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Purpose: Preclinical studies support the JAK2–STAT3 signaling pathway as a key driver in CD44+ CD24− "stem-cell-like" breast cancer cells. Ruxolitinib is an orally bioavailable JAK1/2 inhibitor. We aimed to identify the recommended phase 2 dose (RP2D) of ruxolitinib in combination with paclitaxel in patients with HER2-negative metastatic breast cancer (MBC). Methods: Eligible patients had HER2-negative MBC and had received ≤ 3 chemotherapy regimens for advanced disease. Patients received oral ruxolitinib (10–25 mg bid) in a 3 + 3 dose escalation design in combination with weekly paclitaxel 80 mg/m2 in a 3-week cycle. The primary objective was to determine the maximum tolerated dose (MTD) and the RP2D. Results: Nineteen patients received protocol therapy (mean age 52 years). Eight (42%) had triple-negative breast cancer and 11 (58%) had hormone receptor-positive disease; 12 (63%) had visceral disease. Ten (53%) patients had not received prior treatment for advanced disease. Patients received a median number of 5 cycles of combination therapy (range 1–12) and five patients continued single-agent ruxolitinib. The MTD of ruxolitinib was 25 mg bid when combined with paclitaxel, and the RP2D for the combination was 15 mg bid. Thirteen (68%) patients required dose reductions or holds. Most frequent toxicities reported of any grade were neutropenia (50%) and anemia (33%). There were no grade 4/5 toxicities attributed to study drug. Four (21%) patients had PR, 12 (63%) had SD and three (16%) had PD as their best response. Conclusion: The combination of ruxolitinib and weekly paclitaxel was well tolerated with evidence of clinical activity. Further analysis of this combination is ongoing (NCT02041429). Trial registration: NCT02041429. Date of registration: January 22, 2014. [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]

Service processes, for example in transportation, telecommunications or the health sector, are the backbone of today׳s economies. Conceptual models of service processes enable operational analysis that supports, e.g., resource provisioning or delay prediction. In the presence of event logs containing recorded traces of process execution, such operational models can be mined automatically. In this work, we target the analysis of resource-driven, scheduled processes based on event logs. We focus on processes for which there exists a pre-defined assignment of activity instances to resources that execute activities. Specifically, we approach the questions of conformance checking ( how to assess the conformance of the schedule and the actual process execution ) and performance improvement ( how to improve the operational process performance ). The first question is addressed based on a queueing network for both the schedule and the actual process execution. Based on these models, we detect operational deviations and then apply statistical inference and similarity measures to validate the scheduling assumptions, thereby identifying root-causes for these deviations. These results are the starting point for our technique to improve the operational performance. It suggests adaptations of the scheduling policy of the service process to decrease the tardiness (non-punctuality) and lower the flow time. We demonstrate the value of our approach based on a real-world dataset comprising clinical pathways of an outpatient clinic that have been recorded by a real-time location system (RTLS). Our results indicate that the presented technique enables localization of operational bottlenecks along with their root-causes, while our improvement technique yields a decrease in median tardiness and flow time by more than 20%. [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]