Citations

Background: An obesity paradox, with better long-term survival in obese patients undergoing percutaneous coronary intervention (PCI), has been well described. The association between obesity and health status outcomes after PCI is unknown. Methods: We prospectively enrolled 3,281 PCI patients in a 10-center observational cohort study and categorized their body mass index (BMI) into normal (18.5 to <25), overweight (25 to <30), obese (30 to <35) and morbidly obese (≥ 35).Generalized linear models were used to describe the association between BMI and health status measures at 6 & 12 months, after adjusting for baseline characteristics and health status scores. Health status outcomes included; Seattle Angina Questionnaire [SAQ] Angina Frequency (AF), and Quality of Life (QL) scores, as well as the EQ-5D visual analogue scale (EQ-5D VAS). Interaction with time was not significant, so an estimate of the average benefit over time was generated. Results: The distribution of patients’ BMI revealed that 17% were normal, 35% overweight, 28% obese and 20% morbidly obese. Compared with normal weight patients, morbidly obese individuals were younger (mean 60.8 yr vs. 67.9 yr) and had a higher prevalence of diabetes, hypertension and heart failure. They underwent radial artery access (12.0% vs. 7.0%) and drug eluting stent implantation (80.4% vs. 76.0%) more frequently. Unadjusted changes in scores were lower (worse) among morbidly obese as compared with normal weight patients for SAQ AF (mean difference [MD] -1.52; 95% Confidence Interval [CI] -3.05, -0.02), SAQ QL (MD -2.51; CI -4.48, -0.54), and EQ-5D VAS (MD -5.74;CI -7.52, -3.96). After adjustment, these differences were no longer significantly different for SAQ AF and SAQ QL (figure), although EQ-5D VAS scores remained lower among obese and morbidly obese patients. Conclusion: The overall health status was mildly worse among obese and morbidly obese individuals after PCI, but the benefits of PCI on patients’ disease-specific health status were similar across weight categories. This suggests that PCI is equally effective in improving angina and disease-specific quality of life, independent of patients’ weight.

Abstract Background: APOBEC mutagenesis underlies somatic evolution and accounts for tumor heterogeneity in several cancers, including BC. In our clinical experience, HR+HER2- BC with an APOBEC signature do poorly on standard of care (SOC) first line endocrine therapy (ET) + CDK4/6 inhibitor (CDK4/6i) and need additional treatment options. Here we evaluated the characteristics of a real-world cohort for time-to-treatment discontinuation (TTD) and overall survival (OS) on SOC and immune checkpoint inhibitors (ICI).Methods: Hybrid capture-based comprehensive genomic profiling (CGP) results from 29,833 formalin-fixed paraffin-embedded tissue biopsies of all BC subtypes were analyzed. For outcomes (TTD and OS), this study used a de-identified nationwide (US-based) BC clinico-genomic database (CGDB, ~800 sites of care, 1/2011 - 12/2020). HR+HER2- metastatic BC pts who received first line ET + CDK4/6i were included (CGDB cohort).TTD was defined as the difference between the first and last drug episode within a given line of treatment (LOT). LOT were derived based on FH algorithms. OS was defined as the time from LOT start to the date of death or data cutoff. Log-rank test and Cox model were used to evaluate the difference in outcomes. To reduce the impact of confounding variables (Age at Dx, Stage at Dx, Tumor Type, Metastases sites, TMB group (≥10 vs &lt;10), SOC treatment group, PIK3CA), inverse probability of treatment weighting (IPTW) was used. Eligible pts from Mayo Clinic and Duke University were HR+HER2- mBC with sequencing data from FMI between 9/2013-7/2020. Clinical data were manually extracted from Mayo and Duke EHR. Results: Of all 29,833 BC samples in the CGP cohort, 7.9% were APOBEC+ with high rate in invasive lobular carcinoma (ILC) 16.7% vs. 4.9% in invasive ductal carcinoma (IDC) and metastatic lesions 9.7% vs. 4.3% from breast. APOBEC+ samples had a higher median TMB 12.5 vs. 2.5 mut/Mb. In CGDB, 857 HR+HER2- BC met inclusion criteria; 69 (8%) pts were APOBEC+ and 788 (9.2%) were APOBEC-. APOBEC+ pts had significantly shorter TTD on SOC ET+CDK4/6i than APOBEC- pts, 7.8 (95% CI 4.3-14.6) vs. 12.4 (95% CI 11.2-14.1) months (p=0.0036). APOBEC+ pts also had noticeably shorter OS compared to APOBEC- pts, 32.4 (95%CI 19.8-47.4) vs. 40.5 (95%CI 36.9-45.7) months (p=0.06).Cox regression results indicate that the relative risk of shorter TTD for the APOBEC+ vs the APOBEC- was 1.6 (95%CI 1.03-2.39). Also, APOBEC+ pts had almost twice the risk that APOBEC- pts had of death (HR=1.96, 95%CI 1.2-3.3). In CGDB, there were 10 APOBEC+ pts who received ICI, 9/10 had evaluable TTD data, 4/9 were still on treatment as of Dec 2020. 5/9 received ICI monotherapy, 4 pts received ICI + chemotherapy. TTD ranged from 0.3 to 11.3 mo, 1 pt’s TTD was &gt; 6 mo. In Mayo and Duke cohort, there were 6 pts, 5/6 received ICI + chemotherapy. The TTD was 0.9-40.5 months with longest 2 pts receiving 5-FU plus ICI (11 and 40.5 months). To better understand the ICI treatment landscape, TTD in HR+HER2- hTMB MSS APOBEC- CGDB cohort (N=6) was analyzed: 5/6 had evaluable treatment data, 4/5 finished ICI treatment, 1 pt’s TTD was &gt; 3 mo, 0/5 had TTD &gt; 6 mo. Conclusions: APOBEC+ occurs in ~7% of BC and is more common in ILC and metastatic lesions. APOBEC+ HR+HER2- pts had shorter TTD and OS on SOC ET+CDK4/6i relative to APOBEC- pts. However, TTD on ICI tended to be longer in APOBEC+ pts, but our data is limited, and more research is needed. CGDB APOBEC+ vs. APOBEC- with SOC 1st lineAPOBEC+ (N=69)APOBEC- (N=788)p adjusted (FDR)*Age at Dx, Median (IQR)59.0 (53.0, 65.0)56.0 (47.0, 65.0)0.102Stage at Dx0.067- 0-III52 (75.4%)505 (64.1%)- IV11 (15.9%)245 (31.1%)- Not documented6 (8.7%)38 (4.8%)Metastasis free interval, yrs, Median (IQR)5.2 (3.0, 10.5)5.1 (2.8, 9.3)0.734Tumor Grade0.104- Grade 12 (2.9%)49 (6.2%)- Grade 234 (49.3%)259 (32.9%)- Grade 311 (15.9%)163 (20.7%)- Not documented22 (31.9%)317 (40.2%)Tumor Type0*- IDC7 (10.1%)251 (31.9%)- ILC30 (43.5%)138 (17.5%)- Other /Not documented32 (46.4%)399 (50.6%)Metastases sites0.734- Bone-only17 (24.6%)169 (21.5%)- CNS11 (15.9%)104 (13.2%)- Visceral41 (59.4%)514 (65.3%)TMB, Median (IQR)11.3 (8.8, 18.8)2.5 (1.3, 3.8)0*MSI0.946- MSI-H0 (0.0%)4 (0.5%)- MSI-I0 (0.0%)1 (0.1%)- MSS68 (98.6%)728 (97.2%)- Not documented1 (1.4%)16 (2.1%)BRCA5 (7.2%)45 (5.7%)0.734PIK3CA46 (66.7%)341 (43.3%)0.001*Treatments0.005*- AI + CDK4/6i31 (44.9%)510 (64.7%)- Fulvestrant + CDK4/6i38 (55.1%)278 (35.3%) Citation Format: Saranya Chumsri, Kira Raskina, Sarah Sammons, Laura Alder, Natalie Danziger, Alexa B Schrock, Kim McGregor, Ethan Sokol. APOBEC signature, clinical characteristics, and outcome in hormone receptor-positive (HR+) HER2-negative (HER2-) breast cancer (BC) patients (pts) in real-world data (RWD) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD14-09.

AbstractOptimal perioperative care contributes to improved patient outcomes, as demonstrated in the field of liver transplant (LT). The evolution in perioperative care over the past two decades has been driven by research in areas such as preoperative testing, coagulation management, and intraoperative monitoring. However, much of this research is driven by local institutional pressures and practices with a dearth of studies emanating from research consortia or other groups of experts within the field. To better characterize the top research questions in the field, we queried a group of 128 LT anesthesiologists representing 87 international liver transplant centers with a response from 71 practitioners (59.2%). Three experts then codified the responses into the top 20 questions, which were sent to the survey recipients as a second survey to rank order. Seventy‐five respondents (61.5%) provided responses, which were merged into a weighted ranked priority list and analyzed by respondent location and center size. The highest ranked question was, “What intraoperative anesthetic management/interventions affect graft outcome?” Most of the top research questions focused on preoperative risk factor management or optimization and intraoperative management techniques. In general, this priorities list may serve as a guide for transplant anesthesiology researchers to focus future research endeavors on shared interests that improve patient care.

Abstract Purpose:The incidence of severe combined immunodeficiency (SCID) in the United States was reported as 1 in 58,000 live births. In Arizona, it was anticipated that newborn screening would identify two to four cases of SCID per year. This estimate did not consider ethnic nuances in Arizona, with higher percentages of American Indian and Hispanic populations compared to national percentages. The true incidence of SCID and non SCID T-cell lymphopenia have not previously been reported in Arizona. Methods:A retrospective chart review was performed of abnormal SCID Newborn Screening (NBS) tests from January 1, 2018 to December 31, 2019, using data from the Arizona Department of Health Service and the Phoenix Children’s Hospital’s electronic medical record [IRB# 20-025]. Results: Seven infants were diagnosed with SCID, yielding an incidence of 1 in 22,819 live births. Four of these infants had Artemis type SCID. Eighteen infants were identified with an abnormal initial NBS which ultimately did not lead to a diagnosis of SCID. Four of these infants were diagnosed with congenital syndromes associated with T-cell lymphopenia. Infants of Hispanic ethnicity were over-represented in this cohort. Conclusion: NBS in Arizona confirmed an incidence more than 2.5 times that reported nationally. This increased incidence is likely reflective of Arizona’s unique population profile, with a higher percentage of American Indian population. The findings in our non-SCID cohort are in alignment with previously published data, except for a higher than anticipated number of infants of Hispanic/Latino ethnicity, likely related to Arizona’s higher percentage of Hispanic/Latino population.

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.

474 Background: FLO is a rare variant of liver cancer that disproportionately affects young adults and is frequently progressive and fatal as it is often detected in a clinically advanced stage. It is seldom associated with cirrhosis of liver, viral hepatitis or other risk factors associated with conventional HCC. Treatment options are largely limited to surgical resection, and there is dearth of effective targeted therapies for FLO. Methods: Comprehensive genomic profiling (CGP) was performed using the Foundation Medicine Inc. (FMI) data base on 63 FLO and 1,793 HCC clinically advanced cases between 6/2013-12/2020 using a hybrid capture-based assay of up to 324 genes a to detect genomic alterations (GA), tumor mutational burden (TMB) and microsatellite instability (MSI). PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC and scored using the tumor proportion score (TPS) method. Results: The FLO patients (pts) were significantly younger than HCC pts (median age 20 vs. 64, respectively) and the male preponderance was similar. The HCC group featured significantly more GA/tumor than FLO group (3.74 vs 1.31 p<.0001). In the currently untargetable GA group, CTNNB1, TERT and TP53 GA were significantly more frequent in HCC than FLO. GA in potentially targetable genes were extremely uncommon in both FLO and HCC with HCC featuring slightly more MTOR pathway targets ( PTEN, TSC2, NF1). GA in DNA damage and repair (DDR) pathway including BRCA2 were infrequent in both groups. GA in targetable kinases including EGFR, ERBB2, ALK, RET and PIK3CA were extremely uncommon in both groups. GA associated with intrahepatic cholangiocarcinoma (IDH1, FGFR2) were extremely uncommon in these tumors. Although the mean TMB was significantly higher in HCC than FLO, overall TMB was low with very few cases having TMB > 10 mutations/Mb. PD-L1 expression was relatively low in both groups. GA in genes associated with immune checkpoint inhibitors (ICPI) drug response like PBRM1, CD274, MDM2, STK11 were rarely identified in both groups. Additional details are illustrated in the table. Conclusions: Comparison of CGP of FLO with HCC illustrates the multifarious nature of these cancers. In HCC, there is a high prevalence of GA in TERT, CTNNB1 and TP53. CGP identified certain targetable GA in the MTOR and DDR pathways and TMB was higher in HCC. These findings warrant further evaluation of clinically advanced FLO and HCC pts by CGP to identify possible targetable genomic pathways. [Table: see text]