A nurse-led intervention for fear of cancer progression in advanced cancer: A pilot feasibility study

Abstract

Purpose:

To assess the feasibility, acceptability, and preliminary effects of a nurse-led Intervention for managing fear of cancer progression in advanced cancer patients.

Methods:

A single group mixed methods study was conducted in patients with stage III or IV gynecologic or lung cancer (n=31) with dysfunctional levels of fear of progression or distress. The intervention consisted of seven videoconferencing sessions with skills practice. Feasibility measures included enrollment rate, attendance, attrition, and home practice adherence. Acceptability was based on exit interview responses. Content analysis was used to analyze the qualitative data. Participants completed quantitative questionnaires assessing fear of progression and secondary outcomes at baseline, eight, and 12 weeks. Linear mixed model analysis was used to assess changes in outcome measures.

Results:

The average enrollment rate was seven participants/month over 4.5 months. Participants attended a mean of 5.3 of seven sessions. Attrition rate was 30%. The analysis showed improvements over time in fear of progression and exploratory outcomes. Participants reported feeling calmer and more focused. The skills practice helped to manage anxiety and fears. Themes included: Struggling with fears, Refocusing the fears, and Realizing/reaffirming what is important in life. The most beneficial components included the values clarification exercise, detached mindfulness and worry postponement practices.

Conclusion:

The intervention was acceptable; most feasibility criteria were met. Preliminary data suggest that the intervention reduced fear of progression and improved secondary outcomes. The intervention required a significant time commitment by participants, which may have contributed to increased attrition. To decrease burden, we will shorten the intervention

Introduction

Approximately 49% of cancer survivors overall and up to 70% of patients with advanced cancer experience moderate to high levels of fear of cancer progression/recurrence/(FOP) (Butow et al., 2018). FOP is defined as fear or worry that the cancer will return or progress (Lebel et al., 2016). Patients with FOP have intrusive thoughts about cancer, unhelpful coping behaviors, and difficulty making future plans. Although some degree of FOP is normal, excessive levels adversely affect quality of life and health care costs. For example, patients may request additional clinic visits or surveillance testing or frequently contact their providers about minor symptoms (Lebel et al., 2017; Lebel et al., 2013). Busy clinicians may be uncertain about how to respond to emotional concerns (Butow et al., 2018; Thewes et al., 2014). Recent data suggest that FOP is an even more pressing concern in advanced cancer (AC). Survey data from 56 ovarian cancer survivors revealed that those with multiple recurrences experienced greater distress and worry their cancer would get worse (Lutgendorf et al., 2017). In a survey of 89 lung cancer survivors, anxiety and recurrence concerns were among the most frequent unmet psychological needs (Giuliani et al., 2016). Further, supportive care services remain underutilized (Giuliani et al., 2016; Mosher et al., 2013). With treatment advances, AC patients are living longer, often with remitting and recurring disease. From 2002 to 2017, the lung cancer death rate dropped by 51% and 26% among males and females respectively (Siegel et al., 2020). For ovarian cancer patients, survival rates have increased. Those with recurrent cervical and endometrial cancers now have increased treatment options (Basu et al., 2018; Cantrell and Duska, 2018). Extended treatment courses and frequent monitoring can contribute to increased vulnerability to FOP (Butow et al., 2017; Thewes et al., 2017). Patients report “living in limbo,” isolation, and uncertainty about how to access support services (Park et al., 2020).

Several interventions have been developed to treat FOP; however most have been tested in patients treated with curative intent (Butow et al., 2018). In palliative care settings, psychosocial treatments are underused. Tailored interventions are needed to address distress and emotional support needs in advanced cancer patients (Plumb Vilardaga et al., 2020; Wang et al., 2018). A meta-analysis of “mind-body” interventions assessed the efficacy of interventions ranging from traditional Chinese medicine to cognitive behavior therapies (CBT), concluding that interventions had a small to moderate effect on FOP (Hall et al., 2018). These results were confirmed in a comprehensive meta-analysis of psychological interventions for FOP (Tauber et al., 2019). Some studies used traditional CBT where the beliefs about FOP are challenged; others used contemporary CBT, targeting the process of worry and rumination, not thought content. FOP studies using contemporary CBTs were significantly more efficacious than traditional CBTs (Tauber et al., 2019). Identified gaps included a focus on early stage disease. Further, most interventionists were psychologists. In a review of FOP interventions administered by non-mental health professionals, Liu et al. identified four nurse-led interventions including two small randomized controlled trials (RCTs) (Liu et al., 2019). One was a communication intervention encouraging patients to discuss their fears with the oncologist (Shields et al., 2010) and the other incorporated behavioral modification, relaxation strategies, and coping education (Humphris and Rogers, 2012).

Most FOP interventions are resource intensive and administered by qualified psychologists (Butow et al., 2017). Barriers exist to accessing interventions requiring psychologists. Many community and rural clinics may not have access to psychologists (Fitch, 2019). In academic sites, psychology services often prioritize those with major psychiatric conditions. Alternative delivery models are needed to increase access to psychosocial services (van de Wal et al., 2017). The use of a videoconferencing approach can increase access to care for AC patients (Brebach et al., 2016; Plumb Vilardaga et al., 2020). According to a review of uptake and adherence for psychological interventions, interventions provided by nurses were more often accepted than those by psychologists (Brebach et al., 2016). Since nurses provide much of the emotional support for patients and family members, they may be uniquely positioned to help patients manage FOP (Dawson et al., 2016; Wittenberg et al., 2018). The study aims were to: (1) assess the feasibility and acceptability of a nurse-led intervention for managing FOP and distress in patients with advanced cancer; and (2) obtain preliminary data on the effects on FOP (primary), cancer-related distress, anxiety, depression, metacognitions, and mindfulness (secondary).

Methods

A single-group mixed methods study was conducted to assess the feasibility and preliminary effects of a nurse-led FOP intervention called “Day by Day” (DBD) in patients with stage III or IV GYN or lung cancer. The study was approved by the Institutional Review Board. The intervention consisted of seven sessions delivered over eight weeks, including an in-person assessment followed by six Zoom conferencing sessions. Feasibility measures included enrollment rate, attrition, attendance, and home practice adherence. The participants completed self-report questionnaires assessing FOP and other outcomes at baseline, eight, and 12 weeks. An exit interview was conducted to assess acceptability and experience with DBD. A convergent-parallel mixed methods approach was used to better understand participants’ experience and symptom outcomes (Creswell, 2014). Conventional content analysis was used to analyze the interview data (Hsieh and Shannon, 2005).

Framework and Intervention Design

The intervention was adapted from the Conquer Fear (CF) intervention, which has been rigorously pilot-tested and shown to have greater efficacy than an attention control relaxation training arm in a large RCT of patients with early stage cancer (Butow et al., 2017; Smith et al., 2015). CF is based on a contemporary cognitive-processing model from Metacognitive Therapy (MCT) and Acceptance and Commitment therapy (ACT) principles (Fardell et al., 2016). In this model worry about cancer is considered normal; however, for some patients, these worries create a vicious cycle that exacerbates FOP (Sharpe et al., 2017). Beliefs about the benefits or harms of worry lead people to get caught up in a cycle of worrying and hypervigilance to physical symptoms, triggering intrusive thoughts and rumination. MCT addresses unhelpful metacognitions or beliefs about worry (Wells, 2008). Preoccupation with cancer progression makes it hard for people to engage in valued activities. ACT- based components include a focus on living according to one’s values and setting goals consistent with identified values (Fashler et al., 2018).

Adaptations to CF were made to shorten each session and to reflect the increased risk of progression in advanced cancer. The manual, case studies, and education content were revised to be relevant to advanced cancer. The study team participated in a 2-day curriculum training workshop. The advanced practice nurses (APRNs) followed a training manual and completed session checklists. Checklists and 15% of randomly selected session audiotapes were reviewed with feedback given to maintain fidelity. Both self-reported and independent review indicated 89% protocol adherence.

The intervention consisted of seven nurse-led, one-to-one sessions delivered over eight weeks (Table 1) (Reb et al., 2020). Sessions focused on values clarification (Ciarrochi and Bailey, 2009), worry management, modifying unhelpful beliefs about worry, threat monitoring (unhelpful coping) behaviors, and surveillance/lifestyle education (Butow et al., 2013). Worry management skills included attention training (Wells, 1990), detached mindfulness (Wells, 2005), and worry postponement (Wells, 2008). Experiential exercises and home practice reinforced session content.

Table 1.

Day By Day Session Content

Session	Objectives	Content
1	Orientation to Treatment Model	Use of metaphors to explain the model and goals of treatment.
	Psychosocial Assessment	Focuses on fear of cancer progression (FOP), factors contributing to the development of FOP, and its impact on thoughts and behaviors.
		Discuss existential changes brought about by a cancer diagnosis
2	Discuss potential vulnerability factors.	Discuss impact of past experiences, losses, stressors that contribute to FOP (Butow et al., 2018)
	Introduce exercise to identify life values	Card Sort Exercise-58 value statement cards used to identify important values (Ciarrochi & Bailey, 2009)
3	Values clarification & goal development (Fashler et al., 2018).	Review card sort exercise; help participant clarify non-negotiable values and set goals to assist in living in accordance with their values.
		Complete Values/Goals/Action table.
	Attention Training Techniques (ATT) (Wells, 1990)	Participant listens to flash drive with audio recording of an array of sounds. Participant focus attention on an individual sound, then switch attention to listen to several sounds simultaneously. The aim is to teach patients to not eliminate thoughts but to give them less attention when they occur. This practice helps to alter habitual responses to intrusive thoughts (Wells, 1990).
4	Worry Management Techniques  • Detached Mindfulness	Detached Mindfulness teaches participants to reflect on how they think and understand that their thoughts are separate from themselves. Promotes detachment from engagement with troubling thoughts (Wells, 2005)
	• Worry Postponement	Participants are taught to notice thoughts/worries but delay processing them until a designated time during the day. It helps to challenge beliefs that worry is not controllable and promotes disengagement from judgements about worry (Wells, 2008)
5	Introduction to threat monitoring and avoidance.	Identify excessive behaviors that contribute to increased FOP; e.g. worry about vague symptoms; requests for unnecessary scans. Introduce unhelpful beliefs about worry that underlie threat monitoring behaviors. Develop written agreement if indicated.
	Education about follow-up care and surveillance guidelines	Discuss evidence-based guidelines for follow up surveillance including symptoms to report.
	Introduce healthy lifestyle behaviors and resources.	Discuss healthy lifestyle behaviors tailored to participant.
6	Metacognitive beliefs underlying excessive threat monitoring (Fardell et al., 2016)	Review Metacognitions about Health Anxiety Questionnaire (Bailey & Wells, 2015). Assess beliefs about worry. Use strategies to challenge unhelpful beliefs (positive, negative beliefs or belief that worry is uncontrollable).
	Review recommendations for healthy living tailored to patient.	Review healthy lifestyle strategy handouts and resources
7	Review changes in FOP symptoms achieved over the course of treatment. Address any residual unhelpful metacognitions.	Review Fear of Progression-SF Questionnaire
	Relapse prevention strategies.	Identify comprehensive list of triggers. Develop new plans for responding to future triggers using skills learned in the program. Use “What If” exercise to encourage participant to think about how they would respond to potential cancer progression.
	Review progress on values-based goal setting.	Review Values/Goals/Actions table. Identify and troubleshoot any barriers to working toward goals.

Note: Based on Conquer fear: protocol of a randomized controlled trial of a psychological Intervention to reduce fear of cancer recurrence (Butow et al., 2013) and Conquer Fear Therapist Treatment Manual, The FCR Intervention Writing Team (Butow, Thewes, Gilchrist & Turner).

Participants and Setting

The study was conducted at a free-standing National Cancer Institute designated comprehensive cancer center in Southern California. Patients with stage III or IV GYN or lung cancer were eligible if they were at least three months from initial diagnosis with scores in the dysfunctional range for FOP (≥34 on the FOP-SF) or cancer-specific distress (≥24 on the IES-R). Exclusion criteria were ongoing psychiatric treatment, hospice-enrolled, or non-English speaking. Patients were recruited from the medical oncology outpatient clinics.

Outcome Measures

Aim 1.

Feasibility measures included enrollment rate, attrition, attendance, and compliance with home practice. The enrollment goal was accrual of at least 33 patients within nine months. Attrition was considered acceptable if the drop-out rate did not exceed 25% by T2 and 50% by T3. An average of 5 sessions attended and 50% adherence with home practice would indicate high acceptance and feasibility. Acceptability was also assessed qualitatively based on exit interview responses. A structured interview guide included open-ended questions about participants’ experience with DBD. Questions addressed cancer-related symptoms and concerns; intervention content; session delivery, timing and duration; experience with home practice, benefits, challenges, and suggestions for improving the intervention.

Aim 2.

The change over time in FOP (primary outcome), and cancer-related distress, anxiety, depression, metacognitions, and mindfulness (secondary outcomes) was assessed using validated instruments:

Fear of progression-SF (FOP-SF) consists of 12 items pertaining to four subscales of the original 43-item questionnaire: affective reactions; partnership/family; occupation; and loss of autonomy (Hinz et al., 2015; Mehnert et al., 2006). Scores range from 12–60 with higher levels indicating greater FOP (Herschbach et al., 2010a). A cut-off of ≥34 indicates dysfunctional levels (Herschbach et al., 2010a). The FOP-SF has been comprehensively validated in a large sample of breast cancer patients; with reliability α =.87 (Herschbach et al., 2010b). Validity has been demonstrated by correlation with HADS anxiety (r=.65 to .71 and depression (r=.49). In a study with 135 English-speaking patients, the FOP-SF demonstrated high internal consistency (α=0.88) and was correlated with similar constructs (Curran et al., 2020).

Impact of Event Scale-R measures cancer-related distress. It consists of 22-Likert-type scale items assessing intrusion, avoidance, and hyperarousal subscales (Sundin and Horowitz, 2002). Total scores range from 0–88; higher scores indicate greater distress. A score of 24 or greater indicates “clinical distress”. Across a range of studies, it demonstrates good internal consistency: IES intrusion mean α =.86.; IES avoidance mean α =0.82. The IES has been used in several studies with cancer patients and has been found to be sensitive to change in cancer interventions (Butow et al., 2017).

PROMIS-Anxiety 8a measures fear, worry/dread, hyperarousal, and related somatic symptoms (Cella et al., 2010). It consists of eight items scored on a 0–5 response format. Scores are standardized to continuous T scores with a mean of 50 and SD of 10; higher scores reflect higher distress. PROMIS T score thresholds for anxiety are: <55 normal; 55–64 mild; 65–74 moderate; ≥75 severe (Cella et al., 2014). Psychometrics were established in a large sample of patients with chronic illness including cancer. On average, reliability was > .89. Construct validity was demonstrated using the anxiety scale from the Mood and Anxiety Questionnaire as the convergent measure (r=.80) and the CES-D as the divergent measure (r=.75) (Cella et al., 2010).

Patient Health Questionnaire (PHQ-9) is a nine-item depression screening tool. It includes two major symptom domains: affective and somatic. It is rated on a 0 (not at all) to 3 (nearly every day) scale. Items are summed and a score of 10 or greater indicates clinically significant symptoms of depression. Scores of 0–4, 5–9, 10-–14, and ≥15 represent minimal, mild, moderate, and severe levels of symptom burden, respectively. The PHQ-9 is well-validated and widely used in medical settings. The scale showed good internal consistency (a =.86–.89) and sensitivity to change (Kroenke et al., 2010).

Metacognitions questionnaire (MCQ-30) assesses beliefs about worry. It consists 30 items categorized in five subscales: positive beliefs, negative beliefs, cognitive confidence, need to control thoughts, 0 and cognitive self-consciousness (e.g. focusing attention on thought processes). Total scores range from 30–120; higher scores indicate more dysfunctional metacognitions. Internal consistency for total score was α =.93 and ranged from .72–.93 for the subscale scores (Wells and Cartwright-Hatton, 2004). It has been validated in cancer patients and showed good convergent validity (Cook et al., 2014).

The Memorial Symptom Assessment Scale (MSAS) A modified version of the 32-item MSAS was used to evaluate the symptom occurrence, severity, and distress. Symptom severity is rated on a four-point Likert-type scale (1=slight) to 4=very much). Distress is rated on a 0–4 Likert-type scale ranging from not at all (0) to very much (4). The total MSAS score is the average of the scores of all 32 symptoms; higher scores indicate greater severity and distress. The physical symptom subscale is the average of the severity and distress for 12 prevalent physical symptoms. The psychological symptom subscale is the average of the severity and distress for six prevalent psychological symptoms. For high prevalence symptoms, Cronbach alpha coefficients for the subscales were .83 (psychologic), .and .88 (physical) (Portenoy et al., 1994).

Five Facet Mindfulness Questionnaire (FFMQ-15) assesses 5 facets of overall mindfulness: observing, describing, acting with awareness, non-reactivity to inner experience, and non-judging of inner experience (Baer et al., 2006). Items are rated on a 5-point Likert-type scale ranging from 1 (never/ rarely true) to 5 (very often). Three items comprise each subscale; subscale scores range from 3–15. Higher scores indicate greater engagement with mindfulness skills. The total FFMQ score is calculated by summing four subscale scores (excluding Observing subscale). Internal consistency is adequate with α =.66- .83 for the four subscales. Convergent validity was demonstrated by significant negative correlations with depression and rumination (Gu et al., 2016). The measure is sensitive to change over the course of mindfulness-based cognitive therapy in advanced cancer patients (Chambers et al., 2017).

Procedures

APNs screened medical records and confirmed eligibility with the provider. The research coordinator (RC) or an APRN met with patients to explain procedures and obtain consent. To confirm eligibility, participants completed the FOP-SF and the IES-R. Those not meeting the cut-off criteria were given an NCI booklet and the option to meet with the social worker. Using REDCap platform, participants completed questionnaires at baseline, eight, and 12 weeks and an exit interview. The research team met weekly to review recruitment activities. The team psychologist attended bimonthly meetings to review patients and provide feedback on fidelity. Participants received two $25 gift cards following data collection.

Session Delivery the DBD sessions were delivered weekly over eight weeks. Participants were given instructions and emailed links for zoom videoconferencing sessions. For those without a laptop, tablets with built-in Wi-Fi were provided. Most participants received sessions in their homes (phone or Zoom). Some sessions were delivered in-person following a clinic visit. Using session checklists, APNs documented topics covered, referrals, and homework completion. Participants completed home practice assignments following sessions two through seven. Home practice included values clarification exercises, skills practice, self-assessment questionnaires, and creating a new plan for managing fears and worries. Following session three, participants were asked to practice attention training exercise at least 12 minutes/day and record on weekly practice logs.

Analyses

Statistical analyses were performed using SAS software, version 9.4. Descriptive statistics were calculated to summarize feasibility measures, demographic and clinical characteristics at baseline (T1). Baseline characteristics and outcome measures were compared between those who completed and those who dropped out, using chi square tests for categorical variables and t tests for quantitative variables. Linear Mixed Model (LMM) for repeated-measure design was used to determine the changes in outcome measures across time-points. LMM considers missing data, providing unbiased estimates for data with missing values at random (Gadbury et al., 2003). The model included the time factor, employed compound symmetry covariance structure, and did not adjust for covariates. Post Hoc pairwise comparisons with Tukey adjustment were conducted to test the change in outcomes for each time period. Cohen’s D was used to estimate effect sizes for the changes in outcome measures across time-points (Lakens, 2013).

Two team members independently analyzed the qualitative data using content analysis with an inductive approach (Elo and Kyngas, 2008). Open-ended questions responses were transcribed into a table and categorized according to themes. The researcher used N-Vivo 12 software (QSR International) to identify preliminary categories with supporting quotes. To help identify themes, the number of participants contributing to each response category was tabulated for frequency and response patterns (Sandelowski, 2000). Team members met several times to refine the themes. To address credibility/confirmability, an outside investigator reviewed themes against transcript excerpts. The quantitative and qualitative data were analyzed separately and compared and integrated in the discussion section.

Results

Demographic/Clinical Information

Data collection started in November 2018 and ended in April 2019 (a 4.5-month period). A convenience sample of 31 participants enrolled and completed baseline questionnaires. The majority were female (n=26), Caucasian (n=21), and their median age was 58-year (Table 2). The sample consisted of ovarian (n=8), uterine (n=8) and non-small cell lung cancer (n=15). Twenty participants (64.5%) had experienced a cancer recurrence ($\overline{\mathrm{x}}=2.2$). The median time since initial diagnosis was 44 months (range 10–137). Twenty-one participants (68%) were on active treatment at time of enrollment.

Table 2.

Demographic and Clinical Characteristics at Enrollment

Variable	Total (N = 31) N (%*)
Age
M (SD)	58.9 (10.2)
Mdn (Range)	58.0 (29–76)
Sex
Female	26 (83.9)
Male	5 (16.1)
Race
White	21 (67.7)
Black	1 (3.2)
Asian	4 (12.9)
Middle Eastern	1 (3.2)
Decline to answer	4 (12.9)
Hispanic or Latino
Yes	7 (22.6)
No	22 (71.0)
Decline to answer	2 (6.5)
Education level
Up to high school graduate or equivalency	6 (19.4)
Some college, trade school, or vocational school	11 (35.5)
Bachelor’s degree	8 (25.8)
Graduate or professional degree	6 (19.4)
Employment status
Unemployed	8 (25.8)
Retired	13 (41.9)
Employed full time	7 (22.6)
Employed part time	1 (3.2)
Other job status	2 (6.5)
Marital status
Never married	1 (3.2)
Married/domestic partnered	21 (67.7)
Separated, devoiced, or widowed	9 (29.0)
Annual income, $
<25,000	6 (19.4)
25,000–50,000	2 (6.5)
50,001–100,000	9 (29.0)
>100,000	8 (25.8)
Declined	6 (19.4)
Cigarette smoking status
Never	19 (61.3)
Ever	12 (38.7)
Pack years, M (SD)	13.3 (14.0)
Primary care provider
Yes	24 (77.4)
No	7 (22.6)
Diagnosis
Ovarian cancer	8 (25.8)
Uterine cancer	8 (25.8)
Non-small-cell lung cancer	15 (48.4)
Stage
III	14 (45.2)
IV	17 (54.8)
Prior cancer recurrence	20 (64.5)
No. of recurrence, M (SD)	2.2 (1.1)
Recurrence during the study	5 (16.1)
Local-regional recurrence	2
Distant metastasis recurrence	1
Unknown type	2
Cancer therapy
Received prior to enrollment
Chemotherapy	27 (87.1)
Radiation therapy	15 (48.4)
Surgery	20 (64.5)
Immune therapy	9 (29.0)
Target therapy	14 (45.2)
Active treatment at enrollment	21 (67.7)
Chemotherapy	7
Immunotherapy	5
Target therapy	10
Hormone therapy	1
Months from initial diagnosis to Session 1
M (SD)	51.7 (35.2)
Mdn (range)	44 (10–137)
Comorbidities
M (SD)	2.1 (1.8)
Mdn (range)	2 (0–6)

Abbreviations: M = Mean, Mdn = Median, SD = Standard Deviation.

^*Number in parenthesis is percentage, except where otherwise noted; percentages for each variable may not sum to 100% due to rounding.

Aim 1. Feasibility

Enrollment.

The average enrollment rate was seven participants/month. Of the 99 potentially eligible patients, 51 declined participation (Figure 1). The most common reasons for refusal included “doing well” (n=27), “not wanting to think about it” (n=12) and “not interested” (n=6). Forty-eight patients provided informed consent. Of those, 39 patients met the cut-off criteria and were enrolled.

Figure 1. Patient Flow Chart.

Note: Exit interviews were conducted to assess patients’ experience with the intervention.

Attrition.

Of 39 enrolled participants, eight dropped before completing baseline data. Of the 31 evaluable participants, four dropped out prior to receiving any sessions and six dropped out during the intervention. Of the 10 who dropped out, reasons included “no longer interested/needed (n=3);” lost to follow-up (n=3); referral to psychiatry (n=1); overwhelmed/grief (n=1); family illness (n=1); and death (n=1).

Attendance.

Evaluable participants (n=31) completed a mean of 5.3 of seven sessions (SD= 2.7). Twenty-one (68%) completed all seven sessions; four completed three sessions, and two completed one or two sessions.

Home Practice.

Twenty-six participants (84.5%) reported home practice. Of those, 18 participants (82%) completed all assignments; 2 completed some, and 2 completed none. Seventeen participants (68%) reported attention training practice for at least one week. The median number of weeks practiced was two (range 1–5); with a median practice time of 63 minutes/week (range, 5–840). By week five, only five participants continued to practice attention training.

Sessions.

Of 162 total sessions delivered, 78 (48.1%) were delivered by telephone, 49 (30.1%) by Zoom and 35 (21.6%) in-person. The average duration for session one (intake assessment) was 60.7 minutes (range 25–128) and 49.4 minutes for sessions two through seven (range 21–140).

Aim 2 Exploratory Outcomes

The demographic and clinical factors were similar between those who completed the sessions (n=21) and those who dropped (n=10). Baseline scores for most exploratory outcomes were similar except those who dropped had higher baseline anxiety scores than those who completed the sessions ($\overline{\mathrm{x}}=64.8$, SD 5.3 vs. 56.4, SD 8.8). LMM analyses showed improvements across time for FOP (primary) and all secondary outcome measures (F tests p ≤ 0.004) (Table 3). Compared with baseline, improvement was observed at T2 and T3 for most outcomes except for metacognition score, which was lower only at T3. No significant differences were observed between T2 and T3 for any outcomes. At T2, mean FOP scores and cancer-related distress scores decreased 8 points (SE=1.3) and 19.1 points (SE=2.9) respectively.

Table 3.

Outcomes over time (T1, T2, T3) among 31 participants

Outcome variable	Score range	Least square mean (standard error)a				Mean difference (standard error) between 2 time pointsa,b				Effect size at T2c
		T1	T2	T3	F test p-value	T2-T1	Tukey-adjusted p-value	T3-T1	Tukey-adjusted p-value
FOP-Q-SF	12–60	41.1 (1.3)	33.1 (1.5)	31.3 (1.5)	<0.0001	8.0 (1.3)	<0.0001	9.8 (1.4)	<0.0001	1.3
PROMIS Anxiety- 8ad	37.1–83.1	59.1 (1.5)	52.0 (1.8)	51.4 (1.9)	0.0002	7.1 (1.9)	0.002	7.7 (2.0)	0.001	0.8
PHQ-9	0–27	8.6 (0.9)	3.9 (1.0)	4.2 (1.1)	<0.0001	4.7 (1.0)	<0.0001	4.4 (1.0)	0.0003	0.8
IES-R	0–88	34.9 (2.5)	15.8 (3.0)	16.6 (3.1)	<0.0001	19.1 (2.9)	<0.0001	18.3 (3.0)	<0.0001	1.2
MCQ-30	30–120	53.0 (2.0)	49.4 (2.2)	46.9 (2.2)	0.004	3.6 (1.7)	0.10	6.1 (1.7)	0.003	0.3
FFMQ-15e	12–60	43.9 (1.2)	47.0 (1.3)	47.9 (1.3)	0.001	−3.1 (1.0)	0.02	−4.0 (1.1)	0.002	0.5
MSAS	0–4	0.8 (0.1)	0.5 (0.1)	0.5 (0.1)	0.0002	0.3 (0.1)	0.0009	0.3 (0.1)	0.0007	0.6
Physical	0–4	0.7 (0.1)	0.5 (0.1)	0.5 (0.1)	0.04	0.2 (0.1)	0.06	0.2 (0.1)	0.09	0.4
Psychological	0–4	1.3 (0.1)	0.7 (0.2)	0.7 (0.2)	0.0001	0.6 (0.1)	0.0007	0.6 (0.2)	0.0004	0.7
GDIndex	0–4	1.2 (0.1)	0.8 (0.1)	0.8 (0.1)	0.0008	0.4 (0.1)	0.003	0.4 (0.1)	0.004	0.6

FOP = Fear of Progression, PROMIS-Anxiety (T-score), PHQ-9=Patient Health Questionnaire, IES-R = Impact of Event Scale-Revise (IES-R), MCQ-30 = Metacognitions Questionnaire, FFMQ-15 = Five Facet Mindfulness Questionnaire, MSAS = Memorial Symptom Assessment Scale

FOP-SF, PROMIS-Anxiety-8a, PHQ-9, IES-R, MSAS: higher scores reflect greater distress/symptoms. MCQ-30: Higher scores represent more dysfunctional metacognitions. FFMQ-15: Higher scores reflect greater engagement with mindfulness skills.

^aEstimates from the analyses for repeated measures using Mixed Models that included time variable.

^bMean difference between T2 and T3 was not shown in this table (all Tukey-adjusted p-value ≥ 0.35).

^cAbsolute value of mean difference divided by baseline standard deviation (SD); SDs are 6.4, 8.7, 6.0, 16.3, 11.1, 6.7, 0.5, 0.5, 0.9, and 0.7 for FOP-Q-SF, PROMIS T-score, PHQ-9, IES-R, MCQ-30, FFMQ-15, MSAS: physical, psychological subscales and GDIndex, respectively.

^dPROMIS Anxiety 8a: Scores standardized to continuous T scores with a mean of 50 and SD of 10. T score thresholds are: <55 normal; 55–64 mild; 65–74 moderate; ≥75 severe.

^eExcluded Observing subscale per scoring instructions.

Acceptability (Qualitative Analysis)

Twenty-one participants (n=11 GYN; n=10 lung) completed exit interviews, which were used for the thematic analysis and program evaluation. Participants reported that the intervention helped them to recognize what is important in their lives, identify unhelpful thinking patterns, and learn fear management skills. Three themes emerged from the data: Struggling with fears, refocusing fears, and realizing/reaffirming what is important in life (Table 4).

Table 4.

Qualitative Themes Describing the Process of Managing Fears

Theme	Comments
Struggling with Fears	“I mean it was just a sad, sad thing to find out you have cancer, but the shock and the bargaining and the denial… you can go back and forth in it… And this whole fear of progression fits right in.” “The challenging part is thinking the cancer’s still there… thinking it’s gonna come back, separating those concerns and an outlook to be more positive instead of dwelling.” “I found the whole thing challenging because I had to face maybe being honest and really looking at … my anxiety and where my mind can get to.” “I think I had some fear there that I didn’t- maybe there were things that I didn’t want to see … or address…. I think that’s part of accountability for me of having someone to talk to… I need that accountability sometimes.”
Refocusing the Fears	“There were times when I was kinda stuck- and you (nurse) would give indications of some other participants’ (concerns)… to give me an idea of… a direction to head to.” “I… didn’t work myself up… I waited to hear what the… diagnosis was instead of letting my mind go wander because I had a physical symptom. I detached myself from all of that.” “I gained the mindfulness, calm yourself down, close your eyes, think of the clouds… being able to sit, close my eyes, and just chill- with the clouds has been good for me.” “It gave me the tools and approaches to help me overcome some of the anxiety and worry that I do about certain things”
Realizing/Reaffirming what is important in life	“I didn’t realize how much I loved being around nature… how much it calms me down…. I think that kind of has motivated me… into making sure I’m around nature a little bit more.” “There is hope for me when before I didn’t have that and was just all downhill despair, now I’m thinking positive things in my life and uh… doing them” “I’m thinking of the future right now. And I’m not thinking about dying like I was before. Like I didn’t have any time. I’m dying… it’s like, a freedom from my mind actually from… being locked into that frame of thinking all the time. I would never have got out of that shell to move forward unless I took this course, I believe that because I was so deep in the other way that, uh, I just gave up… But, when I started joining things and doing more and… doing my homework, I was learning all the time and then I- I started to change… I became more positive and I started having hope …. ”

Struggling with Fears.

Prior to the intervention, many participants reported feeling overwhelmed by FOP, resulting in a constant feeling of uneasiness, anxiety, and worry about the future. One stated:

“I was thinking about everything, I’m going to die. My child, my family…It was just a fear that I had.”

They described the “fear” as real and struggled with the belief that the cancer will likely progress although they were trying to maintain a positive outlook. Some participants found the intervention challenging, forcing them to confront their fears and “see things they didn’t want to see.”

Refocusing the Fears.

The program exercises and skills practice helped participants manage their fears. Nurse support helped facilitate this process. Being able to “face it with somebody” was reassuring, helping participants feel less alone. Participants appreciated receiving specific feedback and being able to discuss difficult feelings. The majority found that the skills practice helped them refocus their thoughts and gain insights on ways to manage anxiety. The cloud metaphor (detached mindfulness) helped many worry less about the future:

“It helped me put it in perspective with the rest of my life and see that it doesn’t define me….just to be more in the moment.”

The majority reported that the skills practice helped them feel more mindful and focused in their thinking. They felt reassured knowing there are resources and tools to help manage their fears.

Realizing/reaffirming what is important in life.

The majority believed that the values clarification exercise helped them to refocus their thoughts, recognize their most important values, and identify goals that gave meaning in their life. One commented:

“The most helpful was when I had to pick from the cards. … the plans-- the goals, what was important to me… That did give me a focus on something to strive for.“

The majority experienced an awakening that a new life was possible. Focusing on their values provided inspiration and hope.

Program Evaluation

Session Content:

Participants reported that the most beneficial components were values clarification, detached mindfulness, and worry postponement (Table 5). The majority reported that the skills practice would be helpful in the future. However, most (n=15) did not like the attention training skills practice, finding it annoying to focus on an individual sound in the midst of a variety of competing sounds. Four participants recommended having an attention training app on their device. Another recommended an app with a calmer version of attention training. Detached mindfulness helped to disengage from worrying thoughts. Most preferred either the train or the cloud metaphor; e.g. participants treat their thoughts like passing clouds, knowing they will eventually pass by. For worry postponement, six of nine liked the flexibility and ease of use.

Table 5.

Evaluation of Intervention Components, Timing, and Delivery

Intervention Components	Challenges	Benefits
Values Clarification (Card-Sort Exercise) (Ciarrochi & Bailey, 2009)	“Um for that particular one [Values] not really. I think it’s a good practice, um, something to think about if, you know, going through a illness.” “No, not for me… Yeah, there was one or two that was painful to think about…”	“And the other one [values clarification] I thought was interesting, too… thinking about the values that you have and like how would you in a sense make a road map to- to get to those goals… ” “Even though I have values, I never thought about it before… I wanted to, um, be mindful of those so I could practice those every day… You know, those things are very important to me…”
Attention Training Technique (ATT) (Skills practice) (Wells, 1990)	“The sounds… annoyed me greatly,… Um, it’s just like when I go in and take a hearing test… And then < they got a sound coming over top of this sound, and a sound coming in this direction to the other ear …. it was like okay, um, my mind just can’t jump around like that… ” “… that was challenging for me. But I got better as time went by. You know, passed -listening through it. Sometimes I’d listen to it twice a day ‘cause the first time I’d think, gosh, my mind just wandered too much. So later on in the evening before I’d go to bed, I’d listened to it.”	“I think the ATT probably is the one that, you know, has helped me a little bit the most. I think that just knowing its- its purpose and its intention,…” “I do feel that if I keep practicing it, when I do start getting worse, I do feel that that is going to help me not dwell on that particular incident so much”
Detached Mindfulness (Skills practice) (Wells, 2005; Wells 2008))	“I mean, that’s kind of the works in progress, I think you have to train yourself--and that’s a big buzz word these days to be mindful and all. And it’s sort of a new concept… And so I’m working on that and I don’t … think that happens overnight. So that’s something for me to you know, continue to work on--how to be mindful and- and snap out of some of these negative thoughts. “No, I- I did not find that [detached mindfulness] helpful. Yeah, no, I don’t think it was hard to understand. I think it was the relating part.”	“… like the cloud metaphor… so that they [thoughts]aren’t running me. I felt that was very helpful to… put it in perspective with the rest of my life and see it as, that doesn’t define me. All of the cancer or the worries and the, you know, what’s going to happen in my future. Um, just to be more in the moment.” “Okay, it’s a thought. Let it- let it go by…Put it in a train… so I learned how to do that … yeah it helped me refocus myself into uh, not being so worried, or tense, uptight about it I guess…”
Worry Postponement (Skills practice) (Wells, 2008)	“That- postponement, yes… I never… really found a time where I could … get back to it. “Put it aside and then come back to it. So that- I found that challenging and- so since I didn’t do it, it wasn’t helpful to me.” “I think worry postponement is a fallacy… “Oh! Okay, I’m terrified, I’m worried, but I’ll think about it, you know, at 7 o’clock tonight.”… I think worry postponement, maybe for people that are real OCD can do that, …just seems Strange to me… … Well, no I wouldn’t try it, because I think it’s silly….”	“The worrying component when it… tried to kind of get those worries and try to focus on something else and then have like a set time where you allow yourself to have those worries. Um, that’s something that stuck with me. It’s not something that I can put into practice today. but I feel that it’s something that I can put into practice going forward.” “I was telling (nurse) that’s- comes natural to me, so you kinda-- procrastinate things. Um, but that was a good, you know, like set a time aside for you to- to do that.”
Metacognitions (Fardell et al., 2016)	(only 1 person commented)	“But it was good to… look at each and every one of those things…about how you organize your thoughts. Breaking it down like that ‘cuz I don’t think people normally would think about those things, but I thought that was useful to go through that.”
Home Practice	“I think picking it up on my own to-to do the work. I had some fear there that I didn’t- maybe there were things that I didn’t want to see. Or didn’t want to address. So that was always: oh, I can do it later.” “Because due to personal issues that’s been a challenge to execute the goals.”	“No, I didn’t have any difficulties…. I thought the pamphlet was very helpful. I thought the exercises were very helpful… I would go back and read and read, and then okay, so that’ s good that it’s … written down in the booklet” “No, I- I didn’t mind doing them at all… I enjoyed them … and I feel that the way that it’s being done, you know, having a conversation about the homework and having to do the homework and reading, I think it was just a combination of all three.”
Session Delivery and Timing	Feedback/Suggestions
Method of Delivery	In-Person: “But I think that having the session with you, and you explained it, brought it to life, made it real, made me face it more… When I read it, it’s just more intellectual than emotional… I think the in person or face-to-face was much more effective.” “… you have to think of things generationally. I’m 73. I hate texting. I had to learn software for my work, but I think maybe for younger people they might feel a whole lot differently than I do, but I’m a very face-to-face person.” Zoom: “Zoom worked just fine. Well it’s two-way vis- visuals, you can get some visual contact not just a phone- It was just sit up and use… I’d keep it the same.” Phone: “But I also feel that, um, the phone one works for somebody who’s maybe going back and forth and not feeling well or feeling- you know, that doesn’t really want to get out of the house maybe. I think the phone conversations were really good.”
Timing	“I think they were a good time to get the information. I mean, it was enough to explain things uh, and go over things, and seems right.” “Seven sessions was just … I think it was about right …. the time of- I think thirty minutes would be a nice- for me, it- it would be a better period… Maybe… than let’s say 40 minutes or something like that.” (Timing and Duration) “I think I- it seemed like the study went beyond what it should have, because I was just so miserable…. because I was just so uncomfortable.”
Number of Sessions	“Just what I told you that, you know, maybe a few more sessions--would have been more helpful for me” “…I don’t think they were long enough! I thought they were a little too short to cover everything that needs to be covered… Um, probably increase the number of sessions… ” “… some of the shorter ones we coulda probably condensed. Put them into, um, like one.”

Session Delivery/Timing.

Although Zoom was acceptable to most participants, some preferred telephone (n=7) or in-person sessions (n=5). Participants liked Zoom’s two-way visual interface and the versatility of the phone. Others found in-person sessions easier as they were coming to the clinic for treatments. Some technical difficulties with Zoom included issues with volume or video (n=5); difficulty logging on/disconnecting (n=8); or connection problems when inserting the attention training flash drive (n=2). Most issues were resolved with troubleshooting. Although the majority liked the session timing/duration, two believed that there should be fewer sessions, and two recommended additional sessions including a post-intervention check-in call. Other suggestions included offering a group Zoom session (1), a link to on-line materials (1) and tailoring the intervention to those experiencing progressive disease (1).

Discussion

This nurse-led intervention was feasible and acceptable in patients with advanced cancer. Valuable input was received to refine the intervention. Target enrollment was achieved ahead of schedule with 21 completing all sessions. Attrition was higher than predicted at T2. Since some participants were consented near the holidays and chose to delay starting, the lag time between consent and session one may have contributed to attrition. For those who attended at least one session, one died and 2 needed more specialized care. Although overall adherence with home practice was high, adherence with attention training practice was poor. Explaining the rationale and encouragement helped to increase engagement. Although Zoom was the planned delivery method, several preferred telephone and some preferred in-person sessions. This suggests a need for flexibility to accommodate patients’ preferences and circumstances. Telephone-based delivery may be more feasible for those in remote locations.

We observed a pattern of improvement in FOP, distress, and other outcomes. Although improvement in metacognitions was noted only at T3, baseline scores were low which may have contributed to a floor effect. FOP and cancer-related distress scores decreased into the non-clinical range at T3. These findings are encouraging especially since five patients experienced an on-study progression and seven were receiving chemotherapy; factors associated with increased distress and FOP (Savard and Ivers, 2013). However, these analyses are exploratory; randomized studies are needed to confirm findings.

The qualitative data support acceptability and expand on the exploratory outcomes. Three themes were identified: struggling with fears, refocusing fears, and realizing/reaffirming what is important in life. The intervention helped participants identify unhelpful thought patterns and behaviors that contribute to FOP and learn skills to manage anxiety and fears. Nurse support helped them to discuss difficult feelings and realize they are not alone. With skills practice, participants reported feeling calmer, more focused, and detached from worries. Participants reported decreased frequency of threat monitoring behaviors such as tumor marker inquiries. Participants reported being more mindful, more in control of thoughts, and reassured knowing there are tools to manage fears. Values clarification helped participants set goals and focus on meaningful activities. Focusing on goals provided inspiration, hope, and direction.

Researchers testing other nurse-led FOP interventions have reported improvements in FOP and distress (Lebel et al., 2014; Lengacher et al., 2016; Liu et al., 2019). In the Mini-AFTER trial in patients with breast cancer, a nurse-led, single-session intervention was feasible and found reductions in FOP (Davidson et al., 2018). In the AFTER randomized trial in patients with head and neck cancer, a nurse-led, six-session intervention reported reductions in FCR and anxious preoccupation but no improvements in anxiety and depression (Humphris and Rogers, 2012). A limitation was that the AFTER trial did not target patients with high FOP levels. Although the attrition rate in DBD was similar to that reported in the Conquer Fear trial, it was higher than other cancer interventions targeting distress (Brebach et al., 2016). In a cognitive-existential FOP intervention in breast and ovarian cancer patients, attrition rate was 21% (Lebel et al., 2014). Interventions targeting distress in advanced cancer reported attrition rates of 25–26% (Breitbart et al., 2015; Rodin et al., 2018). The increased attrition in our study could speak to feasibility. A shorter program may be more acceptable to patients with advanced disease. Since most attrition occurred prior to the first session, more in-depth screening may help to identify those most likely to participate.

Limitations

The exploratory outcomes should be interpreted cautiously due to the small sample size with no control group. Non-specific factors such as nurse support may have contributed to the beneficial effects. Larger randomized studies would help control for non-specific elements and establish intervention efficacy (Thabane et al., 2010). The majority of participants were female, in part due to the target population including GYN participants. Among the lung cancer patients, 12 males were approached and seven declined. The most common reasons were doing well now (4), didn’t feel comfortable (1) didn’t want to dwell on it (1), and worry about upcoming back surgery (1). Although the sample size was small, the enrollment patterns were consistent with prior research finding that more women enroll in psychosocial interventions. Future researchers should build in processes to improve men’s uptake of psychosocial interventions; e.g. incorporating role models, psychoeducational materials, and content building on masculine traits (Sagar-Ouriaghli et al., 2019).

Conclusions

The researchers describe an interdisciplinary nurse-led model to manage FOP in patients with advanced cancer. A videoconferencing approach may increase access to care for advanced cancer patients, especially those in community and rural settings. Improvements in FOP and secondary outcomes are promising but require further testing. The qualitative data support these findings and provide insight on benefits, challenges, and suggestions for refinement. The intervention required a significant time commitment which may be challenging for those with advanced disease. Although responses were mixed, some participants would have preferred a shorter program. To decrease burden and increase engagement, we plan to reduce the number of sessions and explore options for self-study components. Since anxiety, uncertainty, and worry about the future were common themes, future content may address fear of death, meaning in life, and spiritual concerns.