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Background Breast cancer patients with estrogen receptor (ER)+/HER2- (and usually node-negative) tumors can avail themselves of Oncotype DX Breast Recurrence Score (ODXRS) testing to predict their risk of distant recurrence within 9 years and, consequently, putative chemotherapy benefit. However, ODXRS testing requires sufficient tumour availability and specimen shipping, which imposes time and financial burdens to testing which have to be met by healthcare systems. The advent of digital pathology offers a potential avenue for exploring computer-aided diagnostic solutions which may overcome these hurdles by extracting the requisite information from hematoxylin and eosin (H&E)-stained tissue whole slide images (WSIs) alone. In turn, this technology could significantly reduce diagnostic turnaround times and cost, and improve accessibility and test reproducibility, thereby enabling healthcare systems to run more efficiently and offer patients more timely results. Ideally, such a platform should incorporate a measure of the underlying tumor biology to provide a fully explainable, white box solution, and may offer further insights into the identification of early recurrence events. Aims The aim of this study was to establish whether our computer-aided solution’s (Q-Plasia OncoReader Breast, QPORB) digital biomarker representing G1/S cell cycle deformations extracted from H&E WSIs was prognostic for disease-free survival (DFS) and could predict disease recurrence, particularly in the setting of low risk ODXRS breast cancers. Methods Primary breast cancer resection/excision specimens (n=70 cases) sent for ODXRS testing from St James’s University Hospital, UK (2016-2019) were collected. Anonymised diagnostic glass slides (n=198 slides) of H&E-stained tumors were scanned at x20 magnification on an Aperio AT2 scanner. In parallel, relevant clinical and histological data were collected from pathology reports and electronic patient records, including both ODXRS and recurrence events during follow-up. The QPORB recurrence scale (QPORB-RS), which combines statistical physics and tumor biology to identify image-based malignant cell cycle deformation, extracts prognostic information from WSIs. The contribution of potential confounders (age, stage, grade, lesion size, Nottingham prognostic index and Charlson score) were accounted for. Results The QPORB-RS was prognostic for DFS for patients with predominantly node-negative (including node micro-metastases) HR+/HER2- tumors over a median follow-up period of 5 years (P=0.02; dichotomized Kaplan Meyer with median cut-off). The QPORB-RS concurred with ODXRS’s high vs. low recurrence risk in 73% (19/26) and 61% (27/44) of cases, respectively, with an overall agreement of 66% (46/70). Moreover, the QPORB-RS identified all 5 patients who had recurrences (with ODXRS of 6, 9, 10, 21 and 26, and ages of 55, 66, 42, 35 and 50 years, respectively) as being high risk in the subset of those given a low (including historically intermediate) ODXRS and who did not receive chemotherapy. Conclusion The QPORB-RS is a good prognostic test of risk of disease recurrence in breast cancer patients with predominantly node-negative (including node micro-metastases) HR+/HER2- tumors within a median 5-year follow-up period. Our efforts are now focussed on extending this cohort and establishing the prognostic value of the QPORB-RS across all breast carcinomas, regardless of molecular subtype, stage/node positivity and menopausal status. Citation Format: Satabhisa Mukhopadhyay, Tathagata Dasgupta, Elizabeth Walsh, Rebecca Millican-Slater, Andrew hanby, Joanne Stephenson, Craig A. Bunnell, Nicolas M. Orsi. Prediction of disease recurrence in low risk Oncotype Dx breast cancers from digital H&E-stained whole slide images of pre-treatment resections alone [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-48.

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.

Clinical pathways have the potential to improve complex clinical decision-making in cancer care. The authors implemented pathways with customized content to assist oncologists to select treatments, aiming for an on-pathway rate of 70%-85%. Treatment decisions were captured as on or off pathway, and metrics were shared monthly with users. Oncologists were categorized into quintiles based on on-pathway performance during the first 90 days of use. On-pathway rates were then calculated for days 91-360 (N = 121). Median on-pathway quintile rates varied from 50% to 100% in the initial 90-day period. During follow-up, median on-pathway rates shifted into the prespecified goal range for all groups. Clinical pathways resulted in greater uniformity in medical oncology practice. Monthly feedback about usage, familiarity with the electronic platform, and regular content updates are some factors that may influence on-pathway rates. Clinical pathways hold promise to manage unwarranted variation in cancer care.

Service systems are often stochastic and preplanned by appointments, yet implementations of their appointment systems are prevalently deterministic. At the planning stage of healthcare services, for example, customer punctuality and service durations are often assumed equal their means—and this gap, between planned and reality, motivated our research. Specifically, we consider appointment scheduling and sequencing under a time-varying number of servers, in a data-rich environment where service durations and punctuality are uncertain. Our data-driven approach, based on infinite-server queues, yields tractable and scalable solutions that accommodate hundreds of jobs and servers. We successfully test our approach against near-optimal algorithms (which exist for merely single-servers). This entails the development of a data-driven robust optimization approach with novel uncertainty sets. To test for practical performance, we leverage a unique data set from a cancer center that combines real-time locations, electronic health records, and appointments log. Focusing on one of the center’s infusion units (roughly 90 daily appointments, 25+ infusion chairs), we reduce cost (waiting plus overtime) on the order of 15%–40% consistently, under a wide range of experimental setups. This paper was accepted by Assaf Zeevi, stochastic models and simulation.

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).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/mNineteen 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.The combination of ruxolitinib and weekly paclitaxel was well tolerated with evidence of clinical activity. Further analysis of this combination is ongoing (NCT02041429).NCT02041429. Date of registration: January 22, 2014.

Background For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention. Materials and methods We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing. Results The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt. Conclusion Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation. Implications for practice This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays.

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 (Onco type DX) and delayed chemotherapy initiation. We sought to reduce the interval between surgery and adjuvant chemotherapy initiation by developing standardized criteria and workflows for Onco type DX testing. Methods: Criteria for surgeon-initiated reflex Onco type DX testing, workflows for communication between surgeons and medical oncologists, and a streamlined process for receiving and processing Onco type 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 Onco type testing for cases falling outside the criteria. We then examined 720 consecutive patients with breast cancer who underwent Onco type DX testing postoperatively between January 1, 2014 and November 28, 2016 and measured intervals between date of surgery, Onco type 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 Onco type DX ordering, 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 Onco type DX testing criteria and implementing streamlined workflows has led to clinically significant reductions in wait times to chemotherapy decision making and initiation.

This abstract was not presented at the symposium.

Introduction The necessity of using granulocyte-colony stimulating factor (G-CSF) during dose-dense (DD) paclitaxel (T) after doxorubicin and cyclophosphamide (AC) is unclear. Methods This was a retrospective cohort study including patients with stage I-III breast cancer treated at Dana-Farber Cancer Institute with adjuvant DD-ACT between January 2011 and December 2013. Descriptive analyses evaluating patterns of G-CSF utilization during T were performed. Results Overall, 156 patients were treated with DD-ACT by 26 providers. The majority of patients (135, 87%) received at least one dose of G-CSF during T (group 1), 17% of these patients received it in only one cycle and 48% received it in all four cycles. Reasons for omitting G-CSF included high baseline absolute neutrophil count and pain. Twenty-one (13%) patients did not receive any G-CSF during T (group 2). Respectively, 94% and 90% of patients completed the treatment in groups 1 and 2. There were no cases of treatment cessation due to neutropenia. Six percent of patients in group 1 had at least one treatment delay. There were no treatment delays reported in group 2. Variation in the use of G-CSF by provider and by patient was found, with 11 providers choosing not to use G-CSF in at least one patient. Conclusions We identified substantial variation in the use of G-CSF within the practice. However, omission of G-CSF was not associated with treatment delays or adverse events. Prospective studies are warranted to formally test whether routine G-CSF is necessary during dose-dense T therapy.

Background The scheduling of mastectomy with immediate reconstruction (M-IR) procedures requires coordination between breast and plastic surgical teams that can contribute to delays in breast cancer treatment and subsequently impact patient outcomes and satisfaction. The breast center leadership at our comprehensive cancer center established a time-to-treatment target of 28 days from initial consultation with a breast surgical oncologist to M-IR. We sought to determine if a centralized breast surgical coordinator (BC) could reduce preoperative delays. Methods We initiated a 60-day pilot program to evaluate the impact of a BC on the workflow, efficiency, and timeliness for patients seen at our breast center. All reconstructive surgery candidates were referred to the BC, who had access to the clinic and operating room schedules of the breast and plastic surgeons. The BC worked with patients and both surgical services to identify the earliest consult and surgery dates and facilitated case booking. Interval days between initial surgical consult and M-IR were calculated. The median time to M-IR and the proportion of M-IR cases that met the time-to-treatment goal was determined. These results were compared to a reference cohort of breast cancer patients undergoing M-IR during the same time period (January-March) in 2013 and 2014, who had their consults and surgeries scheduled independently by breast surgery administrative staff. Patients who received neoadjuvant therapy or did not have a definitive cancer diagnosis at initial consultation were excluded from the time-to-treatment calculation. Results A total of 99 patients were referred to the BC (62% cancer, 21% neoadjuvant, and 17% prophylactic) during the pilot period. Focusing exclusively on patients with a definitive breast cancer diagnosis at initial consultation, an 18.5% increase in the percentage of cases that met the target (p=0.04), and a 7 day decrease in the median number of days to M-IR (p=0.02) was observed with the implementation of the BC (Table 1). Table 1: Days to M-IR Pre and Post Implementation of BCPatients (N)Median Days to M-IR (IQR)% M-IR within 28 daysBaseline (59)40.0 (17.0)23.7%BC (45)33.0 (20.0)42.2%p-value0.020.04 Conclusion The coordination of care between breast surgical and reconstructive services presents timeliness challenges which may be partially alleviated through the implementation of a BC role. Establishing a centralized position to coordinate co-surgeon cases has improved time-to-treatment for M-IR at our cancer center. Further research is warranted to validate these preliminary findings, and determine the impact the BC has on operational efficiency and workflows. Citation Format: Losk K, Mallory M, Caterson S, Camuso K, Cutone L, Roberts P, Lin N, Bunnell C, Golshan M. Implementation of a breast/reconstructive surgery coordinator to reduce preoperative delays for patients undergoing mastectomy with immediate reconstruction. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-13-12.

Background: National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI designated comprehensive cancer center. Methods: We identified 523 patients who received post-operative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target timeframe, and unacceptable delay in chemotherapy initiation (UCD) as more than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype testing in HR+ patients. Results: Median days between LDS and chemotherapy initiation was 34 (IQR 15), with 30% of patients starting within 28 days of LDS and 23% having UCD (Table 1). Tumor characteristics such as subtype and stage affected UCD; patients with HR+ or HER2+ tumors were more likely to be delayed compared to those with TNBC. Patients with stage I disease were more likely to be delayed as well as patients undergoing mastectomy or mastectomy with reconstruction. Patients whose pathology sign-out was more than 10 days post-operatively were more likely to be delayed. A higher proportion of UCD was found in HR+ patients (31%) who received an Oncotype recurrence score compared to those who did not (20%). Table 1: Factors associated with delays in chemotherapy initiation N% DelayOdds Ratio95% CITotal52323 Age10 days)No331191.0--Yes192322.01.3-3.2Post-Op ComplicationsNo506221.0--Yes17412.20.7-6.6Clinical trial considerationNo435231.0--Yes88240.90.5-17 Conclusions: This study provides insight into populations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care. Citation Format: Losk K, Vaz Duarte Luis I, Camuso K, Lloyd M, Kadish S, Hirshfield-Bartek J, Cutone L, Golshan M, Lin N, Bunnell C. Factors associated with delays in chemotherapy initiation among patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-08.

2079 Background: Clinical oncology pathways aim to support clinical decision-making and reduce unwarranted practice variation across an enterprise. The Dana-Farber Cancer Institute (DFCI) implemented web-based oncology pathways with DFCI-customized content in each disease center and at each of its satellites. Our pre-specified aim was an on-pathway rate of 70-85%. Methods: Treatment decisions were electronically captured as on- or off- pathway. Monthly metrics about usage and on-pathway rate were shared with users on a monthly basis. Physicians were categorized into quintiles based on the calculated on-pathway performance during the first 90 days of each individual’s use of the platform. On-pathway rates were then calculated for days 91-360 to study changes in behavior over time. Physician and practice factors were examined to determine any differences by initial on-pathway quintile classification. Results: 122 physicians were eligible for inclusion in this analysis (minimum 5 navigations in each study period). On-pathway rates showed significant variability in the initial 90-day period: quintile 1 median 100%, quintiles 2-4 80.2%, and quintile 5 50% (Table). In the follow-up period, median on-pathway rates shifted into the pre-specified goal range for all groups. Physicians in quintiles 1 or 5 of initial on-pathway rate were more likely to have fewer total navigations than were physicians in quintiles 2-4 (p=0.003). While no other physician or practice characteristic differed significantly by on-pathway rate group, physicians in the first or last quintile were more likely to be in an academic setting, have a PhD, or navigate fewer pathways. Conclusions: Over time, the deployment of a web-based clinical pathways program resulted in greater uniformity in physician practice, based on on-pathway rate. Familiarity with the pathways platform and its navigation, monthly feedback about usage, and evolution of content over time are some factors that might have played a role. [Table: see text]

Purpose To assess the incidence and clinical significance of discrepancy in subspecialty interpretation of outside breast imaging examinations for newly diagnosed breast cancer patients presenting to a tertiary cancer center. Materials and Methods This Institutional Review Board–approved retrospective study included patients presenting from July 2016 to March 2017 to a National Cancer Institute–designated comprehensive cancer center for second opinion after breast cancer diagnosis. Outside and second opinion radiology reports of 252 randomly selected patients were compared by two subspecialty breast radiologists to consensus. A peer review score was assigned, modeled after ACR’s RADPEERTM peer review metric: 1—agree; 2—minor discrepancy (unlikely clinically significant); 3—moderate discrepancy (may be clinically significant); 4—major discrepancy (likely clinically significant). Among cases with clinically significant discrepancies, rates of clinical management change (management alterations including change in follow-up, neoadjuvant therapy use, and surgical management as a direct result of image review), and detection of additional malignancy were assessed through electronic medical record review. Results A significant difference in interpretation (scores = 3 or 4) was seen in 41 of 252 cases (16%, 95% confidence interval [CI], 11.7%-20.8%). The difference led to additional workup in 38 of 252 cases (15%, 95% CI 10.6%-19.5%) and change in clinical management in 18 of 252 cases (7.1%, 95% CI 4.0%-10.2%), including 15 of 252 with change in surgical management (6.0%, 95% CI, 3.0%-8.9%). An additional malignancy or larger area of disease was identified in 11 of 252 cases (4.4%, 95% CI, 1.8%-6.9%). Conclusion Discrepancy between outside and second-opinion breast imaging subspecialists frequently results in additional workup for breast cancer patients, changes in treatment plan, and identification of new malignancies.

Mixed results have been reported regarding whether older cancer patients are at a greater risk for chemotherapy‐induced neuropathy. This article further evaluates the age‐based risk of this adverse event., Purpose. A few previous studies report a direct relationship between older age and chemotherapy‐induced neuropathy. This study further evaluated this adverse event's age‐based risk. Methods. CALGB 40101 investigated adjuvant paclitaxel (80 mg/m2 once per week or 175 mg/m2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age‐based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years. Results. Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55–64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups (p = .14). In univariate analysis, only motor neuropathy had a higher age‐based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively (p = .04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one‐category improvement), showed no statistically significant age‐based differences. In contrast, obesity was associated with neuropathy, and every 2‐week paclitaxel was associated with trends toward neuropathy. Conclusion. Although paclitaxel‐induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number. NCT00041119 (CALGB 40101). Implications for Practice. Age alone is not an independent risk factor for paclitaxel‐induced neuropathy.

Patients referred to comprehensive cancer centers arrive with clinical data requiring review. Radiology consultation for second opinions often generates additional imaging requests; however, the impact of this service on breast cancer management remains unclear. We sought to identify the incidence of additional imaging requests and the effect additional imaging has on patients’ ultimate surgical management. Between November 2013 and March 2014, 153 consecutive patients with breast cancer received second opinion imaging reviews and definitive surgery at our cancer center. We identified the number of additional imaging requests, the number of fulfilled requests, the modality of additional imaging completed, the number of biopsies performed, and the number of patients whose management was altered due to additional imaging results. Of 153 patients, the mean age was 55 years; 98.9 % were female; 23.5 % (36) had in situ carcinoma (35 DCIS/1 LCIS), and 76.5 % (117) had invasive carcinoma. Additional imaging was suggested for 47.7 % (73/153) of patients. After multidisciplinary consultation, 65.8 % (48/73) of patients underwent additional imaging. Imaging review resulted in biopsy in 43.7 % (21/48) of patients and ultimately altered preliminary treatment plans in 37.5 % (18/48) of patients (Fig. 1). Changes in management included: conversion to mastectomy or breast conservation, neoadjuvant therapy, additional wire placement, and need for contralateral breast surgery. Our analysis of second opinion imaging consultation demonstrates the significant value that this service has on breast cancer management. Overall, 11.7 % (18/153) of patients who underwent breast surgery had management changes as a consequence of radiologic imaging review.

Reoperation after breast-conserving surgery (BCS) is common and has been partially associated with the lack of consensus on margin definition. We sought to investigate factors associated with reoperations and variation in reoperation rates across breast surgeons at our cancer center. Retrospective analyses of patients with clinical stage I–II breast cancer who underwent BCS between January and December 2014 were conducted prior to the recommendation of ‘no ink on tumor’ margin. Patient demographics and tumor and surgical data were extracted from medical records. A multivariate regression model was used to identify factors associated with reoperation. Overall, 490 patients with stage I (n = 408) and stage II (n = 89) breast cancer underwent BCS; seven patients had bilateral breast cancer and underwent bilateral BCS procedures. Median invasive tumor size was 1.1 cm, reoperation rate was 22.9% (n = 114) and varied among surgeons (range 15–40%), and, in 100 (88%) patients, the second procedure was re-excision, followed by unilateral mastectomy (n = 7, 6%) and bilateral mastectomy (n = 7, 6%). Intraoperative margin techniques (global cavity or targeted shaves) were utilized in 50.1% of cases, while no specific margin technique was utilized in 49.9% of cases. Median total specimen size was 65.8 cm3 (range 24.5–156.0). In the adjusted model, patients with multifocal disease were more likely to undergo reoperation [odds ratio (OR) 5.78, 95% confidence interval (CI) 2.17–15.42]. In addition, two surgeons were found to have significantly higher reoperation rates (OR 6.41, 95% CI 1.94–21.22; OR 3.41, 95% CI 1.07–10.85). Examination of BCS demonstrated variability in reoperation rates and margin practices among our breast surgeons. Future trials should look at surgeon-specific factors that may predict for reoperations.

BACKGROUND: Despite a growing number of clinical trials and supportive care programs for cancer survivors, recruitment of patients for these opportunities during the survivorship phase of care is challenging. We piloted a novel process to systematically educate patients about available research studies and supportive care programs as part of a survivorship care visit. METHODS: Between 3/2015–8/2015, patients seen in the Adult Survivorship Program who had not previously received a treatment summary and survivorship care plan (TS/SCP) were provided with one accompanied by a list of survivorship research studies and care programs tailored to their diagnosis. Survivorship providers discussed the opportunities and recorded whether the patient was interested in relevant studies and placed referrals to study staff. Following the visit, we tracked study enrollment and surveyed patients about their experience. RESULTS: 50/56 (89%) pilot participants completed the survey. Almost all (96%) reported that the TS/SCP visit and document helped with knowledge of research opportunities and supportive care interventions. Following receipt of the TS/SCP, 44% were interested in at least one study and in further follow-up with research staff. Of the 30 survivors eligible for at least one study, 6 (20%) have enrolled in at least one study to date. CONCLUSION: This pilot program demonstrates that the systematic sharing of available clinical studies and supportive care programming as part of a survivorship care plan visit is feasible, well-received by cancer survivors, and may facilitate and enhance accrual to clinical trials in the survivorship phase of care.

Few studies have examined care processes within providers’ and institutions’ control that expedite or delay care. The authors investigated the timeliness of breast cancer care at a comprehensive cancer center, focusing on factors influencing the time from initial consultation to first definitive surgery (FDS). The care of 1,461 women with breast cancer who underwent surgery at Dana-Farber/Brigham and Women’s Cancer Center from 2011 to 2013 was studied. The interval between consultation and FDS was calculated to identify variation in timeliness of care based on procedure, provider, and patients’ sociodemographic characteristics. Targets of 14 days for lumpectomy and mastectomy and 28 days from mastectomy with immediate reconstruction were set and used to define delay. Mean days between consultation and FDS was 21.6 (range 1–175, sd 15.8) for lumpectomy, 36.7 (5–230, 29.1) for mastectomy, and 37.5 (7–111, 16) for mastectomy with reconstruction. Patients under 40 were less likely to be delayed (OR = 0.56, 95 % CI = 0.33–0.94, p = 0.03). Patients undergoing mastectomy alone (OR = 2.64, 95 % CI = 1.80–3.89, p

110 Background: Emergency Department (ED) visits and subsequent hospitalizations are a major source of healthcare resource utilization and costs among cancer patients, compromising quality of care and patient satisfaction. Emerging evidence, including OCM and other alternative payment models suggest many of these visits may be preventable and effectively managed in oncology-specific urgent care clinics. Little is known about such care delivery models in the comprehensive cancer care arena. Methods: As part of larger effort to provide better, efficient, timely care to patients, an acute care clinic (ACC), appropriately staffed to provide ancillary services, was set up in an academic hospital outpatient setting with hours of operations 10:30- 8:00 pm to effectively manage patients with cancer-related symptoms. The objective was to change the site of care for patients who would otherwise be seen in the ED and discharged home as well as to potentially decrease the frequency of hospitalization following ED evaluation by providing oncology subspecialized care. A retrospective analysis of 4 months pre- and post-intervention was performed with emergency visits per 1000 visits per month as the primary outcome and subsequent hospitalizations as a secondary outcome. Results: A total of 1593 patients (821 pre-intervention and 772 post-intervention) were included. Preliminary analysis revealed a 7% observed reduction in ED visits (0.25 vs 0.23 visits per month per 1000 visits; p = 0.85) for oncology patients which otherwise would have seen a 12% increase, following the historical trend. Data also suggest more effective avoidance of acute care settings with discharge disposition for patients from ED pre-intervention versus ACC post-intervention being 32% vs 72% home, 67% vs 13% inpatient, 1% vs 6% ED respectively. Conclusions: The creation of an ACC to manage urgent patient visits in an ambulatory setting decreased ED visits and the likelihood of patient admission. Although initial findings suggest improved preliminary outcomes, further analysis is required to make any causal inference on the true impact of ACC intervention for reduction of ED and hospitalizations.

Background: We examined the timeliness of breast cancer care at our cancer center, focusing on care processes that affect the time from surgical consultation to surgery, with the goal of identifying improvement opportunities. Methods: We studied 584 women who underwent a mastectomy (with or without reconstruction) or breast conserving therapy at one of two Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) surgical sites between Jan. 1, 2011 and Feb. 28, 2012. We excluded patients who received a DF/BWCC consultation but received surgery elsewhere, those who required neo-adjuvant chemotherapy, and patients whose surgeons had no primary appointment at DF/BWCC. We calculated the delay between consultation and surgery, defined as an interval of greater than two weeks for cases of mastectomy without reconstruction or breast conserving therapy, and four weeks for those with mastectomy with immediate reconstruction. We tabulated the number of patients with a delay, stratified by type of procedure and patient characteristics. We examined factors associated with a delay in bivariate analyses using Chi-square and multivariate logistic regression models with two-tailed tests and p Results. The mean number of days from consultation to surgery was 21 (range 2-104, SD 14) for lumpectomy, 31 (5-230, 28) for mastectomy, and 41 (6-180, 26) for mastectomy with reconstruction. Of women undergoing breast conserving therapy or mastectomy without reconstruction, 296 (67%) experienced a delay compared to 102 (71%) undergoing mastectomy with immediate reconstruction. Although no statistically significant findings were obtained in the bivariate analyses, age over 60 was associated with a two-fold delay in the multivariable model. Delays were also more likely among mastectomy procedures compared to breast conserving therapy. TableCharacteristicsNo Delay (n = 186)Delay (n = 398)OR (95% CI) No. (%)No. (%) Age 70-9528 (15)69 (17)2.6 (1.3-5.5)60-6943 (23)107 (27)2.0 (1.2-3.6)50-5951 (27)103 (26)1.3 (0.8-2.0)18-4964 (34)119 (30)1.0Race Non-White21 (11)43 (11)1.0 (0.6-1.9)White161 (89)346 (89)1.0Missing49 Primary Language Non-English7 (4)14 (4)1.0 (0.4-2.9)English179 (96)384 (97)1.0Insurance Medicare49 (26.3)97 (24)0.6 (0.3-1.0)Medicaid6 (3)8 (2)0.6 (0.2-1.7)Private131 (70)292 (74)1.0Missing01 Procedure Mastectomy with Recon41 (22)102 (26)1.6 (1.0-2.5)Mastectomy without Recon15 (8.1)53 (13)1.9 (1.0-3.6)Lumpectomy130 (70)243 (61)1.0 The 4 highest-volume breast surgeons (n>20 procedures each) varied in the time from initial consultation to plastic surgery consultation, from a mean of 7 to 22 days. Early screening and referral practices accounted for much of this variation. Delayed surgeries among the 50 patients with delays of at least 45 days included the need for additional testing or imaging, pre-operative medical evaluation, or “personal” reasons. Conclusion. Analyses of the interval from consultation to breast surgery identified process variation that may be amenable to improvement initiatives. Cancer centers should invest in efforts to measure, monitor, and improve the timeliness of breast cancer care. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-15.

Background Oncology care is delivered largely in ambulatory settings by interdisciplinary teams. Treatments are often complex, extended in time, dispersed geographically and vulnerable to teamwork failures. To address this risk, we developed and piloted a team training initiative in the breast cancer programme at a comprehensive cancer centre. Methods Based on clinic observations, interviews with key staff and analyses of incident reports, we developed interventions to address four high-risk areas: (1) miscommunication of chemotherapy order changes on the day of treatment; (2) missing orders on treatment days without concurrent physician appointments; (3) poor follow-up with team members about active patient issues; and (4) conflict between providers and staff. The project team developed protocols and agreements to address team members’ roles, responsibilities and behaviours. Results Using a train-the-trainer model, 92% of breast cancer staff completed training. The incidence of missing orders for unlinked visits decreased from 30% to 2% (p

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.

Background National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI-Designated Comprehensive Cancer Center. Patients and methods We identified 523 patients who received postoperative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target time frame, and an unacceptable delay in chemotherapy initiation (UCD) as greater than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype DX testing in patients with hormone receptor (HR)-positive breast cancer. Results Median days between LDS and chemotherapy initiation was 34 (interquartile range, 15), with 30% of patients starting within 28 days of LDS and 26.9% having UCD. Tumor characteristics such as subtype and stage affected UCD; patients with HR-positive or HER2-positive tumors were more likely to be delayed compared with those with triple-negative breast cancer. Patients with stage I disease, those undergoing mastectomy with or without immediate reconstruction, and those whose pathology sign-out was greater than 10 days postoperatively were more likely to be delayed. A higher proportion of UCD was found in HR-positive patients (31%) for whom Oncotype DX testing was ordered compared with those in whom it was not ordered (20%). Conclusions This study provides insight into subpopulations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care.

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 days from initial consultation with the breast surgeon to MIR. 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.

Purpose Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agent-based chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative. Preclinical studies demonstrate that ixabepilone and taxanes produce a similar neurotoxicity profile. Methods We searched databases of phase II/III clinical trials involving patients receiving ixabepilone as a monotherapy or in combination with capecitabine for incidences of neuropathy. Potential risk factors for grade 3/4 PN were identified by a Cox regression analysis on a dataset of 1,540 patients with different tumor types across multiple studies. Results Rates for incidence of ixabepilone-induced severe PN (Common Terminology Criteria for Adverse Events grade 3/4) ranged from 1% in early untreated breast cancer up to 24% in heavily pretreated metastatic breast cancer; grade 4 PN was rare (≤1%). Common symptoms included numbness, paresthesias, and sometimes dysesthesias. Cox regression analysis identified only preexisting neuropathy as a risk factor for increased ixabepilone-associated PN. The management of PN has been primarily through dose adjustments (dose delays and/or dose reduction). Patients had resolution of their neuropathy within a median time of 5 to 6 weeks. Conclusions PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays. Electronic supplementary material The online version of this article (doi:10.1007/s00520-012-1384-0) contains supplementary material, which is available to authorized users.

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.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.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.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.

Purpose There is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline. Patients and Methods Patients were age ≥ 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m2 intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival. Results All 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature. Conclusion Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.

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/m2 or 3-hour infusion of 40 mg/m2 every 3 weeks). Results Of 49 patients treated with 40 mg/m2 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/m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.

The performance of scheduled business processes is of central importance for services and manufacturing systems. However, current techniques for performance analysis do not take both queueing semantics and the process perspective into account. In this work, we address this gap by developing a novel method for utilizing rich process logs to analyze performance of scheduled processes. The proposed method combines simulation, queueing analytics, and statistical methods. At the heart of our approach is the discovery of an individual-case model from data, based on an extension of the Colored Petri Nets formalism. The resulting model can be simulated to answer performance queries, yet it is computational inefficient. To reduce the computational cost, the discovered model is projected into Queueing Networks, a formalism that enables efficient performance analytics. The projection is facilitated by a sequence of folding operations that alter the structure and dynamics of the Petri Net model. We evaluate the approach with a real-world dataset from Dana-Farber Cancer Institute, a large outpatient cancer hospital in the United States.

In the multidisciplinary care model, breast imagers frequently provide second-opinion reviews of imaging studies performed at outside institutions. However, the need for additional imaging and timeliness of obtaining these studies has yet to be established. We sought to evaluate the frequency of additional imaging orders by breast surgeons and to evaluate the impact of this supplementary imaging on timeliness of surgery. We identified 2489 consecutive women with breast cancer who underwent first definitive surgery (FDS) at our comprehensive cancer center between 2011 and 2013. The number of breast-specific imaging studies performed for each patient between initial consultation and FDS was obtained. χ 2 tests were used to quantify the proportion of patients undergoing additional imaging by surgeon. Interval time between initial consultation and additional imaging and/or biopsy was calculated. The delay of additional imaging on time to FDS was assessed by t test. Of 2489 patients, 615 (24.7 %) had at least one additional breast-specific imaging study performed between initial consultation and FDS, with 222 patients undergoing additional biopsies (8.9 %). The proportion of patients receiving imaging tests by breast surgeon ranged from 15 to 39 % (p

Service processes, for example in transportation, telecommunications or the health sector, are the backbone of today’s economies. Conceptual models of such service processes enable operational analysis that supports, e.g., resource provisioning or delay prediction. Automatic mining of such operational models becomes feasible in the presence of event-data traces. In this work, we target the mining of models that assume a resource-driven perspective and focus on queueing effects. We propose a solution for the discovery and validation problem of scheduled service processes - processes with a predefined schedule for the execution of activities. Our prime example for such processes are complex outpatient treatments that follow prior appointments. Given a process schedule and data recorded during process execution, we show how to discover Fork/Join networks, a specific class of queueing networks, and how to assess their operational validity. We evaluate our approach with a real-world dataset comprising clinical pathways of outpatient clinics, recorded by a real-time location system (RTLS). We demonstrate the value of the approach by identifying and explaining operational bottlenecks.

Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly × 12 weeks (60 mg/m 2 ), or every 3 weeks × 4 cycles (135–175 mg/m 2 ). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m 2 per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135–175 mg/m 2 . However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

Purpose Dose-dense, every-2-week adjuvant chemotherapy using doxorubicin/cyclophosphamide (AC; 60/600 mg/m2 every 2 weeks × four cycles) followed by paclitaxel (175 mg/m2 every 2 weeks × 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 μg SQ every 2 weeks for hemoglobin ≤ 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. Recent clinical trials suggest that adjuvant ovarian suppression may be an equally effective and less toxic alternative to systemic chemotherapy in premenopausal women with hormone-responsive breast cancer. We used a decision-analytic framework to evaluate tradeoffs between efficacy and quality of life in the choice between these treatments. Patients and methods. We used a Markov state-transition model to simulate clinical practice in a cohort of 40-year-old premenopausal women with newly diagnosed, hormone-responsive early breast cancer. We assessed three adjuvant treatments: chemotherapy, surgical ovarian suppression, and medical ovarian suppression. Outcomes were recurrence-free, overall, and quality-adjusted survival. Quality-adjusted survival reflected effects of cancer, treatment-related side effects, and menopausal symptoms. Results. Assuming equal efficacy, ovarian suppression was superior to chemotherapy when the relative utility of chemotherapy side effects compared with ovarian suppression side effects was less than 0.95. Results were sensitive to assumptions about the likelihood, duration and consequences of treatment-induced menopause. Treatment choice was affected by a 7% proportional increase in the efficacy of one therapy relative to the others, independent of other factors. Conclusion. If adjuvant chemotherapy and ovarian suppression have similar efficacy, then there may be a subgroup of women for whom quality-of-life considerations dominate the choice of treatment. However, small differences in the relative efficacy of these therapies have a substantial impact on treatment choice, regardless of side effects and menopausal transitions.

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 × 1, then 2 mg/kg/wk × 11) in combination with paclitaxel (175 mg/m2 every 3 weeks × 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.

69 Background: In 2013, Dana-Farber Cancer Institute began an initiative to improve the new patient experience. Our goal was to remove barriers to access and, as much a possible, begin to care for individuals even before they step foot through our door. A key component of this initiative was for each patient to receive a phone call from an oncology nurse shortly after speaking to a new patient coordinator to schedule their first appointment. The purpose of the call was to answer questions about their diagnosis, the care they will receive and to begin the process of assessing their individual needs. Methods: The program was supported by over 40 full and part-time oncology nurses who devote a portion of their time each day to calling new patients prior to their first visit. In total nurses made over 10,000 phone calls per year. Through a survey given to patients after the intake process, we gathered feedback from over 1,200 patients, which overwhelmingly demonstrated a positive response to receiving a phone call from a nurse. We also investigated if receiving a phone call from a nurse prior to the first visit impacted the likelihood of retaining the patient for their treatment. Results: Comparing 9,000 new patients over one year, we found that patients who spoke to a nurse prior to their first appointment had a 13.5% higher relative retention rate compared to patients who did not speak to a nurse (see figure 1, absolute difference is 42.9% vs. 37.8%, odds ratio = 1.24, confidence interval 1.10-1.39, P < 0.0005). Controlling for confounding variables, a logistical regression with 15 variables was performed (e.g. time to first appointment, age,). Receiving a call from a nurse was one of the most predictive, statistically significant variables for patient retention. Conclusions: Given the positive qualitative response from patients and the quantitative impact on retention, we continue to build the program to ensure all patients receive a phone call from a nurse prior to their first visit. [Table: see text]

140 Background: The implementation of electronic medical records (EMR) has been noted to disrupt clinical workflows as providers acclimate to a new EMR. On May 30, 2015, Dana-Farber Cancer Institute (DFCI) implemented a new EMR. Using our Real Time Location System (RTLS), we sought to identify the time required to stabilize the experience for providers. We identified factors that may speed the stabilization rate to guide EMR implementations elsewhere. Methods: DFCI uses an RTLS to timestamp patient and provider locations throughout the day. To adjust for variation in appointment types, we measured the ratio of the actual exam duration (recorded by the RTLS) to the scheduled exam duration. We compared to a 3-month baseline average to quantify the immediate impact of implementation. We tracked the ratio over time to identify when stabilization occurred and compare to baseline performance. To infer influential factors, we performed a regression analysis based on RTLS data from the first 6 months post implementation. Results: The stabilization curve fits the “classical” power function model. Rapid improvement over the first ten days of clinical practice was followed by a gradual period of ongoing stabilization. The EMR impact on exam duration required approximately 30 clinical days for each provider to reach the baseline value with continued improvement over the next 30 clinical days. Factors with a potential to improve the rate of stabilization were provider type (MD, NP or PA), provider gender and provider age. Conclusions: The first ten clinical days experience a fast rate of improvement. Thus, while the initial impact is disruptive, operations improve rapidly. Initial improvement may be attributed to fixing “bugs” in the EMR and rapid learning by providers. Our presentation will explore factors that impact the rate of improvement. Understanding the stabilization rate and factors can aid organizations in training, implementation, and ongoing improvement to minimize the impact of EMR disruption. [Table: see text]

166 Background: Oncotype DX testing in breast cancer is associated with delayed chemotherapy initiation, which may adversely impact clinical outcomes and patient satisfaction. We sought to reduce delays between surgery and adjuvant chemotherapy initiation among patients who undergo Oncotype DX testing by developing standard ordering criteria and modifying surgical oncology, medical oncology, and pathology workflows. Methods: We implemented ‘reflex’ Oncotype DX testing for any patient ≤ 65 with the following tumor characteristics: T1cN0 (grade 2-3), T2N0 (grade 1-2), or T1/T2N1 (grade 1-2). A new process was developed whereby once pathology review is complete surgeons communicate the results to medical oncologists in real-time and initiate requests for Oncotype DX when appropriate. Medical oncologists can order Oncotype for cases outside the criteria. A streamlined pathology system for receiving and processing Oncotype DX requests was also developed. We then examined 649 consecutive breast cancer patients who received postoperative Oncotype DX testing and measured time intervals between surgery date, Oncotype DX order date, Oncotype DX result received date, and chemotherapy initiation date (if applicable) before and after intervention implementation. Results: The interventions reduced the turnaround time (TAT) from surgery to Oncotype DX order and time to when the results were available by 7.7 days and 6.3 days, respectively. A 6.5 day decrease in the mean time from surgery to chemotherapy initiation was observed. The decrease in the standard deviation also suggests a reduction in process variation. Conclusions: Developing Oncotype DX testing criteria and implementing streamlined workflows among providers has led to a significant reduction in Oncotype DX ordering TAT and wait times to chemotherapy initiation. [Table: see text]

To the Editor: The detection and monitoring of preanalytical bias in the clinical laboratory can be challenging, as bias can be introduced at any point from specimen collection to sample processing, and those biases stemming from sample collection or handling before delivery to the laboratory can be difficult to measure and eliminate. In particular, variations in potassium concentrations due to preanalytical sources of error are a pervasive and clinically significant problem (1–3). Initial concern regarding spuriously increased potassium concentrations (>5.2 mmol/L) occurring in the laboratory of the Dana Farber Cancer Institute was raised by clinicians reporting patients displaying increased potassium without any apparent clinical justification. Review of the medical records of the patients involved demonstrated that the majority had potassium values within the reference interval on the draw before the increased value, with a mean increase in potassium of 1.2 (0.7) mmol/L vs the prior value. Retesting on an alternative platform confirmed hyperkalemia. To assess for a preanalytical cause of these values, samples were redrawn on the same day …

PURPOSE: To evaluate the safety and efficacy of weekly docetaxel in women with metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine women were enrolled onto a study of weekly docetaxel given at 40 mg/m2/wk. Each cycle consisted of 6 weeks of therapy followed by a 2-week treatment break, repeated until disease progression or removal from study for toxicity or patient preference. Fifty-two percent of patients had been previously treated with adjuvant chemotherapy; 21% had received prior chemotherapy for metastatic breast cancer, and 31% had previously received anthracyclines. All patients were assessable for toxicity; two patients were not assessable for response but are included in an intent-to-treat analysis. RESULTS: Patients received a median of 18 infusions, with a median cumulative docetaxel dose of 720 mg/m2. There were no complete responses. Twelve patients had partial responses (overall response rate, 41%; 95% confidence interval, 24% to 61%), all occurring within the first two cycles. Similar response rates were observed among subgroups of patients previously treated either with any prior chemotherapy or with anthracyclines. An additional 17% of patients had stable disease for at least 6 months. The regimen was generally well tolerated. There was no grade 4 toxicity. Only 28% of patients had any grade 3 toxicity, most commonly neutropenia and fatigue. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and eye tearing/conjunctivitis became more common with repetitive dosing, although these side effects rarely exceeded grade 2. Dose reductions were made for eight of 29 patients, most often because of fatigue (n = 5). CONCLUSION: Weekly docetaxel is active in treating patients with metastatic breast cancer, with a side effect profile that differs from every-3-weeks therapy.

BACKGROUND Ifosfamide and paclitaxel are antineoplastic agents with broad activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used in combination. METHODS Patients with refractory, incurable solid tumors were entered on a 5-step Phase I trial of ifosfamide, given in doses of 2-3 g/m2 intravenous (i.v.) bolus for 3 days with mesna support, and paclitaxel, given in doses of 135-190 g/m2 i.v. by continuous infusion over 24 hours. Paclitaxel was given after the first dose of ifosfamide on Day 1. RESULTS Twenty-three patients were treated, and the maximum tolerated dose was the highest planned dose level of the trial: ifosfamide, 3 g/m2/day i.v. for 3 days, and paclitaxel, 190 mg/m2 i.v. over 24 hours. Hematologic toxicity was not dose-limiting, and although neutropenia occurred, it was brief (median, 2-4 days) and resulted in hospitalization for neutropenia and fever in only 7 of 111 courses of therapy. For patients treated at the highest dose level, only 1 of 50 courses of therapy resulted in hospitalization for neutropenia and fever. Nonhematologic toxicity also was not severe and no significant neuropathy occurred. Although patients entered into the study were heavily pretreated, responses were observed, particularly in patients with breast or ovarian carcinoma. CONCLUSIONS Ifosfamide and paclitaxel can be administered safely in the doses used in this study and there are indications of significant antitumor effect. Further studies are necessary to explore the antineoplastic activity of this regimen, particularly for patients with breast and ovarian carcinoma. Cancer 1998;82:561-6. © 1998 American Cancer Society.

A multicenter NCI-sponsored phase II study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer.Two cohorts were enrolled: cohort 1 had received no prior chemotherapy or trastuzumab for metastatic disease and cohort 2 had received 1-2 prior trastuzumab-containing regimens for metastatic disease. Patients in both cohorts received ixabepilone 40 mg/m(2) as a 3-h infusion and trastuzumab on day 1 of a 21-day cycle. Tumor biomarkers that may predict response to trastuzumab were explored.Thirty-nine women entered the study with 15 patients in cohort 1 and 24 patients in cohort 2. Across both cohorts, the overall RR was 44%, with a clinical benefit rate (CR + PR + SD for at least 24 weeks) of 56%. Treatment-related toxic effects included neuropathy (grade ≥2, 56%), leukopenia (grade ≥2, 26%), myalgias (grade ≥2, 21%), neutropenia (grade ≥2, 23%), and anemia (grade ≥2, 18%).This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has encouraging activity as first and subsequent line therapy for metastatic breast cancer.

Background: Systemic mastocytosis is characterized by mast cell infiltration of bone marrow and tissues in the absence of identified circulating bone marrow–derived progenitors. A 58-year-old man was first seen with aggressive systemic mastocytosis manifested by urticaria pigmentosa, hepatosplenomegaly, generalized bone lesions, anemia, thrombocytopenia, monoclonal gammopathy, and increased urine histamine levels. OBJECTIVES AND METHODS: A rapidly progressive anemia and thrombocytopenia dictated a splenectomy. We sought to identify the mast cell progenitors in the peripheral blood and to provide evidence of their maturation in tissues with immunohistochemical and ultrastructural analyses. Results: The peripheral blood contained 1% to 3% nonmetachromatic mononuclear cells with eccentric nuclei that expressed the mast cell proteases, tryptase and carboxypeptidase A, along with c- kit, stem cell factor (SCF), and high-affinity IgE receptor (FcϵRI), but not chymase. Similar mononuclear cells colocalized in the spleen and lymph nodes with mature, metachromatic mast cells that expressed tryptase, chymase, carboxypeptidase A, c- kit, SCF, and FcϵRI. Electron microscopy disclosed, at each site, a mature mast cell population with electron-dense, scroll-poor granules. Conclusions: The peripheral blood of a patient with aggressive systemic mastocytosis contained immature mononuclear cells of the mast cell lineage that express c- kit, SCF, tryptase, carboxypeptidase A, and FcϵRI. These cells were also found in the skin, spleen, and lymph nodes where they presumably expand, differentiate, and mature, assuming the mast cell phenotype for those tissues characterized by metachromasia, expression of a full range of mast cell–related secretory granule proteases, and ultrastructural appearance. The presence of SCF on the surface membrane of the circulating, highly immature mast cells suggests an autocrine regulation of the c- kit –SCF interaction. (J ALLERGY CLIN IMMUNOL 1996;98:831-40.)

Introduction: Non-stem cell therapies including cellular vaccines and chimeric antigen receptor (CAR) T cells are experiencing explosive growth in research development and clinical applications. Demand is growing, with several CAR products heading for imminent FDA approval. The variety of products poses a challenge to even experienced cancer centers. Our goal was to create clinical and operational infrastructure to deliver these therapies efficiently and safely. We leveraged existing workflows and care models spanning inpatient and outpatient settings and disease groups previously unfamiliar with cell therapies. Methods: We conducted over 30 internal stakeholder interviews across research, cell processing, nursing, physician, pharmacy, and operational areas and queried experts at other cell-engineering sites. Key areas identified were 1) cell distribution, 2) trial initiation, 3) communication, training, and clinical care, 4) resource utilization, and 5) safety and outcome monitoring. A steering committee formulated guiding principles: make safety paramount, systematically coordinate care, recognize each cell therapy and sponsor's unique requirements, and minimize unnecessary infrastructure. Aspects of the care spectrum evaluated spanned from patient identification, financial clearance, outpatient workup, cell collection, admission/administration, to post-infusion follow-up. Results: 1) Cell distribution: despite product manufacturing at central contracted sites, novel internal workflows were required to ensure chain of identity through multiple hand-offs. A standard questionnaire was devised to determine unique trial hurdles and a consistent approach to labeling, shipping and communication with sponsors and clinicians. Biweekly meetings between apheresis, cell processing, nursing, and pharmacy staff to discuss logistics and impediments were established. (Figure) 2) Trial initiation: A "start up kit" was developed to explain key entities and workflows (e.g. apheresis, pharmacy for tocilizumab, biosafety review) to help investigators unfamiliar with cell therapies navigate submission. 3) Communication, training and clinical care: guidance in budget design, tools to flag high-risk patients in electronic medical records (EMR), and education on nomenclature were developed. Over 20 general education sessions were conducted across clinical and operational areas, in addition to trial-specific training, for financial coordinators, patient safety groups, MDs, residents, PAs and nurses in all disease areas both inpatient and outpatient, even statisticians. We created email distribution lists, EMR flags, a case management system, and toxicity management order sets to ensure awareness of admissions, availability of crucial medications, recognition of cytokine release or neurotoxicity requiring unique intervention, and priming of ICU resources. A weekly forum for MDs and clinical stakeholders to share clinical events and needs was instituted. 4) Resource utilization: shortfalls were identified in cell-collection capacity and scheduling, product distribution, and clinical expertise. Dedicated clinician positions were created, and scheduling was consolidated to optimize capacity within and outside existing BMT infrastructure. 5) Safety and outcome monitoring: a format and forum was developed for quarterly review of major outcomes allowing institutional oversight over the spectrum of investigational cell therapies and standard of care administrations. Discussion: With the explosion in outpatient cancer vaccines and CAR T cells, the need for additional physical resources, new medications, experienced clinicians, and communication tools became evident. We describe our approach to creating novel workflows to ensure patients receive the latest cell therapies safely, timely distribution of cells, educated ED and ICU involvement, and rapid expert management including anti-cytokine therapy. The investment of individual centers to bring cellular therapies safely into clinical care should not be under-appreciated, particularly given the high-risk nature of these treatments and the unique processes and high-coordinated activities these new modalities require. Regulatory agencies, such as FACT, are likewise requesting that such safety measures, standard procedures and oversight be addressed. Figure Figure. Disclosures Soiffer: Kiadis: Membership on an entity's Board of Directors or advisory committees; Juno: Consultancy.

61 Background: Despite a growing number of clinical trials and supportive care programs for cancer survivors, recruitment of patients (pts) for these opportunities during the survivorship phase of care is challenging. We piloted a program to systematically share available research studies and supportive care programs with pts as part of their treatment summary and survivorship care plan (TS/SCP) visit at our institution. Methods: Between 3/2015-8/2015, pts seen in the Adult Survivorship Program who had not previously received a TS/SCP were provided with one that included a list of survivorship research studies and care programscustomized to their diagnosis. Survivorship providers discussed the opportunities and recorded whether the pt was interested in relevant studies and placed referrals to study staff. Following the visit, we tracked study enrollment and surveyed pts about their experience. Results: 50/56 (89%) pts who participated in the pilot responded to the survey.Median age was 51 (range: 26-73); 78% were female; 54% were survivors of breast cancer; 42%, lymphoma; 2%, breast and lymphoma; 2%, colorectal cancer. Only 34% knew what a TS/SCP was before their visit; however 96% said having a TS/SCP would be helpful when visiting a primary care or other provider; 92% said the TS/SCP visit and document had or will help with knowledge of research opportunities and supportive care interventions. 90% responded that the study information they received was useful; 44% were interested in at least 1 study and would follow-up with a research coordinator. Of the 30 survivors eligible for ≥ 1 study, 5 have enrolled to date. Conclusions: This pilot program demonstrated that the systematic sharing of relevant clinical studies and supportive care programming as part of a TS/SCP visit is feasible and well-received by cancer survivors. Expansion of this novel program should help to enhance clinical research accrual for cancer survivors as well as ensure awareness of available supportive care interventions.

The number of cancer patients and cancer survivors continues to increase rapidly amid predictions of a shortfall in physicians to care for them. In addition, newer cancer therapies have become increasingly complex and resource-intensive, compounding the impending workforce shortage. Simultaneously, the growing understanding of the biologic heterogeneity of cancer and the development of pharmacogenomics have opened up the possibility of personalized approaches to cancer diagnosis and treatment. Such personalization has been promulgated as a means of decreasing the cost of drug development, improving the efficacy of treatments, and reducing treatment toxicity. Although there have been notable successes, the fulfillment of these promises has been inconsistent. Providing care for future cancer patients will require the development of innovative delivery models. Moreover, new approaches to clinical research design, to the assessment of therapeutic value, and to the approval of and reimbursement for diagnostics and treatments are needed.