Citations

1597 Background: The impact of COVID19 pandemic on patient health beliefs and healthcare systems has adversely affected mammographic breast cancer screening (MBCS) during the initial stages of the pandemic. The aims of our study were to determine whether the initial decrease in MBCS rates persisted or if there was a rebound in later stages and to quantify the impact on urban and rural populations. Methods: This retrospective observational study analyzed data from March 2017 to March 2023 to assess whether eligible women received annual MBCS during this timeframe. We included women aged 40-75 years, drawn from the integrated Mayo Clinic system, encompassing nearly 60 primary care practices in Arizona, Florida, Iowa, Minnesota, and Wisconsin, representing a broad cross-section of the United States (US) population. US census data was utilized to classify a county as urban or rural. We divided the study period into 4 categories:1) pre-COVID-19 pandemic (March 1, 2017-March 10, 2020), 2) early pandemic (March 11, 2020-March 10, 2021; pre-vaccination period), 3) mid- pandemic (March 11, 2021-March 10, 2022; delta and omicron variant dominant period), and 4) late pandemic (March 11, 2022-March 1, 2023; recovery period). Utilizing the Poisson regression model, we compared the incidence rate ratio (IRR) for rates of MBCS across the 4 predefined time periods. Multivariable modeling was performed to assess the significance of MBCS rates with urbanicity while controlling for the year (2017-2022) and age. Results: By race and ethnicity, the women in this cohort were White (92%), Black (3.1%), Asian (3%) and other (1.9%). The median age was 57 years and the cohort included 239, 804 women aged 40-75 years. MBCS rates was 49.2% in 2017, 47.1% in 2018, 46.4% in 2019, and decreased to 42.1% in 2020 and improved to 44.7% in 2021 and 43.8% in 2022. Compared with the pre-COVID-19 pandemic period, there was a significant decrease in MBCS rate in the early pandemic (IRR= 0.886, 95% CI 0.879, 0.892, p<0.001). Though the MBCS rate improved in the mid-pandemic period, it remained below the pre-pandemic level (IRR=0.941, 95% CI 0.934, 0.948, p<0.001). Similarly, during the late stage of the pandemic, the MBCS rate remained lower than the pre-pandemic level (IRR=0.922, 95% CI 0.915, 0.928, p<0.001). Rural counties had a lower MBCS rate compared with urban counties (IRR = 0.936, 95% CI 0.931, 0.941, p<0.001). Conclusions: This study confirms the negative impact of the early COVID-19 pandemic on MBCS, and it revealed its persistent effect, as the current MBCS rate remains below the pre-pandemic rate. These findings were more evident in rural counties. Factors contributing to the long-lasting impact are being analyzed with the intent to develop and implement targeted solutions to improve the MBCS rate.

Objective: This study investigates Enhanced Recovery After Surgery (ERAS) protocols’ impact on long-term opioid and sedative use following mastectomy with or without implant-based breast reconstruction (IBBR). Background: ERAS protocols for patients undergoing mastectomy with or without IBBR are associated with decreased length of stay, increased rate of same-day discharge, decreased postoperative pain, and decreased postoperative opioid requirements. However, less is known about their effect on opioid and sedative use beyond 90 days after surgery. Methods: A retrospective review of all patients undergoing mastectomy with or without IBBR at a single institution between January 2013 and December 2019. Mastectomy ERAS protocols were implemented in February 2017, creating 2 groups: pre-ERAS and ERAS. Baseline characteristics and prevalence of chronic opioid and sedative use were compared. Univariable and multivariable logistic regression predicted factors associated with increased odds of chronic opioid and sedative use. Results: A total of 756 patients were evaluated: 405 pre-ERAS and 351 ERAS. Post-ERAS, chronic opioid use decreased in opioid-naive (40% vs 30%, P=0.024) and opioid-tolerant patients (58% vs 37%, P=0.002), with no increase in chronic sedative use. There were decreased odds of chronic opioid use for all ERAS patients (OR=0.57, 95% CI: 0.42–0.76), and of IBBR patients, those receiving subcutaneous implants (OR=0.31, 95% CI: 0.20–0.48). There was increased chronic opioid-use odds if undergoing bilateral surgery (OR=1.54, 95% CI: 1.14–2.08), 2-stage reconstruction (OR=9.78, 95% CI: 5.94-16.09), and for patients with higher PACU pain scores (OR=1.09, 95% CI: 1.03–1.14) or >150 discharge OMEs (OR=2.63, 95% CI: 1.48–4.68). Conclusion: ERAS protocols for mastectomy patients with or without IBR are associated with decreases in chronic opioid use, without concomitant increases in chronic sedative use.

Abstract BACKGROUND: The amplification of genes PDL-1, PDL-2, and JAK2 on chromosome 9p24, known as the PDJ amplicon, has been identified in 15% of triple negative breast cancer (TNBC) and is associated with tumor infiltrating lymphocytes and elevated JAK2 mRNA, suggesting a coordinated inflammatory response in TNBC. Adding pembrolizumab to chemotherapy in KEYNOTE trials 355 and 522 has validated the use of PD-1 blockade in TNBC and redefined the standard of care. Despite preclinical data suggesting a role for targeting the IL- 6/JAK2/STAT3 pathway, the JAK1/JAK2 inhibitor ruxolitinib has not shown efficacy as a single Agent in breast cancer. This is the first phase I clinical trial evaluating the combination of pembrolizumab and ruxolitinib in the treatment of metastatic TNBC. METHODS: We conducted a phase I clinical trial with accrual from 2018 to 2023 at Mayo Clinic Arizona. Patients (n=12) received 200 mg of IV pembrolizumab per cycle (every 3 weeks) with 3+3 dose escalation of oral ruxolitinib twice a day (dose level 0: 10 mg PO BID, level 1: 15 mg PO BID, level 2: 20 mg PO BID). The primary endpoint was to determine the maximum tolerated dose (MTD) of ruxolitinib and secondary endpoints were treatment safety and efficacy. Clinical response was assessed by computed tomography of the chest, abdomen, and pelvis every 3 cycles. PD-L1 expression in tumor was measured by immunohistochemistry (IHC). The effect of the combined therapies on T and B cell populations were assessed by flow cytometry and antibody profiling of 695 tumor antigens and 8 viral antigens by nucleic acid protein programmable array. RESULTS: Twelve female patients with chemotherapy refractory metastatic TNBC were treated on study. All received 200 mg IV pembrolizumab every cycle. Due to rapid disease progression of three patients early after treatment initiation, eligibility was restricted to prohibit patients with extensive pulmonary disease or elevated LDH. Those patients were excluded from efficacy or correlative analysis. The most common toxicities were transaminitis (n=12), anemia/leukopenia (n=12), and fatigue (n=9). The majority of adverse events were grade 1 and occurred at dose level 2. There were 5 adverse events grade 3 or higher: respiratory or thoracic complications (n=3), hypertension (n=1), and abdominal pain (n=1), but MTD was not established. The median number of cycles was 4 for each dose level (range n=2.0-9.0) and the median time to progression was 3 months (range n=1.4-6.3). No patient had tumor response by RECIST v1.1 criteria and there was no association of disease stability with PD-L1 tumor expression by IHC. Circulating antibodies to tumor antigens remained stable, and viral-specific antibodies mildly decreased by month 2 in all patients at dose levels 0 and 1. Of the 7 patients reactive to TRIM21 autoantibodies, 2 patients had a transient increase at 2 months. CONCLUSIONS: The combination of pembrolizumab with ruxolitinib was well tolerated at all dose levels, and the number but not the severity of adverse events increased with higher ruxolitinib dose. Two of six patients in dose level 0 and 1 had stable disease for six months on treatment, suggesting that the lower dose levels of ruxolitinib (i.e. 10 mg PO BID) may have more activity in combination with pembrolizumab. Citation Format: Anelia Kassi, Jacqueline Carmona, Sarah M. Green, Heidi Kosiorek, Michael T. Barrett, Barbara A. Pockaj, Donald Northfelt, Karen S. Anderson. Phase I trial of combination pembrolizumab and ruxolitinib in metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-07.

Abstract Purpose: There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin–stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Experimental Design: ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR. Results: Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32–3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42–7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87–2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09–4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers.

Abstract Purpose: Chronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN. Experimental Design: We randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. Results: The Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. Conclusions: With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions. Significance: Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.

162 Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were applied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Performance metrics included log-rank test, hazard ratios and Somers’ Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10-5) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10-11) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10-7) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance.

AbstractIntroductionInpatient hyperglycemia is an established independent risk factor among several patient cohorts for hospital readmission. This has not been studied after kidney transplantation. Nearly one‐third of patients who have undergone a kidney transplant reportedly experience 30‐day readmission.MethodsData on first‐time solitary kidney transplantations were retrieved between September 2015 and December 2018. Information was linked to the electronic health records to determine diagnosis of diabetes mellitus and extract glucometric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30‐day readmission. We report the average performance of the models on the testing set on bootstrapped partitions of the data to ensure statistical significance.ResultsThe cohort included 1036 patients who received kidney transplantation; 224 (22%) experienced 30‐day readmission. The machine learning algorithm was able to predict 30‐day readmission with an average area under the receiver operator curve (AUC) of 78% with (76.1%, 79.9%) 95% confidence interval (CI). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient‐hyperglycemia, inpatient‐hypoglycemia, minimum and maximum glucose values among those with higher 30‐day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper‐ and hypoglycemia, the recipient and donor body mass index (BMI) values, presence of delayed graft function, and African American race as the most predictive risk factors of 30‐day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed.ConclusionsSuboptimal glucose metrics during hospitalization after kidney transplantation are associated with an increased risk for 30‐day hospital readmission. Optimizing hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30‐day readmission.

365 Background: Automated scalp cooling (ASC) is utilized in breast cancer patients to reduce chemotherapy-induced alopecia. Nursing staff and patient perspectives on ASC are limited regarding impact on care delivery and outcomes. Methods: A survey-based study of patient and chemotherapy nurse perspectives of ASC was conducted at three multi-regional Mayo Clinic sites. One-time surveys were sent to breast cancer patients and nurses for self-reporting of the ASC experience. Patients were identified via ICD-10 codes for breast cancer with subsequent chart review to confirm relevant chemotherapy regimen and ASC use. Chemotherapy nurses were identified by their respective chemotherapy unit nurse managers. Patient survey responses were compared between groups that did or did not use ASC by use of Pearson chi-square test for frequency data and the Kruskal-Wallis rank sum test for continuous measures. P values <0.05 were considered statistically significant. Results: Surveys were sent to 181 nurses with 61 (33.7%) completing them. Nurses reported ASC administration to 10-50 patients (n=43, 63.9%) or ≥50 patients (n=18, 29.5%). Most felt they had little or no technical support available (67.2%), witnessed scheduling difficulties (52.5%), were distressed by workload intensity (52.5%), and did not receive adequate training (67.2%). Most felt that ASC demanded greater nursing time compared to other duties (57.4%). Most would not recommend ASC to a friend or family member (88.6%). Surveys were sent to chemotherapy patients with 93 of 465 (20.0%) ASC patients and 56 of 341 (16.4%) without ASC (control) completing them. Controls were significantly more likely to experience hair loss, shave their head, and wear a wig (all p<0.001). There was no significant difference between groups for the EORTC QLQC30, EORTC BR23, and Body Image Scale results or frequency of headaches. Patients who used ASC for less than half of their chemotherapy sessions reported significantly more cold discomfort ( p=0.040) and dizziness ( p=0.003). Time investment (33.3%) and side effects (31.2%) were the most frequent burdens cited. Conclusions: Most nurses indicated that ASC increased nursing workload compared with other duties, and they lacked adequate training and technical support. Increasing formal nurse education and access to technical support documents and live technical support may be options for improving nursing satisfaction with ASC. Patient responses suggest qualitative effectiveness of ASC in reducing hair loss. While those with ASC were less likely to shave or use a wig, this did not translate to significant differences in quality of life or psychosocial body image compared to controls. Cold discomfort and dizziness were the most frequent side effects among those with lower utilization of ASC.

Abstract Purpose: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by systemic symptoms, cytopenias, organomegaly, and bone marrow fibrosis. JAK2 inhibitors afford symptom and spleen burden reduction but do not alter the disease course and frequently lead to thrombocytopenia. TGFβ, a pleiotropic cytokine elaborated by the MF clone, negatively regulates normal hematopoiesis, downregulates antitumor immunity, and promotes bone marrow fibrosis. Our group previously showed that AVID200, a potent and selective TGFβ 1/3 trap, reduced TGFβ1-induced proliferation of human mesenchymal stromal cells, phosphorylation of SMAD2, and collagen expression. Moreover, treatment of MF mononuclear cells with AVID200 led to increased numbers of progenitor cells (PC) with wild-type JAK2 rather than JAK2V617F. Patients and Methods: We conducted an investigator-initiated, multicenter, phase Ib trial of AVID200 monotherapy in 21 patients with advanced MF. Results: No dose-limiting toxicity was identified at the three dose levels tested, and grade 3/4 anemia and thrombocytopenia occurred in 28.6% and 19.0% of treated patients, respectively. After six cycles of therapy, two patients attained a clinical benefit by IWG-MRT criteria. Spleen and symptom benefits were observed across treatment cycles. Unlike other MF-directed therapies, increases in platelet counts were noted in 81% of treated patients with three patients achieving normalization. Treatment with AVID200 resulted in potent suppression of plasma TGFβ1 levels and pSMAD2 in MF cells. Conclusions: AVID200 is a well-tolerated, rational, therapeutic agent for the treatment of patients with MF and should be evaluated further in patients with thrombocytopenic MF in combination with agents that target aberrant MF intracellular signaling pathways.

Background: There is limited research on the impact of revisional surgery after breast reconstruction on patient experience and postoperative quality of life (QoL). Methods: Patients undergoing mastectomy with immediate implant-based or autologous free-flap breast reconstruction from 2008 to 2020 were reviewed. These patients were categorized by revisions (0–1, 2–3, and 4+) and surveyed on QoL metrics using BREAST-Q and Was It Worth It? (WIWI) questionnaires. BREAST-Q QoL, satisfaction, and WIWI metrics between revision groups were evaluated. Results: Among 252 patients, a total of 150 patients (60%) underwent zero to one revisions, 72 patients (28%) underwent two to three revisions, and 30 patients (12%) underwent four or more revisions. Median follow-up was 6 years (range, 1–11 years). BREAST-Q satisfaction among patients with four or more revisions was significantly lower ( P = 0.03), while core QoL domains (chest physical, psychosocial, and sexual well-being) did not significantly differ. Analysis of unplanned reoperations due to complications and breast satisfaction showed no significant difference in QoL scores between groups ( P = 0.08). Regarding WIWI QoL metrics, four or more revisions were associated with a higher rate of worse QoL ( P = 0.035) and worse overall experience ( P = 0.001). Most patients in all revision groups felt it was worthwhile to undergo breast reconstruction (86%), would choose breast reconstruction again (83%), and would recommend breast reconstruction to others (79%). Conclusions: Overall, a majority of patients undergoing revisions after breast reconstruction still have a worthwhile experience. Although reoperations after breast reconstruction do not significantly impact long-term BREAST-Q QoL domains, patients undergoing four or more revisions have significantly lower breast satisfaction, worse QoL, and a postoperative experience worse than expected.