Immune checkpoint inhibitor (ICI)-based combination therapies are standard treatments for advanced hepatocellular carcinoma (HCC). However, the efficacy of sequential ICI regimens remains unclear. We report the case of a 59-year-old woman with advanced HCC with peritoneal dissemination who showed rapid tumor regression after nivolumab plus ipilimumab as a third ICI-based regimen, following confirmed progression on durvalumab plus tremelimumab and atezolizumab plus bevacizumab. After two cycles, tumor markers markedly decreased, and radiological evaluation demonstrated a partial response by Response Evaluation Criteria in Solid Tumors (RECIST) and a complete response by modified RECIST (mRECIST). By late May 20XX+2, the patient had completed four cycles of nivolumab plus ipilimumab without any additional adverse events. The marked biochemical response was maintained, with alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels further decreasing to 173.6 ng/mL and 76 mAU/mL, respectively. The patient is currently scheduled for a follow-up radiological evaluation to confirm the durability of the response. This case suggests that nivolumab combined with ipilimumab may retain efficacy even after multiple prior ICI failures.

Glioblastoma (GBM) is a highly lethal brain tumor resistant to immunotherapy such as immune checkpoint inhibitors, partly because of an immunosuppressive tumor microenvironment and blood-brain barrier (BBB) dysfunction. Although bevacizumab can remodel the tumor vasculature, the relationship between BBB-related vascular changes and immune cell infiltration in GBM remains poorly understood. We analyzed human isocitrate dehydrogenase (IDH)-wildtype GBM tissues obtained after bevacizumab administration. Immunohistochemistry was performed for CD34 and plasmalemma vesicle-associated protein (PLVAP/PV-1), an endothelial marker associated with BBB disruption. Infiltrating T cells (CD3, CD8) and tumor-associated macrophages/microglia (TAMs; CD163) were also examined. PLVAP was broadly expressed in tumor vessels of untreated GBM and significantly reduced after bevacizumab administration, with marked downregulation in 3 of 10 treated cases. Among the 10 treated cases, significant increases in T-cell and cytotoxic T-lymphocyte infiltration were seen in PLVAP-low GBM compared with PLVAP-high GBM. TAM density did not differ significantly between groups but tended to be higher in the PLVAP-low group. These findings suggest that the bevacizumab-associated reduction of PLVAP expression is linked to increased T-cell infiltration in a subset of GBM cases. PLVAP may serve as an auxiliary histological marker for evaluating bevacizumab-related vascular/BBB remodeling in clinical specimens.

Colorectal cancer has well-established metastatic patterns, with the liver and lungs being the most frequent sites of dissemination. Cervical lymph node involvement as an initial manifestation is extremely rare and represents a significant diagnostic challenge. We describe the case of a 68-year-old female patient with no relevant comorbidities, who initially presented with left cervical lymphadenopathy at levels IV and V, associated with weight loss and a marked elevation of carcinoembryonic antigen. Histopathological examination of the cervical lymph node confirmed metastatic adenocarcinoma, and after extension studies and colonoscopy were performed, a primary tumor was identified in the transverse colon. The patient began systemic treatment with a chemotherapy regimen based on capecitabine and oxaliplatin (XELOX) in combination with bevacizumab. Subsequently, after completing the induction phase, maintenance treatment with capecitabine plus bevacizumab was administered. During follow-up, the patient showed a gradual and sustained response, ultimately achieving a complete clinical response, confirmed by imaging studies, including computed tomography, colonoscopy, and positron emission tomography (PET). This case highlights the importance of considering a gastrointestinal origin in patients with atypical cervical lymphadenopathy, as well as the impact of combined systemic treatment and maintenance therapy in achieving complete responses, even in unusual presentations of metastatic disease.

Gastrointestinal (GI) malignancies remain leading causes of cancer-related mortality despite advances in therapeutic strategies. This review was undertaken to provide a comprehensive synthesis of the mechanistic rationale, preclinical evidence, and clinical data supporting the combination of anti-vascular endothelial growth factor (anti-VEGF) agents with immune checkpoint inhibitors (ICIs) in GI cancers, with particular emphasis on optimal sequencing strategies and unresolved challenges. We performed a narrative review of the literature, integrating preclinical studies on tumor microenvironment (TME) dynamics with key phase II/III clinical trials across hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastric/gastroesophageal junction cancers, pancreatic ductal adenocarcinoma, and other GI malignancies. The core rationale for this combination stems from complementary mechanisms: anti-VEGF therapy induces vascular normalization, enhances immune cell infiltration, and reduces immunosuppression within the TME, thereby converting immunologically "cold" tumors into "hot" tumors that are more responsive to checkpoint blockade. Clinically, the strongest evidence comes from the IMbrave150 trial, which established atezolizumab plus bevacizumab as the new first-line standard of care in advanced HCC, with promising signals also emerging in colorectal and gastric cancers (GC). Nevertheless, significant limitations persist, including overlapping toxicities, adaptive resistance mechanisms, and the lack of validated predictive biomarkers. In this regard, anti-VEGF plus ICI combination therapy offers substantial synergistic potential in GI malignancies. Future progress will depend on biomarker-driven patient selection, refined sequencing and dosing strategies, and rationally designed multi-modal regimens to maximize therapeutic benefit while minimizing harm.

Osimertinib is the standard first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC), although acquired resistance remains inevitable. The EGFR C797S mutation is a recognized on-target resistance mechanism; however, the T790M-negative/C797S-only subtype following frontline osimertinib-based combination therapy is rarely reported. We describe a 44-year-old Vietnamese never-smoking woman diagnosed with stage IV lung adenocarcinoma harbouring EGFR exon 21 L858R mutation. First-line treatment with pemetrexed-carboplatin plus osimertinib achieved a near-complete response, followed by maintenance osimertinib monotherapy. After 26 months of disease control, radiologic progression occurred with recurrent bilateral pulmonary metastases and right supraclavicular lymphadenopathy. Repeat biopsy and next-generation sequencing identified persistent EGFR L858R (VAF 13.92%) and acquired EGFR C797S (VAF 6.19%) without detectable T790M, consistent with a C797S-only resistance profile. Subsequent gefitinib plus bevacizumab therapy produced a rapid radiologic response with near-complete resolution of contralateral pulmonary lesions, suggesting retained sensitivity to reversible EGFR tyrosine kinase inhibitor-based therapy in C797S-only disease.

Immune checkpoint inhibitors have not demonstrated a survival benefit in unselected high-grade glioma populations; however, a subset of patients may achieve durable disease control. We report the case of a 30-year-old male patient diagnosed with a right temporoparietal high-grade glioma, initially classified as anaplastic astrocytoma and later evolving to astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 4 according to the 2021 World Health Organization classification. The patient underwent multiple surgical resections followed by radiotherapy with concomitant temozolomide and subsequent adjuvant temozolomide (Stupp protocol). Upon disease recurrence, he received second-line treatment with lomustine plus bevacizumab, with documented progression across successive lines of therapy. In the absence of standard therapeutic options, off-label nivolumab was initiated in November 2018 following further progression. The tumor harbored an IDH1 R132H mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Corticosteroids were discontinued prior to immunotherapy initiation. Serial magnetic resonance imaging demonstrated sustained radiological stability, without evidence of nodular enhancement or increased perfusion suggestive of recurrence. The most recent imaging assessment (March 2026) confirmed ongoing disease stability of more than seven years after treatment initiation. Treatment was well tolerated, with only mild immune-related arthralgias reported. The patient remains functionally independent, with stable mild residual hemiparesis. This case highlights the potential for prolonged disease stability under anti-Programmed cell death protein 1 (PD-1) therapy in selected patients with high-grade glioma. Although immunotherapy has not shown benefit in unselected populations, molecular features such as IDH mutation and MGMT promoter methylation, as well as the absence of corticosteroid use, may contribute to enhanced treatment responsiveness and warrant further investigation.