Neoadjuvant Immunotherapy in Patients Undergoing Liver Transplantation for Primary Liver Cancer at a Single Center

American Journal of Transplantation · 2025-01-01

Reply to: Beyond Detection: Addressing Threshold Definition and Clinical Integration of Circulating Tumor DNA in Post-Curative Hepatocellular Carcinoma

JCO Precision Oncology · 2025-10-01

Correlative Analysis of Tumor-Informed Circulating Tumor DNA (ctDNA) and the Survival Outcomes of Patients with Pancreatic Adenocarcinoma

Biomedicines · 2025-05-06 · 6 citations

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis due to late-stage diagnosis, limited surgical resectability, and frequent recurrence. Traditional biomarkers like CA19-9 and imaging techniques often fail to detect minimal residual disease (MRD) or early recurrence. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker that may provide early detection of disease recurrence, offering a potential improvement in patient management. This study aimed to assess the utility of ctDNA as a prognostic tool for PDAC patients, specifically in predicting recurrence and overall survival (OS). Methods: This retrospective study analyzed data from 39 PDAC patients who underwent surgery and were monitored for ctDNA levels using Signatera™, a tumor-informed multiplex PCR next-generation sequencing assay. Blood samples were collected both preoperatively and postoperatively, and ctDNA levels were measured to detect MRD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctDNA were compared with CA19-9 in detecting disease recurrence. Clinical outcomes, including progression-free survival (PFS) and OS, were evaluated in relation to ctDNA status. Results: Among 39 patients, 153 plasma samples were analyzed, with 17 patients testing positive for ctDNA. Sensitivity of ctDNA in detecting relapse was 91%, compared to 83% for CA19-9, with combined testing reaching 98% sensitivity. ctDNA positivity was associated with significantly shorter OS and PFS, with patients testing negative for ctDNA having a median OS of 37.6 months versus 13.4 months in ctDNA-positive patients (p = 0.003). The median time from ctDNA positivity to imaging-confirmed relapse was 81 days. Positive ctDNA was also linked to higher rates of lymphovascular invasion and positive surgical margins, highlighting the aggressive nature of the disease in these patients. Conclusions: CtDNA is a highly sensitive and specific biomarker for detecting MRD and predicting recurrence in PDAC patients, offering superior performance over CA19-9. Positive ctDNA results were associated with worse prognosis, including shorter OS and PFS, and may help guide treatment decisions. These findings suggest that ctDNA could be a valuable tool for personalized management in PDAC, though further prospective studies are needed to validate its clinical role in treatment stratification.

Ataxia Telangiectasia Mutated (ATM) gene alterations as biomarkers of response to immune checkpoint inhibitors

Immunotherapy · 2025-11-02

AIMS: mutations and response to ICIs in two ICI-treated cohorts and a possible underlying molecular explanation. MATERIALS & METHODS: = 3341). Kaplan-Meier survival was generated using log-rank tests. The TCGA cohort was used to assess neoantigen load and predicted immunogenic mutations. RESULTS: -mutant had higher predicted immunogenic mutations than DDR-mutant or DDR-WT. CONCLUSION: -WT and has higher predicted immunogenetic mutations. Our results are rather hypothesis-generating and would benefit from further validation in prospective trials.

Trend analysis of risk factors for early-onset primary colorectal cancer: A population-based time trend analysis using the SEER database.

Journal of Clinical Oncology · 2025-05-28

e15717 Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. The incidence of early-onset CRC in individuals below 50 years old has been increasing. This contrasts with the declining incidence of late-onset CRC in individuals above 50, likely due to improved early screening. This study aims to investigate the association between CRC and potential risk factors that may contribute to the rising incidence of early-onset CRC. Methods: A time-trend analysis was conducted using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2000–2021. Age-adjusted incidence rates were calculated and compared across patient characteristics, including age ( < 50 years), sex, race/ethnicity, year of diagnosis, age at diagnosis, and urban-rural setting. Rates are reported per 100,000 population, with 95% confidence intervals. Percent changes (PC) were calculated using the first and last years of the study period, and annual percent changes (APC) were calculated using weighted least squares regression, with statistical significance set at p < 0.05. Results: Over the past two decades, there has been an increase in the overall incidence of CRC by 2.1-fold, from 2000 (9.8 per 100,000) to 2021 (15.2 per 100,000). Rates in females increased 2.3-fold and 1.9-fold in males. The largest rise was 6.5-fold in the 20–24 age group versus 1.4-fold in the 45–49 age group. By race/ethnicity, increases were greatest in American Indians (3.6-fold), non-Hispanic whites (2.5-fold), and Hispanics (2.8-fold), versus smaller increases in non-Hispanic blacks (0.9-fold) and Asians (0.5-fold). Patients residing in metropolitan areas with populations over 250,000 experienced a 2.3-fold increase in CRC incidence. Conclusions: SEER population-based data indicates that CRC incidence rates have increased over the past two decades among both genders and may continue to increase. We observed a potentially alarming trend in the increasing incidence in the young 20-24 age group, with a 6.5-fold rise. Future studies should investigate these findings, understand the underlying contributing factors, and determine the necessary actions to address these alarming trends.

Transplantation for Peri-Hilar and Intrahepatic Cholangiocarcinoma With mTOR Immunosuppression

Transplantation Proceedings · 2025-02-12 · 2 citations

Evaluating Standardization of Neoadjuvant Immunotherapy in Transplant-Eligible Hepatocellular Carcinoma Populations

Jordan Medical Journal · 2025-02-10 · 1 citations

In the past decade, immunotherapy has significantly revolutionized the treatment of advanced hepatocellular carcinoma (HCC). Recent phase III trials examining immunotherapy as monotherapy and combination therapy for early to intermediate-stage HCC have produced favorable results, while further phase III trials in this patient cohort are ongoing. Owing to the advantageous data derived from these trials, the utilization of immunotherapy is broadening to include patients with earlier stages of HCC, especially within the transplant-eligible subgroup. Current literature increasingly advocates for the standardized application of neoadjuvant immunotherapy in liver transplantation. Transplantation functions as a potentially curative treatment for HCC and additionally restores normal, healthy liver function. Immunotherapy in pre-transplant patients may improve downstaging efficacy and tumor management, though it carries immunological risks. Immune-related toxicities are substantial in individuals with chronic liver disease, who are particularly susceptible, alongside the risk of acute rejection post-transplantation. The main goal of immunotherapy in this population is to improve access to liver transplantation while preserving pre- and post-transplant results. This concise review analyzes contemporary literature regarding the use of immunotherapy in the neoadjuvant context prior to liver transplantation, explores potential advantages of combination immunotherapy, and synthesizes important recent clinical findings from prominent trials related to HCC transplant oncology treatment.

Tumor-informed circulating tumor DNA assay for surveillance post-liver transplantation in patients with hepatocellular and cholangiocarcinoma

Journal of Gastrointestinal Oncology · 2025-08-01 · 1 citations

Background: Liver transplantation (LT) for primary liver cancers achieves excellent patient outcomes, but a minority recur with poor prognosis. Survival may be improved by earlier recurrence detection. This study aims to evaluate the feasibility and performance of a personalized tumor-informed assay utilizing circulating tumor DNA (ctDNA) from peripheral blood for surveillance after LT in patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA). Methods: Here, we test whether a personalized tumor-informed assay utilizing ctDNA from peripheral blood informs post-LT surveillance. Personalized ctDNA assays were employed for surveillance in 38 LT recipients, alongside standard-of-care imaging and peripheral tumor biomarkers [alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9)]. Results: ). Only 1 patient had ctDNA positive prior to imaging-based diagnosis. Conclusions: This study corroborates the feasibility of ctDNA assays for recurrence surveillance in LT recipients. The results imply that ctDNA assays show promise in confirming recurrence and minimizing the need for invasive biopsy. However, additional prospective studies are needed to confirm ctDNA test utility in surveillance protocols.

Disparities in liver transplantation for metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma

World Journal of Transplantation · 2025-04-18

BACKGROUND Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly common, as is hepatocellular carcinoma (HCC) in the background of MASH. Liver transplantation (LT) provides superior long-term survival for patients with unresectable MASH-HCC, but not all patients have equal access to transplant. MASH-HCC disproportionately affects Hispanic patients, but minorities are less likely to undergo LT for HCC. Additionally, females also undergo LT at lower rates than males. AIM To investigate whether race/ethnicity and sex affect LT waitlist outcomes. METHODS Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed. RESULTS Most of the 3810 patients waitlisted for LT for MASH-HCC were non-Hispanic (NH) white (71.2%) or Hispanic (23.4%), with only 49 (1.1%) NH Black candidates. Hispanics underwent LT at lower rates than NH whites (71.6% vs 78.4%, P < 0.001), but race/ethnicity did not affect waitlist mortality (P = 0.06). Patients with Hispanic [hazard ratio (HR) = 0.85, 95%CI: 0.77-0.95, P = 0.002] or Asian (HR = 0.79, 95%CI: 0.63-0.98, P = 0.04) race/ethnicity were less likely to undergo LT. Women were also less likely to receive LT (male: HR = 1.16, 95%CI: 1.04-1.29, P = 0.01). Patients in regions 1 and 9 were less likely to be transplanted as well (P = 0.07). CONCLUSION Hispanic patients are less likely to undergo LT for MASH-HCC, concerning given their susceptibility to MASH and HCC. There were very few NH Black candidates. Disparities were also unequal across regions, which is particularly concerning in states where at-risk populations have rising cancer incidence. Additional research is needed to identify strategies for mitigating these differences in access to LT for MASH-HCC.

Abstract A046: Association between gender difference in outcomes and immune checkpoint inhibitors in colorectal cancer and esophagogastric cancer

Cancer Research · 2025-03-11

Abstract Background: Immunity, encompassing both cellular and humoral responses, is significantly influenced by sex. Factors such as genetic differences, hormonal variations, environmental influences, and the composition of the commensal microbiome all contribute to these differences. Although numerous studies have examined the relationship between gender and the effectiveness of immunotherapy, the results have often been inconsistent. This study aimed to explore whether an association exists between gender and the therapeutic effect of immune checkpoint inhibitors (ICIs) in Colorectal Cancer (CRC) and Esophagogastric Cancer. Methods: We conducted a cohort study using data from the cBioPortal database, focusing on patients with CRC and esophagogastric cancer who received ICIs. Patients included in the study had been treated with ICIs such as atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, or tremelimumab, either as monotherapy or in combination. We excluded other cancer types from our analysis. Overall survival (OS) was measured from the date of first ICI treatment to time of death or most recent follow-up, with a median follow-up period of 19 months. To assess gender differences in OS, we calculated median OS separately for male and female patients. Survival analysis was performed using the Kaplan–Meier method, and we calculated pooled 95% confidence intervals (CIs) to determine the reliability and precision of our findings. The log-rank P-value was used to assess differences in OS between genders. Results: In cohort study of a total of 1,661 patients, we focused on 110 (6.6%) CRC patients and 126 (7.6%) patients with esophagogastric cancer. Among the CRC patients, 62 (56.4%) were male and 48 (43.6%) were female. In the esophagogastric cancer patients 98 (77%) males and 28 (22%) females. The most common genetic mutations identified in CRC patients were APC 80 (72%), KRAS 57 (51%), and TP53 56 (50%). Among esophagogastric cancer patients, TP53 mutations were found in 92 (72%) patients, and CDKN2A mutations were present in 20 (15%) patients. Out of these, 99 (90%) of CRC patients and 93(73%) of esophagogastric cancer patients received PD-1/PD-L1 inhibitors and the remaining patients received either anti-CTLA-4 or combination of anti-CTLA-4 and anti-PD-1/PD-L1 therapies, as part of their treatment. In studies measuring median OS for CRC patients treated with ICIs, male patients had a median OS of 31 months (95% CI: 13.00–NA), compared to 12 months (95% CI: 8.00–NA) for female patients (p=0.03). For esophagogastric cancer patients, the median OS was 13 months (95% CI: 7.00–21.00) for male patients, while for female patients, it was 20 months (95% CI: 10.00–NA) (p=0.32). Conclusion: Our study highlighted that ICI therapy improves survival outcomes, with males showing greater benefit as, indicated by a longer OS, compared to females in CRC, while the opposite result was observed in esophagogastric cancer. Citation Format: Ebtesam Al-Najjar, Bayan Khasawneh, Raed Zaidan, Abdullah Esmail, Maen Abdelrahim. Association between gender difference in outcomes and immune checkpoint inhibitors in colorectal cancer and esophagogastric cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A046.