Braden Rowley

Variable specimen handling affects hormone receptor test results in women with breast cancer: a large multihospital retrospective study.

CONTEXT Intermountain Healthcare hospitals use a single, standardized laboratory and automated testing process for estrogen receptor/progesterone receptor (ER/PR) tests to minimize testing errors. OBJECTIVES To test the (1) variability in ER/PR negativity among hospitals and (2) association between specimen handling conditions and ER/PR negativity. DESIGN Retrospective study of women who had breast cancer surgery at 7 Intermountain hospitals and ER/PR tests ordered between 1997 and 2003. Data were extracted from cancer registry. Frequency of ER/PR negativity was calculated for each surgery day and compared among hospitals and between 2 groups: regular (specimens obtained Sunday through Thursday, more likely to be tested within 24 hours of surgery) and prolonged (specimens obtained on Friday and Saturday, more likely to be tested more than 24 hours after surgery) specimen handling conditions. RESULTS Five thousand seventy-seven women were tested for ER/PR. The frequency of ER and PR negativity was 20.9% and 27.9%, respectively. It increased with each day of the week for both ER (P = .03) and PR (P = .059) and tended to be higher for prolonged specimens for ER (23.6% versus 20.4%; P = .03) and for PR (30.1% versus 27.4%; P = .11) compared with regular specimens. After controlling for age and tumor size, both ER (P = .02) and PR (P = .02) negativity was significantly different among the hospitals and was associated with prolonged specimens for ER (P = .04) but not for PR (P = .09). CONCLUSIONS Estrogen receptor and PR negativity remained highly variable among hospitals despite use of a single laboratory and tended to be significantly associated with prolonged specimen handling. More studies are needed to confirm these findings.

Use of posttreatment imaging and biomarkers in survivors of early‐stage breast cancer: Inappropriate surveillance or necessary care?

Advanced imaging and serum biomarkers are commonly used for surveillance in patients with early‐stage breast cancer, despite recommendations against this practice. Incentives to perform such low‐value testing may be less prominent in integrated health care delivery systems. The purpose of the current study was to evaluate and compare the use of these services within 2 integrated systems: Kaiser Permanente (KP) and Intermountain Healthcare (IH). The authors also sought to distinguish the indication for testing: diagnostic purposes or routine surveillance.

Use of Imaging for Staging of Early-Stage Breast Cancer in Two Integrated Health Care Systems: Adherence With a Choosing Wisely Recommendation

PURPOSE Advanced imaging is commonly used for staging of early-stage breast cancer, despite recommendations against this practice. The objective of this study was to evaluate and compare use of imaging for staging of breast cancer in two integrated health care systems, Kaiser Permanente (KP) and Intermountain Healthcare (IH). We also sought to distinguish whether imaging was routine or used for diagnostic purposes. METHODS We identified patients with stages 0 to IIB breast cancer diagnosed between 2010 and 2012. Using KP and IH electronic health records, we identified use of computed tomography, positron emission tomography, or bone scintigraphy 30 days before diagnosis to 30 days postsurgery. We performed chart abstraction on a random sample of patients who received a presurgical imaging test to identify indication. RESULTS For the sample of 10,010 patients, mean age at diagnosis was 60 years (range, 22 to 99 years); with 21% stage 0, 47% stage I, and 32% stage II. Overall, 15% of patients (n = 1,480) received at least one imaging test during the staging window, 15% at KP and 14% at IH (P = .5). Eight percent of patients received imaging before surgery, and 7% postsurgery. We found significant intraregional variation in imaging use. Chart abstraction (n = 129, 16% of patients who received presurgical imaging) revealed that 48% of presurgical imaging was diagnostic. CONCLUSION Use of imaging for staging of low-risk breast cancer was similar in both systems, and slightly lower than has been reported in the literature. Approximately half of imaging tests were ordered in response to a sign or symptom.

Adjuvant radiation in early stage, unfavorable histology endometrial carcinoma is associated with improved local control and survival

OBJECTIVE Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer. METHODS We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival. RESULTS The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local-regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local-regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p=0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p=0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value=0.018) was associated with a significant increase in local relapse free survival. CONCLUSIONS Adjuvant radiation therapy was significantly associated with an improvement in local-regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.

Experience with Use of the Oncotype DX Gene Assay Test in a Multicenter Community-Based Healthcare System.

Background:Oncotype DX has been validated to quantify the risk of distant recurrence and predict the benefit of chemotherapy (CT) in ER positive, node negative breast cancer treated with tamoxifen. A retrospective study was undertaken to assess the use of the Oncotype DX test at Intermountain Healthcare. Intermountain is a not-for-profit healthcare system with 21 inpatient facilities, 9 comprehensive cancer centers and 42 affiliated medical oncologists ranging from single practitioners to multiphysician groups.Methods: This study contains a group of T1-3 N0 ER+ breast cancer patients who received an Oncotype DX test paired with a control group of non-tested T1-T3 N0 ER+ patients receiving hormone therapy (HT) from the same period. Data comes from a supplemental database containing treatment and follow-up data from individual physician offices combined with data from Intermountain9s cancer registry. To ensure data completeness, Genomic Health provided a list of relevant Oncotype DX results for study patients. The analysis was done using multivariate logistic regression and controlled for age, tumor size, grade and T stage.Results: From 2005 to 2008, Oncotype DX testing was performed on tumor specimens from 285 patients. 8 patients had positive nodes and 4 patients were ER negative. In addition, 9 patients did not and will not receive HT (5 refused, 4 contraindicated) and 9 patients have yet to begin HT. 11 patients were lost to follow-up. Of the remaining 244 patients who form the study group, six patients were Her-2 neu positive (1 high recurrence score (RS), 3 intermediate and 2 low). Tumor size ranged from 2 cm. Compared to our control group of 688 patients, Oncotype DX-tested patients are younger (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6058.

Use of Imaging for Staging of Localized Breast Cancer in Two Integrated Health Care Systems: Adherence to a Choosing Wisely Recommendation

Purpose: Advanced imaging is commonly used for staging of early-stage breast cancer, despite recommendations against this practice. The objective of this study was to evaluate and compare use of imaging for staging of breast cancer in two integrated health care systems, Kaiser Permanente (KP) and Intermountain Healthcare (IH). We also sought to distinguish whether imaging was routine or used for diagnostic purposes. Methods: We identified patients with stages 0 to IIB breast cancer diagnosed between 2010 and 2012. Using KP and IH electronic health records, we identified use of computed tomography, positron emission tomography, or bone scintigraphy 30 days before diagnosis to 30 days postsurgery. We performed chart abstraction on a random sample of patients who received a presurgical imaging test to identify indication. Results: For the sample of 10,010 patients, mean age at diagnosis was 60 years (range, 22 to 99 years); with 21% stage 0, 47% stage I, and 32% stage II. Overall, 15% of patients (n 1,480) received at least one imaging test during the staging window, 15% at KP and 14% at IH (P .5). Eight percent of patients received imaging before surgery, and 7% postsurgery. We found significant intraregional variation in imaging use. Chart abstraction (n 129, 16% of patients who received presurgical imaging) revealed that 48% of presurgical imaging was diagnostic. Conclusion: Use of imaging for staging of low-risk breast cancer was similar in both systems, and slightly lower than has been reported in the literature. Approximately half of imaging tests were ordered in response to a sign or symptom.

Abstract P6-06-34: Comparing recurrence risk scores derived from 4 immunohistochemistry stains (IHC4) versus oncoType DX

Background: Prognostically relevant biomarkers in breast cancers can be assayed using nucleic acid (e.g. OncoType DX) or protein based (e.g. immunohistochemistry (IHC)) detection stratagies. Nucleic acid tests measure many more markers compared to immunohistochemistry, but are weighted heavily for ER, PR, and HER2 in their prognostic scoring algorithms. Recent data suggest that a panel of 4 IHC stains (IHC4) may have equivalent prognostic ability to multigene assays. The aim of this study was to retrospectively compare IHC4 scores to OncoType DX recurrence scores in a large cohort of patients in our statewide health system. Methods: Formalin-fixed paraffin-embedded breast cancer samples previously submitted for OncoType DX testing between 2008 and 2011 were obtained and sections stained for ER, PR, HER2, and Ki67 (the IHC4 staining panel). Stained slides were scanned digitally and scored using customized pathologist assisted image analysis algorithms (Leica Biosystems Aperio, Vista CA). The resulting data were used in the modified “Magee Equation 3” (Klein et al. Mod Pathol. 2013. PMID: 23503643) to calculate an IHC4 recurrence score on a numerically comparable scale to that used in the OncoType score. The IHC4 and Oncotype DX scores were directly compared for concordance and correlation. Results: 280 breast cancer samples comprised the study cohort. The mean (median) IHC4 score was 20.13 (19), range: 11-42. The mean (median) OncoType score was 18.48 (16), range: 0-75. Using cut-offs of 0-17 for low risk, 18-30 for intermediate risk, and >30 for high risk, the concordance data is shown in Table 1. Pearson9s correlation coefficient for the entire set was 0.6669. The overall concordance was 56.1%; one-step discordance 43.6%; and two-step discordance: 0.3%. Eliminating the intermediate scores, the concordance was 98.8%. Conclusions: Reasonable agreement was seen between risk scores derived by IHC4 and OncoType DX. Only one discrepancy among 280 scores would have resulted in a different treatment recommendation (low risk by IHC4 and high risk by OncoType). If the IHC4 score is clearly high or low, one would not expect a dramatically different result from Oncotype DX, and the Oncotype DX test may not be needed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-34.

Oncology quality improvement as a cornerstone of the transition to accountable care.

141 Background: Accountable care is defined as moving the incentives for health care from a system that rewards volume and procedures to one that rewards improvements in the quality of care for a defined population. To prevent this process from deteriorating into solely a cost reduction exercise, physicians, and hospitals need to develop a valid, reproducible, and effective means of measuring quality and impacting behavior to reduce variation and improve quality of care. The Intermountain Healthcare Oncology Clinical Programs (OCP) experience with Oncology Quality Improvement (OQI) offers several key lessons for enabling this process. METHODS OQI initiatives are developed by a multidisciplinary physician-based team tasked with directing standardization and ensuring optimal care delivery. The team uses clinical knowledge, peer-reviewed literature, and data from an enterprise data warehouse to develop goals. Performance is measured against a goal which focuses on variation between physicians and facilities. Individual physician data is compared to de-identified data of peers, facilities, and the system. A physician champion performs academic detailing for physician groups across the system and is critical to the success of the program. RESULTS Over the past decade, the OCP initiated over 30 projects designed to measure and improve quality of oncology care delivery. Breast cancer projects included breast conservation in surgical management, reducing axillary dissection for ductal carcinoma in situ and sentinel node biopsy rather than axillary dissection. The OCP also explored standardizing lymph node resection during colorectal cancer surgery and subsequently the utilization of adjuvant chemotherapy. Imaging based goals included improving mammography callback rates and using PET/CT during preoperative assessment of lung cancer. In most instances the process resulted in significant, sustainable OQI. CONCLUSIONS The investment in program and clinician staff is significant, and the requirements and costs for a sophisticated data system are real. However, an OQI program can provide meaningful improvements in the quality of cancer care and is an important step to facilitate the transition to accountable care.

Building success in quality improvement: An analysis of what barriers hinder and what catalysts promote the widespread adoption of quality improvement initiatives.

122 Background: Quality improvement initiatives and outcomes research activities at Intermountain Healthcare are regularly conducted across 9 clinical domains, including oncology. The purpose of this abstract is to define some of the projects initiated in the primary management of breast cancer and critically analyze the barriers and catalysts allowing for adoption of quality improvement processes. METHODS Between 2003 and 2010 we initiated approximately 15 projects designed to measure and improve quality of care delivery in the treatment of breast cancer. These projects included increasing the use of breast conservation for primary surgical management, reducing axillary dissections for patients with ductal carcinoma in situ and the adaptation of sentinel node biopsy rather than axillary dissection for primary breast cancer. Quality improvement projects involving diagnostic imaging included evaluation of the time from abnormal mammogram to biopsy and the utility of follow-up mammography following breast conservation. RESULTS Measured variability among practicing clinicians in many instances was substantially reduced or eliminated. Adoption of clinical improvements was most often rapid and noticeable across the entire health care system, however, in some instances quality processes were not completely adopted. The adoption of quality improvement initiatives occurred where obvious clinical benefit could be documented, technical expertise was enhanced and peer supervision existed. Adoption occurred less frequently when financial barriers to adoption existed, clinical benefit was less well defined and peer encouragement was less vigorous. CONCLUSIONS Quality improvement processes across a large healthcare system can be instituted and adopted by a variety of facilities and practicing clinicians. Barriers and catalysts to adoption do exist and this presentation will attempt to document and outline opportunities for success using quality improvement in a large healthcare system.

Impact of Recording of Pre-Analytical Specimen Handling Conditions for ER and PR Testing in Women with Breast Cancer.

Background : Hormone receptor testing is important in the management of women with breast cancer. We previously reported potential adverse effects of variable specimen and prolonged specimen handling conditions on ER (estrogen receptor) test results (2005 SABCS, abstract#5107). Objective : To compare prevalence of ER and PR (progesterone receptor) negative test results following standardization of pre-analytical specimen handling conditions at Intermountain facilities. Methods : Prospective, quasi-experimental study design of 6 Intermountain facilities. Facilities were separated into 2 categories: experimental (2 facilities) and control (4 facilities) groups. Pre-analytical specimen handling conditions (including recording of time to fixative and duration of fixation in neutral buffered formalin) were standardized at experimental facilities but not at control facilities. Standardization consisted of educating operating and grossing room staff about appropriate specimen handling and the value of recording time to fixation and fixative duration as a way to improve pre-analytic standardization. OR staff was called in any cases where times were not recorded. Study population includes women undergoing breast cancer surgery and who were tested for ER/PR status between January 2008 and January 2009. Specimen handling conditions and ER/PR test results were collected manually. Covariates were retrieved from cancer registry and included age, grade, positive lymph nodes, specimen type, and tumor stage. Multivariate logistic regression was used to compare prevalence of ER and PR negativity between experimental and control facilities after controlling for covariates. Results : 1054 women with breast cancer were tested for ER/PR status during the study period. The average age was 60.2 years (59.2 years for control cases and 61.1 years for the experimental group). The overall prevalence of ER and PR negative tests was respectively 18.5% and 27.3%. Average time to fixative at experimental facilities was 18.4 minutes (SE=3.1; 95% CI, 12.2-25.6) and average time in fixative was 18.0 hours (SE=0.4; 95% CI, 17.2-18.8). Compared to experimental facilities, both the prevalence of ER and PR negativity was higher (16.9% vs 19.7%) and (23.9% vs 30.0%) at control facilities. After controlling for covariates there was no difference in prevalence of ER negativity (p=0.13) between the two groups. However, the prevalence of PR negativity remains significantly higher (p Conclusions: The prevalence of ER and PR negative results was lower following staff education and recording of pre-analytical specimen handling conditions. Our data suggest that staff education and recording of pre-analytical specimen handling conditions has the potential to optimize hormone receptor test results. It also shows the feasibility of fixing tissue routinely after less than an hour interval between time of breast cancer tissue removal and fixation and underscores the value of standardization of pre-analytic handling as a method to improve ER and PR testing on breast cancer specimens. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4154.