Jatoi, Aminah

97 Background: A diagnosis of EC significantly impairs patient (pt)’s survival and quality of life (QoL). We explored the relationship between pt-assessed QoL and survival. Methods: The Mayo Clinic Romero (formerly Esophageal Adenocarcinoma-Barrett's Esophagus) Registry prospectively collects clinical data during a pt's treatment course. QoL is recorded at enrollment (baseline) and annually using a validated 12-item Linear Analog Self-Assessment (LASA). A 10-pt scale is applied; ≤5 was termed clinically deficient QoL. Initial TNM staging, clinical (age, sex, prior chemotherapy, and esophagectomy), and socioeconomic variables (marital/employment status) were analyzed using Cox proportional hazards regression models. Results: 836 pts were analyzed. Median age was 64 years. 166, 506 and 164 pts had early, locally advanced, and metastatic EC, with 5-year survival rates of 75.1%, 33.6%, and 8.1%, respectively (P≤.0001). Poorer survival rates were seen in clinically QoL deficient pts in the following categories: Overall QoL (Hazard Ratio [H.R.] 0.66; 95% C.I., 0.54-0.80; P≤.0001) and LASA subsets for physical (H.R. 0.68; 95% C.I., 0.57-0.82; P≤.0001), emotional well-being (H.R. 0.69; C.I., 0.57-0.84; P=.0003), and social activity (H.R. 0.76; C.I., 0.63-0.91; P=.0028). No difference in survival was observed for marital or employment status, familial support, and financial/legal concerns. Pts with esophagectomy prior to LASA evaluation had improved survival (H.R. 0.68; 95% C.I., 0.55-0.85; P=.0005). No survival difference was observed whether pts received chemotherapy, before or after their baseline LASA evaluation. Conclusions: A strong association exists between pt’s overall survival and better overall QOL, physical, emotional well-being, and social activities. Using LASA to clinically monitor QoL at specified intervals may afford providers the opportunity to intervene when patients begin to experience QoL decline. The determinants of clinically deficit QoL and its impact on survival warrant further translational and prospective research.

221 Background: To our knowledge, no study has examined adherence to antiemetic guidelines with soon-to-be-approved or newly approved chemotherapy agents. In 2015, the Food and Drug Administration approved 18 cancer drugs, underscoring the timeliness of this topic. Here, we hypothesize that patients prescribed new drugs are at risk for poor guideline adherence, and we report on antiemetic prescribing practices and outcomes with TAS-102, a recently approved drug for metastatic colorectal cancer. Methods: This study focused on all patients prescribed TAS-102 in 2015 at the Mayo Clinic in Rochester, MN for compassionate use or routine care within 3 months of FDA approval. First-cycle antiemetic prophylaxis was examined for adherence to National Comprehensive Cancer Network Guidelines, version 1.2015, for chemotherapy of low emetogenic potential based on TAS-102 phase 3 data. Results: Among 44 patients, 28 (64%) had nausea and vomiting with prior chemotherapy. With the first cycle of TAS-102, 25 (57%) were prescribed antiemetics in a guideline-adherent manner; 15 (34%) in a non-guideline-adherent/more aggressive manner; and 4 (9%) in a non-guideline-adherent/less aggressive manner. In guideline-adherent patients, rates of nausea and vomiting were 52% and 24%, respectively, with one patient requiring an unscheduled clinic visit and another an emergency department visit and hospital admission - all for nausea and vomiting. In non-guideline-adherent/more aggressive patients (who received more prophylaxis than called for), these rates were 33% and 27%, respectively, with one patient requiring a clinic visit and emergency department visit and another an emergency department visit. In non-guideline-adherent/less aggressive patients, no nausea or vomiting was reported. Conclusions: Poor adherence to antiemetic guidelines occurred often. However, because adherence was not associated with better control of nausea and vomiting, clinical judgment should complement guidelines in patients about to receive new cancer drugs, particularly with drugs of low emetogenic potential and also in patients with a history of chemotherapy-induced nausea and vomiting.

54 Background: After diagnosis and treatment, lung cancer survivors do not return to a health-related quality of life (QOL) and function comparable to pre-diagnosis levels as observed in other adult cancer survivors. We hypothesize that inadequate attention has been paid to addressing and improving QOL and function among lung cancer survivors. Our primary goal is to evaluate existing symptoms and QOL deficits among lung cancer survivors. Methods: We are evaluating patterns of QOL deficits (scored 5 or less on the scale from 0 [worst] to 10 [best]) in relation to time of lung cancer diagnosis, treatments, progression and/or recurrence, and health-related conditions. We are collecting and analyzing relevant health care utilization for selected QOL deficits, and identifying availability, accessibility, and effectiveness of evidence-based interventions. The expected outcomes will be new knowledge on patterns of QOL deficits, quality-adjusted life years in relation to the availability, accessibility, and adequacy of needed care and the effectiveness of interventions targeting improvement in QOL and symptoms. Results: In our initial analysis, among 3,707 lung cancer survivors who were diagnosed in 1999 to 2010, post-cancer treatment, and followed through 2011, 39% (1,442) reported deficits in overall QOL, 71% fatigue, 60% dyspnea, 41% being sedentary, 17% low spiritual well-being (SWB), and 10% currently smoking cigarettes. Among the 1,442 lung cancer survivors with a deficit in overall QOL, 97.5% reported severe fatigue or dyspnea, being sedentary or smoking, or having low SWB. In the remaining 36 of the 1,442, 24 had pain, cough, poor appetite, or other symptoms; only 12 (<1%) did not report deficit in any of the measured QOL domains. Analyses are ongoing. Conclusions: Based on evidence gained to date, we are developing and testing interventions targeting symptoms and QOL deficits. We expect to gain strong evidence for recommendations in redefining and delivering care and support that are necessary for improving the health and QOL of lung cancer survivors.

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P = .0001) for appetite and 11% versus 3% (P = .02) for ≥ 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate–treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.

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]

9 Background: We examined patient-reported fatigue scores and overall survival (OS) in patients with esophageal cancer (EC) enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry (EABE). Methods: 1,481 patients enrolled in the EABE between September 2001 and January 2009 returned a baseline quality of life questionnaire including a Linear Analog Self Assessment (LASA) fatigue score which was scored on a 0-10 scale, with 0 as the most extreme fatigue. Patients were categorized as having clinically deficient fatigue (DF) if they reported a score of ≤ 5 and clinically non-deficient fatigue (nDF) if they reported a score of > 5. Kaplan-Meier methodology and Cox models explored OS in relation to fatigue scores in patients with EC. Results: A total of 667 patients with EC were included in the EABE, of which 659 returned a registry questionnaire with a valid LASA fatigue score recorded. Median age at the time of registry entry was 65 years (range 23-92). A total of 392 (59%) and 267 patients (41%) reported DF and nDF, respectively. On univariate analysis, patients with nDF had improved 5-year survival compared to patients with DF. In patients having esophagectomy prior to LASA, those reporting nDF had improved survival compared to patients with DF. Similarly, in patients having no esophagectomy prior to LASA, those with nDF had improved survival compared to those with DF. Among the 368 patients with locally advanced EC (LAEC), those reporting nDF had improved 5-year overall survival compared to patients with DF (28% vs 17%, HR = 0.67, p = 0.003). This remained significant on multivariate analysis (HR = 0.71, p = 0.015). Conclusions: Patient-reported fatigue is associated with overall survival in patients with LAEC. As a result, fatigue scores should be considered as a stratification factor in future clinical trial design. [Table: see text] No significant financial relationships to disclose.