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Background The ability to identify genetic alterations in cancers is essential for precision medicine; however, surgical approaches to obtain brain tumor tissue are invasive. Profiling circulating tumor DNA (ctDNA) in liquid biopsies has emerged as a promising approach to avoid invasive procedures. Here, we systematically evaluated the feasibility of profiling pediatric brain tumors using ctDNA obtained from plasma, cerebrospinal fluid (CSF), and urine. Methods We prospectively collected 564 specimens (257 blood, 240 urine, and 67 CSF samples) from 258 patients across all histopathologies. We performed ultra-low-pass whole-genome sequencing (ULP-WGS) to assess copy number variations and estimate tumor fraction and developed a pediatric CNS tumor hybrid capture panel for deep sequencing of specific mutations and fusions. Results ULP-WGS detected copy number alterations in 9/46 (20%) CSF, 3/230 (1.3%) plasma, and 0/153 urine samples. Sequencing detected alterations in 3/10 (30%) CSF, 2/74 (2.7%) plasma, and 0/2 urine samples. The only positive results were in high-grade tumors. However, most samples had insufficient somatic mutations (median 1, range 0-39) discoverable by the sequencing panel to provide sufficient power to detect tumor fractions of greater than 0.1%. Conclusions Children with brain tumors harbor very low levels of ctDNA in blood, CSF, and urine, with CSF having the most DNA detectable. Molecular profiling is feasible in a small subset of high-grade tumors. The level of clonal aberrations per genome is low in most of the tumors, posing a challenge for detection using whole-genome or even targeted sequencing methods. Substantial challenges therefore remain to genetically characterize pediatric brain tumors from liquid biopsies.

The purpose of this study is to report cases of choroidal melanoma that developed extrascleral tumour recurrence after treatment with iodine-125 brachytherapy.In this single-institution retrospective observational case series, all instances of biopsy-confirmed orbital melanoma after known intraocular melanoma were reviewed. Tumour characteristics, clinical course, time to recurrence, cytogenetics of initial tumour and recurrence, and presence of intraocular recurrence were documented.Five cases of orbital melanoma following treatment with plaque radiotherapy are described. Tumour staging was Ia (1), IIa (2), and IIb (2). The primary lesion in four of the five appeared to have undergone complete regression for an average of 2 years, with the orbital melanoma developing after this interval. Recurrence of the intraocular tumour was seen in conjunction with an extrascleral component in two cases. Four cases ultimately underwent enucleation or exenteration; three had evidence of direct extension of tumour through the sclera. Four cases in this series had molecular characteristics associated with high metastatic risk (three patients with monosomy 3, one with BAP1 mutation).High-risk tumour biology may predispose to late appearance of extrascleral melanoma despite optimal treatment and adequate control of the intraocular tumour. Extended follow-up with detailed orbital examination and imaging is recommended for this population.

Anti-adhesion therapies interfere with the bacterial adhesion to the host and thus avoid direct disruption of bacterial cycles for killing, which may alleviate resistance development. Herein, an anti-adhesion nanomedicine platform is made by wrapping synthetic polymeric cores with bacterial outer membranes. The resulting bacterium-mimicking nanoparticles (denoted "OM-NPs") compete with source bacteria for binding to the host. The "top-down" fabrication of OM-NPs avoids the identification of the adhesins and bypasses the design of agonists targeting these adhesins. In this study, OM-NPs are made with the membrane of Helicobacter pylori and shown to bind with gastric epithelial cells (AGS cells). Treatment of AGS cells with OM-NPs reduces H. pylori adhesion and such anti-adhesion efficacy is dependent on OM-NP concentration and its dosing sequence.

Background Pancreatic cancer has one of the highest mortality rates of any malignancy, placing a substantial burden on patients and families with high unmet informational and supportive care needs. Nevertheless, access to psychosocial and palliative care services for the individuals affected is limited. There is a need for standardized approaches to facilitate adjustment and to improve knowledge about the disease and its anticipated impact. In this intervention-development paper guided by implementation science principles, we report the rationale, methods, and processes employed in developing an interdisciplinary group psychoeducational intervention for people affected by pancreatic cancer. The acceptability and feasibility of implementation will be evaluated as a part of a subsequent feasibility study. Methods The Schofield and Chambers framework for designing sustainable self-management interventions in cancer care informed the development of the intervention content and format. The Consolidated Framework for Implementation Research served as an overarching guide of the implementation process, including the development phase and the formative evaluation plan of implementation. Results A representative team of stakeholders collaboratively developed and tailored the intervention content and format with attention to the principles of implementation science, including available resourcing. The final intervention prototype was designed as a single group-session led by an interdisciplinary clinical team with expertise in caring for patients with pancreatic cancer and their families and in addressing nutrition guidelines, disease and symptom management, communication with family and health care providers, family impact of cancer, preparing for the future, and palliative and supportive care services. Conclusions The present paper describes the development of a group psychoeducational intervention to address the informational and supportive care needs of people affected by pancreatic cancer. Consideration of implementation science during intervention development efforts can optimize uptake and sustainability in the clinical setting. Our approach may be utilized as a framework for the design and implementation of similar initiatives to support people affected by diseases with limited prognoses. Electronic supplementary material The online version of this article (10.1186/s40814-019-0466-x) contains supplementary material, which is available to authorized users.

PURPOSE: Mentalization has been clearly defined in the literature as a relational concept and yet in surveys and transcript-based measures it is almost universally treated as an individual capacity. That approach has value but may not capture the emergent nature of mentalization, as it is jointly constructed within a relational context. // METHODS: We report here on a critical evaluation of measurement approaches commonly used to conceptualize and assess mentalization and argue for the value of conversation analysis (CA) as an alternative approach. // RESULTS: A variety of approaches have been shown to have utility in assessing mentalization as an individual capacity. We illustrate how conversation analysis allows for an in-depth-analysis of mentalization as it is co-created across different contexts in real-life therapy sessions. This method of analysis shifts the focus from content to process. // CONCLUSIONS: Conversation analysis is a potentially valuable tool to support training, to assess treatment integrity, and to improve outcomes with mentalization-based interventions.

Objective To identify how therapists invite patients with advanced cancer to engage with alternative perspectives about their illness trajectory and their end of life. Methods Sequences of talk in which a therapist introduced a patient to alternative perspectives, were transcribed and analysed using the method of conversation analysis. Results The analysis identifies one subtle way a patient is invited to consider an alternative perspective relating to their disease progression. Meaning expansion enquiries invite the patient to expand on the meaning of an utterance and in doing so, implicitly problematize the singularity of the patient’s assumptions, without directly challenging them. The questions work as preliminary moves, providing the patient with the opportunity to expand on their assumptions. This enables the therapist to subsequently present an alternative perspective in a way that incorporates the patient’s expanded perspective. Conclusion The analysis reveals a skilful way in which therapists can cautiously and collaboratively introduce a patient to alternative perspectives concerning end-of-life, without invalidating the patient’s perspective in this particularly delicate context. Practice Implications Whilst mentalization is considered an important therapeutic process, the present study reveals precisely how this phenomenon can be enacted in therapy and within the particularly challenging context of end-of-life.

Purpose:Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing.Experimental Design:We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma sampling and clinical data collection: 16 patients with ER+/HER2− metastatic breast cancer (MBC) sampled within 6 months following metastatic diagnosis and 142 patients with stage 0 to III breast cancer who received curative-intent treatment with most sampled at surgery and 1 year postoperative. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples.Results:Our approach was 100-fold more sensitive than ddPCR when tracking 488 mutations, but most patients had fewer identifiable tumor mutations to track in cfDNA (median = 57; range = 2–346). Clinical sensitivity was 81% (n = 13/16) in newly diagnosed MBC, 23% (n = 7/30) at postoperative and 19% (n = 6/32) at 1 year in early-stage disease, and highest in patients with the most tumor mutations available to track. MRD detection at 1 year was strongly associated with distant recurrence [HR = 20.8; 95% confidence interval, 7.3–58.9]. Median lead time from first positive sample to recurrence was 18.9 months (range = 3.4–39.2 months).Conclusions:Tracking large numbers of individualized tumor mutations in cfDNA can improve MRD detection, but its sensitivity is driven by the number of tumor mutations available to track.

Purpose Individuals with advanced cancer experience substantial distress in response to disease burden and impending mortality. Managing Cancer And Living Meaningfully (CALM) is a novel, brief, manualized psychotherapeutic intervention intended to treat and prevent depression and end-of-life distress in patients with advanced cancer. We conducted a randomized controlled trial to compare CALM with usual care (UC) in this population. Methods Patients with advanced cancer were recruited from outpatient oncology clinics at a comprehensive cancer center into an unblinded randomized controlled trial. Permuted block randomization stratified by Patient Health Questionnaire-9 depression score allocated participants to CALM plus UC or to UC alone. Assessments of depressive symptoms (primary outcome), death-related distress, and other secondary outcomes were conducted at baseline, 3 months (primary end point), and 6 months (trial end point). Analyses were by intention to treat. Analysis of covariance was used to test for outcome differences between groups at follow-up, controlling for baseline. Mixed-model results are reported. Results Participants (n = 305) were recruited between February 3, 2012, and March 4, 2016, and randomly assigned to CALM (n = 151) or UC (n = 154). CALM participants reported less-severe depressive symptoms than UC participants at 3 months (Δ = 1.09; P = .04; Cohen’s d = 0.23; 95% CI, 0.04 to 2.13) and at 6 months (Δ = 1.29; P = .02; d = 0.29; 95% CI, 0.24 to 2.35). Significant findings for greater end-of-life preparation at 6 months also favored CALM versus UC. No adverse effects were identified. Conclusion Findings suggest that CALM is an effective intervention that provides a systematic approach to alleviating depressive symptoms in patients with advanced cancer and addresses the predictable challenges these patients face.

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models., T- and NK-cell lymphomas (TCL) are a group of lymphoid malignancies characterized by poor prognosis, but the absence of appropriate pre-clinical models has hampered the development of effective therapies. Here the authors establish several pre-clinical models and identify vulnerabilities that could be further exploited to treat patients afflicted by these diseases.

Objectives Fear of death and dying is common in patients with advanced cancer, but can be difficult to address in clinical conversations. We aimed to show that the experience of death anxiety may be deconstructed into a network of specific concerns and to provide a map of their interconnections to aid clinical exploration. Methods We studied a sample of 382 patients with advanced cancer recruited from outpatient clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Patients completed the 15-item Death and Dying Distress Scale (DADDS). We used item ratings to estimate a regularised partial correlation network of death and dying-related concerns. We calculated node closeness-centrality, clustering and global network characteristics. Results Death-related anxieties were highly frequent, each associated with at least moderate distress in 22%–55% of patients. Distress about ‘Running out of time’ was a central concern in the network. The network was organised into two areas: one about more practical fears concerning the process of dying and another about more psychosocial or existential concerns including relational problems, uncertainty about the future and missed opportunities. Both areas were yet closely connected by bridges which, for example, linked fear of suffering and a prolonged death to fear of burdening others. Conclusions Patients with advanced cancer may have many interconnected death-related fears that can be patterned in individual ways. The bridging links between more practical and more psychosocial concerns emphasise that the alleviation of death anxiety may require interventions that integrate symptom management, advance care planning and psychological treatment approaches.

BACKGROUND Demoralization refers to a state in which there is a perceived inability to cope, that is associated with a sense of disheartenment and a loss of hope and meaning. This study investigated the co-occurrence versus independence of demoralization with mental disorders and suicidal ideation to evaluate its features as a concept of distress in the context of severe illness. METHODS In a cross-sectional sample of 430 mixed cancer patients, we assessed demoralization with the Demoralization Scale (DS); the 4-week prevalence of mood, anxiety, and adjustment disorders and suicidal ideation with the standardized Composite International Diagnostic Interview–Oncology (CIDI-O); and depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9). We compared the relative risk (RR) for mental disorders associated with demoralization to that associated with self-reported depression. RESULTS Clinically relevant levels of demoralization were present in 21% of the patients. Demoralization co-occurred with a mood/anxiety disorder in 7%; 14% were demoralized in absence of any mood/anxiety disorder. Demoralization and adjustment disorders co-occurred in 2%. The RR for any mood/anxiety disorder was 4.0 in patients with demoralization (95% confidence interval [CI], 2.5-6.2) and 3.0 in those with depression (95% CI, 1.9-4.6). Demoralization, but not depression, was associated with a significantly increased risk for suicidal ideation after controlling for mental disorders (RR, 2.0; 95% CI, 1.1-3.5). CONCLUSIONS Clinically relevant demoralization frequently occurs independently of a mental disorder in patients with cancer and has a unique contribution to suicidal ideation. Demoralization is a useful concept to identify profiles of psychological distress symptoms amenable to interventions improving psychological well-being in this population. Cancer 2017. © 2017 American Cancer Society.

Context Distress and anxiety about issues related to death and dying is commonly experienced in patients with advanced disease and a limited life expectancy. Objectives To evaluate the psychometric properties of the German version of the Death and Dying Distress Scale (DADDS-G) in advanced cancer patients. Methods We recruited advanced patients with mixed tumor entities (Union for International Cancer Control [UICC] Stage III/IV) treated in two German University Medical Centers during their outpatient treatment. After testing a preliminary version of the state-of-the-art translated original Death and Dying Distress Scale, we analyzed the psychometric properties of the shortened nine-item adapted DADDS-G using validated instruments measuring distress, anxiety, depression, fear of progression, and quality of life. Results We obtained complete questionnaires from 77 of 93 patients with advanced cancer (response rate: 83%). Participants were mostly married or cohabiting (75%), well-educated, and both sexes were almost equally represented (52% men; mean age 58 years, SD = 12). The total mean DADDS-G score was 13.3 (SD = 8.5). Patients reported to be most distressed by the feeling of being a burden to others. The exploratory factor analysis led to one factor that accounted for more than 59% of the variance. The DADDS-G's internal consistency was excellent with Cronbach alpha = 0.91. The confirmatory factor analysis demonstrated a very good model fit. Death-related anxiety was significantly associated with distress, depression, anxiety, fear of progression, and lower quality of life ( P Conclusion Results provide further evidence that the DADDS-G is a valid and reliable instrument of high clinical relevance for use in patients with advanced cancer.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.

Tumor content in circulating cell-free DNA (cfDNA) is a promising biomarker, but longitudinal dynamics of tumor-derived and non-tumor-derived cfDNA through multiple courses of therapy have not been well described.CfDNA from 663 plasma samples from 140 patients with castration-resistant prostate cancer (CRPC) was subject to sparse whole genome sequencing. Tumor fraction (TFx) estimated using the computational tool ichorCNA was correlated with clinical features and responses to therapy.TFx associated with the number of bone metastases (median TFx = 0.014 with no bone metastases, 0.047 with 1-3 bone metastases, 0.190 for 4+ bone metastases; P0.0001) and with visceral metastases (P0.0001). In multivariable analysis, TFx remained associated with metastasis location (P = 0.042); TFx was positively correlated with alkaline phosphatase (P = 0.0227) and negatively correlated with hemoglobin (Hgb) (P0.001), but it was not correlated with prostate specific antigen (PSA) (P = 0.75). Tumor-derived and non-tumor-derived cfDNA track together and do not increase with generalized tissue damage from chemotherapy or radiation at the time scales examined. All new treatments that led to ≥30% PSA decline at 6 weeks were associated with TFx decline when baseline TFx was7%; however, TFx in patients being subsequently maintained on secondary hormonal therapy was quite dynamic.TFx correlates with clinical features associated with overall survival in CRPC, and TFx decline is a promising biomarker for initial therapeutic response.Dana-Farber/Harvard Cancer Center (DF/HCC) protocol no. 18-135.Wong Family Award in Translational Oncology, Dana Farber Cancer Institute Medical Oncology grant, Gerstner Family Foundation, Janssen Pharmaceuticals Inc., and Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute (NCI).

BackgroundManaging Cancer And Living Meaningfully (CALM) is a brief individual psychotherapy for patients with advanced cancer. In an intervention-only phase 2a trial, CALM showed promising results, leading to the present 2b pilot, which introduces procedures for randomisation and improved rigour in preparation for a phase 3 randomised controlled trial (RCT).AimsTo test trial methodology and assess feasibility of a confirmatory RCT.DesignA parallel-arm RCT (intervention vs usual care) with 3 and 6-month follow-ups. Assessment of feasibility included rates of consent, randomisation, attrition, intervention non-compliance and usual care contamination. Primary outcome: depressive symptoms (Patient Health Questionnaire-9; PHQ-9). Secondary outcomes: major depressive disorder (MDD), generalised anxiety, death anxiety, spiritual well-being, attachment anxiety and avoidance, self-esteem, experiential avoidance, quality of life and post-traumatic growth. Bayesian conjugate analysis was used in this low-powered setting.Setting/participants60 adult patients with advanced cancer from the Princess Margaret Cancer Centre.ResultsRate of consent was 32%, randomisation 78%, attrition 25%, non-compliance 37% and contamination 17%. There was support for potential treatment effects on: PHQ-9, OR=1.48, 95% Credible Interval (CRI.95) (0.65, 3.38); MDD, OR=1.56, CRI.95(0.50, 4.84); attachment anxiety, OR=1.72, CRI.95(0.73, 4.03); and attachment avoidance, OR=1.58, CRI.95(0.67, 3.71). There was no support for effects on the seven remaining secondary outcomes.ConclusionsA phase 3 CALM RCT is feasible and should aim to detect effect sizes of d=0.40, with greater attention to issues of compliance and contamination.Trial registration numberNCT02353546.

Background: Breast cancer (BC) may recur years to decades after initial treatment, leading to incurable, metastatic disease. Prior studies have shown blood biopsy can detect minimal residual disease (MRD), but not in all patients and often with very short lead time. Most efforts thus far have focused on tracking one or a few mutations via ctDNA, which may limit sensitivity. Here we sought to maximize the detection sensitivity of blood biopsies by tracking up to hundreds of individualized tumor mutations in cell-free DNA (cfDNA). Doing so enables us to break the detection ceiling imposed by the limited copies of each gene in the cell-free DNA in a blood draw. Methods: cfDNA was extracted from archival plasma samples (n=271) from 142 patients with stage 0-III BC enrolled prospectively onto two IRB-approved studies. We applied whole-exome sequencing (WES) to define up to several hundred mutations from each patient’s tumor. To limit potential errors, we employed strict criteria to select somatic SNVs to track using duplex sequencing in cfDNA. We required detection of ≥ 2 mutations for a cfDNA sample to be MRD+ and excluded any mutations also found in a patient’s own germline DNA. Results: We identified 142 patients treated for stage 0-III BC, who had postoperative blood and plasma samples available, and were monitored for distant recurrences for up to thirteen years. All patients had biopsy-proven BC, with 86 (61%) having HR+/HER2- BC, 31 (22%) having HR-/HER2-, or “triple negative” BC (TNBC), and 25 (18%) having HER2-positive disease. Three (2%) patients had stage 0 disease, 32 (23%) had stage I, 68 (42%) had stage II, and 39 (27%) had stage III BC at diagnosis. Archived plasma samples were collected post-operatively, at year 1, and at year 4. We created individualized assays targeting a median of 57 mutations (range 2 - 346) per patient. Reasoning that MRD status after completion of all local therapy and chemotherapy might best predict for distant recurrence, we conducted a landmark analysis at one year following surgery, and found all patients (n=6/6) with detectable MRD experienced recurrence (HR=21.2 (7.43-60.35)) in a median of 6.7 (range 3.4 - 15.8) months. Median lead time including all timepoints from first positive blood sample to recurrence was 18.9 (range: 3.4 - 39.2) months. Finally, in a multivariate model, MRD remained highly statistically significant independent of stage, subtype, and age at diagnosis. Conclusions: We present a novel approach to MRD tracking based on the premise that tracking many - rather than one or a handful of - mutations inherently increases sensitivity and that assay personalization maximizes sensitivity in a disease without multiple, recurrent mutations. To our knowledge, the lead time we show here is significantly longer than that seen in prior investigations, and if confirmed, could offer an opportunity to treat MRD long before the development of clinically apparent metastatic disease. Prospective studies are needed to determine whether earlier detection of MRD is clinically meaningful for patients. Citation Format: Heather A Parsons, Justin Rhoades, Sarah C. Reed, Greg Gydush, Priyanka Ram, Pedro Exman, Kan Xiong, Christopher Lo, Tianyu Li, Mark Fleharty, Greg Kirkner, Denisse Rotem, Ofir Cohen, Melissa Hughes, Shoshanna Rosenberg, Laura Collins, Kathy Miller, Brendan Blumenstiel, Carrie Cibulskis, Donna Neuberg, Samuel S. Freeman, Niall Lennon, Nikhil Wagle, Gavin Ha, Daniel G. Stover, Atish D. Choudhury, Gad Getz, Matthew Meyerson, Nancy U. Lin, Ian E. Krop, J. Christopher Love, G. Mike Makrigiorgos, Ann Partridge, Erika Mayer, Todd R. Golub, Viktor A. Adalsteinsson. Ultrasensitive detection of minimal residual disease in patients treated for breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-03.

The Edmonton Symptom Assessment System (ESAS) measures the severity of nine symptoms. Constipation and sleep disturbance are common in patients with cancer, but are not currently included in the ESAS.To validate the numerical rating scale (NRS) versions of ESAS and its revised version (ESAS-r), with the additional symptoms of constipation and sleep (CS), and to assess patient preference for either version.Outpatients with advanced cancer (N = 202) completed three assessments during a single clinic visit: ESAS-CS, and an added time window of "past 24 hours"; ESAS-r-CS, with a time window of "now" and symptom definitions; and the Memorial Symptom Assessment Scale (MSAS). Internal consistency was calculated using Cronbach's alpha. Paired t-tests compared ESAS-CS and ESAS-r-CS scores; these were correlated with MSAS using Spearman correlation coefficients. Test-retest reliability at 24 hours was assessed in 26 patients.ESAS-CS and ESAS-r-CS total scores correlated well with total MSAS (Spearman's rho 0.62 and 0.64, respectively). Correlation of individual symptoms with MSAS symptoms ranged from 0.54-0.80 for ESAS-CS and 0.52-0.74 for ESAS-r-CS. Although participants preferred the ESAS-r-CS format (42.8% vs. 18.6%) because of greater clarity and understandability, the "past 24 hours" time window (52.8%) was favored over "now" (21.3%). Shortness of breath and nausea correlated better for the "past 24 hours" time window (0.8 and 0.72 vs. 0.74 and 0.64 in ESAS-r-CS, respectively). The 24-hour test-retest of the ESAS-CS demonstrated acceptable reliability (intraclass correlation coefficient = 0.69).The ESAS-CS and ESAS-r-CS NRS versions are valid and reliable for measuring symptoms in this population of outpatients with advanced cancer. Although the ESAS-r-CS was preferred, patients favored the 24-hour time window of the ESAS-CS, which also may best characterize fluctuating symptoms.

Context Quality of life (QoL) is a central focus of care in advanced cancer. Specialized instruments, such as the Quality of Life at the End of Life-Cancer (QUAL-EC), may be useful to assess psychosocial issues associated with QoL unique to this population. Objectives To evaluate the measurement of the psychosocial dimensions of QoL using the German translation of the QUAL-EC-Psychosocial (QUAL-EC-P) questionnaire, including factor structure and psychometrics. Methods About 183 patients with advanced cancer from the University Medical Center Hamburg-Eppendorf and University Medical Center Leipzig completed the QUAL-EC-P questionnaire. We conducted exploratory factor analysis as well as item and reliability analysis. We examined convergent validity with correlations between the scale and relevant psychological constructs. Results The sample was 60% female with mean age of 57.7 (SD = 11.7). We extracted three factors accounting for 44% of the variance aligning with the structure of the instrument. The QUAL-EC-P questionnaire showed good to acceptable internal consistency for the QoL-psychosocial total score (α = 0.77), the Life completion subscale (α = 0.77), and the Relationship with health care provider subscale (α = 0.81). The Preparation for end of life subscale had adequate albeit low internal consistency (α = 0.64) because concerns about family were less associated with financial worry and fear of death than expected. The psychosocial dimensions of QoL correlated negatively with depression (r = −0.27, P ≤ 0.001), anxiety (r = −0.32, P ≤ 0.001), demoralization (r = −0.63, P ≤ 0.001), and attachment insecurity (r = −0.51, P ≤ 0.001) and positively with spiritual well-being (r = 0.63, P ≤ 0.001). Conclusion The QUAL-EC-P questionnaire may be used to assess the psychosocial aspects of QoL and promote their clinical discussion in patients with advanced cancer.

Context Attachment insecurity refers to difficulty in trusting and relying on others in times of need. Its underlying factors attachment anxiety and attachment avoidance have been empirically associated with impaired coping in advanced cancer and, therefore, should be considered in individually tailored medical and psychosocial treatment. Objectives The objective of this study was to evaluate the psychometric properties of the German translation of the Brief Experiences in Close Relationships Scale (ECR-M16-G). Methods We recruited 182 advanced cancer patients from outpatient psycho-oncology clinics of the University Medical Center Hamburg-Eppendorf and the University Medical Center Leipzig, local and external cancer care facilities. We performed confirmatory factor analysis to replicate the higher order factor structure reported in previous research. We conducted item and reliability analysis, also correlation analysis, to examine concurrent validity. Results One hundred fifty-eight patients completed the ECR-M16-G (women 61%, mean age 57.9, SD = 11.1). We replicated the factor structure with the subscales Attachment Anxiety and Attachment Avoidance as second-order factors and Worrying about relationships , Frustration about unavailability , Discomfort with close others , and Turning away from others as first-order factors. An adjusted model that interchanged factor loadings of items 4 and 10 showed good fit (Comparative Fit Index = 0.94, Non-Normed Fit Index = 0.93, root mean square error of approximation = 0.05). Subscales showed acceptable to good internal consistency (anxiety α = .81 and avoidance α = .78). Attachment insecurity (mean = 3.1, SD = 1.0) was positively associated with depression, anxiety, demoralization ( P P = 0.02) and negatively associated with spiritual well-being ( P Conclusion The ECR-M16-G is a valid and reliable measure of attachment insecurity in patients with advanced cancer and can be recommended as a tool for clinical care and further research.

Background Early palliative care improves the quality of life (QoL) and satisfaction with care of patients with advanced cancer, but little is known about its effect on caregivers. Here, we report outcomes of caregiver satisfaction with care and QoL from a trial of early palliative care. Patients and methods Twenty-four medical oncology clinics were cluster-randomised, stratified by tumour site (lung, gastrointestinal, genitourinary, breast and gynaecological), to early palliative care team referral, or to standard oncology care with palliative care only as needed. Caregivers of patients with advanced cancer (clinical prognosis of 6–24 months, Eastern Cooperative Oncology Group 0–2) in both trial arms completed validated measures assessing satisfaction with care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)], at baseline and monthly for 4 months. We used a multilevel linear random-intercept mixed-effect model to test whether there was improvement in the intervention group relative to the control group over 3 and 4 months. Results A total of 182 caregivers completed baseline measures (94 intervention, 88 control); 151 caregivers (77 intervention, 74 control) completed at least one follow-up assessment. Satisfaction with care improved in the palliative intervention group compared with controls over 3 months (P = 0.007) and 4 months (P = 0.02). There was no significant improvement in the intervention group compared with controls for CQoL-C (3 months: P = 0.92, 4 months: P = 0.51), Physical Component Summary of the SF-36v2 Health Survey (3 months: P = 0.83, 4 months: P = 0.20), or Mental Component Summary of the SF-36v2 Health Survey (3 months: P = 0.87, 4 months: P = 0.60). Conclusion Early palliative care increased satisfaction with care in caregivers of patients with advanced cancer. ClinicalTrials.gov identifier NCT01248624.

Background:Advanced cancer brings substantial physical and psychosocial challenges that may contribute to emotional distress and diminish well-being. In this study, we present preliminary data concerning the effectiveness of a new brief individual psychotherapy, Managing Cancer And Living Meaningfully (CALM), designed to help individuals cope with this circumstance.Aim:To test the feasibility and preliminary effectiveness of CALM to reduce emotional distress and promote psychological well-being and growth.Design:CALM is a brief, manualized, semi-structured individual psychotherapy for patients with advanced cancer. This study employed a phase 2 intervention-only design. The primary outcome was depressive symptoms and the secondary outcomes were death anxiety, attachment security, spiritual well-being and psychological growth. These were assessed at 3 months (t1) and 6 months (t2). Multilevel regression was used to model change over time.Setting/participants:A total of 50 patients with advanced or metastatic cancer were recruited from the Princess Margaret Cancer Centre, Toronto, Canada.Results:A total of 39 patients (78%) were assessed at baseline, 24 (48%) at t1, and 16 (32%) at t2. Analyses revealed reductions over time in depressive symptoms: beta = −0.13, confidence interval (CI.95) = (−0.23, −0.022) and death anxiety: beta = −0.23, CI.95(−0.40, −0.061); and an increase in spiritual well-being: beta = 0.14, CI.95(0.026, 0.26).Conclusions:CALM may be a feasible intervention to benefit patients with advanced cancer. The results are encouraging, despite attrition and small effect sizes, and support further study.

Objective To examine the presence of death anxiety in patients with advanced cancer and to identify the psychosocial and disease-related factors associated with it. Design Cross-sectional analysis of baseline data from a phase 2 pilot intervention trial. Setting Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. Participants 60 adult outpatients with metastatic breast, endocrine, gastrointestinal, gynaecological, genitourinary and lung cancer. Main outcome measure Death anxiety, as measured by the Death and Dying Distress Scale (DADDS). Results Thirty-two per cent of the sample reported death anxiety of at least moderate severity. The most distressing concern involved fears about the impact of one9s death on others, and the least distressing concerns were related to dying alone or suddenly. According to regression analyses, death anxiety was negatively associated with self-esteem, b=−1.73, CI 0.95 (−2.57 to −0.90) and positively associated with physical symptom burden, b=1.38, CI 0.95 (0.44 to 2.31), having children under 18 years of age in the family, b=13.3, CI 0.95 (2.15 to 24.5), and age, b=0.40, CI 0.95 (0.0023 to 0.79). The physical symptoms most strongly associated with death anxiety were changes in physical appearance, b=18.8, CI 0.95 (8.21 to29.5), and pain, b=10.1, CI 0.95 (0.73 to 19.5). Conclusions The findings suggest that death anxiety in patients with advanced cancer is common and determined by the interaction of individual factors, family circumstances and physical suffering. Multidimensional interventions that take into account these and other factors may be most likely to be effective to alleviate this death-related distress.

Objective This study evaluates the quality of life (QOL) and mental health (MH) of caregivers of patients with advanced cancer who are receiving ambulatory oncology care and associations with patient, caregiver and care-related characteristics. Methods Patients with advanced gastrointestinal, genitourinary, breast, lung or gynaecologic cancer, and their caregivers, were recruited from 24 medical oncology clinics for a cluster-randomized trial of early palliative care. Caregivers completed the Caregiver QOL—Cancer scale and the Medical Outcomes Study Short Form, version 2, and a questionnaire including care-related factors such as hours/day providing care and change in work situation. Patients completed a demographic questionnaire and measures of their QOL and symptom severity. Associations of these factors with caregiver QOL and MH were examined using linear regression analyses. Results Of the 191 caregivers, 84% were spouses/partners, 90% cohabited with the patient, half were working and 25% had a change in work situation since the patient's diagnosis. On multiple regression analysis, better caregiver QOL was associated with better caregiver MH and patient physical well-being and with not providing care for other dependents. Worse caregiver MH was associated with female caregiver sex, worse patient emotional well-being, more hours spent caregiving and change in the caregiver's work situation. Conclusions Caregivers of ambulatory patients with advanced cancer may have compromised QOL and MH associated with worse patient physical and emotional well-being and with simultaneously caring for others and working outside the home. Early palliative care interventions directed at patient symptoms and caregiver support may improve QOL in this population. Copyright © 2011 John Wiley & Sons, Ltd.

Thoracic outlet syndrome (TOS) is a well-discussed neurovascular condition in upper limbs that prompted the scientists to conduct several reviews and to write articles on the topic during the last three decades. Most of the treatments are surgery and a series of conservative treatments. However, the variation of conservative treatments is wide and not defined. The aim of this systematic review was to define the effectiveness of physical treatments, as one of the conservative managements, for patients with TOS, in terms of pain relief. Eleven articles published during the period 1990-2009 were selected for this review. Results show that physical treatments can reduce the pain of patients with TOS, which is the primary outcome. However, there is no firm evidence to support their effectiveness. Refereed/Peer-reviewed

Background: Although psychosocial care has been regarded as central to palliative and supportive care, there have been few empirically tested approaches to individual intervention. Aim: The subjective experience of advanced cancer patients receiving a new manualized brief individual psychotherapy, referred to as Managing Cancer and Living Meaningfully (CALM), was examined prior to the initiation of a randomized controlled trial testing the effectiveness of this intervention. Design: Semi-structured interviews were conducted with patients who had a diagnosis of advanced cancer, and who underwent the intervention. Setting/Participants: Patients were recruited from a large urban regional cancer center in Toronto, Canada. The 10 interviewees included seven women and three men. All had completed between three to six CALM sessions prior to the interview. Results: The CALM intervention was associated with profound and unique patient-identified benefits and no patient-identified risks or concerns. Five interrelated benefits of the intervention were identified: (1) a safe place to process the experience of advanced cancer; (2) permission to talk about death and dying; (3) assistance in managing the illness and navigating the healthcare system; (4) resolution of relational strain; and (5) an opportunity to ‘be seen as a whole person’ within the healthcare system. These benefits were regarded by participants as unique in their cancer journey. Conclusions: Findings from a qualitative study suggest that the CALM intervention provides substantial benefits for patients with advanced cancer prior to the end of life. Findings informed the development of a randomized controlled trial to evaluate the effectiveness of this intervention.

The Broad/IBM Cancer Resistance Project has partnered with Broad Genomics to pilot the use of cutting edge sequencing technology for the analysis of cell free DNA in blood biopsies. Working closely with the Broad's Cancer Program, Broad Genomics has developed a suite of liquid biopsy sequencing products designed to provide optimal flexibility in conducting research studies with a broad range of applications including; biomarker discovery, treatment resistance monitoring, and detection of minimal residual disease (MRD) post-surgery. Cell-free DNA is extracted from the blood, and a dual unique-molecular-indexed library is created. From this library, low coverage whole genome (ultra-low-pass 0.1x coverage) data is generated to survey sample quality and evaluate the tumor fraction in the liquid specimen. Utilizing the same library, additional assays can be selected for processing based on the research aim (Targeted Panel Assays, MRD Detection or Whole Exomes). Since our approach utilizes the same genomic material for whole genome and targeted sequencing assays, it is possible to maximize the information learned from each valuable and limited liquid biopsy specimen. Our study design takes advantage of the discovery potential of combined tissue-based sequencing and serial liquid biopsy analysis to elucidate mechanisms of cancer resistance by tracking the evolution of clonal and subclonal populations in patients samples over time. This collaboration will utilize the ultra-low-pass sequencing and whole exome sequencing together with custom analysis pipelines to correlate the genomic events with patient clinical data. We aim to process 3,000 samples from 1,000 patients over the next 3 years. To date we have processed close to 500 samples through the ultra-low-pass pipeline and 100 samples through the whole exome sequencing pipeline (results to be provided).The ability to successfully investigate treatment resistant cancers from non-invasive liquid biopsies presents new opportunities for identifying markers, understanding dynamics and monitoring tumor dissemination and clonal evolution. Citation Format: Gad Getz, Carrie Cibulskis, Ignaty Leshchiner, Megan Hanna, Dimitri Livitz, Kara Slowik, Chaya Levovitz, Filippo Utro, Kahn Rhrissorrakrai, Denisse Rotem, Gregory Gydush, Sarah C. Reed, Justin Rhoades, Gavin Ha, Samuel S. Freeman, Christopher Lo, Mark Fleharty, Justin Abreu, Katie Larkin, Michelle Cipicchio, Brendan Blumenstiel, Matt DeFelice, Jonna Grimsby, Susanna Hamilton, Niall Lennon, Viktor A. Adalsteinsson, Laxmi Parida. Broad/IBM Project: Discovery of treatment resistance mechanisms through use of liquid biopsy genomics services [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3001.

Introduction: Precision medicine approaches to guide therapy selection require routine sampling of tumors. However, tumor biopsies are not always accessible and may be confounded by spatial heterogeneity. Liquid biopsies, including analysis of cell-free DNA (cfDNA), present a non-invasive alternative which may reflect multiple tumors in the body. Previous studies have demonstrated exome-wide concordance between single-site tumor biopsies and cfDNA, but little is known about how cfDNA reflects multiple lesions within a patient. Here we sought to determine how cfDNA reflects the body-wide tumor phylogeny, which will inform the use of cfDNA for cancer precision medicine. Methods: We identified 20 patients with pancreatic cancer who had undergone rapid autopsy. We then screened cfDNA tumor fraction and performed whole-exome sequencing of cfDNA and multiple tumor biopsies for 3 patients with cfDNA tumor fraction >10%. We inferred the tumor phylogeny and then developed a statistical approach to deconvolute the contributions to cfDNA from tumor phylogenetic nodes. Finally, we determined whether shared trunk mutations could be detected in cfDNA and tumor biopsies. Results: For each patient, we found mutations shared between all sites and cfDNA, including putative driver mutations. We found mutations which were clonal in multiple regions were detectable in cfDNA, whereas mutations private to individual sites were never clonal in cfDNA. Through our deconvolution analysis, we found that cfDNA could not be modeled as a simple linear combination of individual sites, but rather that cfDNA represented multiple nodes in the inferred phylogeny. For two pancreatic adenocarcinoma patients, the inferred ancestor of the metastases had high estimated contribution (>70%) to cfDNA, while the ancestors of the primaries had lower contributions ( Conclusions: Through analyzing cfDNA and synchronous tumor biopsies from the same patient, we find trunk mutations are enriched in cfDNA as compared to the average single-site biopsy. We also predict that cfDNA represents multiple nodes in the inferred phylogeny. In cases where tumor biopsies are inaccessible, we demonstrate that cfDNA might be a promising alternative to detect trunk SSNVs. These results suggest that cfDNA may be complementary to tumor biopsies for disease monitoring and treatment selection in personalized medicine. Citation Format: Samuel S. Freeman, Ziao Lin, Gavin Ha, Ignaty Leshchiner, Justin Rhoades, Dimitri Livitz, Daniel Rosebrock, Sarah C. Reed, Gregory Gydush, Christopher Lo, Denisse Rotem, Atish D. Choudhury, Daniel G. Stover, Heather A. Parsons, Jesse S. Boehm, J Christopher Love, Matthew Meyerson, Paul Grandgenett, Michael A. Hollingsworth, Viktor A. Adalsteinsson, Gad Getz. Liquid biopsies identify trunk mutations and reflect multiple tumors in a patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-225.

Brain tumors often require invasive neurosurgical procedures for diagnosis and tissue acquisition to guide precision medicine. Detection of tumor-derived cell-free DNA (cfDNA) would facilitate tumor profiling without risk of surgery-related morbidity and provide a means of tumor surveillance. Our aim is to validate a sample collection procedure and develop highly sensitive and specific methodologies to detect tumor-derived cfDNA in CSF, plasma and urine from pediatric patients with brain tumors to identify clinically relevant genomic alterations. Since July 2016, we have collected blood, urine and CSF samples from 192 patients across all histological subtypes at Dana-Farber Cancer Institute/Boston Children’s Hospital. In parallel, we sequenced the tumors to identify tumor-specific genomic alterations. We optimized a method to process cfDNA and perform ultra-low pass whole genome sequencing (ULP-WGS) using unique molecular identifiers, confirming we can reliably construct sequencing libraries from CSF-, plasma- and urine-derived cfDNA. ULP-WGS has also been used to assess sequencing library quality, copy number variations (CNVs) and tumor fraction. The vast majority of samples undergoing ULP-WGS exhibited no CNVs, consistent with either absence in the tumor or low levels of tumor-derived cfDNA. To distinguish between these, we developed a hybrid capture sequencing panel covering 46 genes, allowing identification of specific mutations and fusions more common in pediatric brain tumors. We are currently assessing the specificity and sensitivity of our assays for detection of tumor-derived cfDNA. Our results will provide insights regarding the feasibility of cfDNA assays to guide clinical care in children with brain tumors.

We provide preliminary psychometric results concerning the use of a modified FAMCARE scale, adapted for patient use, to assess satisfaction with outpatient care in advanced stage cancer patients.Participants were 145 outpatients with advanced cancer who were participating in a phase II trial of an outpatient palliative care intervention. Patients completed our modified FAMCARE measure of patient satisfaction and the Edmonton Symptom Assessment Scale, a measure of symptom burden. Individuals were also assessed for performance status using the Eastern Cooperative Oncology Group scale. We conducted an exploratory factor analysis of the patient satisfaction measure and performed correlations of satisfaction with symptom burden as well as with performance status.Factor analysis of the satisfaction measure revealed a one-factor structure and suggested the removal of one nonloading item, producing a 16-item scale (FAMCARE-P16) with high internal reliability. Patient satisfaction was not correlated with performance status, but was inversely associated with symptom burden, particularly with depression and anxiety.The FAMCARE-P16 may be used to assess satisfaction with outpatient palliative care interventions of patients with advanced stage cancer in both clinical settings and prospective trials.

Background We have developed a novel and brief semi-structured psychotherapeutic intervention for patients with advanced or metastatic cancer, called Managing Cancer And Living Meaningfully. We describe here the methodology of a randomized controlled trial to test the efficacy of this treatment to alleviate distress and promote well-being in this population. Methods/Design The study is an unblinded randomized controlled trial with 2 conditions (intervention plus usual care versus usual care alone) and assessments at baseline, 3 and 6 months. The site is the Princess Margaret Cancer Centre, part of the University Health Network, in Toronto, Canada. Eligibility criteria include: ≥ 18 years of age; English fluency; no cognitive impairment; and diagnosis of advanced cancer. The 3–6 session intervention is manualized and allows for flexibility to meet individual patients’ needs. It is delivered over a 3–6 month period and provides reflective space for patients (and their primary caregivers) to address 4 main domains: symptom management and communication with health care providers; changes in self and relations with close others; sense of meaning and purpose; and the future and mortality. Usual care at the Princess Margaret Cancer Centre includes distress screening and referral as required to in-hospital psychosocial and palliative care services. The primary outcome is frequency of depressive symptoms and the primary endpoint is at 3 months. Secondary outcomes include diagnosis of major or minor depression, generalized anxiety, death anxiety, spiritual well-being, quality of life, demoralization, attachment security, posttraumatic growth, communication with partners, and satisfaction with clinical interactions. Discussion Managing Cancer And Living Meaningfully has the potential to relieve distress and promote psychological well-being in patients with advanced cancer and their primary caregivers. This trial is being conducted to determine its benefit and inform its dissemination. The intervention has cross-national relevance and training workshops have been held thus far with clinicians from North and South America, Europe, the Middle East, Asia and Africa. Trial Registration ClinicalTrials.gov NCT01506492 4 January 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0811-1) contains supplementary material, which is available to authorized users.

LBA10001 Background: Patients with advanced cancer experience substantial distress in response to the burden of disease and the challenge of living meaningfully in the face of impending mortality. We developed a novel, brief, manualized psychotherapeutic intervention called CALM designed to alleviate distress and facilitate adjustment in this population. CALM consists of 3-6 individual sessions delivered over 3-6 months and supports exploration in 4 broad domains: 1) symptom management and communication with health care providers; 2) changes in self and relations with close others; 3) sense of meaning and purpose; and 4) the future and mortality. Methods: Patients with advanced cancer were recruited from outpatient clinics at a comprehensive cancer center and randomized to receive either CALM or usual care (UC). Assessments of depressive symptoms (primary outcome), death-related distress and other secondary outcomes were conducted at baseline, 3 (primary endpoint) and 6 months. ANCOVA was used to test for outcome differences between groups at follow-up, controlling for baseline scores. Results: Three hundred and five participants were recruited and randomized (n = 151 CALM; n = 154 UC). Compliance with the intervention was 77.5% and attrition was 28% (16% deceased, 8% lost to follow-up, 4% withdrew). The CALM group reported less severe depressive symptoms compared to UC at 3 (ΔM1-M2 = 1.09, p < 0.04; Cohen’s d = 0.23) and 6 months (ΔM1-M2 = 1.33, p < 0.01; Cohen’s d = 0.29). Other statistically significant findings in psychological well-being and preparation for the end of life at 3- and 6- months also favored CALM vs UC. Conclusions: CALM is an effective intervention for patients with advanced cancer that provides a systematic approach to alleviate distress and to address predictable challenges. Clinical trial information: NCT01506492.

The experience of death anxiety in patients with advanced cancer has been understudied partly because of the lack of a tailored measure for this population. The Death and Dying Distress Scale (DADDS) was constructed to address this gap. Although an initial version of this instrument has shown promising psychometric properties, validation of the finalized version is needed.This study aims to validate the recent 15-item DADDS by examining its factor structure and construct validity.Sixty participants with advanced or metastatic cancer were recruited from the Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, into a pilot trial of a psychological intervention. This article analyzes the baseline measures on death anxiety, depressive symptoms (Patient Health Questionnaire-9, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis 1 Disorders), generalized anxiety (Generalized Anxiety Disorder-7), and preparation for end of life (Quality of Life at the End of Life-Cancer Scale). Exploratory factor analysis was conducted. Construct validity was assessed by correlations between measures.Factor analysis revealed a dominant single factor explaining more than 75% of the shared variation between items. Factor loadings were high, ranging from 0.57 to 0.86. Item communalities were evenly ranged from 0.33 to 0.75 and with the 15:1 variable to factor ratio, suggest the viability of parameter estimates despite the small sample size. Cronbach's alpha was 0.95. Death anxiety was associated with less preparation for end of life (r = -0.68, P 0.0001), more generalized anxiety (r = 0.63, P 0.0001), and more depressive symptom severity (r = 0.50, P 0.0001). Individuals with major depression had greater death anxiety than the nondepressed (mean difference = 17; 95% CI = 1.5-33), as did individuals with minor depression (mean difference = 25; 95% CI = 10-41).The DADDS is a valid measure of death anxiety in patients with advanced cancer. It may provide useful information in the assessment and treatment of distress in patients near the end of life.

We examined the symptoms and referral rates to specialized palliative care and psychosocial oncology services of patients with acute leukemia. The Memorial Symptom Assessment Scale (MSAS) was completed by 249 adult patients with acute leukemia. Patients reported a median of 9 physical and 2 psychological symptoms, and those with intense lack of energy, difficulty sleeping and pain were more likely to report intense worrying/sadness (P < 0.001). No patients with moderate-severe pain were referred for specialized symptom control and only 13% of those with severe worrying/sadness were referred to psychiatry/psychology within one month of the assessment. Patients in this population have a substantial symptom burden; further research is needed to determine the benefit of early referral to specialized supportive care services.

During the past 40 years, the roles of the pharmacy technician have expanded to services beyond traditional duties within the pharmacy department, correlating with the ever-changing needs of the health care system. In other countries, such as the United Kingdom, the roles of pharmacy technicians go beyond those of their Canadian counterparts to include advising patients about medications, reviewing medication charts, and identifying medication-related problems, which can then be referred to pharmacists for resolution, which is more commonly known as follow-up for drug-related problems. In the United Kingdom, pharmacy technicians can also participate in discharge planning, can work in anticoagulation clinics, and can provide medication information to patients. In that country, voluntary registration to become a pharmacy technician started in 2005 and will be mandatory by 2011. Pharmacy technicians who are not registered by 2011 will no longer be able to call themselves pharmacy technicians or work in that capacity. In Canada, a national initiative is under way to regulate pharmacy technicians. Once regulated, pharmacy technicians will have an expanded scope of practice, for which they will be accountable and responsible. As in the United Kingdom, current technicians who choose not to go through the transition processes will not be able to call themselves pharmacy technicians. Starting with the definition of a national scope of practice in 2005, initiatives that have been explored include education outcomes, entry-to-practice competencies, accreditation of training programs, evaluation and entry-to-practice examinations, and bridging programs to support individuals currently employed as pharmacy technicians. The Canadian Council for the Accreditation of Pharmacy Programs is currently accrediting pharmacy technician programs in Canada in anticipation of the regulation of these allied health professionals. In 2007, the Health Systems Improvement Act was passed by the Ontario Legislature, which enabled the regulation of pharmacy technicians by the Ontario College of Pharmacists. In British Columbia, initiatives are also under way for the regulation of technicians by the College of Pharmacists of British Columbia. The BC legislation allows pharmacists to manage, supervise, teach, or train others, including technicians, to provide pharmaceutical care. Recently, there was an opportunity to place a technician in the oncology unit at Ridge Meadows Hospital in Maple Ridge, British Columbia. No previous publications have described an enhanced role for technicians working in specialized areas. We describe here the unique position of a technician at Ridge Meadows Hospital who specializes as a clinical support technician in oncology and is known as the Specialized Pharmacy Oncology Technician or SPOT.

Objective Acute leukemia is a condition with an acute onset that is associated with considerable morbidity and mortality. However, the psychological impact of this life-threatening condition and its intensive treatment has not been systematically examined. In the present study, we investigate the prevalence and correlates of post-traumatic stress symptoms in this population. Methods Patients with acute myeloid, lymphocytic, and promyelocytic leukemia who were newly diagnosed, recently relapsed, or treatment failures were recruited at a comprehensive cancer center in Toronto, Canada. Participants completed the Stanford Acute Stress Reaction Questionnaire, Memorial Symptom Assessment Scale, CARES Medical Interaction Subscale, and other psychosocial measures. A multivariate regression analysis was used to assess independent predictors of post-traumatic stress symptoms. Results Of the 205 participants, 58% were male, mean age was 50.1 ± 15.4 years, 86% were recently diagnosed, and 94% were receiving active treatment. The mean Stanford Acute Stress Reaction Questionnaire score was 30.2 ± 22.5, with 27 of 200 (14%) patients meeting criteria for acute stress disorder and 36 (18%) for subsyndromal acute stress disorder. Post-traumatic stress symptoms were associated with more physical symptoms, physical symptom distress, attachment anxiety, and perceived difficulty communicating with health-care providers, and poorer spiritual well-being (all p

Acute leukemia is a condition with an acute onset that is associated with considerable morbidity and mortality. However, the psychological impact of this life-threatening condition and its intensive treatment has not been systematically examined. In the present study, we investigate the prevalence and correlates of post-traumatic stress symptoms in this population.Patients with acute myeloid, lymphocytic, and promyelocytic leukemia who were newly diagnosed, recently relapsed, or treatment failures were recruited at a comprehensive cancer center in Toronto, Canada. Participants completed the Stanford Acute Stress Reaction Questionnaire, Memorial Symptom Assessment Scale, CARES Medical Interaction Subscale, and other psychosocial measures. A multivariate regression analysis was used to assess independent predictors of post-traumatic stress symptoms.Of the 205 participants, 58% were male, mean age was 50.1 ± 15.4 years, 86% were recently diagnosed, and 94% were receiving active treatment. The mean Stanford Acute Stress Reaction Questionnaire score was 30.2 ± 22.5, with 27 of 200 (14%) patients meeting criteria for acute stress disorder and 36 (18%) for subsyndromal acute stress disorder. Post-traumatic stress symptoms were associated with more physical symptoms, physical symptom distress, attachment anxiety, and perceived difficulty communicating with health-care providers, and poorer spiritual well-being (all p0.05).The present study demonstrates that clinically significant symptoms of traumatic stress are common in acute leukemia and are linked to the degree of physical suffering, to satisfaction with relationships with health-care providers, and with individual psychological characteristics. Longitudinal study is needed to determine the natural history, but these findings suggest that intervention may be indicated to alleviate or prevent traumatic stress in this population.

Background: Spironolactone is used in the treatment of cardiovascular disease, but is contraindicated in renal dysfunction due to the risk of hyperkalemia. It is not known if patients with end-stage renal disease (ESRD) on hemodialysis are at the same risk for hyperkalemia. The objective of this study was to systematically review the evidence evaluating the incidence of hyperkalemia with spironolactone use in ESRD patients on hemodialysis. Hypothesis: Spironolactone use in ESRD patients on hemodialysis may not lead to greater incidence of hyperkalemia. Methods: We searched the MEDLINE, Embase, CINAHL, Cochrane, and PubMed databases up to January 2010 for English-language, human-subject clinical trials that evaluated the rate of hyperkalemia with spironolactone use in ESRD patients on hemodialysis. Search terms included were “spironolactone,” “eplerenone,” “aldosterone antagonist,” “heart failure,” “kidney failure,” “hemodialysis,” “dialysis,” and “renal replacement therapy.” Results: Six prospective trials demonstrated that spironolactone use was safe in ESRD patients on hemodialysis. The incidence of hyperkalemia with spironolactone treatment in these studies was similar to control groups. The studies involved a small population of compliant subjects who were at low risk for hyperkalemia. Conclusions: Small pilot studies demonstrated that spironolactone treatment in ESRD patients on hemodialysis did not result in higher hyperkalemia rates. Larger studies are needed to confirm these preliminary results before spironolactone is routinely considered in hemodialysis patients. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

1. Chris Lo[1][1],[2][2] 1. 1Psychiatry, University of Toronto, Toronto, Ontario, Canada 2. 2University Health Network, Toronto, Ontario, Canada 1. Chris Lo, 9EN-234A, 200 Elizabeth St., Toronto, Ontario, Canada, M5G 2C4. Email: chrislo{at}uhnresearch.ca Alexithymia refers to difficulty with reflecting on and articulating emotional states. Previous research has found that Asian groups may tend toward greater alexithymia and that cultural values may mediate this difference, although the content of Asian values that form these pathways is unclear. This study examined the relationship between Confucian values, ethnicity, and alexithymia. A sample of 216 undergraduate students completed the Chinese Value Survey and the Toronto Alexithymia Scale. Asian Canadians scored more highly on alexithymia than non-Asian Canadians. Individuals who valued trustworthiness, patience, and kindness were found to be less alexithymic. The ability to be a source of kindness and security to others may be tied to the development of reflective awareness. Individuals who valued purity from desire and respect for social order were found to be more alexithymic. Such individuals may tend not to reflect on impure or socially disruptive thoughts and feelings. Values associated with purity and order mediated the difference between Asians and non-Asians on alexithymia. Asian Canadians may therefore score more highly on alexithymia because they prefer not to reflect on emotions associated with impurity or social disorder. [1]: #aff-1 [2]: #aff-2