Clinical & Translational Oncology最新文献

Objective: To identify key aspects of the lung cancer care process and generate prioritised recommendations to optimise coordination, quality, and equitable access to diagnosis and treatment.

Methods: 24 experts from the National Advisory Committee of the Lung Ambition Alliance in Spain participated in a structured consensus process using an adapted RAND/UCLA method. The process comprised three phases: literature review (Phase I), identification of key issues (Phase II, n = 21), and prioritisation of recommendations (Phase III, n = 24). Each recommendation was scored for impact and feasibility on a 1-9 Likert scale. Agreement was defined when ≥ 66.6% of experts rated within the same range as the median; disagreement when ≥ 33.3% scored in both the 1-3 and 7-9 ranges; other cases were considered indeterminate.

Results: A total of 76 recommendations addressing 34 key aspects were identified (66% related to humanisation and perceived care quality and 34% to coordination and continuity). From which, 62 achieved agreement for impact and 14 were indeterminate; regarding feasibility, 10 reached agreement, 2 met disagreement criteria and 64 were indeterminate. In this regard, 17 high-priority recommendations (high impact and feasibility) were prioritised, covering prevention, access to diagnosis and treatment, standardisation of care processes and communication with patients. In addition, 29 recommendations were classified as high impact, relating to information systems, care coordination, prevention and awareness, equity in access to diagnostic tests and treatment, and patient care and safety.

Conclusions: Implementing these recommendations is essential to enhance equity, coordination, and quality of lung cancer care, requiring a nationwide, multi-stakeholder effort to advance towards an integrated and patient-centred model.

Objective: This study aimed to systematically evaluate the therapeutic efficacy and safety profile of concurrent hyperbaric oxygen therapy (HBOT) as an adjunct to chemoradiotherapy in patients with glioma.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive meta-analysis (PROSPERO registration: CRD420251007610). The search was performed in PubMed, Web of Science, Cochrane, EMBASE, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WanFang (inception to March 2025). Eligible studies were randomized controlled trials (RCTs) assessing tumor response, survival outcomes, quality of life (QoL), and adverse events. Subgroup analyses were performed based on HBOT pressure and session duration. Statistical analysis was performed using Review Manager version 5.3.

Results: Nine RCTs involving 837 patients with glioma were included. Pooled analyses demonstrated that HBOT significantly enhanced objective tumor response rates (odds ratio [OR] = 3.67, 95% confidence interval [CI] 2.59-5.18; p < 0.00001) and 3 year overall survival (OR = 0.52, 95% CI 0.33-0.82; p = 0.005) when combined with chemoradiotherapy. QoL scores showed marked improvement in HBOT-treated groups (mean difference = 12.33, 95% CI 10.69-13.96; p < 0.00001). Subgroup analyses on tumor response demonstrated consistent benefits across HBOT pressures and durations.

Conclusion: This meta-analysis provides evidence that concurrent HBOT with chemoradiotherapy may be associated with superior outcomes compared to chemoradiotherapy alone in glioma patients. These findings warrant verification in large-scale, multicenter Phase 3 trials.

Squamous cell carcinoma of the lip, oral cavity, oropharynx, hypopharynx, and larynx comprises the ninth most common cancer in Spain. While alcohol and tobacco use have long been the primary etiological factors, the role of human papillomavirus (HPV) in oropharyngeal cancer is increasing. Diagnoses and relapses should always be discussed by an expert multidisciplinary team. For localized stages, surgery or radiotherapy should be used as single-modality treatments, while locoregional stages require combined modality approaches. In the case of recurrent or metastatic disease, curative intent should be considered for patients with local recurrence or oligometastatic disease, while systemic treatment is recommended for all other cases. These guidelines, developed by the authors on behalf of the Spanish Society of Medical Oncology (SEOM) and the Spanish Group for the Treatment of Head and Neck Tumors (TTCC), review available evidence and provide expert recommendations based on the current literature.

Introduction: Despite receiving curative radiotherapy (RT) for localized lung cancer, relapse may occur within the first year, and 5-year survival is low. In this study, we evaluated the prognostic ability of the combination of Natural Killer-cell activity (NKA), soluble programmed death-ligand 1 (sPD-L1), and circulating tumor DNA (ctDNA) to predict a relapse within 12-month follow-up.

Materials and methods: Sixty-eight patients had blood samples analyzed from baseline, the first follow-up visit, and 6 and 9 months after treatment. NKA was measured with the NKVue® assay, sPD-L1 was measured with the Quantikine ELISA kit, and ctDNA was measured using in-house developed tumor-agnostic droplet digital polymerase chain reaction (ddPCR) assays for testing methylated loci near the genes HOXA9, TFAP2B, MCIDAS, and SP9. Chi² statistics or Fisher's exact test was used for individual markers, and ROC analyses were used for the combined markers.

Results: Baseline reduced NKA was significantly associated with experiencing a relapse within 12-month follow-up (p = 0.01). Having a positive baseline ctDNA was also significantly associated with experiencing a relapse within 12-month follow-up (p = 0.03). The combination of all four ctDNA markers, sPD-L1, and NKA had an area under the curve of 0.86 (95% CI 0.74-0.98) for predicting a relapse within 12 months of follow-up.

Conclusion: Findings from this study suggest that a combination of all six biomarkers measured at baseline may help predict the risk of relapse following curative RT for lung cancer. Larger studies with longer follow-up are needed to further verify the results.

Objective: This study aimed to explore the role of AURKB (Aurora kinase B) in the progression of cholangiocarcinoma and evaluate its correlation with pathological characteristics, survival, and cellular function.

Methods: We used immunohistochemistry, qRT-PCR, Western blot, CCK-8 cell proliferation assay, scratch assay, colony formation assay, Transwell cell migration assay, lentiviral overexpression and shRNA-mediated knockdown with validation of modulation efficiency, and subcutaneous xenograft tumor model to study the function of AURKB in cholangiocarcinoma. We also collected patients' pathological data, including pathological grade and age, to analyze the correlation with AURKB gene expression.

Results: There were significant differences in the expression of AURKB genes between different pathological grades and age groups. There is a positive correlation with pathological grade, indicating that as the malignancy of the tumor increases, the expression of the AURKB gene also increases. There is a negative correlation with age, indicating that the expression of the AURKB gene decreases as patients age. High expression of the AURKB gene is associated with significantly shortened overall survival in patients with cholangiocarcinoma. The results of the CCK-8 cell proliferation experiment showed that after infection with AURKB lentivirus, the proliferation rate of HCCC-9810 cells significantly increased, while the proliferation rate of HUCCT1 cells significantly decreased. Flow cytometry results showed that in the AURKB high expression group, the apoptosis percentage of HCCC-9810 cells was significantly reduced, while in the AURKB low expression group, the apoptosis percentage of HUCCT1 cells was significantly increased. The results of the colony formation experiment showed that in the AURKB high expression group, the number of clones of HCCC-9810 cells increased significantly, while in the AURKB low expression group, the number of HUCCT1 cell clones did not change significantly. The results of scratch assay and Transwell cell migration assay showed that in the AURKB high-expression group, the migration and invasion abilities of cells were significantly enhanced, while in the AURKB low-expression group, these abilities were weakened. Xenograft tumor experiments showed that AURKB significantly promoted tumor growth.

Conclusion: AURKB plays a key role in the progression of cholangiocarcinoma, and its high expression is associated with increased tumor malignancy, shortened survival, and enhanced cell function. Therefore, AURKB may become a potential therapeutic target for cholangiocarcinoma and provide a new research direction.

Introduction: Esophageal cancer ranks as the eighth most common cancer among human populations and stands as the sixth leading cause of cancer-related deaths. Effective treatment of esophageal tumors necessitates a comprehensive, multidisciplinary approach encompassing surgery, chemotherapy, and radiotherapy.

Method: In our series of 203 esophagectomies conducted at our institution, we identified 28 procedures (13.7%) categorized as "challenging esophagectomies" based on specific predefined criteria outlined in the text. These criteria encompassed factors such as medical comorbidities, local tumor extension, and involvement of lymph nodes. The remaining 175 patients comprised the group of "standard esophagectomies".

Results: We compared our study group with the standard group. There was no statistical difference between the two groups regarding overall 5 year survival and disease-free survival. In the "challenging esophagectomies" group, our overall 5 year survival rate was 34.2%, and the disease-free survival rate was 56, 4%. In the "standard" group, our overall 5 year survival rate was 48, 6%, and the disease-free survival rate was 58, 6%. Specifically, in the "challenging esophagectomies" group, the post-operative mortality rate stood at 8%, with major complications occurring in 33% of cases, in "standard group" the post-operative mortality rate stood at 2%, with major complications occurring in 23% of cases.

Conclusion: Despite the challenges associated with difficult esophagectomies, they play a pivotal role not only as salvage surgeries but also as a crucial component within the integrated multimodal treatment strategy. Patient selection emerges as a critical factor influencing outcomes. For this purpose, we propose a classification system of criteria and scores to define the level of complexity in this surgery.

Purpose: Drug resistance in hepatocellular carcinoma (HCC) presents a substantial therapeutic challenge. Ferroptosis has emerged as a promising therapeutic strategy, yet the mechanisms underlying resistance are not fully elucidated. Here, we highlight the tumor suppressor FAT4 as a crucial regulator of ferroptosis sensitivity in HCC.

Methods: We examined the role of FAT4 in ferroptosis in HCC using a combination of bioinformatics analysis, experiments on tissue samples from patients with HCC, and a subcutaneous xenograft tumor model in nude mice.

Results: FAT4 expression was significantly downregulated in HCC tissues, and this downregulation correlated with poor patient survival. Functionally, FAT4 loss promoted tumor growth and resistance to ferroptosis inducers (RSL3 and sorafenib), evidenced by reduced lipid peroxidation and increased levels of GPX4 and SLC7A11. Mechanistically, FAT4 deficiency was associated with activation of the PI3K/AKT signaling pathway. Notably, pharmacological inhibition of PI3K/AKT restored ferroptosis sensitivity and resensitized FAT4-deficient HCC cells to sorafenib.

Conclusions: FAT4 may enhance ferroptosis sensitivity in HCC by suppressing GPX4 and SLC7A11 expression, potentially by inhibiting PI3K/AKT signaling. Thus, this study presents FAT4 as a biomarker associated with tumor progression and a potential determinant for overcoming ferroptosis resistance in HCC.

Objective: To investigate the diagnostic value of seven lung cancer-related autoantibodies (7-AABs) and four tumor markers (4-TMs) for the early detection of lung cancer, aiming to assess their combined effectiveness compared to individual applications.

Methods: We analyzed serum samples from 110 lung cancer patients and 50 age-matched patients with benign lung nodules. Serum concentrations of 7-AABs (including SOX2, GAGE 7, CAGE, MAGE A1, P53, GBU4-5, and PGP9.5) and 4-TMs (CEA, NSE, CYFRA21‑1, and SCCA) were measured using ELISA. Receiver operating characteristic (ROC) curves were conducted to evaluate the value of combining tumor markers with serum 7-AABs for early diagnosis of lung cancer.

Results: In the malignant group, significantly elevated levels of seven autoantibodies (7-AABs), including SOX2, GAGE 7, CAGE, MAGE A1, P53, GBU4-5, and PGP9.5, as well as four tumor markers (4-TMs), namely CEA, NSE, CYFRA21‑1, and SCCA, were observed compared to the benign group, with markedly higher positivity rates for these biomarkers in the malignant group. The combined analysis of 7-AABs and 4-TMs yielded the highest diagnostic accuracy with an AUC of 0.977, significantly improving sensitivity and specificity. Notably, SOX2 and CEA showed distinct patterns across different lung cancer histological types, enhancing diagnostic differentiation. Furthermore, decision curve analysis (DCA) demonstrated the superior clinical net benefit of the 7-AABs full model over a baseline P53 model across a wide range of risk thresholds, providing a more clinically relevant metric for evaluating diagnostic performance.

Conclusion: Our findings suggest that combining autoantibodies and tumor markers may improve the early detection of lung cancer, offering a potentially non-invasive, cost-effective, and accurate diagnostic tool. However, due to the limitations of our study, such as the relatively small sample size and single-center design, these results need to be validated in larger, multi-center cohorts. This combined biomarker approach could complement existing screening methods, but further research is required to confirm its clinical utility and integration into current screening practices.

Purpose: To evaluate the impact of a patient support program (PSP) on the management of abemaciclib-related diarrhea in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) and its influence on adherence and patient-reported outcomes in routine clinical practice.

Methods: This is a multicenter, prospective, observational Spanish study in patients with locally advanced or MBC receiving abemaciclib and enrolled in the PSP, assessed over 6 months. The primary endpoint was the proportion of patients reducing or discontinuing abemaciclib due to diarrhea. The secondary endpoints included diarrhea-related temporary interruptions, diarrhea management, adherence, HRQoL, and satisfaction with the PSP. Descriptive statistics were applied and treatment modification endpoints were analyzed using Kaplan-Meier.

Results: The study included 39 patients (median age: 58 years), with a median time since diagnosis of MBC of 2 months. Diarrhea occurred in 89.7% of patients, with grade 3 events in 7.7% and no grade ≥ 4 events. Nine patients (23.1%) experienced treatment modifications due to diarrhea; however, no permanent treatment discontinuations were reported. Loperamide (over 75% of patients) and dietary modifications were the most used self-care strategies. At week 24, results from the ad hoc questionnaires showed that over 70% of the patients reported high satisfaction with all PSP aspects, and 80% were classified as treatment adherent.

Conclusions: Episodes of diarrhea were mostly graded 1-2 and no patients discontinued abemaciclib due to diarrhea. Patients reported high satisfaction with abemaciclib PSP, good adherence, and favorable quality of life, supporting the use of PSP in clinical practice.

Introduction: Head and neck cancer is a common malignancy, and its current treatments face major challenges, including recurrence, drug resistance, side effects, and high costs. Epigallocatechin gallate (EGCG) from green tea has anticancer properties, but its low stability and bioavailability limit its clinical use. These limitations may be addressed by nanocarrier-based delivery systems.

Methods: Five different sizes of sodium alginate (SA) nanoparticles (NPs) were synthesized, and EGCG was loaded into the selected particles. Characterizations of SA NPs with and without EGCG were conducted using dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), and Fourier transform infrared spectroscopy (FTIR). Furthermore, loading capacity, entrapment efficiency, and release profile of the EGCG-loaded NPs were evaluated. The cytotoxicity and cell viability were assessed (MTT and LDH) on TSCC-1 cancer cells. Moreover, cellular uptake, wound healing, colony formation, and apoptosis were also tested.

Results: The characterizations of NPs confirmed the successful synthesis of SA NPs. Two NP sizes (type 1 and type 4) were selected for EGCG loading, for which the drug release was around 39% for type 1 and 51% for type 4 NPs after 14 days. The optimal cytotoxicity on cancer cells was observed at a concentration of 80 µg/mL of NPs (type 1). A significant reduction in colony numbers was observed after treatment with these EGCG-loaded NPs compared to controls. Furthermore, the EGCG-loaded NPs could prevent cancer cell migration, with an increase in apoptosis levels in TSCC-1 cells treated with type 1 NPs (80 µg/mL).

Conclusion: It was demonstrated that EGCG-loaded SA NPs effectively inhibit the proliferation and migration and induce apoptosis in head and neck cancer cells.