NCCN Guidelines® Insights: Distress Management, Version 2.2023.

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. All patients experience some level of distress associated with a cancer diagnosis and the effects of the disease and its treatment regardless of the stage of disease. Clinically significant levels of distress occur in a subset of patients, and identification and treatment of distress are of utmost importance. The NCCN Distress Management Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights describe updates to the NCCN Distress Thermometer (DT) and Problem List, and to the treatment algorithms for patients with trauma- and stressor-related disorders.

Meaning-centered pain coping skills training for patients with metastatic cancer: Results of a randomized controlled pilot trial.

OBJECTIVE: For patients with advanced cancer, pain is a common and debilitating symptom that can negatively impact physical, emotional, and spiritual well-being. This trial examined the feasibility and initial effects of Meaning-Centered Pain Coping Skills Training (MCPC), a cognitive-behavioral pain management intervention with an emphasis on enhancing meaning (i.e., a personal sense of purpose, worth, and significance) and peace. METHODS: We enrolled 60 adults with stage IV solid tumor cancers and moderate-severe pain between February 2021 and February 2022. Participants were randomized 1:1 to MCPC + usual care or usual care alone. Meaning-Centered Pain Coping Skills Training consisted of four weekly 60-min individual sessions via videoconference or telephone, delivered by a trained therapist using a manualized protocol. Participants completed validated measures of pain severity, pain interference, pain self-efficacy, spiritual well-being (i.e., meaning, peace, and faith), and psychological distress at baseline and 5-week and 10-week follow-ups. RESULTS: All feasibility metrics exceeded prespecified benchmarks. Fifty-eight percent of screened patients were eligible, and 69% of eligible patients consented. Of those assigned to MCPC, 93% completed all sessions and 100% of those who completed follow-ups reported using coping skills weekly. Retention was strong at 5-week (85%) and 10-week (78%) follow-ups. Meaning-Centered Pain Coping Skills Training participants reported better scores than control participants across outcome measures, including moderate-to-large sized differences at 10-week follow-up in pain severity (Cohen's d = -0.75 [95% confidence interval: -1.36, -0.14]), pain interference (d = -0.82 [-1.45, -0.20]), and pain self-efficacy (d = 0.74 [0.13, 1.35]). CONCLUSIONS: MCPC is a highly feasible, engaging, and promising approach for improving pain management in advanced cancer. Future efficacy testing is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04431830, registered 16 June 2020.

Family functioning and psychosocial symptoms among Latinx patients coping with advanced cancer.

OBJECTIVES: This brief report aims to describe and determine the association of family functioning (e.g., cohesion and expressiveness) with psychosocial needs among Spanish Latinx patients coping with advanced cancers. METHODS: Descriptive and correlation analyses were performed on data from 103 patients coping with advanced cancer (Stages III and IV). The measures used were the Family Relationships Index, the Hospital Anxiety and Depression Scale, and the Functional Assessment of Cancer Therapy: General. RESULTS: Results indicated that most of the participants had low family function (65%). Participants with higher family functioning (35%) had high levels of quality of life [r(103) .318, p < .002]. A higher level of quality of life was also strongly associated with lower levels of anxiety [r(95) -.653, p < .000], lower levels of depression [r(95) -.733, p < .000], and lower levels of hopelessness [r(95) -.585, p = .000]. A total of 22.3% of Latinx advanced cancer patients reported poor cohesiveness; those with low cohesiveness also had higher levels of depression [r(103) -.28, p = .004] and anxiety [r(103) -.27, p = .005]. Correlations between expressiveness and hopelessness were significant; namely, those with higher expressiveness had lower hopelessness [r(103) -.274, p = .005]. SIGNIFICANCE OF RESULTS: Findings present a high correlation between family functioning and psychosocial symptoms.

The Third Annual US Celebration of World Hospice and Palliative Care Day: A virtual coming together to unify the global palliative care community.

OBJECTIVES: On 3-4 October 2022, the Memorial Sloan Kettering Cancer Center Supportive Care Service and Department of Psychiatry and Behavioral Sciences hosted the Third Annual United States (US) Celebration of World Hospice and Palliative Care Day (WHPCD). The purpose of this article is to reflect on the event within the broader context of the international WHPCD theme: "healing hearts and communities." We describe lessons learned in anticipation of the fourth annual conference to be held on 3-4 October 2023. METHODS: Description of the third annual event, conference planning team reflection, and attendee evaluation responses. RESULTS: The Worldwide Hospice Palliative Care Alliance launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care globally. Since 2020, the conference has attracted an increasing number of attendees from around the world. Two primary aims continue to guide the event: community building and wisdom sharing. Fifty-two interprofessional palliative care experts, advocates, patients, and caregivers provided 13 unique interactive sessions. Four hundred and fifty-eight multidisciplinary registrants from at least 17 countries joined the program. Free registration for colleagues in low- and middle-income countries, students and trainees, and individuals experiencing financial hardship remains a cornerstone of inclusion and equitable access to the event. SIGNIFICANCE OF RESULTS: The US WHPCD celebration provides a virtual platform that offers opportunities for scientific dissemination and collective reflection on hospice and palliative care delivery amid significant local and global changes in clinical practice, research, policy and advocacy, and population health. We remain committed to ensuring an internationally relevant, culturally diverse, and multidisciplinary agenda that will continue to draw increased participation worldwide during future annual events.

Cancer-related inflammation and depressive symptoms: Systematic review and meta-analysis.

BACKGROUND: Depressive symptoms in patients with cancer are associated with poor quality of life and decreased survival. Although inflammation is reliably associated with depression in otherwise healthy individuals, the association in patients with cancer remains unclear. Given the high prevalence of cancer-related inflammation, the authors aimed to establish the relationship between inflammation and depression in cancer patients based on extant literature. METHODS: A systematic review and meta-analysis was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered under Prospero ID CRD42021226743. Three databases were searched including PubMed, the Cochrane Library, and PsycINFO using the following criteria for inclusion: 1) measurement of a peripheral inflammatory marker, 2) use of a validated tool/scale to measure depression, and 3) a cancer diagnosis. Risk of publication bias was assessed by Funnel plot and Egger test. RESULTS: Seventy-three studies were included in the systematic review and 54 studies (n = 5017) were included in meta-analyses. Associations with depressive symptoms were significant for peripheral blood interleukin (IL)-6 (standardized mean difference [SMD] = 0.59; 95% confidence interval [CI], 0.35-0.82), I2  = 57.9%; tumor necrosis factor (TNF) (SMD = 0.73; 95% CI, 0.35-1.11), I2  = 74.1%; and C-reactive protein (CRP) (SMD = 0.57; 95% CI, 0.27-0.87), I2  = 0%. IL-5, IL-13, albumin, and neutrophil-to-lymphocyte ratio were associated with depressive symptoms but based on fewer studies. Most cancer settings were represented; the number of studies per inflammatory marker varied from 1 to 52. CONCLUSIONS: Although peripheral inflammatory markers were unevenly studied, the most studied markers (IL-6, TNF, and CRP) were associated with depressive symptoms in cancer patients and may be useful for management of depressive symptoms in the cancer setting. LAY SUMMARY: Peripheral blood inflammatory markers (IL-6, TNF, and CRP) were associated with depressive symptoms in various cancer settings. Although further studies are warranted, these findings may help identify and manage depressive symptoms in patients with cancer.

Potential use of albumin and neutrophil-to-lymphocyte ratio to guide the evaluation and treatment of cancer-related depression and anxiety.

BACKGROUND: Depression and anxiety are common and associated with inflammation in patients with cancer. Inflammatory indices such as albumin and neutrophil-to-lymphocyte ratio (NLR) obtained from metabolic panels and complete blood counts should be available for mental health professionals treating anxiety and depression at cancer centers. We hypothesized that albumin and NLR extrapolated from non-mental health oncology appointments would be associated with anxiety and depression and drawn close enough to psychiatry visits to be useful for the psycho-oncologist. MATERIALS & METHODS: Depression and anxiety were evaluated in patients (n = 97) referred to a cancer center psychiatric service for depression using the Patient Health Questionnaire-9 and General Anxiety Disorder-7. Albumin concentration and NLR were assessed for timing and correlation strength with anxiety and depression by setting (localized/metastatic cancer). RESULTS: Most patients (96%) had albumin or NLR available at any time point of which 45% were drawn within one week of the psychiatric appointment. No significant correlations were noted when evaluating localized cancer or NLR exclusively. For patients with metastatic cancer, anxiety and depression were correlated with albumin at any time point (r = -0.28, p < 0.05; r = -0.40, p < 0.01, respectively) and within a week of psychiatry appointment (r = -0.40, p < 0.05; r = -0.68, p < 0.001, respectively). Albumin evaluated within a week predicted 32% of depression score variance (ß = -0.63, p = 0.002). Hypoalbuminemia (<3.8 g/ul) was associated with anxiety (χ2 = 4.43, p = 0.04) and depression (χ2 = 11.06, p = 0.001). CONCLUSION: Hypoalbuminemia in patients with metastatic cancer may help establish the presence or persistence of anxiety, depression, treatment refractoriness, and the use of inflammation in cancer-related psychological symptom management.

Reconciling the prospect of disease progression with goals and expectations: Development and validation of a measurement model in advanced cancer.

OBJECTIVE: Among patients living with advanced, life-limiting illness, reconciling the prospect of disease progression with future goals and expectations is a key psychological task, integral to treatment decision-making and emotional well-being. To date, this psychological process remains poorly understood with no available measurement tools. The present paper develops and validates a measurement model for operationalizing this psychological process. METHODS: In Phase 1, concept elicitation interviews were conducted among Stage IV lung, gastrointestinal, and gynecologic cancer patients, their caregivers, and experts (N = 19), to further develop our conceptual framework centered on assimilation and accommodation coping. In Phase 2, draft self-report items of common assimilation and accommodation coping strategies were evaluated via patient cognitive interviews (N = 11). RESULTS: Phase 1 interviews identified several coping strategies, some of which aimed to reduce the perceived likelihood of disease progression (assimilation), and others aimed to integrate the likelihood into new goals and expectations (accommodation). The coping strategies appeared to manifest in patients' daily lives, and integrally related to their emotional well-being and how they think about treatments. Phase 2 cognitive interviews identified items to remove and modify, resulting in a 31-item measure assessing 10 assimilation and accommodation coping strategies. CONCLUSIONS: The present work derived a content-valid measure of the psychological process by which patients reconcile the prospect of disease progression with their goals and expectations. Further psychometric validation and use of the scale could identify intervention targets for enhancing patient decision-making and well-being.

The 2nd Annual US Celebration of World Hospice and Palliative Care Day: A virtual coming together to support equity in palliative care access.

OBJECTIVE: On October 5-6, 2021, the Memorial Sloan Kettering Cancer Center Supportive Care Service and Department of Psychiatry and Behavioral Sciences hosted the 2nd Annual United States (US) Celebration of World Hospice and Palliative Care Day (WHPCD). The purpose of this article is to describe the event within the broader context of the international WHPCD theme: "Leave No One Behind - Equity in Access to Palliative Care." We reflect on lessons learned in anticipation of the 3rd annual conference to be held October 3-4, 2022. METHODS: Description of the 2nd annual event, conference planning team reflection, and attendee evaluation responses. RESULTS: The Worldwide Hospice Palliative Care Alliance launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care around the world. The 2021 US-based innovative virtual conference featured 37 interprofessional hospice and palliative care specialists and patient and family caregiver speakers across 11 diverse sessions with a focus on health equity and COVID-19 considerations. Two primary aims continue to guide the event: community building and wisdom sharing at the intersection of art and science. 278 registrants from at least 14 countries and 21 different states across the US joined the program, which served as a global debriefing for hospice and palliative care workers from diverse settings, contexts, and disciplines. SIGNIFICANCE OF RESULTS: The US WHPCD Celebration creates a virtual coming together for collective reflection on hospice and palliative care delivery amid vast changes in clinical practice, research, and policy, both locally and globally. In addition, our goal to ensure an internationally relevant, culturally inclusive, and multidisciplinary agenda will continue to draw increased participation worldwide during future annual events.

Development and preliminary evaluation of EMPOWER for surrogate decision-makers of critically ill patients.

OBJECTIVE: The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates' mental health and patient outcomes. METHOD: Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15-20 min modules, totaling 1.5-2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments. RESULTS: Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = -0.41), peritraumatic distress (d = -0.24), and experiential avoidance (d = -0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = -0.94), depression (d = -0.23), anxiety (d = -0.29), and experiential avoidance (d = -0.30). SIGNIFICANCE OF RESULTS: Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.

Prognostic implications of depression and inflammation in patients with metastatic lung cancer.

Background: Lung cancer-related inflammation is associated with depression. Both elevated inflammation and depression are associated with worse survival. However, outcomes of patients with concomitant depression and elevated inflammation are not known. Materials & methods: Patients with metastatic lung cancer (n = 123) were evaluated for depression and inflammation. Kaplan-Meier plots and Cox proportional hazard models provided survival estimations. Results: Estimated survival was 515 days for the cohort and 323 days for patients with depression (hazard ratio: 1.12; 95% CI: 1.05-1.179), 356 days for patients with elevated inflammation (hazard ratio: 2.85, 95% CI: 1.856-4.388), and 307 days with both (χ2 = 12.546; p < 0.001]). Conclusion: Depression and inflammation are independently associated with inferior survival. Survival worsened by inflammation is mediated by depression-a treatable risk factor.

The Sickness Behavior Inventory-Revised: Sickness behavior and its associations with depression and inflammation in patients with metastatic lung cancer.

BACKGROUND: Inflammation may contribute to the high prevalence of depressive symptoms seen in lung cancer. "Sickness behavior" is a cluster of symptoms induced by inflammation that are similar but distinct from depressive symptoms. The Sickness Behavior Inventory-Revised (SBI-R) was developed to measure sickness behavior. We hypothesized that the SBI-R would demonstrate adequate psychometric properties in association with inflammation. METHOD: Participants with stage IV lung cancer (n = 92) were evaluated for sickness behavior using the SBI-R. Concomitant assessments were made of depression (Patient Hospital Questionniare-9, Hospital Anxiety and Depression Scale) and inflammation [C-reactive protein (CRP)]. Classical test theory (CTT) was applied and multivariate models were created to explain SBI-R associations with depression and inflammation. Factor Analysis was also used to identify the underlying factor structure of the hypothesized construct of sickness behavior. A longitudinal analysis was conducted for a subset of participants. RESULTS: The sample mean for the 12-item SBI-R was 8.3 (6.7) with a range from 0 to 33. The SBI-R demonstrated adequate internal consistency with a Cronbach's coefficient of 0.85, which did not increase by more than 0.01 with any single-item removal. This analysis examined factor loadings onto a single factor extracted using the principle components method. Eleven items had factor loadings that exceeded 0.40. SBI-R total scores were significantly correlated with depressive symptoms (r = 0.78, p < 0.001) and CRP (r = 0.47, p < 0.001). Multivariate analyses revealed that inflammation and depressive symptoms explained 67% of SBI-R variance. SIGNIFICANCE OF RESULTS: The SBI-R demonstrated adequate reliability and construct validity in this patient population with metastatic lung cancer. The observed findings suggest that the SBI-R can meaningfully capture the presence of sickness behavior and may facilitate a greater understanding of inflammatory depression.

The desire for death in Portuguese home-care palliative patients: Retrospective analysis of the prevalence and associated factors.

OBJECTIVE: Desire for death (DfD) is a complex and multifactorial dimension of end-of-life experience. We aimed to evaluate the prevalence of DfD and its associations, arising within the setting of a tertiary home-based palliative care (PC) unit. METHOD: Retrospective analysis of all DfD entries registered in our anonymized database from October 2018 to April 2020. RESULTS: Of the 163 patients anonymously registered in our database, 122 met entry criteria; 52% were male, the average age was 69 years old; 85% had malignancies, with a mean performance status (PPS) of 56%. The prevalence of DfD was 20%. No statistical differences were observed between patients with and without DfD regarding sex, age, marital status, religion, social support, prior PC or psychological follow-up, type of diagnosis, presence of advanced directives/living will, time since diagnosis and PC team's follow-up time. Statistically significant associations were found between higher PPS scores and DfD (OR = 0.96; 95% confidence interval (CI) [0.93-0.99]); Edmonton Symptom Assessment Scale scores for drowsiness (OR = 4.05; 95% CI [1.42-11.57]), shortness of breath (OR = 3.35; 95% CI [1.09-10.31]), well-being (OR = 7.64; 95% CI [1.63-35.81]). DfD was associated with being depressed (OR = 19.24; 95% CI [3.09-+inf]); feeling anxious (OR = 11.11; 95% CI [2.51-49.29]); HADS anxiety subscale ≥11 (OR = 25.0; 95% CI [2.10-298.29]); will-to-live (OR = 39.53; 95% CI [4.85-321.96]). Patients feeling a burden were more likely to desire death (OR = 14.67; 95% CI [1.85-116.17]), as well as those who were not adapted to the disease (OR = 4.08; 95% CI [1.30-12.84]). In multivariate regression analyses predicting DfD, three independent factors emerged: higher PPS scores were associated with no DfD (aOR = 0.95; 95% CI [0.91-0.99]), while the sense of being a burden (aOR = 12.82; 95% CI [1.31-125.16]) and worse well-being (aOR = 7.72; 95% CI [1.26-47.38]) predicted DfD. SIGNIFICANCE OF RESULTS: Prevalence of DfD was 20% and consistent with previous Portuguese evidence on DfD in PC inpatients. Both physical and psychosocial factors contribute to a stronger DfD.

Meaning-centered group psychotherapy in Portuguese cancer patients: A pilot exploratory trial.

OBJECTIVE: To describe the feasibility of a meaning-centered group psychotherapy (MCGP) adaptation in a sample of Portuguese cancer patients. METHOD: The study was carried out according to four steps: 1st - Transcultural adaptation and validation (focus groups); 2nd - Preliminary study with MCGP original version (to test its feasibility); 3rd - Adaptation of MCGP original version to a 4-session version (and internal pilot study); and 4th - Pilot exploratory trial (MCGP-4 session version), implemented between January 1, 2018 and December 31, 2019. Inclusion criteria were >18 years, psychological complaints, and difficulty to adapt to cancer. Allocation was according to participants' preference: MCGP vs. care as usual (CAU). Primary outcomes were: MCGP adapted version improved quality of life (QoL) and spiritual well-being; secondary outcomes were improvement of depression, anxiety, and distress. Assessments were done at baseline (T1) and 1 month after (T2), with self-report socio-demographic and clinical questionnaires, Distress Thermometer (DT), McGill Quality of Life Questionnaire (MQOL), Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being Scale (FACIT-Sp-12), Hospital Anxiety and Depression Scale, and its subscales (HADS - HADS-D, HADS-A). RESULTS: In the 1st step, and through focus groups, the manual was reformulated and tested. The preliminary study (2nd step) with MCGP original version showed a high number of dropouts which could jeopardize the study and, after reframing the sessions content, MCGP was adapted to a 4-session version, and its feasibility was tested by an internal pilot study (3rd step). The pilot exploratory trial (4th step) had 91 participants. Most socio-demographic and clinical characteristics between the groups (51: MCGP; 40: CAU) had no statistically significant differences. A comparison between the two groups at T2 showed that the MCGP group scored significantly higher in the general (U = 552.00, P < 0.001), and existential (U = 727.50, P = 0.018) domains and total score (U = 717.50, P = 0.015) of QoL, and CAU presented statistical higher levels in DT (U = 608.50, P = 0.001). Comparing the groups between T1 and T2, the MCGP group had a statistically significant improvement in the general (Z = -3.67, P < 0.001) and psychosocial (Z = -2.89, P = 0.004) domains and total score (Z = -2.71, P = 0.007) of QoL, and a statistically significant decrease in DT (Z = -2.40, P = 0.016). In terms of group effects, the MCGP group presented increased general (b = 1.42, P < 0.001, η2p = 0.179), and support (b = 0.80, P = 0.045, η2p = 0.048) domains and total score (b = 0.81, P = 0.013, η2p = 0.073) of QoL (small to elevated dimensions), and decreased levels of depression (b = -1.14, P = 0.044, η2p = 0.048), and distress (b = -1.38, P = 0.001, η2p = 0.127) (small to medium dimensions), compared with CAU. At T2, participants who attended ≥3 sessions (n = 38) had a statistically significant higher score in the general domain (U = 130.50, P = 0.009) of QoL, comparing with those who attended 1 or 2 sessions (n = 13). SIGNIFICANCE OF RESULTS: This study supports the benefits of an MCGP adapted version in improving QoL and psychologic well-being. More studies are necessary to address the limitations of this pilot exploratory trial, as its small sample size.

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

BACKGROUND: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. METHODS: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. FINDINGS: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. INTERPRETATION: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. FUNDING: National Institute of Nursing Research.

Tumor Mutation Burden and Depression in Lung Cancer: Association With Inflammation.

BACKGROUND: Patients with lung cancer with greater systemic inflammation have higher rates of depression. Tumor mutation burden (TMB) predicts immunotherapy response in patients with lung cancer and is associated with intratumoral inflammation, which may contribute to systemic inflammation and depression. This study evaluated whether higher TMB was associated with increased depression and systemic inflammation in patients with lung cancer. PATIENTS AND METHODS: Patients with metastatic lung cancers were evaluated for depression severity using the Hospital Anxiety and Depression Scale. TMB was measured using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Inflammation was evaluated using C-reactive protein (CRP) level and neutrophil-to-lymphocyte ratio (NLR). RESULTS: A total of 96 patients with adequate TMB testing were evaluated. The average number of mutations (TMB) was 10.8 (SD, 10.9). A total of 19% of patients endorsed clinically significant depression symptoms. TMB was significantly correlated with depression severity (r = 0.34; P=.001) and NLR (r = 0.37; P=.002) but not CRP level (r = 0.19; P=.07). TMB was also higher in patients receiving chemotherapy (mean, 12.0) and immunotherapy (mean, 14.4) versus targeted therapy (mean, 4.8). A multivariate model found that TMB (ß = 0.30; P=.01) and CRP level (ß = 0.31; P=.01) were independently associated with depression; there was no significant interaction effect of TMB × CRP and depression. A similar multivariate model showed no independent effect for NLR and depression (ß = 0.16; P=.17) after accounting for TMB. CONCLUSIONS: These data provide evidence for biologic depression risk in patients with lung cancer who have high levels of TMB. The underlying mechanism of the association is not clearly related to inflammation but warrants further analysis to broadly elucidate the mechanism of biologically derived depression in cancer.

Long-term efficacy of meaning-centered group psychotherapy for cancer survivors: 2-Year follow-up results of a randomized controlled trial.

OBJECTIVE: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) is an effective intervention to improve personal meaning, psychological well-being, and depressive symptoms until 6 months after the intervention. In this study, the long-term effects of MCGP-CS (i.e., at 1- and 2-year follow-up) on meaning, psychological well-being and posttraumatic growth were assessed, in comparison to supportive group psychotherapy (SGP) and care as usual (CAU). METHODS: Cancer survivors (n = 170) were randomized into MCGP-CS, SGP, or CAU. Assessments were scheduled at baseline, 1 week, 3 months, 6 months, 1 year, and 2 years postintervention. Outcome measures were the Personal Meaning Profile, Ryff's Scales of Psychological Well-Being (SPWB), the Posttraumatic Growth Inventory, and their subscales. Linear mixed models (LMM) were used and results were both reported on an intention-to-treat (ITT) basis, as well as for intervention completers only. RESULTS: LMM and post hoc analyses with Bonferroni correction revealed that MCGP-CS participants reported more improvement on positive relations (subscale of SPWB) than CAU participants of 2-year postintervention (ITT analysis, Cohen's d = .82). Completers also reported more personal growth (subscale of SPWB) after MCGP-CS than after SGP 1-year postintervention (Cohen's d = .94). No long-term effects were found on the other outcome measures. CONCLUSIONS: In the 2 years after MCGP-CS, the short-term significant effects on personal meaning and most positive effects related to psychological well-being faded. However, MCGP-CS had a long-term positive effect on positive relations with others and on survivors' sense of personal growth. TRIAL REGISTRATION: Netherlands Trial Register: NTR3571.

Depression and Inflammation in Patients With Lung Cancer: A Comparative Analysis of Acute Phase Reactant Inflammatory Markers.

BACKGROUND: Depression and inflammation are intertwined, which is particularly relevant for patients with lung cancer who have an abundance of inflammation and experience depression. Acute phase reactants (APRs), albumin and C-reactive protein (CRP), are easily interpretable indirect markers of inflammation that have never been concomitantly compared with depression. Inflammation increases CRP (positive APR) and decreases albumin (negative APR). We hypothesize that albumin will be similarly associated with depression, thereby helping to inform the diagnosis of inflammatory depression. OBJECTIVE: Compares the relationship between depression and representative positive and negative acute phase reactants in patients with metastatic lung cancer. METHODS: Patients (n = 109) with metastatic lung cancer were evaluated for depression using the Hospital Anxiety and Depression Scale. Inflammation as measured by positive (CRP) and negative (albumin) APRs along with demographic and treatment variables were analyzed for associations with depression. RESULTS: Depression was associated with lower albumin (r = -0.35, P < 0.001), higher CRP (r = 0.47, P < 0.001), and the CRP/albumin ratio (r = 0.45, P < 0.001). Hierarchical linear regression modeling found that albumin was associated with depression when controlling for demographics, disease, and treatment types (ß = -0.28, P = 0.01). When both APRs were in the model, only CRP predicted depression (ß = 0.31, P = 0.01), and albumin did not moderate CRP and depression. CRP/albumin ratio did not add to understanding depression variability, but patients with both low albumin and high CRP had particularly severe depression. CONCLUSION: Albumin is associated with depression but not to a greater extent than CRP. The coupling of lower albumin and higher CRP describes more severe depression. Positive and negative APRs may form a distinct biologic signature to help identify patients with inflammatory depression in the lung cancer setting.

A mixed methods analysis of patients' advance care planning values in outpatient oncology: Person-Centered Oncologic Care and Choices (P-COCC).

PURPOSE: Person-Centered Oncologic Care and Choices (P-COCC) combines an advance care planning (ACP) value-focused patient interview with a care goal video decision aid. Our randomized study showed that P-COCC was acceptable but increased participant distress, compared with video-alone and usual care study arms. This mixed methods approach explores the ACP values in the P-COCC arm and their relationship to the distress phenomenon. METHODS: Qualitative thematic analysis of the 46 audio-recorded P-COCC interview transcripts with advanced gastrointestinal cancer patients was performed by multiple reviewers. Quantitative (Likert scale) changes in ACP values were compared across study arms. ACP themes and value change were analyzed in participants with increased distress. RESULTS: Transcript analysis resulted in thematic saturation and identified eight distinct themes on ACP values relating to end-of-life wishes, communication needs, and psychosocial supports. Of 98 participants (33 P-COCC, 43 videos, 22 usual care) who completed the change in value measure, there was no difference detected with P-COCC compared with either video (p = 0.052) or usual care (p = 0.105) arms alone, but P-COCC led to a frequency distribution of more change in personal values compared with the other study arms combined (p = 0.043). Among the subset of P-COCC participants with increased distress, there was no statistical relationship with change in values. CONCLUSIONS: The ACP paradigm P-COCC both informs and supports patients in individualized, value-based decision-making. Distress is not associated with changes in ACP values and may be a necessary, at least transient, byproduct of discussing sensitive but pertinent topics about end-of-life medical care.

Regret and unfinished business in parents bereaved by cancer: A mixed methods study.

BACKGROUND: Prior research has demonstrated that the presence of regret and unfinished business is associated with poorer adjustment in bereavement. Though there is a growing literature on these constructs among caregivers of adult patients, the literature on regret and unfinished business in bereaved parents has been limited. AIM: The aim of this study was to examine regret and unfinished business in parents bereaved by cancer, as well as their associations with caregiving experiences and prolonged grief. DESIGN: This was a cross-sectional mixed methods study that utilized self-report questionnaires with open-ended items. SETTING/PARTICIPANTS: The multisite study took place at a tertiary cancer hospital and pediatric cancer clinical research institution. Participants were 118 parents (mothers = 82, fathers = 36) who lost a child aged 6 months to 25 years to cancer between 6 months and 6 years prior. RESULTS: Results showed that 73% of the parents endorsed regret and 33% endorsed unfinished business, both of which were more common among mothers than fathers (p ⩽ 0.05). Parents were on average moderately distressed by their regrets and unfinished business, and both regret-related and unfinished business-related distress were associated with distress while caregiving and prolonged grief symptoms. CONCLUSION: Findings have implications for how providers work with families, including increasing treatment decision-making support, supporting parents in speaking to their child about illness, and, in bereavement, validating choices made. Grief interventions that use cognitive-behavioral and meaning-centered approaches may be particularly beneficial.

Process of therapeutic changes in Meaning-Centered Group Psychotherapy adapted to the Portuguese language: A narrative analysis.

OBJECTIVE: The aim was to understand the processes of therapeutic changes in Meaning-Centered Group Psychotherapy (MCGP) in a Portuguese sample. METHOD: Adult cancer patients with distress motivated to participate in MCGP were identified; descriptive and narrative analyses were performed on the session content. RESULTS: The sample had 24 participants (mean age: 63.43 years); the majority were females (75%), with a median academic degree (54%). Breast cancer was most frequent (67%) at the localized stage (71%). The narrative analysis defined seven categories according to the MCGP themes. In "Moments with Meaning (MwM)," the most relevant dimensions were related to interpersonal relations, the moment of diagnosis, and personal achievements. This category established relations with almost all other categories, as did the category "historical sources of meaning (SoM)." The category "identity before and after cancer diagnosis" was only related to "attitudinal SoM" and "transitions." Historical SoM had two dimensions, "past" and "present and future" legacies, in which prominent topics related to family, childhood, achieved goals, and values to pass to others explored. Attitudinal SoM established relations only with the category "creative SoM," in which "courage" and "responsibility" were the main dimensions, which were also related to "MwM," "historical," and "attitudinal SoM." Experiential SoM, with the main dimension "love," was related to "MwM" and "historical SoM." Transitions only established relations with "historical SoM" and "identity before and after cancer." SIGNIFICANCE OF RESULTS: The findings that "MwM" and "historical SoM" were the categories which established a solid pattern of relations suggest that these are the main psychotherapy topics that can have more influence for the participants; one explanation is that these categories imply a concrete way of thinking, which is easier to understand. This process of therapeutic changes must be integrated in a cultural context, as it is well known to have an impact upon the "meaning" of life.