Matched Case Control Analysis of Breast Cancer- Specific Factors Affecting Risk of Developing SARS-CoV-2 Infection.

INTRODUCTION: In this retrospective matched case control study, we aim to identify breast cancer-related risk factors associated with developing COVID-19 and describe outcomes of patients with breast cancer diagnosed with COVID-19. METHODS: Women with breast cancer treated at the Medical College of Wisconsin and diagnosed with COVID-19 from March through December 2020 served as cases, and those without COVID-19 within the same timeframe served as controls. Univariate and multivariate comparisons were performed. RESULTS: Twenty-five cases and 77 controls were identified. All cases were fully matched by age, obesity, county, and race. Mean age was 54.6 versus 54.9, body mass index 31.0 versus 31.6, 48% lived in Milwaukee County, and 68% were White. Regarding COVID-19 outcomes, 24.0% (n = 6) of cases were hospitalized, median length of stay was 2 days, 8% (n=2) needed oxygen, 4% (n = 6) were intubated, and 4% (n = 6) died. COVID-19 led to treatment delays in 40% of cases. On univariate analysis, there was no statistically significant difference in hormone receptor status or breast cancer stage. Being on active chemotherapy (OR 5.8, P = 0.043) significantly increased the likelihood of developing COVID-19. CONCLUSIONS: In this matched case control study of patients with breast cancer, active chemotherapy was significantly associated with an increased likelihood of developing COVID-19, with a trend seen for triple negative disease. These findings support continued strict precautions for those on active chemotherapy and warrant further analysis in those with triple negative disease.

Leveraging Social Determinants of Health to Reduce Hospital Length of Stay: A Pilot QI Project for Solid Tumor Oncology Patients During the COVID-19 Pandemic.

PURPOSE: The impact of the social determinants of health (SDOH) on hospitalized cancer patients and hospital length of stay is unknown. At our institution, a hospital-wide SDOH survey that examined patient-specific barriers to various domains of SDOH and facilitated hospital discharge was integrated into the electronic medical record. This study reports the effect of the SDOH survey on length of stay for oncology patients and the outpatient referrals generated to facilitate the discharge. METHODS: We examined length of stay index data on inpatient oncology patients and 2 comparator services (bone marrow transplant, internal medicine). We evaluated the length of stay using a 2-sample t test, and the rate of referrals per discharge using a 2-sample Poisson test. RESULTS: Compared to the baseline length of stay, after the launch of the SDOH survey, there was a significant (8.9%) decrease in the average length of stay for oncology patients (8.14 to 7.41 days, P = 0.004), the LOS decrease for the bone marrow transplant and subset was a nonsignificant trend only (P > 0.1). Average referrals per discharge increased from baseline 1.063 per discharge to 1.159 after implementation (P = 0.004), and the mean values increased by 9%. CONCLUSIONS: The SDOH survey tool assisted in a timely examination of patient-specific barriers to discharge, leveraged care coordination, and facilitated a safe hospital discharge. Such efforts increase the efficiency of health care service delivery in response to public health threats, such as the COVID-19 pandemic.

Long term impact of CTLA4 blockade immunotherapy on regulatory and effector immune responses in patients with melanoma.

BACKGROUND: We previously reported early on-treatment significant modulation in circulating regulatory T cell (Treg), myeloid derived suppressor cells (MDSC) and antigen-specific type I CD4+ and CD8+ T cells that correlated with clinical outcome in regionally advanced melanoma patients treated with neoadjuvant ipilimumab. Here, we investigated the long term immunologic impact of CTLA4 blockade. METHODS: Patients were treated with ipilimumab given at 10 mg/kg IV every 3 weeks for 2 doses bracketing surgery. Blood specimens were collected at baseline and during treatment for up to 9 months. We tested immune responses at 3, 6, and 9 months utilizing multicolor flow cytometry. We compared frequencies of circulating Treg and MDSC on-study to baseline levels, as well as frequencies of CD4+ and CD8+ T cells specific to shared tumor-associated antigens (Gp-100, MART-1, NY-ESO-1). RESULTS: Levels of Treg significantly increased when measured at 6 weeks following ipilimumab but returned to baseline by 3 months, with no significant difference in Treg levels between relapsed and relapse-free groups at 3, 6 or 9 months. However, lower baseline levels of circulating Treg (CD4+CD25hi+CD39+) were significantly associated with better relapse free survival (RFS) (p = 0.04). Levels of circulating monocytic HLA-DR+/loCD14+ MDSC were lower at baseline in the relapse-free group and further decreased at 6 weeks, though the differences did not reach statistical significance including measurements at 3, 6 or 9 months. We detected evidence of type I (interferon-γ producing), activated (CD69+) CD4+ and CD8+ antigen-specific T cell immunity against cancer-testis (NY-ESO-1) as well as melanocytic lineage (MART-1, gp100) antigens in the absence of therapeutic vaccination. These responses were significantly boosted at 6 weeks and persisted at 3, 6 and 9 months following the initiation of ipilimumab. CONCLUSIONS: Lower Treg levels at baseline are significantly associated with RFS and increased Treg frequency after CTLA4 blockade was only transient. Lower MDSC was also associated with RFS and MDSC levels were further decreased after ipilimumab. Tumor specific effector immune responses are boosted with CTLA4 blockade and tend to be durable. Trial registration ClinicalTrials.gov Identifier: NCT00972933.

Phenotypic and functional testing of circulating regulatory T cells in advanced melanoma patients treated with neoadjuvant ipilimumab.

BACKGROUND: We have previously investigated neoadjuvant ipilimumab (ipi) for patients with locally/regionally advanced melanoma. That initial assessment of peripheral blood mononuclear cells (PBMC) showed a significant increase in shared tumor associated antigen specific CD4(+) and CD8(+) T cell activation. We also observed a transient increase in circulating T regulatory cells (Treg) with a parallel increase in total CD4(+) T cells, as well as a significant decrease in circulating myeloid derived suppressor cells (MDSC). The increase in circulating Treg frequency, as assessed at 6 weeks after initiation of ipilimumab, was significantly associated with improved progression free survival (PFS, p = 0.034; HR = 0.57) and returned to baseline levels by 12 weeks. To shed light on the unexpected positive correlation between increased Treg and PFS, we here investigated the suppressive activity of circulating Treg at baseline and 6 weeks. METHODS: Patients were treated with ipi (10 mg/kg intravenously every 3 weeks for 2 doses) bracketing definitive surgery. Treg (CD4(+)CD25(+)CD127(dim/-)) were isolated from pre-ipi (baseline) and post-ipi (6 weeks) PBMC samples. Treg were co-cultured with autologous responder CD4(+) T cells that were stimulated with OKT3/IL-2/CD28 and CFSE-labeled T cells. 1:1, 1:2, and 1:5 ratios were tested. Flow cytometery was used to evaluate the degree of Treg proliferation suppression. RESULTS: Thirty-five patients were enrolled in the study; 18 patients had adequate PBMC samples with sufficient Treg isolated for Treg functional analysis. At 6 weeks following ipi, a decrease in percent of maximal inhibition of Th by Treg compared to baseline was seen for some patients. Scatter plot analysis showed no association between Treg frequency and function at any ratio or between circulating Treg frequency and function at baseline and at 6 weeks post-ipi. An increase in Treg suppressive function was significantly associated with a decrease in PFS (p = 0.02). CONCLUSIONS: We find that Treg frequency measures do not correlate with suppressive activity measured ex vivo. Treg suppressive activity increases correlate with poorer patient outcomes.

Treatment response to transcatheter arterial embolization and chemoembolization in primary and metastatic tumors of the liver.

INTRODUCTION: Transcatheter arterial embolization (TAE) and chemoembolization (TACE) are increasingly used to treat unresectable primary and metastatic liver tumors. The purpose of this study was to determine the objective response to TAE and TACE in unresectable hepatic malignancies and to identify clinicopathologic predictors of response. MATERIALS AND METHODS: Seventy-nine consecutive patients who underwent 119 TAE/TACE procedures between 1998 and 2006 were reviewed. The change in maximal diameter of 121 evaluable lesions in 56 patients was calculated from pre and post-procedure imaging. Response rates were determined using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The Kaplan-Meier method was used to compare survival in responders vs. non-responders and in primary vs. metastatic histologies. RESULTS: TAE and TACE resulted in a mean decrease in lesion size of 10.3%+/-1.9% (p<0.001). TACE (vs. TAE) and carcinoid tumors were associated with a greater response (p<0.05). Lesion response was not predicted by pre-treatment size, vascularity, or histology. The RECIST partial response (PR) rate was 12.3% and all partial responders were in the TACE group. Neuroendocrine tumors, and specifically carcinoid lesions, had a significantly greater PR rate (p<0.05). Overall survival, however, was not associated with histology or radiologic response. DISCUSSION: TAE and TACE produce a significant objective treatment response by RECIST criteria. Response is greatest in neuroendocrine tumors and is independent of vascularity and lesion size. TACE appears to be superior to TAE. Although an association of response with improved survival was not demonstrated, large cohort studies are necessary to further define this relationship.