Deal, Allison

158 Background: There is limited research on methods for alerting clinicians to concerning patient-reported outcome (PRO) responses and how often PROs trigger alerts to nurses during cancer care. Methods: In two randomized trials, adults with advanced cancer receiving chemotherapy were enrolled. Participants were randomized to usual care vs. weekly PROs completed between visits (with automated feedback to nurses). PRO responses in the intervention arm triggered automated email alerts to nurses for frequent, severe, or worsening symptoms in the last 7 days. Alert thresholds for PROs were chosen a priori but were unique to each study. The “Symptom Tracking and Reporting” (STAR) trial was conducted at one academic medical center. The “PROs to Enhance Cancer Treatment” (PRO-TECT [AFT-39]) cluster-randomized trial is being conducted in > 30 community practices. Results: In STAR, 766 patients participated (58% female, 38% ages ≥65, 17% minority, 28% ≤high school). 441 participants were randomized to the intervention arm, where 1,431/84,212 items (2%) triggered a concerning symptom alert, during 1,070/8,498 weeks (13%). Frequent alerts were for fatigue (62%), pain (32%), and appetite (16%). In PRO-TECT (AFT-39), 300 patients have been enrolled (58% female, 49% ages ≥65, 8% minority, 47% ≤high school) out of 1,000. 146 participants have been randomized to the intervention arm, where 1,422/24,739 items (6%) triggered an alert, during 824/2249 weeks (37%). Common alerts were for pain (48%), physical function (35%), and diarrhea (15%). PRO-TECT provided clinical decision support with alerts. Conclusions: In two randomized trials in advanced cancer, PROs collected during care delivery enabled tailored treatment based on issues identified on PROs. Pain, physical function, appetite, and diarrhea commonly triggered alerts for concerning symptoms. Early PRO-TECT results are showing a trend for higher weekly alert rates for concerning symptoms (37% vs. 13% in STAR), which may indicate that the PRO intervention will be even more effective in community practices. Results assist in addressing logistical considerations for implementing PROs into routine care. Clinical trial information: NCT03249090.

LBA2 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Sunday, June 4, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

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.

Purpose There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. Methods We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. Results Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. Conclusion Clinical benefits were associated with symptom self-reporting during cancer care.

Abstract Purpose: Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated the potential role of αB-crystallin in brain metastasis in TNBCs. Experimental Design: αB-crystallin expression in primary breast carcinomas and brain metastases was analyzed by immunohistochemistry among patients with breast cancer with brain metastases. αB-crystallin was overexpressed or silenced in two different TNBC cell lines. The effects on cell adhesion to human brain microvascular endothelial cells (HBMEC) or extracellular matrix proteins, transendothelial migration, and transmigration across a HBMEC/astrocyte coculture blood–brain barrier (BBB) model were examined. In addition, the effects of overexpressing or silencing αB-crystallin on brain metastasis in vivo were investigated using orthotopic TNBC models. Results: In a cohort of women with breast cancer brain metastasis, αB-crystallin expression in primary breast carcinomas was associated with poor overall survival and poor survival after brain metastasis, even among patients with TNBC. Stable overexpression of αB-crystallin in TNBC cells enhanced adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro, whereas silencing αB-crystallin inhibited these events. αB-crystallin promoted adhesion of TNBC cells to HBMECs, at least in part, through an α3β1 integrin–dependent mechanism. αB-crystallin overexpression promoted brain metastasis, whereas silencing αB-crystallin inhibited brain metastasis in orthotopic TNBC models. Conclusion: αB-crystallin is a novel regulator of brain metastasis in TNBC and represents a potential biomarker and drug target for this aggressive disease. Clin Cancer Res; 20(1); 56–67. ©2013 AACR.