Comparing symptom clusters in cancer survivors by cancer diagnosis: A latent class profile analysis.

PURPOSE: Research on symptom clusters in oncology is progressing, but knowledge gaps remain. One question is whether the number and types of symptom subgroups (i.e., latent classes) differ based on cancer diagnosis. The purpose of this study was to: (1) identify and compare latent class subgroups based on four highly prevalent symptoms (pain, fatigue, sleep disturbance, and depression), and (2) examine the differences in sociodemographic and clinical factors in the identified latent classes across the seven cancer types (i.e., prostate, non-small cell lung, non-Hodgkin's lymphoma, breast, uterine, cervical, and colorectal cancer). METHODS: This study is a cross-sectional secondary analysis of data obtained from the My-Health study in partnership with four Surveillance, Epidemiology, and End Results (SEER) cancer registries located in California (two), Louisiana, and New Jersey. The sample included 4,762 cancer survivors 6-13 months following diagnosis of one of the seven cancer types mentioned. Latent class profile analysis was used. RESULTS: Subjects were primarily young (59% age 21-64 years), Caucasian (41%), married/cohabitating (58%) and unemployed (55%). The number and types of symptom subgroups varied across these seven cancer populations: four-subgroups were the common in prostate, lung, non-Hodgkin's lymphoma, and breast cancer survivors. Unmarried, low education, and unemployment status were associated with high risk of symptom burden across the cancer types. CONCLUSION: Identifying symptom subgroups by cancer diagnosis has the potential to develop innovative and effective targeted interventions in cancer survivors. Further research is needed to establish extensive knowledge in symptom clustering between treatment regimens, and short-term and long-term cancer survivors.

Associations of frailty with symptoms, and HRQOL in older cancer survivors after cancer treatments: a systematic review and meta-analyses.

PURPOSE: Frailty in older adult cancer survivors after cancer treatments is associated with various health outcomes. However, there is less agreement on how frailty affects symptoms and health-related quality of life (HRQOL). This systematic review and meta-analysis aimed to evaluate the current literature on frailty, symptoms, and HRQOL, as well as the associations of frailty with these factors in older adult cancer survivors with chemotherapy. METHODS: A review was conducted on peer-reviewed publications from 2008 to 2023, using seven electronic databases. Meta-analyses were performed using random effects models to determine pooled effect estimates for frailty prevalence, symptom severity, and HRQOL scores. RESULTS: A total of 26 studies involving older cancer survivors were included in the analysis. Most of these studies were conducted in Western countries and focused on White survivors, particularly those with breast cancer. The mean pooled prevalence of frailty was 43.5%. Among frail survivors, the most common symptoms reported after cancer treatments were pain (36.4%), neuropathy (34.1%), and fatigue (21.3%). Frailty was associated with higher pooled mean symptom severity (B = 1.23, p = 0.046) and lower functional HRQOL (B = - 0.31, p = 0.051, with marginal significance) after cancer treatments. CONCLUSION: Frail older cancer survivors are at high risk of adverse symptoms and poor HRQOL after cancer treatment. Further research on screening for frailty is needed to prevent older adults from developing worse symptoms burden and maintain HRQOL. It is also essential to understand the mechanisms of the associations between frailty, symptoms and HRQOL in this population.

Latent class symptom profiles of colorectal cancer survivors with cancer-related cognitive impairment.

PURPOSE: Colorectal cancer (CRC) survivors experience cancer-related cognitive impairment and co-occurring symptoms after cancer treatments. There has been little data to inform the risk factors of complex symptom phenotypes in CRC survivors. OBJECTIVES: To determine if subgroups of CRC survivors after cancer treatments could be identified based on the cognitive impairment and common co-occurring symptoms (depression, anxiety, sleep disturbance, fatigue, and pain); and to explore risk factors (sociodemographic and clinical characteristics, perceived stress, and social support) of these subgroups. METHODS: Latent class profile analysis (LCPA) was used to identify subgroups based on self-reported symptoms in 64 CRC survivors. Cognitive impairment was measured by assessing subjective cognitive function using the Patient-Reported Outcome Measurement Information System (PROMIS) measure. The Kruskal-Wallis test and regression analyses were performed. RESULTS: Three distinct latent classes were identified (Class 1: All Low '28.1%'; Class 2: High Psychological Symptoms (depression/anxiety) '25%'; Class 3: High Somatic Symptoms (fatigue, sleep disturbance, and pain) with High Cognitive Impairment'46.9%'). The pain was the most distinguishable symptom across the latent classes. The high symptom burden group was associated with less time since cancer diagnosis, higher perceived stress levels, and poor emotional social support. CONCLUSION: Our study adds to the information on interindividual variability in symptom experience of CRC survivors with cognitive impairment. Findings suggest a need for increased attention to screening for co-occurring symptoms (e.g., high pain) and future interventions focused on stress management and social support.

Risk Factors of Health-Related Quality of Life among Gastrointestinal Cancer Survivors in the U.S.: With a Focus on Social and Behavioral Determinants of Health (SBDH).

BACKGROUND: Increasing numbers of long-term gastrointestinal (GI) cancer survivors highlight the importance of understanding the factors contributing to their health-related quality of life (HRQoL). We investigated the risk factors of HRQoL, including demographics, clinical characteristics, and social and behavioral determinants of health (SBDH). METHODS: Data on adult GI cancer survivors (n = 3201) from the Behavioral Risk Factors Surveillance System (BRFSS) surveys from 2014-2021 (except for 2015) were analyzed. Unadjusted/adjusted logistic regression was used. RESULTS: The majority were women (54%) and white (78%), with a median age of 67. Survivors who were 65 years or older, diagnosed with colorectal cancer, or who had fewer comorbidities were more likely to report significantly better HRQoL. Significant social factors of poor HRQoL included unmarried, racial and ethnic minorities, poor socioeconomic status, and poor healthcare access. Significant behavioral factors of poor HRQoL were lack of physical activity, heavy alcohol consumption, and current smoking, with lack of physical activity being the most significant factor. CONCLUSIONS: The SBDH has a critical role in HRQoL. Future studies are warranted to develop a tailored survivorship intervention, such as physical rehabilitation, and to explore machine learning/artificial intelligence-based predictive models to identify cancer survivors at a high risk of developing poor HRQoL.

Factors associated with long-term gastrointestinal symptoms in colorectal cancer survivors in the women's health initiatives (WHI study).

PURPOSE: Colorectal cancer (CRC) survivors often experience long-term symptoms after cancer treatments. But gastrointestinal (GI) symptom experiences are under-investigated in CRC survivors. We described persistent GI symptoms after cancer treatments in female CRC survivors and assessed GI symptoms' risk and life-impact factors. METHODS: A cross-sectional study utilized data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. Correlation analyses and multivariable linear regression models were used. RESULTS: CRC survivors after cancer treatments were included (N = 413, mean age 71.2 years old, mean time since diagnosis = 8.1 years). 81% of CRC survivors experienced persistent GI symptoms. Bloating/gas was the most prevalent (54.2%± 0.88) and severe GI symptom, followed by constipation (44.1%±1.06), diarrhea (33.4%±0.76), and abdominal/pelvic pain (28.6%±0.62). Significant risk factors for GI symptoms include time since cancer diagnosis (<5 years), advanced cancer stage, high psychological distress, poor dietary habits, and low physical activity. Fatigue and sleep disturbance were the most significant risk factors for long-term GI symptoms (ß = 0.21, t = 3.557; ß = 0.20, t = 3.336, respectively, Ps < .001). High severity of GI symptoms was positively associated with poor quality of life (QOL), increased daily life interferences (social and physical functions), and low body image satisfaction (Ps < .001). CONCLUSIONS: Women CRC survivors experience a high GI symptom burden, highlighting the need to inform policy and improve the QOL of cancer survivors. Our findings will aid in identifying those more vulnerable to symptoms, and inform future survivorship care interventions (i.e., community-based cancer symptom management) by considering multiple risk factors (e.g., psychological distress).

Pre-Surgery Inflammatory and Angiogenesis Biomarkers as Predictors of 12-Month Cancer-Related Distress: Results from the ColoCare Study.

BACKGROUND: Patients with colorectal cancer commonly suffer from complex psychological distress. Elevated distress may be linked to systemic biomarkers. We investigated associations of biomarkers of inflammation and angiogenesis with cancer-related distress (CTXD) score. METHODS: N = 315 patients (stage I-IV) from 2 centers of the ColoCare Study were included: Huntsman Cancer Institute and University of Heidelberg. Biomarkers (e.g., IL6, VEGF-A, VEGF-D) were measured in serum collected pre-surgery and 12 months thereafter. The CTXD overall score and 4 subscales were collected 12 months after surgery and dichotomized to investigate biomarkers as predictors of distress 12 months after surgery; adjusted for age, sex, body mass index, tumor stage, center, and baseline levels of biomarkers. RESULTS: Doubling of IL6 predicted future increased risk of overall distress [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.02-1.41; P = 0.03]. VEGF-A-predicted future increased risk of high family strain (VEGF-A: OR, 1.21; 95% CI, 1.01-1.44; P = 0.04) and VEGF-D was associated with medical and financial demands (OR, 1.34; 95% CI, 1.01-1.74; P = 0.03). CONCLUSIONS: This is the first study to show that systemic biomarkers are significantly associated with future CTXD score. Distress was not measured at baseline; we cannot rule out ongoing associations of inflammation and distress throughout treatment versus a direct effect of inflammation on distress. Nonetheless, these data add to evidence that biobehavioral processes interact and that systemic biomarkers are associated with cancer-related distress one year after surgery. IMPACT: Exercise and diet interventions that lower systemic cytokine levels may impact longer-term CTXD score and improve quality of life of patients with colorectal cancer.

Risk of Breast Cancer Associated with Estrogen DNA Adduct Biomarker.

BACKGROUND: It is biologically plausible that genotoxic estrogens, namely estrogen DNA adducts (EDA), have a role in breast cancer development. Support comes from three prior studies that reported elevated concentrations of EDA relative to estrogen metabolites and conjugates (EDA:EMC) in women with breast cancer relative to control women. METHODS: In postmenopausal women in the Women's Health Initiative (WHI), EDA:EMC in 191 controls was compared with findings in 194 prediagnosis urine samples from breast cancer cases. EDA:EMC determinations were by mass spectrometry as previously described, and logistic regression was employed to estimate ORs. RESULTS: EDA:EMC did not differ in breast cancer cases compared with controls overall [0.93 (95% confidence interval, 0.71-1.23)], with a mean (SD) of 2.3 (0.8) and 2.4 (1.1) in cases and controls, respectively. Similarly, the ratio did not differ when examined by estrogen receptor or recency of biospecimen collection prior to breast cancer. CONCLUSIONS: Despite the demonstrated genotoxic properties of certain catechol estrogens resulting in EDAs, this analysis did not provide evidence for an increased breast cancer risk in relation to an elevated EDA:EMC. IMPACT: This analysis, conducted prospectively within postmenopausal women in the WHI study, suggests that a strong association between EDA:EMC and breast cancer could be ruled out, as this study was powered to detect an OR of 2.2 or greater.

Postdiagnosis Physical Activity: Association With Long-Term Fatigue and Sleep Disturbance in Older Adult Breast Cancer Survivors.

BACKGROUND: Physical activity is frequently proposed as an intervention to reduce fatigue and sleep disturbance in cancer survivors; however, the long-term effects of physical activity are often not reported, and older adults are typically excluded from these intervention studies. OBJECTIVES: This article aimed to examine if postdiagnosis physical activity is associated with lower long-term fatigue and sleep disturbance in older adult breast cancer survivors. METHODS: Data were analyzed of a prospective cohort of 440 breast cancer survivors aged 65 years or older from the Women's Health Initiative study. Multiple linear and logistic regression models were used to examine associations of physical activity with fatigue and sleep disturbance. FINDINGS: Higher postdiagnosis physical activity was associated with lower long-term fatigue but was not associated with lower sleep disturbance after adjusting for demographics, cancer characteristics, and baseline measures.

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

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 12 months 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 12 months. 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.

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.

Design and Preliminary Testing of the Caregiver-Centered Communication Questionnaire (CCCQ).

The study objective was to develop and test a new survey instrument that measures caregiver-centered communication. We developed a questionnaire inspired by the National Cancer Institute framework on patient-centered communication, focusing on family caregiver communication for this tool. The questionnaire includes 5 subscales: exchange of information, relationship with team, emotions, managing care, and decision-making. The initial questionnaire was reviewed by domain experts for face validity and edited further to include 30 items. We administered the modified questionnaire to 115 family caregivers of patients with serious illness in various settings. Cronbach α for the entire scale was 0.97 and ranged from 0.82 to 0.93 for the 5 subscales. Participants found that the survey addressed important concepts and that items were in most cases easy to understand. This instrument provides a structured way to assess caregiver-centered communication, addressing a pressing need for tools that measure the extent to which communication is responsive to the needs and preferences of family caregivers. Further testing and refinement are needed to improve the ease of use and examine the reliability and validity of this measure.

Stability of Symptom Clusters in Patients With Gastrointestinal Cancers Receiving Chemotherapy.

CONTEXT: Limited evidence suggests that patients with gastrointestinal (GI) cancers receiving chemotherapy (CTX) experience an average of 13 co-occurring symptoms. An alternative to counting symptoms is to evaluate for symptom clusters. OBJECTIVES: In a sample of patients with GI cancers receiving CTX (n = 399), we evaluated the occurrence, severity, and distress of 38 symptoms in the week before patients' second or third cycle of CTX (Time 1 [T1]), approximately one week after CTX (Time 2 [T2]), and approximately two weeks after CTX (Time 3 [T3]); evaluated for differences in the number and types of symptom clusters at each of these three assessments using ratings of occurrence, severity, and distress; and evaluated for changes in symptom clusters over time. METHODS: Modified version of the Memorial Symptom Assessment Scale collected data on 38 common symptoms. Exploratory factor analyses were used to create the symptom clusters. RESULTS: Five distinct symptom clusters were identified across the three symptom dimensions and the three assessments (i.e., psychological, CTX-related, weight change, GI, and epithelial). Psychological, CTX-related, and weight change clusters were relatively stable across all three symptom dimensions and time. Across all three symptom dimensions, GI cluster was identified only at T1 and epithelial cluster was identified at T2 and T3. CONCLUSION: The number and types of symptom clusters appear to be relatively stable over time and across the symptom dimensions. Ongoing assessment and management of these clusters is warranted across the entire course of CTX. The underlying mechanism for these clusters warrants investigation.

Symptom Clusters in Patients With Gastrointestinal Cancers Using Different Dimensions of the Symptom Experience.

CONTEXT: Patients with gastrointestinal (GI) cancers undergoing chemotherapy (CTX) experience multiple cooccurring symptoms. OBJECTIVES: The aim of this study was to describe the occurrence, severity, and distress of 38 symptoms and to identify symptom clusters based on three symptom dimensions (i.e., occurrence, severity, and distress) in patients with GI cancers receiving CTX (n = 399). We compared whether the numbers and types of symptom clusters differed based on the dimension of the symptom experience used to create the clusters. METHODS: A modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence, severity, and distress of 38 symptoms before the initiation of the patient's next dose of CTX. Exploratory factor analysis was used to determine the symptom clusters. RESULTS: These patients experienced 13.0 (±7.1) symptoms before their second or third dose of CTX. For all three symptom dimensions, four symptom clusters were identified, namely psychological distress, CTX-related, GI, and weight change. The number and types of symptom clusters were relatively similar using all three symptom dimensions. However, some variability was found in the specific symptoms within each of the clusters. CONCLUSION: Our findings suggest that patients with GI cancers experience multiple cooccurring symptoms. Consistent with previous studies of patients with a variety of cancer diagnoses, psychological and GI clusters are common. Clinicians need to assess for and tailor interventions for these symptom clusters.

Sex Hormones in Women With Elevated Breast Cancer Risk Undergoing Weight Loss.

Sedentary lifestyles and obesity are known risk factors for breast cancer. Elevated estrogen levels correlate with obesity and, independently, with increased breast cancer risk. Lifestyle interventions that reduce obesity may mitigate this risk, potentially via estrogen pathways. In a 6-month lifestyle intervention, overweight/obese women with high breast cancer risk were randomized to control (n = 7) or intervention (n = 6) and analyzed for sex hormone levels. Serum and urine hormones were evaluated by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and sex hormone binding globulin (SHBG) by enzyme-linked immunosorbent assay (ELISA). Serum estrone (E1) and estradiol (E2) were reduced by 12.1% and 50.8%, respectively, at 9 months in the intervention group, which differed from controls (p = .043 and .020). This contrasted with a 73.3% increase in urine E1 at 6 months in the intervention group (p = .035). These results suggest that a lifestyle intervention led to a favorable estrogen profile in relation to breast cancer risk.

Communicating Caregivers' Challenges With Cancer Pain Management: An Analysis of Home Hospice Visits.

CONTEXT: Family caregivers (FCGs) of hospice cancer patients face significant challenges related to pain management. Addressing many of these challenges requires effective communication between FCGs and hospice nurses, yet little empirical evidence exists on the nature of communication about pain management between hospice nurses and FCGs. OBJECTIVES: We identified ways in which FCGs of hospice cancer patients communicated their pain management challenges to nurses during home visits and explored nurses' responses when pain management concerns were raised. METHODS: Using secondary data from audio recordings of hospice nurses' home visits, a deductive content analysis was conducted. We coded caregivers' pain management challenges and immediate nurses' responses to these challenges. RESULTS: From 63 hospice nurse visits, 101 statements describing caregivers' pain management challenges were identified. Thirty percent of these statements pertained to communication and teamwork issues. Twenty-seven percent concerned caregivers' medication skills and knowledge. In 52% of the cases, nurses responded to caregivers' pain management challenges with a validating statement. They provided information in 42% of the cases. Nurses did not address 14% of the statements made by caregivers reflecting pain management challenges. CONCLUSION: To optimize hospice patients' comfort and reduce caregivers' anxiety and burden related to pain management, hospice nurses need to assess and address caregivers' pain management challenges during home visits. Communication and educational tools designed to reduce caregivers' barriers to pain management would likely improve clinical practice and both patient- and caregiver-related outcomes.

Investigation of a Lifestyle Intervention in Women at High Risk of Breast Cancer.

One fourth of breast cancer can be attributed to sedentary lifestyles and being overweight or obese. This pilot study was conducted to explore whether a 6-month lifestyle intervention affected body composition and obesity-related biomarkers among women at high risk of breast cancer. Overweight/obese women at high risk of breast cancer were randomized to the control group or to the intervention. The intervention was an individually tailored, cognitive-behavioral therapy program that assists women in identifying strategies to improve their nutrition and physical activity habits with the goal of reduced adiposity. We compared changes in body composition and plasma biomarkers from baseline to 6 months. Body weight, adiposity, leptin, insulin resistance, and C-reactive protein were significantly reduced in the intervention group versus controls. No significant differences were observed in adiponectin, insulin, glucose, or interleukin-6. Our findings suggest that this intervention improves the metabolic and inflammatory profiles of overweight/obese women at risk of breast cancer.

Breast Cancer Risk in Relation to Ambient Air Pollution Exposure at Residences in the Sister Study Cohort.

BACKGROUND: Some but not all past studies reported associations between components of air pollution and breast cancer, namely fine particulate matter ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2). It is yet unclear whether risks differ according to estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: This analysis includes 47,591 women from the Sister Study cohort enrolled from August 2003 to July 2009, in whom 1,749 invasive breast cancer cases arose from enrollment to January 2013. Using Cox proportional hazards and polytomous logistic regression, we estimated breast cancer risk associated with residential exposure to NO2, PM2.5, and PM10. RESULTS: Although breast cancer risk overall was not associated with PM2.5 [HR = 1.03; 95% confidence intervals (CI), 0.96-1.11], PM10 (HR = 0.99; 95% CI, 0.98-1.00), or NO2 (HR = 1.02; 95% CI, 0.97-1.07), the association with NO2 differed according to ER/PR subtype (P = 0.04). For an interquartile range (IQR) difference of 5.8 parts per billion (ppb) in NO2, the relative risk (RR) of ER(+)/PR(+) breast cancer was 1.10 (95% CI, 1.02-1.19), while there was no evidence of association with ER(-)/PR(-) (RR = 0.92; 95% CI, 0.77-1.09; Pinteraction = 0.04). CONCLUSIONS: Within the Sister Study cohort, we found no significant associations between air pollution and breast cancer risk overall. But we observed an increased risk of ER(+)/PR(+) breast cancer associated with NO2. IMPACT: Though these results suggest there is no substantial increased risk for breast cancer overall in relation to air pollution, NO2, a marker of traffic-related air pollution, may differentially affect ER(+)/PR(+) breast cancer.