Abbreviations
Surveillance, Epidemiology, and End Results Program
sleep onset latency
wake after sleep onset
Introduction
People with advanced cancer experience greater symptom burden than patients with early‐stage disease, with approximately 70% of these patients reporting sleep difficulties compared to 57% with early stage disease [ 1 ]. Sleep disturbance in cancer contributes to inflammation [ 2 ], depression [ 3 ], poorer quality of life [ 4 ], and shorter survival and is associated with circadian rhythm disruption [ 5 ]. Cognitive‐behavioral therapy for insomnia (CBT‐I) is recommended as first‐line treatment for all patients with insomnia [ 6 ]. However, insomnia intervention studies to date have focused on early‐stage breast cancer patients [ 7 ]. People with advanced cancer have unique worries and potentially unique circadian rhythm disruptions [ 8 , 9 ]. Our research team previously reported moderate to strong effects on sleep diary sleep efficiency and sleep onset latency, patient‐reported insomnia severity, worry, uncertainty, depression, and cancer‐related distress in our brief, 6‐week multi‐symptom intervention for people with advanced cancer, Finding Our Center Under Stress (FOCUS) [ 10 ]. FOCUS is an integrated CBT‐ACT (acceptance and commitment therapy) intervention, designed to improve symptoms when possible and focus on valued activities despite symptoms, when symptoms are more difficult to control (advanced disease). This study provides results of the objective actigraphy findings and longitudinal sleep outcomes of this trial.
Sleep‐wake activity rhythms are disrupted from the first administration of chemotherapy and progressively worsen for early‐stage breast cancer patients [ 11 ]. Less is known about the sleep patterns and disruptions for those with advanced disease. One study suggests that disrupted sleep‐wake parameters for advanced cancer patients are associated with physical symptoms, maladaptive sleep behaviors, and lower 24‐h light exposure [ 12 ]. Advanced cancer patients' circadian rhythm disruptions include more frequent and longer daytime naps, lower activity levels during the day, and more fragmented nighttime sleep compared to healthy controls [ 8 ]. Given the greater physical and psychological symptom burden (e.g., fatigue, pain, depression, anxiety) of advanced cancer patients, they may benefit from multi‐symptom interventions to enhance sleep.
Sleep intervention studies with people with cancer that include both subjective self‐report sleep measures and objective actigraphy demonstrate results on different aspects of sleep. Half of these studies (4/8) report between‐subjects effects for objective actigraphy parameters—primarily effects on wake after sleep onset (WASO) or number of awakenings [ 7 , 13 , 14 ], although one study reports improved sleep efficiency [ 13 ] and another improved circadian function [ 15 ]. Five of eight studies report only subjective sleep diary or self‐report changes with broader effects in these studies on insomnia severity, sleep onset latency, sleep efficiency, sleep quality, and total sleep time [ 7 , 15 , 16 , 17 , 18 ]. Only two randomized trials found improvements on both subjective and objective measures, each with changes on different sleep parameters [ 7 , 15 ]. However, these studies exclude stage IV patients.
Prior research with oncology populations has not found strong correlations between actigraphy and patient‐reported insomnia severity [ 19 , 20 , 21 ]. Overall self‐report ratings of sleep quality are more strongly correlated with self‐report sleep efficiency, self‐report of awakening episodes, fatigue, and daytime drowsiness. For advanced cancer patients, the objective number of wake episodes and minutes awake on actigraphy is a main determinant of insomnia severity ratings [ 22 ]. Polysomnographic findings confirm unstable nocturnal sleep continuity for advanced cancer patients [ 23 ]. However, no longitudinal intervention study has studied reasons for nocturnal awakenings in this population.
This study examined the impact of a multi‐symptom intervention on actigraphy sleep parameters. We present longitudinal self‐report sleep findings and identify the most common reasons for nocturnal awakenings pre‐ and post‐intervention for a sample of advanced cancer patients. Based on our sleep diary pilot data, we hypothesized the intervention would improve objective measures of sleep efficiency, sleep onset latency, WASO, awakenings, and activity during sleep as measured by actigraphy. We also hypothesized that patients would maintain sleep improvements longitudinally at 4, 8 and 12‐month post‐intervention in the context of improved secondary symptoms [ 10 ]. We describe reasons for awakenings pre‐ to post‐intervention to identify future targets for intervention enhancement.
Methods
Study Design
This was a randomized, wait‐list control trial approved by the Cancer and Biomedical Institutional Review Boards of The Ohio State University and registered at clinicaltrials.gov ( NCT01929720 ). Eligible participants were randomized via block random assignment by disease type using a computer‐based random assignment program with a 1:1 allocation ratio and were consented in person by PhD‐level research staff.
Sample
Thirty advanced cancer patients were recruited via telephone after medical eligibility review. Advanced cancer was defined as disease types with < 55% chance of 5‐year survival per SEER statistics at study initiation [ 24 ]. This includes cancer patients with lung cancer, stage III or IV colorectal cancer, pancreatic and esophageal cancer, multiple myeloma, leukemia, stage IIIC and IV melanoma, ovarian cancer, stage III and IV cervical cancer, stage III and IV uterine cancer, stage IIIB, IIIC, and IV breast cancer, glioblastoma multiforme, and early relapse (< 1 year) lymphoma. The primary inclusion criterion was patient‐reported sleep difficulties on the first 3 items of the Insomnia Severity Index which includes difficulties with sleep initiation, maintenance, or restless sleep. Exclusion criteria included a comorbid immunologic disease or longer‐term steroid therapy due to biomarker assessment, a neurologic disease (e.g., dementia) that would affect completion of questionnaires, or experiencing a manic phase of bipolar disorder, active substance use disorder (e.g., alcohol, cocaine), or a Palliative Performance Scale [ 25 ] scores < 40% (i.e., mainly in bed, unable to do most activity) due to the impact of these conditions on sleep and circadian rhythms. The CONSORT flow diagram is presented as Supporting Information S1 . The primary reason for exclusion was transportation/travel ( n = 128). Participants who had post‐intervention data did not differ on demographic and disease characteristics from those who discontinued the trial.
Procedures
The study timeline, measurements, and participant visits are presented in Figure 1 . Participants were recruited by telephone and completed a psychodiagnostic assessment to determine eligibility. Consented patients then received Actiwatch‐Score (MiniMitter, Bend, OR) to monitor rest‐activity patterns for consecutive 24‐h periods for 1 week. The Actiwatches were configured with the participant's study ID for confidential data collection, epoch length was set to 1 min, and start and end dates of data collection were set. At their next visit, all participants completed pre‐intervention self‐report measures, returned their Actiwatch and completed a 40 mL blood draw to assess immune and endocrine biomarkers. The intervention group then completed session one of the intervention at the Clinical Research Center (CRC) and watched session two on a DVD at week three. Both groups returned to the CRC at week five to obtain an Actiwatch. The intervention group also completed session three at this visit. All participants wore the Actiwatch again for consecutive 24‐h periods for 1 week during week five of the intervention. At week six, participants returned to the CRC to deliver the Actiwatch, complete questionnaires, and complete a 40 mL blood draw. Wait‐list control participants then began the intervention phase, completing session one, two, and three (see Intervention Content below), and 6 weeks later completed their post‐ intervention visit. For our longitudinal results, participants completed the Insomnia Severity Index, a patient‐reported measure of sleep quality, at 4‐, 8‐, and 12‐months post‐intervention by telephone.
Finding Our Center Under Stress (FOCUS) Intervention
The FOCUS intervention is a standardized, integrated cognitive‐behavioral therapy (CBT) and acceptance and commitment therapy (ACT) intervention that incorporates components of CBT in an overarching ACT framework. The intervention included three 1.5‐h sessions (two in‐person, one via DVD) delivered over 6 weeks by post‐doctoral fellows in psychosocial oncology.
Intervention Content
Session 1 included values clarification, education about the cognitive‐behavioral model of anxiety, sleep hygiene, sleep restriction, relaxation training (i.e., diaphragmatic breathing and progressive muscle relaxation), and constructive worry. A sleep restriction schedule was calculated based on the reported average number of hours spent sleeping during the previous week per the patient's sleep diary plus half an hour. FOCUS participants were instructed to go to bed and wake at set times for 1 week, adding half an hour per week until they felt more rested upon waking (vs. calculating 85% sleep efficiency as participants did this at home on their own between sessions). For home practice, participants were instructed to practice the relaxation exercises three times per day, once before bedtime, and to use constructive worry for at least 30 min each day when they felt most alert. Session 2 was provided via DVD including patient‐recorded videos focused on strategies for coping with worries common to advanced cancer patients (e.g., functional challenges, feelings of burden). Worry‐anxiety education focused on sympathetic and parasympathetic arousal, stress, appraisal and coping, problem solving, and an ACT‐based mindfulness exercise on present‐moment awareness and coping with uncertainty. Home practice included use of a relaxation CD (same exercises, CD format), continued use of constructive worry, and review of the uncertainty exercise. Session 3 (in‐person) focused on values‐based goal setting [ 26 ], behavioral activation, activity pacing, and problem‐solving skills. Components of ACT used throughout included focusing on patient values, cognitive defusion, acceptance of present‐moment experience, and committed action. The primary goal of the FOCUS intervention is to re‐establish meaning and purpose by living consistently with one's values and engaging in valued, albeit sometimes modified, activities despite symptoms.
Intervention Fidelity and Adherence
Psychosocial oncology fellows utilized the standardized manual and practiced with research assistants until treatment fidelity was achieved with the PI (SWD). Fellows received weekly 1‐hour supervision with the PI and adherence was documented in the patient's medical record. They were reminded at week 3 to watch the DVD and begin use of the relaxation CD. Of 30 participants, 21 received the allocated 6‐week intervention and completed post‐intervention assessment. Three versus four control group participants did not receive the intervention because the study was initially designed as a “no‐treatment” control before becoming a wait‐list trial due to patient demand. Three intervention participants withdrew, two because of disease progression, one for employment reasons. One control group participant withdrew due to disease progression, and another died. Participants recorded their relaxation practice on a standardized relaxation monitoring sheet. All participants reported completing the relaxation exercises 1–3 times per day. All were adherent to sleep restriction for most of the week per their sleep diary and actigraphy, with 60% adherence to their sleep schedule on average. We reviewed postdoctoral fellow study notes as well to monitor clinical protocol adherence. One participant was unable to watch the DVD due to technical difficulties but reviewed corresponding materials in the patient workbook with postdoctoral guidance. Per study records and chart review, none of the participants received additional psychosocial support.
Wait‐List Control
Participants in the wait‐list control group received the intervention after 6 weeks in the control arm. They received treatment as usual provided by their oncology team during the control period but were asked to inform study staff of any medication changes during the study. Treatment as usual included referrals for psychosocial services and medication as indicated for study symptoms. No symptom‐related medication changes were made during this 6‐week period for participants and there were no referrals completed to psychosocial services for these participants.
Instruments
Patient‐reported outcome measures used in this study are described in our previous publication [ 10 ]. The focus of the current study is the actigraphy data, longitudinal patient‐reported Insomnia Severity Index, and qualitative sleep diary data focused on reasons for awakening.
Demographic and Medical Characteristics
Patient age, race, cancer type, stage and disease status, diagnosis date, cancer treatments, and medications were collected from the electronic medical record and were verified during the patient diagnostic interview which also assessed patient education and employment status.
Actigraphy
Objective sleep indices were captured via actigraphy. Participants were asked to continuously wear an Actiwatch‐Score actigraph on the non‐dominant wrist for 1 week after their initial interview and again at week 5. The American Academy of Sleep Medicine notes that actigraphy reliably detects sleep and activity patterns in healthy adults [ 27 ]. The actigraph yields data on sleep quality, physical activity, and sleep/activity circadian patterns. Our sleep quality indices include sleep efficiency (i.e., percentage of time in bed spent sleeping), sleep onset latency (i.e., length of time between bedtime and sleep onset), WASO (i.e., minutes awake in bed after falling asleep), number of nighttime awakenings, total sleep time and total time in bed. Bedtime and waketime was denoted by participants pressing the button on Actiwatch or if missing, recorded bedtime and waketime in sleep diary. Scores > 0.85 represent good sleep efficiency, and scores < 0.75 represent poor efficiency [ 28 ].
Rest periods were validated with sleep diary bedtime and out‐of‐bed times when possible. We also report on physical activity and sleep patterns, including activity prior to bedtime and at rest, during sleep. Cases with a two‐standard‐deviation difference in sleep efficiency between the sleep diary and actigraphy were reviewed, including nine pre‐ and four post‐intervention actigrams. Discrepancies were evenly divided between overestimating and underestimating sleep. For this study, we examined the time (in minutes) active during the rest period and time active during the awake period.
Self‐Report Insomnia
Insomnia was measured longitudinally using the Insomnia Severity Index (ISI) [ 29 ]. The ISI asks participants to rate insomnia severity including difficulties falling asleep, staying asleep, and waking early. It also includes items focused on the impact of sleep difficulties such as dissatisfaction with current sleep, impact on daytime function, degree to which others notice changes in function, and level of distress or worry caused by sleep difficulties. The total score is obtained by summing the seven items with scores ranging from 0 to 28 with no insomnia (0–7), sub‐threshold insomnia (8–14), moderate insomnia (15–21), and severe insomnia (22–28). Total scores of 15 or above are considered clinically significant [ 30 ]. Remission rates were calculated as the percentage of patients with scores > 15 from pre‐intervention to post‐intervention. Cronbach's alpha for this sample was 0.82.
Reasons for Awakenings and Napping
The National Sleep Foundation Sleep Diary [ 31 ] was used to assess reasons for waking during the night, and an additional page was included to assess naps during the first and fifth weeks of the trial. Patients were asked to record nap start and end times for 7 days. We examined the number of naps and total minutes napping at each time point. Each morning for 7 days, patients were asked to respond to the prompt, “My sleep was disturbed by (list any mental, physical, or environmental factors),” in addition to other sleep diary items. Responses were coded by the Principal Investigator (SWD) indicating how many times a patient recorded each reason for awakening during a week of sleep. Results are reported as the total number of times each reason for awakening was recorded for each patient for the whole sample pre‐ and post‐intervention.
Statistical Analyses
Demographic and medical characteristics and main outcomes at baseline were compared across randomized groups using t ‐tests and chi‐square tests. Because repeated observations were measured within each subject, linear mixed models were used to test intervention effects while accounting for within‐subjects correlations [ 32 ]. An unstructured variance‐covariance model was fitted to estimate error variance. These models were fitted using PROC MIXED in Statistical Analysis System (SAS) with REPEATED statement (SAS Institute v. 9.3). Each model included fixed effects of visit, intervention group, and their interaction. Pre‐planned contrasts compared group changes (Visit × Group). The Kenward–Roger adjustment to the degrees of freedom was used to control Type I error rates [ 33 ]. Because this was a wait‐list control trial in which the intervention was provided to control participants after the wait‐list period, of primary interest were sensitivity analyses performed by examining the trajectory of change for all participants. Based on prior studies with medium sleep efficiency effects for CBT with cancer patients (Cohen's f = 0.39) [ 34 ], the conservative enrollment goal was 34, providing 80% power to detect a medium effect (Cohen's f = 0.25) given the reduced intervention duration. Enrollment concluded when pilot funding ended. Analyses were based on the intent‐to‐treat sample and used an alpha level of 0.05.
Results
Demographic and Medical Characteristics
Twenty‐eight participants were randomly assigned to the two study arms. There were no significant baseline differences on demographic and medical characteristics between groups. Participants were predominantly women (82%) and White (93%), with an average age of 57 and a high level of education (average years 15.48). The primary cancer diagnoses were advanced breast cancer (25%), ovarian cancer (21%), and leukemia (18%). Most had recurrent or metastatic disease (46%), but others had local (25%) or no current evidence of disease (29%) but a poor prognosis per SEER statistics. There were no significant baseline differences in sleep medication or antidepressant prescriptions between the groups although two control group patients were prescribed benzodiazepines, which may bias results toward better sleep in the control group. Further details are available in our pilot study demographic and disease characteristics description [ 10 ].
Baseline Sleep Characteristics
Table 1 presents baseline sleep data for both groups. The total sample (FOCUS and Wait‐List Control), on average, had sleep efficiency ratios just below the good sleep efficiency cut‐off (0.85). Participants surpassed 20 min to fall asleep and demonstrated almost an hour of awake time after falling asleep. Actigraphy recorded an average of 27 awakenings during the sleep period. Activity during their sleep period averaged 21 min. Total time in bed was 8.32 h with an average total sleep time of 6.83 h.
TABLE 1
Baseline equivalence on actigraphy and sleep diary sleep characteristics ( N = 28).
Note: p ‐values are from Wilcoxon rank sum test. Abbreviation: WASO = wake after sleep onset.
| Objective actrigraphy data | Total sample ( n = 28) | FOCUS intervention ( n = 17) | Wait‐list control ( n = 11) | p value |
| M (SD, range) | M (SD, range) | M (SD, range) | ||
| Actigraphy sleep efficiency | 82.45 (7.48, 64.94–96.09) | 83.87 (7.17, 67.76–96.09) | 80.26 (7.74, 64.94–89.02) | 0.22 |
| Actigraphy sleep latency | 21.74 (19.55, 0.14–83.25) | 19.97 (14.86, 0.14–47.14) | 24.48 (25.80, 3.43–83.25) | 0.94 |
| Actigraphy—WASO (minutes) | 50.66 (30.13, 16.50–130.43) | 49.12 (28.93, 16.50–112.86) | 53.04 (33.18, 17.93–130.43) | 0.71 |
| Actigraphy number of awakenings | 27.01 (13.42, 11.71–65.38) | 25.11 (13.12, 11.71–65.38) | 29.96 (13.98, 14–59) | 0.33 |
| Actigraphy activity at rest | 21.34 (14.65, 3.69–66.38) | 19.83 (15.33, 3.69–66.38) | 23.51 (14.21, 12.78–50.69) | 0.55 |
| Total sleep time, h | 6.83 (0.86, 4.44–8.27) | 7.0 (0.63, 5.96–8.01) | 6.56 (1.10, 4.44–8.27) | 0.26 |
| Total time in bed, h | 8.32 (1.12, 6.37–11.20) | 8.40 (0.74, 7.11–9.65) | 8.19 (1.57, 6.37–11.20) | 0.27 |
| Subjective sleep diary data | ||||
| Sleep diary—number of naps | 2.74 (3.51, 0–14) | 2.06 (2.67, 0–9) | 3.73 (4.43, 0–14) | 0.35 |
| Sleep diary—minutes napping | 161.56 (193.3, 0–708) | 98.31 (102.54, 0–263) | 253.55 (256.27, 0–708) | 0.15 |
On their sleep diary participants reported approximately 3 naps per day, lasting an average of 162 min prior to the intervention. There were no significant differences between the two groups at baseline.
Group × Time Intervention Effects
There were no significant group‐by‐time effects on actigraphy data, naps, or activity during rest other than total sleep time, likely due to the small sample size. There was a non‐significant trend ( p = 0.09) toward improved actigraphy sleep onset latency for the FOCUS group (20–8.4 min) compared to the control group (24–29 min). Total sleep time was reduced from 7 to 6.7 h for the FOCUS group compared to an increase from 6.56 to 7.05 h for the control group, consistent with sleep restriction instructions for the intervention group ( p = 0.024). Due to the small sample size at the conclusion of the study (when funding ended), our primary analyses of interest were our sensitivity analyses to estimate effect sizes for our future randomized trial.
Sensitivity Analyses—Intervention Plus Wait‐List Control Pre to Post Results
Sensitivity analyses with the full sample, are displayed in Table 2 . With the full sample, there were pre‐ to post‐preliminary intervention effects on actigraphy sleep efficiency, WASO, number of awakenings, number and minutes of napping, and reduced activity at rest. Patients demonstrated a large preliminary effect on actigraphy sleep efficiency, with more overall time in bed sleeping, fewer awakenings, and less time in minutes awake after sleep onset. Patients reduced minutes awake in bed from 57 to 44 min (medium effect). Sixty percent (15/25) met the sleep efficiency cut‐off at post‐intervention. There was not an effect on sleep latency ( p = 0.10). Participants fell into the normal range (10–20 min), on average post‐intervention, compared to pre‐intervention. There was no effect on activity patterns when not in bed. Consistent with intervention recommendations, participants reduced naps from 2.6 to 1.4 naps and minutes napping from 166 to 111 min on average. Patients were also getting more restful sleep per activity at rest results.
TABLE 2
Sensitivity analyses: Outcomes for combined sample pre‐ to post‐intervention ( N = 28).
Abbreviation: WASO = wake after sleep onset.
| Outcome | Pre‐intervention | Post‐intervention | p value | Cohen's d |
| Actigraphy sleep efficiency | 82.56 (1.43) | 85.50 (1.21) | < 0.0001 | 0.95 |
| Actigraphy sleep onset latency | 25.14 (6.09) | 17.66 (3.86) | 0.10 | −0.33 |
| Actigraphy minutes awake after sleep onset (WAS0‐M) | 57.08 (6.35) | 44.28 (5.13) | 0.02 | −0.49 |
| Actigraphy number of awakenings | 26.03 (2.59) | 22.39 (2.38) | 0.05 | −0.38 |
| Sleep diary—number of naps | 2.61 (0.48) | 1.40 (0.38) | 0.03 | −0.44 |
| Sleep diary—minutes napping | 166 (31) | 111 (28) | 0.05 | −0.38 |
| Actigraphy activity at rest (minutes) | 19.97 (2.79) | 17.87 (2.40) | 0.04 | −0.41 |
| Actigraphy activity during the day (minutes) | 257.06 (18.07) | 248.22 (18.74) | 0.46 | −0.14 |
Longitudinal Sleep Outcomes
The intervention group demonstrated reduced insomnia severity on the ISI pre‐ to post‐intervention. Results are shown in Figure 2 . These results were maintained at 4 and 8 months with a minor increase at 12 months. Wait‐list control participants also demonstrated a significant decrease post‐intervention with sustained improvement longitudinally. Given an ISI cut‐off of 15 for clinical insomnia, all participants combined demonstrated increasing remission from 61% (17/28) meeting the cut‐off for insomnia at baseline, 36% (9/25) post‐intervention, 7% (1/15, 1/14) at 4 and 8 months, with a slight increase to 18% (2/11) at 12 months. However, we note 50% attrition at 12 months primarily due to difficulty contacting patients.
Qualitative Findings—Reasons for Awakenings
Patients reported over 210 awakenings at baseline and 140 at 6 weeks. Reasons for awakenings are shown in Figure 3 . The distribution of reasons were similar pre‐ and post‐intervention; however, there was a 40% or more reduction in pain, worry/restlessness, spouse and pet/animal disruptions. Nocturia and hot flashes remained the primary reasons for WASO post‐intervention accounting for 55% of all awakenings.
Discussion
Consistent with our pilot trial subjective sleep findings [ 10 ], FOCUS participants demonstrated improved objective sleep efficiency. The combined sample also reduced objective awakenings and time awake after sleep onset. Participants reported 210 reasons for awakening at pre‐intervention versus 140 at post‐intervention with reductions in several sleep barriers amenable to change including pain, worry, and spouse and pet/animal disruptions. In fact, pain and discomfort were reduced by over half. Longitudinally participants demonstrated relative stability of self‐report sleep improvements post‐intervention, with 61% meeting the self‐report cut‐off for insomnia at baseline compared to 18% at 12‐months.
Our results using a CBT‐ACT intervention are consistent with other cancer‐focused behavioral sleep intervention studies which demonstrate improvements primarily on nocturnal awakenings as an actigraphy parameter [ 20 ]. Only one previous cancer intervention study found significant changes on actigraphy sleep efficiency [ 13 ]; however, this study excluded patients with stage IV cancer. Lengacher et al. [ 13 ] found an improvement from 74% sleep efficiency to 78% sleep efficiency using mindfulness‐based stress reduction, but this finding is still below the 85% threshold for optimal sleep efficiency. Our findings contrast with Palesh et al. [ 15 ] who found improved circadian function, or higher average activity level post‐intervention for breast cancer patients with stage I‐III disease. Our results indicate that FOCUS participants were getting more restful sleep given their significantly reduced activity at rest. Our results are consistent with Berger [ 7 ] who reported improved sleep quality and reduced number of awakenings per actigraphy 90 days post‐treatment, though WASO was not maintained longitudinally. The authors note that higher levels of fatigue and anxiety at baseline were associated with poorer sleep at 1 year. These studies combined with our findings suggests that multi‐symptom behavioral interventions may be more effective for advanced cancer patients to maintain longitudinal sleep effects.
This was the first study to examine the reasons for awakenings longitudinally with advanced cancer patients. Similar to previous studies with advanced lung and prostate cancer, we found nocturia to be a prevalent reason for nighttime awakenings [ 35 , 36 ]. The FOCUS intervention advises patients to reduce fluid and caffeine intake prior to bedtime. We have also found bladder retraining a useful adjunct with patients with significant nocturia [ 37 ], but this was not a standard component of the FOCUS intervention. Contrary to a study of patients with advanced lung cancer patients, dyspnea and cough were not predominant reasons for awakenings [ 35 ]. We did observe reductions in spouse and pet/animal disruptions consistent with sleep hygiene instructions. It remains unclear whether the reduction in pain disruption is related to patient collaboration with oncology teams on nocturnal pain management (as reccommended by intervention) or from improved sleep and reduced inflammation [ 38 , 39 , 40 ].
Clinical Implications
Advanced cancer patients demonstrate improved sleep efficiency and reduced wakefulness after sleep onset via this CBT‐ACT multi‐symptom intervention. Based on these pilot results, for patients with more advanced disease, multiple symptoms—worry‐anxiety, mood, and fatigue may need to be addressed to improve sleep. Focusing on values, mindfulness strategies, and committed action, may also be useful for sleep improvement. Further work is needed to reduce primary reasons for awakenings including nocturia, pain, worry, and hot flashes.
Limitations
This represents a small but more diverse sample of people with cancer than previous studies. There were no between‐group differences, likely related to the sample size. However, our focus was on the intervention and wait‐list control groups for this pilot to maximize sample size for effect size estimation in our planned follow‐up randomized trial. It is possible that reasons for awakenings were missed as we did not use a standard checklist. We had difficulty reaching patients at 12 months post‐intervention. Our results could over/underestimate longitudinal sleep effects due to missing data at the 4, 8, and 12‐month phone contacts.
Conclusion
Patients with advanced cancer have more frequent and severe physical symptoms. This is the first study to demonstrate that a multi‐symptom intervention improves multiple self‐report and actigraphy sleep outcomes and facilitates longitudinal sleep improvements. This CBT‐ACT intervention provides effective symptom management in a format accessible to patients with serious illness. Future studies will translate this intervention to an mHealth‐telehealth format to further enhance accessibility and add components to reduce nocturia, incorporate non‐pharmacologic pain management strategies at night, and emphasize practicing strategies to manage bedtime worry.
Author Contributions
Sharla Wells‐Di Gregorio: conceptualization, methodology, actigraphy verification, intervention delivery, data interpretation, writing – original draft, supervision, project administration, funding acquisition. Stacy Flowers: actigraphy verification. Juan Peng: statistical analyses, data interpretation, writing – original draft, visualization, funding acquisition. Donald R. Marks: conceptualization, methodology, intervention delivery, data management, review and editing manuscript. Danielle Probst and Alexandra Zaleta: intervention delivery, data management. Don Benson, David E. Cohn and Maryam Lustberg: patient recruitment, review and editing manuscript. William Carson: methodology, immune assays, funding acquisition. Uly Magalang and Sonia Ancoli‐Israel: methodology, actigraphy interpretation, review and editing manuscript. Sarah Baltimore: table/figure development. Sonia Ancoli‐Israel: behavioral sleep medicine consultation on methodology and data interpretation, review and editing.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Figure S1
Acknowledgments
We would like to acknowledge our study participants for their time and contribution to this study, particularly given the challenges presented by their disease and treatments. We would also like to acknowledge the professional research assistance of Sophie Kowaleski, Samantha Donermeyer, Katie Slaven, Allison Sigler, Brooke Leon, Allison Neuhaus, and Matthew Minotti. All authors have seen and approved the manuscript.
Funding: This work was supported by American Cancer Society Grant (ACS IRG‐67‐003‐47), Lance Armstrong Foundation Survivorship Center for Excellence Grant, Tzagournis Medical Research Endowment Fund, Ohio State Comprehensive Cancer Center Cancer Control Grant (CCP194) with support of the Ohio State Clinical Research Center via the National Center for Advancing Translational Sciences Grant (UL1TR001070).
Data Availability Statement
The data that support the findings of this study are available from the corresponding author, SWD, upon reasonable request.
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Associated Data
Supplementary Materials
Figure S1
Data Availability Statement
The data that support the findings of this study are available from the corresponding author, SWD, upon reasonable request.