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The approval and wide uptake of immune checkpoint inhibitors (ICIs) in oncology practice raise the concerns of possibly worsened racial disparities in cancer treatment due to biological and psychosocial reasons. We propose a multilevel biopsychosocial model to understand the opportunities and challenges to racial disparities in the era of cancer immunotherapy.

Background Cancer-related cognitive decline (CRCD) is an important clinical problem, but limited research exists on assessment of cognitive function in patients with lymphoma. Methods The overall objective of this nationwide, prospective, observational study conducted in the National Cancer Institute Community Clinical Oncology Research Program (NCORP) was to assess changes in memory, attention, and executive function in patients with lymphoma from pre- (A1) to postchemotherapy (A2) and to 6 months postchemotherapy (A3). Individuals without cancer served as noncancer controls, paired to patients by age and sex, and assessed at the same time-equivalent points. Longitudinal linear mixed models (LMM) including A1, A2, and A3 and adjusting for age, education, race, sex, cognitive reserve score, baseline anxiety, and depressive symptoms were fit. We assessed changes in patients compared with control participants without cancer and assessed differences in cognitive function in those patients with Hodgkin vs non-Hodgkin disease and by disease subtype. All statistical tests were 2-sided. Results Patients with lymphoma (n = 248) and participants without cancer serving as controls (n = 212) were recruited from 19 NCORP sites. From pre- to postchemotherapy and from prechemotherapy to 6 months follow-up, patients reported more cognitive problems over time compared with controls (Functional Assessment of Cancer-Therapy-Cognitive Function [FACT-Cog] perceived cognitive impairment effect size (ES) = 0.83 and 0.84 for A1 to A2 and A1 to A3, respectively; P Conclusion Patients with lymphoma experience worse patient-reported and objectively assessed cognitive function from prechemotherapy to 6-month follow-up compared with age- and sex-paired controls without cancer assessed at similar time intervals.

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

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.

PURPOSE/OBJECTIVE(S) Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) near AGT associated with late hematuria following radiotherapy (RT) for prostate cancer. AGT encodes angiotensinogen and, in pre-clinical models, angiotensin pathway inhibition protects against late radiation toxicity in some tissues. Effects on the bladder have not been investigated. We tested the hypothesis that angiotensin converting enzyme inhibitors (ACEi) reduce risk of late hematuria following RT. We additionally investigated the effect of genetically-defined hypertension on hematuria. MATERIALS/METHODS Prostate cancer patients (N = 268) undergoing curative RT (alone or with surgery and/or androgen deprivation therapy) were enrolled from each of two cancer centers pre-RT and followed prospectively for development of hematuria for up to four years using patient reported outcome questionnaires. Hematuria was defined as gross bleeding or medication use for hematuria. Demographic, treatment, and medication data were abstracted from medical records. The cumulative probability of hematuria was estimated by Kaplan-Meier methods, and the log rank test assessed differences by ACEi/ARB, use stratified by enrollment center. Multivariable analyses used Cox models of time to onset of hematuria stratified by enrollment center. A polygenic risk score (PRS) comprising 882 SNPs previously associated with blood pressure was tested for association with time to onset of hematuria in our Radiogenomics Consortium GWAS cohorts (N = 3,608). RESULTS The cumulative probability of hematuria among all participants was 17.1% (N = 19) at four years (median follow-up of two years). Hematuria was seen in 1.4% of those taking vs 22.9% in those not taking ACEi (P = 0.01) at the start of RT, resulting in a hazard ratio (HR) of 0.11 (95% CI 0.01 to 0.83). The protective effect of ACEi on hematuria remained when adjusted for factors associated with ACEi use, including body mass index, hypertension, or diabetes. The protective effect also remained after stratifying by risk factors for hematuria, including prior transurethral prostate resection, smoking status, or prior prostatectomy. A blood pressure PRS was strongly associated with hypertension (odds ratio per standard deviation 1.40, 95% CI 1.30 to 1.50, P < 0.001) but not with hematuria (HR per standard deviation 0.97, 95% CI 0.87 to 1.07, P = 0.52). CONCLUSION Our study is the first to show a radioprotective effect of ACEi on bladder toxicity. This effect appears distinct from presence of hypertension, which is not itself a risk factor. These results point to a promising radioprotector readily available for testing in a randomized clinical trial. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects normal tissues to reduce RT toxicity.

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.

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.

Context Patients with cancer are bothered by its diagnosis, treatment, and associated uncertainty. Lack of concordance (LOC) of patients' reporting of their symptoms and quality of life (QOL) with that of their clinicians has been observed in cancer care. However, information regarding the reporting of patients' bother due to aspects of cancer experience and their clinicians' assessment is lacking. Objectives The objective was to describe cancer patients' bother due to aspects of their disease experience and explore the concordance (LOC) or a lack thereof between patients' and clinicians' reporting of patients' bother and factors associated with it. Methods Data from a prospective study of cancer patients' symptoms were analyzed. LOC was defined as any discrepancy between patient-clinician pairs in reporting patients' bother due to disease, cancer treatment, comorbidity, and side effects of symptom management. The relation of LOC to patients' QOL and distress was also explored. Results Of the 2597 patients analyzed, a perfect concordance was observed in 37%–42%. Clinicians underestimated the severity of bother in 62%–76% of discordant cases. LOC was significantly associated with patient-reported distress and poor QOL. Referral for symptom management was associated with the clinician's rating of patients' bother, and LOC was associated with likelihood of poor compliance with recommendations for symptom management. Conclusion Majority of clinicians tended to underestimate cancer patients' bother, and this was associated with poor QOL of cancer patients and their distress. Future studies should examine the LOC and its correlates to confirm the results of this study.

Background We examined factors associated with postoperative complications, 1-year overall and cancer-specific survival after epithelial ovarian cancer (EOC) diagnosis. Methods Patients who underwent surgery for EOC between 2004 and 2013 were included. Multivariable models analyzed postoperative complications, overall survival, and cancer-specific survival. Results Among 5223 patients, surgical complications were common. Postoperative complications correlated with increased odds of overall and disease-specific survival at 1 y. Receipt of chemotherapy was similar among women with and without postoperative complications and was independently associated with a reduction in the hazard of overall and disease-specific death at 1-year. Extensive pelvic and upper abdomen surgery resulted in 2.26 times the odds of postoperative complication, but was associated with longer 1-year overall 0.53 (0.35, 0.82) and disease-specific survival 0.54 (0.34, 0.85). Conclusions Although extent of surgery was associated with complications, the survival benefit from comprehensive surgery offset the risk. Tailored surgical treatment for women with EOC may improve outcomes.

PURPOSE: Although topical agents are often provided during radiation therapy, there is limited consensus and evidence for their use prophylactically to prevent or reduce radiation dermatitis. METHODS: This was a multi-site, randomized, placebo-controlled, blinded study of 191 breast cancer patients to compare the prophylactic effectiveness of three topical agents (Curcumin, HPR Plus™, and Placebo) for reducing radiation dermatitis and associated pain. Patients applied the topical agent to their skin in the radiation area site three times daily starting the first day of radiation therapy (RT) until 1 week after RT completion. RESULTS: Of the 191 randomized patients, 171 patients were included in the final analyses (87.5% white females, mean age = 58 (range = 36–88)). Mean radiation dermatitis severity (RDS) scores did not significantly differ between study arms (Curcumin = 2.68 [2.49, 2.86]; HPR Plus™ = 2.64 [2.45, 2.82]; Placebo = 2.63 [2.44, 2.83];p = 0.929). Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). In patients with high breast field separation (≥ 25 cm), RDS scores (Curcumin = 2.70 [2.21, 3.19]; HPR Plus™ = 3.57 [3.16, 4.00]; Placebo = 2.95 [2.60, 3.30];p = 0.024) and pain scores (Curcumin = 0.52 [− 0.28, 1.33]; HPR Plus™ = 0.55 [− 0.19, 1.30]; Placebo = 1.73 [0.97, 2.50]; p = 0.046) significantly differed at the end of RT. CONCLUSIONS: Although there were no significant effects of the treatment groups on the overall population, our exploratory subgroup analysis suggests that prophylactic treatment with topical curcumin may be effective for minimizing skin reactions and pain for patients with high breast separation (≥ 25 cm) who may have the worst skin reactions.

12016 Background: CRCI is a debilitating consequence of cancer and its treatment, including difficulties in attention, memory, and executive function. Though CRCI can develop during the course of chemotherapy, interventions targeting CRCI during chemotherapy have not been investigated. Inflammation contributes to CRCI and thus reducing inflammation may ameliorate CRCI. Using a biobehavioral approach, we investigated 2 promising interventions that reduce inflammation: exercise and low-dose ibuprofen. Methods: This is a Phase II RCT with a 2:2 factorial design. Eligible participants were patients with cancer receiving chemotherapy who self-reported cognitive difficulties. Participants were stratified by disease type (breast cancer; gastrointestinal cancer; other) and were randomized to 1 of 4 groups for 6 weeks: exercise alone (+ placebo), ibuprofen alone, exercise + ibuprofen, or placebo only. The exercise intervention, delivered by an exercise physiologist, was Exercise for Cancer Patients (EXCAP), an individually tailored, home-based prescription of walking and resistance band training. Ibuprofen/placebo was over-encapsulated for blinding; 200mg was taken 2 times per day. Participants completed 7 cognitive assessments probing attention, memory, and executive function including the Trail Making Test (TMT) and self-report (FACT-Cog) at baseline and post-intervention. ANCOVA, controlling for baseline, assessed overall Arm effects at post-intervention. Results: Of the 110 who consented to the study, 86 participants (mean age=54; 88% female; 76% breast cancer, 21% GI; 73% Stage I-III) completed baseline assessments and were randomized to one of four study arms. Ninety percent (78/86) of those completed post-intervention. Average pill compliance across all 4 groups was balanced and averaged 90.8%. Participants in the exercise and exercise + ibuprofen arms increased 2,414 and 1,073 steps respectively compared to those in placebo and ibuprofen arms increased only 464 and 412 steps respectively from pre- to post-intervention. No study-related adverse events occurred. Intent to treat ANCOVA analyses revealed a significant improvement in attention (TMT) in exercise alone compared to placebo (21.57 seconds better; p=0.003), ibuprofen alone compared to placebo (11.27 seconds better; p=0.0475), and trend for exercise + ibuprofen (7.98 seconds better; p=0.122). Those participating in both exercise arms exhibited significant improvements in the FACT-Cog Comments from Others subdomain (p

10559 Background: Lung cancer is the leading cause of cancer death in the U.S, accounting for about 25% of all cancer mortality. The U.S Preventive Services Task Force has recommended annual screening for lung cancer using low-dose computed tomography (LDCT) scanning for individuals at higher risk (aged 55-80 years with a >30 pack-year smoking history). Early detection using LDCT scanning reduces lung cancer specific mortality by 20%. Despite its efficacy, the uptake of annual lung cancer screening among high-risk individuals remains low ( < 18%). The purpose of this study was to identify factors associated with the uptake of lung cancer screening in high-risk individuals in the U.S population. Methods: Data for this study were obtained from the 2017-2019 Behavioral Risk Factor Surveillance System (BRFSS), a population-based survey conducted annually by the Centers for Disease Control and Prevention (CDC) in collaboration with health departments in all 50 states, Washington, DC, and the U.S territories. We restricted our sample to high-risk individuals aged 55-80 years with a >30 pack-year smoking history. Only subjects with complete data on all predictor variables (age, gender, race/ethnicity, marital status, education, income, insurance, COPD, current smoking status, primary care provider) and the outcome variable (uptake of lung cancer screening) (n = 11, 714) were included in the final analysis. Chi-square tests were used to compare the uptake of lung cancer screening by demographic and socioeconomic factors. Multivariable logistic regression models were used to model the association between the predictors and the outcome variable. Results: Individuals with no health insurance (OR: 0.64; 95%CI: 0.46-0.90), no primary healthcare provider (OR: 0.40; 95%CI: 0.31-0.52), no chronic obstructive pulmonary disease (COPD) (OR: 0.35; 95%CI: 0.31-0.0.40) and who were females (OR: 0.86; 95%CI: 0.76-0.96) were less likely to participate in annual lung cancer screening. Individuals aged 65–69 years (OR: 1.65; 95%CI: 1.38-1.97), 70–74 years (OR: 1.77; 95%CI: 1.46-2.14) or 75–80 years (OR: 1.42; 95%CI: 1.16-1.76) were more likely to receive annual lung cancer screening compared with those aged 55-59 years. Race/ethnicity, level of education, level of income, marital status, and current smoking status had no significant association with the uptake of annual lung cancer screening. Conclusions: Our study identifies factors associated with lower uptake of annual lung cancer screening (no health insurance coverage, no primary healthcare provider, no COPD, and female gender). The findings from this study have important implications for the design of more effective interventions to target specific subgroups for the uptake of annual lung cancer screening.

Purpose Cancer-related cognitive impairment is an important problem for patients with breast cancer, yet its trajectory is not fully understood. Some previous cancer-related cognitive impairment research is limited by heterogeneous populations, small samples, lack of prechemotherapy and longitudinal assessments, use of normative data, and lack of generalizability. We addressed these limitations in a large prospective, longitudinal, nationwide study. Patients and Methods Patients with breast cancer from community oncology clinics and age-matched noncancer controls completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) at prechemotherapy and postchemotherapy and at a 6-month follow-up as an a priori exploratory aim. Longitudinal models compared FACT-Cog scores between patients and controls at the three assessments and adjusted for age, education, race, menopausal status, and baseline reading ability, anxiety, and depressive symptoms. A minimal clinically important difference cutoff determined percentages of impairment over time. Results Of patients, 581 patients with breast cancer (mean age, 53 years; 48% anthracycline-based regimens) and 364 controls (mean age, 53 years) were assessed. Patients reported significantly greater cognitive difficulties on the FACT-Cog total score and four subscales from prechemotherapy to postchemotherapy compared with controls as well as from prechemotherapy to 6-month follow-up (all P < .001). Increased baseline anxiety, depression, and decreased cognitive reserve were significantly associated with lower FACT-Cog total scores. Treatment regimen, hormone, or radiation therapy was not significantly associated with FACT-Cog total scores in patients from postchemotherapy to 6-month follow-up. Patients were more likely to report a clinically significant decline in self-reported cognitive function than were controls from prechemotherapy to postchemotherapy (45.2% v 10.4%) and from prechemotherapy to 6-month follow-up (36.5% v 13.6%). Conclusion Patients with breast cancer who were treated in community oncology clinics report substantially more cognitive difficulties up to 6 months after treatment with chemotherapy than do age-matched noncancer controls.

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.

On January 1, 2012, reimbursement for inferior vena cava filters (IVCFs) became bundled by the Centers for Medicare and Medicaid Services. This resulted in ICVF placement (CPT code 37191) now yielding 4.71 relative value units (RVUs), a decrease from 15.6 RVUs for placement and associated procedures (CPT codes 37620, 36010, 75825-26, 75940-26). Our hypothesis was that IVCF utilization would decrease in response to this change as other procedures had done once they had become bundled.Including data from 2010 to 2011 (before bundling) and 2012 to 2014 (after bundling), we utilized 5% inpatient, outpatient, and carrier files of Medicare limited data sets and analyzed IVCF utilization before and after bundling across specialty types, controlling for total diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) (ICD-9 codes 453.xx and 415.xx, respectively) and placement location.In 2010 and 2011, the rates/10,000 DVT/PE diagnoses were 918 and 1,052, respectively (average 985). In 2012, 2013, and 2014, rates were 987, 877, and 605, respectively (average 823). Comparing each year individually, there is a significant difference (P 0.0001) with 2012, 2013, and 2014 having lower rates of ICVF utilization. Comparing averages in the 2010-2011 and 2012-2014 groups, there is also a significant decrease in utilization after bundling (P 0.0001).Following the bundling of reimbursement for IVCF placement, procedural utilization decreased significantly. More data from subsequent years will be needed to show if this decrease utilization continues to persist.

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.

33 Background: GA evaluates aging-related domains (e.g., function) known to be associated with cancer treatment toxicity. We found that providing a GA summary with management recommendations to oncologists reduces clinician-rated toxicity in older patients (pts) with advanced cancer receiving high risk treatment (presented @ASCO2020). Herein, we report secondary outcomes on the effects of the GA intervention on aging-related outcomes. Methods: Pts aged ≥ 70 with incurable solid tumors or lymphoma and ≥ 1 impaired GA domain starting a new treatment regimen were enrolled. Community oncology practices were randomized to intervention (oncologists received GA summary/recommendations) or usual care (none given). Secondary analyses examined effects of the intervention on functional outcomes (patient-reported falls, instrumental activities of daily living (IADL), short physical performance battery (SPPB), geriatric depression scale (GDS), and medications [total and prescription]). Outcomes were analyzed using linear mixed effects model, logistic or Poisson regression adjusted for baseline values, time, and site effects as appropriate. Results: From 2013-19, 718 pts were enrolled from 41 practices. Age (mean 77 yrs), sex (43% women), number of impaired GA domains (median 4/8), and treatment type (chemotherapy 88%) were not different by arm. More pts in intervention were black (12% vs 3%, p

PURPOSES: To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison-group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. METHODS: We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants’ understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. RESULTS: A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were racial minority (71% black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff.=0.48, CI: 0.13 – 0.80, p=0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff.=0.58, CI: 0.37–0.78). CONCLUSION: A moderate number of the participants exhibited poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants’ scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.

Background Cancer-related fatigue is a significant problem and is associated with poor quality of life. Behavioral interventions include exercise and cognitive-behavioral therapy, which survivors may be unwilling or unable to adopt. Pharmacologic interventions (e.g., selective serotonin reuptake inhibitors) have been disappointing. One potential therapy is the antidepressant bupropion, a norepinephrine-dopamine reuptake inhibitor that targets both inflammation and the hypothalamic-pituitary-adrenal axis. The current study is intended to provide a rigorous test of the efficacy and tolerability of bupropion for cancer-related fatigue. Methods A randomized, double-blind, placebo-controlled trial will examine the effects of bupropion on cancer-related fatigue. The trial will be conducted nationwide through the University of Rochester Medical Center (URMC) National Cancer Institute Community Oncology Research Program (NCORP). Disease-free breast cancer survivors (n = 422) who completed chemotherapy and/or radiotherapy 12–60 months previously and report significant fatigue will be randomized 1:1 to receive bupropion (300 mg/day) or placebo. Outcomes will be assessed at baseline and the 12-week follow-up. The primary outcome, fatigue, will be measured with the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F). Secondary outcomes include quality of life, depression, and drug tolerability. Exploratory outcomes include cognition and symptomatology. Potential biological mechanisms and genetic moderators of cancer-related fatigue will also be explored. Discussion This study is the first placebo-controlled trial to our knowledge to evaluate bupropion for cancer-related fatigue. Positive results could revolutionize the treatment of cancer-related fatigue, as bupropion is safe, inexpensive, widely-available, and may be more tolerable and acceptable for many patients than current, limited treatment options.

BACKGROUND Supporting patients' decision making about clinical trials may enhance trial participation. To date, few theory-based interventions have been tested to address this issue. The objective of the current study was aimed to evaluate the effect of a multimedia psychoeducation (MP) intervention, relative to a print education (PE) intervention, on patients' decision support needs and attitudes about clinical trials. METHODS Patients with cancer who were eligible for participation in a National Cancer Institute therapeutic cancer clinical trial were recruited through the nationwide University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program from 2014 to 2016 and were randomized to the MP or PE intervention. Assessments at baseline (before intervention), postintervention, and at a 2-month follow-up visit included patients' decision support needs, attitudes regarding clinical trials, and clinical trial participation. RESULTS In total, 418 patients with various types of cancer were recruited (ages 26-89 years). Relative to the PE intervention, the MP intervention did not significantly affect decision support needs. However, patients in the MP arm reported significantly more positive attitudes about clinical trials and were more likely to participate in a clinical trial than those in the PE arm (69% vs 62%; P = .01). Furthermore, an improvement in attitudes about clinical trials significantly mediated the effect of the intervention on participation in clinical trials. CONCLUSIONS The MP intervention was able to improve patient attitudes toward clinical trials compared with the PE intervention, and this improvement led to increased rates of participation in trials. The MP intervention could be disseminated to improve attitudes about clinical trials among patients with cancer.

The aim of this study was to examine the effect of modafinil on depression via a secondary data analysis of a randomized clinical trial of modafinil for fatigue in cancer patients. The primary aim is to elucidate factors that contributed to the effectiveness of modafinil in the parent trial.Five hundred forty-one cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory [BFI] item 3 of ≥3) were randomized to receive 200 mg modafinil (n = 260) or placebo (n = 281) daily from baseline (cycle 2) to posttest (cycle 4). Patients completed the Center for Epidemiological Studies-Depression Scale (CES-D) and Profile of Mood States depression-dejection subscale at baseline and posttest. We used linear regression to address the hypothesis that modafinil would be associated with reduced depression, particularly in those experiencing severe fatigue (BFI ≥7).Modafinil did not have a significant effect on depression, even for those patients with severe fatigue. However, for subjects with severe fatigue (BFI ≥7), those receiving modafinil had lower depression scores than did control subjects. Modafinil significantly moderated the relationship between baseline fatigue and CES-D total scores (P = 0.04) and was marginally significant as a moderator for the relationship between baseline fatigue and Profile of Mood States depression-dejection subscale scores (P = 0.07). Modafinil also significantly moderated the relationship between baseline fatigue and CES-D positive affect subscale scores (P = 0.003), but not CES-D somatic, negative affect, or interpersonal subscale scores.Modafinil differentially impacts depression based on a patient's level of fatigue and reduced depressive symptoms only in those with extreme fatigue. This effect may be driven by increases in positive affective symptoms. These results have significant implications for intervention; in patients with high levels of fatigue, modafinil might also reduce depression. Future randomized clinical trials are needed to confirm these results.

Studies have found disparities in psychological distress between lesbian and gay cancer survivors and their heterosexual counterparts. Exercise and partner support are shown to reduce distress. However, exercise interventions haven't been delivered to lesbian and gay survivors with support by caregivers included.In this pilot randomized controlled trial (RCT), ten lesbian and gay and twelve heterosexual survivors and their caregivers were randomized as dyads to: Arm 1, a survivor-only, 6-week, home-based, aerobic and resistance training program (EXCAPTwenty of the twenty-two recruited survivors were retained post-intervention. At baseline, lesbian and gay survivors reported significantly higher depressive symptoms (P = .03) and fewer average steps walked (P = .01) than heterosexual survivors. Post-intervention, these disparities were reduced and we detected no significant differences between lesbian/gay and heterosexual survivors. Participation in dyadic exercise resulted in a significantly greater reduction in depressive symptoms than participation in survivor-only exercise for all survivors (P = .03). No statistically significant differences emerged when looking across arm (survivor-only vs. dyadic) by subgroup (lesbian/gay vs. heterosexual).Exercise may be efficacious in ameliorating disparities in psychological distress among lesbian and gay cancer survivors, and dyadic exercise may be efficacious for survivors of diverse sexual orientations. Larger trials are needed to replicate these findings.

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.

Cancer-related dyspnea is a common, distressing, and difficult-to-manage symptom in cancer patients, resulting in diminished quality of life and poor prognosis. Buspirone, a non-benzodiazepine anxiolytic which does not suppress respiration and has proven efficacy in the treatment of generalized anxiety disorder, has been suggested to relieve the sensation of dyspnea in patients with COPD. The main objective of our study was to evaluate whether buspirone alleviates dyspnea in cancer patients. We report on a randomized, placebo-controlled trial of 432 patients (mean age 64, female 51 %, lung cancer 62 %) from 16 participating Community Clinical Oncology Program (CCOP) sites with grade 2 or higher dyspnea, as assessed by the Modified Medical Research Council Dyspnea Scale. Dyspnea was assessed by the Oxygen Cost Diagram (OCD; higher scores are better) and anxiety by the state subscale of the State‐Trait Anxiety Inventory (STAI-S; lower scores are better) at baseline and after the 4-week intervention (post-intervention). Mean scores from baseline to post-intervention for buspirone were OCD 8.7 to 9.0 and STAI-S 40.5 to 40.1 and for placebo were OCD 8.4 to 9.3 and STAI-S 40.9 to 38.6 with raw improvements over time on both measures being greater in the placebo group. Analysis of covariance (ANCOVA) controlling for baseline scores showed no statistically significant difference between groups for OCD (P = 0.052) or STAI-S (P = 0.062). Buspirone did not result in significant improvement in dyspnea or anxiety in cancer patients. Thus, buspirone should not be recommended as a pharmacological option for dyspnea in cancer patients.

Older patients with cancer and their caregivers worry about the effects of cancer treatment on aging-related domains (eg, function and cognition). Quality conversations with oncologists about aging-related concerns could improve patient-centered outcomes. A geriatric assessment (GA) can capture evidence-based aging-related conditions associated with poor clinical outcomes (eg, toxic effects) for older patients with cancer.To determine whether providing a GA summary and GA-guided recommendations to oncologists can improve communication about aging-related concerns.This cluster-randomized clinical trial enrolled 541 participants from 31 community oncology practices within the University of Rochester National Cancer Institute Community Oncology Research Program from October 29, 2014, to April 28, 2017. Patients were aged 70 years or older with an advanced solid malignant tumor or lymphoma who had at least 1 impaired GA domain; patients chose 1 caregiver to participate. The primary outcome was assessed on an intent-to-treat basis.Oncology practices were randomized to receive either a tailored GA summary with recommendations for each enrolled patient (intervention) or alerts only for patients meeting criteria for depression or cognitive impairment (usual care).The predetermined primary outcome was patient satisfaction with communication about aging-related concerns (modified Health Care Climate Questionnaire [score range, 0-28; higher scores indicate greater satisfaction]), measured after the first oncology visit after the GA. Secondary outcomes included the number of aging-related concerns discussed during the visit (from content analysis of audiorecordings), quality of life (measured with the Functional Assessment of Cancer Therapy scale for patients and the 12-Item Short Form Health Survey for caregivers), and caregiver satisfaction with communication about aging-related patient concerns.A total of 541 eligible patients (264 women, 276 men, and 1 patient did not provide data; mean [SD] age, 76.6 [5.2] years) and 414 caregivers (310 women, 101 men, and 3 caregivers did not provide data; mean age, 66.5 [12.5] years) were enrolled. Patients in the intervention group were more satisfied after the visit with communication about aging-related concerns (difference in mean score, 1.09 points; 95% CI, 0.05-2.13 points; P = .04); satisfaction with communication about aging-related concerns remained higher in the intervention group over 6 months (difference in mean score, 1.10; 95% CI, 0.04-2.16; P = .04). There were more aging-related conversations in the intervention group's visits (difference, 3.59; 95% CI, 2.22-4.95; P .001). Caregivers in the intervention group were more satisfied with communication after the visit (difference, 1.05; 95% CI, 0.12-1.98; P = .03). Quality of life outcomes did not differ between groups.Including GA in oncology clinical visits for older adults with advanced cancer improves patient-centered and caregiver-centered communication about aging-related concerns.ClinicalTrials.gov identifier: NCT02107443.

Patients who receive cancer chemotherapy are at risk for nausea and vomiting. The incidence and severity of these effects depend on the inherent emetogenic potential of the chemotherapeutic agents and their dosage and administration schedules, and patient factors such as younger age, female gender, low use of alcohol, and perceived susceptibility to nausea.1-3 Chemotherapy-induced nausea and vomiting (CINV) may be responsible for numerous adverse outcomes, including nutritional deficiencies and anorexia, esophageal tears, deterioration of performance and mental status, functional ability, and discontinuation of potentially effective cancer treatment.1 Therefore, overall control of CINV is an important primary goal of preventive treatment. CINV may occur acutely after the start of chemotherapy, or it can be delayed, not appearing until the second day after start of chemotherapy and continuing for 5 or more days.1 Although delayed CINV can occur independently of acute CINV, the risk of delayed CINV is greater if acute CINV is poorly controlled.4 Delayed CINV may be more common.5 In particular, delayed nausea seems to be more common and often more severe than acute nausea and it may be resistant to common preventive treatments.6 Indeed, although vomiting can often be controlled by prophylactic antiemetic therapy administered before emetogenic chemotherapy, patients may still experience acute or delayed nausea.5 Thus, nausea is generally more difficult to control than vomiting,1 and controlling delayed nausea in particular presents a challenge. CINV seems to result from the release of 5-hydroxytryptamine (5-HT; serotonin) from chemotherapy-damaged enterochromaffin cells in the small intestine and the subsequent activation of 5-HT3 receptors on the vagal afferent nerves and stimulation of CNS centers involved in mediating emesis.7,8 Substance P and neurokinin-1 (NK-1) receptors also seem to play a role in CINV, particularly in the delayed phase.7 5-HT3 receptor antagonists (RA) have been widely studied and are standard therapies for cancer patients receiving emetogenic chemotherapy. Older 5-HT3 RA agents such as ondansetron, granisetron, dolasetron, and tropisetron have proven effective in preventing acute CINV in 50%-80% of patients on moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) regimens.9 However, many patients continue to have acute and/or delayed CINV despite such treatment.5,10 Palonosetron is a newer 5-HT3 RA with a distinct molecular and pharmacologic profile, including structural differences,11 stronger binding affinity for the 5-HT3 receptor,12 a different binding profile (ie, allosteric binding, positive cooperativity, and receptor internalization, leading to longer binding, as well as persistent functional effects11 and a longer elimination half-life (about 40 hours)12,13 relative to older agents. Palonosetron also inhibits substance P-mediated responses independent of serotonin14 and has been found to uniquely inhibit cross-talk between 5-HT3 and NK-1 receptor pathways.15 Palonosetron has not been associated with significant QT interval prolongation,16-18 an effect observed with other 5HT3 RAs.1,19 A recent analysis of data from 5 randomized, double-blind, comparative trials (n = 2,057) found that palonosetron was significantly more effective than were older 5-HT3 RAs (ondansetron, dolasetron, granisetron) in preventing acute and delayed CINV associated with MEC or HEC, whether or not corticosteroids were used concomitantly.20 Another recent study reported a lower incidence of nausea with palonosetron (n = 39) compared with granisetron (n = 49) in patients with advanced colorectal cancer who received mFOLFOX6 and FOLFIRI.21 The present analysis evaluates the safety and efficacy of palonosetron compared with older 5-HT3 RAs in preventing nausea in the acute phase (0-24 h) and the delayed phase (24-120 h) after emetogenic chemotherapy. Data were derived from 4 similarly designed comparative studies of palonosetron compared with ondansetron, dolasetron, or granisetron in patients treated with emetogenic chemotherapy.22-25 The primary published reports of the 4 studies focused on the occurrence of emetic episodes; here we report an analysis of pooled data for nausea endpoints.

OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; pr=0.35; pr=0.21; pr=0.37; pr=0.35; pp=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.

11500 Background: Cancer-treatment-induced bone loss (CTIBL) is a side effect of aromatase inhibitors (AIs) and can result in osteoporotic fractures. Vitamin D (VITD) protects against postmenopausal bone loss but it is unclear if the recommended daily allowance (RDA: 600 IU/day) of VITD is sufficient to prevent CTIBL. This phase II RCT aimed to assess the feasibility, safety, and preliminary efficacy of high-dose VITD (with and without exercise) on bone mineral density (BMD) compared to the RDA. Methods: Non-metastatic breast cancer patients starting AIs with low VITD (

11590 Background: Over half of patients receiving “neurotoxic” taxane, platinum, or bortezomib chemotherapy experience CIPN—a dose-limiting toxicity involving numbness and pain in the extremities. There are no FDA-approved drugs for CIPN, but exercise may help. This randomized pilot study explored whether structured exercise during chemotherapy ameliorates CIPN symptoms and whether improvements involve changes in the brain’s sensory processing (interoceptive) circuitry. Methods: Nineteen patients scheduled to receive taxane, platinum, or bortezomib were randomized to exercise (home-based, low-moderate intensity, walking and resistance training; EXCAP) or nutrition education (control) for 12 weeks starting at their first infusion. At 0, 6, and 12 weeks, we assessed CIPN symptoms using the CIPN-20 questionnaire (sensory scale, ranges 9-36, higher is worse) and a finger tactile sensitivity task. We assessed resting functional connectivity between the insula and thalamus via fMRI at 0 and 12 weeks. We used linear regression to model each outcome, tested for an effect of exercise, and controlled for baseline value and age because controls were older. Given the pilot nature of this study we present effect sizes, not p-values. Results: The 19 patients were 65±11 years old, 52% women, with cancer: 42% breast, 32% gastrointestinal, 16% myeloma, and 10% genitourinary. Exercise mitigated CIPN symptoms per the CIPN-20 sensory scale. At 6 weeks, exercisers increased from 11.0 to 12.5 whereas controls increased from 11.0 to 15.5 (+1.5 vs. +4.5; ES = 0.81). At 12 weeks, exercisers increased from 11.0 to 14.8 whereas controls increased from 11.0 to 16.2 (+3.8 vs. +5.2, ES = 0.46). The finger-touching test corroborated results at 6 and 12 weeks (ES = 1.03 and 0.07). Exercisers showed better (reduced) insula-thalamus connectivity vs. controls (ES = 0.41). Reductions in connectivity were correlated with smaller increases in CIPN symptoms (r = 0.74). Conclusions: Exercise during neurotoxic chemotherapy mitigated CIPN symptoms, perhaps via improvements in interoceptive brain circuitry. Future work should test for replication with a larger sample. Clinical trial information: NCT03021174.

e18124 Background: Cancer is the second leading cause of death in the United States. Despite decreases in cancer mortality overall, rural populations continue to have higher prevalence and slower reduction of cancer death rates. As a preventive approach to combat cancer, the National Cancer Institute continues to prioritize providing the public with health information. Yet, little is known about cancer information-seeking across rural America. Methods: Using Rural-Urban Commuting Area Codes (RUCAs), from the 2018 Health Information National Trends Survey (HINTS-5) database we analyze the odds of looking for information about cancer across four geo-political contexts (n = 2,625): urban, large-rural, small-rural, and isolated-rural areas, thus giving us a potentially more detailed understanding of place and health across the urban-rural continuum. Using an established social determinants framework, a series of logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (CIs). Results: Across all models, those living in large rural towns had about 1.5 times the odds of looking for cancer information compared to urban-dwellers (p < 0.05) while those living in remote rural areas had about 0.5 times the odds (p < 0.05). There was no difference for those living in small rural towns. Additionally, gender, race/ethnicity, marital status, education, housing status, and internet availability were independently associated with information-seeking (p < 0.05). Conclusions: In this study, compared to urban-dwellers, those living in large rural towns appeared to have increased odds of looking for cancer information while those living in isolated rural areas had decreased odds. Understanding this relationship between place and health has implication for the allocation of resources and the design of interventions aimed at increasing information about cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70 % of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2 % ketamine plus 4 % amitriptyline (KA) cream for reducing CIPN. Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N = 462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average “pain, numbness, or tingling in [their] hands and feet over the past 24 h” on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N). The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference = −0.17, p = 0.363). This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.

Breast cancer treatments (chemotherapy and hormone therapy) can cause a rapid loss in bone mineral density, leading to osteoporosis and fractures later in life. Fortunately, preventative measures (vitamin D, exercise, etc.) can delay bone loss if employed early enough. This study compares the prevalence of osteoporosis and osteoporosis-related discussions with physicians among female breast cancer survivors and females with no cancer history to determine if breast cancer patients are being correctly advised on their high risk of bone loss.The 2003 Medicare Current Beneficiary Survey, a nationally representative sample of 550 women with a breast cancer history and 6,673 women with no cancer history aged ≥65, was used. The first set of dependent variables collected information on bone health (osteoporosis, falls, and fractures). The second set of dependent variables collected information on bone health discussions with their physician. Multivariate logistic regression models were used to evaluate whether breast cancer was independently associated with bone health issues.After adjustment for confounders, a breast cancer diagnosis was found to be associated with a higher prevalence of an osteoporosis diagnosis over their lifetime (adjusted odds ratio (OR(adj)) = 1.32, 95 % confidence interval (95 % CI) = 1.08-1.61) and falls in the previous year (OR(adj) = 1.23, 95 % CI = 1.01-1.51) compared to respondents without a cancer diagnosis. However, breast cancer respondents were not more likely than respondents without a cancer diagnosis to discuss osteoporosis with their physician (OR(adj) = 1.20, 95 % CI = 0.96-1.50) or be told they are at high risk for osteoporosis (OR(adj) = 1.41, 95 % CI = 0.95-2.10).A breast cancer diagnosis was associated with an increased prevalence of osteoporosis and falls. Nevertheless, breast cancer respondents were not more likely to discuss osteoporosis with their physician nor were they more likely to be considered high risk for osteoporosis. Increased dialogue between physician and breast cancer patient pertaining to bone loss is needed.

Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS = 2.6 vs. 3.4; P = 0.008). Fisher's exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P = 0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients.

Nausea and vomiting are two of the most frequent and troubling side effects patients experience during chemotherapy, interfering with compliance with cancer therapies and quality of life. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still major problems for patients receiving chemotherapy. Many cancer patients consider delaying future chemotherapy cycles and some contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting.The purpose of this article is to provide an overview of the pathopsychophysiology of chemotherapy-induced nausea and vomiting (CINV), the recommended guidelines for treatment, and current agents in late-stage clinical trials, and future research needs to address the continued challenges of treatment-related nausea and vomiting.Despite advances in pharmaceutical and behavioral therapies, and the provision of standard clinical guidelines for effectively managing CINV, patients continue to experience it. Moreover, control of nausea, acute and delayed, and anticipatory nausea and vomiting remains an important, unmet need among cancer patients. It is critical to focus attention on better understanding the mechanisms underlying nausea, anticipatory symptoms and delayed symptoms.

Cancer-related fatigue (CRF) is a prevalent and distressing side effect of cancer and its treatment that remains inadequately understood and poorly managed. A better understanding of the factors contributing to CRF could result in more effective strategies for the prevention and treatment of CRF. The objectives of this study were to examine the prevalence, severity, and potential predictors for the early onset of CRF after chemotherapy cycle 1 in breast cancer patients. We report on a secondary data analysis of 548 female breast cancer patients from a phase III multi-center randomized controlled trial examining antiemetic efficacy. CRF was assessed by the Brief Fatigue Inventory at pre- and post-chemotherapy cycle 1 as well as by the four-day diary. The prevalence of clinically relevant post-CRF was 75%. Linear regression showed that pre-treatment CRF, greater nausea, disturbed sleep, and younger age were significant risk factors for post-CRF (adjusted R2 = 0.39; P

Gabapentin is used for the treatment of hot flashes and neuropathic pain in breast cancer survivors, and is commonly used off-label for the treatment of anxiety. Yet, clinical trial evidence to support the use of gabapentin for anxiety symptoms is lacking. In a randomized, double-blinded controlled trial we compared 300 mg gabapentin versus 900 mg gabapentin versus placebo. Subjects were 420 breast cancer patients who had completed all chemotherapy cycles. Anxiety traits and current (state) anxiety were measured using the Speilberger Strait-Trait Anxiety Inventory at baseline, 4 and 8 weeks. Pain was measured at baseline using a 10-point scale. Analyses included analysis of covariance and ordinary least squares regression. At 4 weeks, state anxiety change scores were significantly better for gabapentin 300 and 900 mg (p = 0.005) compared to placebo. The magnitude of improvement was proportional to baseline state anxiety. At 8 weeks, the anxiolytic effects of gabapentin compared to placebo persisted (p < 0.005). We found no significant interactions. The lower dose (300 mg) was associated with the best treatment outcomes for all patients except those with the highest baseline anxiety. Given its similar pharmacology, efficacy in the treatment of hot flashes, and low cost, gabapentin may provide a low cost and parsimonious alternative treatment choice for breast cancer survivors presenting in primary care practices with anxiety symptoms. Gabapentin is effective for hot flashes, and, therefore, may provide therapeutic benefit for both anxiety and hot flashes at a generic drug price. For patients reluctant to take a controlled substance, such as a benzodiazepine, gabapentin may offer an alternative therapy. Similarly, patients with a history of substance use may benefit from gabapentin without risk of addiction or abuse. For cancer survivors experiencing both hot flashes and anxiety, gabapentin may provide a single effective treatment for both and is an alternative therapy for anxiety for patients unwilling to take a benzodiazepine or those with a history of substance use.

Sleep problems are a frequent distressing symptom in cancer patients, yet little is known about their treatment. Sleep problems and depression frequently co-occur, leading healthcare professionals to treat depression with the expectation that sleep problems will also improve. The purpose of this study was to compare the effect of paroxetine to placebo on sleep problems via a secondary data analysis of a RCT designed to compare the effects of paroxetine to placebo on fatigue in cancer patients undergoing chemotherapy. A previously published report found a significant effect of paroxetine on depression in this cohort.A total of 426 patients were randomized following Cycle 2 of chemotherapy to receive either 20mg of paroxetine or placebo. Sleep problems were assessed using questions from the Hamilton Depression Inventory three times during chemotherapy.A total of 217 patients received paroxetine and 209 received placebo. Significantly fewer patients taking paroxetine reported sleep problems compared to patients on placebo (Paroxetine 79% versus Placebo 88%; p0.05). These differences remained significant even after controlling for baseline sleep problems and depression (p0.05).Paroxetine had a significant benefit on sleep problems in both depressed and non-depressed cancer patients. However, rates of sleep problems remained high even among those effectively treated for depression with paroxetine. There is a need to develop and deliver sleep-specific interventions to effectively treat sleep-related side effects of cancer treatments. These findings suggest that sleep problems and depression are prevalent and co-morbid. Cancer progression, its response to treatment, and overall patient survival are intricately linked to host factors, such as inflammatory response and circadian rhythms, including sleep/wake cycles. Sleep problems and depression are modifiable host factors that can influence inflammation and impact cancer progression and quality of life. Future research should focus on discovering the pathogenesis of sleep dysregulation and depression in cancer so that better treatment approaches can be developed to ameliorate these symptoms.

The purpose of this study is to evaluate the efficacy and safety of intravenous (IV) palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who had incomplete control of CINV during their previous cycle of low emetogenic chemotherapy (LEC).Patients with histologically or cytologically confirmed cancer, ≥18 years of age, with a Karnofsky Performance Scale score of ≥50% who had received LEC that induced vomiting and/or at least moderate nausea during their previous treatment cycle received palonosetron 0.25 mg IV 30 min before chemotherapy. Outcomes were recorded in patient diaries over 120 h and at an end-of-study visit on days 6, 7, or 8 after LEC administration. The primary efficacy variable was the complete response rate, defined as no emetic episodes and no rescue medication at 0-24 h (acute post-chemotherapy phase), 24-120 h (delayed phase), and 0-120 h (overall).Complete responses among the intent-to-treat study population (n = 34) were recorded for 88.2 % of patients in the acute phase, 67.6% in the delayed phase, and 67.6% overall. No emetic episodes occurred in 91.2 and 79.4% of patients during the acute and delayed phases, respectively, and no nausea in 73.5 and 52.9%, respectively. Palonosetron was well tolerated; only two patients experienced treatment-related adverse events.Among the patients with cancer who had a history of CINV with LEC, palonosetron was effective in preventing CINV in both the acute and delayed post-chemotherapy phases, and was well tolerated. Randomized comparative studies in larger populations of patients receiving LEC are needed to confirm these findings.

Learning Objectives After completing this course, the reader will be able to: Describe the influence of cigarette smoking on side effects during cancer treatment and following the end of cancer treatment.Identify areas in your practice in which smoking status can be assessed on a regular basis and devise a plan for disseminating cessation information and free cessation aids. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. Cigarette smoking has long been implicated in cancer development and survival. However, few studies have investigated the impact of smoking on symptom burden in cancer survivors during treatment and at survivorship stage. This study examines the influence of cigarette smoking on side effects among 947 cancer patients during and 6 months following treatment. Methods. Patients diagnosed with cancer and scheduled to receive chemotherapy and/or radiation therapy reported on current smoking status (yes, no) and total symptom burden [the sum of 12 common symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain, concentration, hot flashes, weight loss, skin problems, and dyspnea) scored on an 11-point scale ranging from 0 = “not present” to 10 = “as bad as you can imagine”] during treatment and at 6-month follow-up. The adjusted mean total symptom burden by smoking status was determined by analysis of covariance controlling for age, gender, race, education, occupation, treatment, cancer site, and Karnofsky performance score. Results. During treatment, smokers (S) had a significantly higher total symptom burden than nonsmokers (NS) (S = 46.3 vs. NS = 41.2; p < 0.05). At 6-month follow-up, smokers continued to report a higher total symptom burden than nonsmokers (S = 27.7 vs. NS = 21.9; p < 0.05). Participants who quit smoking before treatment levels had a total symptom burden similar to nonsmokers. Conclusion. Smoking was associated with an increased symptom burden during and following treatments for cancer. Targeted cessation efforts for smokers to decrease symptom burden may limit the likelihood of treatment interruptions and increase quality of life following treatment.

The incidence of overall (acute and delayed) chemotherapy-induced nausea and vomiting (CINV) events among patients treated with single- and multi-day low emetogenic chemotherapy (LEC) is not well established. We studied a cohort of patients receiving LEC and antiemetic prophylaxis with palonosetron (Group 1) versus other 5-HT(3) receptor antagonists (5-HT(3)-RAs) (Group 2), to determine the overall rate of CINV and the proportion of patients experiencing delayed CINV (days 2-7 of a CT cycle) in a hospital outpatient setting.Patients aged ≥18 years with cancer diagnosis initiating single-day and multi-day LEC for the first time between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective database. CINV events (ICD-9-CM codes for nausea, vomiting, or volume depletion or CINV-related rescue medications) were assessed descriptively. A generalized linear multivariate regression model was developed, estimating the overall CINV event rate among Group 1 and 2 patients in the follow-up period (first of eight chemotherapy [CT] cycles or 6 months).In the follow-up period, out of a total of 10,137 overall CINV events (single-day and multi-day LEC), 8783 events (86.6%) were identified in single-day LEC treated patients. Within single-day LEC treated events, in the first cycle, of 3184 events, 2996 (94.1%) events were delayed. Average number of delayed events per patient remained consistent throughout the eight cycles (3.1 [1st cycle] vs. 2.9 [8th cycle]; P = 0.842]). Among 2439 patients on antiemetic prophylaxis with a 5-HT(3)-RA, 10.1% (n = 247) initiated palonosetron. Regression analysis indicated that Group 1 patients (versus Group 2) had a 15.2% reduction in CINV event rate per CT cycle; P = 0.0403. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship.In this retrospective analysis, delayed CINV comprised a major proportion of overall CINV among cancer diagnosed patients on single-day LEC. Additionally, palonosetron prophylaxis was associated with a significantly lower overall CINV event rate versus other 5-HT(3)-RA prophylaxis in single- and multi-day LEC treatment.

The purpose of this review is to summarize the current literature on the effects of cancer treatment-related cognitive difficulties, with a focus on the effects of chemotherapy. Numerous patients have cognitive difficulties during and after cancer treatments and, for some, these effects last years after treatment. We do not yet fully understand which factors increase susceptibility to cognitive difficulties during treatment and which cause persistent problems. We review possible contributors, including genetic and biological factors. Mostly we focus is on cognitive effects of adjuvant chemotherapy for breast cancer; however, cognitive effects of chemotherapy on the elderly and brain tumor patients are also discussed.

Purpose To identify whether a history of cancer is associated with specific geriatric syndromes in older patients. Patients and Methods Using the 2003 Medicare Current Beneficiary Survey, we analyzed a national sample of 12,480 community-based elders. Differences in prevalence of geriatric syndromes between those with and without cancer were estimated. Multivariable logistic regressions were used to evaluate whether cancer was independently associated with geriatric syndromes. Results Two thousand three hundred forty-nine (18%) reported a history of cancer. Among those with cancer, 60.3% reported one or more geriatric syndromes as compared with 53.2% of those without cancer (P < .001). Those with cancer overall had a statistically significantly higher prevalence of hearing trouble, urinary incontinence, falls, depression, and osteoporosis than those without cancer. Adjusting for possible confounders, those with a history of cancer were more likely to experience depression (adjusted odds ratio [OR], 1.15; 95% CI, 1.02 to 1.30; P = .023), falls (adjusted OR, 1.17; 95% CI, 1.04 to 1.32; P = .010), osteoporosis (adjusted OR, 1.21; 95% CI, 1.06 to 1.38; P = .004), hearing trouble (adjusted OR, 1.28; 95% CI, 1.08 to 1.52; P = .005), and urinary incontinence (adjusted OR, 1.42; 95% CI, 1.20 to 1.69; P < .001). Analysis of specific cancer subtypes showed that lung cancer was associated with vision, hearing, and eating trouble; prostate cancer was associated with incontinence and falls; cervical/uterine cancer was associated with falls and osteoporosis; and colon cancer was associated with depression and osteoporosis. Conclusion Elderly patients with cancer experience a higher prevalence of geriatric syndromes than those without cancer. Prospective studies that establish the causal relationships between cancer and geriatric syndromes are necessary.