Clinical & Experimental Metastasis最新文献

The encapsulated histopathological growth pattern (HGP) of colorectal liver metastases (CRLMs) has been reported as a favorable prognostic factor. However, its prognostic relevance in patients undergoing treatment for recurrence after liver resection remains unclear. This study aimed to evaluate the impact of encapsulated HGP on time to surgical failure (TSF) following liver resection, and to assess whether encapsulated HGP at initial resection is associated with outcomes after repeat resection for recurrence. We retrospectively analyzed 272 patients who underwent initial liver resection for CRLMs. HGPs were classified and their associations with postoperative outcomes were examined. 61 patients were classified as having encapsulated HGP. Patients with encapsulated HGP had significantly longer TSF after liver resection than those with non-encapsulated HGP (p < 0.01). Multivariate analysis identified encapsulated HGP as an independent factor for improved TSF (Hazard ratio: 0.35, p < 0.01). Recurrence occurred less frequently in encapsulated HGP than in non-encapsulated HGP (63.9% vs 79.2%, p = 0.02). In addition, patients with encapsulated HGP had a lower incidence of multi-organ recurrence and a higher repeat resection rate for recurrence (64.1% vs 45.6%, p < 0.01). Among patients with repeat liver resection for recurrent CRLMs, post-recurrence survival was significantly longer in encapsulated HGP than in non-encapsulated HGP (p = 0.01) and encapsulated HGP at initial resection was identified as an independent factor of favorable survival after repeat liver resection (Hazard ratio: 0.09, p = 0.04). Encapsulated HGP was associated with improved TSF following liver resection for CRLMs. HGPs at initial resection may predict survival after repeat liver resection for recurrent CRLMs.

Purpose: To identify predictive factors of response in patients with lung metastases from primary colorectal cancer (CRC) treated with stereotactic body radiation therapy (SBRT). This retrospective, single-centre study included patients with histologically confirmed primary CRC, Karnofsky performance status > 60, and age > 18 years. Between 2008 and 2023, 149 lung metastases in 88 patients were treated with SBRT. Among the treated lesions, 23 were synchronous and 126 were metachronous. According to a simplified oligometastatic classification, 9 (6%) were synchronous, 57 (38%) oligorecurrent, 76 (51%) oligoprogressive, and 7 (5%) oligopersistent. Local control (LC) at 1 and 2 years was 76.8% and 64.0%, respectively. Time to polymetastatic conversion (tPMC) at 1 and 2 years was 76.0% and 73.0%. Progression-free survival (PFS) at 1 and 2 years was 76.0% and 73.0%. Overall survival (OS) at 1 and 2 years was 80.7% and 53.0%. On multivariate analysis (MVA), lesion diameter < 16 mm was the only statistically significant favorable prognostic factor for LC. No statistically significant prognostic factors were identified for tPMC or PFS on MVA. For OS, ECOG performance status 0 and female sex were the only statistically significant favorable prognostic factors on MVA. No toxicities ≥ grade 3 were reported. Outcomes and prognostic factors reported herein refer to the present single-centre cohort. In this cohort, SBRT was feasible and was associated with acceptable toxicity and encouraging local control in lung metastases from CRC. Further studies are needed to better define predictive factors and support tailored therapeutic strategies.

Choriocarcinoma is a rare but highly aggressive gestational trophoblastic tumor, characterized by early vascular invasion and distant metastasis. While cure rates exceed 90% with chemotherapy, patients with high-risk, bulky, or chemoresistant disease have a poor prognosis. This review explores the repurposing of statins as a novel therapeutic strategy, hypothesizing that their inhibition of the mevalonate pathway critically disrupts the mechanosignaling networks that drive choriocarcinoma invasion and resistance. By depleting geranylgeranyl pyrophosphate (GGPP), statins inactivate Rho family GTPases, master regulators of cytoskeletal dynamics and cellular mechanics. In choriocarcinoma models, this step leads to the collapse of the actin cytoskeleton, abrogation of cell migration, and suppression of matrix metalloproteinase activity. Preclinical studies demonstrate that achievable concentrations of simvastatin and atorvastatin reduce proliferation, trigger apoptosis, lower β-hCG secretion, and inhibit tumor growth and metastasis, even in chemoresistant lines. GGPP, but not cholesterol, reverses these effects, confirming a prenylation-dependent mechanism. To build a translational rationale, we synthesize the epidemiology, risk factors, and pathophysiology of choriocarcinoma with statin pharmacology. The evidence suggests that statins attack a core vulnerability of this malignancy by impairing mechanotransduction, effectively reprogramming the tumor cell from an invasive to a static state. We argue for early-phase clinical trials of statins in high-risk or refractory choriocarcinoma, positioning them as a promising, low-toxicity adjunct that targets the biomechanical engines of disease progression.

By conducting colorectal cancer liver metastases (CRLM) clinical trials and analyzing treatment and prognostic targets, to provide clinical trial references for CRLM. We analyzed global and Chinese CRLM clinical trials from the Informa database, focusing on fruquintinib, sintilimab, and dual immunotherapy (CTLA-4 + PD-1). The study evaluated oncogenic biomarkers and therapeutic targets, assessing their safety by integrating data from Genotype-Tissue Expression (GTEx)-RNA, Human Protein Atlas (HPA)-RNA and HPA-Protein. Target specificity and future potential were further investigated using Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets and HPA pathology. CRLM clinical trials numbers have stabilized, focusing mainly on combination therapies, with China and the US leading in trial numbers. Single-agent trials emphasize targeted therapy, while chemo plus targeted therapy dominates combinations, reflecting a treatment model based on chemotherapy with targeted therapy breakthroughs. Chinese independently developed drugs-fruquintinib and sintilimab-and dual immunotherapy (CTLA-4 + PD-1) are still emerging, with fruquintinib used for CRLM resistant to multi-line chemo and anti-VEGF. The relevance of VEGFA and EGFR targets highlights targeted therapy's importance and supports drugs like fruquintinib. Targets analysis shows most have low safety and specificity, but CD34, FLT1, and TP53 exhibit good profiles and potential for CRLM therapy and prognosis. This study, by integrating and analyzing the clinical trial data related to CRLM, aims to conduct an in-depth investigation and evaluate the safety specificity of the treatment targets through reference.