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Risk factors for cancer-related distress in colorectal cancer survivors: one year post surgery

J Cancer Surviv

2020 Syrjala, Karen L; Grady, William M; Han, Claire Jungyoun; Li, Christopher I

PURPOSES: Cancer-related distress is known to persist long after completion of treatment. Factors related to distress are largely unexplored in colorectal cancer (CRC) survivors. We examined changes over time and risk factors for distress in CRC patients over the first year after surgery. METHODS: We included 212 CRC patients with data at 6 and 12months post-surgery from the ColoCare Study in Heidelberg, Germany. Sociodemographic and lifestyle factors, social support, and health-related quality of life (HrQOL) prior to surgery were evaluated as predictors of cancer-related distress. Distress was measured with the Cancer and Treatment Distress instrument (CTXD). Linear regression analyses examined associations between risk factors and distress. RESULTS: Distress subscale scores varied significantly over time: health burden subscale score increased (P<.001), while finances (P=.004), medical demands (P<.001), and identity (P<.001) subscale scores decreased over time. Uncertainty and family strain subscale scores did not change. Younger age, lower income, advanced tumor stage, poorer social support, and poorer baseline HrQOL predicted higher level distress at 6 and 12months. CONCLUSION: Cancer-related distress continues unresolved after surgery. Although some risk factors are difficult to alter, those at highest risk can be identified earlier for possible preventive strategies. IMPLICATIONS FOR CANCER SURVIVORS: Screening for risk factors pre-surgery would allow for targeted interventions including strategies to improve resources for those with low support, thereby reducing long-term distress in CRC survivors.

Symptom Experiences in Colorectal Cancer Survivors After Cancer Treatments: A Systematic Review and Meta-analysis

Cancer Nurs

2020 Syrjala, Karen L; Han, Claire Jungyoun

BACKGROUND: With improved survivorship rates for colorectal cancer (CRC), more CRC survivors are living with long-term disease and treatment side effects. Little research exists on CRC symptoms or symptom management guidelines to support these individuals after cancer treatments. OBJECTIVES: The aims of this study were to systematically review symptom experiences, risk factors, and the impact of symptoms and to examine the pooled frequency and severity of symptoms via meta-analyses in CRC survivors after cancer treatments. METHODS: Relevant studies were systematically searched in 7 databases from 2009 to 2019. Meta-analysis was conducted for pooled estimates of symptom frequency and severity. RESULTS: Thirty-five studies met the inclusion criteria. Six studies assessed multiple CRC symptoms, whereas 29 focused on a single symptom, including peripheral neuropathy, psychological distress, fatigue, body image distress, cognitive impairment, and insomnia. The pooled mean frequency was highest for body image distress (78.5%). On a scale of 0 to 100, the pooled mean severity was highest for fatigue (50.1). Gastrointestinal and psychological symptoms, peripheral neuropathy, and insomnia were also major problems in CRC survivors. Multiple factors contributed to adverse symptoms, such as younger age, female gender, and lack of family/social support. Symptoms negatively impacted quality of life, social and sexual functioning, financial status, and caregivers' physical and mental conditions. CONCLUSIONS: Colorectal cancer survivors experienced multiple adverse symptoms related to distinct risk factors. These symptoms negatively impacted patients and caregivers' well-being. IMPLICATIONS FOR PRACTICE: Healthcare providers can use study findings to better assess and monitor patient symptoms after cancer treatments. More research is needed on CRC-specific symptoms and their effective management.

Participant Perceptions on a Fitbit and Facebook Intervention for Young Adult Cancer Survivors: A Qualitative Study

J Adolesc Young Adult Oncol

2020 Syrjala, Karen L; Chow, Eric J; Baker, K. Scott; Ceballos, Rachel M; Mendoza, Jason A

Purpose: Among cancer survivors, physical activity (PA) is associated with reductions in cancer recurrence, morbidity, and mortality. Most young adult (YA) survivors do not attain adequate PA. Digital modalities, specifically wearable activity monitors with a paired mobile application and private social media group for support offer a promising approach for promoting PA among YAs. We conducted a pilot randomized controlled trial of this intervention. To evaluate its acceptability and perceptions of the intervention components, we conducted qualitative interviews with those in the intervention. The results of our interviews serve to refine future interventions to better serve this population. Methods: Semistructured qualitative interviews with 13 YA cancer survivors ages 20-39 who participated in the intervention assessed perceptions of the digital components of the study and buddy system of nominating a friend to participate in PA with the survivor. Analyses included a qualitative thematic analysis of the interview transcripts and coded interview segments into three predetermined categories: facilitators, limitations, and suggestions. Results: Participants described wide-ranging benefits of the intervention, citing the Fitbit device and buddy system as major motivators to engage in PA and reach goals. Most participants noted feelings of increased physical and emotional wellness. The most-cited limitation of the intervention was the automated text messages, which participants found impersonal. Suggestions for improvement included integrating more elements of competition and group challenges. Conclusion: This digital PA intervention was perceived as feasible and acceptable to YA cancer survivors and appears promising for promoting PA and improving long-term health and quality of life. identifier number: NCT03233581; Date of registration: July 28, 2017.

Influence of St. John's Wort on Intravenous Fentanyl Pharmacokinetics, Pharmacodynamics, and Clinical Effects A Randomized Clinical Trial


2020 Shen, Danny D; Syrjala, Karen L

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The popular herbal medicine, St. John's wort, is a potent inducer of several cytochrome P450 enzymes, including CYP3A4, which plays a role in the metabolism of fentanyl. St. John's wort may also influence the expression of P-glycoprotein, which can alter the movement of drugs across the blood-brain barrier. WHAT THIS ARTICLE TELLS US THAT IS NEW: The pharmacokinetics and pharmacodynamics (pupillary diameter over time) were examined in volunteers before and after treatment with St. John's wort. No differences were seen, suggesting that this herbal medication does not influence the clinical behavior of fentanyl. BACKGROUND: Patients often use complementary and alternative herbal medicines, hence, potential exists for adverse herb-drug interactions. Fentanyl is metabolized by hepatic CYP3A4 and considered transported by blood-brain barrier P-glycoprotein. Both disposition processes could be upregulated by the herbal St. John's wort. This investigation evaluated effects of St. John's wort on fixed-dose and apparent steady-state IV fentanyl pharmacokinetics, pharmacodynamics, and clinical effects. METHODS: Healthy volunteers received a fentanyl fixed-dose infusion and an individually tailored target controlled infusion on separate days, before and after 30-day St. John's wort (300mg thrice daily; n = 8) or placebo control (n = 8) in a randomized parallel-group design. Fentanyl plasma concentrations, pupil diameter, analgesic response to experimental pain (cold pressor), subjective side effects, and cognitive effects were measured. Plasma fentanyl concentrations and changes in pupil diameter were subjected to pharmacokinetic-pharmacodynamic modeling. RESULTS: St. John's wort did not alter fentanyl pharmacokinetics. Clearance (l/min) before and after St. John's wort (1.13&nbsp; 0.29 and 1.24&nbsp; 0.26, respectively) or placebo (0.96&nbsp; 0.28 and 1.12&nbsp; 0.27, respectively) were not different. St. John's wort also did not affect fentanyl pharmacodynamics as measured by pupil constriction after fixed-dose and tailored fentanyl infusions. EC50 (ng/ml) was 1.1&nbsp; 0.7 and 1.4&nbsp; 0.9 before and after St. John's wort versus 1.2&nbsp; 0.8 and 1.4&nbsp; 1.7 before and after placebo. Effect site equilibration time, T,ke0 (min), was 12.8&nbsp; 5.3 and 11.3&nbsp; 6.4 before and after St. John's wort versus 11.4&nbsp; 6.4 and 11.1&nbsp; 5.6 before and after placebo. St. John's wort had no influence on analgesia, cognitive performance, or somatic cognitive-affective effects of fentanyl. CONCLUSIONS: St. John's wort did not alter fentanyl pharmacokinetics, pharmacodynamics or clinical effects, suggesting no effect on hepatic clearance or blood-brain barrier efflux. Patients taking St. John's wort will likely not respond differently to IV fentanyl for anesthesia or analgesia.

Worsening cognitive performance is associated with increases in systemic inflammation following hematopoietic cell transplantation

Brain Behav Immun

2019 Syrjala, Karen L

BACKGROUND: Cognitive decline is a frequently cited concern among patients receiving hematopoietic cell transplantation (HCT), and patients often experience neurocognitive deficits (i.e., stable or worsening neurocognitive performance) throughout the transplant course. Deficits can be most severe during the acute transplant period (i.e., 90 days after transplantation), when patients also typically experience elevated systemic levels of inflammation. Previous studies have identified inflammation as a likely mechanism underlying neurocognitive deficits, primarily in women with breast cancer; however, longitudinal studies have been limited. In this study, our aim was to evaluate the relationship between changes in systemic inflammation and changes in cognition from pre- to post-transplant in patients receiving allogeneic HCT. METHODS: Patients scheduled for allogeneic HCT (n=85) were assessed prior to HCT and 90 days after HCT. Biomarkers of inflammation included IL-6, sTNF-RII, CRP, and IL-1ra, which have been previously associated with neurocognitive deficits in cancer patients. Patients completed neuropsychological testing and self-report questionnaires. RESULTS: Mixed models demonstrated that from pre- to post-HCT, increases in IL-6 and sTNF-RII were associated with neurocognitive deficits, and decreases in CRP were associated with better neurocognitive performance. There were no significant associations between changes in inflammation and self-reported cognitive performance. CONCLUSIONS: Our findings are the first to our knowledge to report a robust relationship between increasing inflammation and neurocognitive deficits from pre- to post-HCT. Additional studies are needed to confirm these findings in a larger sample.

Correlates of anxiety and depression symptoms among patients and their family caregivers prior to allogeneic hematopoietic cell transplant for hematological malignancies

Support Care Cancer

2019 Syrjala, Karen L

PURPOSE: Given the complexities and risks of allogeneic HCT, patients and their family caregivers may experience elevated psychological distress, including symptoms of anxiety and depression, in anticipation of the procedure. Patients and caregivers also bring with them their pre-HCT experiences of diagnosis, prior treatment, and associated burdens, thus potentially compounding their acute distress. Identification of clinical, psychosocial, and sociodemographic factors related to pre-HCT distress would allow targeting of patients and caregivers who may require assistance during the HCT process. METHODS: Consecutive patients (n = 111) and their caregivers (n = 110) completed measures of anxiety, depression, cancer distress, perceived threat, perceived control, self-efficacy, relationship quality, and physical quality of life in the week before HCT. Multivariate linear regression analysis was used to identify factors associated with patient and caregiver anxiety or depression, including disease type, donor type, and patient and caregiver sociodemographic, health-related, and psychosocial factors. RESULTS: Family caregivers had higher levels of anxiety and depression symptoms than patients. Thirty percent of caregivers vs. 17% of patients met criteria for clinically significant anxiety and a lesser amount (5% for both) met criteria for clinically significant depression. Patient anxiety was related to younger age (b = - 0.22, p = 0.005) and greater cancer-related distress (b = 0.59, p < 0.001), while caregiver anxiety was related to lower self-efficacy (b = - 0.19, p = 0.011) and greater cancer-related distress (b = 0.58, p < 0.001). Similarly, patient depression was related to lower perceived control (b = - 0.17, p = 0.050), greater cancer-related distress (b = 0.34, p = 0.005), and lower physical functioning (b = - 0.26, p = 0.008), while caregiver depression was related to greater cancer-related distress (b = 0.46, p < 0.001). CONCLUSIONS: Family caregivers may be more emotionally vulnerable than patients before HCT and in need of additional assistance. Cancer-related distress was the strongest correlate of anxiety and depression in both patients and caregivers, suggesting that distress related to their cancer experience and its consequences plays a major role in their emotional functioning prior to HCT.

Tailoring a Survivorship Care Plan: Patient and Provider Preferences for Recipients of Hematopoietic Cell Transplantation

Biol Blood Marrow Transplant

2019 Syrjala, Karen L; Baker, K. Scott

PURPOSE: This study aimed to develop a survivorship care plan (SCP) that could be individualized to facilitate long-term follow-up care of hematopoietic cell transplantation (HCT) survivors. METHODS: A sample SCP was developed that included two documents- a treatment summary and preventive care recommendations that combined data on treatment exposures routinely submitted by HCT centers to the Center for International Blood and Marrow Transplant Research (CIBMTR) with long-term follow-up guidelines. Focus groups were conducted by phone to characterize the critical patient-centered elements of the SCP. Focus group eligibility criteria included: 1) adult patients >1 year post-HCT and their caregivers (3 groups, n=22); 2) HCT physicians and advanced practice providers (APPs) (2 groups, n=14); 3) HCT nurses/social workers (4 groups, n=17), and 4) community health care professionals (3 groups, n=24). Transcripts were analyzed for saturation of key themes using NVivo 10 software. RESULTS: Patients/caregivers suggested combining the treatment summary and care guidelines into one document. They also requested sections on sexual and emotion health and the immune system. Providers wanted the treatment summary to focus only on what they absolutely must know. Themes were similar across healthcare professionals, though screening for psychosocial issues was emphasized more by the nurses/social workers. All preferred to receive the SCP electronically; however, hardcopy was considered necessary for some patients. All felt the SCP would facilitate appropriate post-HCT care. CONCLUSION: This study highlighted the need for an SCP instrument to facilitate HCT survivorship care. Furthermore, it demonstrated the feasibility and value of engaging HCT patients, caregivers and providers in developing a survivorship care tool. Their feedback was incorporated into a final SCP subsequently tested in a randomized trial.

Survivorship, Version 2.2018 Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network

2018 Syrjala, Karen L; Baker, K. Scott

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adultonset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.

Damocles' syndrome revisited: Update on the fear of cancer recurrence in the complex world of today's treatments and survivorship.

Hematology/oncology and stem cell therapy

2018 Syrjala, Karen L

OBJECTIVE/BACKGROUND: Improvements in curative treatments for many types of cancer have emerged over the past several decades, resulting in a growing population of long-term cancer survivors - of both adult and childhood cancers. Despite this incredible medical achievement, long-term survivors of cancer face a unique fear: the fear of relapse. METHODS: We conducted a review of the literature for data on fear of relapse among cancer survivors. RESULTS: The fear of cancer recurrence is present in survivors of childhood and adult cancers as well as family members and often leads to psychological sequelae. CONCLUSION: Literature on the fear of cancer recurrence has begun to emerge. However, herein we provide a unique approach through the use of a metaphor: Cicero's story of Damocles' sword. We aim to outline the many fear-related and emotional challenges faced by cancer survivors with an extensive review of studies demonstrating such challenges.

Severity, course, and predictors of sleep disruption following hematopoietic cell transplantation: a secondary data analysis from the BMT CTN 0902 trial

Bone Marrow Transplant

2018 Syrjala, Karen L; Lee, Stephanie J

Sleep disruption has received little attention in hematopoietic cell transplantation (HCT). The goal of this study was to describe severity, course, and predictors of sleep disruption following HCT. A secondary data analysis was conducted of the Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) 0902 study. Participants completed a modified version of the Pittsburgh Sleep Quality Index prior to transplant and 100 and 180 days posttransplant. Growth mixture models were used to characterize subgroups of patients based on baseline sleep disruption and change over time. A total of 570 patients (mean age 55 years, 42% female) were included in the current analyses. Patients could be grouped into four distinct classes based on sleep disruption: (1) clinically significant sleep disruption at baseline that did not improve over time (20%); (2) clinically significant sleep disruption at baseline that improved over time (22%); (3) sleep disruption that did not reach clinical significance at baseline and did not improve over time (45%); and (4) no sleep disruption at baseline or over time (13%). These data provide a more comprehensive understanding of sleep disruption that can be used to develop interventions to improve sleep in HCT recipients.