The Impact of Prior Single-Gene Testing on Comprehensive Genomic Profiling Results for Patients with Non-Small Cell Lung Cancer.

INTRODUCTION: Tissue-based broad molecular profiling of guideline-recommended biomarkers is advised for the therapeutic management of patients with non-small cell lung cancer (NSCLC). However, practice variation can affect whether all indicated biomarkers are tested. We aimed to evaluate the impact of common single-gene testing (SGT) on subsequent comprehensive genomic profiling (CGP) test outcomes and results in NSCLC. METHODS: Oncologists who ordered SGT for guideline-recommended biomarkers in NSCLC patients were prospectively contacted (May-December 2022) and offered CGP (DNA and RNA sequencing), either following receipt of negative SGT findings, or instead of SGT for each patient. We describe SGT patterns and compare CGP completion rates, turnaround time, and recommended biomarker detection for NSCLC patients with and without prior negative SGT results. RESULTS: Oncologists in > 80 community practices ordered CGP for 561 NSCLC patients; 135 patients (27%) first had negative results from 30 different SGT combinations; 84% included ALK, EGFR and PD-L1, while only 3% of orders included all available SGTs for guideline-recommended genes. Among patients with negative SGT results, CGP was attempted using the same tissue specimen 90% of the time. There were also significantly more CGP order cancellations due to tissue insufficiency (17% vs. 7%), DNA sequencing failures (13% vs. 8%), and turnaround time > 14 days (62% vs. 29%) than among patients who only had CGP. Forty-six percent of patients with negative prior SGT had positive CGP results for recommended biomarkers, including targetable genomic variants in genes beyond ALK and EGFR, such as ERBB2, KRAS (non-G12C), MET (exon 14 skipping), NTRK2/3, and RET . CONCLUSION: For patients with NSCLC, initial use of SGT increases subsequent CGP test cancellations, turnaround time, and the likelihood of incomplete molecular profiling for guideline-recommended biomarkers due to tissue insufficiency.

Patients with non-small cell lung cancer (NSCLC) should have their tumor tissue tested for all recommended biomarkers that can help identify their best treatment options. Traditional tests look at gene biomarkers one by one (single-gene testing), and doctors can order some or all these tests individually or in a group. However, some recommended biomarkers cannot be tested by traditional single-gene tests at all. Newer technology (next-generation sequencing) covers all current recommended treatment biomarkers in one test (comprehensive genomic profiling), but this testing is more expensive and can take more time. Our study shows that NSCLC patients do not get all recommended treatment biomarkers tested when a single-gene testing approach is taken. Single-gene testing also used up some patients' tumor tissue entirely, such that further testing by comprehensive genomic profiling could not be done at all (17% vs. 7% for patients with no prior single-gene tests), resulted in more sequencing failures (13% vs. 8%), and had turnaround time for results greater than 14 days for more patients (62% vs. 29%). When comprehensive genomic profiling was completed, 46% of patients with negative results from prior single-gene testing had positive results for recommended treatment biomarkers that were not included in the initial single-gene tests. To ensure that NSCLC patients receive testing for all recommended biomarkers, comprehensive genomic profiling must be performed first.

The Use of Lavender Aromatherapy for Pain After Total Hip and Total Knee Arthroplasty: A Randomized Trial.

A randomized clinical trial was conducted over a threemonth period with 102 participants undergoing a total hip arthroplasty (THA) or total knee arthroplasty (TKA). The study purpose was to assess whether there was a reduction in the use of opioids in the postoperative period for THA or TKA participants that utilized lavender aromatherapy as an adjunct to pain medication. The participants in the control and intervention group were administered nonopioid pain medication around the clock and opioids as needed after surgery. However, the intervention group also received a pre-packaged lavender essential oil inhaler. Total oral morphine equivalents (OME) were calculated for each participant to determine opioid usage. Although the total OME was similar for the groups overall, the total OME was slightly lower for THA patients that were enrolled in the intervention group (median 22.5) compared to THA patients that were enrolled in the control group (median 31.2). In the intervention group, 58% of participants reported that the lavender inhaler was a useful tool for pain management and 76% indicated they would continue to use the lavender inhaler after discharge.

Predictors of Tri-council Funding Among Nutrition Researchers in Canada.

Purpose: Barriers in research for women and dietitians have been documented. We sought to describe tri-council funding awarded within the nutrition discipline according to institution type, academic rank, gender, dietitian status, and primary research methods used.Methods: Using an online search methodology, faculty members with research appointments were identified from nutrition departments offering accredited dietetic programs and/or at Canada's collective of research-intensive universities known as U15. All data regarding faculty members, their institutions, and funding were collected through publicly available websites and Scopus. Tri-council funding associated with the nominated principal investigator, from a 5-year period, 2013-2014 to 2017-2018, was extracted. Binary logistic regression was used to test for predictors of receiving any tri-council operating funds within the 5-year period.Results: Faculty members (n = 237) from 21 institutions were identified for inclusion. Those from U15 institutions, at the full professor rank, nondietitians, men, and those who engaged in primarily quantitative research methods (vs. qualitative or mixed-methods) were significantly more likely to hold any tri-council funding during the eligible period. Dietitians (n = 76) were significantly less likely to hold tri-council funding, independent of institution, rank, gender, and primary research methods utilized.Conclusions: The apparent under-funding of academic dietitians from federal tri-council sources requires exploration.

BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer.

PURPOSE: Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). PATIENTS AND METHODS: From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. RESULTS: One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. CONCLUSION: Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.

Erratum to: FoundationOne CDx testing accurately determines whole arm 1p19q codeletion status in gliomas.

[This corrects the article DOI: 10.1093/noajnl/vdab017.].

A qualitative analysis of the perceived socio-cultural contexts and health concerns of sugar-sweetened beverages among adults studying or working at a post-secondary institution in Dharwad, India.

BACKGROUND: We sought to explore the perceptions of the socio-cultural contexts and health concerns of consuming sugar-sweetened beverages (SSB) among Indian adults working or studying at a post-secondary institution in Karnataka, India. METHODS: We completed a qualitative study, including 24 semi-structured interviews between 2017 and 2018 at the University of Agricultural Sciences, Dharwad, Karnataka, India. Data were analyzed using thematic content analysis. RESULTS: One over-arching theme emerged, westernization and changing perceptions of food, sugar, and health. Participants discussed SSB and associated health concerns in the broad context of westernization and overall economic development in India. Three sub-themes regarding the health perceptions of consuming SSB were: healthy drinks are clean and natural; hydration and energy; and moderation and body weight. Hygienically-prepared beverages were a consistent concern among participants. Juices and beverages, such as tea or coffee, sweetened with jaggery were viewed positively due to their naturalness and lack of processed sugar. Participants perceived SSB as providing hydration and energy, particularly in hot weather. Lastly, if consumed in moderation, SSB were thought to have no direct adverse health consequences. Though some participants noted excessive, 'addictive' consumption would contribute to weight gain and diabetes. CONCLUSION: Perceived health concerns of SSB reflect dominant health issues in India, namely, food insecurity, food safety, and increasingly, diabetes. Policymakers tend to prioritize acute challenges over long-term concerns. As such, the capacity of any policy to address chronic nutritional concerns related to SSB are likely to be muted in the absence of improvements to food safety and security.

FoundationOne CDx testing accurately determines whole arm 1p19q codeletion status in gliomas.

BACKGROUND: Molecular profiling of gliomas is vital to ensure diagnostic accuracy, inform prognosis, and identify clinical trial options for primary and recurrent tumors. This study aimed to determine the accuracy of reporting the whole arm 1p19q codeletion status from the FoundationOne platform. METHODS: Testing was performed on glioma samples as part of clinical care and analyzed up to 395 cancer-associated genes (including IDH1/2). The whole arm 1p19q codeletion status was predicted from the same assay using a custom research-use only algorithm, which was validated using 463 glioma samples with available fluorescence in-situ hybridization (FISH) data. For 519 patients with available outcomes data, progression-free and overall survival were assessed based on whole arm 1p19q codeletion status derived from sequencing data. RESULTS: Concordance between 1p19q status based on FISH and our algorithm was 96.7% (449/463) with a positive predictive value (PPV) of 100% and a positive percent agreement (PPA) of 91.0%. All discordant samples were positive for codeletion by FISH and harbored genomic alterations inconsistent with oligodendrogliomas. Median overall survival was 168 months for the IDH1/2 mutant, codeleted group, and 122 months for IDH1/2 mutant-only (hazard ratio (HR): 0.42; P < .05). CONCLUSIONS: 1p19q codeletion status derived from FoundationOne testing is highly concordant with FISH results. Genomic profiling may be a reliable substitute for traditional FISH testing while also providing IDH1/2 status.

Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial.

Importance: A significant proportion of patients with early-stage triple-negative breast cancer (TNBC) are treated with neoadjuvant chemotherapy. Sequencing of circulating tumor DNA (ctDNA) after surgery, along with enumeration of circulating tumor cells (CTCs), may be used to detect minimal residual disease and assess which patients may experience disease recurrence. Objective: To determine whether the presence of ctDNA and CTCs after neoadjuvant chemotherapy in patients with early-stage TNBC is independently associated with recurrence and clinical outcomes. Design, Setting, and Participants: A preplanned secondary analysis was conducted from March 26, 2014, to December 18, 2018, using data from 196 female patients in BRE12-158, a phase 2 multicenter randomized clinical trial that randomized patients with early-stage TNBC who had residual disease after neoadjuvant chemotherapy to receive postneoadjuvant genomically directed therapy vs treatment of physician choice. Patients had blood samples collected for ctDNA and CTCs at time of treatment assignment; ctDNA analysis with survival was performed for 142 patients, and CTC analysis with survival was performed for 123 patients. Median clinical follow-up was 17.2 months (range, 0.3-58.3 months). Interventions: Circulating tumor DNA was sequenced using the FoundationACT or FoundationOneLiquid Assay, and CTCs were enumerated using an epithelial cell adhesion molecule-based, positive-selection microfluidic device. Main Outcomes and Measures: Primary outcomes were distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS). Results: Among 196 female patients (mean [SD] age, 49.6 [11.1] years), detection of ctDNA was significantly associated with inferior DDFS (median DDFS, 32.5 months vs not reached; hazard ratio [HR], 2.99; 95% CI, 1.38-6.48; P = .006). At 24 months, DDFS probability was 56% for ctDNA-positive patients compared with 81% for ctDNA-negative patients. Detection of ctDNA was similarly associated with inferior DFS (HR, 2.67; 95% CI, 1.28-5.57; P = .009) and inferior OS (HR, 4.16; 95% CI,1.66-10.42; P = .002). The combination of ctDNA and CTCs provided additional information for increased sensitivity and discriminatory capacity. Patients who were ctDNA positive and CTC positive had significantly inferior DDFS compared with those who were ctDNA negative and CTC negative (median DDFS, 32.5 months vs not reached; HR, 5.29; 95% CI, 1.50-18.62; P = .009). At 24 months, DDFS probability was 52% for patients who were ctDNA positive and CTC positive compared with 89% for those who were ctDNA negative and CTC negative. Similar trends were observed for DFS (HR, 3.15; 95% CI, 1.07-9.27; P = .04) and OS (HR, 8.60; 95% CI, 1.78-41.47; P = .007). Conclusions and Relevance: In this preplanned secondary analysis of a randomized clinical trial, detection of ctDNA and CTCs in patients with early-stage TNBC after neoadjuvant chemotherapy was independently associated with disease recurrence, which represents an important stratification factor for future postneoadjuvant trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02101385.

Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.

Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC-only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3-year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.

Inter-Rater Reliability and Reception of the Michigan Opioid Safety Score.

PURPOSE: The Michigan Opioid Safety Score (MOSS) combines health risk, respiratory rate, and sedation measurement to guide safe opioid administration. This study was designed to assess reliability and nursing acceptance of the MOSS tool. DESIGN: Cross-sectional survey. METHODS: Nurses without prior exposure to the tool were asked to participate in an online survey. In part I, raters utilized the MOSS to answer questions based on four fictional case scenarios. In part II, anonymous opinion of the tool was queried. FINDING: Participants correctly scored 58.1% of patient scenarios, while appropriate clinical action was 80.5%. The intraclass correlation coefficient was 0.83. In terms of opinion, a majority of raters agreed the tool positively impacted patient safety (59.2%), improved confidence in opioid therapy (59.2%), and was easy to use (53%). CONCLUSIONS: Participants interpreted case scenarios with excellent inter-rater reliability and had a generally positive opinion. These study findings suggest the MOSS is a reliable safety instrument.

Training and retaining community pharmacy leaders: Career pathways after completing a PGY1 community pharmacy residency affiliated with a large supermarket chain.

OBJECTIVE: To determine pharmacist career paths and resident perceptions after completion of a PGY1 community pharmacy residency with a national supermarket pharmacy chain. METHODS: Cross-sectional nationwide survey. RESULTS: Overall, 65% (n = 24) of residents who responded accepted a position with Kroger immediately after graduation. When asked about the degree of value the residency had on obtaining the resident's ideal position, 29 (76%) reported that it was "very valuable" and the remaining 9 (24%) reported that it was "somewhat valuable." Positions that these pharmacists held immediately after residency completion were: clinical pharmacist (clinical coordinators, patient care specialists, or patient care managers; 54%), staff pharmacist (21%), split/mixed (mixed clinical and staffing components; 21%), and pharmacy manager (4%). CONCLUSION: Residency trained pharmacists were retained by the pharmacy chain where they practiced, and the majority of those pharmacists held split or full-time clinical pharmacist roles within the chain supermarket pharmacy.

Meta-analysis of academic interventions derived from neuropsychological data.

Several scholars have recommended using data from neuropsychological tests to develop interventions for reading and mathematics. The current study examined the effects of using neuropsychological data within the intervention process with meta-analytic procedures. A total of 1,126 articles were found from an electronic search and compared to inclusion criteria, which resulted in 37 articles that were included in the current study. Each article was coded based on how the data were used (screening-86% or designing interventions-14%), size of the group for which interventions were delivered (small group-45%, individual students-45%, or entire classroom-10%), and type of data collected (cognitive functions-24%, reading fluency-33%, phonemic/phonological awareness-35%, or mixed-8%). A corrected Hedges' g was computed for every study and reported for variables of interest. A Fail-safe N was also computed to determine how many studies with a zero effect would have to be found to change the conclusions. The data resulted in a small effect (g = 0.17) for measures of cognitive functioning, but moderate effects of g = 0.43 and g = 0.48 for measures of reading fluency and phonemic/phonological awareness. There were few studies that examined measures of cognitive functioning within the intervention process. Taken together with previous research, the data do not support the use of cognitive measures to develop interventions but instead favor more direct measures of academic skills (e.g., reading fluency) in a skill-by-treatment interaction. Implications for practice and future research are discussed.

REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia.

This phase 2 study (N = 116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients ≥60 years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (A: 72 mg/m(2)  d 1, 8, 15; B: 72 mg/m(2)  d 1, 8; C: 72 mg/m(2) or 90 mg/m(2)  d 1, 4). The primary endpoint was combined complete remission rate (complete remission [CR] plus CR with incomplete platelet recovery [CRp]). Common (>20%) grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR/CRp rates were 29% and 32%; median overall survival (OS) was 7·0 months; 1-year OS was 34%. Schedule C (72 mg/m(2) ) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27 d) and lowest incidence of aggregate sepsis (24%) and 30-d (7%) and 60-d (17%) all-cause mortality; at this dose and schedule, CR and CR/CRp rates were 31% and 35%, median OS was 7·7 months and 1-year OS was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72 mg/m(2)  d 1, 4 is recommended for further study in this population. Registered at www.clinicaltrials.gov: #NCT00607997.

Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML.

CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission + incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs 51.2%, P = .07), meeting predefined criteria for success (P < .1). Differences in EFS and OS were not statistically significant. A planned analysis of the secondary AML subgroup demonstrated an improved response rate (57.6% vs 31.6%, P = .06), and prolongation of EFS (hazard ratio [HR] = 0.59, P = .08) and OS (HR = 0.46, P = .01). Recovery from cytopenias was slower after CPX-351 (median days to absolute neutrophil count ≥1000: 36 vs 32; platelets >100 000: 37 vs 28) with more grade 3-4 infections but without increase in infection-related deaths (3.5% vs 7.3%) or 60-day mortality (4.7% vs 14.6%), indicating acceptable safety. These results suggest a clinical benefit with CPX-351, particularly among patients with secondary AML, and provide the rationale for a phase 3 trial currently underway in newly diagnosed secondary AML patients. This study is registered at Clinicaltrials.gov as #NCT00788892.

CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies.

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells. This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE. Two 21-day cycles of brentuximab vedotin (1.2 or 1.8 mg/kg intravenously) were administered to 56 patients with CD30-positive hematologic malignancies. Each patient also received either a sensitive CYP3A substrate (midazolam), an effective inducer (rifampin), or a strong inhibitor (ketoconazole). Brentuximab vedotin did not affect midazolam exposures. ADC exposures were unaffected by concomitant rifampin or ketoconazole; however, MMAE exposures were lower with rifampin and higher with ketoconazole. The short-term safety profile of brentuximab vedotin in this study was generally consistent with historic clinical observations. The most common adverse events were nausea, fatigue, diarrhea, headache, pyrexia, and neutropenia. Over a 1-week period, ∼23.5% of intact MMAE was recovered after administration of brentuximab vedotin; all other species were below the limit of quantitation. The primary excretion route is via feces (median 72% of the recovered MMAE). These results suggest that brentuximab vedotin (1.8 mg/kg) and MMAE are neither inhibitors nor inducers of CYP3A; however, MMAE is a substrate of CYP3A.

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation.

Hodgkin lymphoma (HL) relapsing after allogeneic stem cell transplantation (alloSCT) presents a major clinical challenge. In the present investigation, we evaluated brentuximab vedotin, a CD30-directed Ab-drug conjugate, in 25 HL patients (median age, 32 years; range, 20-56) with recurrent disease after alloSCT (11 unrelated donors). Patients were > 100 days after alloSCT, had no active GVHD, and received a median of 9 (range, 5-19) prior regimens. Nineteen (76%) had refractory disease immediately before enrollment. Patients received 1.2 or 1.8 mg/kg of brentuximab vedotin IV every 3 weeks (median, 8 cycles; range, 1-16). Overall and complete response rates were 50% and 38%, respectively, among 24 evaluable patients. Median time to response was 8.1 weeks, median progression-free survival was 7.8 months, and the median overall survival was not reached. Cough, fatigue, and pyrexia (52% each), nausea and peripheral sensory neuropathy (48% each), and dyspnea (40%) were the most frequent adverse events. The most common adverse events ≥ grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in 5 patients (potentially clinically significant in 1). These results support the potential utility of brentuximab vedotin for selected patients with HL relapsing after alloSCT.

Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia.

Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). We evaluated lucatumumab in a phase I clinical trial in chronic lymphocytic leukemia (CLL). Twenty-six patients with relapsed CLL were enrolled on five different dose cohorts administered weekly for 4 weeks. The maximally tolerated dose (MTD) of lucatumumab was 3.0 mg/kg. Four patients at doses of 4.5 mg/kg and 6.0 mg/kg experienced grade 3 or 4 asymptomatic elevated amylase and lipase levels. Of the 26 patients enrolled, 17 patients had stable disease (mean duration of 76 days, range 29-504 days) and one patient had a nodular partial response for 230 days. Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg/kg or greater cohorts. At the MTD, the median half-life of lucatumumab was 50 h following the first infusion, and 124 h following the fourth infusion. In summary, lucatumumab had acceptable tolerability, pharmacokinetics that supported chronic dosing and pharmacodynamic target antagonism at doses of 3.0 mg/kg, but demonstrated minimal single-agent activity. Future efforts with lucatumumab in CLL should focus on combination-based therapy.

The effect of Reiki on work-related stress of the registered nurse.

PURPOSE: The Reiki Master Teacher group at a large academic, urban medical center studied the effects of Reiki on work-related stress in Registered Nurse Reiki I class participants. Research suggests that work-related stress is an influential factor in nursing burn out and retention. Reiki, an ancient form of Oriental "energy work" or healing, has been found to decrease stress. METHODS: The Perceived Stress Scale tool was administered prior to the Reiki I class and after three weeks of practicing self-Reiki. FINDINGS: Seventeen participants returned follow-up data. Results indicated that practicing Reiki more often resulted in reduced perceived stress levels. CONCLUSIONS: Data from this small pilot study supports educating nurses about Reiki practice to decrease work-related stress.