Oxana Palesh

10094 Background: Insomnia is experienced by up to 80% of cancer patients, and it frequently co-occurs with circadian rhythm disruption. The relationship is reciprocal in that disruption in circadian rhythm can cause or result from insomnia and vice versa. There are no effective brief behavioral interventions that can be delivered directly in infusion centers. We aimed to evaluate the efficacy of a novel intervention, BBT-CI, for improving sleep and circadian rhythm disruption in BC patients undergoing chemotherapy. Methods: In our phase II, two-arm, randomized clinical trial, 71 BC patients (mean age = 52.5) who reported moderate insomnia were randomized to: 1) BBT-CI or 2) a healthy eating behavioral control (HEAL). BBT-CI and HEAL were delivered over 6 weeks (2 face-to-face sessions + 4 phone calls) at 5 NCI-funded NCORP clinics by trained assistants. Sleep disruption was measured with the Insomnia Severity Index (ISI) and circadian rhythm with the Actiwatch-64 (Mesor, Amplitude, and Acrophase for 12- and 24-hour cycles). Participants completed the ISI at baseline and post-intervention and wore the Actiwatch for 7 days prior to each visit. Results: The study showed excellent feasibility and acceptability of BBT-CI as reflected by a recruitment rate of over 75% and an intervention adherence of 74%, with 75% of intervention components successfully delivered by trained community staff. ANCOVA results indicate that patients who received BBT-CI exhibited improvements in insomnia compared to HEAL at post-intervention (p = .049) and at 1-month follow-up (p = .002). Furthermore, results reveal a significant treatment effect in circadian rhythm at post-intervention for 24-hour amplitude (p = .009) and 12-hour Acrophase (p = .012) as well as a trend for Mesor in favor of BBT-CI (p = .10). Conclusions: BBT-CI demonstrated greater improvements in insomnia and circadian rhythm than HEAL. In addition, this novel intervention has shown efficacy in community oncology clinics. BBT-CI has the potential of changing clinical practice as it reduces patients’ psychophysiological symptoms and burden due to its behavioral design and capacity to be delivered directly in infusion centers. Clinical trial information: NCT02002533.

10014 Background: Large nationwide studies are needed to assess CRCI. Methods: NCORPs recruited BC patients and age-matched non-cancer controls. Computerized ((CANTAB Delayed Match to Sample (DMS), Rapid Visual Processing (RVP), Verbal Recognition Memory (VRM)), paper-based ((Controlled Oral Word Association (COWA), and Trail Making Test (TMT)) , and phone-based (category fluency, word recall, backward counting and digits backward) cognitive assessments of memory, attention, and executive function at pre-chemotherapy, post-chemotherapy, and 6 months follow-up (or time-equivalent for controls) were completed. Longitudinal mixed model (LMM)s included group, time, time*group, and adjusted for age, education, reading, anxiety, and depression. Results: 580 BC patients (mean age = 54) and 363 controls (mean age = 53) were assessed. In all LMMs, there was a significant group*time interaction depicting lower scores in patients compared to controls (p < 0.005) except for TMT (p = 0.09). For longitudinal change on the DMS memory test (primary aim), we observed no significant difference between groups from pre- to post-chemotherapy but did observe a significant difference from pre-chemotherapy to follow-up (p = 0.017) where patients significantly declined (p = 0.005) and controls did not change. We observed similar results for RVP. For VRM, there was a significant pre- to post-chemotherapy group difference (p = 0.003). For COWA, patients significantly declined and controls significantly improved reflecting a significant between group difference (p < 0.001) from pre- to post-chemotherapy. For TMT, both groups significantly improved with patients improving less than controls reflected by a significant between group difference (p = 0.04) that remained a trend at follow-up (p = 0.06). On all phone tests, there was a significant between group effect from both pre- to post-chemotherapy and at follow-up with patients doing less well than controls (all p < 0.001). Conclusions: This nationwide study shows CRCI in BC patients persists in multiple cognitive domains up to 6 months post-chemotherapy compared to controls. Clinical trial information: NCT01382082.

246 Background: Emerging evidence suggests that circadian disruption is associated with cancer and cancer treatments. Chronotype is defined as a behaviorally manifested preference for a certain timing of sleep and activity. Previous studies have revealed that living out of sync from one’s innate chronotype can have detrimental effects on one’s health. Although there has been research examining the associations between chronotype and health, not much is known about the relationship between chronotype, fatigue, and QOL in cancer survivors. Methods: 68 Breast cancer survivors completed questionnaires to assess their chronotype (Horne-Ostberg), to rate their fatigue (MDASI), and to evaluate their QOL (FACIT). The Horne-Ostberg questionnaire yields a range of values indicating survivors’ preference for early or late activity. The study sample was divided by terciles according to survivors’ “morningness” or “eveningness” preferences (i.e., chronotypes). Results: Morning chronotype was associated with significantly less severe tiredness and drowsiness as well as significantly better physical well-being and fatigue subscale scores as compared to evening chronotype. Tiredness median (M) scores were highest for evening chronotype (M=5.5), moderate for mid-range chronotype (M=4.5), and lowest for morning chronotype (M=3.0), a significant difference (p=0.046). Drowsiness scores were highest for evening chronotype (median=6.0), moderate for mid-range chronotype (M=4.0), and lowest for morning chronotype (M=3.0), p=0.046. The median score for physical well-being was significantly lower for evening compared to morning chronotypes (22.5 vs. 25.0, p=0.038) and morning types reported significantly better health in respect to fatigue compared to evening types (40.5 vs. 35.5, p=0.045). Conclusions: Survivors with early chronotype (early to bed, early to rise) reported less fatigue, drowsiness, and better overall physical well-being. While chronotype is believed to be genetically driven, certain behavioral, pharmacological, and bright light modifications can be used to help patients shift their circadian rhythm towards earlier morning type and may experience improvements in physical well-being.

162 Background: The popularity of acupuncture among cancer patients highlights the need for studying its effectiveness for mitigating side effects of cancer treatments. Insomnia is prevalent among cancer patients and is associated with fatigue and reduced quality of life (QOL). It is also closely linked with depression, sleep apnea, and circadian disruption. Using data form an RCT of acupuncture for insomnia among breast cancer survivors, we examined depression, apnea and circadian factors as moderators of acupuncture effectiveness. Methods: 68 breast cancer survivors (54 years, SD = 9) experiencing insomnia symptoms were randomized to receive 12 sessions of acupuncture (N = 34) or sham (N = 34; using placebo needles). Measures included the Insomnia Severity Index, Brief Fatigue Inventory, and FACT—G, obtained at baseline, mid-treatment (3 weeks), end of treatment (6 weeks), and follow-up (10 weeks). Results: Although acupuncture produced significant improvements from baseline to follow-up in insomnia symptoms, fatigue, and QOL, these improvements did not differ from sham. Compared to sham, the acupuncture produced significantly greater improvements in: 1) insomnia severity (p = 0.03) and QOL (p = 0.02) among those with greater tendency for morning chronotype; 2) fatigue (p = 0.01) among those with lower apnea risk; and 3) QOL (p < 0.001) among those with lower depression scores at baseline. Conclusions: These findings suggest that acupuncture might be more effective among certain subgroups of patients. Moderators of insomnia, fatigue, and QOL include morningness tendency, lower risk for sleep apnea and lower depression scores, respectively. Our findings on depression are in line with prior research that has found that patients with less severe depression may have a greater capacity for acupuncture response perhaps due to higher availability of serotonin. Additional research is needed to test whether acupuncture is a viable treatment option for subgroups of cancer survivors with insomnia. Clinical trial information: NCT01162018.

1 Background: The circadian timing system exerts temporal control over physiology, generating rhythms of about 24 hours. Its alteration in benign conditions has been associated with several systemic symptoms, including fatigue, appetite loss and poor sleep. However, the clinical impact of circadian disruption in cancer patients remains overlooked. We hypothesized that patients with circadian disruption would report more severe symptoms than those with robust circadian function. Methods: Data were available for 237 patients with metastatic colorectal cancer: M/F ratio: 1.66; median age: 60.4 years; range: 20.7-77.6; WHO Performance Status (PS) = 0/1: 59.7%/33.5%. We estimated the occurrence of circadian disruption using a validated parameter (the dichotomy index I < O), derived from wrist-actigraphy for at least 72 consecutive hours. Symptoms were self-reported by the patients using the EORTC QLQ-C30 questionnaire. Mann-Whitney U test was used to compare symptom severity according to the presence or absence of circadian disruption. Cohen’s d effect sizes were computed to evaluate the clinical meaningfulness of the observed differences. Subgroup analyses were performed according to gender, age, and WHO Performance Status (PS). Results: Circadian disruption (I < O lower than or equal to 97.5%) occurred in 130 (54.9%) patients. Fatigue (p < 0.0001), appetite loss (p < 0.0001), difficulty sleeping (p = 0.009), pain (p < 0.0001) and dyspnea (p = 0.001) were significantly more severe in patients with circadian disruption than in those with robust circadian function. Largest effect sizes were observed for fatigue (0.64), appetite loss (0.59) and pain (0.57). Subgroup analyses showed similar results, regardless of gender, age or PS. Conclusions: In this large international study, the presence of circadian disruption was associated with a clinically meaningfully higher severity of fatigue, appetite loss, pain, dyspnea and sleep problems. Correcting circadian dysfunction with the use of pharmacological and/or behavioural interventions could improve these often difficult-to-manage systemic symptoms.

410 Background: Sleep disruption is a prevalent problem among cancer patients and survivors, but clinical correlates of poor sleep are understudied, especially in colorectal cancer. We recently showed that metastatic breast cancer patients with poor sleep efficiency have a shorter overall survival. The primary study objective is to clarify the relationship between subjective sleep disruption and survival in patients with metastatic colorectal cancer (MCC). Methods: 240 pts (63% male, mean age=59; SD=11.0) treated for MCC in 1st to 5th line of 5-fluorouracil based chemotherapy completed the QOL Questionnaire (EORTC QLQ-C30). We considered sleep to be disrupted if patients reported little to severe trouble sleeping (scores >0 ). Multivariate Cox models included age, gender, site of primary tumor, stage at diagnosis, number of metastatic sites, performance status and prior chemotherapy. Results: 65.4% of the patients reported mild to severe sleep disruption according to EORTC QLQ-C30. Patients with trouble sleeping had poorer overall survival as compared to those without sleep disruption (HR: 1.47 [1.11 to 1.95]; p=0.008). Respective median survival times (months) were 14.2 [95% CI: 12.3 to 16.1] and 17.7 [10.0 to 25.3]. The survival benefit observed in patients without sleep disruption remained statistically significant after adjustment for other prognostic factors. The final multivariate prognostic model included subjective sleep disruption (HR: 1.49 [1.11 to 2.00]; p=0.009), number of metastatic sites (p

Purpose: Sleep disruption is prevalent in patients with cancer and survivors, but the prevalence of insomnia, a distressing sleep disorder, in these populations has yet to be determined in large-scale studies.Patients and Methods: A total of 823 patients with cancer receiving chemotherapy (mean age, 58 years; 597 female patients) reported on sleep difficulties in a prospective study.Results: During day 7 of cycle 1 of chemotherapy, 36.6% (n = 301) of the patients with cancer reported insomnia symptoms, and 43% (n = 362) met the diagnostic criteria for insomnia syndrome. Patients with cancer younger than 58 years were significantly more likely to experience either symptoms of insomnia or insomnia syndrome (χ²= 13.6; P = .0002). Patients with breast cancer had the highest number of overall insomnia complaints. A significant positive association was found between symptoms of insomnia during cycles 1 and 2 of chemotherapy (ϕ = .62, P < .0001), showing persistence of insomnia during the first two cycles of chemotherapy. Sixty percent of the patient sample reported that their insomnia symptoms remained unchanged from cycle 1 to cycle 2. Those with insomnia complaints had significantly more depression and fatigue than good sleepers (all P < .0001).Conclusion: The proportions of patients with cancer in this sample reporting symptoms of insomnia and meeting diagnostic criteria for insomnia syndrome during chemotherapy are approximately three times higher than the proportions reported in the general population. Insomnia complaints persist throughout the second chemotherapy cycle for the majority of patients with cancer in this study. Insomnia is prevalent, underrecognized, undermanaged, and understudied among patients with cancer receiving chemotherapy.