists, participated from 11/2019 through 8/2020. Participation in education resulted in significant relative improvements among oncologist learners on IO in GI cancers in (n = 641): 110%: role or eligibility of immune checkpoint inhibitors (ICIs) (p < .001) 38%: clinical trial data of ICIs (p < .001) Subsequent education on unresectable HCC demonstrated a significant relative improvement in both knowledge and competence for oncologist learners (n = 902): 19%: regarding clinical trial data in unresectable HCC (p = .073) 19%; competence identifying role of ICIs in unresectable HCC (p < .05) 59%: competence managing irAEs in unresectable HCC (p < .001). Conclusions: These 2 online CME-certified educational activities resulted in statistically significant gains in oncologist knowledge surrounding the use of IO in advanced GI cancers Follow-up education on HCC demonstrated the value and benefit of multi-modal and sequential activities on improving competence among oncologists caring for patients with unresectable HCC There remains a need for continuous education as more oncologists utilize IO in their practice while the understanding and availability of clinical data continues to expand and evolve in the varying GI cancer subtypes. More than 50% of learners continued to demonstrate a need in understanding the clinical trial data or role of IO in metastatic GI cancers with more than 40% of the learners demonstrating continued need on clinical trial data or role of IO in HCC specifically.

e17076 Background: Cytokine therapy was initially the only immunotherapy for patients with advanced renal cell carcinoma (RCC). The advent of targeted therapies ushered in a new area of precision medicine in the treatment paradigm. Recently, immunotherapy in the form of immune checkpoint inhibitors has shown improved outcomes as compared to targeted therapies and has become a mainstay in treatment. As immunotherapy use moves into earlier stages of disease and combination therapies are explored, education remains essential to optimize patient outcomes. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, educational activities were designed to increase the knowledge and competence among oncologists surrounding the role of immunotherapy in patients with advanced RCC and uncover remaining educational needs. Methods: The 2 educational activities included a 30-minute online, video discussion with 2 faculty presenters and synchronized slides and a text-based online activity with 2 patient cases and interactive questions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. The first activity launched September 19, 2018, the second activity launched December 19, 2018, and the data were collected and are reported through December 27, 2019. Results: A total of 9474 learners participated from September 2018-December 2019 including 1029 oncologists. Participation in education resulted in significant improvements for oncologist who answered all pre/post questions for an activity during the study period (n = 302). Improvements in knowledge and competency were observed in the following areas: Knowledge regarding the latest clinical trial data on the use of cancer immunotherapies for the treatment of RCC (49% vs. 74%, p < .001). Knowledge regarding the immune checkpoint inhibitor regimens on the care of patients with RCC (49% vs. 70%, p < .001). Competence related to choosing the most appropriate regimen for patients with mRCC across the continuum of care (54% vs. 76%, p < .001). Conclusions: Participation in online, video- and case-based CME-certified educational activities resulted in statistically significant gains in oncologist knowledge and competency surrounding the use of immunotherapy in advanced RCC. These results demonstrate the value and benefit of multi-modal and sequential activities on improving knowledge and competence outcomes for oncologists caring for patients with advanced renal cell carcinoma.

e13044 Background: CDK4/6 inhibitors have revolutionized the care of patients with hormone receptor positive (HR+), HER2-negative breast cancer, improving survival outcomes. There are multiple CDK4/6 inhibitors available that differ in their pharmacologic features, reported outcomes, therapeutic indications, and adverse event profiles. Education is needed to empower clinicians to optimally use these agents in practice and personalize breast cancer treatment. The goal of this educational initiative was to increase the knowledge, competence, and confidence of oncologists regarding clinical trial data and factors for selection of CDK4/6 inhibitor. Methods: This educational approach included a 30-minute online video discussion among 3 expert faculty, synchronized with slides to support the discussion. Educational effectiveness was assessed with repeated paired pre/post assessment in which learners served as their own controls. A chi-square test assessed differences from pre- to post-assessment. P values < .05 are statistically significant. Effect size was calculated using Cramer’s V test by determining the strength of the association between CME and the outcomes (V = .16-.26 is considerable and V > .26 is extensive). The activity launched 11/25/2019 and data are reported through 2/4/2020. Results: A total of 889 learners, including 513 physician learners, participated in the activity from 11/2019 through 2/2020. Participation in the education resulted in significant improvements in knowledge among oncologists (n = 81; p < .001; V = 0.16). On average, the proportion of learners who responded correctly to knowledge-based questions about CDK4/6 inhibitors increased from 51% at the pre-assessment to 67% at the post-assessment. Moreover, 41% of oncologists had a measurable positive change in confidence in their ability to incorporate CDK4/6 inhibitors into the treatment of HR+, HER2- advanced breast cancer. Significant improvements in knowledge were observed in the following areas: The clinical trial safety and efficacy data evaluating CDK4/6 inhibitors in the management of patients with HR+/HER2-negative breast cancer (32% vs. 51%, p < .05, V = 0.19). The potential role of patient- and tumor- specific prognostic factors in selection of individual CDK4/6 inhibitors (56% vs. 72%, p < .05, V = 0.17). Conclusions: This CME-certified online discussion resulted in statistically significant gains in oncologists’ knowledge and improved confidence surrounding the personalization of CDK4/6 inhibitor therapy in HR+/HER2- breast cancer.

11026 Background: Glioblastoma multiforme (GBM) is a rare, malignant tumor of the central nervous system (CNS) with poor prognosis. Nearly all patients experience recurrence due to GBM’s heterogeneity and there is currently no standard approach to treatment. Despite having few targeted agents with demonstrated efficacy, molecular testing is utilized due to its value in improving diagnostic accuracy and prognostic stratification. Moreover, recent data has shown an increase in promising data with regards to treating GBM using various mechanisms. Because of the clinical conundrum GBM poses and the lack of available treatment options, clinicians are challenged to stay current with new data and how best to integrate new agents into treatment paradigms. The objective of this study was to assess the changes in oncologists’ and pathologists’ knowledge through participation in education regarding optimal GBM treatment. Methods: The educational activity was a 30-minute online, video discussion segmented into 3 parts with synchronized slides and 2 faculty. Educational effect was assessed with a repeated pairs pre-/post-assessment study with a 3-item, multiple choice, knowledge questionnaire and one confidence assessment question. For all questions, each participant served as his/her own control. Pre- and post-assessment scores were compared to determine the relative changes in the proportion of correct responses. A chi-square test assessed statistical significance at the P < 0.05 level. The activity launched 26th June 2019; data were collected until 19th August 2019. Results: Overall significant improvements were seen after education for oncologists (N = 62, P < .001) and pathologists (N = 67, P < .01). The relative improvement was 67% for oncologists and 45% for pathologists (pre-/post-assessment average correct response rates were 30%/50% and 29%/42%, respectively). Following the activity, 55% of oncologists and 51% of pathologists had a measurable improvement in confidence in their ability to differentiate among late-stage investigational agents for GBM based on mechanism of action. Conclusions: Participation in an online, CME intervention consisting of a series of video discussions, totaling 30-minutes, resulted in statistically significant improvements in knowledge and confidence of oncologists and pathologists, that may lead to improvements in clinical care. As new data and agents emerge, new educational activities are necessary to reinforce knowledge, close persistent gaps, and increase oncologists’ and pathologists’ confidence in this clinical setting.

10533 Background: The indications and use of immune checkpoint inhibitors (ICIs) for the treatment of melanoma have grown since the first drug approval in 2011. The expanding evidence base and number of indications challenges clinicians to stay up to date with how best to integrate these agents into treatment pathways. The objective of this study was to assess trends over time in oncologists’ knowledge, competence, and confidence using ICIs in the treatment of melanoma. Methods: A series of online continuing medical education (CME) activities about the role of ICIs in the treatment of melanoma was launched in April 2014; 18 included multiple-choice knowledge/competence questions and a confidence question assessed on a 5-point Likert-type scale before and immediately after the activity. Activities that had at least 30 oncologists participate pre/post are included in this analysis. A pre-/post-assessment study design was used, and educational effect was assessed with Chi-square tests. Analyses were conducted to examine trends in knowledge, competence, and confidence over four years on a quarterly basis. Weighted averages in each of the outcomes were calculated by quarter. Results: A total of 92,373 learners participated from April 2014-March 2018, including 57,432 physicians, of whom 11,922 were oncologists. The average increases from pre- to post-test for knowledge- (12 activities), competence- (11 activities), and confidence-based (9 activities) questions were 21%, 15%, and 6%, respectively (P < 0.01 for all comparisons). The absolute increase in knowledge from pre-test in 2014 (48%) to post-test in 2018 (78%) was 30 percentage points; and for competence, 6% (from 62% in 2014 to 68% in 2018). The mean confidence rating pre-test in 2015 was 2.51 versus 3.37 post-test in 2018. Conclusions: Online CME improves oncologists’ knowledge, competence, and confidence using ICIs in the treatment of melanoma. As new data emerge and indications expand, new educational activities are necessary to reinforce existing knowledge, close persistent gaps, and increase oncologists’ confidence using ICIs in this clinical setting.

Conditional survival (CS) is a clinically useful prediction measure which adjusts a patient’s prognosis based on their duration of survival since initiation of therapy. CS has been described in numerous malignancies, and recently described in patients with metastatic renal cell carcinoma (mRCC) who received vascular endothelial growth factor tyrosine kinase inhibitor (VEGFTKI) therapy. However, CS has been not reported in the context of mRCC treated with high-dose interleukin-2 therapy (HDIL-2). A total of 176 patients with histologically confirmed metastatic clear cell RCC (mccRCC) treated with HDIL-2 at the University of Utah Huntsman Cancer Institute from 1988–2012 were evaluated. Using the Heng/IMDC model, they were stratified by performance status and prognostic risk groups. Two-year CS was defined as the probability of surviving an additional two years from initiation of HDIL-2 to 18 months after the start of HDIL-2 at three-month intervals. The median overall survival (OS) was 19.9 months. Stratifying patients into favourable (n = 35; 20%), intermediate (n = 110; 63%), and poor (n = 31; 18%) prognostic groups resulted in median OS of 47.5 (HR 0.57, 95% CI 0.35–0.88, p = 0.0106 versus intermediate), 19.6 (HR 0.33, 95% CI 0.10–0.33, p < 0.0001 versus poor), and 8.8 (HR 5.34, 95% CI 3.00–9.62, p < 0.0001 versus favourable) months respectively. Two-year overall CS increased from 43% at therapy initiation to 100% at 18 months. These results have significant ramifications in prognostication. Furthermore, it is important when counseling patients with mccRCC who have completed treatment with HDIL-2 and are in active follow-up.

771 Background: For distal rectal tumors, abdominoperineal resection (APR) may achieve a complete resection; however is associated with significant morbidity. Full thickness local excision (FTLE) via transanal endoscopic microsurgery (TEM) may provide disease control with fewer complications. Additionally, Intensity Modulated Radiation Therapy (IMRT) may minimize toxicity by limiting small bowel exposure to radiation. We report on 14 years of prospective data from Lankenau Medical Center for distal rectal cancer pts treated with neoadjuvant chemotherapy and high dose IMRT followed by FTLE via TEM. Methods: From 2002 to 2016, 44 pts were treated for cT1(n = 4), cT2 (n = 24), cT3 (n = 16), N0, M0 distal rectal cancer using IMRT at 5580 cGy along with concurrent 5FU-based chemotherapy, followed by FTLE. Local recurrence (LR), disease free survival (DFS) and overall survival (OS) was reported using Kaplan-Meier survival analysis. Results: At the time of FTLE complete pathological response was achieved in 18 pts, good response in 25 pts, and 1 pt with poor response. Median time to follow-up is 58 months. 3 of 44 pts (6.8%) had isolated local recurrence, all achieving local control with surgical salvage. Mean DFS is 10.68 years (95% CI 8.77 to 12.60). Mean OS is 11.78 years (95% CI 9.99 to 12.58). 34 pts (77%) are currently alive with NED. 6 pts developed metastatic disease, 5 of whom died, and one who was surgically salvaged. 5 pts died from causes outside of their malignancy. In adjusted analysis, DFS was strongly associated with pathologic response to chemoradiotherapy (p = 0.025). Post-operative Grade I-II complications noted in 17 pts, all managed with conservative measures; Grade III occurred in 2 pts. No pts required a diverting colostomy. Conclusions: Neoadjuvant high dose IMRT and chemotherapy followed by FTLE to treat distal rectal cancers is well tolerated and effective. Local excision surgery may provide excellent tumor control and improved quality of life in appropriately selected pts. A randomized clinical trial is needed to compare it to standard surgery. Also a dose escalation study with IMRT may allow for improvement in pathologic response without increasing toxicity.

In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16–20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment. All sequential treatment naive mRCC patients treated with HDIL-2 at the University of Utah (1988–2013) and University of Michigan (1997–2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months. 391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48–1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39–1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09–0.22, p

Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend.

e18210 Background: We have previously reported on glutathione recycling capacity (GRC) in red blood cells as a predictor of delayed nausea in cancer patients treated with platinum-based chemotherapies [1]. The test identifies individual variations in the efficiency to scavenge reactive oxygen species, produced by chemotherapy-induced cell-damage, which triggers release of serotonin – a know inducer of chemotherapy-induced nausea and vomiting. In this current study, we have examined if the GRC assay and/or changes in substance P (SP), another inducer of nausea, can predict delayed nausea among breast cancer patients receiving doxorubicin- or taxane-based therapies and thereby provide better guidance to individualized antiemetic therapies. Methods: Chemotherapy naïve breast cancer patients were asked to participate in this IRB-approved study. Consented patients donated a tube of blood prior to each treatment cycle. Commercial kits were used to measure GRC (OxPhos, Rockland Inc.) and Substance P (Parameter, R&D Systems). On-set, duration and severity of nausea, and anti-emetics prescribed were documented by the medical staff. Results: Obtained GRC and SP values were compared to documented incidences of nausea. We found that 26.8% of taxane treated patients [N = 42] had moderate/severe nausea and demonstrated a similar GRC pattern to platinum-based induced nausea, i.e. low GRC results in more severe nausea. Among doxorubicin treated [N = 31] patients, 41.9% had moderate/severe nausea but showed no correlation with GRC. However, preliminary evaluation of these patients showed a continuous increase in SP levels (average 1.74 fold increase after one cycle). Conclusions: In this initial evaluation of our on-going study, we found that fewer patients had nausea in the taxane treated group with a similar GRC predictive pattern as previously reported. However, patients in the doxorubicin treated group were more likely to experience nausea with no correlation to GRC but with a steadily rising level of SP during the early part of their regimen. Using SP testing could help identify patients that might have a medical benefit from additional NK1 antagonist therapy. 1. Kutner, T., et al. Supprot Care Cancer (2017) 25:581-587.

756 Background: In patients with distal rectal cancer, preoperative chemoradiotherapy remains the standard of care, however intensity modulated radiation therapy (IMRT) followed by trans-anal endoscopic microsurgery (TEM) may be able to provide more conformal and higher hoses of radiation while sparing normal tissue. It is our intent to present 11 years of experience of patients treated concurrently with chemotherapy and IMRT followed by rectal sparing TEM. We will report on local control, disease free survival (DFS), and toxicity. Methods: Forty-two patients at Lankenau Medical Center were treated for distal rectal carcinoma with IMRT and TEM from 2004 to 2016. Patients staged T1-T3 N0 M0 received 5580 cGy to the pelvis using a 9 field plan or volumetric arc therapy targeting rectal tumor and pelvic lymph nodes. The median age was 68. All patients received concurrent 5FU based chemotherapy; 54% received an infusional regimen and 46% received oral capecitabine. All patients went on to surgery with full thickness local excision via TEM. 38 underwent surgery within 7-12 weeks following neoadjuvant therapy, with median time to surgery at 11 weeks. Results: Median time to follow up time was 33 months. Complete pathologic response was achieved in 38% (n=17) of patients, good partial response in 53% (n=22), and moderate response in 6%. 4 patients had local recurrence all achieving long term control with salvage surgery. 5 patients developed distant metastasis, most commonly to the liver. Of those, 1 died from metastatic disease, occurring 11 years after initial diagnosis. 79% of patients are currently alive with no evidence of disease. Mean DFS calculated with Kaplan Meier analysis was 88 months with 95% confidence interval between 76 and 101 months. Toxicity was acceptable with only one grade 2 toxicity (diarrhea), and two patients with grade 1 neutropenia. Conclusions: Our 11 year patient experience has shown that neoadjuvant chemoradiotherapy with IMRT followed by TEM is an effective and well tolerated treatment regimen for distal rectal carcinoma. In the appropriately selected patients, local excision surgery may provide an excellent option for patients other than low anterior resection (LAR).

Background: Evaluation of comorbidities prior to allogeneic hematopoietic stem cell transplantation (HSCT) is important in predicting patient outcomes and has contributed to the increasing proportion of long-term HSCT survivors. In comparison to the general population, there is a greater burden of cardiovascular disease in HSCT survivors primarily in those who have undergone allogeneic HSCT. It has been hypothesized that these effects are secondary to chronic inflammation and its effect on the vascular endothelium. Prior studies have shown the presence of cardiovascular risk factors, including obesity, dyslipidemia, and hypertension, as well as exposure to chest radiation and anthracyclines, to be associated with an increased risk for the development of post HSCT cardiomyopathy (CM). The evaluation of left ventricular ejection fraction (LVEF) is routine pre-HSCT, however, studies have shown variable results in its utility in predicting cardiac toxicity post-HSCT. In addition, other morbidity outcomes in the setting of pre-existing cardiac dysfunction have yet to be fully explored, including the development of severe acute kidney injury (AKI) requiring renal dialysis. This study examines the role of pre-HSCT cardiac risk factors and LVEF as prognostic tools for post-HSCT development of symptomatic CM, severe AKI requiring dialysis, and early mortality. Methods: We undertook a retrospective analysis of 384 patients who underwent allogeneic HSCT between 2004 and 2014 at Thomas Jefferson University Hospital. LVEF values were collected from transthoracic echocardiograms or multigated acquisition (MUGA) scans. Documentation of symptomatic CM post-HSCT was established based on clinical signs and symptoms (decreased LVEF associated with new need for medical therapy for heart failure including beta blocker, ACE-inhibitor and/or diuretic), within 100 days after HSCT. Assessment of development of severe AKI was determined by the need for dialysis within the 100 days after HSCT. Univariate association of categorical variables with outcomes and potential confounding variables was assessed using exact Chi-square tests. Logistic regression was used to calculate estimates of association between LVEF as a continuous variable and outcomes. Results: The final sample included 364 patients with a median age of 54 (range, 19 to 78); 42% of subjects were female. 20 patients were excluded due to inadequate data available regarding cardiac function and/or disease course. 30-day mortality was 6.3%, 100-day mortality was 15.9%, severe AKI requiring dialysis was 13.7%, and the development of symptomatic CM was 9.9%. Patients with a pre-HSCT LVEF Discussion: When addressing 'fitness' for transplant, a thorough investigation of risk factors and exposures may assist in predicting risk of cardiovascular morbidity as well as overall mortality. Cardiac toxicity may account for nearly 5 to 10% of non-relapse mortality during the first 100 days post-HSCT. Evaluation of cardiac function, using LVEF as a marker, has been standard; however, studies have shown mixed results on its predictive utility. Our study showed a nearly linear relationship between baseline LVEF and the development of CM. It remains difficult to define a precise LVEF value that should be required prior to HSCT. Further study, particularly in patients with low baseline LVEF (i.e. 40-50%), may help our understanding of risk factors relating to post-HSCT development of symptomatic cardiac and renal morbidity as suggested in this study, and better define a reasonable cutoff to use to determine to whom we can safely offer allogenic HSCT. Disclosures No relevant conflicts of interest to declare.

Background: Transplant related mortality(TRM) associated with allogeneic stem cell transplantation (HSCT) has necessitated risk-stratification that allows practitioners to make informed choices regarding patient selection for HSCT. Although pulmonary function testing (PFT) is obtained prior to HSCT at most institutions, and incorporated into common comorbidity indices (e.g. HCT-CI) there is no standard protocol to determine suitability for HSCT specific to lung disease. Also, there is a lack of data regarding the impact of tobacco use prior to HSCT. Recently, the association between smoking and kidney disease has gained attention. Tobacco-mediated kidney disease may be prognostic for renal failure post-HSCT. We studied the impact of tobacco use and lung function prior to HSCT on 30- and 100-day mortality as well as the frequency of post-HSCT respiratory and renal failure. Methods: We reviewed consecutive patients undergoing allogeneic HSCT at our institution from 2004 -2014 for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS). Smoking was categorized as never (0 pack years), low dose ( Results: Of 373 subjects who underwent allogeneic HSCT, 315 (84%) had complete smoking histories (42% female, 58% male). AML (44.1%) accounted for the most frequent diagnosis followed by NHL (22.2%), ALL (14.3%), MDS (12.1%) and MM (7.3%). The 30 day mortality was 6.4%, 100 day mortality was 16.5%. 23.5% of patients required mechanical ventilation while 12.4% required dialysis. 46.7% of patients were smokers; 31.8% high dose smokers, 14.9% low dose smokers. There was an 11% increase in ventilator-dependency among high-dose smokers compared to none or low-dose (p=0.032), with a trend toward higher incidence of 100-day mortality with high dose smokers (31%) compared with low dose smokers (23.4%) and never-smokers (19.1%), (p=0.083). High dose smokers were more likely to have reduced pulmonary function with FEV/FVC < 70% (p=0.0004). Patients with FEV/FVC < 70% had a 14% increase in 100-day mortality with an almost 20% increased chance of ventilator dependency (p=0.022) and 17.6% increased incidence of dialysis dependency (p=0.032). DLCO did not correlate to any endpoint with statistical significance. Patients with MDS had the highest proportion of high dose smokers (47.4%; p=0.0023) and highest percentage of patients with FEV/FVC < 70% (18.4%, p=0.0037). Patients with MDS also had the highest 30-day mortality (18.4%, p=0.023), 100-day mortality (31.6%, p=0.0012), ventilator dependency (47.4%, p=0.0014) and dialysis dependency (31.6%, p=0.0036). Discussion: Our results differ from prior studies looking at the utility of FEV1 and DLCO in pre-HSCT PFTs as predictive markers; neither had prognostic value. We found that high dose smoking history and reduced FEV1/FVC were significantly associated with post-HSCT ventilator dependence, dialysis dependence and mortality. These results underscore the need for future studies that examine the relationship between smoking, lung function and renal failure post-HSCT. Our study did not demonstrate that low dose smoking predicts worse outcomes post-HSCT, but future studies may help provide patients with more accurate pre-HSCT counseling. Patients with MDS were the largest population of high dose-smokers and had the highest proportion of 100-day mortality, ventilator and dialysis dependency. Disclosures No relevant conflicts of interest to declare.

Introduction Acute renal failure (ARF) after hematopoietic stem cell transplantation (HSCT) is an important complication associated with transplant-related mortality (TRM). In the first 100 days after HSCT, ARF can be secondary to other major complications, such as sepsis, sinusoidal obstruction syndrome, acute graft-versus-host disease (GVHD), and viral reactivation.ARF also occurs in the setting of nephrotoxic drugs, such as amphotericin B,and calcineurin inhibitors. We hypothesize that risk factors for ARF after HSCT include pre-transplant comorbidities, such as chronic kidney disease (CKD), acute kidney injury (AKI) prior to HSCT and hypertension. Mortality is greater in patients with ARF after HSCT than those without ARF. When ARF requires hemodialysis (HD), the mortality rate rises to greater than 80%. The aim of this study was to identify prognostic indicators for the development of ARF requiring HD or leading to death within 100 days after HSCT. Methods We performed a retrospective analysis of patients undergoing allogeneic HSCT at Thomas Jefferson University Hospital to identify prognostic indicators for poor outcomes after HSCT. We analyzed data for all patients who underwent allogeneic HSCT between the years of 2004-2014. After initial analysis, we excluded subjects who had diagnoses for which there were less than twenty patients. Univariate analysis was performed to identify risk factors for ARF requiring HD, 30-day mortality and 100-day mortality. Univariate association of categorical variables with outcomes and potential confounding variables was assessed using exact Chi-square tests. All variables associated with outcomes with p Results We analyzed 373 consecutive patients who underwent allogeneic HSCT at our institution between 2004 and 2014. After excluding diagnoses with less than twenty patients, we analyzed the remaining 332 patients. Median age was 54 years (range 19-78) and 42% of subjects were female. Diagnoses included acute myeloid leukemia (44.3 %), non-Hodgkin lymphoma (22.3%), acute lymphoid leukemia (14.8 %), myelodysplastic syndrome (MDS) (11.8%) and multiple myeloma (6.9%). Univariate associations between risk factors and three outcomes- renal failure requiring HD, 30-day mortality and 100-day mortality, were assessed. Within this set of 332 subjects, the incidence of renal failure requiring HD was 11.8%., 30-day mortality was 6.3%, and 100-day mortality was 16.6%. Creatinine >1.5 mg/dL at the time of HSCT was significantly associated with these outcomes. In addition, the diagnosis of MDS was associated with both 100-day mortality (p 1.5 mg/dL on the day of HSCT (p =0.045), use of amphotericin (p =0.052), and diagnosis of MDS (p =0.11). Candidate variables for predicting 100-day mortality were creatinine >1.5 mg/dL on the day of (p =0.023), diagnosis of MDS (p =0.035), and each one year increase in age (p =0.013). Candidate variables for renal failure requiring HD were creatinine >1.5 mg/dL on the day of HSCT (p Discussion Although preexisting renal disease is incorporated into current models of risk at the time of transplant (e.g. HCT-CI), the specific risk for HD has not previously been quantified. Our analysis shows an 11.8% risk of ARF requiring HD following HSCT, with increased risk related to preexisting renal disease and underlying diagnosis of MDS. This suggests that patients should be counseled appropriately about this specific risk of renal failure requiring HD if the creatinine is >1.5 mg/dL. Similarly, patients with creatinine >1.5 mg/dL at time of HSCT are also at increased risk of 30-day and 100-day mortality compared to their counterparts with creatinine ≤1.5. Disclosures No relevant conflicts of interest to declare.

4565 Background: The aim of this study is to determine if achievement of stable disease as a best response to HD IL-2 may improve survival outcomes. Recent data suggest that immunotherapy may impro...