CHI Health St. Francis

An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal-Anal Task Forces of the United States National Cancer Institute convened a panel of multidisciplinary experts to summarize current data on the utility of ctDNA in the management of colorectal cancer and to provide guidance in promoting the efficient development and integration of this technology into clinical care. The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments. The panel also provides general guidelines with relevance for ctDNA-related research efforts, irrespective of indication.

Introduction: Single-agent belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, demonstrated deep and durable responses with a manageable safety profile in patients with heavily pretreated RRMM (median 7 lines of prior therapy) refractory to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and refractory and/or intolerant to an anti-CD38 monoclonal antibody in the pivotal Phase II DREAMM-2 study (NCT03525678). At 13-month follow-up, the overall response rate (ORR) was 32% and the median duration of response (DoR) was 11.0 months in the belamaf 2.5 mg/kg arm (Lonial. ASCO 2020 Poster 436). The multimodal mechanism of action, efficacy and safety profile of belamaf, as well as preclinical data suggest possible synergy with standard of care agents and a potential benefit in combination with IMiDs and PIs. DREAMM-6 (NCT03544281) is an ongoing Phase I/II, two-part study of belamaf in combination with lenalidomide/dexamethasone (Arm A) or BorDex (Arm B) in patients with RRMM who had received ≥1 prior therapy (bortezomib-refractory patients were not excluded); preliminary results from Arm B have been reported (Nooka. ASCO 2020 Oral 8502). Methods: Part 1 (dose escalation) and Part 2 (dose expansion) of Arm B in DREAMM-6 evaluated belamaf (2.5 and 3.4 mg/kg intravenously (IV) every 3 weeks [Q3W]) administered as SINGLE (Day 1) or SPLIT dose (divided equally on Days 1 and 8) plus BorDex (Bor 1.3 mg/m2 [subcutaneously] and Dex 20 mg [IV or orally]). Combination treatment continued for up to 8 cycles, with single-agent belamaf maintenance therapy thereafter. Primary objectives were safety, tolerability, and efficacy (ORR [≥ partial response, PR] per investigator-assessed best confirmed response). We report safety and efficacy results from the 2.5 mg/kg SINGLE dose cohort from Arm B. Results: As of March 30, 2020, 18 patients had received belamaf 2.5 mg/kg SINGLE + BorDex in Parts 1 and 2 of Arm B. The median age was 67 years, 61% were male, and 33% had high-risk cytogenetics; patients had received a median of 3 (range, 1-11) prior lines of therapy. All 18 patients had treatment-related adverse events (AEs), of whom 16 (89%) had Grade 3/4 events (see Table). Treatment-related serious AEs occurred in 5 (28%) patients. There were no Grade 5 AEs of interest. Thirteen (72%) patients had dose reductions (8/13 belamaf) and all patients had dose delays (16/18 belamaf) to manage AEs. Five (28%) patients discontinued a study treatment due to AEs: 4 bortezomib, 2 dexamethasone, no patients discontinued belamaf. Of the AEs of interest, thrombocytopenia occurred in 12 patients (67%; maximum Grade 4 in 8 patients and Grade 3 in 3 patients) and led to dose reduction in 6 (33%) patients, dose delay in 7 (39%) patients, and no discontinuations. Three (17%) patients had Grade 2 infusion-related reactions (with no dose modifications or discontinuations). Changes in the corneal epithelium (keratopathy/microcyst-like epithelial changes [MECs], an eye exam finding with or without symptoms), an anticipated AE associated with monomethyl auristatin F, the payload in belamaf, occurred in all 18 patients (maximum Grade 3 in 10 patients, Grade 2 in 7 patients, and Grade 1 in 1 patient), and led to dose reduction in 7 (39%) patients, dose delay in 15 (83%) patients, with no discontinuations. Response was evaluable in all patients; ORR was 78% (95% CI 52.4-93.6), with very good partial response (VGPR) in 9 (50%) and PR in 5 (28%) patients. One (6%) patient had minimal response, and 3 (17%) patients had stable disease. Clinical benefit rate was 83% (95% CI 58.6-96.4). After a median of 18.2 weeks (range 6.0-46.4 weeks) on treatment, median DoR was not reached. Conclusions: The combination of belamaf 2.5 mg/kg Q3W with standard-of care BorDex demonstrated an acceptable safety profile in patients with RRMM who had received a median of 3 prior lines of therapy, with AEs as expected, and no new safety signals to date. Corneal events were common but manageable with belamaf dose modifications. At interim follow-up, best response data indicate a high ORR of 78%, VGPR of 50%, and clinical benefit rate of 83%. Final data for the 2.5 mg/kg SINGLE + BorDex cohort will be reported at the congress. Funding: GSK (Study 207497); drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Disclosures Popat: AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Nooka:Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Adaptive Technologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Stockerl-Goldstein:Celgene: Consultancy; Abbott Laboratories: Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company; GSK: Research Funding; Takeda: Research Funding; BiolineRx: Research Funding; Janssen: Research Funding; Cellerant: Other: Other relationship. Abonour:Takeda: Consultancy; Janssen: Honoraria, Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding. Khot:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Other: Speaker fees; Novartis: Other: Travel grant. Lee:Janssen: Consultancy; Amgen: Consultancy; Celgene/BMS: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Spencer:AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Celgene, Janssen and Takeda: Speakers Bureau. Mateos:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; PharmaMar-Zeltia: Consultancy; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rogers:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Smith:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Davidge:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yeakey:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Talekar:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Quach:Sanofi: Consultancy, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding.

CONTEXT: COVID-19 caused a worldwide pandemic, and there are still many uncertainties about the disease. C-reactive protein (CRP) levels could be utilized as a prognosticator for disease severity in COVID-19 patients. OBJECTIVES: This study aims to determine whether CRP levels are correlated with COVID-19 patient outcomes and length of stay (LoS). METHODS: A retrospective cohort study was conducted utilizing data obtained between March and May 2020. Data were collected by abstracting past medical records through electronic medical records at 10 hospitals within CommonSpirit Health. Patients were included if they had a positive COVID-19 test from a nasopharyngeal swab sample, and if they were admitted and then discharged alive or had in-hospital mortality and were ≥18 years. A total of 541 patients had CRP levels measured and were included in this report. Patient outcome and LoS were the endpoints measured. RESULTS: The 541 patients had their CRP levels measured, as well as the demographic and clinical data required for analysis. While controlling for body mass index (BMI), number of comorbidities, and age, the first CRP was significantly predictive of mortality (p<0.001). The odds ratio for first CRP indicates that for each one-unit increase in CRP, the odds of death increased by 0.007. For LoS, the first CRP was a significant predictor (p<0.001), along with age (p=0.002). The number of comorbidities also predicted LoS (p=0.007), but BMI did not. The coefficient for the first CRP indicates that, for each one-unit increase in CRP, LoS increased 0.003 days. CONCLUSIONS: The results indicate that there is a positive correlation between the CRP levels of COVID-19 patients and their respective outcomes with regard to death and LoS.

BACKGROUND: The Braden Scale for Predicting Pressure Sore Risk has been tested extensively for reliability and validity, but the validity of each subscale has not been evaluated. Because subscale scores are intended to guide patient care decisions, validity is an important issue. OBJECTIVE: : To establish the convergent construct validity of the mobility subscale of the Braden Scale. METHODS: The study evaluated 16 members at a veterans' home (4 members representing each score on the mobility subscale). Movement, as recorded by a Motionlogger Actigraph, a wristwatch-sized accelerometer and microprocessor that measures physical movement (activity), was measured continuously. Each person wore an Actigraph on the nondominant ankle for 72 hours. RESULTS: The mean activity for each of the four subscale score groups was plotted, producing a histogram in which higher scores were associated with greater activity (F[3, 15] = 31.69;p <.001, one-way analysis of variance), as expected. Pair wise multiple comparisons between groups showed that only the subgroup with a score of 4 was significantly different in mean activity (p <.001) from the other three score groups. CONCLUSIONS: Convergent construct validity for the Braden mobility subscale was supported. A larger sample and establishment of a threshold to eliminate minor, ineffective movements from Motionlogger Actigraph measures may distinguish between significant and nonsignificant movement.

TOPIC: This article presents an overview of the burden of peripheral intravenous catheter infections and current evidence-based recommendations for prevention. CLINICAL RELEVANCE: Peripheral intravenous catheters are ubiquitous in most health care settings, fostering an acceptance of the peripheral intravenous catheter as benign and inevitable. This device, however, is far from benign, with reported failure rates as high as 90% from complications such as infection and phlebitis. Although reported rates of bloodstream infection related to peripheral intravenous catheters are much lower than those attributed to central venous catheters, the exponentially higher use of peripheral intravenous catheters indicates that the absolute number of peripheral venous catheter-related bloodstream infections is likely as high as and may surpass the number of central venous catheter-related bloodstream infections, with significant associated morbidity and mortality. PURPOSE OF PAPER: Sustained improvements in outcomes related to peripheral intravenous catheters will depend on recognition of the root causes of failure and increased commitment to practice patterns consistent with infusion therapy standards of practice, effective education about peripheral intravenous catheters, accurate documentation of all aspects of peripheral intravenous catheter management, and consistent surveillance of patient outcomes related to peripheral intravenous catheters. CONTENT COVERED: This article reviews the significant burden of peripheral intravenous catheter infections, barriers to effective peripheral intravenous catheter management, and current evidence-based recommendations to prevent this source of patient harm.

In critical care, the short peripheral intravenous catheter is an essential venous access route, often used in emergency situations to administer high-risk medications and fluid resuscitation. This route of administration is generally viewed as routine and benign. However, a growing body of evidence indicates that the risks inherent to this route are much higher than reported and represent a significant area of patient harm. Few standardized definitions and surveillance methods exist for peripheral intravenous catheter-related complications such as phlebitis, bloodstream infection, and extravasation. Recommendations for peripheral intravenous catheter replacement are based on clinical indications rather than routine replacement, so standards of practice for catheter insertion and management must be consistently applied. This article reviews recent studies that challenge the need for central catheter placement for vasopressor therapy, current knowledge of peripheral intravenous catheter-related adverse events, and evidence-based standards of care for short peripheral intravenous catheter insertion and maintenance.

BACKGROUND: The goals of infusion therapy are to preserve vascular health and safely deliver needed treatment. Achieving these goals is challenging in critical care because of the complexity of the treatment required. Daily justification of retaining an existing central venous catheter also creates urgency to change to a peripheral vascular access device. The midline catheter has had a resurgence in use because of the need for a long-term peripheral vascular access device not linked to central catheter-associated bloodstream infection risk. OBJECTIVE: To review the characteristics of midline catheters, the benefits and risks of midline catheters, and current evidence regarding midline catheter use in critical care. RESULTS: Research related to midline catheters has greatly expanded the body of knowledge regarding vascular access device selection and midline catheter use. DISCUSSION: Although the quality and results of research on vascular access devices vary widely, a more accurate safety profile is emerging to illustrate how midline catheter use can support the goals of infusion therapy. CONCLUSIONS: Optimizing vascular access device selection requires recognition that every vascular access device can cause patient harm. Although the midline catheter appears to fill an important niche in infusion therapy, use of the midline catheter should be carefully evaluated. Midline catheters should not be used as a catheter-associated bloodstream infection prevention strategy, should be inserted to administer peripherally compatible solutions, and should be considered for short-term continuous vesicant therapy only in emergent situations until more definitive vascular access can be achieved.

BACKGROUND: Enthusiasm for precision oncology may obscure the psychosocial and ethical considerations associated with the implementation of tumor genetic sequencing. METHODS: Patients with advanced cancer undergoing tumor-only genetic sequencing in the National Cancer Institute Molecular Analysis for Therapy Choice (MATCH) trial were randomized to a web-based genetic education intervention or usual care. The primary outcomes were knowledge, anxiety, depression, and cancer-specific distress collected at baseline (T0), posteducation (T1) and after results (T2). Two-sided, 2-sample t tests and univariate and multivariable generalized linear models were used. RESULTS: Five hundred ninety-four patients (80% from NCI Community Oncology Research Program sites) were randomized to the web intervention (n = 293) or usual care (n = 301) before the receipt of results. Patients in the intervention arm had greater increases in knowledge (P for T1-T0 < .0001; P for T2-T0 = .003), but there were no significant differences in distress outcomes. In unadjusted moderator analyses, there was a decrease in cancer-specific distress among women (T0-T1) in the intervention arm but not among men. Patients with lower health literacy in the intervention arm had greater increases in cancer-specific distress and less decline in general anxiety (T0-T1) and greater increases in depression (T0-T2) in comparison with those receiving usual care. CONCLUSIONS: Web-based genetic education before tumor-only sequencing results increases patient understanding and reduces distress in women. Refinements to the intervention could benefit low-literacy groups and men.

Purpose Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented. Methods From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records. A total of 11 different types of monoclonal antibodies that were administered during the study period were identified. Trastuzumab, ofatumumab, and obinutuzumab did not require dose-rounding; thus, they were excluded from the analyses. Available vial size(s) and costs per milligram per average wholesale price for each monoclonal antibody were recorded. Costs of actual amounts prescribed were compared to the costs of theoretically reduced ≤5% and ≤10% doses rounded to the nearest vial sizes. Reduced doses resulting in a decreased number of opened vials qualified for meaningful dose down-rounding and were included in the analysis. Average actual dose reduction percentage resulting in cost savings for both groups was also calculated. Results A total of 728 doses of eight monoclonal antibodies suitable for dose down-rounding were identified. Vial sizes of pembrolizumab and ipilimumab did not allow for a meaningful dose down-rounding. At the ≤5% dose down-rounding, 255 of 728 doses (35%) qualified with a potential annual cost savings of $220,793.80. At the ≤10% dose down-rounding, 526 of 728 doses (72%) qualified with a potential annual cost savings of $454,461.00. The average actual dose reduction was 2.4% for the ≤5% dose reduction group and 4.9% for the ≤10% dose reduction group. Overall average cost savings per qualifying dose reduction was around $865.00. More doses qualified for cost savings in the ≤10% dose reduction group. Significant differences between different monoclonal antibodies for dose rounding at either ≤5% (p = 0.002) or ≤10% (p < 0.001) were observed. Conclusion A practical dose down-rounding procedure may allow significant cost reduction in metastatic cancer setting, where the cure is not the goal. Drug waste can be avoided by convenient vial sizes or can even be eliminated by lyophilized forms like in trastuzumab. Our data reflect the monoclonal antibody use and potential cost savings with the proposed dose down-rounding approach in a community-based cancer program.

As new nurses move from the familiar educational milieu into a work situation they encounter barriers to caring for patients and their families. The characteristics of the contemporary work environment, paired with the competencies of the new graduates, have the potential to threaten the ability of these nurses to provide safe and effective care for patients thus creating ethical distress. Educational interventions in the work place can effectively provide adequate solutions to these problems. The keystone between the healthcare institution and the development of a competent nurse is an effective mentor. As new nurses graduate from school and enter the health care industry they encounter many barriers that distract them from caring for their patients. With limited experience they are ill equipped to prevent ethical distress when confronted with ethical dilemmas. Educational strategies such as an adequate orientation can help a new graduate cope with the complexities of a health care industry confronted by an increase in acuity of patients, progressively more complex medical interventions, and a shortage of nurses.

Solid tumors involving glandular organs express mucin glycoprotein that is eventually shed into the circulation. As a result, these proteins can easily be measured in the serum and be used as potential tumor markers. The most commonly used tumor markers for breast cancer are CA27-29 and CA15-3, which both measure the glycoprotein product of the mucin-1 (MUC1) gene. CA27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in breast cancer patients. Most oncology clinical practice guidelines do not recommend the use of tumor markers for routine surveillance of early stage disease but recognize their utility in the metastatic setting. We present a patient with stage IIIA breast cancer and preexisting hypersensitivity pneumonitis who was found to have an elevated serum tumor marker CA27-29. After successful curative intent treatment of her early stage breast cancer, she developed gradual and progressive worsening of her lung disease with eventual development of severe pulmonary fibrosis requiring bilateral lung transplantation. As part of the pretransplant evaluation, she was found to have an elevation of serum tumor marker CA27-29. While the diagnostic evaluation, including imaging studies, was negative for the presence of recurrent disease, the serial serum tumor marker CA27-29 levels remained persistently elevated. The decision was made for her to undergo bilateral lung transplantation. Shortly after surgery, her CA27-29 tumor marker level returned to normal range, and it has continued to remain in the normal range with no evidence of breast cancer recurrence.

4568 Background: Sitravatinib (MGCD516) is an oral, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including the TAM family (AXL, MER), split RTKs (VEGFR2, PDGFR, KIT), RET and MET. Because of the importance of sitravatinib targets in the pathogenesis of ccRCC and putative roles for MET and AXL in intrinsic and acquired resistance to anti-angiogenic agents, sitravatinib was evaluated in patients (pts) with ccRCC after failure of AAT. Methods: Study 516-001 is a Phase 1/1b study of sitravatinib in pts with advanced solid tumors. After determination of the MTD in Phase 1, pts with ccRCC after failure of AAT and pts with qualifying genetic alterations in sitravatinib targets were enrolled into distinct Phase1b cohorts using respective multi-stage designs. Pts received 150mg sitravatinib once daily in continuous 21-day cycles and were evaluated for safety, PK and clinical activity. Here we report on the completion of Stage 2 enrollment of the Phase1b ccRCC cohort. Results: 89 pts (50 men/39 women; median age 67 years; range 36-84) with advanced solid tumors were enrolled in Phase1b cohorts, including 28 pts (20 men/8 women; median age 67.5 years; range 47-77) in the ccRCC cohort who received a median of 3 prior treatment regimens. Prior AAT included sunitinib (n=17), pazopanib (n=13) and axitinib (n=9); 12 pts received ≥2 prior angiogenesis inhibitors. One partial response (PR) among the first 10 evaluable ccRCC pts in Stage 1 met criteria for enrollment of a total of 20 evaluable pts for Stage 2, where 4 confirmed PRs were observed and an unconfirmed PR in a pt who had received 4 prior AATs. Prolonged stable disease for at least 24 weeks was observed in an additional 5 pts. Treatment-related AEs (>20% of pts; Grades 1-3) included diarrhea, hypertension, nausea, vomiting, fatigue and decreased appetite. Conclusions: Stage 2 enrollment of the Study 516-001 Phase1b cohort of ccRCC refractory to AAT was completed. Sitravatinib treatment resulted in 4 confirmed PRs in a heavily pre-treated patient population and demonstrated a manageable safety profile. Further evaluation of sitravatinib in ccRCC is warranted. Clinical trial information: NCT02219711.

e18500 Background: Within past decade NCI has implemented two major initiatives to improve CT participation and quality of cancer care in the community setting. Catholic Health Initiatives (CHI) St. Francis Cancer Treatment Center in Grand Island Nebraska was one of the privileged community cancer centers to participate in both programs. Methods: During the last 3 years of NCCCP and first 3 years of NCORP, data on CT activities including number/percent of patients, underserved populations on CTs, number/type of CTs, staffing, organizational infrastructure/linkage to National Clinical Trials Network (NCTN), and access to cancer treatment (CRx), cancer control/prevention (CC/P), cancer care delivery (CCDR) trials were gathered and compared. Results: CT enrollment increased from 512 (30%) during NCCCP to 518 (36%) during NCORP (P = 0.0005). All patients were rural Nebraskans, 70% older than 60. Total CTs increased from 45 during NCCCP to 125 during NCORP. Major increases in NCTN trials/accruals were seen during NCORP. Staffing increased by two. Organizational infrastructure/linkage to cooperative group (CG) trials was with CALGB through an academic affiliation and academic IRB during NCCCP and with ECOG-ACRIN, SWOG, NRG, ALLIANCE through CHI-NCORP and central IRB of NCI and/or CHI during NCORP. Conclusions: Participation in both NCI programs positively impacted CT related activities and expanded research with enhanced access to quality cancer care. NCORP provided a robust NCTN linkage resulting in a record high CT portfolio. This preliminary comparison between two strong NCI initiatives may help for design of future programs. Activity July 2011-June 2014 Last 3-year NCCCP July 2014-June 2017 First 3-year NCORP P # Staff (FTE) 7 9 0.02* ∑ # Accruals (range) 512 (140-230) 518 (107-213) ∑% Accruals (range) 30 (26-34) 36 (23-42) 0.0005* ∑ # CG Trials / ∑ # Accruals 23 / 36 98 / 151 0.09 # CRx / # Accruals 18 / 26 81 / 114 0.03* # CC/P / # Accruals 2 / 8 11 / 21 0.41 # CCDR / # Accruals 0 3 / 16 0.25 # Biospecimen / # Accruals 3 / 2 3 / 0 0.91 # Industry / # Accruals 10 / 9 18 / 27 0.33 # Investigator Initiated / # Accruals 12 / 467 9 / 340 0.96 ∑ 45/512 125/518

Trimethoprim-sulfamethoxazole (TMP-SMX), a widely used antibiotic, is associated with both predictable dose-dependent side effects and rare, idiosyncratic adverse reactions. Here, we report the case of a previously healthy, non-G6PD-deficient, 27-year-old male who developed three idiosyncratic reactions: severe thrombocytopenia, aseptic meningitis, and hepatitis concurrently following TMP-SMX administration. The Naranjo adverse reaction probability score was 7, implying TMP-SMX as the probable cause of the clinical presentation. After a comprehensive workup to rule out alternate etiologies, we have established TMP-SMX as the culprit. Our case highlights the importance of early recognition of TMP-SMX-induced rare adverse events for appropriate management to mitigate long-term sequelae and ensure favorable patient outcomes.

To evaluate the effectiveness of an EBM curriculum for neurology residents using AAN’s EBM ONLINE in a flipped classroom model.

Cancer-associated thrombotic microangiopathy (TMA) is a rare and often fatal consequence of solid and hematologic malignancies. We report a 69-year-old woman with metastatic hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer who developed severe anemia without bleeding. Laboratory tests revealed erythrocyte destruction, low platelet counts, and the presence of schistocytes. Imaging suggested a stable tumor burden. A bone marrow biopsy confirmed cancer-associated TMA. This case shows that stable imaging does not rule out cancer progression or TMA. Early diagnosis of cancer-associated TMA is essential for timely therapy, improving survival rates, and quality of life.

The relationship between catecholamine surge and acute traumatic brain injury (TBI) has been shown in the literature.[1] [2] [3] [4] The catecholamines released during acute TBI lead to a higher metabolic rate, increased systemic blood pressure blood flow, and hyperemia in the brain. The brain autoregulation is linear due to TBI,[5] this leads to uncontrolled perfusion and hence cerebral edema. Also, this pathophysiological process is directly related to a significant and potentially life-threatening increase in intracranial pressure (ICP). In patients with TBI, multiple pharmacological tools are used to prevent and treat high ICP. These include nonselective beta-blockers for suppression of hypertensive response, beta-blockers to suppress adrenergic surge, hypertonic saline, osmotic diuresis with mannitol, and sedative agents including midazolam, lorazepam, propofol, pentobarbital, and inhaled anesthesia. In the more extreme cases, an induced coma is introduced with pentobarbital or inhaled anesthesia. This is to decrease cerebral metabolic rate and sometimes even to the point of complete loss of brain activity.

e15064 Background: Immune-checkpoint inhibitor (ICI) therapy related thyroid function test (TFT) abnormalities are not uncommon. No well-established guidelines on the type, frequency, and duration of monitoring of TFTs exist in this setting. We retrospectively evaluated the practice patterns of TFT utilization for ICI treated cancer patients (pts) in our community based cancer program. Methods: Review of records of cancer pts receiving ICIs (Ipilimumab (I), Nivolumab(N) +/- Ipilimumab, Pembrolizumab(P), and Atezolizumab(A)) was performed utilizing electronic medical records at Catholic Health Initiatives St Francis Cancer Treatment Center, Grand Island Nebraska. TFT ordering patterns, results, and clinical management of pts were evaluated. Pts with prior TFT abnormalities were excluded from analyses. Results: Aug-2015 to Jan-2018, 130 pts (66F/64M), ages 32-94, received at least one dose of ICI therapy (N = 94, P = 26, A = 5 and N+I = 5). Median number of TFTs ordered by 8 providers (4 MDs/4PA/APRNs) was 14 (range 0-28). All pts had TSH, free T3 and free T4 tested. 62/130 (47%) pts had abnormal TFTs. Median number of abnormal TFTs was 10 (range 0-23). Median time to abnormal TFTs was 52 days. 34/130 (27 %) pts had TFTs checked every cycle of ICI therapy vs 96/130 (73 %) pts had TFTs checked every 3rd cycle of ICI therapy. All pts had TFTs monitored until the completion of ICI treatment. Both, pts who did not have abnormal TFTs until after 4 cycles and pts with abnormal TFTs who achieved euthyroid levels with treatment, remained euthyroid until the end of ICI treatments. There were no TFT related ICI treatment discontinuations. Conclusions: Incidence of TFT abnormalities with ICI therapy was higher than reported in our community based cancer practice. Monitoring of TFTs beyond initial 4 cycles or after achieving euthyrotid levels did not change the outcome. Our retrospective review suggests that in ICI treated cancer pts monitoring of TFTs with a baseline and every 3 cycles of ICI treatment and less frequently thereafter may be adequate unless clinically indicated. Prospective evaluation of this concept might help establish future definitive guidelines in this setting.

e16600 Background: Gallbladder cancer (GBC) is the most aggressive malignancy of the biliary tract. Though rare, most diagnoses are made in advanced stages, which significantly impacts survival outcomes. In the U.S., only 20% of GBC cases are diagnosed early. In addition to late diagnosis, time to treatment initiation (TTI) after diagnosis may contribute to poor prognosis in GBC patients. The role TTI plays on survival is not well understood in patients with GBC. This study aimed to determine the effect of time to treatment initiation on overall survival and by stage. Methods: Data on 26,952 GBC patients from 2004 to 2012 were obtained from the National Cancer Database (NCDB). The primary outcome was overall survival in months. TTI was defined as the number of days between diagnosis and treatment initiation (surgery, chemotherapy, radiation). The Kaplan-Meier method was used to calculate survival estimates and Cox proportional hazards regression model to evaluate the effects of TTI (continuous variable) stratified by stage. Results: The overall median survival was 8.6 months (I.Q.R. = 2.6-23.9). The effect of TTI on survival (unadjusted Hazard Ration (UHR) 1.0 (p = &lt; 0.0001)) was significant, but not after adjusting for other variables, (adjusted Hazard Ratio (AHR) 1.0 (p = 0.1506)). The trend was different across cancer stages. TTI showed a negative effect on survival in stages III (AHR: 1.00, p = 0.0083) and IV (AHR: 0.99, p &lt; .0001). Other factors associated with lower survival are advanced stage, male, older age, comorbidity, community cancer facility, and whether a patient visited more than one facility for treatment. Conclusions: In general, time to treatment initiation did not affect survival but advanced stage lowered survival significantly. More attention should be given to patients who decide to seek second opinion at or those given treatment referrals to other facilities as the adjustments may contribute to delays in treatment initiation.

2008 Background: Enthusiasm for precision oncology may obscure the complex psychosocial and ethical considerations for tumor genetic testing. Low patient genetic knowledge has been documented and heightens the risk for adverse experiences. We developed a web-based intervention to increase genetic knowledge and decrease distress among advanced cancer patients undergoing tumor genetic testing. Methods: 594 patients (80% from NCORP Community Sites) were recruited and randomized to web-intervention (n = 293) or usual care (n = 301), prior to receipt of tumor genetic test results. Primary outcomes were genetic knowledge, anxiety, depression, and cancer-specific distress measured at T0 (prior to intervention), T1 (post-intervention), T2 (after receipt of tumor results) and T3 (3 months post receipt of tumor results). Secondary outcomes included satisfaction, regret and disappointment. The effect of web-intervention was evaluated using t-test, multiple linear regression and logistic regression, with an intent-to-treat approach. Results: Patients randomized to web-intervention had better knowledge improvement than those randomized to usual care (T1-T0, p &lt; 0.0001; T2-T0, p = 0.003). No difference was observed in change scores for anxiety, depression or cancer-specific distress. To find the moderators of intervention effect (including sex, age, education, and literacy) two 2-way interactions were noted with statistical significance: higher depression among those in the intervention arm versus the control arm for patients with lower literacy (p = 0.03); and lower cancer-specific distress among women in the intervention arm than with usual care but no such effect noted in men (p = 0.01). 71% of patients reported receiving tumor test results and this did not differ by arm. Only 20% of patients reported regret and disappointment at T2, which was more likely for those without a mutation of interest (MOI) detected vs those with a MOI detected (OR = 2.08, 95% CI, 1.13 to 3.83, p = 0.02). Conclusions: Web-based education prior to receipt of tumor genetic test results increases patient understanding of tumor genetic testing. While the intervention did not significantly reduce distress, results suggest that women who received the intervention had lower cancer-specific distress than those with usual care. Future refinements to the web-intervention are needed to address low literacy groups, men and patients with no actionable results. Clinical trial information: NCT02823652.