Improved survival with adding-on strategy after failure of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin in metastatic pancreatic adenocarcinoma.

Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (FL) is indicated after progression on gemcitabine-based therapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). However, salvage therapy after nal-IRI/FL failure remains to be established.

Methods: This study included 260 consecutive patients who initiated nal-IRI/FL therapy reimbursed by the National Health Insurance of Taiwan between January 2019 and March 2023.

Complex Roles of /SHP2 in Carcinogenesis and Prospect of Targeting SHP2 in Cancer Therapy.

The non-receptor tyrosine phosphatase SHP2 has been at the center of cell signaling research for three decades. SHP2 is required to fully activate the RTK-RAS-ERK cascade, although the underlying mechanisms are not completely understood. , coding for SHP2, is the first identified proto-oncogene that encodes a tyrosine phosphatase, with dominantly activating mutations detected in leukemias and solid tumors.

Outcomes of Post-Immunotherapy Durable Responders of Advanced Hepatocellular Carcinoma- with Emphasis on Locoregional Therapy for Oligoprogression.

Introduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized.

Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.

Clinical Outcomes and Histologic Findings of Patients With Hepatocellular Carcinoma With Durable Partial Response or Durable Stable Disease After Receiving Atezolizumab Plus Bevacizumab.

Purpose: Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors.

Patients And Methods: The IMbrave150 study's atezo-bev group was analyzed.

Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma.

Purpose: We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib.

Patients And Methods: Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation.

Shp2 Deficiency in Kupffer Cells and Hepatocytes Aggravates Hepatocarcinogenesis by Recruiting Non-Kupffer Macrophages.

Background & Aims: Complex communications between hepatocytes and Kupffer cells (KCs) are known to drive or suppress hepatocarcinogenesis, with controversial data in the literature. In previous experiments that aimed to decipher hepatocyte/KC interactions, we unexpectedly unveiled a tumor-suppressing effect of polyinosinic-polycytidylic acid, a widely used inducer of MX dynamin like GTPase 1 (Mx1)-cre expression, which questioned a theory of interleukin 1a/6 cytokine circuit in hepatocyte/KC communication. The goal of this study was to clarify the controversy and decipher unique functions of KCs and non-KC macrophages in liver tumorigenesis.

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment.

Background: The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapy for patients with advanced hepatocellular carcinoma (HCC), but the prognosis and treatment pattern after its treatment failure are unclear.

Methods: We reviewed the medical records of patients who failed first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021 in four Taiwan medical centers. Post-first-line survival (PFLS) was defined as the date from the failure of Atezo-Bev treatment to the date of death or last follow-up.

Sarcopenia and myosteatosis are associated with survival in patients receiving immunotherapy for advanced hepatocellular carcinoma.

Objectives: To investigate the association of sarcopenia, myosteatosis, and sarcopenic obesity with survival outcomes among patients who underwent immunotherapy for advanced hepatocellular carcinoma (HCC).

Methods: In this retrospective analysis, patients who initiated immunotherapy for advanced HCC were enrolled. Sarcopenia and myosteatosis were evaluated on pretreatment CT at L3 level by skeletal muscle index and mean muscle attenuation using predefined cutoff values.

ICOS-Positive Regulatory T Cells in Hepatocellular Carcinoma: The Perspective from Digital Pathology Analysis.

Introduction: Inducible co-stimulator (ICOS), an important co-stimulatory receptor on effector T cells (Teffs), may also contribute to tumor growth due to its high expression on regulatory T cells (Tregs). This study explored the clinical significance of ICOS-expressing Tregs in hepatocellular carcinoma (HCC).

Methods: Tumor tissues from HCC patients who received curative hepatectomy were obtained at a referral center.

Polatuzumab vedotin-based salvage immunochemotherapy as third-line or beyond treatment for patients with diffuse large B-cell lymphoma: a real-world experience.

Polatuzumab vedotin (PoV) has recently shown promising activity when combined with rituximab-bendamustine (BR) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, few studies have described the prognostic factors predicting response. Here, we aimed to evaluate the efficacy and safety profile of PoV-based chemotherapy, including regimens other than BR, as third-line or beyond treatment for patients with R/R DLBCL and to explore prognostic factors.

Limited Predictive or Prognostic Role of Tumor-Infiltrating Tissue-Resident Memory CD8 T Cells in Patients with Hepatocellular Carcinoma Receiving Immunotherapy.

Purpose: Tumor-infiltrating tissue-resident memory CD8 T cells (CD8 T; CD103+ CD8+) are considered tumor-specific and may correlate better with the tumor response to immune checkpoint blockade (ICB). This study evaluated the association of tumor-infiltrating CD8 T and their subsets with the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC).

Experimental Design: Consecutive HCC patients who received ICB in prospective trials were analyzed.

Atezolizumab plus bevacizumab combination enables an unresectable hepatocellular carcinoma resectable and links immune exclusion and tumor dedifferentiation to acquired resistance.

We reported a patient with unresectable hepatocellular carcinoma (HCC) who initially received 15 cycles of atezolizumab plus bevacizumab combination and had best tumor response of partial response, but later experienced disease progression. After subsequent surgical resection, the patient enjoyed long-term disease-free status at the last follow-up 19 months after surgery. By investigating paired tumor tissues (pretreatment and post-progression samples) with immunohistochemistry, multiplex immunofluorescence, RNA sequencing, and DNA sequencing, we explored the dynamic changes in the tumor microenvironment (TME) and potential mechanisms underlying acquired resistance to the combination.

Response to Immune Checkpoint Inhibitors in Recurrent or Metastatic Esophageal Squamous Cell Carcinoma May Be Affected by Tumor Sites.

Introduction: Heterogeneous tumor response has been reported in cancer patients treated with immune checkpoint inhibitors (ICIs). This study investigated whether the tumor site is associated with the response to ICIs in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

Methods: Patients with ESCC who had measurable tumors in the liver, lung, or lymph node (LN) according to the response evaluation criteria in solid tumors (RECIST) 1.

An Exploratory Study for the Association of Gut Microbiome with Efficacy of Immune Checkpoint Inhibitor in Patients with Hepatocellular Carcinoma.

Background: Gut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular carcinoma (HCC).

Aims: To investigate the association between gut microbiome and efficacy of ICI in patients with HCC.

Methods: Patients with HCC who were scheduled to receive ICI were prospectively enrolled.

Solving the deficit of cancer pain management skills by education programs.

Background: Suboptimal cancer pain management is a worldwide problem. We examined whether an educational program on cancer pain management implemented during training could benefit primary care physicians.

Methods: We enrolled all the primary care physicians who visited the oncology ward at a medical center for the first time.

Differential Organ-Specific Tumor Response to Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.

Background And Aims: Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs.

Methods: We reviewed the data of patients with advanced HCC who had received ICIs.

Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma.

Background: Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC.

Methods: We reviewed all patients who received ICI therapy for advanced HCC.

Considerations of heterogeneity in clinical trials for hepatocellular carcinoma.

: Clinical trials in hepatocellular carcinoma (HCC) exhibit a high degree of heterogeneity. These heterogeneities may lead to unexpected results among clinical trials. : In this review, we address the heterogeneity noted in early phase HCC trials, trials involving transarterial chemoembolization, and advanced HCC trials.

Targeting myeloid-derived suppressor cells in the treatment of hepatocellular carcinoma: current state and future perspectives.

Systemic therapy for advanced hepatocellular carcinoma (HCC) has been focusing on overcoming tumor angiogenesis and immunosuppression. Myeloid-derived suppressor cells (MDSCs) promote both angiogenesis and immunosuppression in the tumor microenvironment (TME). Multiple clinical studies have demonstrated the prognostic implications of and suggested the translational significance of MDSCs in patients with HCC.

Increased Expression of Programmed Death-Ligand 1 in Infiltrating Immune Cells in Hepatocellular Carcinoma Tissues after Sorafenib Treatment.

Objective: Programmed death-ligand 1 (PD-L1) expression in the tumor microenvironment (TME) has been reported to be related to prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. The impact of sorafenib on PD-L1 expression in the TME of advanced HCC is unclear.

Patients And Methods: Patients with HCC who received sorafenib for advanced disease at National Taiwan University Hospital, Taipei, Taiwan, and who had paired HCC tissues obtained before and after sorafenib treatment were included in the study group.

Targeting tumor-infiltrating Ly6G myeloid cells improves sorafenib efficacy in mouse orthotopic hepatocellular carcinoma.

Sorafenib, a multikinase inhibitor with antiangiogenic activity, is an approved therapy for hepatocellular carcinoma (HCC). It is unclear whether the proinflammatory and immunosuppressive mechanisms may limit the therapeutic efficacy of sorafenib in HCC. We used a syngeneic mouse liver cancer cell line to establish orthotopic liver or subcutaneous tumors to study how proinflammatory and immunosuppressive mechanisms impact on the efficacy of sorafenib.

Prescription Patterns of Sorafenib and Outcomes of Patients with Advanced Hepatocellular Carcinoma: A National Population Study.

Background: Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC). We analyzed national prescription patterns and treatment outcomes of patients who received sorafenib for advanced HCC.

Patients And Methods: We established a nation-wide cohort of patients who started receiving treatment with sorafenib for advanced HCC between August 2012 and July 2013 from the National Health Insurance Research Database of Taiwan and also retrieved demographic and prescription data.

Inhibition of the Wnt/β-catenin signaling pathway improves the anti-tumor effects of sorafenib against hepatocellular carcinoma.

Sorafenib, a multikinase inhibitor, is currently the only approved drug for advanced hepatocellular carcinoma (HCC). The current study tested the hypothesis whether inhibition of the Wnt/β-catenin signaling pathway could improve the anti-tumor effects of sorafenib in HCC. ICG-001, a small molecule which blocks the interaction of β-catenin with its transcriptional coactivator CBP, dose-dependently enhanced the growth-suppressive and apoptosis-induction effects of sorafenib in multiple HCC cell lines.

Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges.

Tumor heterogeneity in hepatocellular carcinoma (HCC), such as that found in second primary tumors after curative treatment, synchronous multifocal tumors of different clonality, or intratumor heterogeneity, poses severe challenges for the development and administration of systemic molecular targeted therapies. Various methodologies, including historical DNA ploidy analysis, integrated hepatitis B virus DNA analysis, DNA fingerprinting, and next-generation sequencing technologies, are used to explore tumor heterogeneity in HCC. It is estimated that 30%-60% of recurrent or metastatic tumors harbor clones different from the primary tumor, 22%-79% of synchronous tumors vary clonally, and 12%-66% of single tumors contain intratumor heterogeneity.