Comprehensive tumor genomic profiling (CTGP) is increasingly used to personalize treatments, providing hope, but potentially disappointment, for patients. We explored psychological outcomes in ...patients with advanced, incurable cancer, after receiving CTGP results.
Participants with advanced, incurable cancer (n = 560, mean age 56, 43% university educated) in this longitudinal substudy of the Molecular Screening and Therapeutics Program (MoST), completed questionnaires before and after receiving CGP results. MoST participants, recruited from Australian oncology clinics, undergo CTGP, and if there are actionable findings, are offered treatment in a related therapeutic trial if available.
Patients who received actionable results, (n = 356, 64%) had lower gene-related distress (MICRA) (p < 0.001) and Impact of Events scores (p = 0.039) than patients with non-actionable results. Those with actionable results offered ensured access to tailored treatment (n = 151) reported lower anxiety (p = 0.002) and depressive symptoms (p = 0.01) and greater hope (p = 0.002) than those not offered. Positive attitudes towards uncertainty and higher self-efficacy for coping with results were associated with lower psychological distress and uncertainty, and higher hope and satisfaction with the decision to have CTGP (ps=0.001–0.047). Those with higher knowledge reported greater anxiety (p = 0.034).
Receiving a non-actionable CTGP result, or an actionable result without ensured access to treatment, may cause increased distress in advanced cancer patients. Coping style was also associated with distress.
Pre-testing assessment and counseling addressing attitudes toward uncertainty and self-efficacy, and post-CTGP result support for patients receiving a non-actionable result or who receive an actionable results without ensured access to treatment, may benefit patients.
•Actionable results and direct access to tailored treatment were associated with reduced distress in advanced cancer patients.•Positive attitudes towards uncertainty and higher self-efficacy was associated with lower levels of psychological distress.•Some patients who do not receive results leading to tailored treatment may benefit from support and counseling at this time.•Addressing attitudes toward uncertainty and self-efficacy may assist patients to cope with results.
Background: Comprehensive tumor genomic profiling (CGP) offers hope for personalized treatment for cancer patients when other treatment options have been exhausted. However, receipt of nonactionable ...or ambiguous results could be an ongoing source of distress. We investigated patterns of hope, anxiety, depression, and CGP-specific anxiety in advanced cancer patients after receiving CGP results and 2-3 months later. Method: Participants were enrolled in a longitudinal psychosocial substudy, embedded in the Molecular Screening and Therapeutics Program, and had advanced solid cancers of any histological type with sufficient and accessible tissue for CGP. At T0 (before receiving CGP results), 1,431 participants completed sociodemographic, disease and psychosocial measures. At T1 (1-4 weeks after receiving CGP results) and T2 (2-3 months post-T1), 374 participants completed psychological outcome measures. Predictors of outcomes at T2 were identified using multinomial logistic regression. Results: Approximately 75% of participants did not experience significant hopelessness or distress at T1 and T2. Hope decreased by T2, yet general anxiety and CGP-specific anxiety also decreased. Receiving actionable results did not impact psychological outcomes at T2. At T2, lower hope, and higher anxiety, depression and CGP-specific anxiety were associated with lower self-efficacy. Psychological and demographic factors (age, socioeconomic status, language, medical occupation, urban living, family history of cancer) independently predicted one or more psychological trajectories. Worse health status and perceived susceptibility to cancer progression predicted hope and anxiety trajectories. Conclusion: Further research on interventions to best support patients undergoing CGP with high anxiety, hopelessness, fear of cancer progression, and poorer health is urgently needed.
Limited research has indicated that despite their overwhelming interest in tumor molecular profiling (MP),11Abbreviations: Accessibility and Remoteness Index of Australia (ARIA): an indication of the ...proximity of service centers relative to where the participant lives. Eastern Cooperative Oncology Group (ECOG): A performance status measure to quantify cancer patients' general well-being and activities of daily life. Molecular Therapeutics (MoST) Program: A research program which forms a component of the Australian Genomic Cancer Medicine Program. The Psychosocial Issues in Genomic Oncology (PiGeOn) Project: a longitudinal, mixed methods psychosocial sub-study of the MoST Program which aims to examine the psychosocial, behavioral and ethical impact of MP. Tumor molecular profiling (MP): a form of genomic testing, that involves characterization of tumor-derived DNA and RNA. cancer patients have poor knowledge about MP. The current study aimed to investigate demographic and psychological predictors of knowledge and perceived importance of MP in an advanced cancer patient cohort. Eligible participants had advanced solid cancers of any histological type with sufficient accessible tissue for MP and were enrolled in the Molecular Screening and Therapeutics (MoST) Program. A questionnaire was completed by 1074 participants (91% response rate) after consent, prior to undergoing MP. Overall, participants had poor to moderate knowledge of MP, yet perceived MP to have high importance. Higher education, speaking English at home, and greater satisfaction with the decision to undergo MP were associated with higher knowledge scores. More negative attitudes towards uncertainty, greater self-efficacy to cope with results, and lower perceived likelihood of cancer progression were associated with greater perceived importance of MP. Less educated participants and those who do not speak English at home will need clear explanations, visual aids and ample opportunity to ask questions about MP at the time of their decision-making. Clinicians also need to consider psychological factors relevant to patients' decision to pursue MP. Given the increased awareness of and demand for cancer genomic information and the rapidly changing nature of the actionability of MP, these findings will help inform an important ongoing debate on how to facilitate ethical and informed consent and manage patient expectations about personalized treatments.
The brain of mammalian hibernators is naturally protected. Hibernating ground squirrels undergo rapid and extreme changes in body temperature and brain perfusion as they cycle between lengthy torpor ...bouts and brief periods of euthermia called interbout arousals (IBAs). Arousal from torpor to IBA occurs rapidly, but there is no evidence of brain injury accompanying this extreme physiological transition. Production of the hormone melatonin accompanies arousal, suggesting that it plays a protective role at this time. Here, we investigated mechanisms of melatonin receptor-mediated protection in the brain of the hibernating ground squirrel. We administered the competitive melatonin receptor antagonist luzindole (30 mg/kg ip) to ground squirrels at the predicted end of a torpor bout, triggering an arousal. We found that luzindole-treated animals exhibited caspase-3 activity two times higher than vehicle-treated animals in the hypothalamus at midarousal (P = 0.01), suggesting that melatonin receptor signaling is important for protection in this brain region. We also found a 30% decline in succinate-fueled mitochondrial respiration in luzindole-treated animals compared with vehicle-treated animals (P = 0.019), suggesting that melatonin receptor signaling is important for optimal mitochondrial function during arousal from torpor. The mitochondrial effects of luzindole treatment were seen only during the hibernation season, indicating that this effect is specifically important for arousal from torpor. These data provide evidence for the protective role of melatonin receptor signaling during the extreme physiological transition that occurs when a hibernating mammal arouses from torpor and provide further evidence for regional and seasonal changes in the hibernator brain.
•Cancer patients/relatives having germline genome sequencing had moderate GS knowledge.•Most participants had high intentions to change behavior if at high risk of cancer.•Men and those from low ...socio-economic background had less behavior change intentions.•Low self-efficacy and high uncertainty tolerance is associated with lower intentions.•Those with low intention to change behavior may need support to aid behavior change.
Germline genome sequencing (GS) is becoming mainstream in cancer diagnosis and risk management. Identifying knowledge gaps and determinants of health behavior change intentions will enable effective targeting of educational and management strategies to translate genomic findings into improved cancer outcomes.
Probands diagnosed with cancer of likely genetic origin that consented to but not yet undergone GS, and their biological relatives, completed a cross-sectional questionnaire assessing GS knowledge and hypothetical intention to change behaviors.
Probands (n = 348; 57% university educated) and relatives (n = 213; 38% university educated) had moderate GS knowledge levels, with greater knowledge associated with higher education. Both populations reported high behavioral change intentions, significantly associated with being female (p = 0.01) and greater perceived importance of GS (p < 0.001), and for probands: being from English-speaking households (p = 0.003), higher socio-economic status (p = 0.01) and greater self-efficacy (p = 0.02).
Increasing GS knowledge will enable realistic participant expectations surrounding germline GS. Actual behavior change should be monitored to determine whether increased cancer risk knowledge results in altered cancer-related behavior and ultimately, cancer outcomes.
Educational resources should target specific populations to ensure informed decision-making and expectation management. Support tools facilitating and maintaining behavioral change may be needed to achieve improved cancer patient outcomes.
This study explored the attitudes of patients with advanced cancer towards MTP and return of results, prior to undergoing genomic testing within a research program.
Participants were recruited as ...part of the longitudinal PiGeOn (Psychosocial Issues in Genomics in Oncology) study involving patients with advanced/metastatic solid cancer who had exhausted therapeutic options and who were offered MTP in order to identify cognate therapies. Twenty patients, selected by purposive sampling, were interviewed around the time they gave consent to MTP. Interviews were audio recorded, transcribed and analysed using thematic analysis. Themes identified in the transcripts were cross-validated via qualitative responses to the PiGeOn study survey (n = 569; 63%).
All interviewed participants gave consent to MTP without reservation. Three themes were identified and further supported via the survey responses: (1) Obvious agreement to participate, primarily because of desire for new treatments and altruism. (2) The black box - while participant knowledge of genomics was generally poor, faith in their oncologists and the scientific process encouraged them to proceed with testing; and (3) Survival is the priority - receiving treatment to prolong life was the priority for all participants, and other issues such as identification of a germline variant were generally seen as ancillary.
Having advanced cancer seemed to abrogate any potential concerns about MTP. Participants valued the research for varied reasons, but this was secondary to their priority to survive. While no negative attitudes toward MTP emerged, limitations in understanding of genomics were evident.
Introduction
Fear of cancer progression (FCP) impacts quality of life and is a prevalent unmet need in patients diagnosed with advanced cancer, particularly as treatment options are reduced. We aimed ...to identify longitudinal patterns in FCP over 6 months in patients with advanced cancer receiving comprehensive tumour genomic profiling (CTGP) results, and their correlates.
Methods
Patients with pathologically confirmed metastatic disease (∼70% rare cancers) receiving or post their last line of standard therapy completed questionnaires at T0 (prior to CTGP), T1 (immediately post CTGP results) and T2 (2 months later).
Results
High stable (N = 52; 7.3%) and low/moderate stable (N = 56; 7.8%) FCP patterns over time typified the largest participant groups (N = 721). Those with an immediately actionable variant versus a non‐actionable variant (p = 0.045), with higher FCP (p < 0.001), and lower Functional Assessment of Chronic Illness Therapy—Spiritual Well‐being (FACIT‐Sp) scores (p = 0.006) at T0, had higher FCP at T1. Those with higher FCP at T0 (p < 0.001) and at T1 (p < 0.001), lower FACIT‐Sp scores at T1 (p = 0.001), lower education (p = 0.031) and female gender (p = 0.027) had higher FCP at T2.
Discussion
Routine screening for psychological/spiritual characteristics in those about to undergo CTGP may help to identify patients who may benefit from closer monitoring and provision of psychosocial support. Future studies should explore interventions to best address FCP in this vulnerable group, as interventions assessed to date have almost all addressed patients with curative cancers or newly diagnosed advanced disease.
Objective
To determine whether the existing Multidimensional Impact of Cancer Risk Assessment (MICRA) scale, which assesses impact of receiving genetic test results on individuals being assessed for ...cancer risk, can be successfully adapted to cancer patients experiencing prolonged waiting for results of germline genome sequencing (GS).
Methods
Patients previously diagnosed with likely hereditary cancer (n = 250) who were waiting for germline GS results completed questionnaires 3 months after baseline. We adapted the MICRA to measure anxiety associated with waiting for results, and assessed factor structure, internal consistency, test–retest reliability and construct validation.
Results
Factor analysis revealed four factors: distress, positive experience, family support and uncertainty. Internal consistency for each sub‐scale was high with the values of Cronbach's alpha for the distress, positive experiences, family support and uncertainty sub‐scales 0.92, 0.88, 0.92 and 0.87, respectively. Test–retest reliability was poor, with intra‐class correlations of 0.53, 0.13, 0.33 and 0.52 for the four factors, respectively. Construct validation showed large correlations between the MICRA distress and uncertainty sub‐scale scores and the Impact of Events score intrusion (0.42 and 0.62, respectively) and IES avoidant thinking sub‐scales (0.40 and 0.58, respectively) but not the Hospital Anxiety and Depression Scale sub‐scales.
Conclusions
The adapted MICRA identified test‐related anxiety and uncertainty in a population of cancer patients waiting for germline GS results. Results suggest that the distress and uncertainty sub‐scales of the adapted measure are most useful in this context.
Key points
The adapted Multidimensional Impact of Cancer Risk Assessment (MICRA) scale identifies germline genome sequencing (GS) test‐related anxiety and uncertainty in cancer patients undergoing prolonged waiting for results
Use of the adapted MICRA scale will enable identification of patients who require psychological support while awaiting germline GS test results
Microengineered liver tissues for drug testing Khetani, Salman R; Berger, Dustin R; Ballinger, Kimberly R ...
Journal of laboratory automation,
06/2015, Letnik:
20, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Drug-induced liver injury (DILI) is a leading cause of drug attrition. Significant and well-documented differences between animals and humans in liver pathways now necessitate the use of ...human-relevant in vitro liver models for testing new chemical entities during preclinical drug development. Consequently, several human liver models with various levels of in vivo-like complexity have been developed for assessment of drug metabolism, toxicity, and efficacy on liver diseases. Recent trends leverage engineering tools, such as those adapted from the semiconductor industry, to enable precise control over the microenvironment of liver cells and to allow for miniaturization into formats amenable for higher throughput drug screening. Integration of liver models into organs-on-a-chip devices, permitting crosstalk between tissue types, is actively being pursued to obtain a systems-level understanding of drug effects. Here, we review the major trends, challenges, and opportunities associated with development and implementation of engineered liver models created from primary cells, cell lines, and stem cell-derived hepatocyte-like cells. We also present key applications where such models are currently making an impact and highlight areas for improvement. In the future, engineered liver models will prove useful for selecting drugs that are efficacious, safer, and, in some cases, personalized for specific patient populations.
Purpose
Fear of cancer recurrence/occurrence (FCR/O) is prevalent and associated with poorer psychological outcomes but can also motivate individuals to pursue genomic information about cancer risk. ...Guided by Protection Motivation Theory, this study investigated FCR/O prevalence and associated factors among probands previously diagnosed with a cancer of likely heritable origin, and their relatives, who had agreed to have germline genome sequencing.
Methods
Three hundred and forty-eight probands and 167 relatives completed the Concerns about Recurrence Questionnaire (adapted for occurrence for some relatives) within 1 month of agreeing to undertake genome sequencing. Linear regressions investigated demographic, disease, attitude and behavioral associations with FCR/O.
Results
Probands demonstrated greater FCR compared to relatives. In
probands
, greater FCR was associated with being female, non-English speaking at home, less time since diagnosis, greater intention to change behavior if gene variant found, lower perceived ability to cope with results, higher perceived susceptibility to having a recurrence, and more negative attitudes towards uncertainty. For
relatives with cancer
, greater FCR was associated with being male, greater intention to change behavior if a gene variant found, and higher perceived susceptibility to recurrence. In
relatives without cancer
, greater FCO was associated with not having had genetic testing prior to this study, lower perceived ability to cope with results, and higher perceived susceptibility to developing cancer.
Conclusion
Current findings on FCR/O prevalence and associated demographic and attitudinal variables in those who pursue genomic risk information might be used to target interventions that can prevent adverse psychological outcomes in vulnerable patients.
PDF
