Atherton, Philip J.

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.

Background/Aims: The use of patient-reported outcomes in clinical trials is a focal point for research and policy. Non-compliance with planned questionnaires and missing data can threaten both internal validity and generalizability. This retrospective analysis was conducted to determine the extent of, and characteristics associated with, missing patient-reported outcomes. Methods: Study characteristics, patient characteristics and adverse events, and reasons for non-compliance were compiled from 14 closed Alliance for Clinical Trials in Oncology, Mayo Clinic Cancer Center, or Mayo Clinic Cancer Research Consortium clinical trials. Compliance rates were calculated for each patient using the number of booklets completed while the patient was on trial divided by the number of booklets the patient was expected to complete. Frequency counts and summary statistics were compiled. Logistic regression techniques were employed. Results: The 1640 included patients had a median age of 58 years and were mostly White (90.8%) and female (73.8%). Compliance rates per study ranged from 84.7% to 97.2%. The primary endpoint of overall compliance rate was 93.1%. A total of 1267 patients were compliant. Those non-compliant were slightly older (mean = 58.6 vs 57.5, p = 0.03) and had different types of cancers (p < 0.01). There were no differences in compliance according to tumor status (p = 0.66), clinical stage (p = 0.81), baseline quality of life (p = 0.42 for ≥8 vs <8 and p = 0.12 for ≥6 vs <6), or maximum adverse event grade incidence (p = 0.33 for grade 2+ incidence and p = 0.36 for grade 3+ incidence). Reasons for non-compliance included patient refusal (N = 136), booklet not administered to patient (N = 199), no clinic visit at the scheduled time for booklet completion (N = 40), and at-home-completed booklet not returned (N = 224). Logistic regression indicates gender (p < 0.01), race (p < 0.01), performance score (p = 0.02), dose delay status (p = 0.01), and incidence of grade 3 or higher adverse event (p = 0.03) were correlates of compliance. Conclusion: Patient-reported outcomes have successfully been implemented into Alliance and Mayo Clinic trials with high rates of patient compliance. Further improvement in compliance can be made with staff commitment and education. Patients are typically non-compliant only when the task at hand is burdensome, unclear, or logistically challenging. Existing tracking systems used for the other trial outcomes should be utilized to ensure successful capture of patient-reported outcomes.

AbstractObjectivesCaregiving can negatively impact well‐being. Cancer caregivers face unique challenges given the intense nature of cancer and treatment, which increases their risk for burden, poor quality of life (QOL), and burnout. Studies to reduce caregiver burden demonstrate QOL improvement and distress reduction in the short term. However, few studies exist to address long‐term benefits. We assessed changes in various QOL domains after participation in a QOL intervention for caregivers of patients having newly diagnosed advanced cancer.MethodsOur institutional review board‐approved study randomized patient–caregiver dyads to either usual care or an in‐person group intervention composed of six 90‐min sessions of structured multidisciplinary QOL components delivered over 4 weeks, with 10 follow‐up phone calls within 20 weeks. Caregivers attended four of the six sessions attended by patients. Sessions included physical therapy, coping and communication strategies, mental health education, spirituality, and social needs. Caregiver QOL (Caregiver Quality of Life Index‐Cancer Scale [CQOLC] and Linear Analogue Self‐Assessment [LASA]) and mood (Profile of Mood States‐Brief [POMS‐B]) were measured at baseline and 4, 27, and 52 weeks. Wilcoxon tests and effect sizes were used to compare the caregiver groups.ResultsOf the 131 caregivers (65 intervention and 66 usual care), 116 completed the study. Caregivers post‐intervention (at 4 weeks) had improved scores on LASA Spiritual Well‐being; POMS‐B total score, Vigor/Activity, and Fatigue/Inertia; and CQOLC Adaptation. At long term (at 27 weeks), caregivers retained improvement in POMS‐B Fatigue/Inertia and gained improvements in CQOLC Disruptiveness and Financial Concerns.ConclusionsCaregivers who received the intervention had higher QOL ratings for specific QOL domains but not for overall QOL. Although a comprehensive intervention was helpful, more specific, targeted interventions tailored for individual needs are recommended. Copyright © 2015 John Wiley & Sons, Ltd.

BACKGROUNDThe objective of this study was to explore relations between patient role preferences during the cancer treatment decision‐making process and quality of life (QOL).METHODSOne‐year cancer survivors completed a survey in 2000 as part of a larger survey conducted by the American Cancer Society. The current report was based on survey respondents from Minnesota (response rate, 37.4%). Standardized measures included the Profile of Mood States (scores were converted to have a range, from 0 to 100, with 100 indicating the best mood), the Medical Outcomes Survey 36‐item short‐form health survey (SF‐36) (standardized scores), and the Control Preferences Scale. Patients' actual and preferred role preference distributions and concordance between roles were compared with QOL scores using 2‐sample t test methodology.RESULTSThe actual role of survivors (n = 594) in cancer care was 33% active, 50% collaborative, and 17% passive. Their preferred role was 35% active, 53% collaborative, and 13% passive. Overall, 88% of survivors had concordant preferred and actual roles. Survivors who had concordant roles had higher SF‐36 Physical Component Scale (PCS) scores (P < .01), higher vitality (P = .01), less fatigue (P < .01), less confusion (P = .01), less anger (P = .046), and better overall mood (P = .01). These results were similar among both women and younger individuals (aged <60 years). Survivors who had active actual roles had higher PCS scores (P < .01), less tension (P = .04), and higher vitality (P = .04) than survivors who were either collaborative or passive. No differences existed in QOL scores according to preferred role.CONCLUSIONSSurvivors who experienced discordance between their actual role and their preferred role reported substantial QOL deficits in both physical and emotional domains. These results indicate the need to support patient preferences. Cancer 2013;119:2342–2349. © 2013 American Cancer Society.

Fatigue is the problematic symptom identified by patients with cancer. However, fatigue has not been widely examined in caregivers of patients with cancer. In this study, 131 caregivers of patients diagnosed with advanced stage cancer and actively receiving radiotherapy reported experiencing the most difficulties with fatigue (mean 46.9; on a 0-100 scale, with a 10-point difference having clinical meaning) at baseline and at a 6-month follow-up (mean 48.3). This is in sharp contrast to other domains of quality of life and functioning being rated in the 60s, 70s and 80s by the caregivers of patients with cancer. Given the level of fatigue reported by the caregivers of patients with cancer, if confirmed by other investigators in larger and more diverse samples, interventions targeting caregiver fatigue should be explored.

PurposeFatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities.Patients and MethodsAdults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change.ResultsIn total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm.ConclusionThis clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.

Purpose Up to 75% of women experience hot flashes, which can negatively impact quality of life. As hot flash physiology is not definitively understood, it cannot be assumed that effective agents represent class effects. Therefore, there is a continued need for rigorous evaluation to identify effective nonhormonal options for hot flash relief. Methods A randomized, double-blind trial evaluated citalopram at target doses of 10, 20, or 30 mg/d versus placebo for 6 weeks. Postmenopausal women with at least 14 bothersome hot flashes per week recorded hot flashes for 7 days before starting treatment and were then titrated to their target doses. The primary end point was the change from baseline to 6 weeks in hot flash score. Results Two hundred fifty-four women were randomly assigned onto this study. Data for hot flash scores and frequencies showed significant improvement in hot flashes with citalopram over placebo, with no significant differences among doses. Reductions in mean hot flash scores were 2.0 (23%), 7.0 (49%), 7.7 (50%), and 10.7 (55%) for placebo and 10, 20, and 30 mg of citalopram, respectively (P ≤ .002). Improvement in secondary outcomes, such as the Hot Flash Related Daily Interference Scale, was statistically superior in the 20-mg arm. Citalopram was well-tolerated, with no significant negative adverse effects. Conclusion Citalopram is an effective, well-tolerated agent in managing hot flashes. There does not appear to be a significant dose response above 10 mg/d, but broader helpful effects of the agent appear to be more evident at 20 mg/d.

Abstract Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (103–109 TCID50). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54–277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3–38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients. Cancer Res; 70(3); 875–82

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.