Faculty Bibliography

BACKGROUND/OBJECTIVES/OBJECTIVE:Peritoneal metastases (PMs) arise from gastrointestinal, gynecologic, hepatobiliary, and colorectal origins and are associated with poor outcomes. Cytoreductive surgery (CRS) with intraperitoneal (IP) chemotherapy offers benefit for select patients, but survival remains limited. This review aims to summarize recent insights into the molecular and tumor microenvironmental (TME) changes characteristic of PMs and the impact of IP chemotherapy. METHODS:A literature review was performed using recent clinical, translational, and preclinical studies examining alterations in molecular signaling, DNA repair alterations, metabolic pathways, and angiogenic factors in PMs before and after IP therapy. RESULTS:Peritoneal metastases exhibit distinct biology after being treated with IP chemotherapy. Treatment induces alterations in gene expression, mutational patterns, and immune infiltrates. Heated intraperitoneal chemotherapy (HIPEC) has been associated with increased CD8+ T-cell activity, macrophage and NK cell shifts, and modulation of PD-1/PD-L1 signaling, which correlate with treatment response and survival. Emerging data on PIPAC similarly suggests induction of favorable gene expression changes with repeated treatment, though supporting evidence remains more limited than for HIPEC. Angiogenic pathways-particularly VEGF and HIF1α-remain key drivers of PM progression and predictors of post-operative outcomes. Early findings suggest potential synergy between IP chemotherapy and immunotherapy though clinical trials are ongoing. CONCLUSIONS:IP chemotherapy induces tumor microenvironmental changes that have potential to shape therapeutic response. Characterizing these measurable biologic changes may allow clinicians to improve patient selection and support the development of combination therapies to enhance outcomes.

BACKGROUND:Colorectal cancer (CRC) is a common malignancy with the propensity to metastasize. Common sites of metastasis include the liver, lungs, and peritoneum, with peritoneal metastases (PMs) having the worst prognosis. Unfortunately, systemic chemotherapy is often less effective in the treatment of PMs. Therefore, removal of all visible tumor via cytoreductive surgery along with intraperitoneal (IP) therapies has been used. METHODS:A comprehensive review of the literature was conducted using MEDLINE/PubMed and Web of Science with an end date of September 1, 2024, regarding cytoreductive surgery and heated IP chemotherapy for CRC PMs. RESULTS:Recent studies have called into question the utility of IP chemotherapy in the treatment of CRC PMs. However, regardless of IP chemotherapy, cytoreductive surgery has demonstrated an additional survival benefit for patients with PM secondary to CRC. DISCUSSION/CONCLUSIONS:This study reviews the pathophysiology of CRC PM, the current treatment paradigms, and a pathway for improving outcomes in patients with CRC PM.

Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC).

INTRODUCTION/BACKGROUND:Liver transplantation for non-resectable colorectal liver metastasis (NRCRLM) has become accepted for select patients meeting strict inclusion criteria. Advancements in patient selection and understanding of cancer biology may expand benefits to patients with CRLM. In this meta-analysis, we sought to assess survival outcomes, recurrence patterns and quality of life (QoL) following liver transplantation (LT) for CRLM. METHODS:PubMed, Embase and Scopus databases were searched. Random-effect meta-analysis was conducted to obtain pooled overall survival, and disease-free survival rates, as well as compare QoL from baseline. Continuous data were analyzed, and standardized mean difference (SMD) were reported. RESULTS:Overall, 16 studies (403 patients, 58.8% male) were included. The pooled 1- 3- and 5- year OS following LT for NRCRLM were 96% (CI-92-99%), 77% (CI-62-89%) and 53% (CI-45-61%) respectively. Moreover, the pooled 1-, 3- and 5-year DFS were 58% (CI-43-72%), 33% (CI-9-61%) and 13% (CI-4-27%), respectively. Overall, 201 patients (49.8%) experienced recurrence during the follow-up period with the lungs being the most common site (45.8%). There was no significant difference in physical and emotional functioning, fatigue, and pain components of QoL at 6 months following LT compared with baseline (all p>0.05). CONCLUSION/CONCLUSIONS:LT for NRCRLM demonstrates good OS outcomes with no differences in QoL of patients at 6 months following transplantation. Transplantation may represent a viable treatment option for NRCRLM.

BACKGROUND:The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC. METHODS:PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990-2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported. RESULTS:Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83-91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%-89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09-9.63), ICI + TKI (OR 3.08, 95% CI 1.63-5.82), and TKI + TACE (OR 2.90, 95% CI 1.61-5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37-1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70-1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29-0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05). CONCLUSION/CONCLUSIONS:The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC.

Until recently, there have been only modest therapeutic advances in the treatment of hepatobiliary malignancies. However, the introduction of immune checkpoint inhibitors in combination with targeted therapy or chemotherapy has changed the therapeutic landscape of hepatocellular carcinoma and biliary tract cancers. As such, revisions have been made to guidelines reflecting therapeutic advances for patients who can be considered for surgical options including resection and liver transplantation. This article highlights recently published studies that have impacted both the oncological and surgical approach to the treatment of patients with hepatobiliary malignancies.

Although the incidence of colorectal cancer (CRC) has decreased as a result of increased screening and awareness, it still remains a major cause of cancer-related death. Additionally, early detection of CRC recurrence by conventional means such as CT, endoscopy, and CEA has not translated into an improvement in survival. Liquid biopsies, such as the detection circulating tumor DNA (ctDNA), have been investigated as a biomarker for patients with CRC in terms of prognosis and recurrence, as well as their use to guide therapy. In this manuscript, we provide an overview of ctDNA as well as its utility in providing prognostic information, using it to guide therapy, and monitoring for recurrence in patients with CRC. In addition, we discuss the influence the site of disease may have on the ability to detect ctDNA in patients with metastatic CRC.