Citations

Abstract Triplet regimens combining an immunomodulatory agent, a proteasome inhibitor (PI), and a steroid are used to treat newly diagnosed and relapsed multiple myeloma (MM). Although ixazomib (Ix), an oral PI with single agent activity, can be combined with lenalidomide (LEN), patients (pts) with relapsed/refractory (R/R) MM are often LEN-refractory. Pomalidomide (POM) has single agent activity in LEN-refractory disease, and both POM and Ix also show activity in poor cytogenetic risk pts. Methods: Primary objectives: 1) determine the maximum tolerated dose (MTD) of Ix in combination with standard dose POM and dexamethasone (DEX), and 2) evaluate the anti-tumor activity of the triplet. The treatment regimen included two dose levels (3 mg and 4 mg) of Ix on days 1, 8, 15; POM 4 mg days 1-21; and DEX 40 mg days 1, 8, 15, 22, of a 28 day cycle. Eligibility: R/R MM after >1 prior therapy, LEN-refractory, and ≤ grade(gr) 1 peripheral neuropathy (PN). Pts were treated until progression or unacceptable toxicity. Design: Phase I study utilizing a standard 3+3 design; dose limiting toxicities (DLTs) defined during cycle 1. Results: 32 pts treated, 31 evaluable for toxicity and response. Pts received a median 4 cycles (range 1-13); median follow-up is 5.5 months (range 1.8-21.1). Six pts treated on DL1, 25 treated on DL2, the MTD/Phase II dose (P2D). Median age: 62 years (range 38-84); median time from diagnosis: 3.7 years (range 1.0-8.9); median number prior therapies: 3 (range 1-5); prior transplant: n = 23 (74%); double (LEN/Bortezomib[BOR]) or triple (LEN/BOR/Carfilzomib[CFZ]) refractory: 19 (61%). Phase I: DL1 expanded to n=6 after 1/3 pts experienced DLT (gr3 lung infection); no further DLT seen on DL 1 or 2. Adverse events (AEs) related to POM and/or Ix: ANC decrease Gr1/2 n=11 (35%), Gr3/4 n=10 (32%), platelet decrease Gr1/2 n=9 (29%), lymphocyte decrease Gr1/2 n=8 (26%), Gr3/4 n=11 (35%), PN Gr1/2 n=9 (29%), no Gr3/4. Response: Phase I and II, n=31 pts treated. ORR: 45% (6 VGPR, 8 PR); Clinical Benefit Rate (CBR): 81% (6 VGPR, 8 PR, 3 MR, 8 SD). In the pts with high risk cytogenetics (7[23%] 1q, 3[10%] 17p, 2[6%] t(4;14)) an ORR of 58% (3 VGPR, 4 PR) was seen, and the CBR was 83%. In the double or triple refractory pts, an ORR of 26% and CBR of 79% (1 VGPR, 4 PR, 3 MR, 7 SD) were observed. Conclusions: Ix/POM/DEX is a well-tolerated oral combination therapy, and responses were seen even at DL1 and in high risk patients, including those with poor-risk cytogenetics or advanced refractory disease. Disclosures Kapoor: Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Kumar:Millennium: Consultancy, Research Funding; AbbVie: Research Funding; Glycomimetics: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy; Kesios: Consultancy; Onyx: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding. Lonial:Novartis: Consultancy; BMS: Consultancy; Janssen: Consultancy; Merck: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Onyx: Consultancy. Nathwani:Carevive Systems, Inc.: Research Funding. Forman:Mustang Therpapeutics: Other: Construct licensed by City of Hope. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding.

Abstract Background: Acute myeloid leukemia (AML) is an aggressive form of blood cancers with a wide range of response and relapse rates using standard chemotherapy regimen (commonly known as 7+3). Several genes (FLT3, IDH1, RAS) have been targeted using small molecule tyrosine kinase inhibitors with encouraging results. The stem cell receptor tyrosine kinase KIT is expressed more than 10% in the blasts in 95% of relapsed AML cases and mediates leukemic proliferation and has anti-apoptotic effects (Domen and Weissman 2000). AML with high KIT expression is associated with poorer outcome (Del Poeta, Venditti et al 2003). Goals: To study the efficacy and safety of combination 7+3 and nilotinib in patients (pts) with AML and KIT expression. Primary goal is to determine the complete response (CR) rate; while secondary goals include 2-year overall survival (OS) and disease free survival (DFS) in addition to safety of DATA regimen. Methods: A single arm, Phase II study, enrolled pts at Mayo Clinic (MN and AZ). Appropriate IRB was obtained and study was registered (NCT 01806571). Pts were enrolled if they were newly diagnosed with AML with KIT (CD117) expression of 20% or higher on myeloblasts by flow cytometry. KIT mutations were allowed if present. Nilotinib 300 mg twice daily was given on days 4-14 of induction and consolidation; and continuous daily maintenance therapy for up to 2 years. Cytarabine 100 mg/m2/day continuous IV x7 days plus daunorubicin 60 mg/m2 IV daily x3 days were used for induction , while consolidation used standard cytarabine 3 gm/m2 twice daily days 1, 3, 5 for a total of 4 cycles. This is a Simon 1-stage design with a safety analysis after enrolling 12 pts, and an interim analysis after enrolling 18 out of 43 pts. If 11 or fewer pts achieve complete remission, the regimen will be considered ineffective. Results: Eighteen pts have been enrolled between July 2013 and July 2015, 17 of which have baseline data. Median age was 58 years (range 24-65) with 76.5% being male. Median laboratory findings include hemoglobin of 9.3 gm/dL, platelets of 52 x109, and white blood count of 7.0 (0.5-125). Cytogenetics were normal in 41% of the pts. Favorable cytogenetics were seen in 2 pts (inv 16). FLT3 testing was done on 15 pts and was positive in 27%. KIT gene sequencing (exon 8, 9, 10, 11, 17) revealed no pathogenic mutation. Median number of cycles was 3 (range 1-7). Six pts had treatment delays, with 2/13 (15%) delays being due to non-hematologic toxicities. No delays or missed doses affected cytarabine and daunorubicin administration. Out of 15 pts evaluable for response, 12 (80%) achieved CR (or CR with incomplete platelet recovery). Six of the 12 pts (50%) who achieved remission needed a second induction on protocol. Two out of 15 did not respond (did not get re-induction on protocol). One pt died before disease assessment due to liver failure (G5, had only one dose of nilotinib and toxicity was attributed to daunorubicin). Of the 14 pts having at least 1 bone marrow biopsy, the overall CR rate was 86%. Five (33%) pts proceeded to allogeneic stem cell transplant, all are alive and none were able to initiate protocol nilotinib maintenance therapy. Only 2 out of 12 (17%) pts relapsed after achieving CR, one was secondary AML from myelodysplastic syndrome with complex karyotype and the other was therapy-related AML with t(9;11). Only 2 (11%) pts died at time of report. Thirteen pts were evaluated for adverse events (AE). Six pts had G4 non-hematological AEs. Five of 12 G4 AEs were related to infection, 2 were electrolyte imbalances, and 2 were heart failures. Most common G3 non-hematological AEs were febrile neutropenia (53%), hypophosphatemia (23%), hyperglycemia (23%), and hypertension (23%). In agreement with the favorable outcomes, the molecular target validation revealed that nilotinib treatment down-regulates the expression of KIT, Sp1, DNA methyltransferase (DNMT) 1, DNMT3a and DNMT3b. Conclusion: Combination daunorubicin and cytarabine with nilotinib (DATA) appears to be safe and effective. Interim results show an acceptable safety profile in the first 12 evaluable pts with most common AE being infection as expected. Thirty day mortality is acceptable (7%). DATA regimen has encouraging CR rates of 80% (intent to treat) and 86% in assessed pts, with half of the pts who achieved remission requiring 2 cycles of induction. Relapse rate seems to be low at 17%. We will continue accrual until all pts accrued for final results. Disclosures Al-Kali: Celgene: Research Funding. Off Label Use: This is a Phase II study of combination nilotinib to standard chemotherapy in patients diagnosed with AML.. Tibes:TetraLogic Pharmaceuticals: Research Funding.

Abstract Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. Higher proportions of non-participants were Hispanic, had a lower performance status and lower disease risk, and received myeloablative conditioning and antithymocyte globulin (ATG) or Campath than the study participants. PB was used more commonly as the graft source in the non-participants as compared to the study participants (65% vs. 50%, p<0.001). In multivariate models, overall mortality (HR 1.09, 95% CI 0.95-1.25, p=0.22), transplant-related mortality (HR 1.08, 95% CI 0.89-1.32, p=0.42) and risks of acute grade II-IV (HR 0.96, 95% CI 0.82-1.12, p=0.57) and chronic GVHD (HR 1.06, 95% CI 0.92-1.23, p=0.41) were comparable between study non-participants and participants. Non-participants were at higher risk for relapse than participants (HR 1.24, 95%CI 1.04-1.49, p=0.02) in the multivariate analysis adjusted for disease risk and other clinical variables. Center effect was examined and was not found to be significant (p=0.10). There was no significant interaction between graft source and trial participation (P=0.22) and the risk of mortality was comparable for BM (HR 0.99, 95% CI 0.80-1.22, p=0.90) and PB recipients (HR 1.17, 95% CI 0.97-1.41, p=0.09) whether on trial or off trial. (Figure) Conclusion: Approximately 29% of patients who appeared eligible and were treated with conditioning and GVHD prophylaxis regimens allowed on the trial were enrolled. Despite some differences in clinical characteristics, most of the outcomes of non-trial participants were comparable to trial participants, suggesting that there is no definitive evidence that the outcomes of patients in a clinical trial are superior to those of the non-participants treated in a similar fashion. The comparable outcomes also indicate that the results of this trial were not seriously affected by selection bias and are therefore representative of the larger population. Figure 1: Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 1:. Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 573 Using high throughput RNA interference screening on 6,722 druggable genes we previously identified XPO1/CRM1 as one of the 50 most vulnerable targets in Multiple Myeloma (MM)1. XPO1 knockdown proved lethal in MM cell lines, but had no effect on human embryonic kidney (293) cells or lung cancer (A549) cells, showing that XPO1 is a specific myeloma vulnerability, and that myeloma cell survival is dependent upon XPO1 expression. XPO1 encodes the protein exportin 1, a nuclear transport protein that exports tumor suppressor proteins from the nucleus, where they are active, to the cytoplasm, where they become inactive. We next analyzed XPO1 in MM via gene expression profiling (GEP). XPO1 expression is up-regulated as the disease progresses: patients with active MM have a higher level of XPO1 compared to normal plasma cells (p<0.04) and to patients with monoclonal gammopathy of undetermined significance or smoldering MM (p<0.0001). The highest levels were in human MM cell lines. TC classification revealed highest levels in t(11;14) and lowest levels in t(4;14) disease. Selective inhibitors of nuclear export (SINE) compounds have recently been developed that irreversibly inhibit XPO1/CRM1 and its nuclear export function. One such inhibitor, KPT-276, decreased the viability of all 12 MM cell lines tested in vitro, as shown by MTT assay. After 72 hours of drug treatment, a median IC50 value of approximately 175 nM (range 30–1000 nM) was observed. No synergy with other commonly used anti-MM therapeutics was observed in vitro. In contrast, the drug had little effect in 8 solid tumor cell lines with the exception of the B cell lymphoma line Ramos. KPT-276 was also consistently active in inducing apoptosis against MM primary patient samples. Using an IC80 dose of KPT-276, drug-treated samples had a reduced population of cells in S phase (8%) compared to cells treated with DMSO (21%). Using the vkappa*myc transgenic MM model, KPT-276 reduced monoclonal spikes (by a mean of 56%) in all mice treated orally with 150 mg/kg dose three times per week for 4 weeks. Furthermore, KPT-276 significantly reduced tumor growth in a xenograft MM1.S mouse model. GEP was performed in the presence or absence of drug in two different MM cell lines. Two genes of probable relevance, cell division cycle 25 homolog A (CDC25A) and Bromodomain-containing protein 4 (BRD4), were dysregulated by SINE treatment. Both are involved in cell cycle control and have been linked to MYC. RT-PCR and western blotting confirm that MYC, CDC25A and BRD4 are down-regulated, as soon as six hours, after treatment with KPT-276. KPT-276 has shown marked anticancer activities against B cell malignancies in vitro and is active and tolerated in Phase I canine studies. KPT-330, a close analog of KPT-276, is currently in Phase 1 studies in human with advanced hematological and solid tumors. Disclosures: Schmidt: Karyopharm: Research Funding. McCauley:Karyopharm Therapeutics Inc: Employment. Shacham:Karyopharm Therapeutics: Employment. Kauffman:Karyopharm Therapeutics Inc: Employment. Stewart:Millenium: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; Celgene: Consultancy.

Abstract Abstract 1940 Background: Chronic graft-versus-host disease (GVHD) is a significant source of morbidity, mortality, impaired patient-reported quality of life (QOL), greater symptom burden, and prolonged duration of immune suppressive therapy following allogeneic hematopoietic cell transplantation (HCT). While available data support the adverse prognosis of overlap subtype of chronic GVHD, the relative importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Methods: We analyzed prospectively acquired observational cohort data to examine whether the site of GI involvement (esophageal, upper GI, lower GI) and type of hepatic laboratory test abnormality (bilirubin, alkaline phosphatase (AP), alanine aminotransferase (ALT) elevation over the upper limit of normal based on study site-specific laboratory reference ranges) among chronic GVHD-affected patients are associated with overall survival (OS) and non-relapse mortality (NRM), symptoms (Lee Symptom Scale), and quality of life (QOL) per SF-36 and FACT-BMT instruments. Results: This analysis included 567 individual subjects with baseline and 1548 follow up visits. The majority were incident cases (59%), adults (98%), and predominantly White/Non-Hispanic. Median time from HCT to cohort enrollment was 11.9 months (range 3–294 months). Overall NIH chronic GVHD severity was mild in 10%, moderate in 52%, and severe in 38% at enrollment. Prior acute GVHD was noted in 66%, KPS < 80% in 17%, and platelet count at chronic GVHD onset of < 100 K/uL in 23%. At enrollment, GI involvement was seen in 40% (upper GI 20%, esophagus 16%, lower GI 13%), and liver involvement was seen in 52% (AP 38%, ALT 38%, bilirubin 10%). Time from transplant to cGVHD onset was not different for patients with or without GI involvement or hepatic involvement. In multivariate analysis utilizing data from enrollment visits only and adjusting for patient and transplant variables, lower GI involvement (HR 1.7, p=0.03) and elevated bilirubin (HR 2.36, p=0.001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR 1.7, p=0.01) and elevated bilirubin (HR 3.7, p<0.001) were associated with OS; results were similar for NRM. Separate models were constructed to examine the relationship of severity of GI and hepatic involvement (0–3 severity score per NIH consensus) and mortality: Increasing lower GI severity at enrollment was significantly associated with non-relapse mortality, with progressively increasing HR for greater severity levels (lower GI score 2/3 vs. 0: HR 5.5, 95% CI 2.3–13.1, p = 0.0001). Increasing bilirubin was also associated with NRM (bilirubin score 2/3 vs. 0: HR 3.3, 95% CI 1.3–8.4, p=0.01). A similar association was observed for bilirubin elevation and NRM in the time-dependent model (bilirubin 2/3 vs. 0: HR 8.9, 95% CI 3.3–24, p < 0.0001). When analyzing all visits, any esophageal involvement and GI score greater than zero were associated with both symptoms and QOL while elevated bilirubin was associated with QOL. We found no consistent evidence that upper GI involvement, AP, ALT, or NIH liver score add prognostic value for survival, overall symptom burden, or quality of life. Conclusion: These data support important differences in patient-reported outcomes according to GI and hepatic involvement among chronic GVHD affected patients, and identify those with elevated bilirubin or higher GI score at any time, or lower GI involvement at cohort enrollment, as patients at greater risk for mortality under current treatment approaches. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1954 Introduction: Vitamin D (VD) deficiency can cause osteomalacia, aching bone pain, muscle weakness, fatigue, increase risk of fracture and precipitate or exacerbate osteopenia/osteoporosis. Allogeneic hematopoietic stem cell transplant (HCT) patients are susceptible to low VD level secondary to poor oral intake, decreased exposure to sunlight and treatment related malabsorption. VD level has been correlated to cancer incidence and VD metabolites have been used in the treatment of myeloid leukemia. VD shows promising immunomodulatory properties and correction of low VD level may mitigate manifestations of graft versus host disease (GVHD). Reports have suggested that low VD level appears to increase the incidence of GVHD. We hypothesize that there is a relationship between low VD level and morbidity (specifically incidence of acute GVHD), mortality and relapse incidence after HCT. We therefore studied VD levels pre- and post-HCT to determine if VD level impacts these outcomes. Patients and Methods: 241 patients underwent myeloblative or non-myeloablative HCT between January 1, 2009 and January 31, 2011 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for pre- and post-transplant VD level. Categories for VD level included normal (>30 ng/ml) or abnormal (<30 ng/ml). Results: 131 (54%) of patients who underwent myeloblative or non-myeloablative HCT had their VD level evaluated either pre-transplant, post-transplant or both. Pre-HCT 57 (56%) patients, 100 days post-HCT 55 (59%) patients and 365 days post-HCT 12 (32%) patients had a low VD level. 51 (38%) of patients had a reduced intensity HCT and 80 patients (62%) had an ablative conditioning regimen. 11 (8.4%) patients had acute GVHD. Comparison of VD level among those with acute GVHD did show a higher incidence of acute GVHD between those with a low or normal VD level (HR=3.14, 95% CI: 0.35–28.33) however this association was not statistically significant (p=0.3079). Survival analysis in those with a low VD level pre-HCT showed there was not a higher risk of mortality (HR=1.14, 95% CI: 0.18–7.38) after adjusting for post- VD level, and this association was not statistically significant (p=0.8921). Survival analysis in those with a low VD level post-HCT did show a higher risk of mortality (HR=2.59, 95% CI: 0.26–25) after adjusting for pre-HCT VD level, however, this association was not statistically significant (p=0.4155). The relationship between VD level and relapse at 1 year post-HCT was not able to be examined because the VD level for patients who relapsed was not available. Conclusions: Half of patients undergoing HCT had VD testing pre- or post- HCT. Just over half of the patients tested had a low VD level pre- and 100 days post-HCT. It is notable that 365 days post HCT the number of patients with low VD level had decreased. This could be attributable to less time in the hospital thus increasing sun exposure, increasing performance status allowing better ingestion and absorption of VD in the gastrointestinal tract or proper supplementation of a low level noted previously. There was no significant difference in incidence of acute GVHD by VD level though there was a trend for increased risk. Pre- and post-HCT VD level did not significantly impact mortality but there was a trend toward higher risk in those with a low VD level post-HCT. This is the first study, to our knowledge, to evaluate the impact of VD level on mortality post-HCT. Our study confirms that many patients have a low VD level pre-and post-HCT. These findings, especially the trend towards a higher mortality risk and higher incidence of acute GVHD in those who have a low VD level post-HCT, warrant further prospective investigation. VD supplementation may be a low cost, easy to implement addition to routine post HCT care that might reduce HCT associated mortality. Disclosures: Reeder: Celgene: Research Funding.

INTRODUCTION: Acute portal vein thrombosis (PVT) is a rare diagnosis frequently associated with cirrhosis. Clinical presentation is typically nonspecific with potentially catastrophic short-term complications including sepsis, bowel infarction, and death. Management strategies differ for acute and chronic PVT. Guidelines for treating acute PVT recommend immediate initiation of systemic anticoagulation. Direct and indirect thrombolytic therapy (mechanical thrombectomy and fibrinolytic therapy) may be used in combination with systemic anticoagulation in the setting of bowel ischemia or as an adjunct in patients with a contraindication to systemic anticoagulation. We aimed to assess the success of thrombolytic therapy for non-malignant acute PVT and to compare the success of direct versus indirect thrombolytic therapy. METHODS: This was a systematic review and meta-analysis in which two independent librarians searched the following databases from the date of inception to March 2019: Ovid Medline, Ovid Embase, Scopus and Web of Science. All included studies provided technical and clinical success data, as well as adverse events, and technique(s) used for the intervention of non-malignant acute PVT. RESULTS: The two independent database searches yielded 143 citations, of which 79 duplicates were removed leaving a total of 64 references and 11 were included in our analyses. The overall success rate of thrombolytic therapy using the random effects model was 83% (95%CI: 0.67, 0.92; P = <0.01; I 2 = 61%). The overall clinical improvement rate of thrombolytic therapy using the fixed effects model was 95% (95%CI: 0.88, 0.98; P = 0.73; I 2 = 0%). The overall mortality of thrombolytic therapy using the fixed effects model was 5% (95%CI: 0.03, 0.11; P = 0.92; I 2 = 0%). In the direct and indirect thrombolytic groups, the rate of technical success was 84% and 52%, respectively, with an odds ratio of 3.37 (95%CI (0.96, 7.67), P -value = 0.127). CONCLUSION: Our analysis demonstrates that thrombolytic therapy successfully eliminates non-malignant acute PVTs with low rates of mortality. Direct thrombolysis may produce increased efficacy compared to indirect thrombolytic therapy. Larger prospective randomized trials comparing these interventions are warranted.

INTRODUCTION: High nursing turnover has long been recognized as a fiscally and emotionally costly phenomenon in gastrointestinal (GI) endoscopy units. Previous studies suggest high turnover may be partly attributed to job-related stress in GI endoscopy units and lack of educational opportunities. A retrospective review of nursing turnover rate in 2016 at Mayo Clinic Florida GI endoscopy unit found the turnover rate to be 25%, which is twice the average of other departments at the clinical site. We aimed to reduce endoscopy staff turnover rate to less than 25% and improve job satisfaction by improving knowledge of GI diseases through structured didactic sessions. METHODS: A descriptive correlational study of the impact of a six-month long optional educational curriculum on professional quality of life and employee turnover was performed. All endoscopy nurses and technicians employed at Mayo Clinic in Florida were recruited, but both study enrollment and participation were blinded and voluntary. Data on clinical gastroenterological knowledge and surveys on professional satisfaction and team cohesion were collected at the initiation of the curriculum and at one month after completion. Pre and post intervention knowledge scores were compared using the Wilcoxon signed rank test. The annual percentage of turnover was estimated by the Wilson score confidence interval. RESULTS: All available GI nurses and endoscopy technicians (n = 71) were invited to participate. 40 (56.3%) participants completed only the initial survey, 30 (42.3%) only the second survey, and 16 (22.9%) both surveys. Of those who completed both surveys, median quiz scores improved by 2 questions for those that attended 6 or more lectures ( P = 0.017). There was a trend towards increased professional satisfaction on the modified perceived cohesion scale in participants who attended 6 or more lectures ( P = 0.095). For participants who have worked in the unit for less than 1 year, the estimated turnover is 14% (6 – 38%, P > 0.05) and 24% (11 – 45%, P >0.05) for those who have worked longer than 1 year. CONCLUSION: Though limited by sample size, there is a trend towards improved job satisfaction for participants that completed all surveys and a reduction in turnover rate for staff who have worked in the unit for less than one year. This study suggests potential benefit in knowledge, professional satisfaction, and turnover for those offered voluntary education.

Abstract The treatment of resected brain metastasis has shifted away from the historical use of whole-brain radiotherapy (WBRT) toward adjuvant radiosurgery (stereotactic radiosurgery [SRS]) based on a recent prospective clinical trial demonstrating less cognitive decline with the use of SRS alone and equivalent survival as compared with WBRT. Whereas all level 1 evidence to date concerns single-fraction SRS for postoperative brain metastasis, there is emerging evidence that fractionated stereotactic radiotherapy (FSRT) may improve local control at the resected tumor bed. The lack of direct comparative data for SRS vs FSRT results in a diversity in clinical practice. In this article, Greenspoon and Roberge defend the use of SRS as the standard of care for resected brain metastasis, whereas Palmer and Brown argue for FSRT.