Parental psychological adjustment in pediatric acute lymphoblastic leukemia: The mediating role of family functioning and resilience

Academic Editor: William Arcese Received: 20 December 2024 Revised: 15 January 2025 Accepted: 16 January 2025 Published: 21 January 2025 Citation: Ferraz, A.; Faria, S.; Jerónimo, M.; Pereira, M.G. Parental Psychological Adjustment in Pediatric Acute Lymphoblastic Leukemia: The Mediating Role of Family Functioning and Resilience. Cancers 2025,17, 338. https://doi.org/10.3390/ cancers17030338 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). Article Parental Psychological Adjustment in Pediatric Acute Lymphoblastic Leukemia: The Mediating Role of Family Functioning and Resilience Ana Ferraz 1, Susana Faria 2, Mónica Jerónimo 3and M. Graça Pereira 1,* 1Psychology Research Centre (CIPsi), School of Psychology, Applied Psychology Department, University of Minho, 4710-057 Braga, Portugal; [email protected] 2Centre of Mathematics (CMAT), Department of Mathematics, University of Minho, 4800-058 Guimarães, Portugal; [email protected] 3Pediatric Oncology Department, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, 3000-602 Coimbra, Portugal; [email protected] *Correspondence: [email protected] Simple Summary: Parents of children with acute lymphoblastic leukemia often face challenges to their psychological well-being due to the nature of the disease and their parental responsibilities. Many experience clinically significant psychological distress, while others seem to adapt. Key factors in this adaptative process include family resilience, family functioning, and parental coping strategies. This longitudinal study aims to explore how psychological well-being, parental distress, coping strategies, and family functioning and resilience change over time. The study also examines the mediator roles of family functioning and resilience and coping strategies in the relationship between parental distress and psychological well-being. The findings highlight that both individual and family factors influence psychological well-being during treatment. Strengthening family resilience and functioning is crucial for supporting parents, and a family-centered approach in healthcare is important in addressing the challenges they face. Abstract: Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with intense treatments affecting both children and their families. Limited information is available on parental distress and psychological well-being during the first treatment year, with most studies focusing on individuals rather than the family system. This study explores longitudinal changes in parental distress (psychological morbidity and traumatic stress symptoms), coping strategies, family resilience and functioning, and psychological well-being. The study also examines the mediating roles of family resilience, family functioning, and coping strategies in the relationships between parental distress and psychological well-being. Methods: A prospective study was conducted with 46 parents of children newly diagnosed with ALL, assessing parental distress, family functioning and resilience, coping, and psychological well-being across three treatment phases: consolidation (T0), delayed intensification (T1), and maintenance (T2). Results: Parental distress and family resilience significantly decreased from T0 to T2, while parental coping improved over time. Family functioning deteriorated from T0 to T1, stabilizing thereafter. Psychological well-being followed a non-linear trajectory, initially declining from T0 to T1 and improving from T1 to T2. Mediation analyses revealed that family resilience and family functioning partially mediated the relationships between parental distress and psychological well-being. Parental coping did not emerge as a mediator. Conclusions: Parental psychological adjustment in the context of ALL is dynamic and influenced by individual and family factors. Interventions that strengthen family functioning and resilience are cruCancers 2025,17, 338 https://doi.org/10.3390/cancers17030338 Cancers 2025,17, 338 2 of 17 cial for supporting parental psychological well-being during treatment. A family-centered approach in healthcare delivery is essential to address individual and systemic challenges. Keywords: pediatric acute lymphoblastic leukemia; parental distress; psychological well-being; family resilience; family functioning; parental coping; family-centered care 1. Introduction Acute lymphoblastic leukemia (ALL) is the most common early childhood type of cancer, characterized as an aggressive form of leukemia marked by an overproduction of lymphocytes in the bone marrow and blood [ 1 ]. Over the last two decades, advancements in clinical trials, supportive care [ 2 ], and therapeutic approaches have significantly improved outcomes for these children, resulting in higher survival rates [ 3 ]. A key factor in this progress is the use of risk stratification, based on patient characteristics, cell biology, and initial treatment response through minimal residual disease (MRD) assessment [ 4 ]. In 2019 , 14 European countries adopted the ALLTogether protocol, which incorporates MRD and genetic profiling for more precise risk stratification [ 5 , 6 ]. This collaborative protocol, with its multi-phase treatment plan (induction, consolidation 1, consolidation 2, delayed intensification, consolidation 3, and maintenance), tailors treatment intensity according to the group risk (standard risk, intermediate risk, and high risk) [ 7 ], optimizing therapy and ultimately improving survival and quality of life (QoL) [ 8 ]. Nonetheless, cancer diagnosis remains a source of fear, often leading to major changes in the parents’ lives [ 2 ], usually considered life-changing [ 9 ]. Thus, the demands of diagnosis and subsequent treatment strategies impact parents’ caregiving roles and well-being [10]. ALL remains a life-threatening condition [ 11 ], with parents perceiving a serious threat to their child’s life and the treatment process as complex and invasive [ 12 ]. Throughout the treatment process, parents experience frequent hospital visits and admissions, invasive and painful procedures, and health crises, alongside disruptions in their physical, emotional, and social lives due to treatment [ 13 ]. The treatment lasts 2 to 3 years, with intensive therapy during the first few months [ 14 ], placing family members at greater risk for distress compared to families coping with other cancer diagnoses [15]. As primary caregivers, parents play a crucial role in their children’s adjustment, supporting their coping with illness and treatment while minimizing psychological effects [ 16 ]. Their psychological well-being is a key factor for effective parenting intervention [ 17 ]. However, studies on parental psychological adjustment and well-being show mixed results, particularly during the first year of treatment, when heightened distress is common [ 18 ]. Parenting is often perceived as demanding and stressful, leading to physical and psychological consequences [ 19 ] such as symptoms of anxiety, depression [ 20 , 21 ], post-traumatic stress [ 21 , 22 ], distress [ 23 ], burnout [ 24 ], sleep disturbances [ 23 ], and psychosocial and financial burdens [ 25 , 26 ]. Additionally, parents also face significant disruptions in social interactions [ 27 ], work-related concerns, and changes in family dynamics [ 22 ], further negatively affecting their QoL [28] and psychological well-being [29]. A recent systematic review emphasized the association between parental distress at diagnosis and subsequent adjustment [ 30 ], with mental health issues potentially lasting for years after diagnosis [ 31 ]. Studies have shown that parents of children with leukemia often report low psychological well-being while caring for their ill child [ 32 , 33 ]. Therefore, these parents may be considered “hidden patients”, requiring special attention to prevent physical and emotional consequences [ 34 ]. However, limited descriptive information is available in most studies regarding parental distress throughout the first year of Cancers 2025,17, 338 3 of 17 treatment [35,36] , underlying the need for longitudinal studies regarding parental distress in childhood ALL [30]. Despite some studies showing that anxiety, depression, and traumatic stress symptoms tend to decrease over time, many caregivers continue to experience clinically significant psychological distress (e.g., [ 35 , 36 ]). Conversely, other studies suggest successful adaptation and coping [ 37 ], highlighting the absence of major psychosocial difficulties among parents [ 38 ]. Key factors in this adaptative process include family resilience [ 39 , 40 ], family functioning [41,42], and parental coping strategies [33]. Family resilience is a potential resource within the family system [ 39 ] that helps parents approach challenges, maintaining stability and avoiding disruptions in family life [ 43 ]. Therefore, resilience is crucial for managing cancer-related challenges effectively [ 44 ], being directly related to psychological well-being [ 45 ]. However, the ability to be resilient changes throughout life and in the presence of a stressor event [ 46 ], with some families still struggling with resilience challenges [ 47 ]. In this way, longitudinal studies are needed to understand the dynamic changes in family resilience over time and across treatment phases [48]. Family functioning, i.e., the way the family as a whole deals and responds to a child’s illness, impacts the family’s adjustment to a stressor event [ 41 ], being positively related to well-being [ 49 ]. However, family conflicts are more prevalent in families of children with cancer compared to families of healthy children [ 50 ]. As a result, families with poor functioning may be more susceptible to adjustment challenges, as they struggle to manage illness and parenting demands [ 41 ]. Research found that family functioning in childhood cancer is negatively impacted, particularly in the first year after diagnosis [ 50 ], but resilience can help restore family functioning [ 39 ]. Although there is growing awareness of the importance of family functioning in the context of pediatric cancer, most studies focus on individual-level factors, neglecting the family-system perspective [51]. Coping strategies are also central to studies on the psychological well-being of parents caring for children with leukemia (e.g., [ 33 ]). Parents adopt several strategies to manage caregiving challenges, which can improve overall well-being [ 52 ]. Research has shown that low emotional coping (i.e., less cognitive avoidance, less acceptance or resignation, and less emotional discharge) is linked to better psychological well-being [ 53 ], while active coping strategies reduce parental distress a year after the diagnosis [ 9 ]. A selforiented parental coping approach, compared to treatmentor children’s daily care-oriented strategies, uniquely contributed to parents’ psychological well-being [ 33 ]. Thus, identifying caregiver coping strategies is essential for developing interventions to improve caregivers’ psychological well-being [54]. The first year of treatment is a particularly vulnerable time for parents [ 35 ], making it crucial to understand the trajectory of their psychological well-being, distress (psychological morbidity and traumatic stress symptoms), coping strategies, family functioning, and family resilience. While most studies rely on cross-sectional designs, limited information is available on how families and their members adapt over time [ 55 ]. Moreover, few studies have explored parental psychological well-being in this context [ 9 ]. Considering the crucial role of the family in childhood cancer [ 51 ], more attention should be directed to the impact of family resources on parental adjustment following their child’s diagnosis [ 42 ], such as family functioning and family resilience. Furthermore, coping strategies remain insufficiently explored in the context of family adaptation to childhood cancer despite their potential significance [ 56 ]. Addressing these gaps could provide valuable insights for the development of family-centered psychological interventions aimed at enhancing the psychological well-being of parents of children with ALL. Studies have emphasized the Cancers 2025,17, 338 4 of 17 unique challenges faced by families of children with hematologic cancers (e.g., ALL) and the importance of tailored support resources [57]. This study is grounded on Livneh’s [ 58 ] model of psychosocial adaptation to chronic disease, which aims to understand the adaptation process within the context of chronic illnesses. According to this model, adaptation is a dynamic process influenced by various factors, ranging from individual characteristics to family and social contexts. Based on this framework, the present study had the following aims: 1. To assess changes over time in parental psychological morbidity, traumatic stress symptoms, coping strategies, family functioning and resilience, and psychological well-being while controlling for being on leave; 2. To explore the mediator role of family functioning, family resilience, and coping strategies between psychological morbidity and psychological well-being; 3. To explore the mediator role of family functioning, family resilience, and coping strategies between traumatic stress symptoms and psychological well-being. 2. Materials and Methods 2.1. Study Design This longitudinal study with three assessment moments is part of a Portuguese multicentric project addressing the family experience of childhood ALL. The study was conducted at three major Portuguese cancer hospitals, between February 2022 and August 2024. This study received approval from the Ethics Committee for Research in Social and Human Sciences of a major public university (CEICSH 067/2021) and the Ethics Committees of the three hospitals where data collection took place (024/CES; CES.13/022; UIC/1474), and it was performed according to the Declaration of Helsinki. The participants were informed about the study and provided written informed consent. 2.2. Participants A total of 50 parents and their children met the eligibility criteria, and 46 agreed to participate in the present study. Children were eligible if they were diagnosed with ALL for the first time, were six years or younger at the time of diagnosis, and were receiving treatment according to the ALLTogether protocol. Institutionalized children, those with a previous clinical history of oncological disease, and those classified in the high-risk group during the final stratification were excluded. Eligibility criteria for parents were to be the child’s primary caregiver, at least 18 years old, and literate. 2.3. Instruments 2.3.1. Sociodemographic and Clinical Questionnaire This questionnaire was developed for this study to assess parents’ and child’s sociodemographic variables (e.g., sex, age, and marital status) as answered by the participants and child’s clinical variables (e.g., time since diagnosis, duration of hospitalization, and risk group) as answered by healthcare professionals. 2.3.2. Psychological Well-Being Scale (PWS) [59,60] We utilized a self-report scale that assesses psychological well-being across six dimensions: autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance. It comprises 18 items rated on a five-point Likert scale ranging from 1 to 5, with higher scores indicating higher levels of psychological well-being. Cronbach’s alphas for the Portuguese version ranged from 0.36 to 0.50. Only the total scale was used in the present study, with a Cronbach’s alpha of 0.84 and McDonald’s omega of 0.82. Cancers 2025,17, 338 5 of 17 2.3.3. Hospital Anxiety and Depression Scale (HADS) [61,62] This questionnaire evaluates psychological morbidity through 14 items equally divided into two subscales: anxiety and depression. Each item is rated on a four-point Likert scale, ranging from 0 to 3. High scores indicate greater psychological morbidity. In the Portuguese version, Cronbach’s alpha was 0.76 for the anxiety subscale and 0.81 for the depression subscale. In the present study, only the total scale was used, with a Cronbach’s alpha of 0.89 and McDonald’s omega of 0.88. 2.3.4. Impact of Event Scale-Revised (IES-R) [63,64] This self-report scale evaluates traumatic stress symptoms caused by a traumatic event, across 22 items divided into intrusion, avoidance, and hyperarousal subscales. Participants answered on a five-point Likert scale, ranging from 0 to 4, with higher scores indicating greater traumatic stress symptoms. In the Portuguese version, Cronbach’s alpha ranged from 0.89 to 0.91. Only the total scale was used in this study, with a Cronbach’s alpha and McDonald’s omega of 0.93. 2.3.5. Family Assessment Device–General Functioning (FAD-GF) [65,66] As a single indicator, the global scale of the FAD evaluates the perception of overall family functioning through twelve items, with six items on healthy and six items on unhealthy family functioning. Scoring is calculated through a four-point Likert scale, ranging from 1 to 4. The higher the score, the more problematic the family’s overall functioning is perceived to be. In the Portuguese version, Cronbach’s alpha was 0.79. In the present study, Cronbach’s alpha and McDonald’s omega were both 0.93. 2.3.6. Family Hardiness Index (FHI) [67,68] This self-report instrument, consisting of 20 items rated on a four-point scale ranging from 0 to 3, evaluates the internal strengths and durability of the family unit when dealing with stress or adversity through three subscales: commitment, challenge, and control. A higher score indicates greater family resilience. Cronbach’s alpha for the overall scale was 0.76 in the Portuguese version. Cronbach’s alpha and McDonald’s omega, in this study, were 0.88 and 0.87, respectively. 2.3.7. Coping Health Inventory for Parents (CHIP) [69,70] This instrument assesses coping strategies and styles among parents of children with severe or chronic illnesses, through 44 items. Three coping pattern subscales are included: (I) maintenance of family integration, cooperation, and an optimistic definition of the situation; (II) maintenance of social support, self-esteem, and psychological stability; and (III) understanding the medical situation through communication with other parents and consultation with medical staff. Items are rated on a Likert scale from 0 to 3, with higher scores indicating higher levels of parental coping. In the Portuguese version, Cronbach’s alphas were found to be 0.80, 0.82, and 0.76 for each scale, respectively, and 0.89 for the overall score. In the present study, Cronbach’s alpha and McDonald’s omega for the total scale were 0.87 and 0.88, respectively. 2.4. Procedure Participants meeting the inclusion criteria were identified by healthcare professionals and informed about the study during the initial phase of treatment. Those who agreed to meet with the researcher in person were subsequently invited to participate in the study. After being informed about the study’s purpose, data confidentiality, voluntary participation, and their right to withdraw without consequences, participants who chose to proceed provided written informed consent. Parents’ psychological morbidity and trau- Cancers 2025,17, 338 6 of 17 matic stress symptoms, coping strategies, family functioning and resilience, and parental psychological well-being were assessed at three different treatment phases: the first week of consolidation 1 (T0) ; the first week of delayed intensification (T1); and the first week of maintenance (T2) (see Figure 1). Cancers 2025, 17, x FOR PEER REVIEW 6 of 18 proceed provided written informed consent. Parents’ psychological morbidity and traumatic stress symptoms, coping strategies, family functioning and resilience, and parental psychological well-being were assessed at three different treatment phases: the first week of consolidation 1 (T0); the first week of delayed intensification (T1); and the first week of maintenance (T2) (see Figure 1). Figure 1. Schematic overview and chronological timeline of the study. The first assessment (T0) was conducted in person, and participants answered several questionnaires (i.e., sociodemographic and clinical, anxiety, depressive and traumatic stress symptomatology; family functioning and resilience; and psychological well-being). In the remaining assessment points (T1 and T2), the data were collected through the online software Qualtrics XM, a licensed tool for creating and distributing questionnaires online, which participants were invited to complete individually. For this purpose, participants were contacted and reminded before the data collection moments to ensure the feasibility of all time points. The researcher subsequently sent the link to the questionnaire. The mean time required to complete the self-report questionnaires was 20 min. 2.5. Data Analysis Sample characterization was performed through frequencies and percentages for categorical variables and means and standard deviations for continuous variables, using IBM SPPS Statistics (Statistical Package for the Social Sciences) version 29. The following statistical analyses were performed using the R Statistical Computing Environment [71]. The courses of parental psychological morbidity (anxiety and depression symptoms), traumatic stress symptoms, family functioning, family resilience, parental coping, and parental psychological well-being over time were modeled using linear mixed models while controlling for parental leave status. The mediation analysis was performed using R and the mediation package [72]. The bootstrapping technique, involving 5.000 samples, was applied to estimate the 95% confidence intervals (CI) for the direct and indirect effects. Indirect effects were considered significant if the 95% CI did not include zero [73]. Figure 1. Schematic overview and chronological timeline of the study. The first assessment (T0) was conducted in person, and participants answered several questionnaires (i.e., sociodemographic and clinical, anxiety, depressive and traumatic stress symptomatology; family functioning and resilience; and psychological well-being). In the remaining assessment points (T1 and T2), the data were collected through the online software Qualtrics XM, a licensed tool for creating and distributing questionnaires online, which participants were invited to complete individually. For this purpose, participants were contacted and reminded before the data collection moments to ensure the feasibility of all time points. The researcher subsequently sent the link to the questionnaire. The mean time required to complete the self-report questionnaires was 20 min. 2.5. Data Analysis Sample characterization was performed through frequencies and percentages for categorical variables and means and standard deviations for continuous variables, using IBM SPPS Statistics (Statistical Package for the Social Sciences) version 29. The following statistical analyses were performed using the R Statistical Computing Environment [ 71 ]. The courses of parental psychological morbidity (anxiety and depression symptoms), traumatic stress symptoms, family functioning, family resilience, parental coping, and parental psychological well-being over time were modeled using linear mixed models while controlling for parental leave status. The mediation analysis was performed using R and the mediation package [ 72 ]. The bootstrapping technique, involving 5.000 samples , was applied to estimate the 95% confidence intervals (CI) for the direct and indirect effects. Indirect effects were considered significant if the 95% CI did not include zero [73]. 3. Results 3.1. Sample Characteristics The study included 46 parents (39 mothers) at baseline (T0), with a mean age of 35.41 years (SD = 6.77). Most parents lived in urban areas (54.3%) and were married (58.7%) Cancers 2025,17, 338 7 of 17 or living with a partner (32.6%). The majority had no higher education (54.3%), and 69.6% of the 42 employed parents were on leave to take care of the children. About 89% of the parents provided more than 18 h of care daily. The children had a mean age of 3.48 years (SD = 1.43), with 63.0% being girls. The subtype of leukemia was predominantly ALL-B (95.7%). On average, children had been hospitalized for 21.96 days (SD = 9.25) and were diagnosed 31.65 days (SD = 5.90) before the assessment. Participants who dropped out after T0 and T1 did not significantly differ from those who remained in the study regarding their sociodemographic and clinical characteristics. The sociodemographic and clinical characteristics of parents and children at each assessment time point (T0, T1, and T2) are presented in Tables 1and 2, respectively. Table 1. Parents’ sociodemographic and clinical characteristics at T0, T1, and T2. T0 (n= 46) T1 (n= 42) T2 (n= 39) Categorical Variables n(%) n(%) n(%) Sex Male 7 (15.2) 6 (14.3) 5 (12.8) Female 39 (84.9) 36 (85.7) 34 (87.2) Residential area Urban 25 (54.3) 23 (54.8) 21 (53.8) Rural 21 (45.7) 19 (45.2) 18 (46.2) Marital status Single 4 (8.7) 4 (9.5) 2 (5.1) Married 27 (58.7) 24 (57.1) 22 (56.4) Living with partner 15 (32.6) 14 (33.3) 15 (38.5) Education With higher education 21 (45.7) 19 (45.2) 21 (53.8) Without higher education 25 (54.3) 23 (54.8) 18 (46.2) Employment status Unemployed 4 (8.7) 5 (11.9) 4 (10.3) Employed 42 (91.3) 37 (88.1) 35 (89.7) On leave 32 (69.6) 27 (73.0) 25 (71.4) Financial impact No 30 (65.2) 17 (40.5) 17 (43.6) Yes 16 (34.8) 25 (59.5) 22 (56.4) Chronic illness No 37 (80.4) 34 (81.0) 32 (82.1) Yes 9 (19.6) 8 (19.0) 7 (17.9) Medication No 34 (73.9) 32 (76.2) 29 (74.4) Yes 12 (26.1) 10 (23.8) 10 (25.6) Daily hours of care <6 h 0 (0) 1 (2.4) 1 (2.6) 6–12 h 0 (0) 4 (9.5) 4 (10.3) 12–18 h 5 (10.9) 4 (9.5) 8 (20.5) >18 h 41 (89.1) 33 (78.6) 26 (66.7) Presence of other informal caregiver No 5 (10.9) 6 (14.3) 8 (20.5) Yes 41 (89.1) 36 (85.7) 31 (79.5) Continuous variables Min–Max Mean (SD) Mean (SD) Mean (SD) Age 23–52 35.41 (6.77) 35.19 (7.00) 35.56 (6.66) Cancers 2025,17, 338 8 of 17 Table 2. Children’s sociodemographic and clinical characteristics at T0, T1, and T2. T0 (n= 46) T1 (n= 42) T2 (n= 39) Categorical Variables n(%) n(%) n(%) Sex Boy 17 (37.0) 16 (38.1) 14 (35.9) Girl 29 (63.0) 26 (61.9) 25 (64.1) Number of siblings 0 24 (52.2) 21 (50.0) 20 (51.3) 1 16 (34.8) 16 (38.1) 15 (38.5) 2 6 (13.0) 5 (11.9) 4 (10.3) ALL subtype ALL B 44 (95.7) 40 (95.2) 37 (94.9) ALL T 2 (4.3) 2 (4.8) 2 (5.1) Induction type Induction A 31 (67.4) 28 (66.7) 29 (74.4) Induction B 12 (26.1) 12 (28.6) 9 (23.1) Induction A + C 3 (6.5) 2 (4.8) 1 (2.6) Risk group Standard NA 12 (28.6) 11 (28.2) Intermediate low NA 14 (33.3) 15 (38.5) Intermediate high NA 16 (38.1) 13 (33.3) Clinical complications No 13 (28.3) 7 (16.7) 2 (5.1) Yes 33 (71.7) 35 (83.3) 37 (94.9) Continuous variables Mean (SD) Min–Max Mean (SD) Min–Max Mean (SD) Min–Max Age 3.48 (1.43) 1.25–6.00 3.39 (1.37) 1.25–6.00 3.49 (1.46) 1.25–6.00 Number of hospitalizations 1.46 (0.66) 1–3 4.90 (1.75) 7–12 7.18 (2.57) 3–16 Time since diagnosis (in days) 31.65 (5.90) 27–57 145.19 (20) 119–192 256.23 (58.81) 167–373 Hospitalizations duration (in days) 21.96 (9.25) 7–58 35.62 (14.01) 7–84 44.44 (15.31) 22–93 Note: NA = not applicable. 3.2. Differences over Time Parents’ psychological morbidity significantly decreased from T0 to T2 ( β = − 3.73, p< 0.01 ) and from T1 to T2 ( β = − 3.29, p< 0.01). Traumatic stress symptoms significantly decreased from T0 to T1 ( β = − 0.66, p< 0.05) and from T0 to T2 ( β = − 0.78, p< 0.01). Family resilience significantly decreased from T0 to T1 ( β = − 2.58, p< 0.05) and from T0 to T2 ( β=−2.24 ,p< 0.05), and family functioning scores significantly increased from T0 to T1 ( β= 0.18 ,p< 0.05). Parental coping strategies significantly increased from T0 to T1 ( β= 4.22 ,p< 0.05), from T0 to T2 ( β = 7.92, p< 0.001), and from T1 to T2 ( β = 3.07; p< 0.05). Psychological well-being significantly decreased from T0 to T1 ( β = − 4.26, p< 0.001) and increased from T1 to T2 (β= 3.53, p< 0.05) (Table 3and Figure 2). Cancers 2025,17, 338 9 of 17 Table 3. Regression coefficient estimates of the linear mixed-effects model. Response Variable Psychological Morbidity Traumatic Stress Symptoms Family Functioning Family Resilience Parental Coping Psychological Well-Being Fixed effects β(SE)β(SE)β(SE)β(SE)β(SE)β(SE) Intercept 16.48 (1.74) *** 3.68 (0.46) *** 1.38 (0.10) *** 47.05 (1.78) *** 101.41(3.21) *** 74.06 (1.97) *** T1 −0.44 (1.04) −0.66 (0.27) * 0.18 (0.07) * −2.58 (0.99) * 4.22 (1.95) * − 4.26 (1.09) *** T2 −3.73 (1.06) ** −0.78 (0.28) ** 0.12 (0.07) −2.24 (1.01) * 7.92 (1.98) *** −0.73 (1.11) On leave 2.02 (1.70) 0.60 (0.45) 0.15 (0.10) 0.38 (1.70) −3.20 (3.14) − 7.20 (1.88) *** Note. * p< 0.05, ** p< 0.01, and *** p< 0.001; β= estimate; SE = standard error. On leave: 0 = no, 1 = yes. Cancers 2025, 17, x FOR PEER REVIEW 9 of 18 Table 3. Regression coefficient estimates of the linear mixed-effects model. Response Variable Psychological Morbidity Traumatic Stress Symptoms Family Functioning Family Resilience Parental Coping Psychological Well-Being Fixed effects β (SE) β (SE) β (SE) β (SE) β (SE) β (SE) Intercept 16.48 (1.74) *** 3.68 (0.46) *** 1.38 (0.10) *** 47.05 (1.78) *** 101.41(3.21) *** 74.06 (1.97) *** T1 −0.44 (1.04) −0.66 (0.27) * 0.18 (0.07) * −2.58 (0.99) * 4.22 (1.95) * −4.26 (1.09) *** T2 −3.73 (1.06) ** −0.78 (0.28) ** 0.12 (0.07) −2.24 (1.01) * 7.92 (1.98) *** −0.73 (1.11) On leave 2.02 (1.70) 0.60 (0.45) 0.15 (0.10) 0.38 (1.70) −3.20 (3.14) −7.20 (1.88) *** Note. * p < 0.05, ** p < 0.01, and *** p < 0.001; β = estimate; SE = standard error. On leave: 0 = no, 1 = yes. Figure 2. Schematic overview and chronological timeline of the study. Figure 2. Graphical representation of differences over time. Cancers 2025,17, 338 16 of 17 42. Van Schoors, M.; De Paepe, A.L.; Norga, K.; Cosyns, V.; Morren, H.; Vercruysse, T.; Goubert, L.; Verhofstadt, L.L. Family members dealing with childhood cancer: A study on the role of family functioning and cancer appraisal. Front. Psychol. 2019,10, 1405. [CrossRef] [PubMed] 43. Kaboudi, M.; Abbasi, P.; Heidarisharaf, P.; Dehghan, F.; Ziapour, A. The effect of resilience training on the condition of style of coping and parental stress in mothers of children with leukemia. Int. J. Pediatr. 2018,6, 7299–7310. [CrossRef] 44. Habibpour, Z.; Mahmoudi, H.; Nir, M.S.; Areshtanab, H.N. Resilience and its predictors among the parents of children with cancer: A descriptive-correlational study. Indian. J. Palliat. Care 2019,25, 79. [CrossRef] 45. Halstead, E.; Ekas, N.; Hastings, R.P.; Griffith, G.M. Associations between resilience and the well-being of mothers of children with autism spectrum disorder and other developmental disabilities. J. Autism Dev. Disord. 2018,48, 1108–1121. [CrossRef] [PubMed] 46. Windle, G. What is resilience? A review and concept analysis. Rev. Clin. Gerontol. 2011,21, 152–169. [CrossRef] 47. Van Schoors, M.; Caes, L.; Verhofstadt, L.L.; Goubert, L.; Alderfer, M.A. Systematic review: Family resilience after pediatric cancer diagnosis. J. Pediatr. Psychol. 2015,40, 856–868. [CrossRef] 48. Shao, M.; Yang, H.; Du, R.; Zhang, M.; Zhu, J.; Zhang, H.; Zhu, J.; Zhang, H.; Ma, B.; Chen, C.; et al. Family resilience in cancer treatment and key influence factors: A systematic review. Eur. J. Oncol. Nurs. 2023,66, 102403. [CrossRef] [PubMed] 49. Wang, Q.; Liu, H.; Ren, Z.; Xiong, W.; He, M.; Li, N.; Fan, X.; Li, X.; Shi, H.; Zha, S.; et al. The associations of family functioning, general well-being, and exercise with mental health among end-stage renal disease patients. Psychiatry Investig. 2020,17, 356. [CrossRef] [PubMed] 50. Pai, A.L.; Greenley, R.N.; Lewandowski, A.; Drotar, D.; Youngstrom, E.; Peterson, C.C. A meta-analytic review of the influence of pediatric cancer on parent and family functioning. J. Fam. Psychol. 2007,21, 407. [CrossRef] [PubMed] 51. Van Schoors, M.; De Mol, J.; Morren, H.; Verhofstadt, L.L.; Goubert, L.; Van Parys, H. Parents’ perspectives of changes within the family functioning after a pediatric cancer diagnosis: A multi-family member interview analysis. Qual. Health Res. 2018,28, 1229–1241. [CrossRef] 52. McEvoy, B.; Creaner, M. The experiences of mothers who have a child diagnosed with cancer. Psychol. Health 2022,37, 597–614. [CrossRef] 53. Bürger Lazar, M.; Musek, J. Well-being in parents of children with cancer: The impact of parental personality, coping, and the child’s quality of life. Scand. J. Psychol. 2020,61, 652–662. [CrossRef] [PubMed] 54. Ismael, N.; Malkawi, S.; Al Awady, S.; Ismael, T. Exploring coping strategies among caregivers of children who have survived pediatric cancer in Jordan. BMJ Paediatr. Open 2024,8, e002453. [CrossRef] 55. Van Schoors, M.; De Paepe, A.L.; Lemiere, J.; Morez, A.; Norga, K.; Lambrecht, K.; Goubert, L.; Verhofstadt, L.L. Family adjustment when facing pediatric cancer: The role of parental psychological flexibility, dyadic coping, and network support. Front. Psychol. 2019,10, 2740. [CrossRef] 56. Prates, P.E.G.; Correa-Júnior, A.J.S.; Russo, T.M.D.S.; Paraizo-Horvath, C.M.S.; Teles, A.A.D.S.; Sonobe, H.M. Effectiveness of family coping interventions in improving problem-solving skills in the care of children and adolescent cancer survivors during and after treatment: A scoping review. Nurs. Rep. 2024,14, 2153–2178. [CrossRef] [PubMed] 57. Fisher, C.L.; Mullis, M.D.; Kastrinos, A.; Wollney, E.; Weiss, E.S.; Sae-Hau, M.; Bylund, C.L. “Home wasn’t really home anymore”: Understanding caregivers’ perspectives of the impact of blood cancer caregiving on the family system. Support. Care Cancer 2021, 29, 3069–3076. [CrossRef] [PubMed] 58. Livneh, H. Psychosocial adaptation to chronic illness and disability. Rehabil. Couns. Bull. 2001,44, 151–160. [CrossRef] 59. Ryff, C.D.; Keyes, C.L.M. The structure of psychological well-being revisited. J. Pers. Soc. Psychol. 1995,69, 719–727. [CrossRef] [PubMed] 60. Fernandes, H.M.; Vasconcelos-Raposo, J.; Teixeira, C.M. Preliminary analysis of the psychometric properties of Ryff’s scales of psychological well-being in Portuguese adolescents. Span. J. Psychol. 2010,13, 1032–1043. [CrossRef] 61. Zigmond, A.S.; Snaith, R.P. The Hospital and Anxiety and Depression Scale. Acta Psychiatr. Scand. 1983,7, 361–370. [CrossRef] [PubMed] 62. Pais-Ribeiro, J.; Silva, I.; Ferreira, T.; Martins, A.; Meneses, R.; Baltar, M. Validation study of a Portuguese version of the Hospital Anxiety and Depression Scale. Psychol. Health Med. 2007,12, 225–237. [CrossRef] [PubMed] 63. Weiss, D.S.; Marmar, C.R. The Impact of Event Scale-Revised. In Assessing Psychological Trauma and PTSD; Wilson, J., Keane, T.M., Eds.; Guilford Press: New York, NY, USA, 1997; pp. 399–411. 64. Pereira, M.; Figueiredo, A. Depressão, ansiedade e stress pós-traumático em doentes com cancro colo-rectal. Validação do Hospital Anxiety and Depression Scale (HADS) e Impact of Events Scale (IES) numa amostra de doentes oncológicos. Onco News 2008,5, 11–19. 65. Epstein, N.B.; Baldwin, L.M.; Bishop, D.S. The McMaster family assessment device. J. Marital. Fam. Ther. 1983,9, 171–180. [CrossRef] Cancers 2025,17, 338 17 of 17 66. Almeida, A.C.; Leandro, M.E.; Pereira, M.G. Psychometric properties of the Portuguese adaptation of General Functioning of Family Assessment Device: A comparative study. Fam. Syst. Health 2020,38, 162–171. [CrossRef] 67. McCubbin, M.A.; McCubbin, H.; Thompson, A. Family Hardiness Index (FHI). In Family Assessment: Resiliency, Coping and Adaptation—Inventories for Research and Practice; McCubbin, H.I., Thompson, A.I., McCubbin, M.A., Eds.; University of Wisconsin System: Madison, WI, USA, 1986; pp. 274–338. 68. Cunha, A.I.; Major, S.; Relvas, A.P. Family Hardiness Index (FHI). In Avaliação Familiar: Vulnerabilidade, Stress e Adaptação; Imprensa da Universidade de Coimbra: Coimbra, Portugal, 2016; pp. 63–80. 69. McCubbin, H.I.; McCubbin, M.A.; Patterson, J.M.; Cauble, A.E.; Wilson, L.R.; Warwick, W. CHIP—Coping Health Inventory for Parents: An assessment of parental coping patterns in the care of the chronically ill child. J. Marriage Fam. 1983,45, 359–370. [CrossRef] 70. Almeida, A.C.; Pereira, M.G. Psychometric properties of the Portuguese version of the Coping Health Inventory for Parents (CHIP) of adolescents with chronic illness. J. Pediatr. Nurs. 2016,31, 528–536. [CrossRef] [PubMed] 71. R Development Core Team. R: A Language and Environment for Statistical Computing [Computer Software]. R Development Core Team: Vienna, Austria, 2023; Available online: https://www.r-project.org/ (accessed on 13 November 2024). 72. Tingley, D.; Yamamoto, T.; Hirose, K.; Keele, L.; Imai, K. Mediation: R package for causal mediation analysis. J. Stat. Softw. 2014, 59, 1–38. [CrossRef] 73. Hayes, A.F.; Preacher, K.J. Conditional process modeling: Using structural equation modeling to examine contingent causal processes. In Structural Equation Modeling: A Second Course, 2nd ed.; Hancock, G.R., Mueller, R.O., Eds.; IAP Information Age Publishing: Charlotte, NC, USA, 2013; pp. 219–266. 74. Halkett, G.K.; Lobb, E.A.; Shaw, T.; Sinclair, M.M.; Miller, L.; Hovey, E.; Nowak, A.K. Distress and psychological morbidity do not reduce over time in carers of patients with high-grade glioma. Support. Care Cancer 2017,25, 887–893. [CrossRef] [PubMed] 75. Kazak, A.E.; Kassam-Adams, N.; Schneider, S.; Zelikovsky, N.; Alderfer, M.A.; Rourke, M. An integrative model of pediatric medical traumatic stress. J. Pediatr. Psychol. 2006,31, 343–355. [CrossRef] [PubMed] 76. Deribe, L.; Girma, E.; Lindström, N.; Gidey, A.; Teferra, S.; Addissie, A. Association of family-centered care with psychological distress among caregivers of children with cancer at a tertiary-level hospital in Ethiopia: Cross-sectional study. JMIR Cancer 2024, 10, e54715. [CrossRef] [PubMed] 77. Huang, Y.; Chen, M.; Wang, Y.; Qi, Y.; Zhang, L.; Dong, C. Resiliency process in the family after childhood leukaemia diagnosis: A longitudinal qualitative study. J. Clin. Nurs. 2024. [CrossRef] [PubMed] 78. Günay, U.; Özkan, M. Emotions and coping methods of Turkish parents of children with cancer. J. Psychosoc. Oncol. 2019,37, 398–412. [CrossRef] 79. McCubbin, H.I.; Thompson, A.I.; McCubbin, M.A. Family Measures: Stress, Coping, and Resiliency: Inventories for Research and Practice; Kamehameha Schools: Honolulu, HI, USA, 2001. 80. Folkman, S.; Lazarus, R.S. The relationship between coping and emotion: Implications for theory and research. Soc. Sci. Med. 1988,26, 309–317. [CrossRef] 81. Ryff, C.D. Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J. Pers. Soc. Psychol. 1989, 57, 1069. [CrossRef] 82. Kars, M.C.; Duijnstee, M.S.; Pool, A.; Van Delden, J.J.; Grypdonck, M.H. Being there: Parenting the child with acute lymphoblastic leukaemia. J. Clin. Nurs. 2008,17, 1553–1562. [CrossRef] 83. Mondal, M.; Dey, T.; Poddar, S. A Study to Assess the Quality of Life (QOL) Among Parents of Children with Acute Lymphoblastic Leukemia (ALL) Attending Oncology Out Patient Department (OPD) in Selected Hospital of Kolkata, West Bengal, India. Mal. J. Med. Health Sci. 2020,16, 125–130. 84. Hosoda, T. The impact of childhood cancer on family functioning: A review. Grad. Stud. J. Psychol. 2014,15, 18–30. [CrossRef] 85. Salvador, A.; Crespo, C.; Barros, L. Parents’ psychological well-being when a child has cancer: Contribution of individual and family factors. Psycho Oncol. 2019,28, 1080–1087. [CrossRef] 86. Doumit, M.A.; Khoury, M.N. Facilitating and hindering factors for coping with the experience of having a child with cancer: A Lebanese perspective. J. Psychosoc. Oncol. 2017,35, 346–361. [CrossRef] 87. European Academy of Paediatrics. Available online: https://www.eapaediatrics.eu/wp-content/uploads/2020/07/DFTB-4990 -EAPS-leaflet-02b.pdf (accessed on 11 December 2024). 88. Registo Oncológico Nacional. Available online: https://ron.min-saude.pt/media/2223/ron-2020.pdf (accessed on 12 December 2024 ). 89. Abate, C.; Lippe, S.; Bertout, L.; Drouin, S.; Krajinovic, M.; Rondeau, E.; Sinnett, D.; Laverdière, C.; Sultan, S. Could we use parent report as a valid proxy of child report on anxiety, depression, and distress? A systematic investigation of father-mother-child triads in children successfully treated for leukemia. Pediatr. Blood Cancer 2018,65, e26840. 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