Background Several cancer therapies have been associated with cardiovascular harm in early‐phase clinical trials. However, some cardiovascular harms do not manifest until later‐phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry‐funded trials (69.2% versus 0.0%; P<0.001), and in trials administering targeted/immunotherapy agents compared with only hormonal/conventional chemotherapy (78.6% versus 22.7%, P<0.001). Conclusions Our findings demonstrate significant under‐representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later‐phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.

e24100 Background: Although some cardiovascular (CV) toxicity is detected in early phase trials of therapeutic agents, most CV toxicities are not appreciated until later phase clinical trials or general clinical practice. The high prevalence of cardiovascular disease (CVD) in the general population warrants study of how later phase oncologic pharmacotherapy clinical trials address eligibility and assess for treatment-related cardiotoxicity. We focused our study on phase 2 and 3 breast cancer trials to limit disease-specific variations. Methods: A methodical Embase search was performed for phase 2 and 3 trials administering breast cancer pharmacotherapy and including > 50 participants. Firstly, we examined CVD as an exclusion criterion. Secondly, we identified what CV safety assessments were reported such as troponin, brain natriuretic peptide (BNP), lipid profile, electrocardiogram (ECG), or CV imaging. Thirdly, we examined whether trials reported adverse CV events. Fischer’s exact test was applied to compare reporting amongst trial characteristics (trial funding source and type of agent administered), and a 2 sided p-value of < 0.05 was considered significant. Results: 50 published articles from 46 separate clinical trials were included. Patients with prevalent CVD were excluded in 67.4% of trials, the most frequently excluded CVD was heart failure/NYHA class > 1 (65.2% of trials). At least one pre or post-treatment CV safety assessment was reported in only 58.7% of trials, most commonly an ECG (52.2% of trials). BNP or troponin assessments were not reported in any trial. Adverse CV events were reported in 82.6% of trials, the most frequently reported event was hypertension (43.5% of trials). CV Safety assessments were more frequently reported in pharmaceutically funded trials compared to non-pharmaceutically funded trials (86.4 vs 10.0%, p < 0.001), and in trials administering targeted/immunotherapy agents compared to those administering only traditional chemotherapy/hormonal therapy (85.2 vs 21.1%, p < 0.001). Conclusions: Later stage breast cancer clinical trials are conducted in populations under-representative of patients with prevalent CVD, a common comorbidity. Trial funding source and type of agent administered impact whether or not CV toxicity is monitored. Despite the frequent exclusion of patients with CVD and poor safety assessment reporting, adverse CV events are frequently encountered and reported. Thus, these trials may underestimate CV toxicity risks for the greater population receiving such agents in clinical practice.

TPS9083 Background: Despite several recent checkpoint inhibitor approvals extensive stage small cell lung cancer (SCLC) is associated with a poor prognosis and remains an area of high unmet need. RRx-001 is a first-in-class, minimally toxic small molecule immunotherapeutic that inhibits c-Myc, downregulates the antiphagocytic checkpoint, CD47, repolarizes tumor associated macrophages (TAM) from protumor M2 to antitumor M1 and resensitizes to previously active first line therapies. On the basis of favorable results from a Phase 2 trial called QUADRUPLE THREAT (NCT02489903) in combination with a platinum doublet in later line SCLC, a Phase 3 trial called REPLATINUM was started in 3rd line or beyond SCLC in Q4 2019. Enrollment is ongoing. Methods: This US-based, open-label, randomized, phase 3 study (NCT03777657) compares RRx-001 4mg + a platinum doublet (carboplatin or cisplatin + etoposide) versus a platinum doublet for pts with 3rd line or beyond SCLC that have previously received a checkpoint inhibitor. Approximately 120 pts from 25 centers will be randomized 1:1 to receive RRx-001 4 mg in combination with a platinum doublet vs. a platinum doublet. The platinum doublet will be administered on both arms for up to 4 cycles; on the RRx-001 arm only patients with stable disease or better are eligible to continue on RRx-001 4 mg + carboplatin AUC 2-4 maintenance therapy. If radiologic progression occurs on the control arm prior to the 4th cycle, patients are eligible to crossover to the RRx-001 treatment arm. PFS is the primary endpoint. Secondary endpoints include OS and ORR. Exploratory endpoints include c-Myc, CD-47 and PD-L1 on circulating tumor cells and SIRP-alpha expression on circulating monocytes. Clinical trial information: NCT03777657.

e19099 Background: P and G are active agents with acceptable toxicity profiles in the treatment of NSCLC. The addition of BV to chemotherapy has resulted in a significant improvement in survival for pts with non-squamous NSCLC. We are currently conducting a phase II trial of P, G and BV on a novel every two week schedule in untreated pts with advanced NSCLC. Methods: Advanced, non-squamous NSCLC pts with measurable/evaluable disease, no prior treatment for advanced disease, PS 0–1, adequate hepatic, renal and bone marrow function, treated brain metastases were eligible. No unstable hypertension/cardiac disease/vascular disease, hemoptysis, anti-coagulation, recent major surgery, no cavitation or close proximity of primary cancer to a major vessel were allowed. Pts received P 500 mg/m 2 , G 1,500 mg/m 2 , and BV 10 mg/kg every 2 weeks for 12 cycles. Doses were reduced to P 400 mg/m 2 and G 1,200 mg/m 2 when grade 4 neutropenia occurred in the first 2 patients. BV was continued until disease progression or toxicity. Planned accrual is 42 patients. Primary endpoint is progression-free survival. Secondary endpoints are response rate (RR), toxicity, time to progression and overall survival. Results: 20 pts have been accrued. Median age 57.5 yrs, males-55%, stage IV 90%, adenocarcinoma 75%. 18 pts are response evaluable (2 were too early to assess). 11/18 (61%) pts had a response (1 CR, 7 PR, 3 unconfirmed PR) (90% CI for RR is 0.42 - 0.77), and 3 had SD ( 17%) for a disease control rate of 78%. Currently the median treatment cycles for all pts are 6 (range 1–12). All pts are evaluable for toxicity. Grade 3- 4 toxicities: neutropenia 4, anemia 1, thrombocytopenia 2, lymphopenia 1, febrile neutropenia 1, fatigue 4, hypertension 1, GI 2, ALT/AST 3, pneumonitis 1, muscular weakness 1, metabolic 2, otitis media 1. Conclusions: The combination of P, G, and BV is a very active and tolerable treatment for NSCLC despite the preliminary nature of these results. Updated information will be presented at the meeting. This research is supported by Lilly Oncology and Genentech. [Table: see text]

Purpose: Lung cancer screening with low-dose CT (LDCT) demonstrated reduced mortality in the National Lung Screening Trial, yet there is debate as to whether the reported efficacy can translate into comparable effectiveness with community-based screening. The authors' purpose is to report the baseline patient characteristics and malignancy rate in the first 18 months after implementing a lung cancer screening program in an integrated community health system.Methods: Patients were screened at 1 of 10 participating community-based centers within a 22-hospital system from 2013 to 2015. LDCT examinations were interpreted by 1 of 20 radiologists using structured reporting and an internally developed tracking system. Manual chart review was performed to ascertain the malignancy detection rate.Results: A total of 357 patients were screened with LDCT. Of these, 80 patients were ineligible and 3 declined enrollment. The remaining 274 patients satisfied accepted screening criteria and were enrolled in the program. Malignancy was detected in a total of 11 enrollees (4.0%), 8 with lung cancer and 3 with extrapulmonary primary malignancies. Three patients (1.1%) were diagnosed with early-stage lung cancer and received definitive therapy.Conclusions: Early-stage lung cancer was detected with LDCT screening in an integrated community health system at a rate similar to other trials.

BACKGROUND 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. METHODS Patients with American Joint Committee on Cancer stage 0 to II breast cancer diagnosed between 2009 and 2010 were identified and the use of imaging and biomarker tests over an 18‐month period were quantified, starting at 1 year after diagnosis. Chart abstraction was performed on a random sample of patients who received testing to identify the indication for testing. Multivariate regression was used to explore associations with the use of nonrecommended care. RESULTS A total of 6585 patients were identified; 22% had stage 0 disease, 44% had stage I disease, and 34% had stage II disease. Overall, 24% of patients received at least 1 imaging test (25% at KP vs 22% at IH; P = .009) and 28% of patients received at least 1 biomarker (36% at KP vs 13% at IH; P <.001). Chart abstraction revealed that 84% of imaging tests were performed to evaluate symptoms or signs. Virtually all biomarkers were ordered for routine surveillance. Stage of disease, medical center that provided the services, and provider experience were found to be significantly associated with the use of biomarkers. CONCLUSIONS Advanced imaging was most often performed for appropriate indications, but biomarkers were used for nonrecommended surveillance. Distinguishing between inappropriate use for surveillance and appropriate diagnostic testing is essential when evaluating adherence to recommendations. Cancer 2016;122:908–16 . © 2015 American Cancer Society .

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.

184 Background: The initial ASCO “Top 5” list, created as part of the Choosing Wisely campaign, recommends against use of imaging for staging of early stage breast cancer in asymptomatic women at low risk for metastasis. The objective of this study was to measure and compare use of imaging for staging in two large integrated health care systems, Kaiser Permanente (KP) and Intermountain Healthcare (IH). We also sought to distinguish whether imaging was used for routine staging or for diagnostic purposes. Methods: We identified stage 0-IIB breast cancer patients diagnosed between January 1, 2010 and December 31, 2012 with first primary malignancy from tumor registries in three KP regions (Southern California, Northwest, and Mid-Atlantic) and IH. Using the KP and IH electronic health records, we identified use of imaging tests (PET, CT, bone scan) during the staging window (30 days prior to diagnosis up to initial surgery). We performed chart abstraction on a random sample of patients who received an imaging test to identify indication. Results: For the total sample of 10,014, mean age at diagnosis was 60 (range 22-99); with 21% stage 0, 47% stage I, 32% stage II. Overall, 8% of patients (792 patients) received at least one imaging test during the staging window, including 8% at KP and 6% at IH (p=0.0005). Chart abstraction (N=129) revealed that overall, almost half of all imaging tests (48%) were performed to evaluate a symptom, sign or prior imaging finding, including 55% at KP and 32% at IH. Conclusions: Use of imaging for staging of low-risk breast cancer was very low in both health care systems, with clinically trivial differences between them. Approximately half of imaging services were in response to a sign or symptom. Strategies to reduce use of imaging at staging for early stage breast cancer patients within these health care systems are unlikely to yield meaningful improvement. [Table: see text]

7518 Background: Non-small cell lung cancer (NSCLC) patients that undergo curative resection are at risk for development of second primary lung cancer (SPLC). The E5597 trial is the largest placebo-controlled lung cancer chemoprevention study conducted in the US. We report on the SPLC diagnosed in this cohort. Methods: E5597 randomized 1,561 (2:1) patients with resected stage I NSCLC to selenium or placebo for a total of four years with the primary objective of decreasing the incidence of SPLC. The study was stopped at first interim analysis for futility in October 2009. The participants were followed for incidence of all second primary tumors (SPT). Results: There were 290 (19%) incidences of SPT, of which 113 (7.2%) were SPLC among 112 cases (1 case with 2 incidences) as of January 2014 with median follow-up time of 5.6 years. 82 incidences in 81 cases occurred in the selenium arm (S) and 31 cases in the placebo arm (P). The median age was 67 years, and there were a higher proportion of women (52.7%). Although several patients continued smoking or had only quit within a year of SPLC (40.2%), most patients had quit smoking for at least one year (57.2%). The most common histology was adenocarcinoma (40.7%), followed by other (30.1%), squamous cell (25.6%), and large cell (1.8%). Almost all SPLC cases were detected by imaging (88.5%), but 31.9% were also clinically evident. Nearly two thirds of SPLC were stage I-II (61%). The incidence rates of SPLC were higher in the S arm compared to P arm: 1.42 versus 1.05 per 100 person years, respectively (95% CI 0.77-2.38). The median time to SPLC from randomization was 3.0 years (range 0.9-9.3 years) and from initial diagnosis of lung cancer was 4.2 years (range 0.8-28.5). Conclusions: SPLC is the most common second primary cancer in NSCLC patients. Continued surveillance even after tobacco cessation, is warranted for earlier detection of SPLC.

Background: Few intervention programs assist patients and their family caregivers to manage advanced cancer and maintain their quality of life (QOL). This study examined (i) whether patient-caregiver dyads (i. e., pairs) randomly assigned to a brief or extensive dyadic intervention (the FOCUS Program) had better outcomes than dyads randomly assigned to usual care and (ii) whether patients' risk for distress and other factors moderated the effect of the brief or extensive program on outcomes.Methods: Advanced cancer patients and their caregivers (N = 484 dyads) were stratified by patients' baseline risk for distress (high versus low), cancer type (lung, colorectal, breast, or prostate), and research site and then randomly assigned to a brief (three-session) or extensive (six-session) intervention or control. The interventions offered dyads information and support. Intermediary outcomes were appraisals (i. e., appraisal of illness/caregiving, uncertainty, and hopelessness) and resources (i. e., coping, interpersonal relationships, and self-efficacy). The primary outcome was QOL. Data were collected prior to intervention and post-intervention (3 and 6 months from baseline). The final sample was 302 dyads. Repeated measures MANCOVA was used to evaluate outcomes.Results: Significant group by time interactions showed that there was an improvement in dyads' coping (p < 0.05), self-efficacy (p < 0.05), and social QOL (p < 0.01) and in caregivers' emotional QOL (p < 0.05). Effects varied by intervention dose. Most effects were found at 3 months only. Risk for distress accounted for very few moderation effects.Conclusions: Both brief and extensive programs had positive outcomes for patient-caregiver dyads, but few sustained effects. Patient-caregiver dyads benefit when viewed as the 'unit of care'. Copyright (C) 2012 John Wiley & Sons, Ltd.

PURPOSE:Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation.PATIENTS AND METHODS:Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence.RESULTS:The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected.CONCLUSION:Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

113 Background: Mammographic screening for women 40-49 years of age remains controversial based on results from earlier large scale, controlled mammography trials. Methods: From 2002-2006, 871 women aged 40-49 were diagnosed with breast cancer at Intermountain. The charts of all patients without a record of a screening mammogram at Intermountain (n= 436) were reviewed to confirm that they had not had a screening mammogram in the prior two years at any facility (Interval Cancers) and their survival was compared to 435 women who had their cancer diagnosed on a screening exam (Screen Detected). All patients were followed for at least 5 years via the tumor registry. Results: Stage distribution for Screen Detected/Interval cancers was 25.3/6.4% stage 0, 36.8/24.8% stage I, 24.6/35.6% stage II, 6.9/20.4% stage III and 0.5/3.4% stage IV. Overall, 67 patients (7.7%) did not have complete staging data. Overall survival was significantly better (p<.0001) for 40-49 year old women with Screen Detected compared to those with Interval cancers. 702 (79.6%) had ER/PR status recorded (83.5% ER/PR positive). Women with DCIS or LCIS did not have tissue sent for markers. 679 patients (76.9%) had HER2 status recorded (78.8% HER2 neg). Of the patients with both HER2 and ER/PR status recorded 10.4% were “triple negative.” Survival following screening mammography was significantly enhanced for women who were ER/PR positive (p<0.0001), HER2 negative (p=0.0065), or HER2 positive (p=0.0013). Survival was not improved by screening mammography for women who were ER/PR negative (p=0.3818) or for women who were triple negative (p=0.416). Conclusions: A minority of women age 40-49 who develop breast cancer (13%) have biologic features suggestive of aggressive disease and, after 5 years of follow up, they are not benefitted by screening mammography. The remaining 87% are clearly benefitted by screening mammography. Our results suggest that the discrepancies noted in the screening mammography trials in 40-49 year old women may have resulted from population variations in the proportion of women with unfavorable biology. Based in part on these results, we continue to recommend regular screening in the 40-49 year old cohort.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin’s lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin’s lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin’s disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin’s lymphoma.

135 Background: Data is essential to achieve meaningful quality improvement. A variety of commercial products are currently available for sophisticated data collection. However, data systems alone are not sufficient to improve quality. Additional resources are required in order to leverage electronic clinical data for meaningful improvement. This abstract outlines the necessary requirements and available methods for data-based oncology quality improvement using the experience of Intermountain Healthcare. Methods: The organizational components required for quality improvement are complex. Successful quality improvement begins with project feasibility, data availability and clinical leadership. Clinical processes are reviewed, data accuracy and availability are confirmed and clinical goals are established. Data collection, validation, and analysis are standardized across multiple facilities and providers. Data must be analyzed and presented in a way that clearly illustrates differences in current performance compared to quality goals, should be tracked over time to ensure real and sustainable progress, and must be combined with other improvement strategies to maximize impact. Results: Once quality reports are generated, a physician champion presents them to clinical staff along with education materials, national guidelines and current evidence from peer-reviewed literature. Clinicians are presented with individualized data comparing their personal performance to de-identified performance of their peers, the facility and the system. Providers are given updated data on a regular basis, the data system is monitored for outliers and the need for subsequent interventions, and additional metrics are tracked to ensure process changes don’t negatively impact quality in other areas. Conclusions: Oncology quality improvement requires both clinical and data infrastructure. Electronic clinical data systems are essential for quality improvement, but are not sufficient by themselves. Additional resources are required to capture, extract, validate and analyze clinical data. Appropriate use of these resources transforms existing electronic data systems into a powerful quality improvement tool.

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 Program’s (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.

With increasing numbers of communities harmed by exposures to toxic substances, greater understanding of the psychosocial consequences of these technological disasters is needed. One community living the consequences of a slow-motion technological disaster is Libby, Montana, where, for nearly 70 years, amphibole asbestos-contaminated vermiculite was mined and processed. Former mine employees and Libby area residents continue to cope with the health consequences of occupational and environmental asbestos exposure and with the psychosocial challenges accompanying chronic and often fatal asbestos-related diseases (ARD). Nine focus groups were conducted with Libby area residents. Transcripts were analyzed to explore patterns of family communication about ARD. The following five patterns emerged: Open/Supportive, Silent/Supportive, Open/Conflictual, Silent/Conflictual, and Silent/Denial. Open/Supportive communication included encouragement to be screened for ARD, information about ARD and related disaster topics, and emotional support for people with ARD. In contrast, communication patterns characterized by silence or conflict have the potential to hinder health-promoting communication and increase psychological distress.

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.

In recent years, there have been significant advances in the management of patients with lung cancer. This progress is associated with increased use of medical intensive care units (ICUs) for the management of a variety of complications related to cancer, its treatment, or comorbid illnesses. At the same time, there are advances in the care of critically ill patients in general. Over the last decade, there are several studies that report progressive improvement in the outcome of lung cancer patients admitted to the medical ICUs. On average, the ICU and hospital mortality rates of lung cancer patients are 36% and 51%, respectively. These rates are approaching those of critically ill general population. However, it is clear that not all lung cancer patients will benefit from this aggressive care. Although there are no absolute predictors, the current evidence suggests that advanced refractory cancer, poor baseline performance status, the need for mechanical ventilation, and multiple organ system failures are factors associated with worse ICU outcome. Further studies are needed to better triage patients who are going to benefit from ICU care; determine the optimal duration of this care; and assess the impact of this therapy on the long-term survival, cancer treatment, and quality of life of these patients.

Background:Pemetrexed has emerged as one of the most active agents for the treatment of patients with advanced non-small cell lung cancer (NSCLC). We conducted a phase II study to assess the efficacy and feasibility of integrating pemetrexed in a concurrent therapy plan for patients with stage III NSCLC. Methods:Patients with stage III NSCLC with performance status 0 to 1, adequate organ function including pulmonary function, and V20 less than 40% were eligible. Patients were treated with cisplatin 75 mg/m2 (first five patients 60 mg/m2) and pemetrexed 500 mg/m2 every 21 days for three cycles with chest radiotherapy to 66 Gy. Patients then received three cycles of docetaxel 75 mg/m2 every 21 days. Tumors were analyzed for Excision Repair Cross Complementation Group 1 and thymidylate synthase. Results:Patient characteristics (N = 28) were median age, 60; males, 68%; stage IIIB, 64%; and squamous cell, 43%. Twenty-four patients (86%) completed all three cycles of cisplatin/pemetrexed. Of the 24 patients eligible for docetaxel, 21 (87%) received it. Grade 3/4 toxicities were neutropenia (39%), febrile neutropenia (14%), esophagitis (14%), and pneumonitis (4%). Median survival was 34 months, and 1-year survival was 66%. Survival was not significantly different in squamous and other histology patients. Tumor analysis in 16 patients showed that moderate/strong expression of thymidylate synthase was significantly associated with progression-free survival and overall survival. Conclusion:Integrating pemetrexed in a concurrent therapy regimen for patients with stage III NSCLC is feasible and was associated with a median survival of 34 months.