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Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Journal Pre-proof Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Katharine E. Duckworth, PhD, Richard P. McQuellon, PhD, Gregory B. Russell, MS, Kathleen C. Perry, BS, Chandylen Nightingale, PhD, MPH, Perry Shen, MD, FACS, Konstantinos I. Votanopoulos, MD, PhD, FACS, Bonny Morris, MSPH, RN, Edward A. Levine, MD, FACS PII:
S1072-7515(20)30105-8
DOI:
https://doi.org/10.1016/j.jamcollsurg.2019.12.020
Reference:
ACS 9715
To appear in:
Journal of the American College of Surgeons
Received Date: 13 December 2019 Accepted Date: 16 December 2019
Please cite this article as: Duckworth KE, McQuellon RP, Russell GB, Perry KC, Nightingale C, Shen P, Votanopoulos KI, Morris B, Levine EA, Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Journal of the American College of Surgeons (2020), doi: https://doi.org/10.1016/j.jamcollsurg.2019.12.020. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons.
Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Katharine E Duckworth, PhD1, Richard P McQuellon, PhD1, Gregory B Russell, MS2, Kathleen C Perry, BS3, Chandylen Nightingale, PhD, MPH2, Perry Shen, MD, FACS3, Konstantinos I Votanopoulos, MD, PhD, FACS3, Bonny Morris, MSPH, RN1, Edward A Levine, MD, FACS3
Author Affiliations: 1. Hematology Oncology, Wake Forest University, Winston-Salem, North Carolina 2. Department of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina 3. Surgical Oncology Service, Department of General Surgery, Wake Forest University, Winston-Salem, North Carolina
Disclosure Information: Nothing to disclose. Support: This work was supported in part by the Orin Smith Family Fund, National Cancer Institute Grant #P30CA012197 to Wake Forest Comprehensive Cancer Center (WFCCC) and the biostatistical and clinical cores facilities of the WFCCC. Dr Nightingale’s work on this manuscript was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (#UL1TR001420). Presented at the Southern Surgical Association 131st Annual Meeting, Hot Springs, VA, December 2019.
For correspondence: Edward A Levine, MD, FACS Surgical Oncology Wake Forest University Medical Center Blvd Winston-Salem, North Carolina 27157 Email:[email protected] Phone: 3367164276 Fax: 3367169758
Short title: Caregiver and Surgical Patient Quality of Life
Background: CRS+HIPEC is a formidable procedure, often impacting the quality of life (QOL) of the caregiver as well as the patient. We explored the impact of quality of life and depressive symptom burdens of CS+HIPEC caregivers prospectively. Study design: Patient and caregiver dyads were both consented per IRB approved protocol. CRS ± HIPEC was performed. The impact on QOL and depressive symptom burdens was assessed on patient-caregivers dyads via the Caregiver Quality of Life (CG QOL-C), CES-D instruments; pre-CS+HIPEC(T1), post-surgical(T2), 6(T3), and 12(T4) months. Results: 77 dyads were approached with 73 participating. Both caregiver and patient depressive symptom trajectories changed significantly. CES-D means for caregivers were (T1-4): 15.1 (SE 1.7), 15.0 (1.4), 10.3 (1.4), 13.1 (2.1), p=0.0008; for patients were: 10.3 (SE 1.1), 13.7 (1.4), 9.0 (1.2), and 10.3 (1.5), p= 0.0002. Pre-surgery, caregivers scored 4.8 points (SD 13.4) (p=0.026) higher than patients. Patients experienced an increase in depression scores at the post-surgical visit. At T3, both groups dropped to less concerning levels; yet caregiver CES-D scores increased again at T4 4.7 points (SD 12.5) higher than the patients, and financial well-being became worse from T1 – T3 . Possible, probable and “cases” of depression were higher for caregivers were at all measured time points. Conclusions: Significant numbers of caregivers endorsed high depressive symptom burdens and financial concerns. Different caregiver-patient trajectories reflect the need for differential timing of supportive interventions. Evaluation of quality of life and impact of CRS+HIPEC procedures must move beyond assessment of only the patient.
Introduction
Caregiving in cancer care is psychologically and physically demanding.1 This is especially true for late stage disease or intensive treatments, such as cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). Cancer caregivers, usually family members, fulfill an essential role for patients during treatment and rehabilitation,2,3 ; most spend nearly 33 hours per week caring for their loved one, but alarmingly, 32% are required to provide 41 hours or more of care per week.4 Caregivers assist patients with activities of daily living (e.g. eating, bathing), instrumental activities (shopping, bill paying), and address patient emotional and health care needs, including symptom management, and communication with health care providers.1,2,46
. Extensive patient engagement places caregivers at higher risk of depressive symptoms, 7-9
sleep disturbance and fatigue, 9-11 as well as inattention to preventive health care as compared to noncaregivers.12 In previous studies involving patients with advanced cancer, caregivers were described as having poorer physical health and lower quality of life (QOL) than their carerecipients. 13 While there is a growing body of QOL studies on patients treated with CRS + HIPEC, 14-16 to our knowledge, QOL and caregiver depression have not been assessed in this population of caregivers. CRS + HIPEC is an aggressive surgical procedure indicated for peritoneal carcinomatosis that accompanies advanced disease. Past research has monitored the QOL trajectory of patients,17,18 long-term survivorship 19 and general physical and mental status pre- and post-treatment.20 These studies demonstrate that hospitalization and the period immediately following discharge are characterized by a decrease in QOL for the patient. Postoperative decline in QOL is usually improved by 6 months after the CRS + HIPEC procedure.14-19 Demands on caregivers may be
intense and the potential for psychological morbidity and poor QOL likely is high for both the patient and their loved ones during this time-period. However, to our knowledge, no studies have measured caregiver outcomes for this population. Additionally, the reciprocal relationships between patient and caregiver QOL outcomes is unknown The purpose of this study was to assess and compare caregiver and patient-reported QOL and depressive symptoms before and after CRS+HIPEC and to determine factors associated with poorer QOL for caregivers over 12 months post-treatment. We hypothesized that patient QOL and depressive symptoms would influence caregiver outcomes on these same variables.
Methods
This study was approved by the Wake Forest University Institutional Review Board (IRB). Participants were eligible if they were at least 18 years of age, English speaking, scheduled for CRS + HIPEC (patients) or the patient-designated caregiver of someone scheduled for CRS + HIPEC. Patient and caregiver dyads were both consented per IRB approved protocol. Potentially eligible participants identified by the surgeon were approached by a research nurse during their outpatient preoperative evaluation. At that time, the nurse confirmed eligibility and reviewed consent forms and study questionnaires. The patient was asked to identify the primary informal caregiver (defined as an unpaid person who is responsible for the majority of their care). If not present at the initial visit and verbal consent was obtained from the patient, the caregiver was contacted for preliminary verbal consent to participate. Formal consent was obtained either through an in-person clinic visit or by mail.
Surveys were administered at the initial CRS+HIPEC preoperative consultation (T1), prior to their follow-up surgical visit (3-6 weeks post-procedure; T2), and approximately 6 (T3) and 12 months (T4) post-procedure (reference participation flow chart). Participants completed surveys in clinic or by mail. Patients and caregivers were instructed to share their work to encourage authentic responses. A research coordinator called patients for clarification about any survey responses that were unclear. Participants received a $5 Starbucks card for each completed survey.
Instruments: Quality of life assessment
Functional Assessment of Cancer Therapy (Patients)21
The Functional Assessment of Cancer Therapy- Colon (FACT-C) is a 27-item (total score = 108) self-report questionnaire that measures QOL in cancer patients, and includes a10-item colon subscale. 14 because it corresponds to the symptoms experienced by this patient population. The FACT itself consists of four subscales measuring physical (PWB, 7 items, range=0-28), functional (FWB, 7 items, range=0-28), social/family (SFWB, 7 items, range=0-28), emotional well-being (EWB, 6 items, range=0-24) and a Treatment Outcome Index (TOI). The TOI combines physical well-being, functional well-being, and the colon subscale to measure symptoms and functioning that may change over the course of treatment. The FACT can be either self-administered or used in an interview format and can be completed in 5-10 minutes. Patients were asked to rate themselves on how they feel today and over the past seven days on a
Likert scale from 0 (not at all) to 4 (very much). The FACT-G provides subscale scores and a total QOL score. A higher score indicates better QOL. Cronbach's Alpha for each subscale has been reported as follows: PWB (0.82); FWB (0.80); SFWB (0.69); EWB (0.74); and total FACTG (0.89).The FACT-Treatment Satisfaction is an optional module for the FACT-G. The instrument has 8 quantitative items (using both a 3-point and 5-point Likert scale) and one space for open-ended narrative commentary on the treatment. The questions are intended to gauge a survivor’s satisfaction with his/her respective treatment.
Caregiver Quality of Life Index-Cancer Scale (CQOL-C) (Caregivers)22 The CQOL-C scale consists of 35 five-point Likert-type items designed to assess dimensions of cancer caregiver quality of life (burden, disruptiveness, positive adaptation, financial concerns). 5-point Likert scale responses range from “not at all” to “very much.” The total score ranges from 0-140, with higher scores indicating better quality of life. The CQOL-C has demonstrated good reliability and internal consistency, with a test-retest correlation of 0.95 and a Cronbach’s α of 0.91.
Center for Epidemiologic Studies-Depression (CES-D) (Patients and Caregivers)23 The CES-D is a 20-item self-report measure developed to screen for depressive disorders. It has high sensitivity and positive predictive value for detecting depressive disorders (major depression and dysthymia). Cut-off scores indicate the likelihood that a subject meets diagnostic criteria for depression. A score of ≥ 16 has been used as the cut-off score with higher scores indicating significant depressive symptoms. We defined “possible”, “probable” and “cases” of depression by <16= not depressed; 16- < 23 = “possible”; 23- <28 = “probable”; 28+ = “case”.
Medical Outcomes Study Social Support Survey (MOS-SSS) (Patients and Caregivers)24 Self-reported social support was assessed in both patients and caregivers using the Medical Outcome Study Social Support Survey (MOS-SSS). The MOS-SSS contains 19 functional support items hypothesized to measure five dimensions of social support: 1) emotional support, 2) informational support, 3) tangible support, 4) positive social interaction, and 5) affectionate support. Responses are on a five-point Likert-type scale ranging from ‘none of the time’ to ‘all of the time’.
Statistical Analysis: Summary statistics, including means and standard deviations for continuous data and frequencies and proportions for categorical data, were calculated for all study measures. Repeated measures regression models were created to assess change over time and between visits in QOL outcomes (FACT, CQOL-C, CES-D, MOS-SSS); pairwise comparisons between baseline values and subsequent visits were analyzed using the Dunnett adjustment for multiple comparisons. These models were also used to assess the relationship between dyadic QOL and depression measures, with the caregiver score the dependent outcome (CQOL-C and CES-D) and the patient score the predictor (FACT, patient CES-D, MOS-SSS). The beta coefficients from these models estimate the strength of the relationship between QOL measures. To compare QOL scores/values within dyads (CES-D, MOS-SSS), differences were calculated by subtracting the caregiver’s value from the corresponding patient’s value. SAS (version 9.4, Cary, NC, USA) was used for all analyses.
Results
The study team approached 77 dyads, with 73 (95%) consenting. All surgical procedures were preformed between February, 2016 and November, 2017. After consent, 6 patients had their procedure cancelled due to progression of disease, comorbidity or insurance coverage issues. The average age of the patients was 56 with 60% female. Patient primary site leading to the peritoneal metastases were: appendiceal 50, colorectal 15, mesothelioma 6, small bowel 1, and gastric 1. Fourteen patients received systemic chemotherapy prior to surgery. The median PCI found at laparotomy was 14. The median length of stay was 8 days. A colostomy was created in 4, ileostomy in 4 and 1 patient had a pre-existing colostomy closed at the time of surgery. Cytoreductive surgery without HIPEC was performed in 5 cases due to an inability to achieve a satisfactory resection. Patients were postoperatively admitted to the ICU (n=14, 20%) or the ward (n=56, 80%). The 30 day readmission rate was 18% and the 90 day mortality was 4%. The 1 and 3 year overall survival rates were 90.0% and 69.7%, respectively, for patients receiving HIPEC, and 77.8% and 0% for those without HIPEC, (p=.0007).
Of the 73 consenting dyads, 58 pairs returned at least one questionnaire. See Figure 1 for patient and caregiver flow chart. A total of 84% (N=49) of informal caregivers were spouses or partners; 10% (N=6) were daughters or sons; while the remaining 6% (N=1 in each category) were siblings, parents or other relatives, respectively. Over 50% of the patient population traveled over 100 miles to the Comprehensive Cancer Center of Wake Forest Baptist Medical Center to receive CRS + HIPEC and for follow-up visits. (Table 1)
Medical Outcomes Study Social Support Survey:
Caregivers reported lower perceived social support availability than patients across all time points. See tables 2 and 3. While patient and caregiver trajectories remained similar over time, the difference between dyads is significant for all models when fitting a repeated measures regression (estimated differences for total MOS-SSS scores: 17.4 (5.2), p= 0.0013). Overall MOS-SSS scores for patients were: T1 (94.9; SD 7.7), T2 (94.7, SD 9.0), T3 (95.9, SD 8.1), T4 (94.6, SD 8.7); caregivers reported: T1 (74.7, SD 20.7), T2 (78.4, 24.8), T3 (80.6, SD 18.3), T4 (77.5, SD 24.7).
Depressive symptoms: Caregiver and patient depressive symptom scores changed significantly over time. (Figure 2 or 3) CES-D means for caregivers were (T1-4): 14.4 (SD 12.0), 13.1 (9.3), 10.0 (9.2), 12.9 (11.3), global p=0.0008; for patients were: 9.3 (SD 7.9), 12.3 (8.3), 6.8 (6.7), and 8.6 (8.2), global p= 0.0002. Pre-surgery, caregivers scored 4.8 points (SD 13.4) (p=0.026) higher than patients on the CES-D, indicating more depressive symptoms. Patients reported more depressive symptoms at the post-surgical visit. At T3, both groups’ scores declined; yet caregiver CES-D scores increased again at T4, reflecting an average of a 4.7 point difference between caregiver and patient scores (SD 12.5; p= 0.165). Numbers of possible, probable and “cases” of depression at T1 for caregivers were 17 (39%), 11 (25%), and 6 (14%) versus 7 (16%), 4 (9%), and 1 (2%) for patients. Patient overall QOL (FACT) and subscale scores and Caregiver QOL are reported in Table 3. Patient QOL T1 mean total= 105.6 (SD 18.2), T2= 90.1(18.8), T3= 112.7 (15.8), T4= 116.1 (13.7). This trend indicates a drop on QOL from the pre- to post-intervention measurement
points, followed by QOL improvement at the 6-month time point. Figure 3 plots patient and caregiver QOL and depression trajectories over time.
All caregiver QOL subscales on the CQOL-C (Burden, p= 0.00035; Disruptiveness, p<0.0001; Financial p=0.0004) and overall scores (p<0.0001), with the exception of the Adaptation scale (p=0.34), changed significantly over the course of the four measurement time points: T1= 95.6 (SD 21.9), T2= 101.6 (SD 18.6), T3= 108.8 (SD 18.7), T4= 105.8 (SD 21.6). Least square means indicate estimated mean score improvement in QOL of 11.5 points (4.9, 18.2), p=0.0002 and estimated mean score improvement of 8.7 points (0.3, 17.1), p =0.040 between pre- surgery and the 12-month time period. For caregivers, QOL scores were lowest at the pre-surgery time point and demonstrated significant improvement by six months-post intervention.
Repeated measures regression analysis of variance models assessed the effect of patient QOL and CES-D scores on caregiver depression and QOL scores. In these models, caregiver outcomes were significantly associated with patient QOL scores; Over the 4 visits, caregiver CES-D scores were significantly correlated with FACT EWB, FWB, TOI, FACT G, and FACT total scores. Poorer caregiver QOL scores were associated with worse depressive scores in patients. In modeling the CQOL-C total score, all FACT scores, with the exception of the disease related (colon) subscale, predicted higher caregiver QOL scores. The CES-D model revealed that higher depressive symptoms in patient were associated with lower caregiver QOL. To estimate the impact of patient emotional well-being (EWB) on CESD-D, beta coefficient were calculated; caregivers experienced an average of 0.58 units of improvement (lower) in CES-D scores for every unit increase in patients’ reported EWB (p=0.003). Additionally, caregivers were
estimated to have a 1.47 unit improvement on the CQOL-C for every unit of increased EWB endorsed by patients (p<0.0001).
Discussion In this study, we assessed and compared caregiver and patient-reported QOL and depressive symptoms before and after CRS + HIPEC. We also explored factors associated with poorer QOL among caregivers over a 12 month post-treatment period. Our results showed that caregivers reported higher levels of depressive symptoms and lower social support relative to their patient counterparts at all time points. Though caregiver depressive symptoms exceeded patients, no group mean score exceeded the defined significant cut off point of 16.23 Nevertheless 16% of patients and 39% of caregivers reported depressive symptoms significant enough to warrant professional attention at baseline. Similarly, in another study focused on caregiver spouses of patients with advanced disease, nearly 40% of caregivers and 23% of patients recorded significant symptoms of depression,8 suggesting caregivers of patients with advanced disease are at high risk for developing depression. All CRS + HIPEC patients have advanced, but not necessarily terminal disease. Caregiver depressive symptoms were highest pre-CRS + HIPEC and continued to stay elevated post-surgery, ultimately dropping significantly at the 6-month time point prior to elevating again at the 12-month time point. It is not surprising that caregivers, relative to their patients, reported lower social support that declined over time. Though this decline in social support was similarly reported in another study for patients, we believe this is the first study to demonstrate declining social support for caregivers of CRS + HIPEC patients. With oncologic care focused primarily on the patient, it is not surprising that caregivers reported lower support than patients in this study. In contrast,
caregivers may be viewed as a source of support for the patient rather than in need of support themselves. However, there is a growing literature in cancer care documenting the amount of time and types of activities caregivers undertake in supporting the patient4, as well as the critical need for increased support for caregivers of patients with cancer.25-27 Caregiver QOL improved over the study time period from baseline to one year. However, caregiver QOL at baseline (mean = 95.6; SD=21.9) was lower than another study of lung, breast, and prostate cancer caregivers (mean = 106.4; SD = 16.3).22 Patient QOL followed a pattern similar to that reported in many previous studies15 in that it was worse at the post-surgery followup (T2), returning close to baseline levels at six months and leveling off at one year. It is thought the period of hospitalization and discharge, prior to the post-surgical visit, places significant physical demands on the caregiver given the patient’s decline in functional status; they also face additional challenges, including geographical distance from home, where, presumably additional help would be available. Our caregivers reported improvement in QOL after CRS + HIPEC suggesting that caregiver QOL scores may improve due to the significant level of patient supportive care received in the hospital. Caregivers may experience relief at finally receiving treatment for their loved ones, particularly if it goes well. We do not know the extent to which the primary caregiver received additional help from other “non-primary” caregivers; both in the hospital and at home, as only one primary caregiver was identified in our study. Clinical experience suggests that there is often more than one caregiver helping with patient care, possibly influencing QOL scores post-hospitalization. The pattern of improved QOL for caregivers may be unique to the CRS + HIPEC setting since the burdens of treatment are significant at one time point and likely diminish over weeks. In a setting of radiotherapy treatment for head and neck cancer, a different pattern was reported, with increased burden and
worsened QOL for caregivers over time.28 Our QOL findings, coupled with our depressive symptoms findings, suggest that the time immediately preceding CRS + HIPEC is challenging for caregivers and perhaps the time to initiate a pre-habilitation intervention. Regarding patient and caregiver depressive symptoms, caregiver mean scores on the CES-D exceed those of patients at every time point. However, no group’s mean score exceeds the defined significant cut off point of 16. Nevertheless 16% of patients and 39% of caregivers reported depressive symptoms significant enough to warrant professional attention at baseline. In a study focused on caregiver spouses of patients with advanced disease, nearly 40% of caregivers and 23% of patients recorded significant symptoms of depression. 8 Caregivers of patients with advanced disease are a high-risk population for depression. All CRS + HIPEC patients have advanced, but not necessarily terminal disease. Caregiver depressive symptoms were highest preCRS + HIPEC and continued to stay elevated post-surgery, ultimately dropping significantly at the 6-month time point prior to elevating again at the 12-month time point. The anticipation of the demanding CRS + HIPEC procedure, the symptoms of the patients, and the cumulative demands on caregivers prior to the actual treatment may contribute to increased depressive symptomatology and QOL decrements. Unlike patients, who experience more acute physical and functional status changes, caregiver scores may reflect the emotional and instrumental toll inherent in their roles. Perhaps caregiver QOL does not follow a similar pattern as we hypothesized due to additional help at home, increased familiarity with patient care due to instruction at the hospital and an increased sense of caregiver self-efficacy due to experience. By the six-month assessment point, most caregivers reported improved mood and QOL. At 12 months, QOL declines and depressive symptoms increase somewhat, perhaps related to patient disease or continued role demands. Lower perceived social support, higher depressive
symptomatology and possible increased demands on the caregiver are most prominent at the preintervention time-period. Caregivers are entering the CRS + HIPEC already somewhat depleted. The inpatient stay with 24/7 monitoring of the patient and ongoing contact with professionals for the caregiver may provide a boost to morale and reduced caregiver burden, which has improved by the time of the post-surgery visit. The unique patterns (Figure 3) in caregiver- and patient-reported QOL underscore the different challenges for patients and caregivers throughout the CRS + HIPEC treatment process. We found that patient QOL predicted both caregiver depression and QOL, and patient depressive symptoms predicted caregiver overall QOL. Improvement in the emotional well-being of patients was associated with reduced depressive symptoms in caregivers. Watching a loved one suffer exacts its toll on caregivers in the form of significant depressive symptoms at baseline and the post-surgical visit. Seeing improvement in the patient’s emotional well-being, more so than physical functioning, acts as a welcome relief for the caregiver’s suffering. Impairments in both patient and caregiver emotional well-being further underscores the need to address emotional adaptation within both patients and caregivers. Caregivers are not contending with the same physical demands as patients; however the emotional and logistical demands of caregiving can be daunting, and clearly have an impact on QOL. We acknowledge both the limitations and strengths of this study. A major strength is this represents the first study evaluating quality of life in both patients and caregivers after CRS & HIPEC. First, we asked patients to identify a single primary caregiver. Many patients have no, or multiple caregivers, thus, caregiver feedback may reflect the perspective of only one of many caregivers. Second, there was significant attrition over time and it is possible that those who did not return data or who dropped out of the study were those who were struggling the most with
depressive symptoms and impaired QOL. Findings are limited by the modest sample size, particularly at the final 12 month assessment, where attrition was 65%. Additionally, there is an active inpatient psychosocial oncology consultation service and a weekly caregiver support group that serves the surgical oncology service, primarily to assess and treat depressive symptoms, and we did not record which participants may have utilized those options. Finally, our assessments of caregiver functioning were limited to a 12-month period and longer term follow up should be considered. Subsequent studies should continue to assess the status and needs of caregivers, establishing normative data with the goal of developing intervention strategies to help reduce caregiver depressive symptoms and improve QOL. Despite these limitations, this is the first study to our knowledge to assess depressive symptoms, QOL, and social support in this vulnerable and understudied population of caregivers. Further, this study is strengthened by assessing outcomes among both members of the dyad, as well as exploring associations between patient and caregiver outcomes. Finally, we undertook a longitudinal approach in this study to provide key data on QOL changes before and after CRS + HIPEC.
The unique role demands caregivers experience likely influenced their own and the patients’ depressive symptoms, and QOL over time in a complex reciprocal manner. Our data underscore the importance of caregivers in the treatment equation. Cancer is a disease of the family that especially affects caregivers. Caregivers experience comparatively more suffering (depressive symptoms, impaired QOL) than patient counterparts at various junctures, and there are significant associations between patient and caregiver functioning. What happens to the patient reverberates in the caregiver and likely is mediated by a number of factors, including the quality of the caregiver patient relationship.7,8
In light of these data we suggest initiating systematic caregiver assessment and support interventions at the pre-operative and at the first post-operative visits, where depressive symptoms are prominent and QOL is impaired. Patients and caregivers are likely burdened with the uncertainty of outcome, complexity of the treatment modality, and the logistics of CRS + HIPEC. Since most dyads travel to medical institutions for pre- and post-op visits, clinical staff could assess needs and intervene both pre- and post-operation in the clinic setting. In other intensive treatment settings, psychosocial assessment of patient and caregivers is standard of care. Telephone or self-directed web-based interventions may be an additional modality to reach this population. Regardless of approach, assessment and intervention for the patient and caregiver may enhance social support, address depressive symptoms and improve quality of life and the experience for both. Conclusions: Significant numbers of caregivers endorsed high depressive symptom burdens and financial concerns. Different caregiver-patient trajectories reflect the need for differential timing of supportive interventions. Evaluation of quality of life and impact of CRS+HIPEC procedures must move beyond assessment of only the patient.
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Nightingale CL, Curbow BA, Wingard JR, Pereira DB, Carnaby GD. Burden, quality of life, and social support in caregivers of patients undergoing radiotherapy for head and neck cancer: A pilot study. Chronic illness. 2016;12(3):236-245.
Table 1. Demographics Demographic Data Age, y, mean (SD), range Patient 56 (12), 24–75 Caregiver 57 (13), 22–74 Sex, n (%) Patient Female 35 (60) Male 23 (40) Caregiver Female 30 (52) Male 28 (48) Race, n (%) Patient White 48 (83) Black 7 (12) Other 3 (5) Caregiver White 50 (86) Black 8 (14) Caregiver employment status, n (%) Not employed 29 (50) Full-time 25 (43) Part-time 3 (7) Average distance of patient from WFBMC, n (%) 0-25 miles 3 (5) 26-50 miles 12 (21) 51-75 miles 6 (10) 75-100 miles 7 (12) 100+ miles 30 (52) Designated caregiver relationship, n (%) Spouse/partner 49 (84) Son/daughter 6 (10) Sibling 1 (2) Parent 1 (2) Other relative 1 (2) N = 58* (100%) *58 pairs where at least the caregiver provides data WFBMC, Wake Forest Baptist Medical Center
Table 2. Caregiver Quality of Life Mean (SD) Scores
CQOL-C
Preoperative Postoperative (n = 44) (n = 37)
6 mos (n = 34)
12 mos (n = 17)
p Value
Burden
22.4 ± 9.5
26.6 ± 8.1
29.1 ± 8.0
29.0 ± 8.8
0.0035†
Disruptiveness
23.4 ± 3.6
22.9 ± 4.4
25.6 ± 3.0
25.8 ± 3.6
<0.0001†
Adaptation
18.3 ± 5.7
18.4 ± 5.8
18.8 ± 5.3
17.1 ± 6.7
0.34†
Financial
8.1 ± 3.6
10.0 ± 2.5
9.6 ± 2.9
9.6 ± 3.2
0.0004†
CQOL-C
95.6 ± 21.9
101.6 ± 18.6
108.8 ± 18.7
105.8 ± 21.6
<0.0001†
Data are presented as mean ± SD. † Statistically significant CQOL-C, caregiver quality of life
Table 3. Patient Quality of Life (FACT-C) Mean (SD) Scores
FACT PWB SFWB
Preoperative (n= 46) Mean SD 22.8 5.7 24.0 3.7
Postoperative (n= 34) Mean SD 16.6 6.6 23.9 3.7
6 mos (n= 34) Mean SD 23.6 5.1 24.9 3.3
12 mos (n=16) Mean SD 24.6 3.4 25.1 3.4
p Value <0.0001* 0.19
EWB 18.4 4.2 18.5 4.1 20.2 3.5 20.8 3.2 0.015* FWB 19.5 6.6 14.9 6.0 21.9 6.0 23.8 4.2 <0.0001* FACT-G 84.8 14.9 73.8 15.4 90.5 13.1 94.3 11.0 <0.0001* CCS 20.8 4.4 16.3 4.8 22.2 4.5 21.8 5.3 0.0013* Total 105.6 18.2 90.1 18.8 112.7 15.8 116.1 13.7 <0.0001* TOI 63.1 14.2 47.8 14.0 67.6 12.6 70.2 10.4 <0.0001* *Statistically significant CCS, colon cancer subscale; EWB, emotional well-being; FACT, Functional Assessment of Cancer Therapy; FACTG, Functional Assessment of Cancer Therapy-General; FWB, functional well-being; PWB, physical well-being; SFWB, social/family well-being; TOI, treatment outcome index
Figure 1. Quality of life pilot study in patients receiving intraperitoneal hyperthermic chemotherapy and their designated primary caregivers Figure 2. Caregiver and patient Center for Epidemiologic Studies-Depression (CES-D) mean scores at baseline, postoperative, 6, and 12 months Figure 3. Percent of maximum quality of life for caregivers and patients at study time points. FACT-G, Functional Assessment of Cancer Therapy-General; QOL, quality of life.
Precis: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is a formidable procedure. The impact on the quality of life of the patient and primary caregiver were evaluated in this prospective study.
S1072-7515(20)30105-8
DOI:
https://doi.org/10.1016/j.jamcollsurg.2019.12.020
Reference:
ACS 9715
To appear in:
Journal of the American College of Surgeons
Received Date: 13 December 2019 Accepted Date: 16 December 2019
Please cite this article as: Duckworth KE, McQuellon RP, Russell GB, Perry KC, Nightingale C, Shen P, Votanopoulos KI, Morris B, Levine EA, Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Journal of the American College of Surgeons (2020), doi: https://doi.org/10.1016/j.jamcollsurg.2019.12.020. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons.
Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
Katharine E Duckworth, PhD1, Richard P McQuellon, PhD1, Gregory B Russell, MS2, Kathleen C Perry, BS3, Chandylen Nightingale, PhD, MPH2, Perry Shen, MD, FACS3, Konstantinos I Votanopoulos, MD, PhD, FACS3, Bonny Morris, MSPH, RN1, Edward A Levine, MD, FACS3
Author Affiliations: 1. Hematology Oncology, Wake Forest University, Winston-Salem, North Carolina 2. Department of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina 3. Surgical Oncology Service, Department of General Surgery, Wake Forest University, Winston-Salem, North Carolina
Disclosure Information: Nothing to disclose. Support: This work was supported in part by the Orin Smith Family Fund, National Cancer Institute Grant #P30CA012197 to Wake Forest Comprehensive Cancer Center (WFCCC) and the biostatistical and clinical cores facilities of the WFCCC. Dr Nightingale’s work on this manuscript was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (#UL1TR001420). Presented at the Southern Surgical Association 131st Annual Meeting, Hot Springs, VA, December 2019.
For correspondence: Edward A Levine, MD, FACS Surgical Oncology Wake Forest University Medical Center Blvd Winston-Salem, North Carolina 27157 Email:[email protected] Phone: 3367164276 Fax: 3367169758
Short title: Caregiver and Surgical Patient Quality of Life
Background: CRS+HIPEC is a formidable procedure, often impacting the quality of life (QOL) of the caregiver as well as the patient. We explored the impact of quality of life and depressive symptom burdens of CS+HIPEC caregivers prospectively. Study design: Patient and caregiver dyads were both consented per IRB approved protocol. CRS ± HIPEC was performed. The impact on QOL and depressive symptom burdens was assessed on patient-caregivers dyads via the Caregiver Quality of Life (CG QOL-C), CES-D instruments; pre-CS+HIPEC(T1), post-surgical(T2), 6(T3), and 12(T4) months. Results: 77 dyads were approached with 73 participating. Both caregiver and patient depressive symptom trajectories changed significantly. CES-D means for caregivers were (T1-4): 15.1 (SE 1.7), 15.0 (1.4), 10.3 (1.4), 13.1 (2.1), p=0.0008; for patients were: 10.3 (SE 1.1), 13.7 (1.4), 9.0 (1.2), and 10.3 (1.5), p= 0.0002. Pre-surgery, caregivers scored 4.8 points (SD 13.4) (p=0.026) higher than patients. Patients experienced an increase in depression scores at the post-surgical visit. At T3, both groups dropped to less concerning levels; yet caregiver CES-D scores increased again at T4 4.7 points (SD 12.5) higher than the patients, and financial well-being became worse from T1 – T3 . Possible, probable and “cases” of depression were higher for caregivers were at all measured time points. Conclusions: Significant numbers of caregivers endorsed high depressive symptom burdens and financial concerns. Different caregiver-patient trajectories reflect the need for differential timing of supportive interventions. Evaluation of quality of life and impact of CRS+HIPEC procedures must move beyond assessment of only the patient.
Introduction
Caregiving in cancer care is psychologically and physically demanding.1 This is especially true for late stage disease or intensive treatments, such as cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). Cancer caregivers, usually family members, fulfill an essential role for patients during treatment and rehabilitation,2,3 ; most spend nearly 33 hours per week caring for their loved one, but alarmingly, 32% are required to provide 41 hours or more of care per week.4 Caregivers assist patients with activities of daily living (e.g. eating, bathing), instrumental activities (shopping, bill paying), and address patient emotional and health care needs, including symptom management, and communication with health care providers.1,2,46
. Extensive patient engagement places caregivers at higher risk of depressive symptoms, 7-9
sleep disturbance and fatigue, 9-11 as well as inattention to preventive health care as compared to noncaregivers.12 In previous studies involving patients with advanced cancer, caregivers were described as having poorer physical health and lower quality of life (QOL) than their carerecipients. 13 While there is a growing body of QOL studies on patients treated with CRS + HIPEC, 14-16 to our knowledge, QOL and caregiver depression have not been assessed in this population of caregivers. CRS + HIPEC is an aggressive surgical procedure indicated for peritoneal carcinomatosis that accompanies advanced disease. Past research has monitored the QOL trajectory of patients,17,18 long-term survivorship 19 and general physical and mental status pre- and post-treatment.20 These studies demonstrate that hospitalization and the period immediately following discharge are characterized by a decrease in QOL for the patient. Postoperative decline in QOL is usually improved by 6 months after the CRS + HIPEC procedure.14-19 Demands on caregivers may be
intense and the potential for psychological morbidity and poor QOL likely is high for both the patient and their loved ones during this time-period. However, to our knowledge, no studies have measured caregiver outcomes for this population. Additionally, the reciprocal relationships between patient and caregiver QOL outcomes is unknown The purpose of this study was to assess and compare caregiver and patient-reported QOL and depressive symptoms before and after CRS+HIPEC and to determine factors associated with poorer QOL for caregivers over 12 months post-treatment. We hypothesized that patient QOL and depressive symptoms would influence caregiver outcomes on these same variables.
Methods
This study was approved by the Wake Forest University Institutional Review Board (IRB). Participants were eligible if they were at least 18 years of age, English speaking, scheduled for CRS + HIPEC (patients) or the patient-designated caregiver of someone scheduled for CRS + HIPEC. Patient and caregiver dyads were both consented per IRB approved protocol. Potentially eligible participants identified by the surgeon were approached by a research nurse during their outpatient preoperative evaluation. At that time, the nurse confirmed eligibility and reviewed consent forms and study questionnaires. The patient was asked to identify the primary informal caregiver (defined as an unpaid person who is responsible for the majority of their care). If not present at the initial visit and verbal consent was obtained from the patient, the caregiver was contacted for preliminary verbal consent to participate. Formal consent was obtained either through an in-person clinic visit or by mail.
Surveys were administered at the initial CRS+HIPEC preoperative consultation (T1), prior to their follow-up surgical visit (3-6 weeks post-procedure; T2), and approximately 6 (T3) and 12 months (T4) post-procedure (reference participation flow chart). Participants completed surveys in clinic or by mail. Patients and caregivers were instructed to share their work to encourage authentic responses. A research coordinator called patients for clarification about any survey responses that were unclear. Participants received a $5 Starbucks card for each completed survey.
Instruments: Quality of life assessment
Functional Assessment of Cancer Therapy (Patients)21
The Functional Assessment of Cancer Therapy- Colon (FACT-C) is a 27-item (total score = 108) self-report questionnaire that measures QOL in cancer patients, and includes a10-item colon subscale. 14 because it corresponds to the symptoms experienced by this patient population. The FACT itself consists of four subscales measuring physical (PWB, 7 items, range=0-28), functional (FWB, 7 items, range=0-28), social/family (SFWB, 7 items, range=0-28), emotional well-being (EWB, 6 items, range=0-24) and a Treatment Outcome Index (TOI). The TOI combines physical well-being, functional well-being, and the colon subscale to measure symptoms and functioning that may change over the course of treatment. The FACT can be either self-administered or used in an interview format and can be completed in 5-10 minutes. Patients were asked to rate themselves on how they feel today and over the past seven days on a
Likert scale from 0 (not at all) to 4 (very much). The FACT-G provides subscale scores and a total QOL score. A higher score indicates better QOL. Cronbach's Alpha for each subscale has been reported as follows: PWB (0.82); FWB (0.80); SFWB (0.69); EWB (0.74); and total FACTG (0.89).The FACT-Treatment Satisfaction is an optional module for the FACT-G. The instrument has 8 quantitative items (using both a 3-point and 5-point Likert scale) and one space for open-ended narrative commentary on the treatment. The questions are intended to gauge a survivor’s satisfaction with his/her respective treatment.
Caregiver Quality of Life Index-Cancer Scale (CQOL-C) (Caregivers)22 The CQOL-C scale consists of 35 five-point Likert-type items designed to assess dimensions of cancer caregiver quality of life (burden, disruptiveness, positive adaptation, financial concerns). 5-point Likert scale responses range from “not at all” to “very much.” The total score ranges from 0-140, with higher scores indicating better quality of life. The CQOL-C has demonstrated good reliability and internal consistency, with a test-retest correlation of 0.95 and a Cronbach’s α of 0.91.
Center for Epidemiologic Studies-Depression (CES-D) (Patients and Caregivers)23 The CES-D is a 20-item self-report measure developed to screen for depressive disorders. It has high sensitivity and positive predictive value for detecting depressive disorders (major depression and dysthymia). Cut-off scores indicate the likelihood that a subject meets diagnostic criteria for depression. A score of ≥ 16 has been used as the cut-off score with higher scores indicating significant depressive symptoms. We defined “possible”, “probable” and “cases” of depression by <16= not depressed; 16- < 23 = “possible”; 23- <28 = “probable”; 28+ = “case”.
Medical Outcomes Study Social Support Survey (MOS-SSS) (Patients and Caregivers)24 Self-reported social support was assessed in both patients and caregivers using the Medical Outcome Study Social Support Survey (MOS-SSS). The MOS-SSS contains 19 functional support items hypothesized to measure five dimensions of social support: 1) emotional support, 2) informational support, 3) tangible support, 4) positive social interaction, and 5) affectionate support. Responses are on a five-point Likert-type scale ranging from ‘none of the time’ to ‘all of the time’.
Statistical Analysis: Summary statistics, including means and standard deviations for continuous data and frequencies and proportions for categorical data, were calculated for all study measures. Repeated measures regression models were created to assess change over time and between visits in QOL outcomes (FACT, CQOL-C, CES-D, MOS-SSS); pairwise comparisons between baseline values and subsequent visits were analyzed using the Dunnett adjustment for multiple comparisons. These models were also used to assess the relationship between dyadic QOL and depression measures, with the caregiver score the dependent outcome (CQOL-C and CES-D) and the patient score the predictor (FACT, patient CES-D, MOS-SSS). The beta coefficients from these models estimate the strength of the relationship between QOL measures. To compare QOL scores/values within dyads (CES-D, MOS-SSS), differences were calculated by subtracting the caregiver’s value from the corresponding patient’s value. SAS (version 9.4, Cary, NC, USA) was used for all analyses.
Results
The study team approached 77 dyads, with 73 (95%) consenting. All surgical procedures were preformed between February, 2016 and November, 2017. After consent, 6 patients had their procedure cancelled due to progression of disease, comorbidity or insurance coverage issues. The average age of the patients was 56 with 60% female. Patient primary site leading to the peritoneal metastases were: appendiceal 50, colorectal 15, mesothelioma 6, small bowel 1, and gastric 1. Fourteen patients received systemic chemotherapy prior to surgery. The median PCI found at laparotomy was 14. The median length of stay was 8 days. A colostomy was created in 4, ileostomy in 4 and 1 patient had a pre-existing colostomy closed at the time of surgery. Cytoreductive surgery without HIPEC was performed in 5 cases due to an inability to achieve a satisfactory resection. Patients were postoperatively admitted to the ICU (n=14, 20%) or the ward (n=56, 80%). The 30 day readmission rate was 18% and the 90 day mortality was 4%. The 1 and 3 year overall survival rates were 90.0% and 69.7%, respectively, for patients receiving HIPEC, and 77.8% and 0% for those without HIPEC, (p=.0007).
Of the 73 consenting dyads, 58 pairs returned at least one questionnaire. See Figure 1 for patient and caregiver flow chart. A total of 84% (N=49) of informal caregivers were spouses or partners; 10% (N=6) were daughters or sons; while the remaining 6% (N=1 in each category) were siblings, parents or other relatives, respectively. Over 50% of the patient population traveled over 100 miles to the Comprehensive Cancer Center of Wake Forest Baptist Medical Center to receive CRS + HIPEC and for follow-up visits. (Table 1)
Medical Outcomes Study Social Support Survey:
Caregivers reported lower perceived social support availability than patients across all time points. See tables 2 and 3. While patient and caregiver trajectories remained similar over time, the difference between dyads is significant for all models when fitting a repeated measures regression (estimated differences for total MOS-SSS scores: 17.4 (5.2), p= 0.0013). Overall MOS-SSS scores for patients were: T1 (94.9; SD 7.7), T2 (94.7, SD 9.0), T3 (95.9, SD 8.1), T4 (94.6, SD 8.7); caregivers reported: T1 (74.7, SD 20.7), T2 (78.4, 24.8), T3 (80.6, SD 18.3), T4 (77.5, SD 24.7).
Depressive symptoms: Caregiver and patient depressive symptom scores changed significantly over time. (Figure 2 or 3) CES-D means for caregivers were (T1-4): 14.4 (SD 12.0), 13.1 (9.3), 10.0 (9.2), 12.9 (11.3), global p=0.0008; for patients were: 9.3 (SD 7.9), 12.3 (8.3), 6.8 (6.7), and 8.6 (8.2), global p= 0.0002. Pre-surgery, caregivers scored 4.8 points (SD 13.4) (p=0.026) higher than patients on the CES-D, indicating more depressive symptoms. Patients reported more depressive symptoms at the post-surgical visit. At T3, both groups’ scores declined; yet caregiver CES-D scores increased again at T4, reflecting an average of a 4.7 point difference between caregiver and patient scores (SD 12.5; p= 0.165). Numbers of possible, probable and “cases” of depression at T1 for caregivers were 17 (39%), 11 (25%), and 6 (14%) versus 7 (16%), 4 (9%), and 1 (2%) for patients. Patient overall QOL (FACT) and subscale scores and Caregiver QOL are reported in Table 3. Patient QOL T1 mean total= 105.6 (SD 18.2), T2= 90.1(18.8), T3= 112.7 (15.8), T4= 116.1 (13.7). This trend indicates a drop on QOL from the pre- to post-intervention measurement
points, followed by QOL improvement at the 6-month time point. Figure 3 plots patient and caregiver QOL and depression trajectories over time.
All caregiver QOL subscales on the CQOL-C (Burden, p= 0.00035; Disruptiveness, p<0.0001; Financial p=0.0004) and overall scores (p<0.0001), with the exception of the Adaptation scale (p=0.34), changed significantly over the course of the four measurement time points: T1= 95.6 (SD 21.9), T2= 101.6 (SD 18.6), T3= 108.8 (SD 18.7), T4= 105.8 (SD 21.6). Least square means indicate estimated mean score improvement in QOL of 11.5 points (4.9, 18.2), p=0.0002 and estimated mean score improvement of 8.7 points (0.3, 17.1), p =0.040 between pre- surgery and the 12-month time period. For caregivers, QOL scores were lowest at the pre-surgery time point and demonstrated significant improvement by six months-post intervention.
Repeated measures regression analysis of variance models assessed the effect of patient QOL and CES-D scores on caregiver depression and QOL scores. In these models, caregiver outcomes were significantly associated with patient QOL scores; Over the 4 visits, caregiver CES-D scores were significantly correlated with FACT EWB, FWB, TOI, FACT G, and FACT total scores. Poorer caregiver QOL scores were associated with worse depressive scores in patients. In modeling the CQOL-C total score, all FACT scores, with the exception of the disease related (colon) subscale, predicted higher caregiver QOL scores. The CES-D model revealed that higher depressive symptoms in patient were associated with lower caregiver QOL. To estimate the impact of patient emotional well-being (EWB) on CESD-D, beta coefficient were calculated; caregivers experienced an average of 0.58 units of improvement (lower) in CES-D scores for every unit increase in patients’ reported EWB (p=0.003). Additionally, caregivers were
estimated to have a 1.47 unit improvement on the CQOL-C for every unit of increased EWB endorsed by patients (p<0.0001).
Discussion In this study, we assessed and compared caregiver and patient-reported QOL and depressive symptoms before and after CRS + HIPEC. We also explored factors associated with poorer QOL among caregivers over a 12 month post-treatment period. Our results showed that caregivers reported higher levels of depressive symptoms and lower social support relative to their patient counterparts at all time points. Though caregiver depressive symptoms exceeded patients, no group mean score exceeded the defined significant cut off point of 16.23 Nevertheless 16% of patients and 39% of caregivers reported depressive symptoms significant enough to warrant professional attention at baseline. Similarly, in another study focused on caregiver spouses of patients with advanced disease, nearly 40% of caregivers and 23% of patients recorded significant symptoms of depression,8 suggesting caregivers of patients with advanced disease are at high risk for developing depression. All CRS + HIPEC patients have advanced, but not necessarily terminal disease. Caregiver depressive symptoms were highest pre-CRS + HIPEC and continued to stay elevated post-surgery, ultimately dropping significantly at the 6-month time point prior to elevating again at the 12-month time point. It is not surprising that caregivers, relative to their patients, reported lower social support that declined over time. Though this decline in social support was similarly reported in another study for patients, we believe this is the first study to demonstrate declining social support for caregivers of CRS + HIPEC patients. With oncologic care focused primarily on the patient, it is not surprising that caregivers reported lower support than patients in this study. In contrast,
caregivers may be viewed as a source of support for the patient rather than in need of support themselves. However, there is a growing literature in cancer care documenting the amount of time and types of activities caregivers undertake in supporting the patient4, as well as the critical need for increased support for caregivers of patients with cancer.25-27 Caregiver QOL improved over the study time period from baseline to one year. However, caregiver QOL at baseline (mean = 95.6; SD=21.9) was lower than another study of lung, breast, and prostate cancer caregivers (mean = 106.4; SD = 16.3).22 Patient QOL followed a pattern similar to that reported in many previous studies15 in that it was worse at the post-surgery followup (T2), returning close to baseline levels at six months and leveling off at one year. It is thought the period of hospitalization and discharge, prior to the post-surgical visit, places significant physical demands on the caregiver given the patient’s decline in functional status; they also face additional challenges, including geographical distance from home, where, presumably additional help would be available. Our caregivers reported improvement in QOL after CRS + HIPEC suggesting that caregiver QOL scores may improve due to the significant level of patient supportive care received in the hospital. Caregivers may experience relief at finally receiving treatment for their loved ones, particularly if it goes well. We do not know the extent to which the primary caregiver received additional help from other “non-primary” caregivers; both in the hospital and at home, as only one primary caregiver was identified in our study. Clinical experience suggests that there is often more than one caregiver helping with patient care, possibly influencing QOL scores post-hospitalization. The pattern of improved QOL for caregivers may be unique to the CRS + HIPEC setting since the burdens of treatment are significant at one time point and likely diminish over weeks. In a setting of radiotherapy treatment for head and neck cancer, a different pattern was reported, with increased burden and
worsened QOL for caregivers over time.28 Our QOL findings, coupled with our depressive symptoms findings, suggest that the time immediately preceding CRS + HIPEC is challenging for caregivers and perhaps the time to initiate a pre-habilitation intervention. Regarding patient and caregiver depressive symptoms, caregiver mean scores on the CES-D exceed those of patients at every time point. However, no group’s mean score exceeds the defined significant cut off point of 16. Nevertheless 16% of patients and 39% of caregivers reported depressive symptoms significant enough to warrant professional attention at baseline. In a study focused on caregiver spouses of patients with advanced disease, nearly 40% of caregivers and 23% of patients recorded significant symptoms of depression. 8 Caregivers of patients with advanced disease are a high-risk population for depression. All CRS + HIPEC patients have advanced, but not necessarily terminal disease. Caregiver depressive symptoms were highest preCRS + HIPEC and continued to stay elevated post-surgery, ultimately dropping significantly at the 6-month time point prior to elevating again at the 12-month time point. The anticipation of the demanding CRS + HIPEC procedure, the symptoms of the patients, and the cumulative demands on caregivers prior to the actual treatment may contribute to increased depressive symptomatology and QOL decrements. Unlike patients, who experience more acute physical and functional status changes, caregiver scores may reflect the emotional and instrumental toll inherent in their roles. Perhaps caregiver QOL does not follow a similar pattern as we hypothesized due to additional help at home, increased familiarity with patient care due to instruction at the hospital and an increased sense of caregiver self-efficacy due to experience. By the six-month assessment point, most caregivers reported improved mood and QOL. At 12 months, QOL declines and depressive symptoms increase somewhat, perhaps related to patient disease or continued role demands. Lower perceived social support, higher depressive
symptomatology and possible increased demands on the caregiver are most prominent at the preintervention time-period. Caregivers are entering the CRS + HIPEC already somewhat depleted. The inpatient stay with 24/7 monitoring of the patient and ongoing contact with professionals for the caregiver may provide a boost to morale and reduced caregiver burden, which has improved by the time of the post-surgery visit. The unique patterns (Figure 3) in caregiver- and patient-reported QOL underscore the different challenges for patients and caregivers throughout the CRS + HIPEC treatment process. We found that patient QOL predicted both caregiver depression and QOL, and patient depressive symptoms predicted caregiver overall QOL. Improvement in the emotional well-being of patients was associated with reduced depressive symptoms in caregivers. Watching a loved one suffer exacts its toll on caregivers in the form of significant depressive symptoms at baseline and the post-surgical visit. Seeing improvement in the patient’s emotional well-being, more so than physical functioning, acts as a welcome relief for the caregiver’s suffering. Impairments in both patient and caregiver emotional well-being further underscores the need to address emotional adaptation within both patients and caregivers. Caregivers are not contending with the same physical demands as patients; however the emotional and logistical demands of caregiving can be daunting, and clearly have an impact on QOL. We acknowledge both the limitations and strengths of this study. A major strength is this represents the first study evaluating quality of life in both patients and caregivers after CRS & HIPEC. First, we asked patients to identify a single primary caregiver. Many patients have no, or multiple caregivers, thus, caregiver feedback may reflect the perspective of only one of many caregivers. Second, there was significant attrition over time and it is possible that those who did not return data or who dropped out of the study were those who were struggling the most with
depressive symptoms and impaired QOL. Findings are limited by the modest sample size, particularly at the final 12 month assessment, where attrition was 65%. Additionally, there is an active inpatient psychosocial oncology consultation service and a weekly caregiver support group that serves the surgical oncology service, primarily to assess and treat depressive symptoms, and we did not record which participants may have utilized those options. Finally, our assessments of caregiver functioning were limited to a 12-month period and longer term follow up should be considered. Subsequent studies should continue to assess the status and needs of caregivers, establishing normative data with the goal of developing intervention strategies to help reduce caregiver depressive symptoms and improve QOL. Despite these limitations, this is the first study to our knowledge to assess depressive symptoms, QOL, and social support in this vulnerable and understudied population of caregivers. Further, this study is strengthened by assessing outcomes among both members of the dyad, as well as exploring associations between patient and caregiver outcomes. Finally, we undertook a longitudinal approach in this study to provide key data on QOL changes before and after CRS + HIPEC.
The unique role demands caregivers experience likely influenced their own and the patients’ depressive symptoms, and QOL over time in a complex reciprocal manner. Our data underscore the importance of caregivers in the treatment equation. Cancer is a disease of the family that especially affects caregivers. Caregivers experience comparatively more suffering (depressive symptoms, impaired QOL) than patient counterparts at various junctures, and there are significant associations between patient and caregiver functioning. What happens to the patient reverberates in the caregiver and likely is mediated by a number of factors, including the quality of the caregiver patient relationship.7,8
In light of these data we suggest initiating systematic caregiver assessment and support interventions at the pre-operative and at the first post-operative visits, where depressive symptoms are prominent and QOL is impaired. Patients and caregivers are likely burdened with the uncertainty of outcome, complexity of the treatment modality, and the logistics of CRS + HIPEC. Since most dyads travel to medical institutions for pre- and post-op visits, clinical staff could assess needs and intervene both pre- and post-operation in the clinic setting. In other intensive treatment settings, psychosocial assessment of patient and caregivers is standard of care. Telephone or self-directed web-based interventions may be an additional modality to reach this population. Regardless of approach, assessment and intervention for the patient and caregiver may enhance social support, address depressive symptoms and improve quality of life and the experience for both. Conclusions: Significant numbers of caregivers endorsed high depressive symptom burdens and financial concerns. Different caregiver-patient trajectories reflect the need for differential timing of supportive interventions. Evaluation of quality of life and impact of CRS+HIPEC procedures must move beyond assessment of only the patient.
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Table 1. Demographics Demographic Data Age, y, mean (SD), range Patient 56 (12), 24–75 Caregiver 57 (13), 22–74 Sex, n (%) Patient Female 35 (60) Male 23 (40) Caregiver Female 30 (52) Male 28 (48) Race, n (%) Patient White 48 (83) Black 7 (12) Other 3 (5) Caregiver White 50 (86) Black 8 (14) Caregiver employment status, n (%) Not employed 29 (50) Full-time 25 (43) Part-time 3 (7) Average distance of patient from WFBMC, n (%) 0-25 miles 3 (5) 26-50 miles 12 (21) 51-75 miles 6 (10) 75-100 miles 7 (12) 100+ miles 30 (52) Designated caregiver relationship, n (%) Spouse/partner 49 (84) Son/daughter 6 (10) Sibling 1 (2) Parent 1 (2) Other relative 1 (2) N = 58* (100%) *58 pairs where at least the caregiver provides data WFBMC, Wake Forest Baptist Medical Center
Table 2. Caregiver Quality of Life Mean (SD) Scores
CQOL-C
Preoperative Postoperative (n = 44) (n = 37)
6 mos (n = 34)
12 mos (n = 17)
p Value
Burden
22.4 ± 9.5
26.6 ± 8.1
29.1 ± 8.0
29.0 ± 8.8
0.0035†
Disruptiveness
23.4 ± 3.6
22.9 ± 4.4
25.6 ± 3.0
25.8 ± 3.6
<0.0001†
Adaptation
18.3 ± 5.7
18.4 ± 5.8
18.8 ± 5.3
17.1 ± 6.7
0.34†
Financial
8.1 ± 3.6
10.0 ± 2.5
9.6 ± 2.9
9.6 ± 3.2
0.0004†
CQOL-C
95.6 ± 21.9
101.6 ± 18.6
108.8 ± 18.7
105.8 ± 21.6
<0.0001†
Data are presented as mean ± SD. † Statistically significant CQOL-C, caregiver quality of life
Table 3. Patient Quality of Life (FACT-C) Mean (SD) Scores
FACT PWB SFWB
Preoperative (n= 46) Mean SD 22.8 5.7 24.0 3.7
Postoperative (n= 34) Mean SD 16.6 6.6 23.9 3.7
6 mos (n= 34) Mean SD 23.6 5.1 24.9 3.3
12 mos (n=16) Mean SD 24.6 3.4 25.1 3.4
p Value <0.0001* 0.19
EWB 18.4 4.2 18.5 4.1 20.2 3.5 20.8 3.2 0.015* FWB 19.5 6.6 14.9 6.0 21.9 6.0 23.8 4.2 <0.0001* FACT-G 84.8 14.9 73.8 15.4 90.5 13.1 94.3 11.0 <0.0001* CCS 20.8 4.4 16.3 4.8 22.2 4.5 21.8 5.3 0.0013* Total 105.6 18.2 90.1 18.8 112.7 15.8 116.1 13.7 <0.0001* TOI 63.1 14.2 47.8 14.0 67.6 12.6 70.2 10.4 <0.0001* *Statistically significant CCS, colon cancer subscale; EWB, emotional well-being; FACT, Functional Assessment of Cancer Therapy; FACTG, Functional Assessment of Cancer Therapy-General; FWB, functional well-being; PWB, physical well-being; SFWB, social/family well-being; TOI, treatment outcome index
Figure 1. Quality of life pilot study in patients receiving intraperitoneal hyperthermic chemotherapy and their designated primary caregivers Figure 2. Caregiver and patient Center for Epidemiologic Studies-Depression (CES-D) mean scores at baseline, postoperative, 6, and 12 months Figure 3. Percent of maximum quality of life for caregivers and patients at study time points. FACT-G, Functional Assessment of Cancer Therapy-General; QOL, quality of life.
Precis: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is a formidable procedure. The impact on the quality of life of the patient and primary caregiver were evaluated in this prospective study.