Search

197 Background: Lung Cancer Screening provides a mechanism to detect lung cancers at stages more amendable to curative resection. Nonetheless, data suggests Low Dose Computed Tomography (LDCT) is underutilized as a screening tool; preventing medically eligible patients from diagnosis at earlier stages; leading to reduced treatment options and, ultimately, decreased survival. The Duke Cancer Network (DCN) consists of 12 affiliated cancer programs in 5 states. As several affiliates shared a common goal of improving the uptake of LDCT screening in the community, the DCN created a platform for process improvement in LDCT screening, individualized for participating sites. Methods: DCN-developed surveys for patients and providers explored attitudes toward LDCT screening, and identified targetable access issues and barriers to LDCT screening at DCN-affiliated community cancer centers (aCCC). Armed with the survey data, five aCCC self-selected to work with an experienced Quality/Process Improvement coach to develop individualized projects focusing on one or more aspects of the LDCT screening process. The Q/PI coaches utilized Bite-Size-QI software to facilitate the project and train participants in the QI/PI process. Results: Information from 312 patient and 28 of 50 surveyed providers identified numerous targetable LDCT screening barriers: lack of knowledge about and educational materials to address the benefits of LDCT and tools/analytics to track patients following LDCT screening. Additional, more systematic, barriers identified included: lack of consistent national guidelines for screening, variable insurance coverage and limited availability of smoking cessation programs. Five aCCC self-selected to create individualized process improvement activities were matched to experienced Q/PI coaches. Four sites completed the yearlong project. Three of the aCCC were able to realize improvement in LDCT screening rates with 38%, 27% and 8% increase in rates, respectively, despite overlap with COVID-19 driven shutdowns. Conclusions: An assessment of current state linked to formal Q/PI activities improved uptake of LDCT screening in the majority of participating community cancer programs despite limited resources. Geographically variable COVID-19 required closures did compromise the outcomes. The process led to creation of a number of tools and process improvements to increase awareness of LDCT screening through education and foster collaboration among providers with streamlined referral processes and improved mechanisms of tracking patients. Funding: Provided by AstraZeneca in collaboration with the Duke Cancer Network. Keywords: lung cancer, screening, community, oncology, improvement process, barriers.

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.

e19218 Background: Lung cancer screening (LCS) has potential to detect earlier stage cancer, favorably impacting patient outcomes, however evolving data suggest that LCS is underutilized. Because LCS is an extensive process with diverse barriers specific to each clinical setting, a multidisciplinary quality improvement (QI) initiative was undertaken to develop and test LCS processes to improve effective LCS. Baseline findings and approaches are presented. Methods: To inform the development of effective strategies to improve LCS, a survey was developed to examine perceptions and barriers to LCS across a group of community oncology programs in the Duke Cancer Network (DCN). The survey analyzed contextual, institutional, and patient factors influencing utilization of LCS. Survey results were used to support purpose-driven multidisciplinary teams to develop site-specific improvement plans for LCS with the support of QI consultants from Bite-Size QI. Results: Surveys were sent to 62 administrators and providers at 12 community oncology programs, with 36 respondents across 9 sites. LCS rates ranged between 4%-16% at participating sites. Respondents identified the lack of processes and infrastructure to support LCS as the most common challenges. Processes related to identification of LCS candidates, conduct of shared decision-making (SDM), follow up of lung nodules, and recurring screens were named specifically. Contributing factors identified were lack of robust community outreach, patient education, and protocols for providers. With regard to SDM, both administrators and providers reported systematic issues including provider time constraints and nonexistent or inconsistent identification/tracking systems, with patient compliance and health literacy as further barriers. The lack of these processes not only affected patients receiving initial LCS, but also how recurrent screenings were tracked. Conclusions: Identifying challenges in processes facilitated creation of improvement projects for participating sites. Initial improvement projects focus on patient notification of LCS results through follow up letters, integration of tracking LCS into hospital systems, development of patient education, community outreach and smoking cessation programs. Follow-up analyses will be undertaken to evaluate each approach.

Background: In CALGB-49907 (NEJM 2009;360:2055), older patients (pts) with ESBC were randomized to standard adjuvant chemo (AC or CMF versus capecitabine). The objective of this secondary QoL analysis is to assess if pts’ BL chemo preference (CP, defined as high or low), is associated with the following during and after completion of chemo: self and professional-reported toxicity, changes in mental health, function, QoL, recurrence-free (RFS) and overall (OS) survival. Patients and Methods: Of 633 trial pts 350 participated in the QoL substudy; 145/350 pts completed the BL assessment regarding CP. CP was measured by asking the amount of benefit women would require to choose adjuvant chemo in a hypothetical situation, irrespective of chemo agents. Women who chose chemo for an increase in OS of ≤12 months (mo) were designated as high chemo preference (HCP) and those who chose >12 mo were designated low chemo preference (LCP). CP associations were evaluated with: BL perception of self-health and perceived QoL on chemo; patient reported outcomes (PROs), changes in function and QoL (based on EORTC-QLQ-C30); anxiety and depression (Hospital Anxiety and Depression Scale); observed grade 3-5 adverse events (AEs) by NCI common toxicity criteria (CTC v2.0). Pts were assessed at midtreatment and at 1, 12, 18 and 24 mo post-treatment. Chi-square tests, t-tests, and Cox models were used for categorical, continuous, and time-to-event variables, respectively. Results: The demographic and tumor characteristics of women (median age 71) who provided CP at BL were not different from women in the QoL subset or from non-QoL pts. 68/145 (47%) women had a HCP. CP groups did not differ based on age, surgery type, tumor and nodal stage, hormone receptor status, performance status, chemo assignment, education, marital or employment status except the LCP group had a higher proportion of white women (95% vs. 78%, p=0.004). At BL, there were no differences in perception of self-health based on CP but women with LCP predicted QoL on chemo to be worse than women with HCP (p=0.006) and reported greater nausea/vomiting. Mid-treatment, LCP pts reported worse nausea/vomiting, financial worries, and cancer symptoms. Post-treatment, LCP pts had worse constipation (at 1 mo) and financial worries (at 24 mo). There were no differences based on CP for dyspnea, pain, fatigue, insomnia, anxiety or depression at any timepoint. Mid-treatment, LCP women reported lower QoL and worse social, emotional and physical function compared to HCP women. These scores were not significantly different after treatment completion. LCP women had significantly higher rates of grade 3-5 AEs (53 vs. 34%, p=0.02) during treatment but these did not persist post-therapy. CP was not significantly associated with OS (HR =0.75, p=0.36) or RFS (HR=0.94, p=0.84). Conclusions: LCP at BL was associated with lower QoL, worse physical symptoms, AEs and function mid-therapy, but not mental health. Mid-therapy declines in women with LCP largely reversed post-therapy. This information may be useful for oncology professionals to counsel older ESBC pts with LCP receiving adjuvant chemo. Citation Format: Ajeet Gajra, Linda McCall, Hyman B Muss, Harvey J Cohen, Aminah Jatoi, Karla V Ballman, Ann H Partridge, Linda Sutton, Barbara A Parker, Gustav Magrinat, Jaqueline M Lafky, Arti Hurria. Association of patient preference for adjuvant chemotherapy (chemo) at baseline (BL) with toxicity, mental health, function, quality of life (QoL) and survival in older women with early stage breast cancer (ESBC) [CALGB 49907 Alliance] [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-07.

Purpose. For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC. Methods. Fifty patients with refractory mCRC were enrolled and received bevacizumab at 10 mg/kg every 2 weeks and everolimus at 10 mg orally daily. Results. Of the 50 patients enrolled, the median age was 56 years and the median number of prior regimens was four. Forty-seven patients (96%) had prior bevacizumab exposure and 42 patients (84%) had documented progression on prior bevacizumab-based therapy. Forty-nine patients were evaluable for response; eight patients had minor responses (16%) and an additional 15 patients (30%) had stable disease (SD). No complete or partial responses were seen. The median progression-free survival interval was 2.3 months; however, 26% of patients achieved prolonged SD for ≥6 months, and three patients (6%) were on study for >1 year. The median overall survival duration was 8.1 months. The most common grade 1–2 toxicities were mucositis (68%) and hyperlipidemia (64%). Clinically significant grade ≥3 toxicities included hypertension (14%), fistula/abscess/perforation (8%), mucositis (6%), and hemorrhage (2%). Conclusions. Bevacizumab plus everolimus is generally tolerable but may have risks related to mucosal damage and/or wound healing. Bevacizumab plus everolimus appears to have modest activity in refractory mCRC in patients.

92 Background: Cancer survivors have high rates of sedentary behavior leading to obesity and cardiovascular disease. Physical activity improves quality of life (QOL) and reduces morbidity and mortality. However, cancer survivors commonly cite motivation as a barrier to increasing physical activity. We hypothesized that a motivational text-messaging feedback system linked to a Fitbit Flex activity tracker would increase the activity level of survivors and those undergoing cancer treatment. Methods: 29 participants were enrolled in an IRB-approved single-institution study. Eligibility allowed any cancer/stage, ≤2 days of exercise per week, life expectancy of 12+ months, and smartphone access. After baseline fitness/QOL testing, participants were provided a Fitbit Flex activity tracker. A text-messaging program automatically uploaded data from the tracker via an application programming interface and provided personalized text message feedback to subject’s smartphone daily for 3 months. Primary endpoint was change in step count from baseline to 3 months, with additional endpoints of change in 6 minute walk/QOL measures at 3 months, and continued exercise/use of tracker at 6 months. Results: To date, 24 have completed the 3 month program. Both academic and community sites participated, including areas with limited internet access. Most participants were female (71%) and white (63%). Eight cancer types and all stages were represented. Three participants withdrew – one because of lost tracker, one cancer death, and one “disappointed” with tracker function. Median daily steps at baseline were 3773 (IQR 2928) and 4365 at 3 months (IQR 4864). 42% had at least a 20% increase in median step count at 3 months. Improvement was noted in 45% of survivors and 38% of active treatment participants. Participants frequently used research nurses for guidance on use of wearable tracker (e.g. syncing, charging, features). Conclusions: Activity tracker with personalized daily feedback via text message successfully motivates cancer patients to increase daily activity. Patients are interested in health technology, but require technical support and coaching to maintain use. Clinical trial information: NCT02627079.

TPS10128 Background: Adjuvant endocrine therapy (AET) is a crucial component of treatment used to prevent recurrence and reduce mortality for women with hormone receptor positive breast cancer. Poor adherence to AET is a significant problem, with rates of non-adherence ranging from 28% to 59%. Non-adherence to AET contributes to increased medical costs and increased mortality. Symptoms (e.g., pain, hot flashes, sleep problems, vaginal dryness) associated with AET are related to non-adherence and early discontinuation of treatment. Our goal is to test the efficacy of a novel self-management intervention (SMAET) that teaches patients skills for enhancing adherence to AET and coping with AET-related symptoms. Methods: Trial participants will be recruited from a tertiary care medical center and community clinics that are located in medically underserved areas. Target enrollment is 400 patients. Prospective participants must meet the following criteria: diagnosis of Stage I to III breast cancer; hormone receptor positive tumor; local definitive cancer treatment complete; within 12 months of beginning AET; have at least 18 months of AET recommended; and at least 21 years of age. We will test the effects of the SMAET intervention (n = 200) by comparing it to a general health education intervention (n = 200; attention control). The SMAET protocol includes 7 sessions providing systematic training in coping skills for managing symptoms that interfere with adherence and 3 maintenance calls delivered over 6 months by a nurse via the phone. The intervention also includes interactive voice messaging that is tailored based on real-time adherence data. The primary study outcome, adherence to AET, will be assessed in real-time for 18 months using wireless smart pill bottles (i.e., bottle opening and percent of pills remaining). Symptom interference will be examined as a secondary outcome and will be assessed over 18 months. If effective, the intervention may reduce the burden of AET use. Clinical trial information: NCT02707471.

Several reports have suggested that breast cancer patients with elevated serum levels of interleukin-6 (IL-6) have a worse prognosis than patients with lower levels. We have studied IL-6 in breast cancer cell lines and have shown that autocrine production of IL-6 can confer multi-drug resistance in vitro by inducing multidrug resistance gene-1 transcription with subsequent overexpression of P-glycoprotein (PGP). Both IL-6 and PGP expression can be measured in malignant cells using immunohistochemical (IHC) techniques. We hypothesized that patients whose tumors expressed higher amounts of IL-6 or PGP would be less likely to respond to paclitaxel, an agent affected by the PGP pathway. If so, then IL-6 could serve as a predictive factor for paclitaxel sensitivity. Both IL-6 and PGP expression were measured in patients treated in a randomized trial that compared three doses of single agent paclitaxel (175, 210, and 250 mg/m(2) over 3 h every 3 weeks) in 469 women with metastatic breast cancer (CALGB 9342). No difference in complete and partial response was found among the three treatment arms. Tissue blocks in this trial were analyzed for IL-6 (154 patients) and PGP (149 patients) in paraffin-embedded sections from tumor samples; clinical characteristics of these patients were similar to the total sample of 469 patients. There were no significant differences among IL-6 or PGP scores whether measured as continuous or dichotomous variables, or by other scoring, and response to paclitaxel. In multivariate analysis neither IL-6 nor PGP was a significant predictor of time to progression or overall survival. IHC expression of IL-6 and PGP levels in tumor cells is not a predictive marker for response to paclitaxel in women with metastatic breast cancer.

PURPOSE: Eniluracil (776C85), a potent inactivator of dihydropyrimidine dehydrogenase, allows fluorouracil (5-FU) to be administered orally on a schedule that simulates continuous-infusion 5-FU. The primary objective of this study was to estimate the objective tumor response rate of orally administered eniluracil and 5-FU in the treatment of anthracycline- and taxane-resistant advanced breast cancer. PATIENTS AND METHODS: Patients with anthracycline- and taxane-resistant advanced breast cancer were enrolled onto this open-label, phase II, multicenter study. Patients received orally administered 5-FU 1.0 mg/m2 with eniluracil given in a 10:1 ratio (eniluracil:5-FU) twice daily for the first 28 days of each 35-day cycle. RESULTS: Eighty-four patients were enrolled. Eight partial responses were observed in 84 patients (10%; 95% confidence interval [CI], 4.2% to 17.9%), and 20 patients (24%) had stable disease. The median duration of partial response was 20.1 weeks (95% CI, 12 to 26.7 weeks). The median duration of progression-free survival and overall survival for all patients was 9.9 weeks and 40.4 weeks, respectively. Most adverse events were grade 1 or 2 in intensity. Diarrhea, nausea, malaise/fatigue, vomiting, and mucositis were the most common treatment-related nonhematologic adverse events. The most frequently occurring grade 3 or 4 treatment-related adverse events were malaise/fatigue and diarrhea, occurring in 17% and 7% of patients, respectively. The incidence of grade 3 or 4 hematologic toxicity was low. Grade 3 or 4 hyperbilirubinemia occurred in 17% of patients. CONCLUSION: Eniluracil–5-FU has modest antitumor activity and an acceptable safety profile in anthracycline- and taxane-resistant breast cancer. Treatment was convenient, and patient compliance was high.

Purpose: The purpose of this trial was to evaluate tumor cytoreduction by all-trans retinoic acid (ATRA) in patients with metastatic breast cancer and to characterize the initial pharmacokinetics of this agent. Methods: The study was a single institution, phase II study. The treatment regimen consisted of ATRA administered orally at a dose of 50 mg/m2 three times a day for 14 consecutive days of a 21-day cycle. Cycles were repeated until disease progression, unacceptable toxicity or patient withdrawal. Plasma samples were obtained following the first dose of ATRA for pharmacokinetic analysis. Results: A total of 17 patients with metastatic breast cancer were enrolled in the study, and 14 completed at least one cycle of therapy and were evaluable for response. One patient achieved a partial response in soft tissue of 4 months duration. Three patients had stable disease for 4, 2, and 2 months duration. The remainder had progressive disease. ATRA was reasonably well tolerated. Pharmacokinetic analysis revealed a high degree of interpatient variability in systemic exposure following the initial dose of ATRA. Conclusions: We conclude, that in the dose and schedule tested, ATRA does not have significant activity in patients with hormone-refractory, metastatic breast cancer. Future studies should focus on more intensive investigation of those individuals with very high or low ATRA initial systemic exposure in the hope of expanding our understanding of ATRA's clinical pharmacology, ultimately leading to improved efficacy.

251 Background: Chemotherapy administration is a complex process involving several steps and checkpoints. Any of these can improve or delay efficiency in patients receiving timely care. We conducted a time study auditing delays to the start of chemo infusion to determine the main causes of treatment delays and identify areas for improvement. Methods: Within the Duke Oncology Network (DON), an outreach network assisting rural cancer clinics with clinical operations, we identified one site for the study. A DON nurse practitioner and chemotherapy nurse analyzed records from 157 patients who received intravenous (IV) chemotherapy from January to March of 2011. We collected data on timepoints from administrative schedules, nurses’ infusion records and faxes to and from the lab and pharmacy, and median times and ranges were calculated. Results: Causes of chemotherapy infusion delays can be investigated through usual patient and operational documentation. Clear and accurate data could be obtained regarding patient arrival times, time seated in infusion chair, time IV access was obtained, times labs were sent/resulted, times chemotherapy drugs were requested/received and times infusions were started. The longest delays generally involved the earlier steps, including from arrival to treatment start (see Table). Surprisingly, a thorough search did not find any literature-based benchmarks for comparison. Conclusions: It is logistically feasible and clinically helpful to conduct a time study of chemotherapy infusion delays by compiling data from timepoints available in infusion records, admin notations and faxed reports. Interestingly, in our study lab and pharmacy turnaround times were not the main cause of delays as initially expected, nor were MD visits. We identified concrete areas for improvement and will use this data to design a plan for administrators, nurses and clinicians to reduce delays to infusion start by 50%. [Table: see text]

325 Background: Creating an effective platform for multidisciplinary tumor conferences can be challenging in the rural community setting. The Duke Oncology Network, which is affiliated with hospitals in rural locations throughout North Carolina, created an internet-based platform for a multidisciplinary conference to enhance the care of lung cancer patients in the community. This conference incorporates providers from different physical locations within the community and affiliated providers from a university-based cancer center two hours away. An electronic approach connects providers through space and time vocally and visually. Methods: Development of the virtual conference began in February 2009. Biweekly conferences were set up using the Adobe Connect web conferencing platform. This provides a secure website and phone line to ensure patient confidentiality. Case information is de-identified and incorporated into a slideshow uploaded to the platform. Multiple disciplines are invited to participate, including radiology, radiation oncology, thoracic surgery, pathology, pulmonology, and medical oncology. Participants only need telephone access and internet connection to participate. Results: The first virtual tumor board occurred December 14, 2009. Patient histories and physicals are presented, and the web conferencing platform allows radiologic and histologic images to be reviewed. Treatment plans for patients are discussed, allowing providers to coordinate care among the different subspecialties. Patients are identified that need referral to the affiliated university-based cancer center for specialized services. Pertinent treatment guidelines and journal articles are reviewed. In 2011, there were 9-10 participants per session, with 2-3 cases presented, on average. Conclusions: The use of a web conferencing platform allows subspecialty providers throughout the community and hours away to participate in discussing lung cancer patient cases. This platform increases convenience for providers, eliminating travel time to a central location. Coordination of care for patients requiring multidisciplinary care is facilitated, shortening evaluation time prior to definitive treatment plan.

3541 Background: BV, a monoclonal antibody against vascular endothelial growth factor, provides a survival advantage when added to first line therapy for metastatic colorectal cancer. CAP allows for fluoropyrimide treatment without the inconvenience of an infusion pump. We aimed to investigate the combination of OX, CAP, and BV (XeloxA) as a more convenient and active regimen. Methods: Pts with untreated metastatic colorectal cancer received OX 85 mg/m2 d1, CAP 1000 mg/m2 BID d1–5 and 8–12, and BV 10 mg/kg d1. Cycles were repeated every two weeks. The starting dose of CAP was changed to 850 mg/m2 BID due to toxicity in the first 28 patients. Data were analyzed under an intention to treat method. Results: 50 pts received therapy (28M, 22F), median age 55 (range 24–81). Data were available on 49 pts. The most common toxicity was diarrhea, with 12/49 (24%) having grade 3 diarrhea, and 22% with grade 2. After the dose reduction of CAP, 3/21 (14%) pts had grade 3 diarrhea and 2/21 (10%) with grade 2 as compared to 32% grade 3 and 32% grade 2 at the higher dose. At the higher dose of CAP 4% of pts had grade 3 hand-foot syndrome (HFS) and 39% had grade 2. At the lower dose, 10% had grade 3 and 5% had grade 2. Other grade 3 toxicities were minimal, including neurotoxicity (8%), vomiting (6%), and neutropenia (4%). There were 23 responses, 1 CR and 22 PR (RR=47%; 95% CI: 33%-62%). 21 pts had stable disease (43%). Median progression free survival (PFS) was 10.7 months (95% CI: 8.6–13.6). Conclusions: XeloxA is a well tolerated, active regimen in the first line treatment of metastatic colorectal cancer. RR and PFS data approximate that of infusional 5-FU regimens in combination with BV without the necessity of an infusion pump. [Table: see text]