Katherine Enright

Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design.

BACKGROUND Clinical experience suggests that many women with triple-negative metastatic breast cancer (MBC) relapse quickly. This has implications for clinical practice and trial design. We evaluated the duration of first-, second-, and third-line chemotherapy as a surrogate for duration of treatment response. PATIENTS AND METHODS We performed a retrospective multicenter chart review of patients with triple-negative MBC receiving palliative chemotherapy. Primary outcome was duration of palliative chemotherapy, and secondary outcome was to identify prognostic variables. RESULTS A total of 111 patients were analyzed. Median age at diagnosis was 51 years (range, 26-82 years). Fourteen percent of patients presented with MBC. Twenty-seven percent received neoadjuvant chemotherapy, and 48% received adjuvant chemotherapy. Median distant disease-free interval (DDFI) was 18 months (range, 0-172 months). At presentation of MBC, 68% had visceral and 71% had multiple sites of disease. Median survival with MBC was 13.3 months (range, 0.8-99.8 months). Median duration of first-line palliative therapy was 11.9 weeks (range, 0-73.1 weeks). Eighty-seven patients (78%) went on to receive second-line therapy with a median duration of 9 weeks (range, 0-120.9 weeks), and 55 (49%) received third-line therapy with a median duration of 4 weeks (range, 0-59 weeks). Multivariate analysis revealed that age < 50 years, ALP > 120 U/L, history of previous chemotherapy, DDFI < 12 months, and visceral presentation were all independently associated with a poor prognosis. CONCLUSION Despite the poorer overall prognosis of patients with triple-negative disease, there remains considerable heterogeneity in individual outcomes. Many women with recurrent triple-negative disease will progress quickly on first-, second-, and third-line palliative treatment. Future clinical trials in this population must take into account their shorter time to progression when determining optimal trial design.

Population-based assessment of emergency room visits and hospitalizations among women receiving adjuvant chemotherapy for early breast cancer.

PURPOSE Adjuvant chemotherapy is considered standard care for patients with lymph node (LN) -positive and high-risk LN-negative early breast cancer (EBC). Although chemotherapy-associated toxicities are documented in clinical trials, the impact of toxicities on emergency room (ER) visits and hospitalizations (ER + Hs) at a population level with contemporary chemotherapy is unknown. We undertook a population-based study of ER + Hs in patients with EBC receiving adjuvant chemotherapy compared with noncancer controls (NCCs). METHODS All patients diagnosed with EBC between January 2007 and December 2009 in Ontario, Canada, were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up. All patients received ≥ one cycle of adjuvant chemotherapy. Patient cases of EBC (n = 8,359) were matched to NCCs (n = 8,359) on age, comorbidity, and geographic location. ER + Hs within 30 days of chemotherapy were identified. If the primary reason for the visit was a common chemotherapy toxicity, the visit was considered chemotherapy associated. All-cause and chemotherapy-associated visits were compared between patient cases and controls. Logistic regression models were used to identify covariates associated with ER + Hs. RESULTS The proportion of patients with at least one ER + H was significantly higher in patients with EBC undergoing chemotherapy compared with NCCs (43.4% v 9.4%; P < .001). Patients with EBC were also more likely to have multiple ER + Hs (17.9% v 2.4%; P < .001). On multivariable analysis, comorbidity, receiving a regimen containing docetaxel, and certain geographic regions were associated with increased odds of ER + Hs. CONCLUSION ER + Hs are common among patients with EBC receiving chemotherapy and significantly higher than among controls. This represents a potential opportunity for quality improvement.

Establishing achievable benchmarks for quality improvement in systemic therapy for early-stage breast cancer

Setting realistic targets for performance is a consistent challenge in quality improvement. In the current study, the authors used administrative data to define achievable targets for a panel of 15 previously developed quality indicators (QIs) focusing on systemic therapy in patients with early‐stage breast cancer.

Setting Quality Improvement Priorities for Women Receiving Systemic Therapy for Early-Stage Breast Cancer by Using Population-Level Administrative Data

Purpose Routine evaluation of quality measures (QMs) can drive improvement in cancer systems by highlighting gaps in care. Targeting quality improvement at QMs that demonstrate substantial variation has the potential to make the largest impact at the population level. We developed an approach that uses both variation in performance and number of patients affected by the QM to set priorities for improving the quality of systemic therapy for women with early-stage breast cancer (EBC). Patients and Methods Patients with EBC diagnosed from 2006 to 2010 in Ontario, Canada, were identified in the Ontario Cancer Registry and linked deterministically to multiple health care databases. Individual QMs within a panel of 15 QMs previously developed to assess the quality of systemic therapy across four domains (access, treatment delivery, toxicity, and safety) were ranked on interinstitutional variation in performance (using interquartile range) and the number of patients who were affected; then the two rankings were averaged for a summative priority ranking. Results We identified 28,427 patients with EBC who were treated at 84 institutions. The use of computerized physician electronic order entry for chemotherapy, emergency room visits or hospitalizations during chemotherapy, and timely receipt of chemotherapy were identified as the QMs that had the largest potential to improve quality of care at a system level within this cohort. Conclusion A simple ranking system based on interinstitutional variation in performance and patient volume can be used to identify high-priority areas for quality improvement from a population perspective. This approach is generalizable to other health care systems that use QMs to drive improvement.

Can we accurately identify chemotherapy-related acute care visits in administrative data?

185 Background: Administrative data is increasingly being used to study treatment related complications that lead to acute care visits such as emergency department visits or hospitalizations (ED+H). We evaluated the accuracy of diagnosis codes for identifying chemotherapy related acute care visits (CRVs) among women with breast cancer. METHODS We prospectively developed algorithms to identify CRVs from administrative data in women receiving adjuvant chemotherapy for breast cancer in Ontario, Canada. Sensitivity (SN) and specificity (SP) were calculated for 3 scenarios: chemotherapy related ED visit, chemotherapy related H, and febrile neutropenia (FN) related visit using the chart as the gold standard. Since there is no specific diagnosis code for FN, three definitions of FN were considered: general (defined as fever or infection or neutropenia as main reason for visit), moderate (neutropenia as main reason for visit) or strict (fever or infection plus neutropenia). The population based cohort was generated by linking several health databases to identify women who had at least one ED+H during adjuvant chemotherapy for breast cancer between 2007-2009. The validation cohort consisted of 490 randomly selected cases from this cohort. RESULTS The population-based cohort consisted of 8,359 patients of whom 43.4% had at least one ED+H including 1,496 women who had multiple visits resulting in 6,293 unique ED+H. Of these, 73.1% were considered CRVs based on our algorithm. The algorithm performed well in identifying CRVs that included an H either from ED (SN 90%, SP 100%) or directly from home (SN 91%, SP 93%) but less well for ED visits that did not result in H (SN 65%, SP 80%). Depending on which FN algorithm was used, 1.4-24% of visits were considered FN related. The general FN algorithm had excellent SN regardless of whether the visit involved H (94-98%) but SP was moderate (66-80%). The strict FN algorithm had good SP (78-99%) but SN was highly variable (13-89%). The moderate FN algorithm provided the best tradeoff between SN (69-97%) and SP (76-98%). CONCLUSIONS CRVs can be identified from administrative data with reasonable confidence, obviating the need for chart abstraction to evaluate chemotherapy related serious events.

Benefits and Pitfalls of Using Administrative Data to Study Hospitalization Patterns in Patients With Cancer Treated With Chemotherapy

The study by O’Neill et al adds to the growing number of population studies that have reportedhigh rates of emergency room visits and hospitalizations in patients with cancer treated with chemotherapy in both the curative and metastatic setting. In the study by O’Neill et al, 92% of patients receiving chemotherapy for advanced cancers had an unplanned hospitalization, a rate that was up to 1.9 times higher than the matched nonchemotherapy control group and much higher than would be expected from clinical trial reports. This not only raises a significant concern regarding quality of care of patients with advanced cancers but also has important implications for health care use at the end of life. The use of administrative databases to study chemotherapy toxicities is both powerful and limited. On the one side, administrative data reflect the real-world experience of patients being treated in nontrial settings. Patients on clinical trials represent a minority of all patients with cancer; they are usually younger, healthier, and have higher socioeconomic status than thegeneral cancerpopulationand therefore are less likely to experience serious toxicity of chemotherapy. The outcomes reported in large administrative database studies such as O’Neill et al are more informative of the expected outcomes of the majority of patients seen in daily practice and are important for patients, providers, and health systems to understand some of the risks and health-system implications of therapy. Such information is important for both individual decision making regarding therapy and to assist with health-system planning and quality improvement. However, administrative data contain limited clinical information, which can make it challenging to attribute negative outcomes (such as hospitalizations) to the chemotherapy as opposed to other unmeasured clinical confounders, such as performance status or symptom burden, or to understand how to prevent future events. In the study by O’Neill and colleagues, the matched patients receiving chemotherapy hadworse survival thanunmatchedpatients receiving chemotherapy and thus may reflect the sickest patients treated with chemotherapy. In an attempt to determine the role of chemotherapy in driving hospitalization rates in patients with cancer, studies have used various approaches and algorithms to define hospitalizations that are likely chemotherapy associated. In general, these algorithms have been generated to reflect the common toxicities of chemotherapy using clinical experience and consensus. Although the algorithms used in the literature in general reflect the same scope of toxicities, they each vary in the complement of diagnoses considered, and,

Improving documentation of oral chemotherapy at a community cancer center.

PURPOSE Safe administration of oral chemotherapy is a complex process that represents a potential threat to patient safety. Clear documentation of the plan of care for patients receiving oral chemotherapy can improve patient safety by ensuring complete health information is available to the health care team. METHODS We undertook a rapid-cycle improvement project to improve documentation of oral chemotherapy by increasing the number of components of an oral chemotherapy care plan (as outlined by American Society of Clinical Oncology and Oncology Nursing Society) documented in the medical record before starting a new oral chemotherapy drug. Three improvement cycles were implemented, including: introduction of a standardized nursing flow sheet, use of computerized physician order entry for oral chemotherapy prescribing, and a review of computerized physician order entry to ensure all oral chemotherapy regimens were included. RESULTS Our intervention resulted in a meaningful and sustained improvement in the number of components of oral chemotherapy care plans documented in the medical record, from a mean of 67% (eight of 12 components) to a mean of 92% (11 of 12). CONCLUSION We are hopeful that this improvement project will enhance patient safety by improving communication within the health care team regarding the details of the chemotherapy care plan.

Acute care utilization (ACU) among women receiving adjuvant chemotherapy for early breast cancer (EBC).

65 Background: Adjuvant chemotherapy is considered standard care for patients with lymph node (LN) positive and high risk LN negative EBC. While toxicities of chemotherapy are documented in clinical trials, the impact of toxicities on ACU at a population level is unknown. We undertook a population based study of ACU in patients undergoing adjuvant chemotherapy for EBC compared with controls. METHODS All EBC patients diagnosed 01/07 - 12/09 in Ontario, Canada, were identified from the Ontario Cancer Registry. Pt records were linked deterministically to provincial healthcare databases. All patients received ≥1 cycle of adjuvant chemotherapy. EBC cases (n = 4,718) were matched to non-cancer controls (n = 4,718) on age and geographic location. ACUs (emergency room or hospitalizations) within 30 days of chemotherapy were identified. If the primary reason for visit was a common toxicity of chemotherapy, the visit was considered chemotherapy associated (CA). All cause and CA visits were compared between cases and controls. Logistic regression models were used to identify covariates associated with ACU. RESULTS ACU was significantly higher in EBC pts compared with controls for both all cause (42.1% vs 9.1%, p<.001) and CA (30.7% vs 2.4%, p<.001) visits. Fever was the most common CA toxicity (22.9% vs 1.2%, p<.001). Taxanes were significantly associated with increased ACU compared with anthracycline only. CONCLUSIONS ACU is common among EBC receiving chemotherapy and significantly higher than among controls. Interventions aimed at mitigating CA toxicity, particularly with the use of taxanes may reduce ACUs. [Table: see text].

Standardization of oral chemotherapy delivery to improve patient safety: A pilot study.

90 Background: Oral chemotherapy (OC) presents unique challenges to patient safety. In contrast with parenteral chemotherapy, patient education and comprehension are crucial to the safe administration of OC, appropriate toxicity interventions and patient adherence. At Trillium Health Partners we identified a lack of standardization to OC education and monitoring, that resulted in gaps in patient care. Using the American Society of Clinical Oncology/Oncology Nursing Society 2013 chemotherapy safety standards as guidance, we developed and piloted a multi-disciplinary oral chemotherapy care pathway (OCCP) to improve the approach to education and monitoring of patients newly started on OC. METHODS Patients newly started on OC between 03/15-06/15 were enrolled by 2 participating physicians representing a predominantly lung/GI practice. Baseline data was abstracted retrospectively in the 3 months prior to the pilot to reflect all study participants. The OCCP included in-person and telephone assessments by an oncology pharmacist and nurse over 2 cycles of OC. Pilot outcomes included pharmacy interventions, dose modification for toxicity, medication errors, the percent of prescriptions on computerized physician order entry (CPOE), adherence documentation and comprehension of treatment plan. RESULTS The pilot enrolled 20 patients and compared them against 21 baseline patients. During the pilot there were improvements in the percentage of patients who had pharmacy interventions, documentation of adherence and assessment of comprehension of the treatment plan as well as a reduction in dose modifications due to toxicity (Table 1). CONCLUSIONS Use of a newly developed oral chemotherapy care pathway demonstrated both feasibility as well as improvements in a variety of key patient safety indicators. These results suggest that implementation of a standardized oral chemotherapy care pathway can feasibly improve patient safety outcomes. [Table: see text].

Can Chemotherapy-Related Acute Care Visits Be Accurately Identified in Administrative Data?

PURPOSE There is increasing interest in using administrative data to examine treatment-related complications that lead to emergency department (ED) visits or hospitalizations (H). The purpose of this study was to evaluate the reliability of billing codes for identifying chemotherapy-related acute care visits (CRVs) among women with early-stage breast cancer. MATERIALS AND METHODS The cohort was identified by using deterministically linked health databases and consisted of women who were diagnosed with early-stage breast cancer who started adjuvant chemotherapy between 2007 and 2009 in Ontario, Canada. A random sample of 496 patient cases was chosen as the validation cohort. Sensitivity (SN) and specificity (SP) were calculated for three scenarios: chemotherapy-related ED visit, chemotherapy-related H, and febrile neutropenia (FN)-related visit. For FN-related visits, three definitions were considered: general, moderate, and strict. RESULTS The administrative cohort consisted of 8,359 patients, 43.4% of whom had at least one ED or H, including 1,496 women who had multiple visits that resulted in 6,293 unique visits. Of these, 73.1% were considered CRVs. The algorithm performed well in identifying CRVs that included H either from ED (SN, 90%; SP, 100%) or directly from home (SN, 91%; SP, 93%), but less well for ED visits that did not result in H (SN, 65%; SP, 80%). Depending on which FN algorithm was used, 4.8% to 24% of visits were considered related. The moderate FN algorithm provided the best tradeoff between SN (69% to 97%) and SP (83% to 98%). CONCLUSION Administrative data can be valuable in evaluating chemotherapy-related serious events. Algorithm validation in other cohorts is needed.