Effectiveness and moderators of cancer patient-caregiver dyad interventions in improving psychological distress: A systematic review and meta-analysis.

Introduction

The International Agency for Research on Cancer 1 estimated that 19.3 million new cancer cases were diagnosed globally in 2020. The cancer trajectory often presents a tiresome and difficult challenge, not only for patients but also for family caregivers. Family caregivers, defined as family members or significant others who provide emotional and physical support for patients, often do so without expecting anything in return. 2 , 3 Physical discomfort, fatigue, sleep problems, overload, and mental distress are the main problems reported by patients with cancer and their family caregivers. 4 , 5 In addition, primary caregivers are frustrated by the high caregiving burden, lack of independence and freedom, and the need, at times, to hide their depression symptoms. 6 Negative emotions are infectious to make cancer dyads suffer more. Multiple studies have produced statistics which indicate that varying degrees of emotional problems exist among patients with cancer and family caregivers. A cross-sectional study found one-third of cancer survivors and family caregivers experienced anxiety and depression. 7 The consecutive challenges of “dealing with the emotions of the initial diagnosis or recurrence, uncertainty about the future, managing cancer pain, caring for the patient and managing emotions” can be difficult for both cancer survivors and informal caregivers. 8 Many psychosocial interventions have been developed to address the overwhelming distress in recent years. Non-pharmacological methods have been utilized to change an individual's behavior, including psychological, educational, and behavioral components, 9 , 10 such as informational sessions, mindfulness meditation, teaching cognitive and behavioral coping strategies, and peer support. Therefore, a critical analysis is necessary to determine the most effective interventions to manage the symptoms of emotional distress in patients and their family caregivers.

With the introduction of various dyadic theories, 11 , 12 , 13 the concept of the patient-caregiver dyad was proposed and is, indeed, worthy of attention. Patient-caregiver dyad states are an interdependent whole and not just a “receiver” or “giver”; it requires work together to cope with the illness. Considering the patient and the family caregiver as a unit and promoting joint physical and psychological outcomes for each other was a new perspective proposed to address their psychosocial problems. In recent years, several meta-analyses have been conducted to better understand the impact of psychosocial interventions on cancer dyads. The majority of studies have focused on the domains of physical symptoms, psychological, social functioning, and overall quality of life (QoL). In addition, the few published systematic reviews or meta-analyses that have assessed the impact of psychosocial interventions on the mental health of cancer dyads have limitations. For instance, Badr 14 and Wang et al 15 did carry out a meta-analysis, but they are mainly focused on couple-based interventions while not analyzing other caregiver roles related to the effect of dyadic emotional outcomes. Gabriel 16 and Regan et al 17 conducted systematic reviews for cancer dyads without performing meta-analyses. Hence, it is indisputable that treating patients and their family caregivers as a dyadic unit can provide new directions and perspectives for improving emotional outcomes and overall QoL for both populations. 18 , 19

Numerous researchers highlight physical and mental health problems among cancer dyads. Although these non-pharmacological interventions have shown some degree of effectiveness, 20 , 21 what remains unknown is whether the interventions will affect this group differently and whether interventions delivered in varied forms, durations, and frequency will impact emotional distress differently. Only limited conclusions can be drawn from the available reviews regarding the effectiveness of psychosocial interventions in improving emotional distress in cancer dyads. This systematic review aims to find and synthesize available evidence to bridge the gap, providing insight and direction for clinical staff to address these emotional problems.

The objectives of this systematic review are as follows: (1) explore the effects of current interventions on patients with cancer and their family caregivers’ emotional outcomes (symptoms of depression, anxiety, cancer-related distress); (2) conduct further analyses targeting variables of interest that may influence the effect of the intervention to clarify potential moderating effects.

Methods

Review and synthesis were performed following the PRISMA 2020 statement. 22 This study was registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/WXTUV ).

Inclusion and exclusion criteria

Population: patients diagnosed with cancer and their family caregiver (The caregiver is the family member who undertakes the primary care, including the spouse, children, parents, siblings, etc.); any patients/caregivers aged ≤ 18 years old and receiving palliative care at the end of life were excluded.

Intervention: dyad intervention or treatment that consider the patient and family caregiver as a holistic unit.

Comparison: control group was not restricted; usual routine care, waitlist control, or other types of interventions were eligible.

Outcome: any emotional outcomes, such as anxiety, depression, despair, and distress, were measured, while studies that only reported patient or partner outcomes but not both were ineligible. It is worth noting that the emotions mentioned above should be a symptom rather than a disorder.

Study type: randomized control trial design study.

Literature search

We searched for journal articles published from inception until June 2021 in the electronic databases PubMed, Cochrane Library, Web of Science, CINHAL, Embase, Clinical Trials, and reviewed the reference lists of selected publications. Medical Subject Headings (MeSH) and free text terms were combined to form the search strategy. The search terms reflected combinations of the following keywords: (neoplasm∗ OR tumor∗ OR cancer∗) AND ((patient∗ OR client∗) AND (caregiver∗ OR carer)) AND (dyad∗ intervention OR dyad∗ pattern) AND (emotion OR mood). The detailed search strategies are presented in the Supplementary Table.

Data extraction

We entered all records into EndnoteX9, and two reviewers (PXN and JYF) sifted the articles independently. All search results were screened twice. Any disagreements were addressed through discussion and consensus by the third member (WHH). Two reviewers separately extracted data using Microsoft Excel software. Double-checks were conducted after entering all data. The synthesis table included the primary author, published year, setting, cancer type, intervention (therapy, delivery/dosage, refusal rate, follow-up, retention rate), psychological measurement tool, and main findings.

Quality appraisal

We used the Cochrane risk of bias tool of the Review Manager 5.4.1 software to evaluate quality assessment. The RoB 2.0 tool provides a framework for assessing the risk of bias in a single RCT result, 23 which contains six items in five domains. All studies included were evaluated independently by two reviewers, who classified the risk of bias for each study as “low risk,” “unclear,” or “high risk.” The third reviewer resolved discrepancies.

Data synthesis

Since standard mean deviation could pool the different units of various rating instruments in the meta-analysis, we used standard mean deviation and 95% confidence interval ( CI ) to calculate the effect size of the continuous variables. We used Hedges’ adjusted g as effect size to provide a better estimate when the sample size was small. 24 I 2 ≥ 50% suggested significant heterogeneity, and further sensitivity analyses reduce it. A random-effects model was used since the interventions included in the analysis varied by method, population, measurement tools, and follow-up time. In most cases, the baseline influence two group effects when performing pre-post design studies. When only including post-test results tend to exaggerate in statistics, thus the true effect values are underestimated. We, therefore, weighted the differences between pre- and post-means, as recommended by Morris 25 because effect sizes were defined using pretest and post-test information.

The moderator analysis explores the direction and strength of the relationship between dyadic negative emotions (independent variables) and the intervention effects (dependent variables). Based on previous studies, we identified several factors that may influence the effect of dyadic interventions. The moderator analysis in this paper was limited to groups with at least three studies. Usually, the number of studies is represented by k in a meta-analysis, while n is the number of participants in each study.

We used Duval and Tweedie's trim-and-fill method 26 through the computer program CMA 3.0 to generate funnel plots containing observed studies and imputed studies. Egger's regression test 27 was also used to clarify publication bias.

Results

Search outcomes

In total, 28 full-text articles were extracted and tabulated, 12 of which were synthesized as part of a meta-analysis. As illustrated in the PRISMA flow chart ( Fig. 1 ), a total of 4135 study records were identified. After reading 3413 titles/abstracts, we reviewed 130 full texts. Ninety-one studies were excluded after a full-text screening, and the main reasons for exclusion were shown in Fig. 1 . In addition, we identified eight cited references and finally included four studies. Ultimately, 28 eligible studies were identified for this systematic review.

Study characteristics

Most of the studies were conducted in the United States ( k ​= ​19); the rest were performed in China ( k ​= ​3), Australia ( k ​= ​2), the United Kingdom ( k ​= ​2), Denmark ( k ​= ​1), and Belgium ( k ​= ​1). The characteristics of the 28 studies included in the systematic review are summarized in Table 1 and are described in detail in Table 2 .

Participants

The patients/family caregivers recruited at baseline totaled 4784 participants from 28 studies, ranging from 30 28 to 968, 29 with eight studies involving a sample size of fewer than 50. The average age ranged from 43.70 to 67.50 for patients and 48.27 to 63.56 for family caregivers. The roles played by the family caregivers varied: the spouse was the family member involved most often, followed by adult children, parents, siblings, friends, or significant other. Mixed cancer (30%) was the most common cancer type, followed closely by prostate (21%) and breast (14%). The mean refusal rate varied from 5.2% 30 to 82.2%. 31 The mean retention rate at final follow-up ranged from 16.67% 28 to 95.9%. 32 Distress screenings, which assess participants with high distress levels, were conducted at the beginning of four studies. 29 , 33 , 34 , 35 Some studies paid more attention to patients 36 than to family caregiver involvement or the dyad intervention, while Badr et al 37 and Clark et al 38 assigned patients and family caregivers to different sessions.

Interventions

The frequency of the intervention ranged from 4 times 32 , 34 , 39 , 40 , 41 , 42 , 43 to daily, 44 and the total duration varied from 78 ​min 34 to 24 ​h. 30 Nearly half of the interventionists were nurses 28 , 29 , 32 , 36 , 48 , 54 , 56 or psychologists, 37 , 40 , 42 , 43 , 53 even for both. 33 , 41 Interventions included supportive communication, coping skill development, family-oriented supportive education, health management, mindfulness, yoga, and music therapy.

Couple-based interventions were more common ( k ​= ​13) compared to treatments that mixed various family caregiver roles. They often focused on dyad coping 34 , 37 , 45 , 46 and communication. 31 , 39 , 40 , 42 Half of the studies examined face-to-face interventions ( k ​= ​14); five programs involved technology-based interventions, 31 , 35 , 37 , 43 , 47 while others involved telephone ( k ​= ​3).

Comparison group

Six studies compared the experiential group with groups who had undergone other interventions. 29 , 31 , 32 , 33 , 42 , 48 , 49 Chambers et al , 33 respectively, compared nurse-led and psychologist-led interventions. Two studies considered multiple comparison groups: two versions of one program were implemented: brief or extensive 48 and Milbury et al 42 compared the effects of couple-based meditation, supportive-expressive, and TAU (Treatment as usual).

Outcome measures and timing

Anxiety, depression, distress, and hopelessness were included when measuring mood states. Many studies have involved specific anxiety or depression scales to measure this outcome, while some studies also used QoL emotional subscales. Most studies measured negative emotions, only three 41 , 48 , 50 investigated positive ones, such as well-being, satisfaction, hopefulness, and calmness. An appropriate cortisol level, a hormone produced by the adrenal glands, can help the body cope with stress, 51 and the hormone is a closely relevant emotional state. However, only one study 48 employed this objective laboratory indicator to indirectly reflect anxiety or depression levels. No follow-up was done for 13 studies; 4 recorded one follow-up. Outcomes were measured at two time-points in five studies and at three time-points in three studies. Follow-up ranged from 1 to 14 months.

Results of the meta-analysis

Although numerous rating tools were used to measure emotional outcomes, variables that could be pooled and meta-analyzed were symptoms of depression, anxiety, and cancer-related distress ( Fig. 2 , Table 3 ). Inevitably, varying degrees of heterogeneity were introduced due to differences in interventions, study subjects, measurement tools, and so on. The following will be described in different dimensions.

Depressive symptom

The eight studies on patients 34 , 36 , 37 , 40 , 44 , 48 , 52 , 53 were combined into subgroups from baseline to immediately post-intervention; pooled results were not statistically significant ( g ​= ​0.04; 95% CI : ​−0.41 to 0.48; P ​= ​0.86; I 2 ​= ​88%). When the study 48 with an intervention comparison was excluded, they showed small but statistically significant results ( g ​= ​−0.19; 95% CI : ​−0.36 to −0.01; P ​= ​0.04; I 2 ​= ​16%). However, as seen in the subgroup containing three studies 40 , 48 , 53 from the post-intervention follow-up at 5 weeks to 14 months, the reduction in patient depression had a long-term effect at follow-up and had a medium clinical effect compared to the immediately post-intervention subgroup ( g ​= ​−0.68; 95% CI : ​−1.77 to 0.41; P ​= ​0.22; I 2 ​= ​93%).

In terms of family caregivers, greater heterogeneity was demonstrated in seven studies 34 , 37 , 40 , 44 , 48 , 52 , 53 from baseline to post-intervention ( g ​= ​−0.44; 95% CI : ​−1.03 to 0.15; P ​= ​0.15; I 2 ​= ​91%), even two studies 34 , 53 showed better results for reducing depression in the control group. We found some interesting results when we explored the reasons for the high heterogeneity in caregiver depression. Lambert et al 34 provided a health education booklet and a short follow-up to the control group contributed better results for them. Mosher et al 53 speculated peer help plus coping skills would have less impact than only coping skills for patients with advanced cancer, but draw a contrastive conclusion. Participants in this study had high coping self-efficacy levels at baseline, so there was little potential to produce positive change in them through such interventions. From the same three follow-up studies on patients, the long-term depression status of the caregivers did not change noticeably ( g ​= ​−0.56; 95% CI : ​−1.82 to 0.69; P ​= ​0.38; I 2 ​= ​95%). Notably, Hsiao et al 48 found a greater effect in the couples' support group among caregivers when comparing couples' and individuals’ support groups.

Anxiety

Seven studies measuring patient anxiety 34 , 36 , 40 , 44 , 48 , 52 , 53 showed a statistically significant difference and small clinical effect from baseline to post-intervention ( g ​= ​−0.31; 95% CI : ​−0.51 to −0.12; P ​= ​0.001; I 2 ​= ​17%). Similarly, after excluding the Hsiao et al 48 study, only a small clinical significance was observed from post-intervention to follow-up phase ( g ​= ​−0.32; 95% CI : ​−0.65 to 0.02; P ​= ​0.06; I 2 ​= ​0%). However, family caregiver outcomes in the category of anxiety were not statistically significant either at post-intervention ( g ​= ​0.12; 95% CI : ​−0.16 to 0.44; P ​= ​0.37; I 2 ​= ​63%) or during follow-up ( g ​= ​−0.08; 95% CI : ​−0.34 to 0.19; P ​= ​0.57; I 2 ​= ​0%). This demonstrates that these interventions reviewed in this study were highly effective in reducing patients’ anxiety compared to care as usual but had no significant effect on family caregivers other than those reported by Hsiao et al. 48

Cancer-related distress

Cancer-related distress was conceptualized in this meta-analysis as other negative emotions triggered by cancer, such as despair, sadness, stress, apprehension, symptom distress, and so on. Seven studies 31 , 32 , 37 , 44 , 52 , 53 , 54 measured this outcome. Although different assessment tools were used, the final pooled results showed that patients’ cancer-related distress was statistically significant and without heterogeneity at post-intervention ( g ​= ​−0.32; 95% CI : ​−0.46 to −0.18; P ​< ​0.0001; I 2 ​= ​0%). The impact of family caregivers on improving a negative mood was not obvious ( g ​= ​0.02; 95% CI : ​−0.23 to 0.26; P ​= ​0.89; I 2 ​= ​52%).

Moderator analysis

To further explore the intervention effects, we conducted a moderator analysis ( Table 4 ). Four variables were included as moderators: intervention delivery type (face-to-face, online, telephone), interventionist role (nurse, psychologist, therapist), frequency of intervention (time), and duration of sessions (hour). An individual with a psychologist's background provided a significant intervention effect compared to what an experienced therapist or nurse provided, related to either anxiety ( k ​= ​5, g ​= ​−0.36, P ​= ​0.001) or distress ( k ​= ​3, g ​= ​−0.31, P ​= ​0.01). The face-to-face approach produced more significant effects in reducing distress ( k ​= ​3, g ​= ​−0.42, P ​= ​0.04). The effect was better if the frequency was lower (fewer than 6–7 times) and the duration shorter (fewer than 6–7 ​h).

Quality assessment

Three studies 31 , 33 , 34 were ranked as high-quality, meaning each bias rating was “low risk.” The lack of allocation concealment and blinding were major causes for the poor quality of these studies. Seven studies 28 , 37 , 39 , 45 , 50 , 54 , 55 declared randomized allocation but did not describe the process. About three-fifths of the studies ( k ​= ​15) described the allocation concealment, and 14 were blinded (5 single-blind and 2 double-blind). Blinding was not conducted largely because the nature of psychosocial intervention makes it difficult to blind, but some studies 50 minimized the adverse effects of non-blinding by informing participants that they had been randomly assigned to one of two different interventions. Although the baseline of some studies 32 , 34 , 37 , 40 , 43 , 53 , 55 , 56 was unbalanced, we retained them because baselines were analyzed to reflect intra-individual changes. Nearly all the studies demonstrated no other biases; only one 50 was rated “high risk” due to unequal allocation to groups ( Fig. 3 ).

Publication bias

Visual inspection of the filled funnel plot after using the trim-and-fill method 26 and the Egger test 27 ( P ​= ​0.96, P ​= ​0.33, P ​= ​0.45, P ​= ​0.23, P ​= ​0.74) identified no publication bias ( Fig. 4 ).

Discussion

This systematic review places cancer family caregivers and patients in equally important positions, and it demonstrates a better change effect of intervention when adding baseline into the meta-analysis. Moderator analysis and publication bias checks ensured that our results were more rigorous and objective. The results showed that dyadic intervention had a short-term improvement with a statistical effect on patient anxiety and cancer-related distress. For family caregivers, the effect sizes of cancer-related distress and depressive symptoms were only small to medium at follow-up without statistical significance. Regarding the type of intervention, face-to-face (compared with telephone and online) and shorter interventions (compared with session duration longer than 6–7 ​h) led by psychologists with professional backgrounds (compared with nurses and therapists) seem to have a better performance.

Of the studies we included, although the emotional distress of most patients or family caregivers improved to some extent, two-thirds of the studies did not show a statistically significant change. Among these psychosocial interventions that promote communication, disclosure, mutual support, and ultimately deepen intimacy, such as active meditation, skill training, and relaxation training, seem to be more effective. In addition, our study showed a statistically significant improvement in anxiety and cancer-related distress in patients with cancer from baseline to immediate intervention completion, but not statistically significant improvements over the follow-up period, which was consistent with the findings of Hu 57 and Wang et al. 15 Notably, neither anxiety nor cancer-related distress among family caregivers showed significant improvement from baseline to follow-up. Thus, cancer involves a long-term struggle between dyads and disease, and various factors, such as disease progression, treatment options, and family social support, may affect dyads differently. It is undeniable that family caregivers and cancer patients have an interdependent relationship 58 therefore, dyadic interventions are still necessary for this population. While incorporating family caregiver involvement in the treatment, many interventions ultimately put more emphasis on improving physical and psychological patient outcomes. 36 Future studies need to design better interventions that enhance the dyadic mental health of all involved.

Although this article does not emphasize the moderator analysis results, we found some thought-provoking conclusions. First, the face-to-face intervention delivery format produced the most significant results. This finding is similar to those of a recent systematic review for patients with colorectal cancer. 59 The face-to-face sessions can increase participant adherence, making for a deeper, more trusted relationship between interventionist and participant. As technology continues to emerge, more and more researchers are using new techniques to practice intervention effects. Some studies suggested that social media may be a useful tool to communicate health-related information and support cancer dyads. 60 However, fewer online interventions ( k ​= ​7) were included in this review compared to face-to-face modalities ( k ​= ​14), which could may have led to the conclusion be one of the reasons why we conclude that face-to-face interventions are better. Compen et al 61 conducted a cost-utility analysis for in-person and online formats. Both groups can reduce costs while improving poor cancer patients’ QoL. It should be clear that online interventions are not only beneficial but also not inferior to face-to-face ones. 62 , 63 As interventions via the Internet or videoconferences are more creative and shorter, more large-sample and high-quality studies are needed in the future to compare these two forms of interventions.

Our conclusion related to intervention duration and frequency contrasts with those from other research. In our review, shorter interventions seem to have better performance, while some studies suggested longer intervention duration might produce more lasting effects. 59 , 64 Northouse et al 29 designed the FOCUS program to include two experiment groups of different lengths but did not find a difference between the two groups. However, both the Brief version and the Extensive version improved emotional QoL. This may provide us with a new idea about the duration and frequency of the study. A well-designed, shorter intervention may generate more desirable effects. Moreover, this approach brings other benefits, such as saving resources and increasing participant involvement rates.

In comparing the types of interventionists, psychologists had the best intervention effects compared to nurses and therapists, consistent with Bard's moderator analysis findings. 65 It might be attributed to a lack of training, experience, or professional dialog among nurses when providing psychosocial care. 66 However, regardless of who leads the intervention, participant perspectives need to be considered. Appropriate tailored therapies for participants are much better than intensive psychosocial interventions implemented by medical professionals. 67

Finally, we need to point out that the evidence available in this systematic review is limited. Our review's quality was uneven, with many studies not addressing specific allocation concealment strategies and blinding details. In addition, we found that most studies have focused on developed countries and middle-aged and elderly populations. A lack of reflection in some low- and middle-income areas, young cancer dyads, and other races limits the generalizability of our results. Therefore, higher-quality and broader randomized controlled trials of the patient-caregiver dyad are needed.

Limitations

There are several limitations in our meta-analysis. (1) When searching the database, we only reviewed literature published in English. This may have led us to omit other results that were reported in articles published in minor languages. (2) Publication bias is inevitable for all systematic reviews. However, we tried to reduce this bias by refining the search strategy, finding alternative citation sources, and using specific statistical methods whenever possible. (3) To control the quality of the studies included, we included only RCTs; other quasi-experiments or pretest-post-test designs that met the inclusion criteria were excluded. (4) Patients with terminal cancer often face more intense stressful emotions, and their family caregivers may also experience grief. Cancer does not simply bring on these emotions but another fear of imminent death. Articles introducing palliative interventions may have biased results. So we excluded some studies designed for advanced cancer dyads with only a few months left in the life cycle. But this may have missed some meaningful results.

Clinical implications

This review clarifies the current state of the literature on dyadic interventions for patients with cancer and their family caregivers and provides some credible data. Much remains to be done in this area, however. First, the control group in most studies was not rational. Only one study 48 compared couple intervention with patient individual intervention. Many studies used the dyadic intervention as the experimental group and usual care as the control group. At this point, we cannot clarify whether the effect was produced by the group therapy or by the dyadic intervention. Therefore, in the study design phase, we can set up multiple control groups, such as individual interventions for patients and routine care as a control group at the same time. If only one control group can be used, considering the resource issues, perhaps some form of blank group intervention can be added to the usual care group as well. Second, with the advent of new technology such as the Internet, some studies examined various electronically implemented interventions. 68 , 69 However, the patients with cancer we included were generally older, and these middle-aged and older groups may be less adaptable to new technology. 70 Future studies should consider the acceptability of this population at the study design stage. Third, with cancer rejuvenation, more interventions designed for younger dyadic units need to be considered because they may face different challenges than the old—balancing cancer with work, family, and child-rearing issues. 71 Finally, despite the scope of the review being large, studies on low- and middle-income country regions remain missing. 72 Cancer is a global problem, and populations in low-income areas may face more emotional distress. At the same time, in low- and lower-middle-income countries, advanced cancer stage, and low education levels also affect anxiety and depression levels. 73

Conclusions

We reviewed the various types of dyad cancer interventions. Face-to-face, relatively shorter interventions led by psychologists seem to have a moderating effect. In conclusion, the results of this systematic review suggest that cancer dyad-based interventions can improve emotional distress. However, patients showed a greater improvement in their negative emotions than family caregivers. How to better address caregivers’ psychological distress and how to maintain the long-term effects of the intervention need to be explored by further high-quality investigations in the future.

Funding

Nil.

Authors' contributions

Xuenan Pang: literature search, software, data curation, writing original draft preparation. Yanfei Jin: conceptualization, methodology, literature search, data curation. Honghong Wang: visualization, writing/reviewing, editing.

Declaration of competing interest

None declared.

Acknowledgments

The authors would like to thank Professor James Wiley from the University of California, San Francisco, for his expert advice and encouragement throughout this study.

Footnotes

Supplementary data to this article can be found online at https://doi.org/10.1016/j.apjon.2022.100104 .

Supplementary data

The following is the Supplementary data to this article:

Multimedia component 1

References

1. Sung H., Ferlay J., Siegel R.L., et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660.

2. Caregiving AaNAf . 2020. Caregiving in the United States. Washington, DC: AARP May 2020 2020.

3. Ellis K.R., Janevic M.R., Kershaw T., Caldwell C.H., Janz N.K., Northouse L. The influence of dyadic symptom distress on threat appraisals and self-efficacy in advanced cancer and caregiving. Support Care Cancer. 2017;25(1):185–194. doi: 10.1007/s00520-016-3385-x.

4. Chan J.S.M., Yu N.X., Chow A.Y.M., et al. Dyadic associations between psychological distress and sleep disturbance among Chinese patients with cancer and their spouses. Psycho Oncol. 2017;26(6):856–861. doi: 10.1002/pon.4240.

5. Ellis K.R., Oh S., Hecht H.K., Northouse L. Symptom distress and quality of life among Black Americans with cancer and their family caregivers. Psycho Oncol. 2021;30(8):1356–1365. doi: 10.1002/pon.5691.

6. Leroy T., Fournier E., Penel N., Christophe V. Crossed views of burden and emotional distress of cancer patients and family caregivers during palliative care. Psycho Oncol. 2016;25(11):1278–1285. doi: 10.1002/pon.4056.

7. Li Q., Lin Y., Xu Y., Zhou H. The impact of depression and anxiety on quality of life in Chinese cancer patient-family caregiver dyads, a cross-sectional study. Health Qual Life Outcome. 2018;16(1):230. doi: 10.1186/s12955-018-1051-3. 230.

8. Mosher C.E., Adams R.N., Helft P.R., et al. Family caregiving challenges in advanced colorectal cancer: patient and caregiver perspectives. Support Care Cancer. 2016;24(5):2017–2024. doi: 10.1007/s00520-015-2995-z. official journal of the Multinational Association of Supportive Care in Cancer.

9. Airth M. Psychosocial Intervention: Definition & Examples. https://study.com/academy/lesson/psychosocial-intervention-definition-examples.html ..

10. Psychosocial Interventions for Mental and Substance Use Disorders: A Framework for Establishing Evidence-Based Standards. National Academies Press (US); Washington (DC): 2015. Committee on developing evidence-based standards for psychosocial interventions for mental disorders, board on health sciences policy, medicine io.

11. Berg C.A., Upchurch R. A developmental-contextual model of couples coping with chronic illness across the adult life span. Psychol Bull. 2007;133(6):920–954. doi: 10.1037/0033-2909.133.6.920.

12. Coyne J.C., Smith D.A. Couples coping with a myocardial infarction: a contextual perspective on wives' distress. J Pers Soc Psychol. 1991;61(3):404–412. doi: 10.1037//0022-3514.61.3.404.

13. Lyons K.S., Lee C.S. The theory of dyadic illness management. J Fam Nurs. 2018;24(1):8–28. doi: 10.1177/1074840717745669.

14. Badr H., Bakhshaie J., Chhabria K. Dyadic interventions for cancer survivors and caregivers: state of the science and new directions. Semin Oncol Nurs. 2019;35(4):337–341. doi: 10.1016/j.soncn.2019.06.004.

15. Wang F., Luo D., Fu L., et al. The efficacy of couple-based interventions on health-related quality of life in cancer patients and their spouses: a meta-analysis of 12 randomized controlled trials. Cancer Nurs. 2017;40(1) doi: 10.1097/ncc.0000000000000356.

16. Gabriel I., Creedy D., Coyne E. A systematic review of psychosocial interventions to improve quality of life of people with cancer and their family caregivers. Nurs Open. 2020;7(5):1299–1312. doi: 10.1016/j.conctc.2021.100802.

17. Regan T.W., Lambert S.D., Girgis A., Kelly B., Kayser K., Turner J. Do couple-based interventions make a difference for couples affected by cancer?: a systematic review. BMC Cancer. 2012;12(1):279. doi: 10.1186/1471-2407-12-279.

18. Otto A.K., Gonzalez B.D., Heyman R.E., Vadaparampil S.T., Ellington L., Reblin M. Dyadic effects of distress on sleep duration in advanced cancer patients and spouse caregivers. Psycho Oncol. 2019;28(12):2358–2364. doi: 10.1002/pon.5229.

19. Streck B.P., Wardell D.W., LoBiondo-Wood G., Beauchamp J.E.S. Interdependence of physical and psychological morbidity among patients with cancer and family caregivers: review of the literature. Psycho Oncol. 2020;29(6):974–989. doi: 10.1002/pon.5382.

20. Nimbi F.M., Rossi R., Simonelli C. Telephone sexual counselling and current technologies: are helplines still effective in the social media era? Sexologies. 2018;27(3):E77–E84. doi: 10.1016/j.sexol.2018.05.004.

21. Shaffer K.M., Tigershtrom A., Badr H., Benvengo S., Hernandez M., Ritterband L.M. Dyadic psychosocial eHealth interventions: systematic scoping review. J Med Internet Res. 2020;22(3):e15509. doi: 10.2196/15509.

22. Page M.J., McKenzie J.E., Bossuyt P.M., et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Br Med J. 2021;372:n71. doi: 10.1136/bmj.n71.

23. Higgins J.P.T.S.J., Page M.J., Elbers R.G., Sterne J.A.C. In: Cochrane Handbook for Systematic Reviews of Interventions Version 6.2. Higgins J.P.T.T.J., Chandler J., Cumpston M., Li T., Page M.J., Welch V.A., editors. Cochrane; 2021. Assessing risk of bias in a randomized trial.

24. Grissom Robert J., John J., Kim . Lawrence Erlbaum Associates; Mahwah NJ: 2005. Effect Sizes for Research: A Broad Practical Approach.

25. Morris S.B. Estimating effect sizes from pretest-posttest-control group designs. Organ Res Methods. 2007;11(2):364–386. doi: 10.1177/1094428106291059.

26. Duval S., Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–463. doi: 10.1111/j.0006-341x.2000.00455.x.

27. Sterne J.A.C., Sutton A.J., Ioannidis J.P.A., et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002. doi: 10.1136/bmj.d4002.

28. Mazanec S.R., Miano S., Baer L., Campagnaro E.L., Sattar A., Daly B.J. A family-centered intervention for the transition to living with multiple myeloma as a chronic illness: a pilot study. Appl Nurs Res. 2017;35:86–89. doi: 10.1016/j.apnr.2017.03.003.

29. Northouse L.L., Mood D.W., Schafenacker A., et al. Randomized clinical trial of a brief and extensive dyadic intervention for advanced cancer patients and their family caregivers. Psycho Oncol. 2013;22(3):555–563. doi: 10.1002/pon.3036.

30. Lau B.H.P., Chow A.Y.M., Ng T.-K., et al. Comparing the efficacy of integrative body-mind-spirit intervention with cognitive behavioral therapy in patient-caregiver parallel groups for lung cancer patients using a randomized controlled trial. J Psychosoc Oncol. 2020;38(4):389–405. doi: 10.1080/07347332.2020.1722981.

31. Porter L.S., Keefe F.J., Baucom D.H., Olsen M., Zafar S.Y., Uronis H. A randomized pilot trial of a videoconference couples communication intervention for advanced GI cancer. Psycho Oncol. 2017;26(7):1027–1035. doi: 10.1002/pon.4121.

32. Paterson C., Primeau C., Nabi G. A pilot randomised controlled trial of a multimodal supportive care (ThriverCare) intervention for managing unmet supportive care needs in men with metastatic prostate cancer on hormonal treatment and their partner/caregivers. Eur J Oncol Nurs. 2018;37:65–73. doi: 10.1016/j.ejon.2018.10.007.

33. Chambers S.K., Girgis A., Occhipinti S., et al. A randomized trial comparing two low-intensity psychological interventions for distressed patients with cancer and their caregivers. Oncol Nurs Forum. 2014;41(4):E256–E266. doi: 10.1188/14.ONF.E256-E266.

34. Lambert S.D., McElduff P., Girgis A., et al. A pilot, multisite, randomized controlled trial of a self-directed coping skills training intervention for couples facing prostate cancer: accrual, retention, and data collection issues. Support Care Cancer. 2016;24(2):711–722. doi: 10.1007/s00520-015-2833-3.

35. Steel J.L., Reyes V., Zandberg D.P., et al. The next generation of collaborative care: the design of a novel web-based stepped collaborative care intervention delivered via telemedicine for people diagnosed with cancer. Contemp Clin Trials. 2021;105:106295. doi: 10.1016/j.cct.2021.106295.

36. Li Y.W., Ling L., Pan Z.Y. Effect of wellness education on quality of life of patients with non-small cell lung cancer treated with first-line icotinib and on their family caregivers. Integr Cancer Ther. 2019;18 doi: 10.1016/j.currproblcancer.2018.03.006.

37. Badr H., Herbert K., Chhabria K., Sandulache V.C., Chiao E.Y., Wagner T. Self-management intervention for head and neck cancer couples: results of a randomized pilot trial. Cancer. 2019;125(7):1176–1184. doi: 10.1002/cncr.31906.

38. Clark M.M., Rummans T.A., Atherton P.J., et al. Randomized controlled trial of maintaining quality of life during radiotherapy for advanced cancer. Cancer. 2013;119(4):880–887. doi: 10.1002/cncr.27776.

39. Christensen D.N. Postmastectomy couple counseling: an outcome study of a structured treatment protocol. J Sex Marital Ther. 1983;9(4):266–275. doi: 10.1080/00926238308410913.

40. Gremore T.M., Brockstein B., Porter L.S., et al. Couple-based communication intervention for head and neck cancer: a randomized pilot trial. Support Care Cancer. 2021;29(6):3267–3275. doi: 10.1007/s00520-020-05848-5.

41. Ledderer L., la Cour K., Mogensen O., et al. Feasibility of a psychosocial rehabilitation intervention to enhance the involvement of relatives in cancer rehabilitation: pilot study for a randomized controlled trial. Patient-Patient Centered Outcomes Research. 2013;6(3):201–212. doi: 10.1007/s40271-013-0019-y.

42. Milbury K., Li Y., Durrani S., et al. A mindfulness-based intervention as a supportive care strategy for patients with metastatic non-small cell lung cancer and their spouses: results of a three-arm pilot randomized controlled trial. Oncol. 2020;25(11):e1794–e1802. doi: 10.1634/theoncologist.2020-0125.

43. Tiete J., Delvaux N., Liénard A., Razavi D. Efficacy of a dyadic intervention to improve communication between patients with cancer and their caregivers: a randomized pilot trial. Patient Educ Counsel. 2021;104(3):563–570. doi: 10.1016/j.pec.2020.08.024.

44. Kubo A., Kurtovich E., McGinnis M., et al. A randomized controlled trial of mHealth mindfulness intervention for cancer patients and informal cancer caregivers: a feasibility study within an integrated health care delivery System. Integr Cancer Ther. 2019;18 doi: 10.1177/1534735419850634. 1534735419850634.

45. Campbell L.C., Keefe F.J., Scipio C., et al. Facilitating research participation and improving quality of life for African American prostate cancer survivors and their intimate partners - a pilot study of telephone-based coping skills training. Cancer. 2007;109(2):414–424. doi: 10.1002/cncr.22355.

46. Kayser K., Feldman B.N., Borstelmann N.A., Daniels A.A. Effects of a randomized couple-based intervention on quality of life of breast cancer patients and their partners. Soc Work Res. 2010;34(1):20–32. doi: 10.1093/swr/34.1.20.

47. Wolff J.L., Aufill J., Echavarria D., et al. A randomized intervention involving family to improve communication in breast cancer care. NPJ Breast Cancer. 2021;7(1):14. doi: 10.1038/s41523-021-00217-9.

48. Hsiao F.-H., Jow G.-M., Kuo W.-H., et al. The long-term effects of mindfulness added to family resilience-oriented couples support group on psychological well-being and cortisol responses in breast cancer survivors and their partners. Mindfulness. 2016;7(6):1365–1376. doi: 10.1007/s12671-016-0578-9.

49. McCaughan E., Curran C., Northouse L., Parahoo K. Evaluating a psychosocial intervention for men with prostate cancer and their partners: Outcomes and lessons learned from a randomized controlled trial. Appl Nurs Res. 2018;40:143–151. doi: 10.1016/j.apnr.2018.01.008.

50. Manne S.L., Kissane D.W., Nelson C.J., Mulhall J.P., Winkel G., Zaider T. Intimacy-enhancing psychological intervention for men diagnosed with prostate cancer and their partners: a pilot study. J Sex Med. 2011;8(4):1197–1209. doi: 10.1111/j.1743-6109.2010.02163.x.

51. Sutherby R. 2020. Cortisol Levels and Stress: How Cortisol Levels and Stress Are Connected. https://www.everlywell.com/blog/sleep-and-stress/cortisol-levels-and-stress/

52. Milbury K., Li J., Weathers S.-P., et al. Pilot randomized, controlled trial of a dyadic yoga program for glioma patients undergoing radiotherapy and their family caregivers. Neuro-Oncology Practice. 2018;6(4):311–320. doi: 10.1093/nop/npy052.

53. Mosher C.E., Secinti E., Johns S.A., et al. Examining the effect of peer helping in a coping skills intervention: a randomized controlled trial for advanced gastrointestinal cancer patients and their family caregivers. Qual Life Res. 2018;27(2):515–528. doi: 10.1007/s11136-017-1620-7.

54. Northouse L., Kershaw T., Mood D., Schafenacker A. Effects of a family intervention on the quality of life of women with recurrent breast cancer and their family caregivers. Psycho Oncol. 2005;14(6):478–491. doi: 10.1002/pon.871.

55. Dvorak A.L. Music therapy support groups for cancer patients and caregivers: a mixed-methods approach. Can J Music Ther. 2015;21(1):69–105.

56. Giesler R.B., Given B., Given C.W., et al. Improving the quality of life of patients with prostate carcinoma - a randomized trial testing the efficacy of a nurse-driven intervention. Cancer. 2005;104(4):752–762. doi: 10.1002/cncr.21231.

57. Hu Y., Liu T., Li F. Association between dyadic interventions and outcomes in cancer patients: a meta-analysis. Support Care Cancer. 2019;27(3):745–761. doi: 10.1007/s00520-018-4556-8.

58. Yan Z., Zhang Q., Chang L., Liu Y., Li Y. Dyadic effects of family resilience on post-traumatic stress symptoms among breast cancer patients and their primary family caregivers: a cross-sectional study. Eur J Oncol Nurs. 2021;53:101998. doi: 10.1016/j.ejon.2021.101998.

59. Son H., Son Y.J., Kim H., Lee Y. Effect of psychosocial interventions on the quality of life of patients with colorectal cancer: a systematic review and meta-analysis. Health Qual Life Outcome. 2018;16(1):119. doi: 10.1186/s12955-018-0943-6.

60. Badr H., Carmack C.L., Diefenbach M.A. Psychosocial interventions for patients and caregivers in the age of new communication technologies: opportunities and challenges in cancer care. J Health Commun. 2015;20(3):328–342. doi: 10.1080/10810730.2014.965369.

61. Compen F., Adang E., Bisseling E., van der Lee M., Speckens A. Cost-utility of individual internet-based and face-to-face Mindfulness-Based Cognitive Therapy compared with treatment as usual in reducing psychological distress in cancer patients. Psycho Oncol. 2020;29(2):294–303. doi: 10.1002/pon.5246.

62. Northouse L., Schafenacker A., Barr K.L.C., et al. A tailored Web-based psychoeducational intervention for cancer patients and their family caregivers. Cancer Nurs. 2014;37(5):321–330. doi: 10.1097/NCC.0000000000000159.

63. Matthys O., De Vleminck A., Dierickx S., et al. Effectiveness of a nurse-delivered (FOCUS+) and a web-based (iFOCUS) psychoeducational intervention for people with advanced cancer and their family caregivers (DIAdIC): study protocol for an international randomized controlled trial. BMC Palliat Care. 2021;20(1):193. doi: 10.1186/s12904-021-00895-z.

64. Song L.X., Qan'ir Y., Guan T., et al. The challenges of enrollment and retention: a systematic review of psychosocial behavioral interventions for patients with cancer and their family caregivers. J Pain Symptom Manag. 2021;62(3):E279–E304. doi: 10.1016/j.jpainsymman.2021.04.019.

65. Badr H., Krebs P. A systematic review and meta-analysis of psychosocial interventions for couples coping with cancer. Psycho Oncol. 2013;22(8):1688–1704. doi: 10.1002/pon.3200.

66. Dilworth S., Higgins I., Parker V., Kelly B., Turner J. Patient and health professional's perceived barriers to the delivery of psychosocial care to adults with cancer: a systematic review. Psycho Oncol. 2014;23(6):601–612. doi: 10.1002/pon.3474.

67. Daem M., Verbrugghe M., Schrauwen W., Leroux S., Van Hecke A., Grypdonck M. How interdisciplinary teamwork contributes to psychosocial cancer support. Cancer Nurs. 2019;42(3) doi: 10.1097/NCC.0000000000000588.

68. Luo X.J., Gao L.H., Li J.Y., Lin Y., Zhao J., Li Q.P. A critical literature review of dyadic web-based interventions to support cancer patients and their caregivers, and directions for future research. Psycho Oncol. 2020;29(1):38–48. doi: 10.1002/pon.5278.

69. Willems R.A., Bolman C.A.W., Lechner L., et al. Online interventions aimed at reducing psychological distress in cancer patients: evidence update and suggestions for future directions. Curr Opin Support Palliat Care. 2020;14(1):27–39. doi: 10.1097/SPC.0000000000000483.

70. Deng Z., Mo X., Liu S. Comparison of the middle-aged and older users' adoption of mobile health services in China. Int J Med Inf. 2014;83(3):210–224. doi: 10.1016/j.ijmedinf.2013.12.002.

71. Junkins C.C., Kent E., Litzelman K., Bevans M., Cannady R.S., Rosenberg A.R. Cancer across the ages: a narrative review of caregiver burden for patients of all ages. J Psychosoc Oncol. 2020;38(6):782–798. doi: 10.1080/07347332.2020.1796887.

72. Gabriel I., Creedy D., Coyne E. Feasibility of a socio-spiritual intervention to improve quality of life of adult Nigerians with cancer and their family caregivers: protocol for a randomised controlled trial. Contemporary Clinical Trials Communications. 2021;22:2451–8654. doi: 10.1016/j.conctc.2021.100802. (Electronic)):100802. https://doi.org/ARTN 100802.

73. Walker Z.J., Xue S., Jones M.P., Ravindran A.V. Depression, anxiety, and other mental disorders in patients with cancer in low- and lower-middle-income countries: a systematic review and meta-analysis. JCO global oncology. 2021;7:1233–1250. doi: 10.1200/GO.21.00056.

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