Faculty Bibliography

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.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) comprise the two most common primary liver malignancies. Curative treatment options often include hepatectomy or liver transplantation; however, many patients present with advanced disease that is not amenable to surgical management. In turn, many patients are treated with systemic or targeted therapy. The tumor microenvironment (TME) is a complex network of immune cells and somatic cells, which can foster an environment for disease development and progression, as well as susceptibility and resistance to systemic therapeutic agents. In particular, the TME is comprised of both immune and non-immune cells. Immune cells such as T lymphocytes, natural killer (NK) cells, macrophages, and neutrophils reside in the TME and can affect tumorigenesis, disease progression, as well as response to therapy. Given the importance of the immune system, there are many emerging approaches for cancer immunotherapy. We herein provide a review the latest data on immunotherapy for primary HCC and BTC relative to the TME.

Background: Immune checkpoint inhibitors (ICIs) have recently been introduced into the treatment algorithm of patients with hepatocellular carcinoma (HCC). However, the cost effectiveness of ICIs compared with pre-existing therapies for HCC has not been assessed. We performed a meta-analysis to understand the incremental cost effectiveness of ICIs compared with sorafenib. Methods: PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (2000"“2022). The incremental cost, incremental effectiveness, incremental cost effectiveness ratio (ICER) of ICI compared with sorafenib and willingness to pay (WTP) were extracted from each study. The variables were used to derive the incremental net benefit (INB). Random-effect meta-analysis was then conducted to derive the pooled INB of ICI compared with sorafenib. Results: Five studies (3265 patients, 82.1 % male) met inclusion criteria. All studies assessed the cost effectiveness of ICIs compared with sorafenib. Studies used Quality adjusted life years to assess incremental effectiveness and reported ICER values ranging from $21,000 to $221,000 for ICIs and sorafenib. Four out of five studies reported that ICI had a higher ICER compared with sorafenib at WTP $150,000. The overall pooled INB was US$-42,000 (95 % CI[dbnd]US$-96,000, US$11,528) suggesting that ICI was not cost effective compared with sorafenib. Conclusion: When compared with sorafenib, ICIs were not a cost-effective option for systemic therapy for patients with HCC. More work focusing on cost effective options for patients with HCC is warranted.

BACKGROUND:Immune checkpoint inhibitors (ICIs) have recently been introduced into the treatment algorithm of patients with hepatocellular carcinoma (HCC). However, the cost effectiveness of ICIs compared with pre-existing therapies for HCC has not been assessed. We performed a meta-analysis to understand the incremental cost effectiveness of ICIs compared with sorafenib. METHODS:PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (2000-2022). The incremental cost, incremental effectiveness, incremental cost effectiveness ratio (ICER) of ICI compared with sorafenib and willingness to pay (WTP) were extracted from each study. The variables were used to derive the incremental net benefit (INB). Random-effect meta-analysis was then conducted to derive the pooled INB of ICI compared with sorafenib. RESULTS:Five studies (3265 patients, 82.1 % male) met inclusion criteria. All studies assessed the cost effectiveness of ICIs compared with sorafenib. Studies used Quality adjusted life years to assess incremental effectiveness and reported ICER values ranging from $21,000 to $221,000 for ICIs and sorafenib. Four out of five studies reported that ICI had a higher ICER compared with sorafenib at WTP $150,000. The overall pooled INB was US$-42,000 (95 % CIUS$-96,000, US$11,528) suggesting that ICI was not cost effective compared with sorafenib. CONCLUSION/CONCLUSIONS:When compared with sorafenib, ICIs were not a cost-effective option for systemic therapy for patients with HCC. More work focusing on cost effective options for patients with HCC is warranted.