Clinical & Experimental Metastasis最新文献

Tumorigenesis and metastasis of solid tumors are coupled to profound biophysical changes that alter cancer cells' mechanobiology, critically impacting metastatic progression. In particular, cell stiffness determines the ability of cancer cells to invade surrounding tissues, withstand shear fluid stress and evade immune surveillance. Here, we summarize the biological factors, pathological factors, and therapeutic modalities that affect the mechanobiology of cancer cells. We focus on clinically utilized chemotherapeutics and targeted therapies that show direct and indirect modulation of cancer cells' stiffness and discuss how these treatments can be used in combination with other treatment modalities to improve patient outcomes. Finally, we list the outstanding challenges in the field and provide a perspective on expanding the clinical utilization of experimental therapeutics that can act as "mechanotherapeutics" by regulating mechanobiology of cancer cells.

Brain metastases and leptomeningeal carcinomatosis (LC) are complications of advanced-stage malignancies, associated with a poor prognosis. This study aimed to evaluate the role of prognostic factors and radiotherapy (RT) treatment approaches while taking toxicity into account. We performed a retrospective study and compared clinical characteristics, prognostic factors, toxicities and outcomes in patients with (1) parenchymal brain metastases (PM) (n = 275) vs. LC (n = 35) and (2) in patients with whole brain radiotherapy (WBRT) (n = 52) vs. WBRT + boost (n = 201). We found poorer survival (OS) of the LC group compared to PM patients in univariable analysis (not in multivariable analysis). LC patients predominantly underwent WBRT only, received surgical resection before RT less frequently and had more RT discontinuations than PM patients. OS was better in the WBRT + boost group than in the WBRT only group. In patients who received WBRT + boost, the primary tumor was more often controlled, and the number of PM was lower compared to the WBRT only group. WBRT + boost was associated with higher rates of alopecia than WBRT only. Patients with LC had a worse prognosis compared to patients with PM. WBRT + boost resulted in higher toxicity than WBRT only but resulted in better OS in the presented study. WBRT + boost patients had more favorable prognostic factors prior to RT, so OS improvement is not likely due to boost. Treating brain metastases requires a careful assessment of benefits and risks. Optimal RT planning should consider prognostic factors and potential side effects individually.

Electrochemotherapy (ECT) is a local treatment combining chemotherapy with electroporation. This prospective multicentre study aimed to evaluate the efficacy of ECT in the treatment of patients with skin metastases from breast cancer and confirm whether "luminal A-like" tumors are more responsive to treatment. One-hundred and ninety-five patients were included in the analysis. 55% achieved complete response, 27% partial response (objective response OR 82%); 12% stable disease and 5% experienced progressive disease. The analysis by tumor phenotype showed a significant better response rate in Luminal A-like (p = 0.0060) and Luminal B-like (p = 0.0271) groups compared to Triple-Negative. Patients were divided into 4 groups based on the number and size of cutaneous metastases. Higher response rate was observed in patients with small (≤ 3 cm), single or multiple, metastases (OR rate 95% and 90%, respectively); larger tumors (> 3 cm) showed an OR rate of 85%. Tumor response was not affected by the presence of distant metastases, whereas patients with large cutaneous lesions and distant metastases showed a OR rate of 58%. One-year local progression-free survival (LPFS) was 86% (C.I. 82-89%). In the multivariate analysis, patient age and response to ECT were significantly associated with longer LPFS. This study confirms the efficacy of ECT in small-volume cutaneous metastases from breast cancer regardless the presence of systemic disease and suggests higher efficacy in patients with luminal A- and luminal B-like tumors. ECT can be utilized not only as a palliative measure but also as an alternative treatment for patients not eligible for standard treatments, or in combination with them. Trial registered on https://clinicaltrials.gov/study/NCT06683404 (date of registration 11/11/2024) retrospectively registered.

Accumulating evidence suggests local consolidative therapy may delay resistance and benefit metastatic NSCLC patients with oligo-residual disease (ORD) after effective systemic therapy. However, the incidence and clinical features of ORD in Alectinib-treated metastatic ALK-positive NSCLC remain unclear. We retrospectively reviewed serial scans of metastatic ALK-positive NSCLC patients treated with Alectinib. ORD was defined as the presence of five or fewer residual metastatic lesions (including the primary site) among those developed partial response as the best response after Alectinib treatment. Initial patterns of recurrence were classified as involving only residual-site recurrence (RR), only new-site recurrence (NR), or a combination of both (RNR). Among 128 patients, 62 patients had PR as the best response, among whom 18 (29.0%) had ORD. The median time to tumor volume nadir was 4.9 (range, 1.1-19.2) months and no independent predictor of ORD was found. To date, 50.0% (9/18) patients with ORD developed their initial progressive disease (PD), mostly (5, 55.6%) with only residual sites. Among the 9 PD patients, 6 patients (6/9, 66.7%) with brain lesions at baseline. Half (3/6, 50.0%) were involved in only brain residual sites. Our study found ORD is not rare in Alectinib treated ALK-positive NSCLC, with 55.6% having initial PD at originally involved sites. Similar recurrence pattern is also observed in PD patients with baseline BMs. These findings indicate that residual disease may enable the emergence of acquired resistance in both CNS and other organs, thus supporting potential clinical benefits for LCT in these ORD patients. Clinical trial number Not applicable.

Local recurrence and distant metastasis were a common manifestation of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) after neoadjuvant chemoradiotherapy (NACT). To validate the clinical value of MRI radiomic models based on deep learning for predicting the recurrence of LA-NPC patients. A total of 328 NPC patients from four hospitals were retrospectively included and divided into the training(n = 229) and validation (n = 99) cohorts randomly. Extracting 975 traditional radiomic features and 1000 deep radiomic features from contrast enhanced T1-weighted (T1WI + C) and T2-weighted (T2WI) sequences, respectively. Least absolute shrinkage and selection operator (LASSO) was applied for feature selection. Five machine learning classifiers were conducted to develop three models for LA-NPC prediction in training cohort, namely Model I: traditional radiomic features, Model II: combined the deep radiomic features with Model I, and Model III: combined Model II with clinical features. The predictive performance of these models were evaluated by receive operating characteristic (ROC) curve analysis, area under the curve (AUC), accuracy, sensitivity and specificity in both cohorts. The clinical characteristics in two cohorts showed no significant differences. Choosing 15 radiomic features and 6 deep radiomic features from T1WI + C. Choosing 9 radiomic features and 6 deep radiomic features from T2WI. In T2WI, the Model II based on Random forest (RF) (AUC = 0.87) performed best compared with other models in validation cohort. Traditional radiomic model combined with deep radiomic features shows excellent predictive performance. It could be used assist clinical doctors to predict curative effect for LA-NPC patients after NACT.

Colorectal cancer (CRC) often leads to liver metastases, which may be resistant to systemic therapy. This study assessed outcomes and toxicity of computed tomography (CT) guided high-dose-rate (HDR) brachytherapy (BRT) in oligopersistent liver metastases from CRC. The study included patients with liver metastases classified as EORTC/ESTRO-defined induced oligopersistence after multiple systemic therapy lines. Up to four persistent liver metastases per patient were treated with CT-guided brachytherapy (CT-BRT). Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The analysis focused on overall survival (OS), progression-free survival (PFS), tumor burden score (TBS), and the prognostic value of changes in metastasis size. Sixty-eight CRC patients were enrolled. During a median follow-up of 17 months, the median OS was 16 months, and the median PFS was 13 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were observed in 7%, 35%, 44%, and 6% of patients, respectively. Patients with an objective response (ORR) of 42% had longer OS and PFS than those without it. OS was affected by lymph node metastases and metastasis size reduction, while PFS was additionally influenced by the administered dose. Multivariate analysis showed OS was linked to lymph node metastases (p = 0.001) and ORR (p = 0.004), and PFS to tumor burden score (TBS) difference (p = 0.017) and post-CT-BRT single metastasis size (p = 0.026). CT-BRT for CRC oligopersistent liver metastases is effective, improving PFS and OS, with TBS difference identified as a key response parameter for future strategies.

Liver metastases, a hallmark of systemic disease, carry a poor prognosis despite advancements in systemic therapies. Stereotactic body radiation therapy (SBRT) has emerged as a promising local treatment, offering durable tumor control with minimal toxicity. However, the optimal dosimetric strategies to maximize outcomes remain an area of active investigation. This retrospective study evaluated 76 patients with 101 liver metastases treated with SBRT between November 2012 and June 2024. Dosimetric parameters were analyzed, including prescribed dose (PD) and dose metrics for planning target volume (PTV) and gross tumor volume (GTV), with doses converted to equivalent doses in 2 Gy fractions (EQD2, α/β = 10). Tumor control probability (TCP) models and survival outcomes were assessed, with a focus on the prognostic impact of dosimetric and clinical factors. Median overall survival (OS) was 33 months, with 1-year and 3-year OS rates of 74.1% and 39.4%, respectively. Freedom from local progression (FFLP) was 82.5% at 12 months. PD emerged as the strongest independent predictor of local control, with an optimal threshold of 77.44 Gy EQD2 significantly improving 1-year FFLP rates (96.8% vs. 67.2%; p = 0.007). Advanced motion management techniques, including internal breath-hold (iBH) with image-guided radiotherapy (IGRT), demonstrated superior local control outcomes. Predictive modeling confirmed PD as the most robust dosimetric metric, correlating with a high TCP and outperforming other dose metrics. Toxicity was minimal, with only 3.9% experiencing grade ≥ 3 adverse events. SBRT represents a highly effective and safe approach for liver metastases, with PD and advanced imaging emerging as pivotal determinants of tumor control. These findings underscore the importance of precise dosimetric planning and motion management in optimizing SBRT outcomes. This study provides a robust framework for personalized treatment strategies, contributing to the integration of SBRT as a cornerstone in the multidisciplinary management of liver metastases.

This study investigated hypofractionated stereotactic radiotherapy (HSRT) for resected brain metastases and how the dose-fractionation affects local control (LC) and radionecrosis (RN). We retrospectively evaluated patients with brain metastases who were treated between 2010 and 2023. Post-operative HSRT was delivered in three or five fractions. The primary objective was to determine the effect of dose escalation and fractionation on LC. Secondary objectives included identifying factors associated with RN. Statistical analyses were conducted using Chi-square or Fisher's exact tests for categorical data and Mann-Whitney U tests for continuous variables (significance level: p < 0.05). After a median follow-up of 19 months, 34 patients out of 212 (16%) had local recurrence. A biologically effective dose (BED₁₀) > 28.8 Gy was associated with better LC (p = 0.002), but no benefit was found for a BED₁₀ > 48 Gy. RN developed in 34 patients (16%). A prescription BED₁₀ > 48 Gy was associated with an increased incidence of symptomatic RN (p = 0.002). For HSRT in three fractions, a CTV D99% ≥ 29 Gy significantly improved the LC (p = 0.04), and V30Gy, V23.1 Gy, and V18Gy were significantly associated with an increased risk of RN. The fractionation was not found to affect the LC or RN. This large, retrospective cohort study on post-operative HSRT indicates that a BED₁₀ of 40.9-48 Gy (3 × 7,7 Gy or 5 × 6 Gy) to the planning target volume results in excellent LC while limiting the risk of RN. No difference in LC or RN was found for different fractionations.

This study investigates crucial genes involved in lung cancer metastasis and their interactions within a Competitive endogenous RNA (ceRNA) regulatory network using comprehensive transcriptomic data from the TCGA and GEO databases. Differential expression analysis identified ten genes associated with lung cancer metastasis, with Glypican-3 (GPC3) emerging as a key mRNA through survival analysis. A ceRNA network involving GPC3, hsa-miR-135b-3p, and FTLP3 was constructed and validated in both cellular and animal models, elucidating their roles in cell migration, invasion, and tumorigenic potential. The analysis confirmed the significance of key genes like GPC3, with the FTLP3/hsa-miR-135b-3p/GPC3 axis playing a fundamental role in lung cancer progression. Additionally, the study identified correlations between GPC3 expression, immune cell infiltration and immune checkpoints, underscoring its impact on the immune landscape of lung cancer. Overexpression of FTLP3 effectively suppressed the migratory, invasive, and metastatic abilities of lung cancer cells, demonstrating the pivotal role of the FTLP3/hsa-miR-135b-3p/GPC3 ceRNA network in modulating tumor progression and immune responses. These results underscore its potential as a therapeutic target for managing lung cancer metastasis.