Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND & AIMS: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032). CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies.

Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

INTRODUCTION: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 298 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. RESULTS: Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001). CONCLUSIONS: Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.

Cardiac Paraganglioma in a Young Patient Presents with Angina-like Symptoms: A Case Report and Literature Review.

Paragangliomas are rare extra-adrenal neuroendocrine tumors originating from chromaffin tissue that present a diagnostic and therapeutic challenge due to their diverse clinical manifestations and low incidence. While these tumors often manifest as catecholamine-secreting functional tumors, their clinical presentation can vary, leading to delayed diagnosis and challenging management. This study presents the case of a 22-year-old patient with cardiac paraganglioma who initially presented with angina-like symptoms, highlighting the importance of considering this rare condition in young individuals with nonspecific complaints. Diagnostic imaging, including transthoracic echocardiography, CT angiography, and MRI, played a crucial role in identifying the tumor's location and vascularization. Surgical excision, including pulmonary artery graft and CABG, was the primary management approach, which was accompanied by intraoperative complications that later led to CCU admission, followed by postoperative complications, ultimately leading to the patient's death. This case highlights the significance of early recognition and management of complications following a surgical approach to treat paragangliomas.

Focal Update on Immunotherapy and Liver Transplantation in the Era of Transplant Oncology.

Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and "bridging" previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update's utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance.

Advances in Immunotherapy for Transplant Oncology.

The increasing incidence of global cancer rates has created an entirely new demand for curative treatment modalities to improve patient outcomes [...].

Comparative molecular profiling of pancreatic ductal adenocarcinoma of the head versus body and tail.

Pancreatic ductal adenocarcinoma (PDAC) of the head (H) and body/tail (B/T) differ in embryonic origin, cell composition, blood supply, lymphatic and venous drainage, and innervation. We aimed to compare the molecular and tumor immune microenvironment (TIME) profiles of PDAC of the H vs. B/T. A total of 3499 PDAC samples were analyzed via next-generation sequencing (NGS) of RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Significance was determined as p values adjusted for multiple corrections (q) of <0.05. Anatomic subsites of PDAC tumors were grouped by primary tumor sites into H (N = 2058) or B/T (N = 1384). There were significantly more metastatic tumors profiled from B/T vs. H (57% vs. 44%, p < 0.001). KRAS mutations (93.8% vs. 90.2%), genomic loss of heterozygosity (12.7% vs. 9.1%), and several copy number alterations (FGF3, FGF4, FGF19, CCND1, ZNF703, FLT4, MUTYH, TNFRS14) trended higher in B/T when compared to H (p < 0.05 but q > 0.05). Expression analysis of immuno-oncology (IO)-related genes showed significantly higher expression of CTLA4 and PDCD1 in H (q < 0.05, fold change 1.2 and 1.3) and IDO1 and PDCD1LG2 expression trended higher in B/T (p < 0.05, fold change 0.95). To our knowledge, this is one of the largest cohorts of PDAC tumors subjected to broad molecular profiling. Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs. B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.

The Impact of Infections in Patients Treated with Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.

Background: The therapeutic landscape of unresectable hepatocellular carcinoma (uHCC) continues to evolve. Atezolizumab, an anti-programmed cell death ligand 1 (PD-1) immune checkpoint inhibitor (ICI), in combination with bevacizumab, has substantially improved outcomes. This study aims to evaluate the incidence, risk factors, and outcomes in patients who develop infections while receiving atezolizumab and bevacizumab for uHCC. Methods: Patients who received atezolizumab and bevacizumab for uHCC at a single hospital network were included. Types and rates of infections were reported. Covariates compared among infected and non-infected cohorts included age, sex, race, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, immunosuppressive use, chronic infections, number of cycles of ICIs given, antibiotic or antiviral therapies at ICI initiation, and line of therapy (first-line, second-line, greater than second-line). Results: Out of 810 evaluable patients, 34 uHCC patients were treated with atezolizumab plus bevacizumab. The mean ± SD age was 66.29 ± 9.39; 28 (82.35%) were males. There were 17 (50%) patients with reported infection, with bacterial infection occurring in 12 (70.59%) patients and COVID-19 in 4 (23.5%). Of the infected patients, eight (47.06%) had one infection, five (29.41%) had two infections, and two (11.76%) had three or more infections. Infected and non-infected patients received a median of 12 (IQR: 5-17) and 4 (IQR: 3-12) ICI cycles (p = 0.18), respectively. Infections did not negatively impact OS or PFS but resulted in treatment delays and discontinuation in 11 (64.71%) and 7 (41.18%) patients, respectively. At the last follow-up, 19 (55.88%) patients died, 9 (52.94%) in the non-infected group vs. 10 (58.82%) in the infected group (p = 1.0). Conclusions: While a broad array of infections occurred in 50% of the patients in this cohort, it did not negatively impact survival outcomes. However, it did impact morbidity, with more all-cause admissions and treatment delays.

Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation.

Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.

Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.

Pancreatic ductal adenocarcinoma: the latest on diagnosis, molecular profiling, and systemic treatments.

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC.

Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection.

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants in-vitro, by utilizing Murine Leukemia Virus (MLV) based pseudovirus particles. We demonstrated that NP-101, TQ, and other individual ingredients, including oleic, linoleic, and palmitic acids inhibited SARS-CoV-2 infection in the MLV-based pseudovirus model. A large, randomized phase 2 study of NP-101 is planned in outpatient COVID-19 patients.

Practical guide: Glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus.

In 2005, exenatide became the first approved glucagon-like peptide-1 receptor agonist (GLP-1 RA) for type 2 diabetes mellitus (T2DM). Since then, numerous GLP-1 RAs have been approved, including tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, which was approved in 2022. This class of drugs is considered safe with no hypoglycemia risk, making it a common second-line choice after metformin for treating T2DM. Various considerations can make selecting and switching between different GLP-1 RAs challenging. Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.

Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology.

The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk-benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.

Transplant Oncology: An Emerging Discipline of Cancer Treatment.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.

Newest Therapies for Cholangiocarcinoma: An Updated Overview of Approved Treatments with Transplant Oncology Vision.

A minority of cholangiocarcinoma (CCA) can be cured by surgical intervention (i.e., liver resection (LR) and liver transplantation (LT)). When modern criteria for LT are met, this intervention along with neoadjuvant treatments may achieve unprecedented survival in selected patients. Liver resection is associated with a median overall survival (OS) of 40 months, this number drastically decreases for unresectable advanced cholangiocarcinoma (CCA), which is treated with systemic therapy. The first-line chemotherapy regimen of gemcitabine and cisplatin is associated with a median overall survival of only 11.7 months. Since the Food and Drug Administration (FDA)'s approval of the isocitrate dehydrogenase (IDH) 1 inhibitor ivosidenib in August 2021, there has been increasing interest in targeted therapy for CCA patients harboring mutations in fibroblast growth factor receptor (FGFR) 2, neurotrophic receptor tyrosine kinase (NTRK), B-raf kinase (BRAF), and HER2. At the same time, immunotherapy with immune checkpoint inhibitors isalso being used in relapsed CCA. This review looks into the most recently completed and ongoing studies of targeted therapy as monotherapy or in combination with chemo- and/or immunotherapy. Whether it is resection, liver transplant, radiotherapy, chemotherapy, immunotherapy, targeted therapy, or any combination of these treatment modalities, great strides are being made to improve outcomes for this challenging disease.

Timeline of FDA-Approved Targeted Therapy for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) represents approximately 3% of gastrointestinal malignancies worldwide and constitutes around 10-15% of all primary liver cancers, being only second to hepatocellular carcinoma. Mortality from CCA has been on the rise in recent decades, and in the United States alone there has been a 36% increase in CCA from 1999 to 2014, with over 7000 CCA mortalities since 2013. Targeted therapies, which have been gaining interest due to their greater specificity toward cancer cells, have only recently started gaining FDA approval for the treatment of CCA. In this manuscript, we will go through the timeline of current FDA-approved targeted therapies as well as those that have gained FDA breakthrough therapy designation.

Recent Trends and Advancements in the Diagnosis and Management of Gastric Cancer.

Gastric cancer is an enigmatic malignancy that has recently been shown to be increasing in incidence globally. There has been recent progress in emerging technologies for the diagnosis and treatment of the disease. Improvements in non-invasive diagnostic techniques with serological tests and biomarkers have led to decreased use of invasive procedures such as endoscopy. A multidisciplinary approach is used to treat gastric cancer, with recent significant advancements in systemic therapies used in combination with cytotoxic chemotherapies. New therapeutic targets have been identified and clinical trials are taking place to assess their efficacy and safety. In this review, we provide an overview of the current and emerging treatment strategies and diagnostic techniques for gastric cancer.

Case report: Efficacy and safety of regorafenib plus fluorouracil combination therapy in the treatment of refractory metastatic colorectal cancer.

Background: More than half of patients with colorectal cancer (CRC) present with metastatic disease or develop recurrent disease on first-line and second-line options. Treatment beyond the second line remains an area of unmet need for patients with progressive or recurrent disease. Methods: We retrospectively reviewed data of adult (>18 years old) patients with mCRC who received regorafenib + 5FU combination therapy at Houston Methodist Hospital with outcomes of interest including response rate, discontinuation due to side effects, and overall survival. Results: Seven patients received regorafenib + 5FU combination therapy for mCRC after receiving at least two other lines of therapy (including at least one fluorouracil-based therapy). Four patients (57%) achieved disease control in 7-12 weeks after therapy initiation while three patients developed recurrent disease. In patients who achieved disease control, no new adverse events were reported among patients with this combination. Conclusion: Regorafenib and Fluorouracil combination could be considered an option beyond the second line for patients with treatment-refractory metastatic colorectal cancer. Further studies, including a prospective trial, are needed to investigate the efficacy and safety of regorafenib plus 5FU therapy compared to other limited available therapies.

Immunotherapy as a Neoadjuvant Therapy for a Patient with Hepatocellular Carcinoma in the Pretransplant Setting: A Case Report.

Systemic combination therapy of immune checkpoint inhibitors and vascular endothelial growth factors have provided the basis for improved outcomes in select patients with unresectable or metastatic hepatocellular carcinoma. However, for patients with resectable disease, surgery alone or an orthotopic liver transplant remains the standard of care. Within the realms of transplant oncology, neoadjuvant systemic therapy is currently being evaluated as a potential strategy to improve outcomes in patients with HCC. Here, we report excellent response with significant downstaging in a safe manner after neoadjuvant treatment with atezolizumab and bevacizumab in a patient diagnosed with poorly differentiated HCC. As a result of the significant response observed with safe outcomes, the patient was listed for orthotopic liver transplant (OLT) evaluation and transplanted successfully.