Correlates of posttraumatic stress in cancer patients and their family caregivers across two years following diagnosis

To examine risk‐factors of cancer‐related PTSS in the 2‐years post‐diagnosis in adult colorectal cancer patients and caregivers.


| BACKGROUND
The traumatic nature of cancer is linked to intrusive thoughts, avoidance of its reminders, altered physiological arousal and reactivity, and negative changes in cognitions and mood (i.e., posttraumatic stress symptoms: PTSS). 1 Elevated PTSS or clinically diagnosable posttraumatic stress disorder (PTSD) following non-medical traumas (e.g., accidents, assault, war) are associated with various morbidities and early mortality. 2Cancer-related trauma is distinct due to its somatic nature and the subsequent ongoing physical cues to the threat of the illness 3 ; nonetheless, cancer-related PTSS have been documented in not only patients, but also family or close friends ("caregivers"). 1,4,5wever, there is limited information regarding sub-groups of adult cancer patients and caregivers at elevated risk for PTSS. 6ausible risk factors reflecting both the overlap with nonmedical PTSS and unique cancer-specific features of cancer-related PTSS deserve consideration.The trauma literature, mainly in nonmedical populations, has established risk factors (e.g., female 1736 -Psycho-Oncology. 2023;32:1736-1743.wileyonlinelibrary.com/journal/pon© 2023 John Wiley & Sons Ltd. gender, younger age, lower socioeconomic status, greater neuroticism, lower social support). 7,8Regarding cancer-related PTSD, a recent meta-analysis identified younger age and higher cancer stage as risk factors but studies were largely cross-sectional and limited to patients. 1 Moreover, most studies that have measured PTSS/D have used now outdated.Diagnostic and Statistical Manual of Mental Disorder (DSM) (e.g., DSM-III and DSM-IV) criteria that defined PTSD/PTSS in three symptom clusters.A fourth symptom cluster, Negative Alterations in Cognitions and Mood (NACM), which includes negative affect, self-blame, and anhedonia, was added to the current version of the DSM (DSM-5). 9Similar symptoms have been identified in cancer patients and caregivers, 10 but rarely within the constellation of PTSS.
According to the Enduring Somatic Threat model, 3 medical trauma is distinguished by its persistent, internal (i.e., unescapable), and somatic threat.For cancer patients, undergoing repeated treatments and tests serve as constant cues to threat.Persistent somatic symptoms are unavoidable internal reminders of their illness and mortality, perpetuating the perceived threat.More distressing somatic symptoms in medical populations are therefore thought to be associated with higher levels and longer duration of PTSS in patients. 3As for caregivers, the Secondary Traumatic Stress model 11 suggests that helping or desiring to help a suffering person can lead to consequences similar to those in individuals directly exposed.
Longer duration of exposure to others' suffering has been shown to predict higher levels of PTSS. 11 examined correlates of PTSS among adult patients and caregivers facing colorectal cancer, a high prevalence, high risk cancer involving challenging and painful treatments 12 in 2 years following diagnosis at timepoints demarcating distinct illness phases (i.e., treatment initiation, treatment completion, early survivorship).
We tested the extent to which risk factors with robust evidence as predictors of non-medical PTSS/D [sociodemographic (i.e., age, gender, SES) and psychosocial (i.e., neurotic personality, social support)] 7,8,13 extend to cancer-related PTSS.In light of the unique nature of cancer-related PTSS and the abovementioned theories, we also examined patient-specific (i.e., physical symptom distress) and caregiver-specific (i.e., hours spent caregiving) risk factors.We hypothesized that younger age, female gender, lower education, higher neuroticism, lower social support, greater patient physical symptom distress (in patients and caregivers), and longer hours spent caregiving (in caregivers) would relate to higher concurrent and subsequent PTSS.

| METHODS
This was a secondary analysis of an investigation of ethnic disparities in cancer patient and caregiver health.Study method and results follow the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement. 14Procedures performed were in accordance with the 1964 Helsinki declaration and its later amendments and the University of Miami and Northwestern University Institutional Review Boards (IRB approval #20111150).
Written informed consent was obtained from all individual participants included in the study.The authors declare no conflicts of interest.

| Participants and procedures
Patients diagnosed with colorectal cancer were identified from medical records at the University of Miami and Northwestern University oncology clinics and recruited in-person or via phone.Eligibility criteria for patients were newly and recently (within 4 months) diagnosed with colon or rectal cancer (stage I-IV), 21 years of age or older, English or Spanish speaking or reading/writing proficiency at a fifth grade level, and able to identify an unpaid family member or friend (i.e., caregiver) involved in their cancer experience.Eligible caregivers were 21 years or older, with English or Spanish speaking or reading/writing proficiency at a fifth grade level (to complete selfadministered survey), and self-identified as Non-Hispanic Black, Non-Hispanic White, or Hispanic (due to aims of the parent study).
Exclusion criteria were active yet untreated psychosis, substance abuse/dependence, or suicidal ideation within the past year.Patients and caregivers individually completed questionnaires in clinic or at home and were provided a $40 incentive at all three timepoints.

| Measures
Posttraumatic Stress Symptoms (PTSS).The 22-item Impact of Events Scale Revised (IES-R) 15 measured three PTSS (i.e., intrusions, avoidance, and alterations in arousal and reactivity).Items referred to the patients' cancer as the traumatic event (e.g., "I had waves of strong feelings about [my/his or her] cancer", "I tried to remove [my/ his or her] cancer from my memory" and "reminders of [my/his or her] cancer caused me to have physical reactions, such as sweat-ing…").All items were evaluated on a 5-point Likert response format ranging from 0 = "not at all" to 4 = "extremely." As the current study was a secondary analysis, the fourth (most recently established) symptom, negative alterations in cognitions in mood (NACM) that is not included in the IES-R, was assessed by six questionnaire items from measures well-validated in cancer samples [16][17][18][19] (supplemental material) corresponding with the NACM subscale of the PTSD Checklist for DSM-5 (PCL-5). 20Items were converted to a 5-point Likert response format and referred to the experience of symptoms in the 7-days prior to completing the measure for consistency with the IES-R.The NACM items had good internal consistency (supplemental material).Total PTSS was calculated with the mean of the four symptom scores (intrusions, avoidance, alterations in arousal and reactivity, NACM).As we previously reported, 5 the four-symptom measure had good internal consistency.
Neuroticism was assessed by two items ("anxious or easily upset" and, reverse coded, "calm or emotionally stable") from the Ten-Item Personality Inventory 21 on a 7-point Likert response format ranging from 1 = "disagree strongly" to 7 = "agree strongly."This brief scale has established convergence with gold-standard measures of personality traits, such as the 44-item Big-Five Inventory (r 2 = 0.69, p < 0.001), while internal consistency (α = 0.50) is lower as it is a two-item measure. 22In the current sample, the measure had similar internal consistency to the validation study 22 : patients (α = 0.60) and caregivers (α = 0.55).Because personality is considered a trait characteristic, neuroticism was assessed only at T1. Perceived overall availability of social support was assessed by the 6-item Interpersonal Support Evaluation List (ISEL) 23  caregivers in an open-ended question: "about how many hours a day have you been helping this person through his/her experience with cancer?" (0-24 h).

| Statistical methods
Descriptive statistics are reported in Table 1.To test associations between the proposed correlates and PTSS, we conducted path analysis using structural equation modeling in Mplus Version 7 (Supplemental Material). 25For the patients (Table 2) and caregivers (Table 3) separately, models specified concurrent and prospective associations of the proposed correlates with PTSS cross-sectionally and in a time-lagged manner across timepoints (i.e., T1 variables predicting PTSS at T2, T1 variables predicting PTSS at T3, and T2 variables predicting PTSS at T3).To account for potential effects of one's PTSS on their partner's PTSS (i.e., interdependence), patients' PTSS was controlled for when predicting caregivers' PTSS at each timepoint, and vice versa.Four model-fit indices are reported: Chisquare (χ 2 ), the comparative fit index (CFI), root mean squared error of approximation (RMSEA), and standardized root mean squared residual (SRMR).χ 2 < two times of degree of freedom, CFI> 0.95, RMSEA< 0.06, and SRMR< 0.08 indicate adequate fit of a specified model to the data. 26Missing data were handled using the Full Information Maximum Likelihood (FIML) method.Statistical significance was set at a 2-tailed p-value< 0.05.Participants were mostly Hispanic-identifying middle-aged females with some college or higher education (Table 1).Most patients (73%) were diagnosed with advanced stage cancers (III -IV).Caregivers were largely either the patients' spouses/partners (37%) or adult children (21%).Compared with caregivers, patients were older, more likely male, less likely to decline reporting their education, lower on neuroticism and reported higher levels of social support at T2 and T3, ps < 0.05.There were no differences between patients and caregivers in other examined correlates of PTSS, ps > 0.05.Patients and caregivers reported "a little bit" of the four PTSS symptoms at all three timepoints.PTSS levels were stable with no significant differences across timepoints for both patients and caregivers, and no associations with other sample characteristics ps > 0.10.  2 (upper half).Patients' higher neuroticism at T1 and T3, greater physical symptom distress at T1 and T3, and their caregivers' higher PTSS at T2 were associated with the patients' higher concurrent PTSS.

A
Presented in Table 2 (bottom half), higher PTSS at T1 was associated with higher PTSS at T2.Greater physical symptom distress at T1 were associated with higher PTSS at T3.Finally, higher PTSS and greater social support at T2 were associated with higher PTSS at T3. Next, the degree to which the proposed sociodemographic, psychosocial, and medical correlates were associated with PTSS among caregivers was tested.Model fit to the data was acceptable: χ 2 (32) = 47.27,RMSEA = 0.03 [90% CI: 0.00-0.06],CFI = 0.97, and SRMR = 0.05.Unstandardized path coefficients for concurrent associations are presented in Table 3 (upper half).Female gender was related to higher caregiver PTSS as T3.Caregivers' higher neuroticism at T1 and T3 and lower social support at T1 and T2 were associated with their higher concurrent PTSS.Also supporting conceptual consistency with non-medical PTSS, patients and caregivers higher on neuroticism reported higher PTSS.

Presented in
Neuroticism is linked to greater threat sensitivity, 28 which could apply to the existential threat of cancer that produces and maintains PTSS. 3 This association emerged at diagnosis and the beginning of the treatment-free survivorship phase.These periods, marked by uncertainty, anticipatory anxiety, and concerns about cancer recurrence 29 could be most difficult to tolerate for those high on neuroticism.
The final association supporting conceptual consistency was between lower social support and greater PTSS in caregivers around diagnosis/initiation of treatment and treatment completion, reflecting the well-established protective role of social support on caregiver health. 30Support earlier in the cancer treatment trajectory might buffer caregiver PTSS.Caregivers lacking assistance with tasks or someone close with whom to share may be prone to lasting distress.
Contrary to our hypotheses and among patients only, higher levels of social support early on related to higher PTSS in early survivorship.Not all forms of social support are helpful.For example, unsupportive relationships related to depressive and anxiety symptoms in breast cancer patients. 31Caregivers may be uncertain how to appropriately engage with their loved ones and overbearing discouraging the patient's autonomy and interfering with their trauma processing.The higher perceived social support may also indicate the use of instrumental support with activities of daily living and nursing tasks, and thus reflect patient greater reliance on others and related distress.
Regarding cancer-specific risk factors, initial physical symptom distress related to higher PTSS among patients at around time of diagnosis and 2 years follow-up, highlighting the role of internal cues to threat consistent with the Enduring Somatic Threat model. 3vasive treatments and symptoms are constant reminders of disease and mortality.Cancer-related symptoms can be confounded with physiological PTSS (e.g., elevated heart rate, muscle tension), 3 which may perpetuate distress as patients perceive a health risk.Moreover, discomfort early in treatment or around the time patients worry about recurrence could lead to maladaptive thinking about symptoms (e.g., "my illness is getting worse") 32 perpetuating PTSS.
Contrary to our hypotheses, patients' lower physical symptom distress at diagnosis/treatment initiation related to their caregivers' higher PTSS around a year later.Caregivers of patients with low symptom distress early on may be less prepared for increasing symptom burden and accompanying caregiver responsibilities as treatment unfolds, which could contribute to higher PTSS.Preparedness for caregiving is a well-established predictor of distress. 33sults could also reflect caregivers of patients slightly earlier in the treatment trajectory who had more distressing medical events or symptoms closer to the 1-year assessment.Future studies with more frequent assessments of symptoms and treatment-related events will better elucidate somatic precipitants.
Finally, longer hours spent caregiving at 1-year post-diagnosis were associated with higher PTSS around 2-years post-diagnosis.
More exposure to trauma tends to predict higher PTSS, 11 and thinking about or tending to a loved one can be exposure.Caregiving requiring more time may be especially distressing in the early survivorship period when caregiver resources are drained.Results may also reflect higher PTSS in caregivers of patients requiring more of their time due to greater functional impairment/poorer health status.

| Clinical implications
There is a need to intervene early and consistently during the prolonged stressor of cancer and caregiving to prevent expected stress from developing into chronic PTSS.Several of the risk factors are likely modifiable with intervention.Though personality factors themselves are largely unchangeable, recent literature suggests neuroticism is more malleable than thought, and indeed amenable to change from Mindfulness-Based Cognitive Therapy, 34 which was also effective in cancer patients. 35

| Study limitations
Certain study limitations can inform future investigations.Although attrition was not systematically related to study variables, we experienced participant drop-out.Longitudinal research in larger samples should maximize retention and employ more frequent, brief assessments, perhaps using digital assessment methods as PTSS may change more frequently than can be detected at approximately yearly follow-ups.Additionally, we did not assess trauma history.
Participants with complex trauma or multiple traumas may be higher risk.We did not assess caregiver direct observation or perception of patient suffering.Future investigations should comprehensively assess these factors.Some findings were in contrast with our hypotheses, the literature, and theory.These should be replicated but could reflect nuances in the patient and caregiver experiences at certain treatment phases.

| Conclusions
This theoretically grounded study supports similarities between cancer-related and non-medical PTSS, while highlighting unique cancer-specific risk factors in patients and caregivers.Healthcare systems and clinicians should target the subgroups identified for early and ongoing trauma-focused assessment and intervention to mitigate psychological and physical health outcomes secondary to cancer-related trauma.
on a 4-point Likert response format ranging from 1 = "very false" to 4 = "very true."In the current sample, the scale demonstrated overall acceptable internal consistency at T1 (α = 0.76, 0.69), T2 (α = 0.72, 0.81), and T3 (α = 0.66, 0.81) among patients and caregivers, respectively.Cancer-related physical symptom distress was assessed in the patients by the 23-item Rotterdam symptom checklist modified (by YK) 24 measuring common symptoms associated with cancer treatment (e.g., low appetite, tiredness, sore muscles).Items referred to the extent of symptom distress experienced over the past week on a 4-point Likert response format ranging from 1 = "not at all" to 4 = "very much."The scale demonstrated high internal consistency in the current sample of patients at T1 (α = 0.93), T2 (α = 0.93), and T3 (α = 0.95).Hours spent caregiving per-day was assessed only for total of 130 dyads (108 University of Miami, 22 Northwestern) enrolled and completed assessments from April 2012 to April 2017 around the time of the cancer diagnosis/treatment initiation (T1).A total of 80 and 68 patient-caregiver dyads were retained at approximately 1-(T2) and 2-year follow-up (T3), respectively.Reasons for participant attrition at T2 included loss to follow-up (N = 23), study withdrawal (N = 16), and patient death (N = 11).At T3, participants withdrew from study (N = 4), were lost to follow-up (N = 4), died (N = 3), and were medically unstable (N = 1).No study variables nor recruitment site were associated with participant attrition (ps > 0.10).

Table 3
Participant characteristics and study variables.
27ottom half), caregivers' higher PTSS and lower patients' physical symptom distress at T1 were associated with caregivers' higher PTSS at T2.Caregivers who perceived lower social T A B L E 14| DISCUSSION Findings suggest cancer-related PTSS has certain overlapping risk factors with non-medical PTSS, and others unique to cancer.PTSS was stable but had distinct correlates across timepoints.First, female gender was associated with higher caregiver PTSS only well after the end of treatment.Caregiving may feel more expected for female caregivers due to social and developmental learning of gender27; however, they could feel less prepared for responsibilities and illness consequences occurring later in treatment, resulting in delayed distress.Moreover, the point when this association emerged-early survivorship-may demarcate a transition back to the patient's relative independence, with female caregivers returning to the workforce or adopting other social roles.
T A B L E 3MITCHELL ET AL.