Faculty Bibliography

INTRODUCTION/UNASSIGNED:The OncotypeDX test for patients with breast cancer with early-stage, hormone-receptor-positive, HER2-negative disease can predict the benefit of adjuvant chemotherapy in addition to hormone therapy. Delivering OncotypeDX results in a timely manner is important to inform treatment decisions. We implemented a strategy to reduce the turnaround time (TAT) from breast surgery to OncotypeDX report at a large urban public safety-net hospital in New York City. METHODS/UNASSIGNED:The Plan-Do-Study-Act model was used to implement quality improvement changes. The goal was to improve efficiency to get treatment information for treatment decisions for patients with breast cancer and encourage teamwork with existing resources in the large public hospital. The primary measure was TAT from surgery to receiving OncotypeDX results in the electronic medical record (EMR). We compared TAT before and after the implementation of our strategy. The historical control included patients from May 2021 through March 2022, whereas the timeline after strategy implementation was from June 2023 to February 2024. The strategy involved the creation of a smartphrase in the EMR for breast surgery to identify and order OncotypeDX in eligible patients, and collaboration between breast surgery, pathology, vendor, and medical oncology. RESULTS/UNASSIGNED:= 0.65). Our strategy reduced the average TAT from 42 to 30 days. CONCLUSION/UNASSIGNED:We developed a strategy to optimize the OncotypeDX workflow in a large safety net health system despite an increase in patients from MUAs and MUPs. Initiating ordering of OncotypeDX by breast surgery, along with communication with pathology, vendor, and medical oncology, significantly reduced TAT.

INTRODUCTION/UNASSIGNED:Regression of malignancy in the absence of cancer-directed therapy is an uncommon and poorly understood phenomenon. Its occurrence is particularly rare for pancreatic ductal adenocarcinoma (PDAC). The interaction between tumor and microenvironment may induce an immune response in which both innate and acquired immunity have been found to be implicated. An immunogenic tumor may promote antigen presentation and effector T-cell activity, leading to cancer cell death and tumor inhibition. CASE PRESENTATION/UNASSIGNED:We present the case of a 57-year-old man diagnosed 3 years ago with a borderline-resectable PDAC confirmed by biopsy. The patient received first-line 5-fluorouracil-based chemotherapy with progression of disease including new hepatic metastases. He then received twelve cycles of gemcitabine and nab-paclitaxel with successful reduction in the number and size of liver metastases. Upon patient request, a treatment holiday was initiated, during which his abdominal imaging showed continued tumor regression. After 11 months without any systemic therapy, there are no remaining metastases in the liver, and the primary pancreatic mass continues to recede. He currently remains on surveillance. CONCLUSION/UNASSIGNED:Our patient's rare clinical course raises questions including the optimal next steps in treatment, such as continued observation or local treatment such as surgical resection. The decision to continue observation results from our belief that minimal disruption of the tumor microenvironment may allow for continued control and cancer regression. More laboratory and clinical studies are imperative to understanding the physiological basis of sustained tumor regression after chemotherapy discontinuation and may impact real-world clinical decision-making. Additionally, the definition of spontaneous tumor regression may need revision to distinguish between prolonged therapeutic response and regression due to immunogenic features in the absence of prior therapy.

BACKGROUND/UNASSIGNED:The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). The present study sought to investigate the role of NOVA2 in the processes of self-renewal, carcinogenesis, and lenvatinib resistance in liver CSCs. METHODS/UNASSIGNED:experiments were used to assess the effects of NOVA2 on liver CSC expansion and lenvatinib resistance. RESULTS/UNASSIGNED:A) methylation were linked to upregulation of NOVA2 in HCC. Furthermore, it was shown that the expression of METTL3 was elevated in cellular models of type 2 diabetes mellitus (T2DM). CONCLUSIONS/UNASSIGNED:NOVA2 is involved in the process of liver CSC self-renewal and carcinogenesis. In addition, NOVA2 expression may help identify patients with a higher chance of benefiting from lenvatinib treatment and can be a promising therapeutic target for HCC.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths, with the incidence of HCC increasing in regions of the world with a high incidence of hepatitis B and C. The therapeutic landscape for HCC management has substantially transformed over recent years, shifting towards a multimodal treatment paradigm. This approach provides a range of medical and surgical interventions aimed at managing the disease effectively. Radiotherapy (RT) has surfaced as a critical player in the preoperative management of inoperable HCC, demonstrating potential in downstaging the disease and achieving disease stability. This advantage may potentially be attributed to the abscopal effect, where localized radiation leads to the regression of metastatic cancer outside of the irradiated site through upregulation of the immune system. The advent of recent technological breakthroughs has paved the way for innovative approaches, notably the integration of immunotherapy and RT. This strategy is emerging as a promising avenue for managing HCC. Preliminary findings from the fusion of RT and immunotherapy are encouraging, with ongoing trials keenly evaluating the optimal parameters for therapy administration, such as timing, dosage, and sequence. The development of combined treatments involving immune checkpoint inhibitors (ICIs) has opened new avenues for advanced HCC treatment. Several immunotherapeutic agents with RT are concurrently being explored for their potential contributions to HCC management.

Hepatocellular carcinoma (HCC) is presented frequently in late stages that are not amenable for curative treatment. Even for patients who can undergo resection for curative treatment of HCC, up to 50% recur. For patients who were not exposed to systemic therapy prior to recurrence, recurrence frequently cannot be subjected to curative therapy or local treatments. Such patients have several options of immunotherapy (IO). This includes programmed cell death protein 1 (PD-1) and cytotoxic T- lymphocyte associated protein 4 treatment, combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate. There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors. This mini-review explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis. We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

Bones are categorized as the second most prevalent location of extra-hepatic metastasis in Hepatocellular Carcinoma (HCC), which is linked to an extremely poor prognosis due to limited therapeutic options. N⁶-methyladenosine (m⁶A) is a prominent modification involved in HCC, but the exact mechanisms on how m⁶A modifications induce HCC bone metastases (BM) remain unclear. The key modulators responsible for the abundant m⁶A RNA modification-induced HCC BM was found to be the METTL3 and YTHDF1. The expression of Anillin actin-binding protein (ANLN) was dramatically higher in HCC with BM tissues, and its messenger RNA (mRNA) stability was enhanced via m⁶A epitranscriptomic regulation by METTL3 and YTHDF1. High METTL3 and YTHDF1 expression along with nuclear ANLN protein was clinically correlated with BM in HCC patients. Furthermore, HCC BM was attributed to over-expression of nuclear ANLN forming a transcriptional complex with SP1 which enhanced KIF2C transcriptional activity to activate the mTORC1 pathway, therefore increased the expression of RANKL and disproportionated RANKL-OPG expression in bone microenvironment leading to malignant neoplasms invade bone tissue. In addition, inhibition of ANLN m⁶A modification by DZNeP attenuated HCC BM. This data provides meaningful understanding of the modulation and association of m⁶A epitranscriptomic-regulated BM in HCC, and moreover, defines potentially valuable therapeutic targets.

Barcelona clinic liver cancer (BCLC) intermediate stage hepatocellular carcinoma is a heterogenous disease. Transarterial chemoembolization is offered as the first line therapy in this disease stage. Recent advances in systemic therapy have markedly improved outcomes even in advanced stage disease. The use of systemic therapy in BCLC intermediate stage disease may now be of therapeutic benefit in selected patients. We will focus on "the up to seven" criteria and its utility in selecting systemic therapy.

PURPOSE/UNASSIGNED:The recruitment of underserved patients into therapeutic oncology trials is imperative. The National Institutes of Health mandates the inclusion of minorities in clinical research, although their participation remains under-represented. Institutions have used data mining to match patients to clinical trials. In a public health care system, such expensive tools are unavailable. METHODS/UNASSIGNED:The NYU Clinical Trials Office implemented a quality improvement program at Bellevue Hospital Cancer Center to increase therapeutic trial enrollment. Patients are screened through the electronic medical record, tumor board conferences, and the cancer registry. Our analysis evaluated two variables: number of patients identified and those enrolled into clinical trials. RESULTS/UNASSIGNED:Two years before the program, there were 31 patients enrolled. For a period of 24 months (July 2017 to July 2019), we identified 255 patients, of whom 143 (56.1%) were enrolled. Of those enrolled, 121 (84.6%) received treatment, and 22 (15%) were screen failures. Fifty-five (38.5%) were referred to NYU Perlmutter Cancer Center for therapy. Of the total enrollees, 64% were female, 56% were non-White, and overall median age was 55 years (range: 33-88 years). Our participants spoke 16 different languages, and 57% were non-English-speaking. We enrolled patients into eight different disease categories, with 38% recruited to breast cancer trials. Eighty-three percent of our patients reside in low-income areas, with 62% in both low-income and Health Professional Shortage Areas. CONCLUSION/UNASSIGNED:Prescreening at Bellevue has led to a 4.6-fold increase in patient enrollment to clinical trials. Future research into using prescreening programs at public institutions may improve access to clinical trials for underserved populations.

Background/UNASSIGNED:The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. Objective/UNASSIGNED:To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. Methods/UNASSIGNED:A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model's performance. Results/UNASSIGNED:< 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. Conclusions/UNASSIGNED:The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.

OBJECTIVE:To evaluate the perioperative morbidity and mortality of patients with COVID-19 who undergo urgent and emergent surgery. SUMMARY BACKGROUND DATA:Although COVID-19 infection is usually associated with mild disease, it can lead to severe respiratory complications. Little is known about the perioperative outcomes of patients with COVID-19. METHODS:We examined patients who underwent urgent and emergent surgery at 2 hospitals in New York City from March 17 to April 15, 2020. Elective surgical procedures were cancelled throughout and routine, laboratory based COVID-19 screening was instituted on April 1. Mortality, complications, and admission to the intensive care unit were compared between patients with COVID-19 detected perioperatively and controls. RESULTS:Among 468 subjects, 36 (7.7%) had confirmed COVID-19. Among those with COVID-19, 55.6% were detected preoperatively and 44.4% postoperatively. Before the routine preoperative COVID-19 laboratory screening, 7.7% of cases were diagnosed preoperatively compared to 65.2% after institution of screening (P = 0.0008). The perioperative mortality rate was 16.7% in those with COVID-19 compared to 1.4% in COVID-19 negative subjects [aRR = 9.29; 95% confidence interval (CI), 5.68-15.21]. Serious complications were identified in 58.3% of COVID-19 subjects versus 6.0% of controls (aRR = 7.02; 95%CI, 4.96-9.92). Cardiac arrest, sepsis/shock, respiratory failure, pneumonia, acute respiratory distress syndrome, and acute kidney injury were more common in those with COVID-19. The intensive care unit admission rate was 36.1% in those with COVID-19 compared to 16.4% of controls (aRR = 1.34; 95%CI, 0.86-2.09). CONCLUSIONS:COVID-19 is associated with an increased risk for serious perioperative morbidity and mortality. A substantial number of patients with COVID-19 are not identified until after surgery.