A Systematic Review and Meta-Analysis of Interventions to Promote Adjuvant Endocrine Therapy Adherence Among Breast Cancer Survivors.

PURPOSE: Adjuvant endocrine therapy (AET) adherence among breast cancer survivors is often suboptimal, leading to higher cancer recurrence and mortality. Intervention studies to promote AET adherence have burgeoned, more than doubling in number since this literature was last reviewed. The current aim is to provide an up-to-date systematic review and meta-analysis of interventions to enhance AET adherence and to identify strengths and limitations of existing interventions to inform future research and clinical care. METHODS: Systematic searches were conducted in three electronic databases. Studies were included in the systematic review if they examined an intervention for promoting AET adherence among breast cancer survivors. Studies were further included in the meta-analyses if they examined a measure of AET adherence (defined as compliance or persistence beyond initiation) and reported (or provided upon request) sufficient information to calculate an effect size. RESULTS: Of 5,045 unique records, 33 unique studies representing 375,951 women met inclusion criteria for the systematic review. Interventions that educated patients about how to manage side effects generally failed to improve AET adherence, whereas policy changes that lowered AET costs consistently improved adherence. Medication reminders, communication, and psychological/coping strategies showed varied efficacy. Of the 33 studies that met the inclusion criteria for the systematic review, 25 studies representing 367,873 women met inclusion criteria for the meta-analysis. The meta-analysis showed statistically significant effects of the adherence interventions overall relative to study-specified control conditions (number of studies [k] = 25; odds ratio, 1.412; 95% CI, 1.183 to 1.682; P = .0001). Subgroup analyses showed that there were no statistically significant differences in effect sizes by study design (randomized controlled trial v other), publication year, directionality of the intervention (unidirectional v bidirectional contact), or intervention type. CONCLUSION: To our knowledge, this is the first known meta-analysis to demonstrate a significant effect for interventions to promote AET adherence. The systematic review revealed that lowering medication costs and a subgroup of psychosocial and reminder interventions showed the most promise, informing future research, policy, and clinical directions.

A randomized controlled trial of a multi-modal palliative care intervention to promote advance care planning and psychological well-being among adults with advanced cancer: study protocol.

BACKGROUND: Up to half of adults with advanced cancer report anxiety or depression symptoms, which can cause avoidance of future planning. We present a study protocol for an innovative, remotely-delivered, acceptance-based, multi-modal palliative care intervention that addresses advance care planning (ACP) and unmet psychological needs commonly experienced by adults with metastatic cancer. METHODS: A two-armed, prospective randomized controlled trial (RCT) randomizes 240 adults with Stage IV (and select Stage III) solid tumor cancer who report moderate to high anxiety or depression symptoms to either the multi-modal intervention or usual care. The intervention comprises five weekly two-hour group sessions (plus a booster session one month later) delivered via video conferencing, with online self-paced modules and check-ins completed between the group sessions. Intervention content is based on Acceptance and Commitment Therapy (ACT), an acceptance, mindfulness, and values-based model. Participants are recruited from a network of community cancer care clinics, with group sessions led by the network's oncology clinical social workers. Participants are assessed at baseline, mid-intervention, post-intervention, and 2-month follow-up. The primary outcome is ACP completion; secondary outcomes include anxiety and depression symptoms, fear of dying, and sense of life meaning. Relationships between anxiety/depression symptoms and ACP will be evaluated cross-sectionally and longitudinally and theory-based putative mediators will be examined. DISCUSSION: Among adults with advanced cancer in community oncology settings, this RCT will provide evidence regarding the efficacy of the group ACT intervention on ACP and psychosocial outcomes as well as examine the relationship between ACP and anxiety/ depression symptoms. This trial aims to advance palliative care science and inform clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov NCT04773639 on February 26, 2021.

A mixed-methods study of the technical feasibility and patient acceptability of a real-time adherence monitor in breast cancer survivors taking adjuvant endocrine therapy.

PURPOSE: Oral anti-cancer medications are increasingly common and endocrine therapies represent the most common oral anti-cancer medications in breast cancer. Adjuvant endocrine therapies reduce the likelihood of recurrence and mortality in the approximately 80% of women diagnosed with hormone-receptor-positive breast cancer, thus rendering adherence essential. Real-time medication adherence monitors, such as the Wisepill electronic pillbox, transmit adherence data remotely, allowing for early intervention for non-adherence. However, their feasibility and acceptability have yet to be examined among breast cancer survivors taking endocrine therapies. METHODS: This study presents quantitative patient-report and technical support data and qualitative patient acceptability data on Wisepill, a common real-time adherence monitor, among 88 breast cancer survivors prescribed adjuvant endocrine therapy. RESULTS: This mixed-methods study of a common real-time adherence monitor, among the first in breast cancer survivors taking adjuvant endocrine therapy, demonstrates its technical feasibility and patient acceptability. CONCLUSION: The use of wireless medication monitors that transmit real-time adherence data is uniquely promising for maximizing the benefits of adjuvant endocrine therapy by allowing for continuous tracking, ongoing communication with oncologic or research teams, and early intervention. This study demonstrates the feasibility and patient acceptability of one such real-time adherence monitor.

Randomized Controlled Pilot Trial of a Low-Touch Remotely-Delivered Values Intervention to Promote Adherence to Adjuvant Endocrine Therapy Among Breast Cancer Survivors.

BACKGROUND: Oral anti-cancer treatments such as adjuvant endocrine therapies (AET) for breast cancer survivors are commonly used but adherence is a challenge. Few low-touch, scalable interventions exist to increase ET adherence. PURPOSE: To evaluate the acceptability, feasibility, and initial efficacy of a low-touch, remotely-delivered values plus AET education intervention (REACH) to promote AET adherence. METHODS: A mixed-methods trial randomized 88 breast cancer survivors 1:1 to REACH or Education alone. Wisepill real-time electronic adherence monitoring tracked monthly AET adherence during a 1-month baseline through 6-month follow-up (FU) (primary outcome). Patient-reported outcomes were evaluated through 3- and 6-month FU (secondary). Multiple indices of intervention feasibility and acceptability were evaluated. Qualitative exit interviews (n = 38) further assessed participants' perceptions of feasibility/acceptability and recommendations for intervention adaptation. RESULTS: The trial showed strong feasibility and acceptability, with an eligible-to-enrolled rate of 85%, 100% completion of the main intervention sessions, and "good" intervention satisfaction ratings on average. For Wisepill-assessed AET adherence, REACH outperformed Education for Month 1 of FU (p = .027) and not thereafter. Participants in REACH maintained high adherence until Month 4 of FU, whereas in Education, adherence declined significantly in Month 1. Conditions did not differ in self-reported adherence, positive affective attitudes, future intentions, or necessity beliefs. REACH trended toward less negative AET attitudes than Education at 3-month FU (p = .057) reflecting improvement in REACH (p = .004) but not Education (p = .809). Exploratory moderator analyses showed that average to highly positive baseline AET affective attitudes and oncologist-patient communication each predicted higher adherence following REACH than Education; low levels did not. Participants identified recommendations to strengthen the interventions. CONCLUSIONS: REACH, a low-touch values intervention, showed good feasibility and acceptability, and initial promise in improving objectively-assessed AET adherence among breast cancer survivors (relative to education alone). Future research should target improving REACH's tailoring and endurance.

Randomized trial of acceptance and commitment therapy for anxious cancer survivors in community clinics: Outcomes and moderators.

OBJECTIVE: Anxiety symptoms are common among cancer survivors. This study evaluated whether an acceptance-based group intervention delivered by social workers in community oncology clinics improved anxiety and related symptoms, and healthcare use, relative to enhanced usual care (EUC). METHOD: This multi-site trial included 135 survivors of various cancers with moderate to high anxiety about cancer/survivorship, 1.5-24 months after treatment. Participants were randomized 1:1 to a 7-session acceptance and commitment therapy (ACT)-based group (Valued Living) or EUC (access to onsite supportive care plus resource list). Questionnaires were administered at baseline, 1, 2, 5, and 8 months post-randomization, diagnostic interviews at baseline, 2, and 8 months, and healthcare use tracked throughout. Outcomes included anxiety symptoms (primary), related symptoms, and healthcare use. Putative moderators included age, anxiety, and avoidance. RESULTS: In intent-to-treat comparisons to EUC, Valued Living (VL) showed a nonsignificant pattern of greater improvement on anxiety symptoms (p = .08), improved significantly more on cancer-related post-traumatic stress (p = .002), fear of recurrence (p = .003), and energy/fatigue (p = .02), and missed significantly fewer medical appointments (p < .05). Conditions improved similarly on depressive symptoms, sense of meaning, and most severe anxiety or depressive disorder. Effects were moderated: VL participants with higher baseline anxiety or avoidance (+1SD) improved more on anxiety, meaning (ps ≤ .01), and disorder severity (p = .05) than their EUC counterparts. CONCLUSIONS: An acceptance-based group intervention delivered in community oncology clinics enhanced psychological recovery and energy levels, and reduced missed medical appointments for anxious cancer survivors, with stronger effects for more distressed participants. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Presence and predictors of anxiety disorder onset following cancer diagnosis among anxious cancer survivors.

PURPOSE: Despite cancer survivors' frequent endorsement of anxiety symptoms, assessing the full range of anxiety disorders (AD), their timing of onset relative to cancer diagnosis, co-morbidity with mood disorder, and predictors of post-cancer onset, is rare or absent to date. This study provides a step toward addressing these gaps. METHODS: Cancer survivors at re-entry after primary treatment completion who screened positively for anxiety symptoms (N = 133) and sought care through an intervention trial completed standardized diagnostic interviews, dimensional assessment of disorder severity, and timing of disorder onset relative to cancer diagnosis. We evaluated sociodemographic and medical predictors of developing a first AD after cancer diagnosis. RESULTS: Most ADs began after cancer diagnosis (58%); for 68% of affected patients, this represented their first AD episode. The most common was generalized anxiety disorder (GAD; 41%), where "cancer-focused GAD" was distinguished from "typical GAD"; the next most common were specific phobia (14%) and social anxiety disorder (13%). A minority (31%) of ADs were comorbid with major depression. Relative to having no AD, experiencing more lingering treatment side effects predicted developing a first AD after cancer diagnosis. Relative to having an AD that began before cancer diagnosis, reporting a higher cancer stage predicted developing a first AD after diagnosis. CONCLUSIONS: Cancer survivors at re-entry seeking care for anxiety symptoms manifested a broad range of ADs which most commonly developed after cancer diagnosis and were prompted by the experience of cancer. Such disorders represent an unusually late-life, cancer-linked etiology that warrants further investigation and clinical attention.

A randomized controlled trial of a group acceptance-based intervention for cancer survivors experiencing anxiety at re-entry ('Valued Living'): study protocol.

BACKGROUND: Anxiety is a common concern of cancer survivors during the transition from active cancer treatment to cancer survivorship (the re-entry phase). This paper presents the study protocol for a novel group-based behavioral intervention to improve mental health, well-being, and medical use outcomes among anxious cancer survivors at re-entry. METHODS/DESIGN: This two-armed, prospective randomized controlled trial will randomize a minimum of 100 re-entry-phase cancer survivors with moderate to high anxiety to the intervention or a usual care control condition. The intervention is delivered in a group format over 7 weeks; content is based on Acceptance and Commitment Therapy (ACT), an acceptance, mindfulness, and values-based intervention. Participants will be recruited from community cancer care centers and the intervention will be led by the onsite clinical social workers. Participants will be assessed at baseline, mid-intervention, post-intervention, and 3- and 6-month follow-up. ACT participants will complete process measures before the beginning of group sessions 2, 4, and 6; all participants will complete the process measures during the regular assessments. The primary outcome is anxiety symptoms; secondary outcomes include anxiety disorder severity, fear of recurrence, depressive symptoms, cancer-related trauma symptoms, sense of life meaning, vitality/fatigue, and medical utilization. DISCUSSION: This clinical trial will provide valuable evidence regarding the efficacy of the group ACT intervention in community oncology settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT02550925 .