Trial Outcome Index Research Articles

Associations between health-related quality of life and physical activity in bladder cancer survivors: A cross-sectional study.

432 Background: Physical activity has been shown to significantly improve health-related quality of life (HRQOL) and survivorship in a variety of cancer patients. However, little is known about the physical activity patterns of bladder cancer survivors and how these are related to HRQOL in the United States. Our objective was to describe HRQOL and self-reported physical activity patterns and examine the association between these measures in a large cohort of bladder cancer survivors. Methods: Bladder cancer survivors identified through an institutional database were mailed a survey that included the Functional Assessment of Cancer Therapy Bladder Cancer (FACT-Bl) and the International Physical Activity Questionnaire (IPAQ-L). Results: A total of 466 subjects (49% response rate) completed the survey. The mean age was 73 years, 80% were male, and 88% were White. Linear regression indicated a positive correlation between physical activity and physical well being (PWB, P < 0.001), emotional well being (EWB, P < 0.001), and functional well being (FWB, P < 0.001) subscales, as well as the FACT-Bl (P < 0.001), FACT general (P < 0.001), and trial outcome index (TOI, P < 0.001) composite scores. Conversely, total daily sitting time was negatively correlated with all of the aforementioned indices. Adjusting for demographic factors did not alter the findings. Conclusions: Physical activity is positively associated with HRQOL in bladder cancer survivors. Further studies investigating the causal relationship between physical activity and HRQOL in the post-treatment setting in bladder cancer survivors are warranted.

Primary Results of the Health-Related Quality of Life Assessment from the Phase III Gadolin Study of Obinutuzumab Plus Bendamustine Compared with Bendamustine Alone in Patients with Rituximab-Refractory, Indolent Non-Hodgkin Lymphoma

BackgroundMeaningful improvement in, or maintenance of, pre-treatment health-related quality of life (HRQoL) is important for rituximab-refractory (R-ref), indolent non-Hodgkin lymphoma patients. GADOLIN (NCT01059630) is an open-label, phase III study of bendamustine (B) with or without obinutuzumab (GA101; Gazyva/Gazyvaro; G) in patients with CD20+ R-ref, indolent non-Hodgkin lymphoma. In GADOLIN, independent review facility (IRF)-assessed median progression-free survival (PFS) was 14.9 months (mo) in the B arm and not reached in the G-B arm (HR=0.55; 95% CI, 0.40, 0.74; p=0.0001), with an acceptable safety profile. Here, we present patient-reported HRQoL data from GADOLIN.MethodsThe Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire (Webster K, et al. Qual Life Res 2005;14:2103) was used to assess overall HRQoL, physical and functional well-being, and disease- and treatment-related symptoms. It was administered on day 1 of cycles 1, 3 and 5 during treatment, at the end of induction (EOI) treatment and every other month for 2-years (where non-progressing G-B patients received G maintenance and B patients were observed), and during follow-up. Time to ³6 point worsening from baseline in the FACT-Lym Trial Outcome Index (TOI) was estimated for each treatment group using a Kaplan-Meier curve. Minimally important differences at the individual subscale and total score levels were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma subscale (³3 points), TOI (³6 points), and lymphoma total score (³7 points).ResultsThe primary study analysis was undertaken when 396 patients had been randomized (194 to G-B and 202 to B [198 treated]); median observation time was 21 mo. Baseline characteristics were balanced between arms. Median age was 63 years and patients had a median of two prior therapies. Questionnaire completion rates were generally good and balanced in the G-B vs B arms (91.2% vs 89.1% at baseline, 74.2% vs 69.8% at EOI, and 33.0% vs 31.2% at final follow up, respectively). Time to ³6 point worsening from baseline on the FACT-Lym TOI was 8.0 mo (95% CI, 5.8, 15.1) in the G-B arm and 4.6 mo (95% CI, 3.8, 6.4) in the B arm (HR, 0.74; 95% CI, 0.56, 0.98; Figure 1). In addition, a greater proportion of patients reported meaningful improvement on the lymphoma subscale, lymphoma TOI, and total score in the G-B arm than in the B arm throughout the study (Table 1).ConclusionsG combined with B, followed by G maintenance, resulted in a greater proportion of patients reporting a meaningful improvement in HRQoL throughout the course of the study. This improvement occurred even during induction, despite similar clinical response rates. A longer time to clinically meaningful deterioration of lymphoma-related HRQoL compared with patients who received B alone was also observed. These results are consistent with the improvement in PFS and suggest that the improvement in PFS is not at the expense of an increase in treatment-related toxicity that could lead to a reduction in a patient's HRQoL. [Display omitted] [Display omitted] DisclosuresCheson:Celgene: Consultancy, Research Funding; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; MedImmune: Research Funding; Teva: Research Funding; Pharmacyclics: Consultancy, Research Funding; Ascenta: Research Funding; Roche/Genentech: Consultancy, Research Funding; Astellas: Consultancy. Off Label Use: Obinutuzumab (GA101; Gazyva/Gazyvaro) is a CD20-directed cytolytic antibody and is indicated, in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia). This abstract reports on bendamustine with or without obinutuzumab in patients with CD20+ R-ref, indolent non-Hodgkin lymphoma.. Trask:Genentech: Employment. Gribben:Janssen: Honoraria; Pharmacyclics: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria; Roche/Genentech: Honoraria. Dimier:Roche: Employment. Kimby:Pfizer: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Thieblemont:St. Louis Hospital, Paris, France: Employment. Wassner Fritsch:Roche: Employment. Sehn:Roche/Genentech: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria.

Comparative Effectiveness of Fludarabine and Busulfan Versus Fludarabine and 400 cGy Total Body Irradiation Reduced Intensity Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation for AML/MDS

Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P<0.001) and in the first year was 40 vs. 16 days (P<0.001). Post-transplant outcomes are shown in the Table. The most common causes of death were relapse and infection for both the FluTBI (44% and 13%) and BuFlu (57% and 14%) groups. Quality of life assessments using the FACT-BMT were performed pre-alloHCT, at day 100, 6 months and 1 year. There was no difference in physical, social, emotional, and functional well-beings, additional concerns, trial outcome index or total score between the two groups at baseline or any of the follow-up timepoints. We conclude that alloHCT using FluTBI or BuFlu reduced intensity conditioning regimens results in comparable outcomes in patients with AML/MDS. The greater RBC transfusion requirement and need for inpatient hospitalization with the BuFlu regimen have implications for healthcare resource utilization. Future prospective investigation comparing these regimens with larger patient cohorts and cost-effectiveness analyses are warranted.Table 1Patient outcomesVariableFluTBI N (%)BuFlu N (%)P-valueT-cell complete donor chimerism29 (78)26 (81)0.83Graft failure/rejection3 (8)3 (9)0.87Grade II-IV acute GvHD13 (34)17 (52)0.24Grade III-IV acute GvHD3 (8)6 (18)0.21Any Chronic GvHD16 (42)14 (42)0.91Extensive chronic GvHD8 (21)13 (39)0.06CMV reactivation12 (32)13 (39)0.66Fungal Infection2 (5)1 (3)0.83Relapse (2-years)20 (53)17 (52)0.96100 day mortality13 (95% CI 6-29 )9 (95% CI 3-26 )0.59Non-relapse mortality (2-years)29 (95% CI 15-44)29 (95% CI 14-45)0.56Relapse mortality (2-years)34 (95% CI 20-49)36 (95% CI 20-53)0.86Overall survival (2-years)37 (95% CI 22-52)35 (95% CI 19-51)0.73 DisclosuresMajhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Age and Gender Moderate the Impact of Early Palliative Care in Metastatic Non-Small Cell Lung Cancer.

Studies demonstrate that early palliative care (EPC) improves advanced cancer patients' quality of life (QOL) and mood. However, it remains unclear whether the role of palliative care differs based upon patients' demographic characteristics. We explored whether age and gender moderate the improvements in QOL and mood seen with EPC. We performed a secondary analysis of data from a randomized controlled trial of patients with metastatic non-small cell lung cancer. Patients received either EPC integrated with oncology care or oncology care alone. We assessed the degree to which QOL (Trial Outcome Index [TOI]) and mood (Hospital Anxiety and Depression Scale [HADS] and Patient Health Questionnaire 9 [PHQ-9]) outcomes at week 12 varied by patient age (<65) and gender. The week 12 data of 107 patients are included in this analysis. At 12 weeks, younger patients receiving EPC reported better QOL (TOI mean = 62.04 vs. 49.43, p = .001) and lower rates of depression (HADS-Depression = 4.0% vs. 52.4%, p < .001; PHQ-9 = 0.0% vs. 28.6%, p = .006) than younger patients receiving oncology care alone. Males receiving EPC reported better QOL (TOI mean = 58.81 vs. 48.30, p = .001) and lower rates of depression (HADS-Depression = 18.5% vs. 60.9%, p = .002; PHQ-9 = 3.8% vs. 34.8%, p = .008) than males receiving oncology care alone. At 12 weeks, QOL and mood did not differ between study groups for females and older patients. Males and younger patients who received EPC had better QOL and mood than those who received oncology care alone. However, these outcomes did not differ significantly between treatment groups for females or older patients. This study found that early palliative care improves patients' quality of life and mood differentially based on their age and gender. Specifically, males and younger patients receiving early palliative care experienced better quality of life and mood than those receiving oncology care alone. Conversely, females and older patients did not experience this treatment effect. Thus, palliative care interventions may need to be tailored to patients' age- and gender-specific care needs. Studying how patients' demographic characteristics affect their experience with palliative care will enable the development of interventions targeted to the distinct supportive care needs of patients with cancer.

Objectively measured physical activity and sedentary behavior and quality of life indicators in survivors of breast cancer.

The primary purpose of the current study was to determine prospective associations of accelerometer-assessed physical activity intensity and sedentary time with health-related quality of life (HRQOL) indicators among survivors of breast cancer. A total of 358 survivors of breast cancer wore an accelerometer for 7 days at baseline to assess different activity intensities (light, lifestyle, and moderate to vigorous) and sedentary behavior. Six months later, survivors completed online questionnaires that assessed HRQOL indicators (disease-specific HRQOL, fatigue, depression, and anxiety) and relevant covariates. Relationships between activity and sedentary behavior quartiles and HRQOL indicator scores were examined using generalized liner models with Bonferroni multiple comparison adjustment. After adjustment for covariates and sedentary time, each increasing lifestyle activity quartile was associated with reduced fatigue duration (P for trend, .03). Each increasing baseline moderate-to-vigorous physical activity (MVPA) quartile was found to be significantly associated with higher Physical Well-Being, Functional Assessment of Cancer Therapy-Breast (FACT-B) total, and trial outcome index scores; fewer breast cancer-specific concerns; and lower fatigue interference, and these differences were statistically and clinically significant between survivors in quartile 1 and quartile 4. After controlling for covariates and MVPA, relationships between sedentary time and HRQOL were mostly null with the exception of lower fatigue duration. Objectively measured MVPA was found to be positively associated with many HRQOL indicators. Lifestyle activity was found to be only inversely associated with fatigue duration whereas sedentary time was found to be positively associated with fatigue duration. Future research is warranted to explore these relationships further.

Pilot Study of a Brief Behavioral Intervention for Dyspnea in Patients With Advanced Lung Cancer

ContextDyspnea is a common symptom in patients with advanced cancer that interferes with functional ability and quality of life (QOL). Although few evidence-based treatments for dyspnea exist, prior studies show support for nonpharmacological interventions that include elements of cognitive-behavioral therapy. ObjectivesTo examine the feasibility and utility of delivering a brief behavioral intervention for dyspnea in patients with lung cancer. MethodsFor this single-group pilot study, eligible patients included those with advanced lung cancer (Stage III or IV non-small cell or extensive-stage small cell lung cancer) receiving outpatient cancer treatment who reported at least moderate breathlessness. The manualized intervention consisted of two sessions in which nurse practitioners taught participants breathing and relaxation techniques within the infusion clinic and encouraged home practice. Participants completed measures of breathlessness (Modified Medical Research Council Dyspnea Scale), QOL (Functional Assessment of Cancer Therapy-Lung Trial Outcome Index), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale) at baseline and within six weeks after enrollment. ResultsOf the 32 patients enrolled in the study (56.3% females; mean age 63.34 [SD] = 7.96 years), 84.4% (N = 27) completed all study procedures. Comparing the baseline to postassessments, we found significant improvements in Modified Medical Research Council Dyspnea Scale (P < 0.001), Functional Assessment of Cancer Therapy-Lung Trial Outcome Index (P = 0.01), and Hospital Anxiety and Depression Scale-depression subscale (P < 0.001) scores. ConclusionIn this sample of patients with advanced lung cancer and dyspnea, we observed a high completion rate for the two-session behavioral intervention. Patients also reported improvements in dyspnea, QOL, and mood. Follow-up randomized controlled trials are needed to examine the efficacy of brief behavioral interventions for cancer-related dyspnea.

Abstract P3-12-01: Impact of treatment on quality of life (QOL) and menstrual history (MH) in the NSABP B-36: A randomized phase III trial comparing six cycles of 5-fluorouracil (5-FU), epirubicin, and cyclophosphamide (FEC) to four cycles of adriamycin and cyclophosphamide

Abstract Background NSABP B-36 compares 6 cycles of FEC-100 with 4 cycles of standard AC in pts with node-negative breast cancer. As reported separately, no significant differences between the two treatment arms were observed in the primary endpoint of disease-free survival or in the secondary endpoints of overall survival, recurrence-free, or distant recurrence-free intervals. Greater toxicity was reported in pts who received FEC compared to AC. We present here the results of the QOL and MH studies obtained prospectively in conjunction with the treatment study. We hypothesized that pts on FEC would experience greater treatment toxicity in the first 12 months of the study, and would have greater rates of amenorrhea at 18 months compared to pts on AC. Methods Among the 1,357 pts enrolled in the QOL study, 1,332 (675 AC, 657 FEC) submitted the baseline form and had QOL follow-up (fup) information. Pts completed: 1) the FACT-B instrument; 2) a symptom checklist; and 3) the SF-36 Vitality Scale, all at baseline, day 1 of cycle 4, and at 6, 12, 18, 24, 30, and 36 months after random assignment. FACT-B Trial Outcome Index (TOI), symptom severity, and vitality scores were compared between the two treatment arms using a mixed model for repeated measures analysis with adjustment for the baseline scores, type of surgery, and hormone receptor status, examining the first 12 months and the later time points separately. Menstrual status was collected at baseline for all enrolled pts, with subsequent assessments on day 1 of cycle 4, and at 6, 12, 18, 24, 30, and 36 months for pts with menstrual bleeding within 12 months prior to random assignment and not having had a hysterectomy and/or bilateral oophorectomy (1, 096 pts). Post-chemotherapy amenorrhea was defined as the lack of menstrual periods during the 12 months preceding the 18-month fup evaluation. Data from 921 pts (475 AC, 446 FEC) were available for analysis. Logistic regression, adjusted for type of surgery and hormone receptor status, was used to test for association of amenorrhea status and treatment. Results Both TOI and vitality scores were worse for pts on FEC compared to those on AC at 6 months (p&amp;lt;0.01) with no significant difference at 12 months and beyond. No significant differences in symptom severity between the two treatment arms were observed. The rates of post-chemotherapy amenorrhea were significantly different between FEC and AC (66.8% vs. 58.7%, p=0.01) with positive hormone receptor status as an independent risk factor (p=0.03). Conclusions Women receiving FEC had diminished QOL at 6 months after random assignment, but no difference at 12 months or later. Premenopausal women receiving FEC experienced a higher rate of post-chemotherapy amenorrhea than women receiving AC. Support NCI grants U10-CA-12027, -37377, -69974, -69651 and -44066-26, and Pharmacia &amp; Upjohn Company, a subsidiary of Pfizer, Inc. Citation Format: Patricia A Ganz, John W Wilson, Hanna Bandos, André Robidoux, Alexander HG Paterson, Johnathan Polikoff, Luis Baez-Diaz, Adam M Brufsky, Louis Fehrenbacher, Aroop Mangalik, Patrick J Ward, Louise Provencher, John T Hamm, Philip J Stella, Robert L Carolla, Richard G Margolese, Henry R Shibata, Edith A Perez, Norman Wolmark. Impact of treatment on quality of life (QOL) and menstrual history (MH) in the NSABP B-36: A randomized phase III trial comparing six cycles of 5-fluorouracil (5-FU), epirubicin, and cyclophosphamide (FEC) to four cycles of adriamycin and cyclophosphamide [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-01.

Psychometric properties of Functional Assessment of Cancer Therapy-Prostate (FACT-P) in Chinese patients with prostate cancer.

The aim of the study was to assess the validity, reliability and sensitivity of the FACT-P (version 4) in Chinese males with prostate cancer. Construct validity was assessed using Spearman's correlation test against the 12-item Short Form Health Survey (SF-12v2). Internal consistency and test-retest reliability were assessed using Cronbach's α coefficient and intra-class correlation coefficient, respectively. Sensitivity was determined by performing known-group comparisons by independent t test. FACT-P subscale scores had a moderate correlation with the corresponding SF-12v2 domain score that conceptually measures the similar construct providing evidence for adequate construct validity. Internal consistency was acceptable (α: 0.687-0.900) for all subscales aside from the Prostate Cancer Subscale (α: 0.505) and Trial Outcome Index (α: 0.562). FACT-P subscale and total scores showed good test-retest reliability (range 0.753-0.913). All total scales and most of the subscales were sensitive in detecting differences between patients with different levels of functional impairment but not different cancer stages or levels of prostate-specific antigen. The measure is a valid and reliable measure to assess the health-related quality of life of Chinese males with prostate cancer. The FACT-P is sensitive to detect difference between patients with varying functional status.

Post-operative exercises after breast cancer surgery: Results of a RCT evaluating standard care versus standard care plus additional yoga exercise

IntroductionThere is a lack of standardisation in the guidelines for post-operative exercises following breast cancer surgery. Adherence to exercise programmes is low, and complementary therapies such as yoga often appeal to patients and may encourage practise. A step-by-step guide to yoga DVD was evaluated in addition to the standard care exercises (SC) compared to SC alone. MethodsWomen with early-stage breast cancer were randomised to SC plus or minus a yoga DVD for 10-weeks. Patient-reported outcomes were collected at baseline, 10 weeks and 6 months. The primary study-endpoint was the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Treatment-Breast; a recognised quality of life (QoL) tool with an arm morbidity subscale (FACT-B+4). Results92/103 (89%) women were randomised to the study. The SC group reported practising post-operative exercises more often than the yoga DVD group. There was a 69% improvement from baseline in FACT-B+4 TOI, which included an arm subscale, at 10 weeks and 6 months in the SC group. This was 62% and 81% respectively for the yoga DVD group. Numbness in the affected arm was greater in the SC group (OR=2.5, 95% CI: 1.1, 5.6) and in patients receiving chemotherapy (OR=2.17, 95% CI: 1, 4.6). Despite no group differences, 74% of women would definitely recommend following the yoga DVD after surgery. ConclusionsPractising post-operative exercises does improve arm and shoulder morbidity following breast cancer surgery. The addition of a self-practise general yoga programme was well received and appeared to improve QoL at 6 months.

Conservative interventions for preventing clinically detectable upper-limb lymphoedema in patients who are at risk of developing lymphoedema after breast cancer therapy.

Conservative interventions for preventing clinically detectable upper-limb lymphoedema in patients who are at risk of developing lymphoedema after breast cancer therapy.

Quality of Life Analyses from the Randomized, Open-Label, Phase III PointBreak Study of Pemetrexed-Carboplatin-Bevacizumab followed by Maintenance Pemetrexed-Bevacizumab Versus Paclitaxel-Carboplatin-Bevacizumab followed by Maintenance Bevacizumab in Patients with Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer

Treatment impact on quality of life (QoL) informs treatment management decisions in advanced nonsquamous non-small-cell lung cancer (NS NSCLC). QoL outcomes from the phase III PointBreak trial are reported. Chemonaive patients (n = 939) with stage IIIB/IV nonsquamous non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status 0 to 1 were randomized (1:1) to pemetrexed-carboplatin-bevacizumab (pemetrexed arm) or paclitaxel-carboplatin-bevacizumab (paclitaxel arm). Patients without progressive disease received maintenance pemetrexed-bevacizumab (pemetrexed arm) or bevacizumab (paclitaxel arm). QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-General (FACT-G), FACT-Lung (FACT-L), and FACT/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) instruments. Subscale scores, total scores, and trial outcome indices were analyzed using linear mixed-effects models. Post hoc analyses examined the association between baseline FACT scores and overall survival (OS). Mean score differences in change from baseline significantly favored the pemetrexed arm for the neurotoxicity subscale score, FACT-Ntx total scores, and FACT-Ntx trial outcome index. They occurred at cycle 2 (p < 0.001) and persisted through induction cycles 2 to 4 and six maintenance cycles. Investigator-assessed, qualitative, drug-related differences in grade 2 (1.6% versus 10.6%) and grade 3 (0.0% versus 4.1%) sensory neuropathy and grade 3/4 fatigue (10.9% versus 5.0%, p = 0.0012) were observed between the pemetrexed and paclitaxel arms. Baseline FACT-G, FACT-L, and FACT-Ntx scores were significant prognostic factors for OS (p < 0.001). Randomized patients reported similar changes in QoL, except for less change from baseline in neurotoxicity on the pemetrexed arm; investigators reported greater neurotoxicity on the paclitaxel arm and greater fatigue on the pemetrexed arm. Higher baseline FACT scores were favorable prognostic factors for OS.

Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology–Gynecologic Oncology Group protocol 240)

GOG 240 was a practice-changing randomised phase 3 trial that concluded that chemotherapy plus bevacizumab for advanced cervical cancer significantly improves overall and progression-free survival, and the proportion of patients achieving an overall objective response, compared with chemotherapy alone. In this study, we aimed to analyse patient-reported outcomes in GOG 240. Eligible adult participants (aged ≥18 years) had primary stage IVB or recurrent or persistent carcinoma of the cervix with measurable disease and GOG performance status of 0-1. Participants were randomly assigned by web-based permuted block randomisation (block size 4) in a 1:1:1:1 ratio to the four treatment groups: cisplatin (50 mg/m(2) intravenously on day 1 or 2 of the treatment cycle) and paclitaxel (135 mg/m(2) intravenously over 24 h or 175 mg/m(2) intravenously over 3 h on day 1), with or without bevacizumab (15 mg/kg intravenously on day 1 or 2), or paclitaxel (175 mg/m(2) over 3 h on day 1) and topotecan (0·75 mg/m(2) for 30 min on days 1-3) with or without bevacizumab (15 mg/kg intravenously on day 1). Treatment assignment was concealed at randomisation (everyone was masked to treatment assignment, achieved by the use of a computer encrypted numbering system at the National Cancer Institute) and became open-label when each patient was registered to the trial. Treatment cycles were repeated every 21 days until disease progression or unacceptable toxicity, whichever occurred first. The coprimary endpoints of the trial were overall survival and safety; the primary quality-of-life endpoint was the score on the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index (FACT-Cx TOI). For our analysis of patient-reported outcomes, participants were assessed before treatment cycles 1, 2, and 5, and at 6 and 9 months after the start of cycle 1, with the FACT-Cx TOI, items from the FACT-GOG-Neurotoxicity subscale, and a worst pain item from the Brief Pain Inventory. All patients who completed baseline quality-of-life assessments and at least one further follow-up assessment were evaluable for quality-of-life outcomes. This study is registered with ClinicalTrials.gov, number NCT00803062. Between April 6, 2009, and Jan 3, 2012, a total of 452 patients were enrolled in the trial, of whom 390 completed baseline quality-of-life assessment and at least one further assessment and were therefore evaluable for quality-of-life outcomes. In these patients, patient-reported outcome completion declined from 426 (94%) of 452 (at baseline) to 193 (63%) of 307 (9 months post-cycle 1), but completion rates did not differ significantly between treatment regimens (p=0·78). The baseline FACT-Cx TOI scores did not differ significantly between patients who received bevacizumab versus those who did not (p=0·27). Compared with patients who received chemotherapy alone, patients who received chemotherapy plus bevacizumab reported FACT-Cx TOI scores that were an average of 1·2 points lower (98·75% CI -4·1 to 1·7; p=0·30). Improvements in overall survival and progression-free survival attributed to the incorporation of bevacizumab into the treatment of advanced cervical cancer were not accompanied by any significant deterioration in health-related quality of life. Patients responding to anti-angiogenesis therapy who maintain an acceptable quality of life could be suitable at progression for treatment with other novel therapies that might confer additional benefit. National Institutes of Health.

Impact of a telehealth intervention on quality of life and symptom distress in patients with head and neck cancer.

Patients undergoing treatment for head and neck cancer commonly experience signi•cant changes in quality of life (QoL) and levels of symptom distress. It is not known if a telehealth intervention would mitigate these changes. To evaluate the impact of a telehealth intervention on QoL and symptom burden in patients undergoing initial treatment for head and neck cancers. A randomized clinical trial comparing the impact on QoL and symptom distress of telehealth intervention and standard care was conducted with 80 patients (45 treatment, 35 control) who had been diagnosed with head or neck cancer and were receiving 1 or more treatment modalities. Treatment group participants responded daily to symptom management algorithms using a simple telehealth messaging device. QoL was evaluated by the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACTHN) and symptom burden by the Memorial Symptom Assessment Scale (MSAS). Control group participants completed assessments while they received routine care. In the posttreatment phase, the telehealth participants had signi•cantly better scores than the controls for physical well-being (20.6 vs 17.0, P = .02) and trial outcome index (59.9 vs. 50.2, P = .04) on the FACT-HN, and total scores on the MSAS (0.9 vs. 1.2, P = .04). The moderate sample size of 80 patients limits the power to measure more subtle impacts of the intervention. Using telehealth to provide support to patients with head and neck cancer during the acute phase of treatment improved some aspects of posttreatment QoL and symptom burden.

Prognostic Significance of Quality of Life in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Patient-reported outcomes and quality of life (QOL) are becoming increasingly recognized as important factors in cancer clinical trials and patient care. Many studies have described the predictive value of QOL in cancer survival beyond the standard clinical measures. Allogeneic hematopoietic cell transplant (HCT) is the only curative option for many hematologic malignancies, however is often complicated by a high incidence of treatment related morbidity and mortality. While the HCT comorbidity index (HCT-CI) has been developed to assess the impact of co-morbidities and risk of death in patients undergoing allogeneic HCT, we hypothesized that QOL prior to transplant may also add to the assessment of patient risk for post-transplant survival. We thus undertook an analysis to determine the prognostic impact of pre-transplant QOL scores, as captured by the FACT-BMT, on post-HCT non-relapse (NRM) and overall mortality.From 2003-2012, 512 adult patients underwent a first allogeneic transplant at our institution. Prospective psychometric instruments (FACT-BMT) were administered to 409 patients. No significant differences were found between the study cohort and the 103 patients who did not participate in a baseline assessment during the same time period in regards to transplant outcomes or baseline characteristics, except for year of transplant, higher proportion of females, and a shorter time from diagnosis to transplant in the study cohort. Patients with QOL assessments underwent HCT for malignant (n=395) and non-malignant (n=14) diseases. Most patients (n=314, 77%) underwent a myeloablative HCT, while the remaining received a reduced-intensity (RIC) preparative regimen (n=95, 23%). At the time of analysis, median time to follow up was 49 months, range (1.2-128). 41% of patients remained alive, 23% of patients died from relapse and 36% from NRM. We examined the association of overall mortality and NRM with: (1) individual QOL domains captured by the FACT-BMT instrument (physical wellbeing (PWB) functional wellbeing (FWB), social wellbeing (SWB), emotional wellbeing (EWB) and additional concerns (AC), (2) trial outcome index (TOI; PWB+FWB+AC), and (3) total score. In univariable analysis, poor performance status, high risk disease, and high (≥3) HCT-CI score were found to be significant factors for overall mortality but not NRM; umbilical cord, unrelated and mismatched donor transplants were risk factors for both overall mortality and NRM. Additionally, worse FACT-BMT PWB scores (HR 0.97, 95% CI 0.94-0.99, p=0.004), TOI score (HR 0.94, 95% CI 0.88-0.99, p=0.043), and total score (HR 0.95, 95% CI 0.90-0.99, p=0.043) were significant variables associated with overall mortality, but not NRM. In multivariable analyses evaluating individual FACT-BMT QOL domains and adjusted for patient and disease factors, including HCT-CI score, only PWB score was associated with overall mortality, but not NRM (Table). TOI scores which is representative of changes in physical and functional outcomes were associated with overall mortality but not NRM (Table). Total score was not associated with overall or NRM (Table). High (≥3) HCT-CI score remained prognostic for adverse overall mortality but not NRM in all multivariable models.In summary, QOL assessments, particularly PWB and the TOI, may provide independent prognostic information beyond standard clinical measures. While the magnitude of difference of these measures is small, further study on how QOL may be reflected by disease burden or co-morbidities and how patient-reported outcomes and behaviors may further impact survival is warranted.Table:Results of multivariable analysis (separate models were built for each QOL domain)VariableOverall MortalityNon-relapse mortalityHR95% CIP-valueHR95% CIP-valuePWB*0.970.94-0.990.030.970.94-1.010.20SWB*1.000.97-1.040.760.990.95-1.030.57EWB*1.000.96-1.040.950.990.94-1.040.57FWB*0.950.95-1.010.161.000.96-1.050.80AC†1.040.95-1.140.381.030.91-1.170.60TOI‡0.930.87-0.990.040.970.89-1.070.56Total score‡0.950.90-1.000.060.970.90-1.050.46Abbreviations: PWB- physical well-being; SWB- social well-being; EWB- emotional wellbeing; FWB- functional well-being; AC- additional concerns; TOI- total outcome index*per 1 point increase†per 5 point increase‡per 10 point increase DisclosuresNo relevant conflicts of interest to declare.

Preliminary International Validation of the Quality of Life in Myelodysplasia Scale (QUALMS)

Background: Disease-specific measures of quality of life (QOL) can allow for improved assessment of disease-specific symptomatology and psychosocial factors. We recently reported on the development of the QUALMS, a 33-item QOL assessment tool for patients with myelodysplastic syndromes (MDS). We now report preliminary internal consistency and validity results from an international prospective study.Methods: From December of 2013 to July of 2014,an international cohort of MDS patients completed the QUALMS as well as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy Anemia Scale (FACT-An). Eligible patients were 18 or older, and had to have biopsy-proven MDS; those who had undergone stem cell transplantation were excluded. Baseline medical record review was performed at the time of enrollment to document key clinical and laboratory data, including bone marrow pathology and treatments; a second QUALMS administration and medical record review is planned for each patient to assess responsiveness. Participants were recruited from MDS centers across the United States, Canada and Italy. Individual QUALMS items were scored on a 5-point scale ranging from “Never” to “Always”. Overall mean score was calculated by transforming the raw mean to a 100 point scale, with higher scores indicating better MDS-related QOL. Baseline QUALMS scores were compared to clinical factors such as hemoglobin (Hg) and transfusion dependence as well as with scores on the other QOL scales. Preliminary exploratory factor analysis was also undertaken to identify candidate subscales.Results: As of this analysis, 201 patients had enrolled. The mean age was 71.7 years; there were 55% men, and the IPSS distribution was 44% LO, 43% INT-1, 10% INT-2, 1% HI and 2% unclassifiable. The majority of patients (53%) were receiving an erythropoiesis-stimulating agent, hypomethylating agent or lenalidomide, and 29% of the overall cohort was transfusion-dependent. The geographical distribution was as follows: 20% from the Dana-Farber Cancer Institute (Boston, MA); 9% from Columbia University (New York, NY); 15% from the Moffitt Cancer Center (Tampa, FL); 25% from the Odette Cancer Center (Toronto, Canada); and 31% from two GIMEMA hospitals (Rome and Sardegna, Italy). Scores on the QUALMS ranged from 19 to 78; the mean and median scores were 49.6 and 50.0 respectively. The measure had excellent internal consistency (α=.91), and was moderately correlated with the EORTC QLQ-C30: correlations (r’s) with the global health status scale, functional scales (i.e., physical, role, emotional, cognitive and social) as well as fatigue, nausea and pain scales ranged from 0.33 to 0.63 (all p’s <.001). Moderate correlations were also found with the FACT Anemia Score and the FACT Trial Outcomes Index (r’s 0.70 and 0.73; p’s <.001). Patients with Hg less than 10 had consistently lower QUALMS scores than those with higher Hg (46.9 v 51.7, p =.008), as did those who were transfusion-dependent (44.3 v 52.1; p <.001). QUALMS scores significantly differed between those with lower (LO/INT-1) versus higher (INT-2/HI) IPSS scores (50.0 v 44.3, p <.05). Finally, preliminary factor analysis revealed several potentially useful QUALMS subscales, including physical burden, emotional burden, disease information and uncertainty, and disease-associated positives.Conclusions: Our analyses suggest that the QUALMS is a valid measure of disease-specific QOL in MDS. As would be expected, it is moderately (but not highly) related to measures of cancer- and anemia-related QOL, but contributes unique, disease-specific QOL information valued by patients. The QUALMS is a new tool that promises to help clinicians and researchers to better evaluate MDS-specific QOL in the modern treatment era. DisclosuresNo relevant conflicts of interest to declare.

Which patients experience improved quality of life (QOL) and mood from early palliative care (PC)?

16 Background: Prior research has demonstrated improved patient outcomes with early PC integrated with standard oncology care (SC), but it is not clear if these associations exist in all patient demographic groups. This study examined whether early integrated PC was associated with improvements in QOL and mood in different demographic groups. Methods: This is a secondary analysis of data from a randomized controlled trial of 151 patients with newly diagnosed metastatic non-small-cell lung cancer presenting to an outpatient cancer center from June 2006 to July 2009. Patients received either early PC integrated with SC or SC alone. QOL (Functional Assessment of Cancer Therapy–Lung [FACT-L] and Trial Outcome Index [TOI]) and mood (Hospital Anxiety and Depression Scale depression subscale [HADS-D] and Patient Health Questionnaire 9 [PHQ-9], scored categorically) were assessed at baseline and 12 weeks. Data were analyzed to assess relationships between outcome variables and patient demographic characteristics (age and gender). Results: At baseline, QOL and mood outcomes did not differ significantly between treatment groups for age or gender. At 12 weeks, the PC group showed better QOL and lower rates of depressive symptoms for males and those &lt; age 65. In comparison, QOL and mood did not differ significantly between study groups for females and those ≥ age 65. Conclusions: Males and patients &lt; age 65 experienced improved QOL and mood with early, integrated PC. However, these outcomes did not differ significantly between treatment groups for patients ≥ age 65 or for females. Further research should confirm these findings and tailor interventions to meet the unique needs of all patients with cancer. [Table: see text]

Improving management of breathlessness in lung cancer.

220 Background: Dyspnea is a common and debilitating symptom of advanced lung cancer that interferes with quality of life (QOL). Though few evidence-based treatments for dyspnea exist, there is support for non-pharmacological interventions that include elements of cognitive-behavioral therapy (CBT). The purpose of this study was to pilot a brief nurse-delivered CBT intervention for dyspnea in patients with lung cancer, assessing feasibility and effect. Methods: For this single-group, nonrandomized pilot trial, 20 patients receiving outpatient chemotherapy for advanced lung cancer (ECOG Performance Status 0-2) and reporting dyspnea participated in a two-session CBT intervention. We enrolled a convenience sample of patients referred by their medical oncologists based on self-reported dyspnea. Two nurse practitioners taught the participants breathing and relaxation techniques within the infusion clinic and encouraged home practice. Patients completed measures of dyspnea (Modified Medical Research Council Dyspnea Scale [MMRCDS]), QOL (Functional Assessment of Cancer Therapy-Lung [FACT-L] and Trial Outcome Index [TOI]), and depression symptoms (Hospital Anxiety and Depression Scale depression subscale [HADS-D]) at baseline and within 6 weeks after enrollment. We used dependent-samples t-tests to analyze treatment effect on dyspnea and QOL and sign test to analyze depressions symptoms. Results: Of the 20 patients (50% Female; Mean Age=64.80 years) enrolled in the study, 85% (17) completed post-assessment. We observed significant improvement in MMRCDS (p=.001), FACT –L (p=.029), and FACT-TOI (p=.008) scores from baseline to post-assessment. The proportion of patients reporting depression symptoms (e.g. HADS-D &gt;7) decreased from 50% (n=10/20) to 12 % (n=2/17) (p=.016). Conclusions: In this sample of patients with advanced lung cancer and dyspnea, we observed a high completion rate for the 2-session CBT intervention. Patients also showed improvements in dyspnea, QOL, and mood. Follow-up randomized controlled trials are needed to examine the efficacy of brief CBT interventions for dyspnea. Clinical trial information: NCT01937637.

Patient-reported outcomes (PROs) from the systemic therapies for HER2-positive metastatic breast cancer (MBC) registry study (SystHERs): Eliciting the patient experience.

286 Background: Patients with HER2-positive MBC are, on average, living longer. Data are limited on patient-reported quality of life (QoL) and economic burden during these extended survival periods. In accordance with guidelines for comparative effectiveness research in oncology (Basch et al, 2012), SystHERs, initiated in 2012, includes PROs to capture the patient experience. Here we report baseline (at enrollment) PRO results from SystHERs. Methods: SystHERs is a US-based prospective observational cohort study that aims to enroll 1000 patients with HER2-positive MBC within 6 months of metastatic diagnosis. Patients will be followed for 5–8 years.PROs, including QoL, economic burden, and symptoms related to neuropathy, alopecia, and cognition, are collected at baseline and ~90-day intervals during clinic visits, including after disease progression. Results: As of Feb 17, 2014, 319 patients were enrolled, and baseline data from 306 eligible patients are reported. Median time to enrollment since MBC diagnosis was 2.4 months. At least 1 PRO item was completed by 90% of eligible patients. Scale reference ranges (higher scores indicate better status) and median scores at baseline were: overall HRQoL (0–100)=80.0; FACT-B Trial Outcome Index (0–96)=58.0, and the Rotterdam Activities of Daily Living Scale (0–100)=85.7. One hundred patients (40.3%) were employed. These patients reported on average 36% work time missed (absenteeism) and 30% decreased on-the-job effectiveness (presenteeism) due to MBC. Patients reported a median out-of-pocket MBC-related expenditure of $735 in the past 3 months (range $0–11,700). Of this, the median deductible and copay-related cost was $350. Conclusions: To our knowledge, this is the only HER2-positive MBC patient registry that includes comprehensive PROs to supplement clinical data. To date, participation in PROs is high at baseline (90%).QoL and economic burden were consistent with other studies (Cortés et al, 2013; Zafar et al, 2013). Baseline results for ~500 patients are expected by the time of the congress presentation and will include data on symptoms related to neuropathy, alopecia, and cognition. Clinical trial information: NCT01615068.

885PD - Health-Related Quality of Life (Hrqol) During Olaparib Maintenance Therapy in Patients with Platinum-Sensitive Relapsed Serous Ovarian Cancer (Psr Soc) and a Brca Mutation (Brcam)

ABSTRACT Aim: Maintenance monotherapy with the PARP inhibitor olaparib significantly prolonged progression-free survival (PFS) versus placebo in patients with PSR SOC, and subsequent analysis has shown that patients with a BRCAm receive greater treatment benefit (Ledermann et al Lancet Oncol 2014). As preserved HRQoL may support chronic administration in the maintenance setting, the effect of olaparib on HRQoL was evaluated in this randomized, double-blind Phase II trial (NCT00753545). Methods: Patient-reported HRQoL and disease-related symptoms were evaluated using the Functional Assessment of Cancer Therapy Ovarian (FACT-O) questionnaire, FACT/NCCN Ovarian Symptom Index (FOSI) and Trial Outcome Index (TOI). Patients completed the FACT-O questionnaire at baseline and every 28 days until progression. Individual symptom severity over 7 days was measured using the five-item Likert scale; physical, social/family, emotional, functional wellbeing and specific concerns to ovarian cancer patients were assessed. The TOI of the FACT-O was the primary HRQoL endpoint. FOSI is the sum of a subset of eight symptom-related items. Results: Of patients randomized to olaparib (n = 136) or placebo (n = 129), BRCA mutation status data were available for 254/265 (96%), of whom 136/254 (53.5%) had a known deleterious/suspected deleterious germline or somatic BRCA mutation. Most patients reported a best response of ‘improved’ or ‘no change’ on TOI (Table); this trend was also seen in other HRQoL measures. There were no statistically significant differences in improvement rates or time to worsening of TOI, FOSI and Total FACT-O. Overall BRCAm BRCAwt Olaparib Placebo Olaparib Placebo Olaparib Placebo TOI N = 115 N = 111 N = 64 N = 53 N = 49 N = 54 Improved * 23 (20.0) 20 (18.0) 16 (25.0) 10 (18.9) 7 (14.3) 10 (18.5) No change† 72 (62.6) 67 (60.4) 38 (59.4) 30 (56.6) 32 (65.3) 36 (66.7) Worsened†† 16 (13.9) 20 (18.0) 7 (10.9) 10 (18.9) 9 (18.4) 8 (14.8) Non-evaluable 4 (3.5) 4 (3.6) 3 (4.7) 3 (5.7) 1 (2.0) 0 BRCAwt, BRCA wild type, includes patients with no known BRCAm or a variant of unknown significance. * Best response of improved defined as two visit responses of 'improved' a minimum of 21 days apart without an intervening visit response of 'worsened'. †Defined as two visit responses of 'no change' or a response of 'no change' and a response of 'improved' a minimum of 21 days apart without an intervening visit response of 'worsened'. No change is defined as a change from baseline of greater than -7 but less than +7.††Defined as a visit of 'worsened' without a response of 'improved' or 'no change' within 21 days. Worsened is defined as a change from baseline of less than or equal to -7. Conclusions: HRQoL was not negatively impacted during maintenance therapy with olaparib. Phase III trials are enrolling. Disclosure: J.A. Ledermann: Travel grants from AstraZeneca; P. Harter: Received a grant from AstraZeneca; C. Gourley: Served on advisory boards for, and received travel grants from, AstraZeneca; G.J.S. Rustin: Served on advisory boards for AstraZeneca, Oxigene, Roche, Amgen, Boehringer Ingelheim and Clovis; C. Scott: Received travel grants from AstraZeneca; A. Fielding, S. Spencer, B. Bennett and D. Parry: Employee of AstraZeneca and stock ownership. All other authors have declared no conflicts of interest.

Fact- B and Esas in Metastatic Breast Cancer (Mbc) Patients (Pts) Treated with Eribulin: Results of a Multicenter Prospective Observational Study

ABSTRACT Aim: Eribulin (E) is a non taxane microtubule inhibitor indicated for treatment of MBC. To evaluate its tolerability, impact on Quality of Life (QoL) and symptoms improvement in MBC pts, from April 2012, we conducted a prospective observational study. Methods: Pts pretreated with anthracyclines (A) and taxanes (T) who have received 2 CHT lines for MBC, scheduled to be treated with E, were considered eligible. Pts completed ESAS at each cycle and FACT-B every 2 cycles. Outcome of QoL included the FACT-B total score, FACT-General (FACT-G) score and the Trial Outcome Index (TOI) score. Paired data were analyzed with non parametric Wilcoxon, McNemar and Friedman tests. Kaplan-Meier method was used for survival calculation. Results: 50 consecutive MBC pts entered the study. Median age 64 (range 31-85), 83% of pts had PS (ECOG) 0-1, 23% had triple-negative MBC, 75% ER/PgR positive and 63% HER2 positive. All pts were pretreated with A and T, 19 (76%) also with capecitabine. Median E cycles administered was 5 (range 1-17), 31% of pts received more than 6 cycles. Main side effects G2-G3 were: 42% alopecia, 38% asthenia, 15% peripheral neuropathy,16% neutropenia. At a median follow-up of 7 months (mo) (range 2-21), 17% (CI 95% 6-28) of pts achieved partial response (PR), 39% stable disease (SD) and 44% progressive disease; disease control rate (PR + SD ≥ 6 mo) occurred in 40% of pts. Median PFS is 4 mo (95% CI, 3-5); median OS is 9 mo (CI 95% 2-16); 1-yr overall survival is 49%. Items in ESAS which at baseline had score more than >5 in at least 25% of pts were anorexia, drowsy, anxiety, loss of activity and wellbeing; all these symptoms not worsened in subsequent evaluations. Data of ESAS and QoL are reported in table. ESAS and QoL assessments were adjusted for response, PS and age. Conclusions: Our results shows that treatment with E is associated with a good maintenance of QoL and ESAS scores with expected and manageable toxicities. Basal median score(range) Final median score (range) P value ESAS 30 (3-63) 28 (3-60) 0.91 FACT- B 79 (55-117) 81(45-119) 0.36 FACT-G 59 (40-88) 60 (30-93) 0.98 TOI 53 (33-78) 52 (29-78) 0.23 Disclosure: All authors have declared no conflicts of interest.