Citations

Purpose: The purpose of this study was to evaluate and compare the anatomic characteristics of eyes with Fuchs endothelial corneal dystrophy (FECD) with eyes without FECD. Methods: This study was a retrospective chart review performed at an academic medical center. Patients with FECD were identified through a search of the electronic medical records. Eligible patients underwent Scheimpflug imaging and optical biometry and were compared with age and sex-matched control subjects who underwent similar testing in preparation for cataract surgery. Several measurements of the cornea, anterior chamber, and eyes were evaluated using multivariable linear regression models and multivariable logistic regression models. Results: A total of 404 eyes (202 eyes with FECD and 202 control eyes) were included in this study. Compared with controls, eyes with FECD had shallower AC depths, lower AC volumes, and narrower angles. Conversely, the spherical equivalent before cataract surgery, corneal pachymetry, and corneal volume were higher in eyes with FECD. On Scheimpflug imaging analysis, these anatomical differences were present in FECD eyes with and without corneal edema. After adjusting for sex, these differences remained statistically significant. Shorter axial length was found to be statistically significant in male eyes but not in female eyes with FECD. Conclusions: This study reports new ocular characteristics in FECD eyes with and without edema. Optical biometry and Scheimpflug imaging established that the anatomic findings in eyes with FECD were not simply due to the larger volume of an edematous cornea but rather unique to eyes with FECD. These findings will provide reliable, normative data for future studies examining surgical, medical, and anatomical factors in FECD.

Background: The Clinical Treatment Score post-5 years (CTS5) is a risk stratification tool used to determine the risk of late recurrence in hormone receptor–positive (HR+), HER2-negative breast cancer (BC). Limited data exist on its use in HR+, HER2-positive (HER2+) BC. Patients and Methods: CTS5 was evaluated in HR+, HER2+ BC in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials. Results: A total of 1,862 patients with HR+, HER2+ BC without recurrence 5 years after enrollment were included. Overall, the CTS5 score was significantly associated with recurrence-free survival (RFS), with a hazard ratio (HR) of 1.35 (95% CI, 1.12–1.63; P=.002), but did not reach statistical significance in patients who received trastuzumab (n=829; HR, 1.29; 95% CI, 0.98–1.71; P=.07). CTS5 risk category was not significantly associated with RFS. In patients who received trastuzumab, other variables used in CTS5, including patient age and tumor size, were not significantly associated with RFS. N3 was significantly associated with worse outcomes (HR, 1.86; 95% CI, 1.09–3.17; P=.02) compared with N0–N1. Paradoxically, higher tumor grade was associated with better outcomes after 5 years in the multivariate analysis (HR, 0.71; 95% CI, 0.50–1.00; P=.05). The incidence of recurrences or deaths between years 5 to 10 was 10.6% in the CTS5 low-risk category, 5.6% in the intermediate-risk category, and 9.8% in the high-risk category. Conclusions: The CTS5 model does not accurately predict the risk of late recurrence in HR+, HER2+ BC treated with adjuvant trastuzumab in the N9831 and B-31 trials. This study underlines the need to develop a new prognostic model to better delineate the risk of late recurrence in patients with HR+, HER2+ BC receiving adjuvant trastuzumab. ClinicalTrials.gov identifiers: NCT00005970 (NCCTG N9831) and NCT00004067 (NRG/NSABP B-31).

Abstract Background: Tertiary lymphoid structure (TLS) is an organized form of ectopic lymphoid aggregates (LA) with secondary lymphoid organ structure. Several studies showed that the presence of TLS associates with improved outcomes in multiple cancers when treated with immune checkpoint inhibitors. However, data is currently limited regarding TLS and outcomes in HER2+ breast cancer patients (pts) treated with adjuvant trastuzumab. Furthermore, distinguishing TLS and simple LA is challenging in standard hematoxylin and eosin (H&E) staining, particularly when the germinal center is absent. Emerging studies also showed the prognostic value of MHC expression in breast cancer but mainly in triple-negative breast cancer. In this study, we evaluated integrated pathological quantification and genomic data to assess functional TLS in association with MHC expression and outcomes in the N9831 trial. Methods: Pathological evaluation of LA in H&E slides from pts treated in Arm A (chemotherapy alone) and Arm C (chemotherapy with concurrent trastuzumab) in N9831 was performed. NanoString was used to quantify mRNA of MHC class I and II expression as well as TLS-related immune genes, including IFNG, ICOSLG, CXCL13, CXCR3, BCL6, IL21R, ICOS, PDCD1, CXCR5, CXCL9, TBX21, CD38, CXCL10, CLXCL11, IL21, CD200, CD19, MS4S1. Wilcoxon rank sum test, Chi-squared test, Kaplan-Meier method, and Cox regression model were used to evaluate the association between LA and baseline characteristics, MHC expression, and outcomes. Results: LA was evaluated in 526 pts in Arm A and 485 in Arm C. Greater number of LA was significantly associated with stromal tumor-infiltrating lymphocytes (sTILs), hormone receptor negative, and higher tumor grade, but not stage and age. Using multivariable Cox regression analysis, increasing numbers of LA were associated with improved recurrence-free survival in both arms combined (RFS, p 0.028). However, when evaluating each arm separately, LA was associated with improved RFS only in Arm A (HR 0.6, 95%CI 0.43-0.84, p 0.003) but not in Arm C (HR 0.72, 95%CI 0.47-1.1, p 0.134). We further evaluated TLS-related immune genes in 252 pts in Arm C with LA ≥ 1. As a continuous variable, higher expression of BCL6 (HR 0.61, 95%CI 0.41-0.92, p 0.019) and IL21R (HR 0.78, 95%CI 0.62-0.98, p 0.03) were associated with improved RFS in Arm C pts with LA ≥ 1. However, these genes were not significantly associated with outcomes in Arm C pts without LA with BCL6 (HR1.07, 95%CI 0.67-1.71, p 0.776) and IL21R (HR 0.96, 95%CI 0.71-1.29, p 0.775). Moreover, we evaluated differential gene expression between tumors with LA ≥ 1 with high BCL6 vs. LA 0. All MHC class I and II (HLA A, B, C, E, DQ, DM, DO, DP, and DQ) were significantly higher in tumors with LA ≥ 1 with high BCL6 (p < 0.001). Conclusion: A greater number of LA was associated with improved outcomes in pts with early-stage HER2+ breast cancer, particularly when treated with chemotherapy alone. Using histologic and genomic integration with the combination of pathological LA and TLS-related immune genes, we identified that pts with functional TLS with LA ≥ 1 and higher expression of BCL6 or IL21R had significantly improved outcomes when treated with trastuzumab. High MHC class I and II expressions are associated with the presence of functional TLS, underscoring the crucial role of antigen presentation in the generation of an effective adaptive immune response. Support: U10 CA180821, U10 CA180882, U24 CA196171, https://acknowledgments.alliancefound.org; Genentech; Clinicaltrials.gov Id: NCT00005970 Citation Format: Saranya Chumsri, Tracy Shachner, Zhuo Li, Nadine Norton, Alvaro Moreno-Aspitia, Gerardo Colon-Otero, Edith Perez, Aziza Nassar, E. Thompson, Keith Knutson. MHC Class I and II Expression, Functional Tertiary Lymphoid Structure (TLS), and Outcomes in Early-Stage HER2-Positive (HER2+) Breast Cancer in NCCTG N9831 (Alliance) [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 PO4-25-04.

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value < 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [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 PO3-06-04.

Objectives: CABG and PCI are used for revascularization of multivessel coronary artery disease (MVCAD). However, limited information is available comparing the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular event (early MACCE), including early death, stroke, myocardial infarction (MI), and repeat revascularization, among patients with multiple arterial CABG (MultArt) vs PCI. Methods: We reviewed 12,615 MVCAD patients with isolated primary CABG or PCI from 1993 through 2009. CABG patients (n=6,667) were grouped by number of arterial grafts into left internal mammary artery/saphenous vein (LIMA/SV) (n=5,712) or MultArt (n=955); PCI patients (n=5,948) into balloon angioplasty (BA) (n=1,020), bare metal stent (BMS) (n=3,242), and drug-eluting stent (DES) (n=1,686). Results: Early MACCE rate was significantly greater for PCI than CABG (8.5% vs 4.1% [P<.001]) and lower for MultArt than LIMA/SV or PCI (1.5% vs 4.5% and 8.5%, respectively [P<.001]). Stroke and early death rates were higher in CABG vs PCI (2.2% vs 0.4% [P<.001], and 1.5% vs 1.0% [P=0.01], respectively), whereas MI and repeat revascularization were lower (0.5% vs 6.0% and 0.3% vs 2.2%, respectively [P<.001]). Stroke and early death were similar in MultArt and PCI and lower vs LIMA/SV (0.6% and 0.4% vs 2.6%, and 0.5% and 1.0% vs 1.7%, respectively [P<.001]); MI and repeat revascularization rates were similar in MultArt and LIMA/SV and lower vs PCI (0.4% and 0.6% vs 6.0%, and 0.3% and 0.3% vs 2.3%, respectively [P<.001]). In propensity score-matched analysis, CABG had significantly improved early MACCE rate compared with BA (4.7% vs 13.2% [P<.001]), BMS (4.3% vs 8.3% [P<.001]), and DES (2.9% vs 5.5% [P=.008]), and MultArt compared with PCI (1.8% vs 7.8% [P<.001]) fig. Conclusions: In MVCAD patients undergoing isolated primary revascularization, CABG conferred lower early MACCE rate vs PCI. Early MACCE rate was markedly decreased after MultArt compared with LIMA/SV, BA, BMS, and DES.

Objectives. The use of the left internal mammary artery (IMA) in revascularization of multivessel coronary artery disease has been shown to improve survival following coronary artery bypass graft surgery (CABG), however the incremental survival benefit of multiple arterial grafts is still debated. Methods. We reviewed outcome of 8,622 pt that had isolated primary CABG for multivessel disease from 1993 to 2009.Pt were stratified according to the number of arterial grafts; (1) single IMA plus saphenous vein (SV) IMA/SV group (n=7,435; 83% 3VD) and (2) multiple arterial (MultArt) group (n=1,187; 74% 3VD) Results. Early mortality rate was 0.8% (n=10) in the MultArt group and 2.1% (n=154) in the IMA/SV group (P=0.004). However, the difference was not statistically significant (P=0.996) after adjusting for age, gender, chronic lung disease, renal failure, PVD, MI, EF, and number of diseased vessels. Late survival was significantly greater for the MultArt group compared to IMA/SV group (5-, 10- and 15-year survival rates were 95%, 84% and 71% versus 85%, 61% and 35% p<0.001). MultArt subgroups with the use of bilateral internal mammary artery (BIMA)/SV (n=589) and BIMA only (n=271), had significantly improved 15-years survival (97%, 86%, 76% and 94%, 82%, 75% at 5-, 10- and 15-years, p<0.001), and BIMA/RA (n=147) and LIMA/RA (n=169), had significantly greater 10-years survival (95%, 84% and 93%, 78% at 5- and 10-years, p<0.001) compared to IMA/SV group. In multivariate analysis, use of multiple arterial grafts remained a strong independent predictor of survival (HR=0.78, 95% CI 0.66 - 0.93, p=0.006). Conclusion. Use of the right IMA or radial artery in addition to the left IMA is associated with significantly better overall and late survival compared with single IMA and saphenous vein in patients with two and three-vessel disease undergoing isolated CABG.

Abstract Enduring shortages of infectious disease physicians across the United States continue despite efforts to mitigate the problem. The recent fellowship match results underscore the difficulty in rectifying that shortage. Our report sheds light on the current geographic distribution of US infectious disease physicians and highlights the challenges faced by rural communities.

Abstract Background: Previous studies demonstrated that obesity is associated with poor outcomes and significantly worse pathological complete response (pCR) in triple-negative breast cancer (TNBC) treated with conventional chemotherapy. Emerging studies described a phenomenon termed the obesity paradox, which referred to improved outcomes observed in obese patients treated with immune checkpoint inhibitors (ICIs). Our study aimed to determine distinct immune features in TNBC across body mass index (BMI). Methods: Characteristics and outcomes of TNBC patients treated with neoadjuvant pembrolizumab-based chemotherapy at Mayo Clinic were collected. Normal BMI was defined as 18-25 kg/m2, overweight 25-30, and obese BMI ≥ 30. NanoString CosMx, a spatial multi-omics single-cell imaging (SMI), was performed in 75 samples from the Mayo Clinic TNBC cohort (Leon-Ferre BCRT 2018). Differential expression as log 2-fold change (FC) was estimated from the linear mixed model with significance defined as two-sided p&lt; 0.05. Results: Between 2021-2023, there were 108 TNBC patients treated with neoadjuvant pembrolizumab. 25.9% were obese, 32.4% were overweight, and 41.7% had normal BMI. In contrast to previous studies with conventional chemotherapy, obese patients numerically had a higher pCR rate of 71.4% with pembrolizumab-based chemotherapy compared to 55.6% in normal and 62.9% in overweight patients. However, this difference did not reach statistical significance (obese vs. normal weight, OR 2.26, 95%CI 0.89-6.06, p 0.094). We further evaluated spatially-resolved immune features associated with obesity using CosMx SMI in 75 samples from the MC TNBC cohort. Obese patients had significantly higher intratumoral B cells (log2FC 1.88, p 0.017), stromal B cells (log2FC 2.79, p 0.001), stromal plasmablasts (log2FC 1.94, p 0.047), and stromal macrophages (log2FC 1.80, p 0.017) compared to patients with normal BMI. Obese patients also had significantly lower intratumoral myeloid dendritic cells (mDC) (log2FC -1.27, p 0.037). Similar trends were observed after standardizing cell counts per 100 tumor or stromal cells, including higher intratumoral B cells (log2FC 3.00, p 0.001), intratumoral plasmablasts (log2FC 2.00, p 0.006), intratumoral natural killer (NK) cells (log2FC 1.66, p 0.044), and stromal B cells (log2FC 1.50, p 0.008). Differential gene analyses for intratumoral B cells revealed that genes (CD74, HLA-C, HLA-DRB1, HLA-DRA, HLA-DRB) associated with the positive regulation of type 2 immune or chemokine response were upregulated. Conclusions: Using in-depth analysis with spatially defined context, our study showed that obese TNBC patients had significantly higher B cell infiltration, which is associated with improved outcomes with ICIs. Future research on how obesity alters the immune microenvironment is needed to identify potential pathways to improve outcomes with ICIs in TNBC. Citation Format: Songhan Pang, Yi Liu, Yaohua Ma, Zhuo Li, Roberto A. Leon-Ferre, David Zahrieh, David W. Hillman, Judy C. Boughey, James N. Ingle, Krishna R. Kalari, Fergus J. Couch, Matthew P. Goetz, Keith L. Knutson, Saranya Chumsri, E. Aubrey Thompson. Tumor-immune microenvironment associated with obesity in triple-negative breast cancer in the Mayo Clinic cohort [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 1162.