Clinical & Translational Oncology最新文献

Since the 1990s, the incidence of early-onset colorectal cancer (EOCRC) and other cancers sharing risk factors with CRC, has been increasing in numerous countries, particularly in high-income settings. This increase shows a birth cohort effect, possibly due to a progressive Westernization of lifestyles resulting from exposure to risk factors during early life, with their delayed effects on incidence. Until 2016, in Spain, the increase in the incidence of EOCRC was limited to those aged 20-29 years, and this phenomenon may gradually affect older age groups, albeit later than in other Western countries. Although the absolute number of EOCRC cases is low, the increasing incidence in younger age groups indicates changes in risk factor exposure and likely heralds an increase in the future cancer burden. This increase highlights the need for research, diagnosis, treatment, public health awareness, and initiatives to mitigate the growing burden of EOCRC, but does not justify, at this time, reducing the age at which screening begins.

Background: Liver is the most common metastatic site in colorectal cancer. This study aims to evaluate the effectiveness of different machine learning (ML) models in predicting liver metastasis in CRC patients using routine biochemical tests.

Patients and methods: Cross-sectional study employed various ML algorithms for predictive modeling. The study was conducted at two academic reference centers in Ankara, Turkey: a total of 810 CRC patients diagnosed between January 2010 and December 2023 were included. The training and internal validation dataset comprised 710, and external validation dataset included 100 patients. Inclusion criteria were patients aged ≥ 18 years with a pathological CRC diagnosis, pre-treatment biochemical tests, and known initial staging. Exclusion criteria encompassed non-adenocarcinoma histologies, incomplete biochemical data, other malignancies.

Results: Logistic regression achieved the highest internal validation AUC (0.956), accuracy (0.901), and F1 score (0.936), with a sensitivity of 0.971 and specificity of 0.703. ElasticNet and Lasso regression followed closely with AUCs of 0.958. In external validation, logistic regression maintained high performance (AUC 0.951, accuracy 0.900), while the K-nearest neighbors (KNN) model achieved perfect sensitivity (1.0) with an AUC of 0.891. The optimal predictor combination included ALP, LDH, CEA, and CA-19-9.

Conclusion: Different ML models, can effectively predict liver metastasis in CRC patients using routine biochemical tests. Further refinement and prospective clinical trials are necessary to validate and implement these predictive tools in clinical practice.

Objective: Emerging evidence highlights diverse roles of FSTL1 across various malignancies, though its biological significance in bladder carcinogenesis remains unexplored.

Methods: This study systematically interrogated FSTL1 using multidimensional bioinformatics approaches-including tumor microenvironment characterization, survival pattern evaluation, and differential expression profiling-through multiple bladder cancer datasets from TCGA and GEO repositories, with subsequent experimental validation employing in vitro cellular models.

Results: Our findings demonstrate that FSTL1 exhibits significant overexpression in bladder tumors, promotes cancer cell motility through pro-migratory mechanisms, and potentially modulates key components of the tumor microenvironment.

Conclusion: FSTL1 might be a therapeutic target or biomarker for the advancement of bladder cancer.

Purpose: Cancer frequently leads to reduced cardiorespiratory fitness (CRF), altered body composition, and increased fatigue, negatively impacting quality of life. This study aimed to evaluate the effects of a multimodal oncological exercise program on CRF, body composition, functional capacity, fatigue, and quality of life in breast cancer survivors.

Methods: Seventy-four breast cancer survivors (stages IA-IIIB) were randomized to either an intervention group (n = 40), participating in a 16-week, twice-weekly multimodal exercise program (in-person or online), or a control group (n = 34). CRF was the primary outcome. Measurements were taken at baseline and post-intervention.

Results: The intervention group showed significant improvements in CRF (+22.4%), fat mass (-10%), and lean mass (+5.24%). Functional capacity and physical activity levels also increased. No significant differences were found between in-person and online delivery formats, suggesting the effectiveness of remote interventions.

Conclusions: A 16-week structured, multimodal exercise program significantly improved CRF, body composition, and physical function in breast cancer survivors. Comparable outcomes between in-person and online formats support the feasibility and utility of remote exercise programs in oncology care.

Purpose: Most patients with BRAF-mutant melanoma eventually develop resistance to BRAF/MEK inhibitors (BRAF/MEKi) and immune-checkpoint blockade. Emerging evidence from retrospective cohorts indicates promising activity from re-exposure to BRAF/MEKi after a treatment-free interval of targeted therapy (TT), probably due to tumor regression and proliferation of sensitive clones. However, there is limited prospective evidence on this approach.

Methods/patients: GEM1801 is a prospective observational study by the Spanish Melanoma Group (GEM), including 1123 patients treated at 37 centers. We conducted a descriptive analysis of baseline characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for the 24 patients who received a second course of BRAF/MEKi, either as retreatment (after relapse following prior adjuvant TT) or rechallenge (following prior progression on TT in the metastatic setting).

Results: Five patients underwent retreatment, and 19 received rechallenge. The BRAF/MEKi median free interval for retreatment was 20.9 months (range 12.4-57.3), with an ORR of 20%, and median PFS and OS of 5.5 and 8.4 months, respectively. The median free interval of TT for rechallenge was 6.8 months, with an ORR of 31.6%, and median PFS and OS of 5.7 and 7.6 months. Patients with ECOG ≤ 1 experienced longer survival with rechallenge (8.2 vs 4.3 months; HR 9.07 [95% CI 1.37-59.8]; p = 0.022).

Conclusion: Retreatment or rechallenge with BRAF/MEKi in the metastatic setting has shown clinical activity in patients with metastatic melanoma who lack therapeutic alternatives to prolong survival. Therefore, in our experience, it may represent a valid therapeutic strategy for selected patients.

Clinicaltrials: GOV: NCT03605771 (REGISTRATION DATE: 20-07-2018): NCT03605771.

Ovarian cancer is one of the most lethal cancers among gynecological tumors, with most cases diagnosed at an advanced stage. Despite advancements in medical science, current therapeutic options remain somewhat constrained, leading to a persistently high mortality among patients. The tumor microenvironment (TME) critically drives ovarian cancer progression by orchestrating tumorigenesis, metastasis, and chemoresistance via intercellular crosstalk, metabolic reprogramming, and immunosuppression. Tumor-associated macrophages (TAMs) and platelets are pivotal components of the ovarian cancer immune microenvironment. These components facilitate critical oncogenic processes, including tumor cell dissemination, immune evasion, and chemoresistance. Both TAMs and platelets have emerged as promising therapeutic targets. Furthermore, bidirectional crosstalk between platelets and TAMs dynamically shapes the immunosuppressive TME. This review synthesizes the roles and mechanisms of TAMs and platelets in ovarian cancer progression, discusses emerging therapeutic strategies targeting these components, and establishes a framework for advancing novel therapies in ovarian cancer treatment.

Metastatic castration-resistant prostate cancer (mCRPC) remains a formidable clinical challenge, with conventional therapies yielding limited efficacy. Immunotherapy combined with radiotherapy (iRT) holds synergistic potential for mCRPC, though mechanistic complexities-including dose-dependent immunomodulation, temporal sequencing dynamics, and tumor microenvironment (TME)-mediated resistance-require further clarification. Radiotherapy enhances tumor immunogenicity by inducing antigen release, improving HLA expression, and activating T cells, thereby potentiating immunotherapy. Clinical trials validate iRT's efficacy: for example, ¹⁷⁷Lu-PSMA-617 plus standard care prolonged median progression-free survival (PFS) from 3.4 to 8.7 months and overall survival (OS) from 11.3 to 15.3 months in PSMA+ mCRPC patients. In addition, avelumab combined with stereotactic ablative radiotherapy achieved a median PFS of 8.4 months and OS of 14.1 months in treatment-refractory mCRPC. Key challenges include optimizing treatment parameters (e.g., dosing, sequencing) and identifying predictive biomarkers. While early results are promising, ongoing research aims to refine iRT protocols and translate mechanistic insights into personalized strategies. This review synthesizes current advances, highlighting synergistic mechanisms, clinical evidence, and unresolved translational hurdles.

Epigenetic dysregulation has been identified as a key hallmark of cancer. Histone acetylation is a major factor in regulating tumour formation among these alterations. Acetylation of histone is balanced by the coordination between the HDACs and HATs enzymes. HDACs remove an acetyl group from the histone, leading to chromatin condensation and aiding in oncogenesis. Studies have established HDACIs as potential therapeutics for the treatment of various malignancies. Therefore, the pharmacokinetics and pharmacodynamics of HDACIs need a thorough understanding. HDACIs have been approved for tackling haematological malignancies, but their role in solid tumours as monotherapeutic agents is questionable. In this review, we have discussed the functions of HDACs in tumourigenesis. Additionally, we attempt to deliver a thorough analysis of the HDACIs under clinical trials and address the synergistic effect of combination therapies with FDA-approved drugs to overcome the limitations of monotherapy, offering a novel perspective on improving cancer treatment outcomes.

Reirradiation in gynecological cancer presents significant clinical challenges due to the complexities of prior treatments and anatomical constraints. In response to the lack of standardized protocols, a Delphi-based consensus was conducted by the GINECOR group of the Spanish Society of Radiation Oncology (SEOR) and the Spanish Society of Medical Physics (SEFM). A multidisciplinary panel of radiation oncologists and medical physicists developed expert-based recommendations through a structured tow-round process. Key findings emphasize the pivotal role of brachytherapy for central and vaginal recurrences and support the use of stereotactic body radiation therapy (SBRT) for nodal disease. Other modalities such as intraoperative radiotherapy and proton therapy are considered in specialized settings. The consensus highlights the importance of individualized treatment planning, especially regarding cumulative dose constraints and organ-at-risk tolerance. Futhermore, it underscores the need for further research and prospective clinical trials to refine treatment indications and optimize outcomes in this clinical context.