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PURPOSE: Cancer trial participants do not reflect the racial and ethnic diversity in the population of people with cancer in the United States. As a result of multiple system-, patient-, and provider-level factors, including implicit bias, cancer clinical trials are not consistently offered to all potentially eligible patients. MATERIALS AND METHODS: ASCO and ACCC evaluated the utility (pre- and post-test knowledge changes) and feasibility (completion rates, curriculum satisfaction metrics, survey questions, and interviews) of a customized online training program combined with facilitated peer-to-peer discussion designed to help research teams identify their own implicit biases and develop strategies to mitigate them. Discussion focused on (1) specific elements of the training modules; (2) how to apply lessons learned; and (3) key considerations for developing a facilitation guide to support peer-to-peer discussions in cancer clinical research settings. We evaluated discussion via a qualitative assessment. RESULTS: Participant completion rate was high: 49 of 50 participating cancer programs completed training; 126 of 129 participating individuals completed the training (98% response rate); and 119 completed the training and evaluations (92% response rate). Training increased the mean percentage change in knowledge scores by 19%-45% across key concepts (eg, causes of health disparities) and increased the mean percentage change in knowledge scores by 10%-31% about strategies/actions to address implicit bias and diversity concerns in cancer clinical trials. Knowledge increases were sustained at 6 weeks. Qualitative evaluation validated the utility and feasibility of facilitated peer-to-peer discussion. CONCLUSION: The pilot implementation of the training program demonstrated excellent utility and feasibility. Our evaluation affirms that an online training designed to raise awareness about implicit bias and develop strategies to mitigate biases among cancer research teams is feasible and can be readily implemented in cancer research settings.

A concerted commitment across research stakeholders is necessary to increase equity, diversity, and inclusion (EDI) and address barriers to cancer clinical trial recruitment and participation. Racial and ethnic diversity among trial participants is key to understanding intrinsic and extrinsic factors that may affect patient response to cancer treatments. This ASCO and Association of Community Cancer Centers (ACCC) Research Statement presents specific recommendations and strategies for the research community to improve EDI in cancer clinical trials. There are six overarching recommendations: (1) clinical trials are an integral component of high-quality cancer care, and every person with cancer should have the opportunity to participate; (2) trial sponsors and investigators should design and implement trials with a focus on reducing barriers and enhancing EDI, and work with sites to conduct trials in ways that increase participation of under-represented populations; (3) trial sponsors, researchers, and sites should form long-standing partnerships with patients, patient advocacy groups, and community leaders and groups; (4) anyone designing or conducting trials should complete recurring education, training, and evaluation to demonstrate and maintain cross-cultural competencies, mitigation of bias, effective communication, and a commitment to achieving EDI; (5) research stakeholders should invest in programs and policies that increase EDI in trials and in the research workforce; and (6) research stakeholders should collect and publish aggregate data on racial and ethnic diversity of trial participants when reporting results of trials, programs, and interventions to increase EDI. The recommendations are intended to serve as a guide for the research community to improve participation rates among people from racial and ethnic minority populations historically under-represented in cancer clinical trials. ASCO and ACCC will work at all levels to advance the recommendations in this publication.

Purpose To assess the safety and feasibility of neoadjuvant short-course radiation therapy (RT) concurrent with continuous infusion 5-fluorouracil (5-FU) for the treatment of locally advanced rectal cancer. Methods and Materials Patients with cT3-4 or N + rectal adenocarcinoma based on ultrasound or magnetic resonance imaging were prospectively enrolled in this study. Study treatment consisted of continuous infusion 5-FU combined with short-course RT (5 Gy x 5 fractions) followed by 4 cycles of mFOLFOX, total mesorectal excision (TME), and 6 cycles of adjuvant mFOLFOX. To mitigate the potential added toxicity from concurrent 5-FU, intensity modulated RT was used. Using the continual reassessment method, the dose of 5-FU was escalated from 100 to a maximum-tolerated dose of 200 mg/m2/d. Results Fourteen patients were accrued. All patients completed continuous infusion 5-FU and short-course RT and the 5-FU dose was safely escalated to 200 mg/m2/d with no dose-limiting toxicity. Thirteen patients received the neoadjuvant mFOLFOX, and only 1 patient went straight to surgery after chemoradiation. Clinical response was 21% complete, 63% partial, 14% stable disease, and no patients had progression. Three patients with cCR had negative biopsies and did not have TME. Pathologic response was 64% partial response and 14% stable disease. No patients had pathologic progression. The most common grade 3 and 4 toxicities were cytopenias. The most common grade 1 and 2 toxicities were cytopenia, fatigue, diarrhea, and nausea. Conclusions Our findings suggest that concurrent chemotherapy with neoadjuvant short-course RT is feasible and can be safely given with concurrent continuous infusion 5-FU. This works adds to the growing evidence that short-course RT is not only equivalent to long-course RT, but also may provide additional benefits, such as allowing for a transition to full dose systemic therapy in the neoadjuvant setting, selective organ preservation in complete responders, and providing a more convenient and cost-effective way of delivering pelvic RT.

e18599 Background: Low participation of Black, Hispanic, Latinx and other underrepresented racial/ethnic groups in clinical research remains a problem across the U.S. Recent studies have highlighted that stereotypes, assumptions, and bias play a role in lack of diversity in cancer trial participation. To help address this, the Association of Community Cancer Centers (ACCC) and American Society of Clinical Oncology (ASCO) piloted an implicit bias training program for clinical research teams. Methods: Adapted from the Duke University Just Ask™ program, the pilot program is comprised of eLearning modules which can be completed in about 60 minutes. Features include education on diversity, equity, and bias in clinical trial participation, case vignettes, and strategies to mitigate disparities. A call was issued to members of both organizations. After completing the training, all individual participants were asked to complete a retrospective pre/post survey to assess change in knowledge and attitude. Focus groups explored participants’ experience with the training. Another survey was administered 6 weeks later to assess sustainability of changes. Results: Research teams from 50 programs were selected for the pilot. 129 individuals consented, and 126 completed the training and evaluations (98% response rate). 48% of participants reported that they had completed training on implicit bias and/or related topics prior to the pilot. Increased levels of knowledge were reported across all key training concepts, with an average % increase from 19% to 45%. Similar increases were observed for strategies for addressing implicit bias, with an average % increase from 10% to 31%. At 6 weeks post-training, there was a slight decrease in knowledge across most items, from -1% to -8%. Most (92%) participants reported satisfaction with the course, and most (92%) indicated they would recommend it to a colleague and would recommend implementing it at their program. Suggestions to improve the course included streamlining content and providing additional tools and resources. Conclusions: Pilot findings support the feasibility and utility of the training, which can help cancer programs to address disparities in clinical research. Next steps include modifying the course based on participant feedback, disseminating the training and supplementary resources, and exploring options for assessing the impact on upstream outcomes such as diversity in trial participation.[Table: see text]

Patients’ ability to access their provider’s clinical notes (OpenNotes) has been well received and has led to greater transparency in health systems. However, the majority of this research has occurred in primary care, and little is known about how patients’ access to notes is used in oncology. This study aims to understand oncologists’ perceptions of OpenNotes, while also establishing a baseline of the linguistic characteristics and patterns used in notes. Data from 13 in-depth, semistructured interviews with oncologists were thematically analyzed. In addition, the Linguistic Inquiry and Word Count (LIWC) program evaluated over 200 clinician notes, measuring variables encompassing emotions, thinking styles, social concerns, and parts of speech. Analysis from LIWC revealed that notes contained negative emotional tone, low authenticity, high clout, and high analytical writing. Oncologists’ use of stigmatized and sensitive words, such as “obese” and “distress,” was mainly absent. Themes from interviews revealed that oncologists were uncertain about patients’ access to their notes and may edit their notes to avoid problematic terminology. Despite their reluctance to embrace OpenNotes, they envisioned opportunities for an improved patient–provider relationship due to patients initiating interactions from viewing notes. Oncologists believe notes are not intended for patients and altering their content may compromise the integrity of the note. This study established a baseline for further study to compare notes pre-implementation to post-implementation. Further analysis will clarify whether oncologists are altering the style and content of their notes and determine the presence of patient-centered language.

Background Providers have expressed concern about patient access to clinical notes. There is the possibility that providers may linguistically censor notes knowing that patients have access. Purpose Qualitative interviews and a pre- and post- linguistic analysis of the implementation of OpenNotes was performed to determine whether oncologists changed the content and style of their notes. Methods Mixed methods were utilized, including 13 semi-structured interviews with oncologists and random effects modeling of over 500 clinical notes. The Linguistic Inquiry and Word Count program was used to evaluate notes for emotions, thinking styles, and social concerns. Results No significant differences from pre- and post-implementation of OpenNotes was found. Thematic analysis revealed that oncologists were concerned that changing their notes would negatively impact multidisciplinary communication. However, oncologists acknowledged that notes could be more patient-friendly and may stimulate patient-provider communication. Conclusions Although oncologists were aware that patients could have access, they felt strongly about not changing the content of notes. A comparison between pre- and post-implementation confirmed this view and found that notes did not change. Practice Implications Patient access to oncologist’s notes may serve as an opportunity to reinforce important aspects of the consultation.

e16268 Background: The multi-kinase inhibitor sorafenib (S) and HDAC inhibitor vorinostat (V) demonstrated synergism against preclinincal pancreatic cancer (PaCa) models. The combination of S & V also potently radiosensitized pancreatic cancer cells and enhanced the activity of gemcitabine (G). This led to a phase 1 trial to determine the doses and schedule appropriate for phase 2 study of S & V with weekly G and intensity modulated radiotherapy (IMRT) as neoadjuvant treatment of PaCa following chemotherapy. Methods: Using a 3+3 dose-escalation design, adult patients with resectable, borderline resectable, unresectable, and lymph node positive PaCa were enrolled to 6 dose levels. Enrolled patients had completed at least 8w of neoadjuvant chemotherapy prior to IMRT. The schedule of administration was weekly 200mg/m2 G weekly during IMRT, S & V were dosed either 3x or 5x weekly during IMRT. Primary endpoint was to identify the dose and schedule for S & V with G based chemoradiation. Key secondary endpoints included antitumor activity, R0 resection rate, OS. Correlative studies to evaluate a variety of biomarkers and Nanostring expression analysis on pre- and post-therapy tumor specimens were also performed. Results: 22 patients were enrolled and 21 treated at 6 dose levels. Due to thrombocytopenia limiting drug exposure, the trial was modified to reduce G to 200mg/m2/wk and S & V to 3 d/wk instead of 5 d/wk. 13 patients were eligible for surgery, and 9 had R0 resections. Conclusions: Our findings indicate that the study regimen was well tolerated, typical toxicities of S (hand foot syndrome) were not observed with intermittent dosing. Uncomplicated cytopenias limited drug exposure, which was improved with intermittent S&V dosing. The RP2D of the combination is S (400mg po BID 3d/wk), V (200mg po qd 3d/wk), G 200mg/m2 IV weekly, with IMRT (50.4 Gy over 28 fractions, 5d/wk). Antitumor activity was observed across dose levels, with an encouraging R0 resection rate. These results warrant further investigation of combining S and V with G and IMRT as neoadjuvant treatment of PaCa following chemotherapy. Analyses of correlative studies and OS are underway. Clinical trial information: NCT02349867. [Table: see text]

Context Many advanced patients with cancer have unrealistic prognostic expectations. Objectives We tested whether offering life expectancy (LE) statistics within palliative chemotherapy (PC) education promotes realistic expectations. Methods In this multicenter trial, patients with advanced colorectal and pancreatic cancers initiating first or second line PC were randomized to usual care versus a PC educational tool with optional LE information. Surveys at two weeks and three months assessed patients' review of the LE module and their reactions; at three months, patients estimated their LE and reported occurrence of prognosis and end-of-life (EOL) discussions. Wilcoxon tests and proportional odds models evaluated between-arm differences in LE self-estimates, and how realistic those estimates were (based on cancer type and line of treatment). Results From 2015 to 2017, 92 patients were randomized to the intervention and 94 to usual care. At baseline most patients (80.9%) wanted “a lot” or “as much information as possible” about the impact of chemotherapy on LE. Among patients randomized to the intervention, 52.0% reviewed the LE module by two weeks and 66.7% by three months—of whom 88.2% reported the information was important, 31.4% reported it was upsetting, and 3.9% regretted reviewing it. Overall, patients' LE self-estimates were very optimistic; 71.4% of patients with colorectal cancer estimated greater than five years; 50% pancreatic patients estimated greater than two years. The intervention had no effect on the length or realism of patients' LE self-estimates, or on the occurrence of prognostic or EOL discussions. Conclusions Offering LE information within a PC educational intervention had no effect on patients' prognostic expectations.

Objective To compare the efficacies of various post-percutaneous coronary intervenetion (PCI) bivalirudin doses on net adverse clinical events (NACEs) and mortality. Background In primary PCI, lower risk of bleeding with bivalirudin (vs. unfractionated heparin [UFH]) is counterbalanced by an increased risk of acute stent thrombosis (ST). Several randomized clinical trials (RCTs) and a recent meta-analysis suggest that acute ST risk may be eliminated without compromising the bleeding benefit, but only if the full dose, not a low dose, of bivalirudin is continued post-PCI. However, it is not known whether this improved risk leads to lower rates of NACEs and mortality. Methods Scientific databases and Web sites were searched for RCTs. Trials were included if study patients were undergoing primary PCI for acute ST-segment elevation myocardial infarction and were randomly assigned to bivalirudin or UFH treatment. The bivalirudin arm was divided based on post-PCI bivalirudin dosage: The Biv-Full group received 1.75 mg/kg/h, the Biv-Low group, 0.25 mg/kg/h, and the Biv-No group, none. Results Six RCTs involving 16,842 patients were found. In pairwise meta-analysis, bivalirudin improved 30-day all-cause mortality by 35% and cardiac mortality by 32%, but did not yield a NACE rate better than that achieved with UFH. Subgroup analysis showed the Biv-Full group had a 46% lower NACE rate and 47% lower all-cause mortality than UFH. These effects were not seen in the other two groups. Network meta-analysis yielded similar results. At treatment ranking, the Biv-Full group yielded the best treatment efficacy. Conclusions In primary PCI, full-dose bivalirudin infusion for 3-4 hr after PCI appeared to improve NACE rates compared to UFH. It also seemed to be the most effective strategy for improving cardiac mortality and all-cause mortality. © 2016 Wiley Periodicals, Inc.

Importance Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote. Objective To determine whether a PC educational video and booklet at treatment initiation could improve patients’ understanding of its benefits and risks. Interventions Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review. Design, Setting, and Participants Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019. Main Outcomes and Measures The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding “not at all likely” to “What is your understanding of how likely the chemotherapy is to cure your cancer?” (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy–General emotional well-being subscale). Results Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted “a lot” of information or “as much information as possible” about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%;P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar. Conclusions and Relevance Provision of an educational video and booklet did not alter patients’ expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies. Trial Registration ClinicalTrials.gov Identifier:NCT02282722

e19006 Background: There are convincing data that suggest that lifestyle factors play a strong role in colorectal cancer. Obesity in particular is associated with higher incidence of colorectal cancer (CRC) and increased mortality. Racial and ethnic minorities are more likely to develop colorectal cancer when compared to the general population in the US, and the population in Richmond is made up of 47% of African Americans (AA), with 24% of the total persons in poverty and a median household income of $45,117, allowing us to uncover important factors that may affect the development of CRC. Purpose: We aim to uncover trends in the AA population as compared to the Caucasian population to determine the effect of health disparities in obesity-related risk factors in patients with CRC. Methods: We used the Virginia Commonwealth University (VCU) network within TriNetX, a global federated health research network that provides access to statistics in electronic medical records of diagnoses, laboratory values and vitals. We compared Caucasian and AA patients with a diagnosis of CRC from 14 different health networks in the US from 2010-2019. Results: In the TriNetX network, we found that the African American population exhibited higher rates of obesity (33% vs. 26%), irritable bowel disease (38% vs. 33%) and hypertension (71% vs. 33%) as compared to AA patients in the other 14 networks. Increased rates of diabetes (33% vs. 22%), hyperlipidemia (33% vs. 28%) and hypertension (71% vs. 56%) were found in the African American population compared to the Caucasian population in the VCU Network. Notably, we also observed increased rates of homelessness & unemployment (5% vs. 3%) in the AA population. Conclusions: These data suggest that important comorbidities are more prevalent in AA populations population than in the Caucasian populations. Our findings demonstrate the fundamental importance of considering racial and socioeconomic factors when designing screening, treatment and management plans in an effort to reduce the mortality of CRC in an underserved community.

25 Background: There have been reports implicating underweight status as well as obesity with lower survival in colorectal cancer patients, but data has been inconsistent. Methods: In this retrospective observational study, we gathered pre-treatment data on BMI and other co-morbidities from 423 colon cancer patients who underwent surgical resection (stages I to III) or were metastatic at diagnosis (stage IV) at VCU Medical Center from 2005 to 2018 and analyzed their survival outcomes. Results: Compared to patients with a normal BMI, patients with underweight status (BMI < 18.5) have a trend towards higher all-cause mortality (HR 1.66, 95% CI 0.67-4.12). Patients with overweight BMI (25-29.9) and obese BMI ( > 30) have a trend towards improved mortality (HR 0.67, 95% CI 0.46-0.98) (HR 0.75, 95% CI 0.53-1.07) respectively. The p-value was 0.0675. We also found that pre-existing diabetes mellitus is associated with increased all-cause mortality (HR 1.43, CI 1.03 to 1.98, p < 0.05), as well as the use of aspirin at diagnosis (HR 1.60, CI 1.16 to 2.21, p < 0.05). Conclusions: Our results are similar to previous findings that patients with underweight status have worse mortality outcome, suggesting the importance of nutritional status prior to starting treatment. We also found that overweight and obese patients have trends towards improved survival compared to normal weight patients. Future focus can be directed to see whether overweight or obesity status past diagnosis affect survival trends. Aspirin use at diagnosis in our study population is associated with worse mortality outcome; literature is conflicting with outcomes and pre-diagnosis aspirin use. Our findings are similar for both locoregional colon cancers as well as metastatic disease. Research should be directed at seeing what kind of interventions such as nutrition or rehabilitation can be used to ameliorate the increased mortality trend in the underweight status group of patients.

Objectives To evaluate the efficacy of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion (at full PCI dose) to prevent stent thrombosis (ST) compared with heparin monotherapy. Background Early randomized controlled trials (RCTs) have shown that compared with heparin use, bivalirudin use during primary PCI is associated with an increased risk of ST. However, bivalirudin was stopped in those trials at the end of the procedure and glycoprotein IIb/IIIa inhibitors (GPIs) were routinely used with heparin. The increased risk of ST may be eliminated by continuing bivalirudin infusion post-procedure for few hours. Indeed, in most recent trials, a trend of lower ST risk has been observed with a post-procedure infusion of bivalirudin compared with heparin monotherapy (without the routine use of GPI). Methods Relevant RCTs were included and risk ratios (RRs) were calculated using random effect models. The primary outcome of interest was the risk of early definite ST. Results Four RCTs involving 13,505 patients were included in this meta-analysis. Compared with heparin monotherapy, bivalirudin (with a post-procedure infusion) was associated with a 55% decrease in the risk of early definite ST (RR: 0.45, 95% confidence interval: 0.23-0.85; P = 0.015). There was no difference in the risk of early ST between bivalirudin (with a post-procedure infusion) and heparin with GPI. Conclusions For primary PCI, a bivalirudin-based anticoagulant strategy (with post procedure infusion) is associated with a lower risk of early definite ST compared with treatment with heparin monotherapy (without GPI).

Patient portals are becoming widespread throughout health-care systems. Initial research has demonstrated that they positively impact patient-provider communication and patients' health knowledge, but little is known about the impact of patient portals in the cancer setting, where highly complex and uncertain medical data are available for patients to view. To better understand communicative behaviors and perceptions of the patient portal and how it is utilized in oncology, in-depth, semi-structured interviews were conducted with 48 participants: 35 patients and 13 oncologists. Thematic analysis identified that portals help to enhance participation during in-person consultations, increase patients' self-advocacy, and build rapport with providers. However, patients' comfort level with reviewing information via the portal depended upon the severity of the test. Oncologists worried about patient anxiety and widening health disparities, but acknowledged that the portal can motivate them to expedite communication about laboratory and scan results. As patient portals become more widely used in all medical settings, oncologists should become more engaged with how patients are viewing their medical information and consider the portal within the framework of patient-centered care by valuing patients' communication preferences.

BACKGROUND Providing patients with unrestricted access to their electronic medical records through patient portals has impacted patient-provider communication and patients’ personal health knowledge. However, little is known about how patient portals are used in oncology. OBJECTIVE The aim of this study was to understand attitudes of the portal’s adoption for oncology and to identify the advantages and disadvantages of using the portal to communicate and view medical information. METHODS In-depth semistructured interviews were conducted with 60 participants: 35 patients, 13 oncologists, and 12 medical informaticists. Interviews were recorded, transcribed, and thematically analyzed to identify critical incidents and general attitudes encountered by participants. RESULTS Two primary themes were discovered: (1) implementation practices influence attitudes, in which the decision-making and execution process of introducing portals throughout the hospital did not include the input of oncologists. Lack of oncologists’ involvement led to a lack of knowledge about portal functionality, such as not knowing the time period when test results would be disclosed to patients; (2) perceptions of portals as communication tools varies by user type, meaning that each participant group (patients, oncologists, and medical informaticists) had varied opinions about how the portal should be used to transmit and receive information. Oncologists and medical informaticists had difficulty understanding one another’s culture and communication processes in their fields, while patients had preferences for how they would like to receive communication, but it largely depended upon the type of test being disclosed. CONCLUSIONS The majority of patients (54%, 19/35) who participated in this study viewed lab results or scan reports via the portal before being contacted by a clinician. Most were relatively comfortable with this manner of disclosure but still preferred face-to-face or telephone communication. Findings from this study indicate that portal education is needed for both patients and oncologists, especially when portals are implemented across entire health systems since highly specialized areas of medicine may have unique needs and uses. Patient portals in oncology can potentially alter the way diagnoses are delivered and how patients and oncologists communicate. Therefore, communication about the portal should be established during initial consultations so patients can decide whether they want to be informed in such a manner.

To compare the efficacies of various post-percutaneous coronary intervenetion (PCI) bivalirudin doses on net adverse clinical events (NACEs) and mortality.In primary PCI, lower risk of bleeding with bivalirudin (vs. unfractionated heparin [UFH]) is counterbalanced by an increased risk of acute stent thrombosis (ST). Several randomized clinical trials (RCTs) and a recent meta-analysis suggest that acute ST risk may be eliminated without compromising the bleeding benefit, but only if the full dose, not a low dose, of bivalirudin is continued post-PCI. However, it is not known whether this improved risk leads to lower rates of NACEs and mortality.Scientific databases and Web sites were searched for RCTs. Trials were included if study patients were undergoing primary PCI for acute ST-segment elevation myocardial infarction and were randomly assigned to bivalirudin or UFH treatment. The bivalirudin arm was divided based on post-PCI bivalirudin dosage: The Biv-Full group received 1.75 mg/kg/h, the Biv-Low group, 0.25 mg/kg/h, and the Biv-No group, none.Six RCTs involving 16,842 patients were found. In pairwise meta-analysis, bivalirudin improved 30-day all-cause mortality by 35% and cardiac mortality by 32%, but did not yield a NACE rate better than that achieved with UFH. Subgroup analysis showed the Biv-Full group had a 46% lower NACE rate and 47% lower all-cause mortality than UFH. These effects were not seen in the other two groups. Network meta-analysis yielded similar results. At treatment ranking, the Biv-Full group yielded the best treatment efficacy.In primary PCI, full-dose bivalirudin infusion for 3-4 hr after PCI appeared to improve NACE rates compared to UFH. It also seemed to be the most effective strategy for improving cardiac mortality and all-cause mortality. © 2016 Wiley Periodicals, Inc.

e15673Background: Short course (SC) RT is equivalent to long course (LC) RT for local control, disease free survival (DFS) and overall survival with similar rates of sphincter preservation and late...

Background: There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure. Methods: EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m2 on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m2. Gefitinib, 250 mg/day orally, was given continuously. Results: Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m2 (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9–5.7). Conclusion: The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.

Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI.Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P.001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018).In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Malignancies of the gastrointestinal tract have a high incidence and great impact on both cancer mortality and economic resources. Specifically colorectal cancer is the third most commonly diagnosed cancer in men and second in women throughout the world [1]. In 2012, there were over 1.2 million new cases of colorectal cancer and an estimated 608,700 deaths attributed to it worldwide. Both incidence and mortality have been slowly declining in the United States, but still account for nearly 10 % of all cancer deaths [2]. Elsewhere in the world, the incidence of colorectal cancer is on the rise, especially in Eastern Asia and Eastern Europe [3] (Fig. 12.1).

Objective: We tested the hypothesis that the combination of trimetrexate (TMTX) and capecitabine (CAP) would be active in patients with previously treated metastatic colorectal cancer (CRC). Because the optimum dose of this combination was unknown, we used a phase I/II design. Methods: In the phase I cohort, patients received 110 mg/m2 TMTX intravenously weekly ×6 and CAP starting at 750 mg/m2 orally twice daily from days 2 to 15 and 23 to 36 (one cycle). Cycles were repeated every 8 weeks. The phase II doses were 110 mg/m2 TMTX and 1000 mg/m2 CAP orally twice daily. Results: Thirty-two patients were entered. All patients had prior 5-fluorouracil therapy and 94% had prior exposure to irinotecan. Grade 3/4 toxicities included abdominal pain in 4 patients (12.5%) and vomiting in 3 patients (9.4%). Twenty-seven patients were evaluable for response: one patient each had a complete response and a partial response for an overall response rate of 7.4%. The median time to progression was 3.3 months (95% confidence interval [CI], 1.6-3.7 months) and the median overall survival was 5.9 months (95% CI, 5.2-10.2 months). Conclusions: The combination of TMTX and CAP is well tolerated. However, recent studies have shown more active regimens in the second- and third-line metastatic setting. Copyright

Purpose. Preclinical data indicate that progestational agents (progesterone, medroxyprogesterone acetate and megestrol acetate) interact with p-glycoprotein (P-gp) and reverse P-gp-associated resistance to vinca alkaloids and other natural products. Based on these data, we performed a phase I study of high-dose oral megestrol acetate and vinblastine to evaluate the safety of this regimen. Patients and methods. Enrolled in the study were 61 patients with advanced solid tumors, refractory to standard therapy. Cohorts of patients received megestrol acetate according to the following escalation scheme (loading dose/maintenance dose, twice daily for 7 days): 750 mg/250 mg, 750 mg/375 mg, 1000 mg/500 mg, 1500 mg/1000 mg, 3000 mg/2000 mg, 4500 mg/3000 mg, 6000 mg/4000 mg, and 7500 mg/5000 mg. They also received 1.5 mg/m2 per day of vinblastine by continuous infusion for 5 days (days 2 to 6). Results. Of the 61 patients, 59 were evaluable for toxicity. A maximum tolerated dose (MTD) was not reached. The regimen was well tolerated. Of the 59 patients, 10 (17%) experienced grade 4 leukopenia. All of these cases were at dose levels 3 to 8. There was an increase in the steady-state concentration (Css) of megestrol acetate with increasing dose up to the sixth dose level. Further increases in the dose produced no change in the megestrol acetate Css. Only 2.4% of megestrol acetate was free in the plasma as compared to 65.6% in RPMI culture medium. Megestrol acetate administration was associated with profound suppression of ACTH and cortisol levels. Conclusions. The combination of vinblastine and megestrol acetate was well tolerated. An MTD for this combination was not achieved as a result of the saturable absorption of megestrol acetate. Although potentially therapeutic serum concentrations of megestrol acetate were achieved, it is unlikely that MDR was reversed given the high protein-binding of the drug. Profound suppression of the pituitary-adrenal axis was also observed during the administration of megestrol acetate.

102 Background: Chemotherapy has clinical benefit for elderly patients with careful selection. Selection is based on ECOG Performance Status determination. Patients with ECOG PS of 0-2 are considered chemotherapy candidates whereas patients with PS > 3 are considered unlikely to benefit from it. Recommended tools such as a Comprehensive Geriatric Assessment (CGA) to help stratify patients further are not widely adopted. This study looks at disparity in use of supportive resources in patients > 65 years of age undergoing chemotherapy at the Virginia Commonwealth University (VCU) Hospital. Methods: We conducted a retrospective analysis for all patients 65 and above with gastrointestinal malignancies (gastroesophageal, colorectal, and pancreatic) treated between January 2005 and July 2016 that received chemotherapy in any setting. ECOG performance status at initiation of therapy was required. Data collected on receipt of supportive resources such as Physical Therapy (PT), Occupational Therapy (OT), Nutrition, Mental Health, Geriatrics and Palliative Care. Exact Pearson’s chi-square tests were used for comparison of services and ECOG PS, race, etc. Results: 226 patients met criteria. Majority of patients were male (56%), white (63%) and had advanced malignancies (80% Stage III/IV disease). Mean age was 72.2 (SD = 5.6). ECOG PS was ≤1 in 88% and ≥2 in the remainder. 61% of patients utilized at least one resource (Palliative care: 46%, Nutrition: 21%, Mental Health: 15%, PT: 13%). Patients with an ECOG PS 0 or 1 tended to use more services; nutrition statistically significant (p = 0.037). Racial disparities observed in receipt of PT (P = 0.002), mental health (P = 0.012), palliative care (P = 0.039) with white patients more likely to receive the service in each case. More white than non-white patients received services (66% vs. 55%, P = 0.067). Conclusions: ECOG PS 0 or 1 correlated with increased utilization as compared to less robust ECOG 2 patients; tools such as CGA for appropriate service allocation are needed. We identified racial disparity in the utilization of certain services and these need further exploration, including patters for referral of these services as a factor.

6575 Background: Misconceptions about the curative potential of PC are common, and may arise from gaps in informed consent. Another contributing factor could be patients’ desire, or lack of desire, for information about prognosis and PC outcomes. Methods: We surveyed 137 patients with advanced colorectal (N = 102) or pancreatic cancer (N = 35) within 2 weeks of consultation about 1st or 2ndline PC, as part of randomized trial of a PC education intervention at 6 US sites. Patients rated how much information they wanted about PC risks/benefits, including impact on prognosis. Responses ranged from no information to as much as possible on a 5-point Likert scale. They reported decision-making preferences; whether a doctor discussed curability, and how likely they thought PC was to cure their cancer. Chi square and Wilcoxon tests examined whether information and decision-making preferences, or curability discussions were associated with expectations of cure. Multivariable logistic regressions evaluated whether associations were modified by age, race, gender, marital status, or cancer type. Results: Only 44.5% of patients accurately reported that their cancer was not at all likely to be cured by PC. Most patients wanted a lot, or as much information as possible about PC risks/benefits, including likelihood of cure (81.7%), cancer control (84.7%), and impact on length of life (80.3%). Most patients preferred shared (70.8%) versus active or passive decision-making. Neither decision-making nor prognostic information preferences were associated with expectations of cure. Patients (13.9%) who did not recall curability discussions were less likely to have accurate expectations (21% v 48%; OR, 0.29; 95% CI, 0.07-.97). Patient characteristics did not significantly confound this association. Conclusions: Most patients value shared decision-making and want maximal information about PC risks/benefits, including impact on prognosis. Despite wanting prognostic information and reporting curability discussions, many patients report inaccurate expectations about cure from PC. Future studies should examine whether these assertions reflect misunderstandings, differences in belief, or expressions of hope.

Background: Rubitecan (RFS-2000, 9NC, Orathecin™ is an orally bioavailable camptothecin analogue, with evidence of preclinical activity in colon cancer cell lines. We evaluated oral rubitecan (5 days on, 2 days rest per week) on a continuous schedule, in patients with advanced colorectal cancer (CRC), who progressed after 5-flurouracil based chemotherapy. Patients and results: Fourteen eligible patients were treated with rubitecan at 1.5 mg/m2/day on a 5 day/week continuous schedule. Therapy was well tolerated with most adverse events in the mild to moderate category. Grade 3/4 toxicity consisting of anemia, diarrhea and elevated bilirubin was seen in 4 patients. No responses were seen in 13 evaluable patients. Overall median survival (95% confidence interval) was 10.1 (range 3.1–12.6) months, and median time to progression was 2.1 months. Conclusions: Administration of rubitecan was well tolerated, but this schedule does not appear to have clinical activity in patients with advanced previously treated CRC.

4586 Background: Gemcitabine is the standard-of-care for APC; the epidermal growth factor receptor (EGFR) inhibitor erlotinib is sometimes added to initial therapy. Pre-clinical data supports the addition of the EGFR inhibitor gefitinib to docetaxel, an agent with activity in APC. Because there is no standard treatment after gemcitabine failure, this combination was examined in a phase II study. Methods: Pts were required to have APC and have failed one prior treatment regimen; EGFR over-expression was not required. The initial docetaxel dose was 75 mg/m2 on day one every 21 days . Due to febrile neutropenia in 8 of 18 pts, the dose was reduced to 60 mg/m2. Gefitinib 250 mg/day orally was given continuously. Accrual of 41 pts was planned in a one-stage design to identify a targeted 50% improvement in median survival from 3.5 to 5.3 months (mo) by one-sided log-rank test (80% power, a = 0.05). Results: Forty five pts met eligibility and signed consent; 41 pts received treatment and were evaluable. Pt characteristics: 68% male, median age 63 yrs. (range 47 - 82). ECOG performance status (PS) 0 - 1 in all pts, except for 3 with PS of 2. Common treatment-related Grade 3 - 4 toxicities were: febrile neutropenia / infection in 11 pts (27%), with most events occurring at docetaxel dose of 75 mg/ m2 (8 of 18 pts); fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). Only 3 pts discontinued treatment due to toxicities and more than 2 cycles were administered to 40% of patients. The median survival was 4.7 mo (95% CI 2.9 - 5.7 mo). Time to progression was 1.8 months. There was one partial response (PR) and stable disease (SD) in 14 pts. Conclusion: The combination of gefitinib (250 mg/d) and docetaxel (60 mg/ m2) had evidence of some efficacy with one PR and SD in 14 pts. The median survival was 4.7 mo, somewhat lower than our intended target (5.3 mo). The tolerability and feasibility of second-line therapy for APC was demonstrated, and results of this study can be used as a benchmark to evaluate novel therapies in subsequent studies. (Supported by Astra Zeneca Pharmaceuticals) No significant financial relationships to disclose.