Gabriel, Emmanuel M

ABSTRACT Background and Objectives NCCN guidelines recommend right hemicolectomy (RHC) for appendiceal neuroendocrine tumors (aNETs) > 2 cm and observation for < 1 cm. However, optimal surgical management of 1–2 cm tumors remains controversial. This study compared long‐term survival and recurrence between patients undergoing RHC versus appendectomy (APY) for 1–2 cm aNETs. Methods Patients with pathologically confirmed 1–2 cm aNETs treated at three Mayo Clinic sites (1972–2024) were included. Primary outcomes were recurrence and all‐cause mortality after resection. Associations with lymph node (LN) metastasis were assessed in patients with lymphadenectomy. Results Sixty‐five patients were identified: 29 (45%) underwent APY, 35 (54%) RHC, and one ileocecectomy. Median age at diagnosis was 39 years; 71% were female and 94% white. LN positivity was 15.2% for tumors with nodes examined. Tumor size > 1.5 cm, stage T3/T4, and lymphovascular invasion were not associated with nodal metastasis. No survival differences were observed between APY and RHC. LN positivity did not impact survival. No recurrences occurred during a median follow‐up of 6.25 years (IQR 2.44–12.63). Conclusions Among patients with 1–2 cm aNETs, RHC conferred no survival benefit over APY. Absence of recurrence and the limited prognostic value of nodal disease suggest APY alone may suffice for this population.

Pulsed Electric Field (PEF) ablation is a non-thermal cancer treatment that disrupts tumor cell membranes while preserving the immune microenvironment and promoting immunogenic cell death. We present a case of a patient with metastatic hormone receptor-positive, HER2-low breast cancer who achieved a durable clinical response after PEF in combination with an immune checkpoint inhibitor (pembrolizumab). The patient remained off systemic therapy for 14 months without disease progression. Single-cell spatial molecular imaging (SMI) and gene set enrichment analysis (GSEA) were performed to evaluate immune microenvironment changes pre- and post-PEF treatment. Spatial transcriptomics of the tumor cell compartment revealed a post-PEF enrichment of immune-related pathways, including interferon alpha/beta and gamma signaling and MHC class I antigen processing and presentation, alongside increased infiltration of immune cells: CD8+ T cells, plasmablasts, and monocytes within the tumor neighborhood. This hypothesis-generating case suggests PEF’s potential to reshape the tumor-immune microenvironment when combined with immune checkpoint blockade, warranting further studies on its role in combination immunotherapy strategies.

Abstract Intravital microscopy enables dynamic and real‐time visualisation of microscopic structures in living tissues without the need for fixation, with real‐life applicability being illustrated by several first‐in‐human studies in different cancers. Its use in preclinical models has yielded important observations of the microvasculature of both healthy and diseased tissues. It has further enabled the observation of the interactions between important components of the tissue microenvironment such as immune cells and neighbouring microvessels. Important recent technological advances, however, have enabled the translation of this technology to human use. Here, we review the main advances in intravital microscopy and some of the most recent uses in different human disease settings.

The National Cancer Database (NCDB) is a large data set of cancer patients treated in the United States. In recent decades, many papers have utilized this database to study disparities in cancer care and outcomes. In this review, we present the strengths and limitations of using the NCDB to study cancer disparities, which should be taken into account by researchers who use the NCDB in this setting.

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 &lt; 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.

Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1–T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan–Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77–0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients.

We aimed to review the molecular characteristics of metastatic melanoma and the role of surgery in metastasectomy for metastatic melanoma. We performed a systematic literature search on PubMed to identify relevant studies focusing on several mutations, including NRAS, BRAF, NF1, MITF, PTEN, TP53, CDKN2A, TERT, TMB, EGFR, and c-KIT. This was performed in the context of metastatic melanoma and the role of metastasectomy in the metastatic melanoma population. A comprehensive review of these molecular characteristics is presented with a focus on their prognosis and role in surgical metastasectomy.