Clinical & Experimental Metastasis最新文献

Metastatic cancer has been considered uniformly fatal in the past with very poor outcomes for most cancer sites. However, novel systemic and targeted therapies have rendered unique responses with longer survival across several cancer types and metastatic sites. In addition, improved surgical experience and safety with good outcomes has made metastasectomy as an alternative curative-intent treatment across multiple organ sites. The pancreas is an uncommon site for metastasis, even if >30 different primary tumor entities have been described to metastasize to the pancreas. More than half of all resected metastasis in the pancreas are from renal cell carcinoma (RCC). RCC demonstrates a particular capacity to metastasize to nearly any site in the body-including uncommon sites like the tongue, salivary glands, spleen, testes, and pancreas-and, have remarkable plasticity and specific molecular trajectories with clinical implications. Cancer cells have a propensity to metastasize to specific organ sites, such as the lungs, liver or skeleton, called "organotropism" and the inherent tumor biology as well as the concept of 'oligometastatic' disease is still controversial and conflicting. Pancreatic metastasis has a very different biology from other RCC metastatic sites. Clinical observations suggest an indolent biology that warrants further investigation. Survival times are very long and approaching up to 10 years in recent series. In this paper we discuss the specific situation of pancreatic metastasis from RCC, the relation to oligometastasis and organotropism and how this can be viewed as a model to better understand cancer biology.

Background: Neutrophil infiltration in tumors and tumor-draining lymph nodes (TDLNs) influences oral squamous cell carcinoma (OSCC) progression and metastasis. Neutrophils can exhibit an immunosuppressive phenotype, with CD18 and CD36 potentially linked to this. This study characterizes CD18/CD36 expression on neutrophils from different OSCC microenvironments and their association with metastasis.

Methods: We assessed CD18 and CD36 expression on neutrophils from OSCC tumors, TDLNs, and healthy lymph nodes using flow cytometry. We also examined whether co-culture with the CAL27 oral cancer cell line influenced CD18/CD36 expression in blood neutrophils from healthy donors.

Results: Neutrophils from OSCC tumors and TDLNs exhibited higher CD18 expression than those from healthy lymph nodes, while CD36 was increased only in OSCC tumors. The highest CD18/CD36 expression was observed in metastasis. In vitro co-culture with CAL27 cells prolonged neutrophil survival and enhanced CD18 expression but had no impact on CD36 levels.

Conclusion: Increased CD18/CD36 expression in OSCC neutrophils, particularly in metastasis, suggests their role in tumorigenesis. The elevated CD18 expression in TDLNs highlights enhanced neutrophil-lymphocyte interactions during cancer progression. Our in vitro findings underscore the ability of cancer cells to modulate neutrophil lifespan and phenotype, though this may not fully replicate the tumor microenvironment. This study provides insight into neutrophil contributions to OSCC progression and supports their potential as therapeutic targets.

Mediastinal oligometastases represent a clinical and technical challenge, due to the need to combine optimal treatment with the risk of severe toxicity. In this retrospective multicentre experience, we report the data of a cohort of patients treated with stereotactic body radiotherapy (SBRT) for oligometastatic mediastinal lymph-nodes. Inclusion criteria of the study were: written informed consent for the treatment, ECOG PS ≤ 2, diagnosis of oligometastatic mediastinal lymph-nodes up to 5 lesions being the mediastinum the only active site of disease, patients treated with radiotherapy schedules applying a minimum 6 Gy per fraction. Prior radiotherapy to the mediastinum was not considered as an exclusion criterion. A total of 63 lymph-node metastases in 49 patients with median age of 69.5 years (range 47-83 years) received SBRT between September 2020 and April 2024, for a median total dose of 30 Gy (range 21-50 Gy) in 5 fractions (range 3-5). With a median follow-up of 15 months, 1- and 2-year local control rates were 96.9% and 91.8%, while distant progression-free survival rates were 66.7% and 30.2%. Median time to new systemic therapy was 12 months, while 1- and 2-year polymetastatic-free survival (PMFS) and overall survival (OS) were respectively 78% and 64%, and 86.2% and 75.8%. At statistical analysis, patients who develop a further oligoprogression treated with a second course of SBRT have a longer time to new systemic treatment (p = 0.017), being genitourinary and gynecological malignancies related to improved PMFS and OS at univariate analysis. Only one late G3 adverse event was observed, consisting of dysphagia treated with intravenous steroids. In our series, SBRT for oligometastatic mediastinal lymph-nodes was safe with a single G3 late adverse event, with promising results in terms of local control and time to activation of a new systemic therapy.

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.