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Vaccine hesitancy in the wake of the COVID-19 pandemic is a major public health concern in the US. Cancer patients are especially vulnerable to adverse COVID-19 outcomes and require targeted prevention efforts against COVID-19.We used longitudinal survey data from patients seen at Moffitt Cancer Center to identify attitudes, beliefs, and sociodemographic factors associated with COVID-19 vaccination acceptance among cancer patients. Patients with confirmed invasive cancer diagnosis through Cancer Registry data were asked about vaccine acceptance through the question "Now that a COVID-19 vaccine is available, are you likely to get it?" and dichotomized into high accepters (already received it, would get it when available) and low accepters (waiting for a doctor to recommend it, waiting until more people received it, not likely to get it).Most patients (86.8% of 5,814) were high accepters of the COVID-19 vaccine. High accepters had more confidence in the effectiveness and safety of the vaccine than low accepters. Multivariable logistic regression showed older individuals (70-89 vs.18-49: OR:2.57, 95% CI:1.33-4.86), those with greater perceived severity of COVID-19 infection (very serious vs. not at all serious: OR:2.55, 95% CI:1.76-3.70), practicing more risk mitigation behaviors (per one standard deviation OR:1.75, 95% CI:1.57-1.95), and history of receiving the flu shot versus not (OR:6.56, 95% CI:5.25-8.20) had higher odds of vaccine acceptance. Individuals living with more than one other person (vs. alone: OR: 0.53, 95% CI: 0.35, 0.79) and those who were more socioeconomically disadvantaged (per 10 percentile points: OR: 0.89, 95 %CI: 0.85, 0.93) had lower odds of reporting vaccine acceptance.Most patients with cancer have or would receive the COVID-19 vaccine. Those who are less likely to accept the vaccine have more concerns regarding effectiveness and side effects, are younger, more socioeconomically disadvantaged, and have lower perceptions of COVID-19 severity.

Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.

Background:Physical activity and obesity are well-established factors of colorectal cancer risk and prognosis. Here, we investigate associations of individual and combined physical activity and body mass index (BMI) groups with proinflammatory biomarkers in colorectal cancer patients.Methods:Self-reported physical activity levels were classified as “active” (≥8.75 MET-hours/week) versus “inactive” (n = 579 stage I–IV colorectal cancer patients enrolled in the ColoCare Study. BMI [normal weight (≥18.5–2), overweight (≥25–2), and obese (≥30 kg/m2)] was abstracted from medical records. Patients were classified into four combinations of physical activity levels and BMI. Biomarkers [C-reactive protein (CRP), SAA, IL6, IL8, and TNFα] in presurgery serum samples were measured using the Mesoscale Discovery Platform. Regression models were used to compute relative percent differences in biomarker levels by physical activity and BMI groups.Results:“Inactive” patients had non-statistically significant higher IL6 levels compared with “active” patients (+36%, P = 0.10). “Obese” patients had 88% and 17% higher CRP and TNFα levels compared with “normal weight” patients (P = 0.03 and 0.02, respectively). Highest CRP levels were observed among “overweight or obese/inactive” compared with “normal weight/active” patients (P = 0.03).Conclusions:We provide evidence of associations between individual and combined physical activity and BMI groups with proinflammatory biomarkers. Although BMI was identified as the key driver of inflammation, biomarker levels were higher among “inactive” patients across BMI groups.Impact:This is the largest study in colorectal cancer patients investigating associations of energy balance components with inflammatory biomarkers. Our results suggest that physical activity may reduce obesity-induced inflammation in colorectal cancer patients and support the design of randomized controlled trials testing this hypothesis.

Supplementary Data from Associations of Individual and Combined Physical Activity and Body Mass Index Groups with Proinflammatory Biomarkers among Colorectal Cancer Patients

Background: Cell-to-cell adhesion and angiogenesis are hallmarks of cancer. No studies have examined associations of adhesion molecules and angiogenesis biomarkers with clinical outcomes in colorectal cancer. Methods: In presurgery serum from n = 426 patients with colorectal cancer (stage I–III), we investigated associations of CRP, SAA, adhesion molecules (sICAM-1, sVCAM-1), and angiogenesis markers (VEGF-A and VEGF-D) with overall survival (OS), disease-free survival (DFS), and risk of recurrence. We computed HRs and 95% confidence intervals; adjusted for age, sex, BMI, stage, site, and study site, stratified by tumor site in exploratory analyses. Results: N = 65 (15%) were deceased, and 39 patients (14%) had a recurrence after a median follow-up of 31 months. We observed significant associations of biomarkers with OS, DFS, and risk of recurrence on a continuous scale and comparing top to bottom tertile, with HRs ranging between 1.19 and 13.92. CRP was associated with risk of death and recurrence in patients in the top tertile compared with patients in the bottom tertile, for example, risk of recurrence HRQ3-Q1: 13.92 (1.72–112.56). Significant heterogeneity between biomarkers and clinical outcomes was observed in stratified analysis by tumor site for CRP, SAA, sICAM-1, sVCAM-1, and VEGF-D. VEGF-D was associated with a 3-fold increase in risk of death for rectal cancer (HRlog2: 3.26; 95% CI, 1.58–6.70) compared with no association for colon cancer (HRlog2: 0.78; 95% CI, 0.35–1.73; Pheterogenity = 0.01). Conclusions: Adhesion molecules and angiogenesis biomarkers are independent prognostic markers for colorectal cancer, with differences by tumor site. Impact: There is need for tailored treatment for colon and rectal cancer.

There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined changes in exercise behaviors since the pandemic and identified characteristics associated with these changes among cancer patients.Cancer patients (n = 1,210) completed a survey from August to September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into three groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups.One-third of the patients reported a decreased amount of regular exercise, while 10% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired and have poor health status and psychosocial stressors such as disruptions in daily life while less likely to be former smokers (all p 0.05). In contrast, patients who exercised more were younger, had stage IV diagnosis, and also reported disruptions in daily life (all p 0.05). Patients who were living in rural areas were also more likely not to experience changes in exercise habits (all p 0.05), although rural-urban status was not identified as a strong predictor.A significant proportion of cancer patients experienced changes in exercise habits, especially exercising less, during the first 6 months of the COVID-19 pandemic. Age, employment status, tumor stage, health status, smoking status, and psychosocial factors were associated with changes in exercise behaviors. Our results highlight the importance of promoting physical activity guidelines for cancer survivorship during the COVID-19 pandemic and may help improve the identification of cancer patients susceptible to exercising less.

INTRODUCTION: Telomere shortening, as seen with aging, can cause chromosomal instability and promote cancer progression. We investigated the association between circulating telomere length and overall and disease-free survival in a sub-cohort of patients with colorectal cancer. METHODS: Baseline genomic DNA from blood leukocytes was extracted from N=92 newly diagnosed stage I-IV patients with colorectal cancer enrolled at the ColoCare Study site in Heidelberg, Germany. Detailed information on clinicodemographic (including age) and lifestyle risk factors, and clinical outcomes (including recurrence and survival) was collected. Telomere length was measured in DNA using multiplex quantitative polymerase chain reaction. Kaplan Meier survival curves were generated comparing shorter to longer telomere lengths with log-rank testing. RESULTS: The mean T/S ratio for study patients was 0.5 (range: 0.3-0.9). Shorter telomeres were associated with older age at baseline. Patients with shorter telomeres experienced a worse overall and disease-free survival, although this association did not reach statistical significance. Kaplan-Meier survival curves for those with circulating telomere length below vs. above the median showed poorer overall (log-rank p=0.31) and disease-free survival (long-rank p=0.23). CONCLUSIONS: Our results suggest that individuals with shorter telomeres, as seen with aging, may experience a worse overall and disease-free survival after colorectal cancer diagnosis. Larger sample sizes with longer follow-up are needed to further evaluate telomere length as a prognostic biomarker in colorectal cancer progression.

We aimed to identify patient-level demographic and behavioral characteristics associated with higher social isolation among patients with cancer throughout the coronavirus disease 2019 (COVID-19) pandemic.Moffitt Cancer Center patients seen on or after January 1, 2015, had a last known alive vital status, a valid e-mail address, and were 18-89 years old, were emailed a survey regarding social isolation. We collected information on age, sex, race, ethnicity, marital status, smoking, self-reported cancer diagnosis, cancer treatment, and perceived life changes due to the COVID-19 pandemic. We calculated a COVID-19 risk mitigation score by summing the frequency of risk mitigation behaviors (e.g., mask wearing). Social isolation was assessed with the self-reported Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation Short Form. Logistic regression models compared characteristics of participants reporting higher versus lower social isolation (T-scores60 vs. ≤60).Most participants (N = 9,579) were female (59.2%), White (93.0%), and non-Hispanic (92.5%). Participants at greater odds of higher social isolation were younger (per 10 years decrease odds ratio [OR] = 1.36, 95% confidence interval, CI [1.30, 1.43]), female (vs. male OR = 1.54, 95% CI [1.36, 1.74]), unmarried (vs. married OR = 1.83, 95% CI [1.62, 2.08]), current smokers (vs. never OR = 2.38, 95% CI [1.88, 3.00]), reporting more risk mitigation behaviors (per 1 SD; OR = 1.33, 95% CI [1.24, 1.42]), and more perceived life changes (vs. little/no change; OR = 2.64, 95% CI [2.08, 3.35]).We identified younger age, females, unmarried, current smokers, more risk mitigation behaviors, and more perceived life changes increased odds of social isolation for patients with cancer during the COVID-19 pandemic. This can inform identification of patients with cancer at higher risk of social isolation for targeted mitigation strategies. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background:Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.Methods:A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.Results:Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10−8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20–1.30] compared with the other genotypes (OR Conclusions:Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.Impact:These findings can guide potential prevention treatments.

Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06–1.17; OR for AA genotype = 1.22; 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

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.

Background: Physical activity and obesity are well-established factors of colorectal cancer risk and prognosis. Here, we investigate associations of individual and combined physical activity and body mass index (BMI) groups with proinflammatory biomarkers in colorectal cancer patients. Methods: Self-reported physical activity levels were classified as “active” (≥8.75 MET-hours/week) versus “inactive” ( Results: “Inactive” patients had non-statistically significant higher IL6 levels compared with “active” patients (+36%, P = 0.10). “Obese” patients had 88% and 17% higher CRP and TNFα levels compared with “normal weight” patients (P = 0.03 and 0.02, respectively). Highest CRP levels were observed among “overweight or obese/inactive” compared with “normal weight/active” patients (P = 0.03). Conclusions: We provide evidence of associations between individual and combined physical activity and BMI groups with proinflammatory biomarkers. Although BMI was identified as the key driver of inflammation, biomarker levels were higher among “inactive” patients across BMI groups. Impact: This is the largest study in colorectal cancer patients investigating associations of energy balance components with inflammatory biomarkers. Our results suggest that physical activity may reduce obesity-induced inflammation in colorectal cancer patients and support the design of randomized controlled trials testing this hypothesis.

Diabetes is an established risk factor for colorectal cancer; however, the mechanisms underlying this relationship are not fully understood and the role of genetic variation is unclear. We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes and joint testing of Gxdiabetes, G-colorectal cancer association and/or G-diabetes correlation (2,3-degrees of freedom joint tests; d.f.). Based on the joint tests, variant rs3802177 inSLC30A8(p-value3-d.f.:5.46×10−11; regulates phosphorylation of the insulin receptor and phosphatidylinositol-3 kinase activity) and rs9526201 inLRCH1(p-value2-d.f.:7.84×10−09; regulates T cell migration and Natural Killer Cell cytotoxicity) were associated with colorectal cancer. These results suggest that variation in genes related to insulin signalling and immune function may modify the association of diabetes with colorectal cancer and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

BACKGROUND: Cachexia is a multifactorial metabolic syndrome associated with higher risk of mortality. The precise molecular mechanisms and biological pathways involved remain poorly characterized. A specific criterion of cachexia is loss of muscle mass. Myokines affect muscle mass and have profound effects on glucose and lipid metabolism, thus contributing to energy homeostasis and potentially cachexia. Only sparse data for patients with non-metastatic colorectal cancer exist. This study aims to investigate associations of systemic myokine concentrations with onset of cachexia in non-metastatic colorectal cancer patients. METHODS: Serum samples from n=125 colorectal cancer patients (stage I-III) recruited from the ColoCare Study site at Huntsman Cancer Institute were collected prior to surgery (baseline). Assays were run with the Milliplex Human Myokine Magnetic panel containing beads such as FABP3, Oncostatin M, and FGF21. Patients were defined as cachectic, pre-cachectic, or non-cachectic based on the criteria by Fearon et al. based on sex, BMI, and weight loss over a period of six months. ANOVA were applied to analyze associations of myokines with cachexia at 12 month after surgery, adjusted by age at diagnosis, sex, tumor stage, and tumor site. RESULTS: At the 12 months follow-up, 11% of patients were diagnosed with cachexia (n=14), 14% of patients with pre-cachexia (n=18), and 74% of patients were defined as non-cachectic. Patients with cachexia were more likely to be diagnosed with rectal cancer (57%) compared to pre-cachectic (17%) or non-cachectic patients (42%; p ONCLUSIONS: Cachectic patients presented higher FABP3 concentrations (p=0.02) which were associated with increased risk of cachexia, however these results were not significant after adjustment. In this study, cachectic patients were more likely to be diagnosed with rectal cancer. In summary, larger studies are needed to further evaluate FABP3 and other myokines as potential prognostic biomarkers for cachexia and consider differences by tumor site. Citation Format: Jennifer Ose, Ellen Beswick, Simon Ta Van, Richard H. Viskochil, Christy A. Warby, Jeffrey T. Yap, Matthew F. Covington, Anne H. Nguyen, Jordan W. Stanford, Tengda Lin, Anita R. Peoples, Sheetal Hardikar, Christopher I. Li, William M. Grady, David Shibatta, Adetunji T. Toriola, Martin Schneider, Jane C. Figueiredo, Daniel Jeong, Erin M. Siegel, Cornelia M. Ulrich, Biljana Gigic. Examination of systemic myokine concentrations with risk of cachexia in non-metastatic colorectal cancer patients - Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 355.

Ovarian cancer is the fifth most common female cancer in the United States. There have been very few studies investigating mental health diagnoses among ovarian cancer survivors with long-term follow up. The aim of this study is to examine the incidence of mental illness among ovarian cancer survivors compared to a general population cohort. A secondary aim is to investigate risk factors for mental illnesses among ovarian cancer survivors.Cohorts of 1689 ovarian cancer patients diagnosed between 1996 and 2012 and 7038 women without cancer matched by age and birth state from the general population were identified. Mental health diagnoses were identified from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios (HRs).Ovarian cancer survivors experienced increased risks of mental illnesses within the first 2 years after cancer diagnosis (HR = 3.55, 95% CI = 3.04-4.14). The risks of depression among ovarian cancer survivors were nearly 3-fold within the first 2 years of cancer diagnosis (HR = 2.59, 95% CI = 1.94-3.47), and 1.69-fold at 2-5 years after cancer diagnosis (HR = 1.69, 95% CI = 1.18-2.42). Ovarian cancer survivors experienced an 80% increased risk of death with a mental illness diagnosis (HR = 1.80, 95% CI = 1.48-2.18) and a 94% increased risk of death with a depression diagnosis (HR = 1.94, 95% CI = 1.56-2.40).Higher risks of mental illnesses were observed among ovarian cancer survivors throughout the follow-up periods of 0-2 years and 2-5 years after cancer diagnosis. Multidisciplinary care is needed to monitor and treat mental illnesses among ovarian cancer survivors.

CONTEXT: Pain can be a debilitating side effect of radiation therapy (RT). Data from the general population has shown that sleep disturbance can influence pain incidence and severity; however, less is known about this relationship in breast cancer patients receiving RT. OBJECTIVES: This secondary analysis examined the association of pre-treatment moderate/severe levels of sleep disturbance with subsequent RT-induced pain after adjusting for pre-RT pain. METHODS: We report on 573 female breast cancer patients undergoing RT from a previously completed phase II clinical trial for radiation dermatitis. Sleep disturbance, total pain, and pain subdomains – sensory pain, affective pain, and perceived pain intensity were assessed at pre- and post-RT. At pre-RT, patients were dichotomized into 2 groups: those with moderate/severe sleep disturbance (N=85) vs. those with no/mild sleep disturbance (control; N=488). RESULTS: At pre-RT, women with moderate/severe sleep disturbance were younger, less likely to be married, more likely to have had mastectomy and chemotherapy, and more likely to have depression/anxiety disorder and fatigue than the control group (all p’s

Background B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear. Objectives To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis. Methods We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing. Results Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (β = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (β = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers. Conclusions Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life.

The COVID-19 pandemic has disrupted many facets of life. We evaluated pandemic-related health care experiences, COVID-19 prevention behaviors and measures, health behaviors, and psychosocial outcomes among rural and urban cancer patients.Among 1,472 adult cancer patients, who visited Huntsman Cancer Institute in the past 4 years and completed a COVID-19 survey (August-September 2020), we assessed the impact of the pandemic on medical appointments, prevention/health behaviors, and psychosocial factors, stratified by urbanicity.Mean age was 61 years, with 52% female, 97% non-Hispanic White, and 27% were residing in rural areas. Rural versus urban patients were more likely to be older, not employed, uninsured, former/current smokers, consume alcohol, and have pandemic-related changes/cancellations in surgery appointments (all P.05). Changes/cancellations in other health care access (eg, doctor's visits) were also common, particularly among urban patients. Urban versus rural patients were more likely to socially distance, use masks and hand sanitizer, and experience changes in exercise habits and in their daily lives (all P.05). Less social interaction and financial stress were common among cancer patients but did not differ by urbanicity.These findings suggest that the COVID-19 pandemic had a substantial impact on cancer patients, with several challenges specific to rural patients. This comprehensive study provides unique insights into the first 6 months of COVID-19 pandemic-related experiences and continuity of care among rural and urban cancer patients predominantly from Utah. Further research is needed to better characterize the pandemic's short- and long-term effects on rural and urban cancer patients and appropriate interventions.

Background The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. Results The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P Conclusion Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

PURPOSE: 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. CONCLUSIONS: 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.

Purpose There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined the impact of the pandemic on changes in exercise behaviors and identified characteristics associated with these changes among cancer patients. Methods Cancer patients (n = 1,361) completed a survey from August-September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into 3 groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. Results One-third of the patients reported a decreased amount of regular exercise, while 11% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired, undergoing active treatment, and had increased pandemic-related alcohol consumption and psychosocial stressors such as loneliness and financial stress (all p p p

Objective Chemotherapy-induced nausea is challenging to predict and treat. Research indicates that pretreatment psychological variables including patients' perceptions of their susceptibility to nausea, expectancies of treatment-related nausea and nausea history (i.e., motion sickness, morning sickness and baseline levels of nausea) may aid in predicting nausea severity during chemotherapy. However, this research is dated and limited in quantity. We investigated whether psychological variables could improve prediction of nausea severity to inform interventions targeting chemotherapy-induced nausea. Methods In this secondary analysis, a subgroup of women receiving chemotherapy (for the first time) for breast cancer completed pretreatment measures: perceived nausea susceptibility, nausea expectancies, nausea history and baseline nausea. They rated subsequent nausea severity across 4-days, during treatment and posttreatment in a self-report diary. Structural Equation Modelling was used to explore associations. Results Across the women (N = 481), perceived nausea susceptibility predicted subsequent nausea severity (β = 0.16), but nausea expectancies did not (β = 0.05). Nausea history variables demonstrated small-moderate associations with perceived susceptibility (β = 0.21-0.32) and negligible-small associations with nausea expectancies (β = 0.07-0.14). Conclusion Perceived nausea susceptibility appears to capture patients' nausea history, to a degree, and is related to nausea severity during treatment. This is an important variable to include in pretreatment prediction of patients at risk of severe nausea.

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (&lt, 50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

BACKGROUND Surveys play a vital role in cancer research. During the COVID-19 pandemic, the use of electronic surveys is crucial to improve understanding of the patient experience. However, response rates to electronic surveys are often lower compared with those of paper surveys. OBJECTIVE The aim of this study was to determine the best approach to improve response rates for an electronic survey administered to patients at a cancer center during the COVID-19 pandemic. METHODS We contacted 2750 patients seen at Moffitt Cancer Center in the prior 5 years via email to complete a survey regarding their experience during the COVID-19 pandemic, with patients randomly assigned to a series of variations of prenotifications (ie, postcard, letter) or incentives (ie, small gift, modest gift card). In total, eight combinations were evaluated. Qualitative interviews were conducted to understand the level of patient understanding and burden with the survey, and quantitative analysis was used to evaluate the response rates between conditions. RESULTS A total of 262 (9.5%) patients completed the survey and 9 participated in a qualitative interview. Interviews revealed minimal barriers in understanding or burden, which resulted in minor survey design changes. Compared to sending an email only, sending a postcard or letter prior to the email improved response rates from 3.7% to 9.8%. Similarly, inclusion of an incentive significantly increased the response rate from 5.4% to 16.7%, especially among racial (3.0% to 12.2%) and ethnic (6.4% to 21.0%) minorities, as well as among patients with low socioeconomic status (3.1% to 14.9%). CONCLUSIONS Strategies to promote effective response rates include prenotification postcards or letters as well as monetary incentives. This work can inform future survey development to increase response rates for electronic surveys, particularly among hard-to-reach populations.

PURPOSE: Research by our group has shown that acupressure bands are efficacious in reducing chemotherapy-induced nausea (CIN) for breast cancer patients who expect nausea, and that their effectiveness in controlling CIN can largely be accounted for by patients’ expectations of efficacy, i.e., a placebo effect. The present research examined if the effectiveness of acupressure bands could be enhanced by boosting patients’ expectation of the bands’ efficacy. METHODS: 242 Chemotherapy-naïve patients with breast cancer who expected nausea were randomized. Arms 1 and 2 received acupressure bands, plus a relaxation MP3 and written handout that were either expectancy-enhancing (Arm 1) or expectancy-neutral (Arm 2). Arm 3 was the control without bands or MP3, and received standard care. All participants received guidelines specified antiemetics. RESULTS: Peak CIN for Arms 1, 2, and 3 on a 1–7 scale was 3.52, 3.55, and 3.87, respectively (p=0.46). Because no differences were observed between Arms 1 and 2 (primary analysis), we combined these two arms (intervention) and compared them to controls for the following analyses. Significant interaction was found between intervention/control and receiving doxorubicin-based chemotherapy (yes/no) and pre-treatment anxiety (high/low). Intervention patients receiving doxorubicin had lower peak CIN than controls (3.62 vs. 4.38; p=0.02). Similarly, intervention patients with high pre-treatment anxiety had a lower peak CIN than controls (3.62 vs. 4.62; p=0.01). CONCLUSIONS: In breast cancer patients undergoing chemotherapy and having high CIN expectation, acupressure bands combined with a relaxation recording were effective in reducing CIN for patients who received doxorubicin or had high anxiety.

Background: Older patients (>65 years) are frequently under-represented in clinical trials that determine cancer treatment guidelines. We sought to characterize treatment patterns among older patients and identify factors for receipt of non-standard of care (SOC) treatment. Methods: The National Cancer Database (NCDB) was queried to describe treatment patterns in stage I-III colorectal cancer patients (2004-2017) over 65 years of age. Patients with metastatic disease and non-adenocarcinoma histology were excluded. SOC therapy was defined as any recommended treatment option listed within site- and stage-specific National Comprehensive Cancer Network guidelines. Clinicodemographic characteristics and treatment patterns were compared between colon and rectal cancer patients by ten-year age-groups. Multivariable logistic regression analysis was used to determine factors associated with receipt of treatment, by tumor site and stage. Results: Of the 498,285 patients who met inclusion criteria, 47% were 65-75 years while 15% were >85 years old (median age: 76 years). The majority were non-Hispanic White (88%), female (52%), Medicare insured (86%), colon cancer patients (76%) with a Charlson comorbidity index (CCI) of 0 (63%). Significant differences in treatment patterns by age were observed; for e.g., 11% of stage I colon cancer patients >85 years of age did not receive SOC surgical treatment but rather received radiation-only treatment compared to only 2% patients 65-75 years of age who received radiation-only treatment. In logistic regression analyses adjusted for diagnosis year, sex, race/ethnicity, CCI, insurance, income, education, hospital type, treatment facility, rurality, and geographic region, older patients were more likely to receive non-SOC treatments for colon cancer stage I [OR(95% CI) for 76-85 years 1.31(1.23,1.40); >85 years 3.41(3.17,3.66)], stage II-III [OR(95% CI) for 76-85 years 1.96(1.92,2.01); >85 years 3.50(3.40,3.60)], rectal cancer stage I [OR(95% CI) for 76-85 years 2.06(1.89,2.24); >85 years 6.36(5.77,7.02)], and stage II-III [OR(95% CI) for 76-85 years 2.14(2.07,2.22); >85 years 9.02(8.33,9.77)] compared to 65-75 year old patients. Other predictors of receiving non-SOC treatments for both colon and rectal cancers included Black race (p3 (p Discussion: Compared to 65-75 year-old stage I-III colorectal cancer patients, older patients at all disease stages are more likely to not receive SOC treatment. Other predictors for receiving non-SOC treatment are Black race, presence of comorbidities, lack of insurance, and treatment at a community cancer clinic. Future observational and randomized studies are needed to define the optimal treatment paradigms in older colorectal cancer patients, identify and address disparities, and better support these patients. Citation Format: Sheetal Hardikar, Christopher R. Weil, Shane Lloyd, Jessica N. Cohan, Mark A. Supiano, Jennifer Ose, Anita R. Peoples, Sumati V. Gupta, Kaitlyn Pelletier, Martine Extermann, Erin M. Siegel, David Shibata, Cornelia M. Ulrich. Treatment patterns in stage I-III colorectal cancer patients over 65 years of age [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 36.

Background Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood. Patients and Methods We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naive CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models. Results Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival. Conclusion Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naive CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.

PURPOSE: Despite advances in medical technology, radiation dermatitis occurs in 95% of patients receiving radiation therapy (RT) for cancer. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The goal of the study was to determine the efficacy of oral curcumin, one of the biologically active components in turmeric, at reducing radiation dermatitis severity (RDS) at the end of RT, using the RDS scale, compared to placebo. METHODS: This was a multisite, randomized, double-blinded, placebo-controlled trial of 686 breast cancer patients. Patients took four 500 mg capsules of placebo or curcumin three times daily throughout their prescribed course of RT until one week post-RT. RESULTS: A total of 686 patients were included in the final analyses (87.5% white females, mean age = 58). Linear mixed model analyses demonstrated that curcumin did not reduce radiation dermatitis severity at the end of RT compared to placebo (B (95% CI) =0.044 (−0.101, 0.188), p=0.552). Fewer curcumin patients with RDS > 3.0 suggested a trend toward reduced severity (7.4% vs. 12.9%, p=0.082). Patient-reported changes in pain, symptoms, and quality of life were not statistically significant between arms. CONCLUSIONS: Oral curcumin did not significantly reduce radiation dermatitis severity compared to placebo. The skin rating variation and broad eligibility criteria could not account for the undetectable therapeutic effect. An objective measure for radiation dermatitis severity and further exploration for an effective treatment for radiation dermatitis is warranted.

Background Surveys play a vital role in cancer research. During the COVID-19 pandemic, the use of electronic surveys is crucial to improve understanding of the patient experience. However, response rates to electronic surveys are often lower compared with those of paper surveys. Objective The aim of this study was to determine the best approach to improve response rates for an electronic survey administered to patients at a cancer center during the COVID-19 pandemic. Methods We contacted 2750 patients seen at Moffitt Cancer Center in the prior 5 years via email to complete a survey regarding their experience during the COVID-19 pandemic, with patients randomly assigned to a series of variations of prenotifications (ie, postcard, letter) or incentives (ie, small gift, modest gift card). In total, eight combinations were evaluated. Qualitative interviews were conducted to understand the level of patient understanding and burden with the survey, and quantitative analysis was used to evaluate the response rates between conditions. Results A total of 262 (9.5%) patients completed the survey and 9 participated in a qualitative interview. Interviews revealed minimal barriers in understanding or burden, which resulted in minor survey design changes. Compared to sending an email only, sending a postcard or letter prior to the email improved response rates from 3.7% to 9.8%. Similarly, inclusion of an incentive significantly increased the response rate from 5.4% to 16.7%, especially among racial (3.0% to 12.2%) and ethnic (6.4% to 21.0%) minorities, as well as among patients with low socioeconomic status (3.1% to 14.9%). Conclusions Strategies to promote effective response rates include prenotification postcards or letters as well as monetary incentives. This work can inform future survey development to increase response rates for electronic surveys, particularly among hard-to-reach populations.

Ovarian cancer is the fifth most common female cancer in the United States. Although there have been many studies on self-reported QOL among ovarian cancer patients, there have been very few studies investigating mental disease diagnoses among ovarian cancer survivors with long term follow up. The aim of this study is to examine the incidence of mental illness among ovarian cancer survivors compared to a general population cohort. A secondary aim is to investigate risk factors for mental illnesses among ovarian cancer survivors. Cohorts of 1,689 ovarian cancer patients diagnosed between 1996 and 2012 and 7,038 women without cancer matched by age, birth state and follow up time from the general population were identified. Mental health diagnoses were identified from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios (HRs). Ovarian cancer survivors experienced increased risks of mental illnesses within the first two years after cancer diagnosis (HR=3.48, 95%CI=2.98-4.05) compared to the general population. The risks of depression among ovarian cancer survivors were 3-fold within the first two years of cancer diagnosis (HR=3.11, 95%CI=2.53-3.83), and 1.67-fold at 2-5 years after cancer diagnosis (HR=1.67, 95%CI=1.17-2.38). The risk of anxiety disorder among ovarian cancer survivors was 3.54-fold at 0-2 years (HR= 3.54, 95% CI= 2.87-4.38), and 1.86-fold at 2-5 years (HR= 1.86, 95% CI= 1.14-3.01). Elevated risk for adjustment disorders was observed among ovarian cancer survivors compared with the general population cohort between 0-2 years (HR= 3.96, 95% CI= 1.00-15.84) and between 2-5 years (HR= 3.96, 95% CI= 1.00-15.84). Cancer treatment and later diagnosis year were associated with increased risk of any mental illness at 0-2 years after cancer diagnosis among ovarian cancer survivors. Distant-stage cancer was an important risk factor compared to early-stage for both mental illness and depression among ovarian cancer survivors in all time periods. Ovarian cancer patients who had a mucinous histology subtype had 47% decreased risk of any mental illness and 67% decreased risk of depression at 0-2 years, compare to those with high-grade serous histology subtype. In addition, a baseline CCI score of 1+ and older age at diagnosis (>60 years old) were important for the increased risk of depression at 0-2 years or >5 year after cancer diagnosis, respectively. Ovarian cancer survivors experienced an 80% increased risk of death with a mental illness diagnosis (HR=1.80, 95% CI=1.48-2.18) and a 94% increased risk of death with a depression diagnosis (HR=1.94, 95% CI=1.56-2.40).Higher risks of mental illnesses were observed among ovarian cancer survivors throughout the follow-up periods of 0-2 years and 2-5 years after cancer diagnosis. Multidisciplinary care is needed to monitor and treat mental illnesses among ovarian cancer survivors. Citation Format: Siqi Hu, David Baraghoshi, Esther Chang, Kerry Rowe, John Snyder, Vikrant Deshmukh, Michael Newman, Alison Fraser, David Gaffney, Ken Smith, Kimberly Herget, Anita Peoples, Mia Hashibe. Mental health disorders among ovarian cancer survivors in a population-based cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 900.

Objective: High-throughput metabolomics assays can generate thousands of biomarker measurements and provide novel opportunities for prognostic modeling in colorectal cancer (CRC) research. The high dimensionality of metabolic data brings unforeseen statistical challenges and traditional variable selection methods may not perform well due to simultaneous challenges of computational expediency, statistical accuracy, and algorithmic stability. The Iterative Sure Independence Screening (ISIS) has demonstrated superior theoretical properties in handling such situations, and may be a viable alternative. Methods: In a prospective study of 77 newly diagnosed CRC patients (stage I-IV), pre-surgical urinary samples were analyzed on a gas chromatography-mass spectrometry platform. After exclusion of metabolites with >30% coefficient of variation, 168 metabolites remained for statistical analysis. Raw measures were processed following a standard normalization pipeline. The primary outcome was overall survival (OS) as measured from date of cancer diagnosis. In addition to metabolomics data, the predictor set included baseline clinical characteristics, such as age, sex, body mass index, tumor site, tumor stage, and receipt of neo-adjuvant and/or adjuvant treatment. We applied the ISIS method with Lasso penalty on a Cox regression model (ISIS-Lasso) to identify features associated with OS. Cox models with either Lasso regularization or backward selection were also considered as competing methods. The performance of the models was assessed through two standard performance matrices: Uno's time-dependent Area Under the Curve (tAUC) and Brier's score, both with resample-based validation. Results: Based on bootstrapped tAUC curves, we demonstrated that the screening step in ISIS can significantly improve model performance, since its predicted mean (and median) AUC are larger across clinically relevant follow-up time points (2 and 5 years after diagnosis) relative to the corresponding measures from the other two models. The prediction error based on Brier's score with 0.632+ bootstrap from ISIS-Lasso was also noticeably lower compared to the model from backward selections. Based on the ISIS-Lasso model, we identified two features, that were predictive of OS in CRC patients: tumor stage and cystine. When fixing all other clinical measures, patients with early stage (I-III) had 52% lower risk of death, compared to late stage (IV); 1 standard deviation of increase of cystine level was associated with 62% increased risk of death. Conclusion: We have demonstrated the feasibility and effectiveness of an ISIS-based method to improve selection of prognostic models derived from metabolomics data. This may be especially useful for studies with moderate sample sizes. We have identified cystine as a potentially important prognostic biomarker. Citation Format: Tengda Lin, Biljana Gigic, Kenneth Boucher, Ben Haaland, David Liesenfeld, Robert Owen, Petra Schrotz-King, Jourgen Boehm, Anita Peoples, Augustin Scalbert, Martin Schneider, Jane Figueiredo, William Grady, Christopher Li, David Shibata, Erin Siegel, Adetunji Toriola, Alexis Ulrich, Neli Ulrich, Jincheng Shen, Jennifer Ose. Application of iterative sureindependence screening to improve urinary metabolomics-based prediction of survival in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 892.

Purpose: The COVID-19 pandemic has substantially changed social practices, economic stability, and access to medical care that may significantly affect cancer patients, especially those undergoing active treatment. We characterized the pandemic's influence on healthcare delivery, behavioral health, and financial stress in cancer patients. Methods: We included data from N = 1,253 adult cancer patients, who visited HCI in the last 4 years, consented to the Total Cancer Care study, and completed a COVID-19 survey as part of the COPES consortium. The survey was administered between Aug and Sept 2020 and included questions on change/cancellation of medical visits, change in exercise and alcohol consumption, daily life, social interactions, and financial stress since March 2020. Results: The cohort's mean age was 60.4 (19–92) years, with 54% female, 68% non-Hispanic White, 41% retired, 43% employed full or part-time, and 24% living in rural counties. Among the 27% of patients who reported receiving current treatment at HCI, 30% had to change or cancel a medical visit due to the pandemic, with 2% reported a change/cancellation in a biopsy, surgery, radiotherapy, and chemotherapy; 5% reported a change/cancellation in imaging; and 3% and 23% reported a change/cancellation in cancer screening and doctor's visit, respectively. 18% rescheduled an appointment to a telehealth visit. Changes in exercise habits due to the pandemic were common (47%), with 10% no longer exercising regularly, 21% exercising less, and 11% exercising more than before. 5% reported increased alcohol consumption, while 6% reported a decrease. Most patients (84%) experienced a change in their daily lives (ranging from somewhat to a lot of change). 69% had fewer social interactions, and 49% reported financial stress due to the pandemic, with 11% reporting being quite a bit/very much financially stressed. Conclusions: These findings suggest that within approximately the first 6 months, the COVID-19 pandemic had a substantial impact on cancer patients' lives, with adverse effects on health behaviors and financial stress. Healthcare delivery continued for essential cancer care but was disrupted for other services, such as cancer screening. Further analyses are underway. Funding: U01CA206110 and R01CA211705.

While cognitive-behavioral therapy for insomnia (CBT-I) has been shown to be efficacious in treating cancer survivors' insomnia, 30-60% of individuals have difficulty adhering to intervention components. Psychosocial predictors of adherence and response to CBT-I, such as social support, have not been examined in intervention studies for cancer survivors.Data from a randomized placebo-controlled 2 x 2 trial of CBT-I and armodafinil (a wakefulness promoting agent) were used to assess adherence. Ninety-six cancer survivors participated in the trial (mean age 56, 86% female, 68% breast cancer).CBT-I and armodafinil were administered over the course of seven weeks, and participants were assessed at baseline, during intervention, postintervention, and at a three-month follow-up. Social support was assessed using a Functional Assessment of Chronic Illness Therapy subscale, insomnia severity was assessed using the Insomnia Severity Index, and adherence was measured based on CBT-I sleep prescriptions.At baseline, social support was negatively correlated with insomnia severity (r = -0.30, p = 0.002) and associations between social support, CBT-I, and insomnia were maintained through the three-month follow-up. Social support was positively associated with adherence to CBT-I during intervention weeks 3, 4, and 5, and with overall intervention adherence. At postintervention, both social support and treatment with CBT-I independently predicted decreased insomnia severity (p0.01) when controlling for baseline insomnia severity.Higher social support is associated with better intervention adherence and improved sleep independent of CBT-I. Additional research is needed to determine whether social support can be leveraged to improve adherence and response to CBT-I.

Cancer-related insomnia is associated with diminished quality of life (QOL), suggesting that improvement in insomnia may improve QOL in cancer survivors. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia, but less is known regarding its effect on QOL and whether improvement in insomnia corresponds to improved QOL. The present analysis examines the effects of CBT-I, with and without armodafinil, on QOL both directly and indirectly through improvements of insomnia.This is an analysis of 95 cancer survivors for a specified secondary aim of a four-arm randomized controlled trial assessing the combined and individual effects of CBT-I and armodafinil to improve insomnia. QOL and insomnia severity were assessed before, during the intervention, at post-intervention, and 3 months later by Functional Assessment of Cancer Therapy-General and Insomnia Severity Index, respectively.Mean change in QOL from pre- to post-intervention for CBT-I + placebo, CBT-I + armodafinil, armodafinil, and placebo was 9.6 (SE = 1.8; p 0.0001), 11.6 (SE = 1.8; p 0.0001), -0.2 (SE = 3.2; p = 0.964), and 3.3 (SE = 2.0; p = 0.124), respectively. ANCOVA controlling for pre-intervention scores showed that participants receiving CBT-I had significantly improved QOL at post-intervention compared to those not receiving CBT-I (p 0.0001, effect size = 0.57), with benefits being maintained at the 3-month follow-up. Path analysis revealed that this improvement in QOL was due to improvement in insomnia severity (p = 0.002), and Pearson correlations showed that changes in QOL from pre- to post-intervention were significantly associated with concurrent changes in insomnia severity (r = -0.56; p 0.0001). Armodafinil had no effect on QOL for those who did or did not receive it (p = 0.976; effect size = -0.004).In cancer survivors with insomnia, CBT-I resulted in clinically significant improvement in QOL via improvement in insomnia. This improvement in QOL remained stable even 3 months after completing CBT-I.Considering the high prevalence of insomnia and its detrimental impact on QOL in cancer survivors and the effectiveness of CBT-I in alleviating insomnia, it is important that evidence-based non-pharmacological sleep interventions such as CBT-I be provided as an integral part of cancer care.

Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary metabolic profiles in newly diagnosed colorectal cancer patients (stage I&ndash, IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (n = 16), pre-cachectic (n = 13), or non-cachectic (n = 23) based on standard criteria on weight loss over time at two time points. Urine samples were collected pre-surgery, and 6 and 12 months thereafter. Fat and muscle mass area were assessed utilizing computed tomography scans at the time of surgery. N = 152 compounds were detected using untargeted metabolomics with gas chromatography&ndash, mass spectrometry and n = 154 features with proton nuclear magnetic resonance spectroscopy. Thirty-four metabolites were overlapping across platforms. We calculated differences across groups and performed discriminant and overrepresentation enrichment analysis. We observed a trend for 32 compounds that were nominally significantly different across groups, although not statistically significant after adjustment for multiple testing. Nineteen compounds could be identified, including acetone, hydroquinone, and glycine. Comparing cachectic to non-cachectic patients, higher levels of metabolites such as acetone (Fold change (FC) = 3.17, p = 0.02) and arginine (FC = 0.33, p = 0.04) were observed. The two top pathways identified were glycerol phosphate shuttle metabolism and glycine and serine metabolism pathways. Larger subsequent studies are needed to replicate and validate these results.

The COVID-19 pandemic has led to extensive social changes, which may increase the risk of experiencing social isolation, particularly in cancer patients who are at high risk of having poor outcomes if infected with COVID-19. It is unclear if pandemic-related risk mitigation behaviors (e.g., limiting attendance at social gatherings, mask wearing) influence social isolation. We leveraged data from 9,514 patients with cancer, or at high risk for cancer, from Moffitt Cancer Center to examine whether social isolation is associated with sociodemographic factors and risk mitigation behaviors. Eligible patients who had an appointment at the cancer center in the past five years, reported an email address, and had consented to the institutional biobanking protocol were invited to complete a survey regarding demographic, behavioral, and lifestyle factors as well as social isolation measured using the 4-item PROMIS Social Isolation scale. The raw PROMIS score was converted to a T-score and was split at 50, the average for the general U.S. population, and univariable and multivariable logistic regression was performed. Behavioral factors were measured on a Likert scale, ranging from “never” or “not at all”, to “very often” or “a lot”, and were evaluated continuously. Most participants were female (60.5%), Non-Hispanic White (90.3%), and had been diagnosed with cancer (89.6%); mean age was 64 years old. Only 3.5% reported ever testing positive for COVID-19, and 4.6% reported currently smoking. In univariable models, younger age, women, current smokers, and Hispanic ethnicity or Non-White race were associated with higher odds of social isolation. Among risk mitigation behaviors, leaving the house less often, attending social gatherings less often, a greater change in day-to-day life due to the pandemic, less physical contact with others outside their home, and wearing a mask more often were also associated with increased odds of social isolation. In the multivariable model including significant univariate factors, older patients (OR, per one year: 0.97; 95%CI: 0.97-0.98) and males (OR, vs. females: 0.64; 95%CI: 0.58-0.71) had lower odds of social isolation. Further, perceived changes in day-to-day life (OR, per one unit increase: 1.64 95%CI: 1.56-1.73), leaving the house less often (OR, per one unit increase: 0.75; 95%CI: 0.71-0.80), and attending social gatherings less often (OR, per one unit increase: 0.92 95%CI: 0.84-0.95) remained associated with social isolation. Overall, behavior change to mitigate risk of COVID-19 infection was associated with more social isolation for cancer patients and survivors. Women, younger patients, and current smokers may be particularly at risk, suggesting targeted interventions to reduce feelings of social isolation in these populations may be warranted. Citation Format: Cassandra A. Hathaway, Brian D. Gonzalez, Amanda Bloomer, Erin M. Siegel, Cornelia M. Ulrich, Anita R. Peoples, Frank J. Penedo, Shelley S. Tworoger. Effects of demographic and behavioral factors on social isolation in a cancer center population during COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S04-02.

Purpose: The COVID-19 pandemic has disrupted many facets of life for rural and urban patients with cancer. Here, we characterize the impact of the pandemic on social and health behaviors of rural and urban cancer patients. Methods: N=1,326 adult cancer patients, who visited HCI in the last 4 years and enrolled in either Total Cancer Care or Precision Exercise Prescription studies, completed a COVID-19 survey. The survey was administered between Aug and Sept 2020 and included questions on demographic and clinical information as well as employment status, health behaviors, and COVID-19 prevention measures. Results: The mean age was 61 (19-92) years, with 54% female, 97% non-Hispanic White, 80% stage I-III, 42% employed full or part-time, 25% living in rural counties, and 85% reporting good to excellent overall health. Cancer patients in rural compared to urban counties were more likely to be older (rural=63 vs. urban=60 years; p=0.01), retired or not employed (rural=63% vs. urban=56%; p=0.04), not have health insurance coverage (rural=4% vs. urban=2%; p=0.01), and have ever smoked (rural=35% vs. urban=24%; p=0.001). However, urban patients reported “somewhat” to “a lot” of change in their daily lives more frequently than rural patients (urban=86% vs. rural=77%; p Citation Format: Bailee Daniels, Caroline Himbert, Cassandra A. Hathway, Tengda Lin, Karen Salas, Anjelica Ashworth, Anne C. Kirchhoff, Anna Beck, Cindy Matsen, Courtney Scaife, Cristina Christenson, Douglas Grossman, Howard Colman, Jason P. Hunt, Jennifer Ose, Jonathan Tward, Kevin B. Jones, Michael Deininger, Mikaela Larson, Paul LaStayo, Thomas Varghese, Tracy Onega, Wallace L. Akerley, Frank J. Penedo, Erin M. Siegel, Cornelia M. Ulrich, Shelley S. Tworoger, Anita R. Peoples. Impact of the COVID-19 pandemic on social and health behaviors among rural and urban cancer patients at Huntsman Cancer Institute (HCI) [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S04-03.

Study Objectives This study involves the analysis of a secondary outcome of a trial examining whether cognitive behavior therapy for insomnia (CBT-I), a wake-promoting medication (armodafinil), or both results in greater improvement in prospectively assessed sleep continuity and daytime sleepiness than a placebo-alone group among a heterogeneous group of cancer survivors. Whether or not armodafinil alone, and/or when combined with CBT-I, affected adherence with CBT-I was evaluated. Design This study is a randomized, placebo-controlled, clinical trial. Setting This study was conducted at two northeastern academic medical centers. Participants Eighty-eight cancer survivors with chronic insomnia were recruited between October 2008 and November 2012. Participants were assigned to one of four conditions: 1) CBT-I and placebo (CBT-I+P); 2) CBT-I and armodafinil (CBT-I + A); 2) armodafinil alone (ARM); or 4) placebo alone (PLA). Interventions CBT-I was delivered in seven weekly individual therapy sessions (three in person, four via telephone). The armodafinil dosage was 50 mg BID. Measurements and Results Sleep continuity was measured with daily sleep diaries assessing sleep latency (SL), wake after sleep onset (WASO), and total sleep time (TST). The Epworth Sleepiness Scale (ESS) measured daytime sleepiness. Compared to the PLA group, the CBT-I+P and CBT-I+A groups reported a significant reduction in SL with effect sizes of 0.67 and 0.58, respectively. A significant reduction was observed in WASO in the CBT-I+A group with an effect size of 0.64. An increasing trend of TST was observed in the CBT-I+P, CBT-I+A, and PLA groups, but not in the ARM group. No statistically significant reductions in daytime sleepiness (ESS) were observed for any of the groups. Conclusion CBT-I alone and in combination with armodafinil caused significant improvement in sleep continuity. The addition of armodafinil did not appear to improve daytime sleepiness or enhance adherence to CBT-I.

Fatigue is a prevalent, distressing side effect of cancer and cancer treatment which commonly coexists with insomnia. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia in cancer patients, but less is known about its ability to impact fatigue. This work is the analysis for a secondary aim of a four-arm randomized controlled trial (RCT) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent, armodafinil (A), to improve sleep and daytime functioning in cancer survivors. Herein, we examine the effect of CBT-I, with and without A, on fatigue in cancer survivors.This study was a four-arm factorial study with CBTI-I (yes/no) versus A (yes/no). It consisted of 96 cancer survivors (average age 56 years; 88 % female; 68 % breast cancer). Fatigue was assessed by the brief fatigue inventory (BFI) and the FACIT-Fatigue scale. The analysis assessed the additive effects of CBT-I and A and possible non-additive effects where the effect of CBT-I changes depending on the presence or absence of A.Analyses adjusting for baseline differences showed that CBT-I improved fatigue as measured by two separate scales (BFI: P = 0.002, Std. error = 0.32, effect size (ES) = 0.46; FACIT-Fatigue: P 0.001, Std. error = 1.74, ES = 0.64). Armodafinil alone did not show a statistically significant effect on fatigue levels (all Ps 0.40) nor did the drug influence the efficacy of CBT-I. Structural equation analysis revealed that reductions in insomnia severity were directly responsible for improving cancer-related fatigue.CBT-I with and without armodafinil resulted in a clinically and statistically significant reduction of subjective daytime fatigue in cancer survivors with chronic insomnia. Armodafinil did not improve cancer-related fatigue (CRF) and did not change the efficacy of CBT-I. Patients reporting CRF should be screened and, if indicated, treated for insomnia as part of a comprehensive fatigue management program.

Background: Increased physical activity (PA) and higher overall tumor lymphocytic reaction score (LRS) are independently associated with improved outcomes in colorectal cancer (CRC) patients. However, the contribution of immune function to energy balance effects on CRC prognosis remains unclear. Methods: PA was self-reported prior to surgery (baseline) from nineteen stage I-III CRC patients enrolled in the ColoCare Study and computed into metabolic equivalent (MET) hr/week using the VITAL questionnaire. Objective PA measures were assessed using accelerometers (Actigraph GT3X+) worn 24 hr/day for 4+ consecutive days 12 months post-surgery. PA volume and intensity were derived from raw accelerometer data using ActiLife software and Freedson activity cut-points (moderate to vigorous exercise in bouts of >10 min). Clinicodemographic features were assessed by medical chart review. Clinical tumor blocks were pathologically scored for components of lymphocytic reaction (Crohn's-like reaction, peritumoral reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes [TILs]; individually scored: 0-3) and overall LRS (sum score: 0-12). Patients were categorized by mean overall LRS into low (0-4) and high (5-12) LRS groups. Mean and standard deviation values were calculated for PA and clinicodemographic features, and compared by overall LRS group using ANOVA tests. Spearman correlation coefficients were calculated to investigate the association between PA and lymphocytic reaction. Results: CRC patients were on average 58 years old, obese (mean body mass index=31.1 kg/m2), had a mean overall LRS of 4, reported 13.4 baseline MET hr/week and 11.5 MET hr/week 12 months post-surgery. Baseline body mass index was inversely correlated with intratumoral periglandular reaction (r=-0.32, p=0.002) and overall LRS (r=-0.62, p=0.005). Self-reported baseline MET hr/week had a strong positive correlation with overall LRS (r=0.83, p Conclusion: Together, findings from this pilot study suggest a correlation of energy balance components (PA and body composition) with lymphocytic reaction to colorectal cancer. Citation Format: Andreana N. Holowatyj, Richard Viskochil, Caroline Himbert, Tengda Lin, Jennifer Ose, Anita R. Peoples, Lyen C. Huang, Bartley Pickron, Courtney Scaife, Juergen Boehm, Sheetal Hardikar, Mary Bronner, Jane C. Figueiredo, Christopher Li, Martin Schneider, David Shibata, Erin Siegel, Adetunji T. Toriola, Maria Pletneva, Eric A. Swanson, Cornelia M. Ulrich. Physical activity is associated with lymphocytic reaction to colorectal cancer: A pilot study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5745.