6567 Background: Time toxicity is increasingly recognized as an important factor in quality of life in cancer patients, and this effect may be amplified in under-resourced oncology settings. In the safety-net oncology center at Parkland Health (PH), wait time from infusion appointment check-in to treatment start was 147 minutes in June 2022, which led to significant patient frustration, delays in care, and staff dissatisfaction. We aimed to decrease wait time by 20% by December 2022. Methods: Baseline wait time data for patients getting infusions in the oncology infusion center was collected daily from the electronic medical record (EMR) time stamps of check in and infusion start (first IV medication given), and the average time was calculated. A value stream map detailing the steps required to start infusion with time stamps was produced. Stakeholders were queried to identify causes of delay, an Ishikawa diagram was constructed, and a priority matrix was developed to determine the most impactful interventions. The first PDSA cycle (July-Oct 2023) intervention consisted of working group formation and implementation of separate infusion pathway for patients getting injections (“fast track”). The second PDSA cycle (Nov-Dec 2023) intervention was rescheduling infusion-only patients to the least congested times of the day to relieve the bottleneck that occurred in the late mornings for patients with labs or provider visit prior to infusion. Patients and infusion center providers were surveyed about their perception of wait times. Results: Average wait times decreased from 147 minutes to 131 minutes during first PDSA cycle, a 10.8% improvement from baseline. From Nov-Dec 2023 during second PDSA cycle, wait time improved to 127 minutes, a 15.7% improvement from baseline. The average daily number of infusions and injections increased from 106/day baseline to 115/day by Dec 2023; an increase of 8.5%. Qualitative surveys of patients and infusion providers endorsed increased satisfaction with infusion process. Conclusions: Using established quality improvement methods, we improved average wait times for Parkland Health oncology infusion patients by 15.7% over a 6 month period. While we did not meet our goal, we increased daily capacity to treat patients by 8.5% while improving overall infusion wait time. We also improved perceptions of quality of care.
47 Background: Parkland Health and Hospital System (PHHS) is the safety-net health system for Dallas County. In a resource-limited health care system, no-shows create waste and delay care. We sought to decrease the no-show rate (NSR) for patients scheduled for infusions, transfusions, and injections in the PHHS medical oncology infusion center by 33% in a 4-month period. Methods: A multidisciplinary team reviewed the NSR from January 2020 to May 2020. The reasons for missed appointments were investigated via chart review to better develop an intervention for meaningful change. A telephone follow-up protocol by the infusion nurses with standardized documentation and communication with the clinic and scheduling teams (intra-clinic communication) was implemented for each missed infusion appointment starting in February 2020. Results: The infusion center had a 16.4% NSR in January 2020. Of the 306 missed appointments, there was no documented reason for 44% (159). 19% (70) were related to change in plan-of-care; 19% (67) were in patients who had been admitted. Patient-related issues (transportation, illness, work/family obligations, etc.) were 13% of no-shows. Only 40 (11%) of the no-shows had a follow-up call. After implementation of follow-up telephone calls, the NSR was 11.2% by May 2020, a 32% decrease. 57.8% (204/1822) of patients who no-showed received a follow-up call to document reason for the missed appointment. Conclusions: We decreased the NSR in the PHHS medical oncology infusion center by 32% over a 4-month period, nearly reaching our goal, by implementing standardized post-no-show follow-up calls. Through our process, we discovered that communication, with the patient and intra-clinic, accounted for the most missed appointments rather than patient-related or other factors. Perhaps confounding our results were changes brought about by the COVID-19 pandemic, including mandatory telephone screening of patients prior to infusion appointments. Next steps include integrating pre-appointment calls into the workflow, standardizing change-in-plan communication, and cost analysis of interventions in our resource-limited setting.
126 Background: HAIP (hepatic arterial infusion pump) therapy is a promising intervention for metastatic colorectal cancer (mCRC) with liver metastases, addressing significant challenges in management and prognosis. It offers targeted treatment to maximize efficacy while minimizing systemic toxicity. We present a retrospective analysis of patients with metastatic colorectal adenocarcinoma treated with HAIP therapy at an academic center and safety net hospital. Methods: Patients with mCRC and hepatic metastasis who received at least one HAIP floxuridine (FUDR) cycle from 2013 to 2023 were included. Baseline data, including demographics, tumor characteristics, and treatment history, were collected pre-HAIP. The main outcome was overall survival (OS) post-pump placement, with secondary outcomes being real-world progression-free survival (rwPFS) and HAIP-related complications. Results: In total, 88 patients were evaluated for inclusion, of whom 63 met inclusion criteria and were included for analysis. The median age of included patients was 46 years (interquartile range (IQR) 41-57) and 54% were male. Prior to HAIP, 38 (60%) of patients received one line of systemic therapy, while 18 (29%) had two. The median OS from HAIP placement was 28.0 months (95% CI 21.9-NR) and median rwPFS was 11.2 months (95% CI 7.1-16.1). Baseline bilirubin, KRAS mutant status, and CEA were associated with OS in the multivariate cox model. The most common complication from HAIP placement was hematoma (n=4, 6.3%), followed by pump infection (n=2, 3.2%). Grade 3 toxicities from FUDR infusion were infrequent, involving alkaline phosphatase (n=6), AST or ALT elevation (n=3), bilirubin increase (n=2), and platelet count decrease (n=1). Conclusions: HAIP treatment is associated with durable responses and few complications, making it well-tolerated by patients. For individuals with colorectal cancer and hepatic metastases, HAIP chemotherapy using FUDR presents a viable and effective treatment option, potentially improving overall outcomes and quality of life. Further prospective and randomized work may establish the role for HAIP in mCRC with liver metastases.
Abstract Background: Our research aimed to evaluate and compare the genetic variations in the primary and metastatic sites of patients with metastatic pancreatic cancer. Methods: In this study, we selected individuals with metastatic pancreatic cancer from the data provided by the American Association for Cancer Research Project GENIE (version 14.1). The comparison of genetic mutations between primary and metastatic tumor sites was conducted using the Fisher exact test, augmented with the Benjamini-Hochberg adjustment technique. Results: In a study of 3,108 patients with metastatic pancreatic cancer, 38.9% had metastatic site tumor samples, while 61.1% had samples from the primary tumor. The most frequent mutations were KRAS (89.4%), TP53 (72.9%), SMAD4 (21.2%), and CDKN2A (17.4%). Metastatic samples showed higher rates of CDKN2A, CDKN2B, and MTAP mutations compared to primary site samples (40.1% vs. 29.1%; 20.3% vs. 10.4%; and 20.8% vs. 8.9%, respectively, all with p<0.001 and q<0.001). In patients with young-onset pancreatic cancer (younger than 50 years), there was no notable difference in gene mutations between the two sample groups. Conclusion: Our findings corroborate the notion that identifying the precise genes that contribute to the development of metastatic pancreatic cancer is vital for gaining a more comprehensive understanding of the biological mechanisms. Moreover, genomic profiling could be a key in pinpointing potential biomarkers for diagnosis and therapy. Citation Format: Suleyman Y. Goksu, Muhammet Ozer, Busra Bacik Goksu, Nina N. Sanford, Amy Jones, Nilesh Verma, Syed Kazmi. Genomic characterization of metastatic pancreatic cancer according to tumor sample sites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4978.
82 Background: Clinicians have difficulty predicting longitudinal changes in patient symptom burden and quality of life, and then how those changes might affect treatment preference. The primary aim of this pilot study was to investigate how self-reported symptom burden, quality of life, and treatment preference change over time in mCRC patients with limited life expectancy. Methods: Eligible mCRC patients had incurable disease, received chemotherapy at Duke or Duke Raleigh, were > = 18 years old, and spoke English. Patients were surveyed at each clinic visit and followed for up to 3.8 years on study. Measures included FACT-C (Functional Assessment of Cancer Therapy-Colorectal), PCM (Patient Care Monitor; a validated, 87-item review of systems survey; items measured on a 0-10 scale), and QQQ (Quality-Quantity Questionnaire; a validated, 8-item measure of cancer patient preference for quantity vs. quality of life; items measured on a 1-5 Likert scale). Demographic, disease, and treatment data were abstracted from the medical record. Results: The 56 patients were primarily male (68%) and Caucasian (79%) with a mean age of 55 at diagnosis of metastatic disease. Patients answered surveys a mean of 6.8 times each, with a median 364 days between first and last surveys. Over time, patients reported most symptoms improved or stayed the same (72%, n = 63 symptoms). Mean symptom scores that improved the most from first to last survey were fatigue (3.92 to 3.03) and nausea (2.1 to 1.4), while pain (1.9 to 2.5) and cough (0.4 to 0.7) worsened the most. Decision making about treatment preference also did not change over time, with mean QQQ scores from first survey (22, n = 28) to last survey (22, n = 16) remaining stable. Mean QQQ length and quality scores likewise were unchanged (12.9 to 12.8; 12.4 to 12.2 respectively). Conclusions: In this pilot study of mCRC patients with limited life expectancy, reported symptom burden scores remained stable or modestly improved over time, while preferences for quality vs. quantity of life remained stable. These findings suggest that patients with advanced cancer might perceive symptom burden differently over the course of their treatment.
e15522 Background: Hypertension (HTN) and hyperlipidemia (HLD) are widely prevalent diseases, but their effect on colorectal cancer (CRC) outcomes is limited. We aimed to study the effects of baseline HTN and HLD on CRC survival. Methods: We identified patients with stage 1-4 colorectal cancer diagnosed between 2011 and 2017 from tumor registry of a large safety-net hospital and NCI-designated Comprehensive Cancer Center. Patients with a diagnosis of HTN (ICD-9/10: I10, 401.9) and HLD (ICD 9/10: E78.0-E78.5, 272.0-272.4) at CRC diagnosis were compared with patients who did not have these comorbidities. Chi-square tests were used to compare categorical differences between groups. Multivariable logistic regression was used to identify factors associated with HTN and HLD. Overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazards model with an index date of tumor diagnosis until death. Patients who did not meet endpoint of interest were censored at the date of last clinical contact. Results: We identified 1,921 patients - 627 (33%) had HTN, 403 (21%) had HLD and 309 (16%) had HTN and HLD. The median age of diagnosis of CRC was 61 (IQR: 54-68) for HTN patients and 61 (IQR: 53-69) for HLD patients. Compared to patients without HTN or HLD, patients with HTN or HLD were more likely to be non-Hispanic Blacks (HTN: 39% vs 19%; HLD: 30% vs 24%), uninsured (HTN: 33% vs 17%; HLD: 36% vs 18%) and treated at safety-net hospital (HTN: 53% vs 24%; HLD: 55% vs 27%). These patients had a higher prevalence of other comorbidities including diabetes mellitus (HTN: 39% vs 7%; HLD: 50% vs 9%), anxiety (HTN:12% vs 3%; HLD: 14% vs 4%), and tobacco use (HTN: 16% vs 5%; HLD: 14% vs 7%). On multivariable analysis, HTN and HLD patients were older (HTN-OR: 1.05, 95CI: 1.04-1.06; HLD-OR: 1.03, 95CI: 1.02-1.05), had concurrent diabetes mellitus (HTN-OR: 4.2, 95CI: 2.9-6.3; HLD-OR: 4.5, 95CI: 3.2 - 6.4), depression (HTN-OR: 2.0, 95CI: 1.3-3.2; HLD-OR: 1.9, 95CI: 1.2-3.0), and cirrhosis (HTN-OR: 2.6, 95CI: 1.3-5.2; HLD-OR: 2.1, 95CI: 1.1-3.9) and treated at safety-net hospital (HTN-OR: 2.7, 95CI: 1.7-4.3; HLD-OR: 1.4, 95CI: 0.9-2.2). Compared to patients without HTN or HLD, OS was improved for HLD alone patients (HR: 0.58; 95CI: 0.38-0.89; P: 0.01), while it was not different for patients with HTN without HLD (HR: 0.99; 95CI: 0.81-1.2; P: 0.55) or HTN and HLD (HR: 0.92; 95CI: 0.75-1.13; P: 0.34). The 5-year yr OS for these groups were 65%, 77%, 66%, and 69% respectively. Conclusions: In this single institution cohort that includes a safety-net hospital, the prevalence of HTN or HLD at CRC diagnosis was higher among older and non-Hispanic Black CRC patients and associated with coexisting diabetes mellitus, anxiety, and tobacco use. CRC patients with HLD alone had a significantly better 5-yr OS compared to those without HTN or HLD, with HTN alone, and with HTN and HLD.
110 Background: Rat sarcoma virus mutation testing (RASmt) is critical in guiding systemic therapy selection for patients with metastatic colorectal cancer (mCRC) in the first-line setting. Missing results at the initial medical oncology visit can negatively impact patient outcomes by delaying treatment or leading to inappropriate treatment selection. This quality improvement (QI) project aims to increase the percentage of patients with newly diagnosed mCRC with RASmt results available by their first outpatient medical oncology appointment at a large safety net hospital to 20% over an 8-month period. Methods: A multidisciplinary team of key stakeholders including clinicians, a pathologist, and administrators was assembled to determine factors associated with failure to obtain RASmt. A baseline analysis of all patients referred to the gastrointestinal (GI) oncology clinic from June 2022 to April 2023, with manual review of electronic medical records by investigators, showed that only 6% (3/46) of newly diagnosed patients with mCRC had RASmt results available by their first GI oncology appointment. Two Plan-Do-Study-Act (PDSA) cycles were conducted to assess interventions that were implemented based on process mapping and reasons for unavailable test results. To increase the percentage of patients with RASmt results available, starting December 2023, patients initially diagnosed with mCRC as inpatients who were being followed by the oncology consult service had RASmt ordered on the tissue biopsy prior to discharge (PDSA1). Starting April 2024, the medical directorfor outpatient GI oncology clinics ordered RASmt for all patients with mCRC referred to the clinic at the point of referral (PDSA2) . New patient referrals were reviewed through July 3, 2024. Results: At baseline, the most common reason for unavailable RASmt results was the lack of test orders, with 70% (32/46) of new patients with mCRC not having RASmt ordered prior to their first appointment. Once RASmt was ordered, the average time for results was 13 days. After the first intervention, 4% (1/23) of patients with mCRC had RASmt results available at their first appointment. After the second intervention, 42% (5/12) of patients had RASmt results available. Additionally, median time from diagnosis of mCRC to first appointment decreased from 23 days at baseline to 17 days during PDSA1 to 12 days during PDSA2. Conclusions: By ordering RASmt at the point of referral, the percentage of patients who had RASmt available at their first appointment markedly increased from 6% to 42%. This QI initiative additionally demonstrates the importance of multidisciplinary teams to enhance patient care efficiency at a large safety net hospital. Further efforts are ongoing to increase RASmt availability beyond 42% with a focus on reducing the turnaround time of the test.
TPS324 Background: A critical clinical challenge in microsatellite stable (MSS) metastatic colorectal (mCRC) patients is to identify strategies to overcome lack of response to immune checkpoint inhibitors. An immunosuppressive tumor microenvironment comprising myeloid-derived suppressor cells (MDSC), endothelial cells, regulatory T cells, tumor associated macrophages, and cancer associated fibroblasts promotes immune evasion and resistance to these agents. MDSCs are bone marrow derived myeloid cells that suppress T-cell function and promote tumor growth. Among all cancers, mCRC patients have one of the highest frequency of MDSC (CD11b+, CD33+, CD14+ HLA-DRneg) in blood (1). It was demonstrated that altering the MDSC% in the tumor microenvironment by ATRA and anti-VEGF therapy (bevacizumab) can enhance the effects of immune checkpoint inhibitors (2-4). The hypothesis of the current clinical trial is that the combination of ATRA, bevacizumab and atezolizumab will lead to a decrease in MDSC population in tumor microenvironment leading to a clinically meaningful improvement in response rates among refractory MSS mCRC patients. Methods: This is a single-arm, open-label, phase 2 clinical trial combining ATRA, bevacizumab, and atezolizumab in refractory MSS mCRC patients. It will enroll a total of 21 patients over 24 months at UT Southwestern Medical Center that are MSS by PCR or NGS testing or are proficient in immunohistochemical expression of all four mismatch repair enzymes (MLH1, MSH2, MSH6, PMS2). ATRA will be administered orally at 45 mg/m2/day in 2 divided doses on days 1-7 and repeated every 14 days; atezolizumab will be given intravenously on day 1 at 840 mg dose every 14 days, and bevacizumab will be administered intravenously on day 1 at 10 mg/kg dose every 14 days. The first six patients enrolled on this study will contribute to the safety lead-in phase of this study. The primary outcome is to assess the overall response rate by RECIST v1.1. Secondary outcomes include assessment of disease control rate and frequency of adverse events using CTCAE v5.0. Exploratory outcomes include assessment of PFS and OS and collecting blood and tissue samples at defined timelines to study the changes in the MDSC population among responders and non-responders (NCT05999812). 1. Kobayashi, M. et. al., Clin Cancer Res, 2019. 2. Mirza, N., et al., Cancer Res, 2006. 3. Tobin, R.P., et al., Int Immunopharmacol, 2018. 4. Tobin, R.P., et. al., Clin Can Res, 2023. Clinical trial information: NCT05999812 .
e16085 Background: KRAS mutation is associated with poor prognosis in metastatic colon cancer (mCC). However, the age-dependent prognostic value of KRAS status is unknown. We aimed to confirm if the prognostic impact of KRAS is dependent on the age of diagnosis in mCC. Methods: We identified adult patients with mCC diagnosed between 2004 and 2016 using the NCDB. We compared patients with KRAS mutation and KRAS wild type, stratified according to age group < 50, 50-70, and ≥70. Categorical variables were compared using the chi-square test. We performed the Kaplan-Meier and Cox regression methods for survival analyses. We adjusted for patient and tumor characteristics (included KRAS status, MSI, 18q loss of heterozygosity, side of the primary tumor). Results: A Total of 19,875 patients had KRAS status reported; 43% had KRAS mutation, and 57% were KRAS wild type. Patients with KRAS mutation were more likely to be female, black, have elevated CEA, and have right-sided tumors (all p < .001). In the overall population, patients with KRAS mutation had significantly worse OS compared to patients with KRAS wild type (20 vs. 22 months, p < .001), and this difference was maintained after multivariable Cox regression analysis ( p < .001) (Table). Young patients ( < 50 years) with KRAS mutation had a worse prognosis than those with KRAS wild type in the tumor (23 vs. 29 months, p < .001). KRAS status did not maintain its prognostic value among older age (≥70 years) patients (14 vs. 14 months, p = NS). Conclusions: In this analysis of a national cancer registry, we confirmed that KRAS mutation was an independent poor prognostic factor for mCC. This effect persisted after adjusting for patient and tumor characteristics, including sidedness and MSI status. However, we identified that this prognostic value of KRAS mutation is significant in young mCC patients < 50 years, as compared to older patients. [Table: see text]
