Dueck, Amylou C.

AbstractBackgroundWe aimed to provide a simple, descriptive health‐status profile for cancer patients with bone metastases, based on the EuroQol EQ‐5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain‐assessment tool. Although pain is one of five health‐status dimensions measured by the EQ‐5D, our understanding of how pain relates to the other EQ‐5D dimensions is limited.MethodsWe derived data from 5500 patients with bone metastases who completed the EQ‐5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ‐5D utility scores and how BPI items associated with EQ‐5D items, for the entire sample and by disease‐type subgroup.ResultsRegardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ‐5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self‐care, 26%. BPI pain interference explained more of the variability in the EQ‐5D utility scores than did pain severity (R2 = 41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ‐5D pain/discomfort, with odds ratio estimates <1.ConclusionsPain/discomfort was the worst‐rated dimension of the EQ‐5D in this population, but the relationship of this item to BPI pain severity was modest, suggesting that the single pain item of the EQ‐5D may be of limited utility in studies for which pain is an endpoint.SignificanceHealth‐status dimensions include more than pain. We examine the contribution of pain severity and pain‐related functional interference in determining the health status of cancer patients with bone metastases. The pain dimension from a health‐status measure may be an inadequate metric in clinical trials/clinical practice when pain is an important outcome.

Key Points After hydroxycarbamide therapy in high-risk ET, ruxolitinib showed no improvement for complete or partial response rates compared with BAT. Ruxolitinib significantly improved some disease-related symptoms, but rates of thrombosis, hemorrhage, or transformation were not different.

LBA2 Background: We previously reported significant benefits in quality of life, patient satisfaction, and emergency room utilization outcomes from a large single-center randomized controlled trial comparing web-based symptom monitoring with patient-reported outcomes (PROs) vs. usual care in patients receiving chemotherapy for metastatic solid tumors (Clinicaltrials.gov: NCT00578006). We now present overall survival results from this trial. Methods: Patients receiving routine outpatient chemotherapy for metastatic solid tumors at Memorial Sloan Kettering Cancer Center were randomly assigned to self-report 12 common symptoms via tablet computers (“PRO intervention”), or to usual care. Treating physicians received symptom printouts at visits and nurses received email alerts when participants reported severe or worsening symptoms. Overall survival was tabulated based on medical records and Social Security Death Index data, estimated using the Kaplan-Meier method, and compared between arms using a log-rank test and Cox proportional hazards regression adjusting for age, sex, race, education level, and cancer type. Results: Between September 2007 and January 2011, 766 patients were randomized, with median age 61 (range 26-91), 86% white, 58% female, and 22% with less than high school education. Cancer types included genitourinary (32% of patients), gynecologic (23%), breast (19%), and lung cancer (26%). Survival results were assessed in June 2016 after a median follow up of 7 years and 517/766 (67%) of participants had died. Median overall survival in the PRO intervention arm was 5 months longer than the control arm (31.2 vs. 26.0 months, p = 0.03). In the multivariable model, results remained statistically significant with a hazard ratio of 0.832 (p = 0.04; 95% CI; 0.696, 0.995). Conclusions: Systematic symptom monitoring during outpatient chemotherapy using web-based patient-reported outcomes confers overall survival benefits. These single-center results are being further evaluated in a national multicenter implementation trial. Clinical trial information: NCT00578006.

Abstract Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism of trastuzumab resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2+ adjuvant N9831 trial. Experimental Design: IGF1R protein expression was determined in tissue microarray sections (three cores per block; N = 1,197) or in whole tissue sections (WS; N = 537) using IHC (rabbit polyclonal antibody against IGF1R β-subunit). A tumor was considered positive (IGF1R+) if any core or WS had ≥1+ membrane staining in &gt;0% invasive cells. Median follow-up was 8.5 years. Results: Of 1,734 patients, 708 (41%) had IGF1R+ breast tumors. IGF1R+ was associated with younger age (median 48 vs. 51, P = 0.007), estrogen receptor/progesterone receptor positivity (78% vs. 35%, P &lt; 0.001), nodal positivity (89% vs. 83%, P &lt; 0.001), well/intermediate grade (34% vs. 24%, P &lt; 0.001), tumors ≥2 cm (72% vs. 67%, P = 0.02) but not associated with race or tumor histology. IGF1R did not affect DFS within arms. Between Arms A and C, patients with IGF1R+ and IGF1R− tumors had DFS HRs of 0.48 (P ≤ 0.001) and 0.68 (P = 0.009), respectively (Pinteraction = 0.17). Between Arms A and B, patients with IGF1R+ and IGF1R− tumors had DFS HRs of 0.83 (P = 0.25) and 0.69 (P = 0.01), respectively (Pinteraction = 0.42). Conclusions: In contrast to preclinical studies that suggest a decrease in trastuzumab sensitivity in IGF1R+ tumors, our adjuvant data show benefit of adding trastuzumab for patients with either IGF1R+ and IGF1R− breast tumors. Clin Cancer Res; 23(15); 4203–11. ©2016 AACR.

ASCO believes that high-quality observational studies can advance evidence-based practice for cancer care and are complementary to randomized controlled trials (RCTs). Observational studies can generate hypotheses by evaluating novel exposures or biomarkers and by revealing patterns of care and relationships that might not otherwise be discovered. Researchers can then test these hypotheses in RCTs. Observational studies can also answer or inform questions that either have not been or cannot be answered by RCTs. In addition, observational studies can be used for postmarketing surveillance of new cancer treatments, particularly in vulnerable populations. The incorporation of observational research as part of clinical decision making is consistent with the position of many leading institutions. ASCO identified five overarching recommendations to enhance the role of observational research in clinical decision making: (1) improve the quality of electronic health data available for research, (2) improve interoperability and the exchange of electronic health information, (3) ensure the use of rigorous observational research methodologies, (4) promote transparent reporting of observational research studies, and (5) protect patient privacy.

Aims: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference. Methods: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. Results: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was −0.20 (−0.20) for 1-week recall, −0.36 (−0.31) for 2-week recall, −0.45 (−0.39) for 3-week recall, and −0.47 (−0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54–0.82), for 2-week recall was 0.74 (range: 0.58–0.83), for 3-week recall was 0.72 (range: 0.61–0.84), and for 4-week recall was 0.72 (range: 0.64–0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. Conclusion: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.

Abstract Effective assessment and management of pain in patients with cancer is strengthened by the patient's report of how much pain interferes with daily functioning. This requires a clear delineation of different levels of pain interference. We derived optimal cutpoints for differentiating between mild, moderate, and severe pain interference assessed by the Brief Pain Inventory (BPI) and describe the prevalence and characteristics of pain-induced functional impairment in patients with cancer. Data were pooled across 3 Phase III pivotal trials. Patient-completed questionnaires included the EuroQol 5 dimensions questionnaire (EQ5D), Functional Assessment of Cancer Therapy–General Measure (FACT-G), and BPI. Optimal cutpoints for categorizing pain interference into 3 levels were derived using analysis of variance, with different cutpoint sets for BPI total interference (BPI-PITS, the average score of all 7 items), activity-related interference (BPI-WAW, the average score of work, general activity, and walking), and mood-related interference (BPI-REM, the average score of relations with others, enjoyment of life, and mood) as independent variables and EQ5D–visual analog scale and total FACT-G score as dependent variables. To validate the cutpoints, we assessed whether interference categories were in concordance with Eastern Cooperative Oncology Group performance status (ECOG-PS) levels. The optimal cutpoints were (2,5) for BPI-PITS, (2,6) for BPI-WAW, and (2,5) for BPI-REM. The mild (<2), moderate (2-5 or 2-6), and severe (>5 or >6) pain interference groups were significantly concordant with ECOG-PS levels (P < 0.0001). We empirically derived patient-reported pain interference categories in relation to clinician-rated performance status. These cutpoints may facilitate the conduct and interpretation of clinical evaluation, symptom epidemiology, and clinical trials.

55 Background: The aim of this retrospective study was to examine the overall survival (OS) of metastatic breast cancer patients over a decade and assess for any differences with respect to age, tumor characteristics, and ECOG status. Methods: Data on metastatic breast cancer cases from 1999-2010 were retrieved from the institutional cancer registry and linked to electronic medical records. Through chart review of 240 metastatic breast cancer cases, we determined hormone receptor (HR), HER2/neu (HER2), ECOG, age at diagnosis of metastatic cancer and mortality data. Kaplan-Meier survival curves for OS were used and compared between HR status, HER2 status, ECOG, and age at diagnosis using log-rank regression and Cox Regression analysis was performed to control for these variables. A 95% confidence interval (CI) was used. Results: The median OS of the sampled cases was 2.2 years (CI: 1.8-2.5 years). Analysis for overall survival by pre-determined age groups demonstrated no significant difference between the age groups (p value 0.46), but did yield a statistical difference based on ECOG status (p value 0.0001). Cox regression analysis showed consistent findings where survival was significantly affected by HR, HER2 status and ECOG but not age (HR: p value <0.0001; HER2: p value 0.0132; ECOG: p value <0.0001; age at diagnosis: p value 0.8462). Analysis for OS based on HR yielded a median survival of 1.4 years (CI: 0.9-1.6 years) for HR negative and 2.5 years (CI: 2.2-3.0 years) for HR positive (p value 0.0018). HER2 yielded a median survival of 1.8 years (CI: 1.4-2.3 years) for no amplification and 3.0 years (CI: 2.5 - 3.4 years) for amplification (p-value 0.0043). HR negative, HER2 non-amplified tumors had the poorest median OS at 0.7 years (CI: 0.5 - 1.1 years) whereas those tumors with HR positive, HER2 amplified had the best median OS at 3.0 years (CI: 2.5 - 4.7 years) with a p value < 0.0001. Conclusions: In this retrospective analysis, there was no significant survival difference with respect to age. Age continued to have no significant effect on survival when adjusting for ECOG, hormone status, and HER2/neu status. Those factors that did act as determinants of survival were ECOG status, hormone status and HER2/neu status of the tumor.