Citations

187 Background: Patient-reported evaluations of interpersonal quality of care are essential elements of quality of cancer care assessment. At times, patients may be unable to report themselves on their care experience and systems may rely on proxy reports. The validity of this approach is dependent on the degree to which family caregiver assessments are concordant with patient assessments. Methods: A VA cohort of colorectal cancer (CRC) patients and their caregivers both completed a self-administered questionnaire on the quality of VA cancer care in 3 specific domains: surgery, chemotherapy overall and chemotherapy nursing care, all measured on a 5-point Likert scale. Because the kappa statistic penalizes skewed distributions which are commonly seen in patient satisfaction reports, agreement between patients and caregivers on perceptions of quality care were measured using Gwet’s AC2 statistic. Stratified analyses on caregiver burden, race, education, and age as well as patient’s stage of disease were used to assess variation in agreement. Results: 417 caregiver-patient dyads completed the survey (70% response rate), of whom 362 (86.8%) had surgery and 195 (46.8%) had chemotherapy. Overall agreement was high for the 3 quality of care domains: AC2 (95% CI): 0.870 (0.838, 0.903) for surgery, 0.835 (0.786, 0.884) for chemotherapy overall and 0.906 (0.868, 0.944) for chemotherapy nurses. Stratified analyses of agreement showed particular populations of higher or lower agreement; however the findings were inconsistent across the three domains and most were not statistically significant. Patients with lower stage (I-II) had higher agreement than higher stages (III-IV) (AC2: 0.967 and 0.879 respectively, P = 0.006) but only in the chemotherapy nurses domain. For the surgery domain, age was the only significant difference in agreement (0.816, 0.912, and 0.838 for < 50, 51-65, and > 65 respectively, P = 0.03). Conclusions: Family caregiver reports on the quality of CRC care were highly concordant with patient reports. Therefore, family caregivers may be able to provide reasonable proxy report on measures of quality of cancer care when patient reports are unavailable.

226 Background: Patients undergoing cancer treatment often need support from an informal caregiver to help manage symptoms. Self-efficacy (SE) in caregiving refers to confidence in being able to care for the patient’s needs. Low SE has been associated with increased caregiver burden and mental health symptoms, which in turn, can affect the quality of informal care provided. The objective of this study was to examine the relationship between caregiver training received from cancer care providers and SE in caregivers of patients with colorectal cancer (CRC). Methods: Caregivers of CRC patients diagnosed in 2009 were invited to complete a self-administered questionnaire. Caregivers were asked about specific patient problems (pain, bowel, fatigue, medications, and other). Caregiver perceptions of training adequacy and SE were assessed on a problem specific basis. The patient’s stage of disease was obtained from cancer registry data. Associations between training and SE were examined for each problem using multivariate logistic regression and adjusted for age, relationship to patient, race, care burden, level of education, stage of disease, perception of patient’s health, and general confidence as a caregiver. Results: 417 caregivers completed the survey (70% response rate), of whom 374 (90%) were female and 284 (68%) were the patient’s spouse/partner. The number of caregivers reporting inadequate training for CRC-related problems were pain 77 (38%), bowel 80 (38%), fatigue 121 (48%), medication 65 (26%), and other 101 (40%). The odds of having low SE were significantly higher among those with perceptions of inadequate training across the following CRC-related problems: pain, 10.10 (3.36, 30.39); bowel, 5.04 (1.98, 12.82); fatigue, 8.45 (3.22, 22.15); managing medications, 9.00 (3.30, 24.51); and other, 3.87 (1.68, 8.93). Conclusions: This study showed a significant association between caregiver training and SE in a cross-sectional study. Given that the perception of inadequate training among caregivers was common, further exploration of the longitudinal impact of training on caregiver SE should be done to identify interventions to help improve the experience of cancer caregivers.

LBA7005 Background: The phase III HELIOS study evaluated the first-in-class, oral covalent BTK inhibitor ibrutinib in combination with BR (BR+ibr) vs BR plus placebo (BR+plb) in patients (pts) with previously treated CLL/SLL. The preplanned interim analysis reported here showed that the primary end point was met, upon which the IDMC recommended unblinding the study. Methods: Pts received BR ( ≤ 6 cycles) and were randomized 1:1 to ibr (420 mg daily) or plb. Purine analog refractoriness was a stratification factor. Pts with del17p ( > 20% of cells) were excluded. Primary end point was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR) per IRC. Results: 578 pts were randomized (289 per arm); median age 64 yrs; 38% Rai Stage III/IV; median 2 prior therapies. 6 cycles of BR were completed in 83% and 78% of pts in the ibr and plb arms, respectively. At a median follow-up of 17.2 months, IRC-assessed PFS was significantly longer with BR+ibr vs BR+plb (median not reached vs 13.3 months; HR: 0.203, 95% CI: 0.150-0.276, P< 0.0001); PFS results were consistent across high-risk subgroups. ORR and CR/CRi rates were 82.7% vs 67.8% (P< 0.0001) and 10.4% vs 2.8%. Median OS was not reached. 90 pts (31%) in the BR+plb arm with confirmed PD crossed over to receive ibr, as permitted per the protocol. Incidence of most AEs was similar between arms. The most common all-grade AEs with BR+ibr and BR+plb were neutropenia (58.2% vs 54.7%) and nausea (36.9% vs 35.2%); most common grade 3/4 AEs were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15.0% each arm). Rates of grade 3/4 atrial fibrillation were 2.8% and 0.7%, and major hemorrhage were 2.1% and 1.7%. Fatigue (FACIT-Fatigue) was improved with BR+ibr vs BR+plb. Conclusions: The addition of ibr to BR reduced the risk of progression or death by 80% compared with BR+plb. ORR was also significantly improved. Safety of BR+ibr was consistent with the known profiles for BR and ibr. The data further support ibr as an important treatment option for pts with previously treated CLL/SLL. Clinical trial information: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745.

LBA3 Background: Irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6), combined with bevacizumab (BV) or cetuximab (CET), are first-line treatments for metastatic adenocarcinoma of the colon or rectum (MCRC). The optimal antibody combination is unknown. Methods: Patients (pts) with KRAS wild-type (wt)(codons 12 and 13) MCRC and performance status 0-1 received FOLFIRI or mFOLFOX6 (MD/pt choice at enrollment) and randomized to either CET 400 mg/m2 X 1, then 250 mg/m2 qw or BV 5 mg/kg q2w. The original study included unselected MCRC pts receiving FOLFIRI or mFOLFOX6 and randomized to CET, BV, or both. After 1,420 pts accrued the study amended as follows: only pts with KRAS wt tumors (codon 12 and 13) were included and the combination CET + BV arm was deleted. Rx continued until progression, death, unacceptable toxicity, curative surgery; treatment holidays of 4 wks permitted. Subsequent Rx not mandated. Accrual goal was 1,142 pts. One° endpoint was overall survival (OS). Results: Between November 2005 and March 2012, 3,058 unselected pts enrolled, 2,334 KRAS wt pts randomized; final N =1137 (333 pre-amend eligible retrospective KRAS test, 804 post-amend), median f/u = 24 mos; Median age – 59 y; 61% male. Chemo/BV – 559; chemo/CET – 578. FOLFIRI = 26.6%, mFOLFOX6 = 73.4%. OS analysis planned at 849 events; efficacy futility boundary crossed at 10th interim analysis on 1/29/14. OS - chemo/BV v. chemo/CET = 29.04 (25.66 - 31.21) v. 29.93 (27.56 - 31.21) mos; HR = 0.92 (0.78, 1.09) (p value = 0.34). PFS (by investigator): chemo/BV v. chemo/CET: 10.84 (9.86 - 11.4) v. 10.45 (9.66 - 11.33) mos. There were 94 pts free of disease following surgery, median f/u 40 mos (range 8.0 - 86.0). Outcomes similar by gender. On-study toxicity and deaths as expected. Analyses underway: Expanded RAS, FOLFOX v. FOLFIRI, subsequent therapies, long-term survivors, correlates. Conclusions: Chemo/CET and chemo/BV equivalent in OS in pts KRAS wt (codons 12 + 13) MCRC; either is appropriate in first line. Overall OS of 29 + mos and 8% long-term survivors confirms progress in MCRC. The preference for FOLFOX limits chemotherapy comparison. Expanded RAS and other molecular and clinical analyses may identify subsets of pts who get more or less benefit from specific regimens. Clinical trial information: NCT00265850.

446 Background: MutKRAS and mutBRAF are important predictive and prognostic markers, respectively, in colorectal cancer (CRC). However, little is known about why some tumors harbor these mutations. N0147 is a phase III adjuvant trial for stage III CRC patients (N=3397) in which patients completed questionnaires and tumor variables and KRAS/BRAF mutation status was assessed. Methods: 2,323/3,397 patients who were enrolled prior to a 2008 amendment requiring KRAS testing completed a Patient Questionnaire. Primary tumors were assessed for mutKRAS and mutBRAF using standard methods; MMR status was determined using IHC. Multivariate analysis was performed to identify predictors of mutation status. Results: 60% and 86% of mutKRAS and mutBRAF tumors were right-sided, respectively. MutKRAS was less likely if there was a family history of CRC and in ever-smokers, and was nearly mutually exclusive with mutBRAF. MutBRAF was associated with deficient MMR (dMMR), high grade histology, and 4+ positive lymph nodes at surgery. MutBRAF was more likely in patients age > 70, retired persons, ever-smokers, but was less likely in non-whites and men. Conclusions: Smoking, family history of CRC, and dMMR status are associated with lower frequency of mutKRAS , but higher mutBRAF. Both mutations tend to be right sided, and mutBRAF is more common in the elderly, females, and non-Hispanic whites. [Table: see text]

314 Background: Small bowel adenocarcinoma (SB-ACA) is rare, having little prospective data guiding management. A prior phase I study evaluated UGT1A1 genotype specific dosing of oxaliplatin, irinotecan, and capecitabine. Our prospective, multicenter clinical trial assessing tumor response in pts having metastatic SB-ACA, used a similar dosing strategy. Methods: Genotypes were determined via central lab. Previously untreated pts were dosed by UGT1A1*28 genotypes 6/6, 6/7, and 7/7 receiving 100/85/85 mg/m2 oxaliplatin d1, 150/150/75 mg/m2 irinotecan d1, and 1600/400/200 mg/m2 capecitabine (BID) d2-15 of 21 days. The study design was such that 1 confirmed response in 16 pts expanded enrollment to 33 pts, with 7 required for demonstrating efficacy. Results: 28 pts (13-6/6, 10-6/7, 5-7/7) have been enrolled [75% male, mean age 62.5 (range 41-77)]. Location of primary included: duodenum (63%), jejunum (26%), and ileum (7%), with pts having >1 metastatic site (abdominal-41%, bone-7%, liver-56%, lung-30%, nodal-52%, subcutaneous-4%, other-19%). Gr 3+ treatment related toxicity was not significantly different by genotype (50%-6/6, 44%-6/7, 20%-7/7, p=0.48) and included (pts): diarrhea(5), vomiting(5), leukopenia(5), neutropenia(7), and nausea(6). 57% (13 of 23) pts achieved responses during therapy, with a confirmed response rate of 39% (95% CI 0-58%). 18 have died, with a median follow-up of 8.3 mos (range 0-43). Conclusions: UGT1A1 genotype directed dosing with oxaliplatin, irinotecan, and capecitabine appears to result in prolonged response in this population. Larger studies are needed to determine comparability to CapeOx alone or if response/toxicity differs among genotypes. Supported by NIH Grant CA25224, Sanofi-Aventis, and Pfizer. [Table: see text]

Despite the widespread inclusion of diversity-related curricula in U.S. medical training, racial disparities in the quality of care and physician bias in medical treatment persist. The present study examined the effects of both formal and informal experiences on non-African American medical students’ ( N = 2,922) attitudes toward African Americans in a longitudinal study of 49 randomly selected U.S. medical schools. We assessed the effects of experiences related to medical training, accounting for prior experiences and attitudes. Contact with African Americans predicted positive attitudes toward African Americans relative to white people, even beyond the effects of prior attitudes. Furthermore, students who reported having witnessed instructors make negative racial comments or jokes were significantly more willing to express racial bias themselves, even after accounting for the effects of contact. Examining the effects of informal experiences on racial attitudes may help develop a more effective medical training environment and reduce racial disparities in healthcare.

Abstract Objective: Sleep disturbance and sexual dysfunction are common in menopause; however, the nature of their association is unclear. The present study aimed to determine whether sleep characteristics were associated with sexual activity and sexual satisfaction. Methods: Sexual function in the last year and sleep characteristics (past 4 wk) were assessed by self-report at baseline for 93,668 women age 50 to 79 years enrolled in the Women's Health Initiative (WHI) Observational Study (OS). Insomnia was measured using the validated WHI Insomnia Rating Scale. Sleep-disordered breathing (SDB) risk was assessed using questions adapted from the Berlin Questionnaire. Using multivariate logistic regression, we examined cross-sectional associations between sleep measures and two indicators of sexual function: partnered sexual activity and sexual satisfaction within the last year. Results: Fifty-six percent overall reported being somewhat or very satisfied with their current sexual activity, and 52% reported partnered sexual activity within the last year. Insomnia prevalence was 31%. After multivariable adjustment, higher insomnia scores were associated with lower odds of sexual satisfaction (yes/no) (odds ratio [OR] 0.92, 95% CI, 0.87-0.96). Short sleep duration (<7-8 h) was associated with lower odds of partnered sexual activity (yes/no) (≤5 h, OR 0.88, 95% CI, 0.80-0.96) and less sexual satisfaction (≤5 h, OR 0.88, 95% CI, 0.81-0.95). Conclusions: Shorter sleep durations and higher insomnia scores were associated with decreased sexual function, even after adjustment for potential confounders, suggesting the importance of sufficient, high-quality sleep for sexual function. Longitudinal investigation of sleep and its impact on sexual function postmenopause will clarify this relationship.