Progress on the molecular mechanism of portal vein tumor thrombosis formation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with poor prognosis and high mortality. Early-stage HCC has no obvious clinical symptoms, and most patients are already at an advanced stage when they are diagnosed. Portal vein tumor thrombus (PVTT) is the most common complication and a poor prognostic factor for HCC, which frequently leads to portal vein hypertension, ascites, gastrointestinal bleeding, and tumor metastasis. The formation of PVTT is related to the complex structure and hemodynamic changes of the portal vein and is closely related to changes at the cellular and molecular levels. The differentially-expressed genes (DEGs) between PVTT and primary tumor (PT) suggest that the two tissues may have different clonal origins. Epigenetic and proteomic analyses also suggest complex and diverse mechanisms for the formation of PVTT. In addition, the tumor microenvironment and energy metabolism pathways are interrelated in regulating the invasion and progression of PVTT. Aerobic glycolysis and the tumor immune microenvironment have been the focus of recent studies on PVTT. In this review, we summarize the mechanism of PVTT formation at the cellular and molecular levels to provide information to guide better prevention and treatment of PVTT in the clinic.

Successful treatment using targeted therapy, radiotherapy, and intrathecal chemotherapy in a patient with leptomeningeal metastasis with an epidermal growth factor receptor exon 20 insertion mutation: a case report.

Leptomeningeal metastasis (LM) is a disastrous complication in lung cancer. LM patients with oncogene-addicted non-small cell lung cancer (NSCLC) have a relatively better prognosis than those with the wild-type counterpart; however, overall post-LM survival is short. Additionally, the high heterogenicity of the LM entity creates a treatment challenge, and to date, no standard strategy has been established. This article describes a female lung adenocarcinoma patient with a resistant epidermal growth factor receptor (EGFR) exon20ins mutation who developed LM only 11 months after radical surgery IIIA (pT1bN2). Intrathecal chemotherapy (ITC), whole-brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) followed by Osimertinib was initiated. The cerebrospinal fluid (CSF) cytology turned negative. The first remission lasted 6 months, then bone metastases occurred, and the LM progressed. An Ommaya reservoir was implanted. ITC with pemetrexed and anlotinib was administered. A CSF next-generation sequencing (NGS) examination revealed EGFR exon20ins (p. A767_V769 dup 1.5%), which was different from that of the primary tumor (p. V769_D770 ins ASV 17.48%). The CSF cytology then turned negative again; however, the patient succumbed to the disease in December 2020. The patient's post-LM overall survival (OS) time was 13.5 months. This case is novel and of great value. Clinicians should pay special attention to populations at high risk of developing LM. Early detection followed by active intervention, including ITC, RT, and systemic treatment, will result in a better prognosis. The NGS of CSF is fundamental to understanding the genetic profiles of LM and providing effective and precise treatment.

EGFR-mutated stage IV non-small cell lung cancer: What is the role of radiotherapy combined with TKI?

Lung cancer is the leading cause of cancer-related death globally and poses a considerable threat to public health. Asia has the highest prevalence of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). Despite the reasonable response and prolonged survival associated with EGFR-tyrosine kinase inhibitor (TKI) therapy, the acquisition of resistance to TKIs remains a major challenge. Additionally, patients with EGFR mutations are at a substantially higher risk of brain metastasis compared with those harboring wild-type EGFR. The role of radiotherapy (RT) in EGFR-mutated (EGFRm) stage IV NSCLC requires clarification, especially with the advent of next-generation TKIs, which are more potent and exhibit greater central nervous system activity. In particular, the feasible application of RT, including the timing, site, dose, fraction, and combination with TKI, merits further investigation. This review focuses on these key issues, and provides a flow diagram with proposed treatment options for metastatic EGFRm NSCLC, aiming to provide guidance for clinical practice.