Virtual Molecular and Precision Medicine Clinic to Improve Access to Clinical Trials for Patients With Metastatic Breast Cancer: An Academic/Community Collaboration.

PURPOSE: There is a demand for improved care delivery surrounding genomic testing and clinical trial enrollment among patients with metastatic breast cancer (MBC). We sought to improve the current process via real-time informal consultation and prescreening assessment for patients with MBC treated by community and academic medical oncologists by implementing a virtual molecular and precision medicine (vMAP) clinic. METHODS: The vMAP program used a virtual referral system directed to a multidisciplinary team with precision medicine expertise. Providers contacted vMAP regarding patients with MBC, and on receipt of referral, the vMAP team engaged in discussion to identify if further diagnostics were needed (including genomic testing) and to identify potential clinical trials or standard treatment options. Recommendations were then sent to the referring provider within 72 hours. Pre-/postsurveys were issued to network physicians to assess for barriers, clinical trial access, and vMAP referral experience. Program implementation was evaluated with the Squire 2.0 reporting guidelines for quality improvement in health care as a framework. RESULTS: Eighty-one cases from 22 providers were referred to vMAP over a 26-month period. The average response time to the referring provider with a finalized recommendation was 1.90 ± 1.82 days. A total of 86.4% of cases had clinical trial options on vMAP prescreen, with 40.7% initiating formal screening assessments and 27 patients (33.3%) ultimately enrolling on trials. On resurvey, 92% of survey responses across community oncology referring providers said that they were very likely to use vMAP again. CONCLUSION: In the initial 2-year period, vMAP demonstrated an efficient means to offer real-time interpretation of genomic testing and identification of clinical trials for patients with MBC, with effective clinical trial enrollment and high rates of referring provider satisfaction.

Implementation and Clinical Adoption of Precision Oncology Workflows Across a Healthcare Network.

BACKGROUND: Precision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows. METHODS: Workflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network. RESULTS: Development of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P < .001), compliance with testing recommendations (9%; P < .001), and the fraction of "abnormal" results (6%; P < .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network. CONCLUSION: Our study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.

Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581.

PURPOSE: We conducted a randomized trial comparing adjuvant treatment with edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome. PATIENTS AND METHODS: After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of edrecolomab at 28-day intervals or observation without adjuvant therapy. RESULTS: Final accrual included 1,738 patients; 865 patients received edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer. CONCLUSION: Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.

Chemotherapy-related hospitalization among community cancer center patients.

PURPOSE: To describe the frequency, nature, trends, predictors, and outcomes of chemotherapy-related hospitalizations (CRHs) among a nonselected population of cancer patients treated at a community cancer center, and to explore the feasibility of implementing continuous quality improvement methodologies in routine oncology practice. METHODS: We conducted a prospective cohort study of consecutive adult cancer patients who received chemotherapy at a community cancer center January 2003 to December 2006. Demographic, comorbidity, diagnosis, treatment, and laboratory data were collected via medical record abstraction. Hospitalizations were classified as chemotherapy related or unrelated by a multidisciplinary panel. Patients who experienced CRHs were compared with those who did not. Using a randomly sampled subset of cases and controls, we built a logistic regression model to identify independent predictors of CRH. RESULTS: Of 2,068 chemotherapy recipients, 179 (8.7%) experienced 262 CRHs. Most hospitalizations were not chemotherapy related (73.7%). The mean monthly rate of CRH was 1.5%, the median length of stay was 5 days, the most common type of CRH was gastrointestinal (46.1%) followed by infectious (31.4%), and 0.9% of chemotherapy recipients had a fatal CRH. Significant predictors of CRH included having a comorbidity score of 3-4 versus 0 and having a higher creatinine level. CONCLUSIONS: Although the vast majority of chemotherapy recipients did not experience a CRH, these events were, unfortunately, not without serious consequences. Care should be taken when offering chemotherapy to patients with multiple comorbid conditions. Systematic efforts to monitor toxicity can lead directly to improvements in quality of care.

Racial differences in clinical outcomes from metastatic breast cancer: a pooled analysis of CALGB 9342 and 9840--Cancer and Leukemia Group B.

PURPOSE: African American women are more likely to be diagnosed with metastatic breast cancer at the time of presentation than whites, and have shorter survival once diagnosed. This study examines racial differences in clinical outcomes in the setting of two large cooperative group randomized clinical trials. PATIENTS AND METHODS: The study cohort consisted of 787 white (80%) and 195 African American (20%) patients with metastatic breast cancer enrolled in two successive Cancer and Leukemia Group B (CALGB) trials using taxanes in the metastatic setting. Differences in overall survival (OS), response incidence, and time to treatment failure (TTF) were examined by race. In addition, differences in the incidence of baseline and treatment-related toxicities were examined. RESULTS: With 779 deaths (166 African Americans and 613 whites), median OS was 14.3 months for African Americans and 18.75 months for whites (hazard ratio [HR] = 1.37; 95% CI, 1.15 to 1.63). When adjusted for prognostic factors, African Americans had a 24% increase in the hazard of death compared with whites (HR = 1.24; 95% CI, 1.02 to 1.51). No significant differences in TTF or overall response to therapy were seen. No clinically significant toxicity differences were seen. CONCLUSION: African Americans with metastatic breast cancer have an increased hazard of death compared with whites despite the receipt of similar per-protocol treatment, but experience no differences in TTF or overall response to therapy. We hypothesize that more direct and robust measures of comorbidities, and perhaps other factors such as receipt of subsequent therapy could help further explain the observed survival difference.

Relations between emotion, illusory word perception, and orthographic repetition blindness: tests of binding theory.

This study reports effects of meaning and emotion (taboo vs. neutral words) on an illusory word (IW) phenomenon linked to orthographic repetition blindness (RB). Participants immediately recalled rapid serial visual presentation (RSVP) lists consisting of two critical words (C1 and C2) containing shared letters, followed by a word fragment: for example, lake (C1) brake (C2) ush (fragment). For neutral critical words, participants often recalled C1, but not C2 or the fragment, reporting instead a nonoccurring or illusory word: here, brush (a blend of C2 and the fragment). Forward RB (defined as reduced report of orthographically similar C2s) was more common for neutral than for taboo C2s, and taboo IWs were reported significantly more often than were neutral IWs. Moreover, when both C2 and the potential IW were taboo, a new phenomenon emerged: Participants reliably reported both the IW and the intact C2. These and other results supported a binding theory of the IW phenomenon and orthographic RB.