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PURPOSE: Several allelic variants of the gene DPYD encoding dihydropyrimidine dehydrogenase (DPD) are associated with impaired metabolism of the systemic fluoropyrimidine fluorouracil (5FU) and its oral prodrug, capecitabine, which elevates the risk for severe toxicity. Following a patient death related to capecitabine toxicity in which DPD deficiency was suspected, a multidisciplinary advisory panel was convened to develop an institution-wide approach to future patients planned for a systemic fluoropyrimidine. METHODS: The panel selected an opt-out testing strategy which focused on developing reliable processes to collect and report test results and targeted education. An electronic health record–based automated reminder was designed to activate when a 5FU- or capecitabine-containing chemotherapy regimen was ordered for a patient without prior exposure to either agent and without a prior DPYD sequencing test result. DPYD testing was standardized across all sites of care, and a closed loop reporting system for abnormal test results was created. Before implementation, targeted education was provided to providers, pharmacists, and nurses, and a failure mode and effects analysis was performed. Program rollout was staged over a 6-month period. RESULTS: At 10 months, the rate of preemptive testing increased from a baseline of 26% to a sustained rate of >90%. In the six network sites, the testing rate increased from 9% to 96%. A total of 1,043 patients have been tested preemptively; allelic variants have been identified in 43 (4.1%). Among 25 evaluable patients, dose reduction or change to a non–fluoropyrimidine-based regimen was accomplished in 96%. CONCLUSION: Preemptive DPYD testing is feasible, and high rates of testing can be achieved using an opt-out, reminder-based program. We provide the details of the implementation and encourage others to emulate it. [ABSTRACT FROM AUTHOR]

PURPOSE To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019- 2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Multidisciplinary clinics (MDCs) play a prominent role in coordinating complex cancer care delivered by multiple providers from different disciplines. The structure of such clinics and clinicians' perceptions of the advantages and disadvantages of practicing in MDCs have not been well characterized. Methods: We surveyed and interviewed medical providers who participate in cancer MDCs at our comprehensive cancer center about the structure of the MDCs in which they work, their satisfaction working in these clinics, and the perceived benefits and disadvantages. Press-Ganey patient satisfaction scores were also examined. Results: We identified two care models: one in which patients are seen sequentially by physicians from each discipline, and a second model in which patients are seen concurrently by physicians from each discipline. Of the 141 survey respondents from surgical oncology, medical oncology and radiation oncology, more than 90% of providers enjoyed working in an MDC and more than 75% preferred to see new patients in an MDC. Additionally, 90% believed that patients perceived the clinics to be valuable for comprehensive, coordinated, and appropriate care. However, one third of the phsyicians thought the clinics were not an efficient use of their time. Participants who practice in the concurrent model of care and surgical oncologists were more likely to express frustration with the inefficiency of MDCs. Patients seen in each clinic model uniformly expressed high satisfaction with the coordination of care. Conclusion: MDCs are valued by oncology patients and providers. Although they are personally and professionally satisfying for physicians, the use of this care model is perceived as inefficient by some caregivers. [ABSTRACT FROM AUTHOR]

Purpose Delays to adjuvant chemotherapy initiation in breast cancer may adversely affect clinical outcomes and patient satisfaction. We previously identified an association between genomic testing (Oncotype DX) and delayed chemotherapy initiation. We sought to reduce the interval between surgery and adjuvant chemotherapy initiation by developing standardized criteria and workflows for Oncotype DX testing. Methods Criteria for surgeon-initiated reflex Oncotype DX testing, workflows for communication between surgeons and medical oncologists and a streamlined process for receiving and processing Oncotype DX requests in pathology were established by multidisciplinary consensus. Criteria for surgeon-initiated testing included patients ⩽ 65 years old with T1cN0 (grade 2 or 3), T2N0 (grade 1 or 2), or T1/T2N1 (grade 1 or 2) breast cancer on final surgical pathology. Medical oncologists could elect to initiate Oncotype testing for cases falling outside the criteria.Wethen examined 720 consecutive patients with breast cancer who underwent Oncotype DX testing postoperatively between January 1, 2014 and November 28, 2016 and measured intervals between date of surgery, Oncotype DX order date, result received date and chemotherapy initiation date (if applicable) before and after intervention implementation. Results The introduction of standardized criteria and workflows reduced time between surgery and OncotypeDXordering and time from surgery to receipt of result, by 7.3 days (P,.001) and 6.3 days (P<.001), respectively. The mean number of days between surgery and initiation of chemotherapy was also reduced by 6.4 days (P = .004). Conclusion Developing consensus on Oncotype DX testing criteria and implementing streamlined workflows has led to clinically significant reductions in wait times to chemotherapy decision making and initiation. [ABSTRACT FROM AUTHOR]

Purpose Mastectomy with immediate reconstruction (MIR) requires coordination between breast and reconstructive surgical teams, leading to increased preoperative delays that may adversely impact patient outcomes and satisfaction. Our cancer center established a target of 28 daysfrom initial consultation with the breast surgeon to MI R.We sought to determine if a centralized breast/reconstructive surgical coordinator (BRC) could reduce care delays. Methods A 60-day pilot to evaluate the impact of a BRC on timeliness of care was initiated at our cancer center. All reconstructive surgery candidates were referred to the BRC, who had access to surgical clinic and operating room schedules. The BRC worked with both surgical services to identify the earliest surgery dates and facilitated operative bookings. The median time to MIR and the proportion of MIR cases that met the time-to-treatment goal was determined. These results were compared with a baseline cohort of patients undergoing MIR during the same time period (January to March) in 2013 and 2014. Results A total of 99 patients were referred to the BRC (62% cancer, 21% neoadjuvant, 17% prophylactic) during the pilot period. Focusing exclusively on patients with a cancer diagnosis, an 18.5% increase in the percentage of cases meeting the target (P = .04) and a 7-day reduction to MIR (P = .02) were observed. Conclusion A significant reduction in time to MIR was achieved through the implementation of the BRC. Further research is warranted to validate these findings and assess the impact the BRC has on operational efficiency and workflows. [ABSTRACT FROM AUTHOR]

This article describes how trust among team members and in the technology supporting them was eroded during implementation of an electronic health record (EHR) in an adult outpatient oncology practice at a comprehensive cancer center. Delays in care of a 38-year-old woman with high-risk breast cancer occurred because of ineffective team communication and are illustrated in a case study. The case explores how the patient's trust and mutual trust between team members were disrupted because of inaccurate assumptions about the functionality of the EHR's communication tool, resultant miscommunications between team members and the patient, and the eventual recognition that care was not being effectively coordinated, as it had been previously. Despite a well-established, team-based culture and significant preparation for the EHR implementation, the challenges that occurred point to underlying human and system failures from which other organizations going through a similar process may learn. Through an analysis and evaluation of events that transpired before and during the EHR rollout, suggested interventions for preventing this experience are offered, which include: a thorough crosswalk between old and new communication mechanisms before implementation; understanding and mitigation of gaps in the communication tool's functionality; more robust training for staff, clinicians, and patients; greater consideration given to the pace of change expected of individuals; and development of models of collaboration between EHR users and vendors in developing products that support high-quality, team-based care in the oncology setting. These interventions are transferable to any organizational or system change that threatens mutual trust and effective communication.

Purpose: Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy., Patients and Methods: MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m(2) or 3-hour infusion of 40 mg/m(2) every 3 weeks)., Results: Of 49 patients treated with 40 mg/m(2) ixabepilone during 3 hours, 35 (73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate., Conclusion: Ixabepilone (40 mg/m(2) as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.

Purpose: Few studies have examined the influence of diet on survival and chemotherapy-associated toxicities in patients with cancer. Although several comprehensive dietary questionnaires have been validated and calibrated in healthy populations, similar studies have not been performed among cancer patients., Methods: Two hundred patients with colorectal, breast, or neuroendocrine cancer undergoing treatment with cytotoxic chemotherapy completed a self-administered, 131-item, semiquantitative food frequency questionnaire. Using the questionnaire, we calculated dietary intakes of carotenoids, tocopherols, and fatty acids, and correlated these values with relevant biomarkers measured in simultaneously collected plasma specimens., Results: The Pearson correlation coefficients for various carotenoids as measured by the questionnaire, with the corresponding measurements in plasma specimens, ranged from 0.33 to 0.44 (all P < .001), adjusted for total energy intake, body mass index, age, sex, smoking status, and total plasma cholesterol. Similarly, the adjusted correlation between self-reported total vitamin E intake and plasma alpha-tocopherol was 0.34 (P < .001). Correlations between questionnaire and plasma measurements of trans-fat, eicosapentaenoic acid, and docosahexaenoic acid were 0.55, 0.29, and 0.42 (all P < .001), respectively. These levels of correlation are consistent with those reported in similar studies of self-reported diet in otherwise healthy populations., Conclusion: Among patients with cancer receiving cytotoxic chemotherapy, questionnaire-based measurements of various micronutrients and dietary factors appeared to predict meaningful differences in the corresponding measurements in plasma specimens. This dietary questionnaire could offer an informative and practical means for assessing the influence of diet in cancer patients receiving chemotherapy.

Purpose: Dose-dense, every-2-week adjuvant chemotherapy using doxorubicin/cyclophosphamide (AC; 60/600 mg/m2 every 2 weeks x four cycles) followed by paclitaxel (175 mg/m2 every 2 weeks x four cycles), requiring filgrastim on days 3 through 10 of each cycle has been shown to improve survival compared with every-3-week treatment schedules but is associated with greater risk of RBC transfusion (13%). The role of long-acting hematopoietic growth factors in facilitating every-2-week chemotherapy and minimizing hematologic toxicity has not been established., Patients and Methods: Women with stage I to III breast cancer received dose-dense AC --> paclitaxel as neoadjuvant or adjuvant chemotherapy. Patients received pegfilgrastim 6 mg subcutaneous (SQ) on day 2 of each cycle. Darbepoetin alfa was initiated at 200 microg SQ every 2 weeks for hemoglobin < or = 12 g/dL, and administered thereafter, according to a preplanned algorithm. The primary end points were to evaluate the percentage of patients with febrile neutropenia and the percentage of patients requiring RBC transfusion., Results: Among 135 women treated on this single arm study, there were two cases of febrile neutropenia (incidence 1.5%). No patients received RBC transfusion. Darbepoetin alfa therapy was initiated in 92% of patients. The modest leukocytosis seen during paclitaxel cycles was attributable, in part, to corticosteroid premedication. Other toxicity and dose-delivery were similar to dose-dense AC --> paclitaxel in Cancer and Leukemia Group B 9741., Conclusion: Pegfilgrastim and darbepoetin alfa are effective and safe in facilitating every-2-week AC --> paclitaxel, minimizing rates of febrile neutropenia and RBC transfusion.

Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools., Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction >or= 50%. Serial testing for HER2 extracellular domain (ECD) was performed., Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression., Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Purpose: Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer., Patients and Methods: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially., Results: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment., Conclusion: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.