Clinical & Translational Oncology最新文献

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.

Background: Colorectal cancer (CRC) is considered one of the major global health concerns, often managed with surgical interventions followed by stoma creation. Although stomas are lifesaving, they can significantly affect patients' physical and psychological well-being, particularly their quality of life (QoL). The prevalence of stoma-related complications and psychosocial challenges highlights the need for multidisciplinary research to inform patient care.

Aim: This study aims to identify the clinical and psychosocial factors that affect QoL among CRC patients with a stoma.

Patients and methods: A cross-sectional study was conducted on 84 CRC patients with a colostomy or ileostomy. We used a validated questionnaire assessing QoL, including sleep behavior, self-image, and sexual and social activities. Demographic and tumor data were collected and analyzed using a multiple linear regression model to determine associated factors for stoma-related low QOL in CRC patients (measured as a continuous Stoma-QOL score).

Results: CRC patients with a stoma showed low QOL with high frequencies reported on several questionnaire items related to anxiety, social interactions, and body image concerns. 61% of patients responded 'always' to the item indicating reduced sexual attractiveness, and 47% were frequently concerned about family stress. Multivariate linear regression analysis revealed that low social status, temporary stoma, and longer baseplate retention time were associated with lower QoL, while advanced cancer stage and colostomy were linked to better QoL.

Conclusion: Despite the mandatory need for a stoma in CRC patients who underwent surgical intervention, it significantly impacts the psychological well-being, with various sociodemographic and clinical factors affecting QoL. Individualized education and follow-up may enhance stoma adaptation and patient well-being.

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumors that appear as metastases for which a standard diagnostic work-up fails to identify the tissue of origin. There is now high-level evidence showing that actionable genomic alterations should be routinely determined in patients with CUP to enable molecularly guided therapy as appropriate. In this guideline (updated in 2025), we summarize diagnostic processes and therapeutic options for CUP, as well as new developments in molecular medicine that will help to improve the poor outcomes associated with this unique disease entity.

Background and purpose: Cervical carcinoma, exhibits distinctive hallmarks, including sustained proliferation and replicative immortality. Ki-67 is a well-established marker of cell proliferation, while the presence of telomerase, particularly its catalytic subunit human Telomerase Reverse Transcriptase (hTERT), is associated with the uncontrolled proliferation seen in many cancers.

Method: The expression of Ki-67 and the hTERT component of telomerase was investigated in various cervical lesions. Tissue microarray blocks were prepared from a total of 586 paraffin-embedded cervical tissue specimens received at Sultan Qaboos University Hospital and Royal Hospital between January 2010 and December 2018. Immunohistochemistry was performed to assess the expression of both markers.

Results: The results showed that Ki-67 expression increased significantly with the severity of cervical lesions (p < 0.05), with SCC displaying high Ki-67 expression in more than 50% of tumor cells. However, statistical analysis revealed no significant correlation between Ki-67 expression and lesion prognosis. On the other hand, hTERT showed a significantly higher expression in low-grade LSIL (p < 0.05), whereas high-grade squamous intraepithelial lesions and SCC predominantly showed negative hTERT expression. hTERT staining was mainly localized to the nucleus across all cervical lesions, with some cytoplasmic and combined expressions, and it was generally of mild intensity; however, this correlation was not statistically significant. Additionally, the percentage of hTERT-positive cells was mostly below 10% in all lesion types, with no statistically significant differences observed.

Conclusion: Our findings suggest that the use of Ki-67 and hTERT component of telomerase combination might not be sufficient to predict the prognosis of cervical lesions. Nonetheless, the observed expression patterns of each biomarker indicate a potential role in early carcinogenesis.

Background: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors (SSTR). Despite robust trial and real-world data, heterogeneity persists regarding patient selection, therapeutic sequencing, and follow-up strategies.

Methods: A Delphi consensus was conducted by the Galician Multidisciplinary Group on Neuroendocrine and Endocrine Tumors (GGNET). Ten experts in oncology, endocrinology, nuclear medicine, and radiology participated. 29 clinical statements were developed after a systematic review and rated using a 4-point Likert scale. Consensus was defined as ≥ 70% agreement.

Results: Consensus (defined a priori as ≥ 70% agreement) was achieved for all statements although the level of agreement varied across domains. PRRT was endorsed for patients with unresectable or metastatic, progressive, well-differentiated GEP-NETs (grades 1-3, Ki-67 ≤ 55%) with confirmed SSTR expression. SSTR-targeted imaging (PET or scintigraphy) was considered mandatory for eligibility, with PET identified as the preferred modality. [¹⁸F]-FDG-PET was recommended selectively as a complementary prognostic tool in higher-grade tumors, rapid progression, or discordant imaging. Multidisciplinary tumor board review was universally supported. Guidance was provided on treatment administration, including standard dosing, renal protection, hematologic monitoring, and individualized risk assessment. Routine interim imaging was not recommended. Structured follow-up with CT/MRI was endorsed, with indication-driven use of SSTR or FDG-PET and limited routine value of non-specific biomarkers. Functional biomarkers, such as 5-HIAA and peptide hormones, retained utility in functioning tumors.

Conclusions: This Delphi consensus provides pragmatic, multidisciplinary, and evidence-informed guidance to harmonize routine clinical practice in the use of PRRT for well-differentiated, SSTR-positive NETs. The proposed statements and the algorithm aim to harmonize practice across centers, reduce variability in care, enhance safety, and ultimately improve patient outcomes.

Objective: This study sought to retrospectively investigate the clinical utility of a radiomics nomogram based on MRI for stratifying HER2 expression status in breast tumors into three categories.

Materials and methods: This study recruited females from two centers who had a pathological confirmation of invasive breast cancer (BC) between January 2024 and March 2025. Based on the T2-weighted image (T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), radiomic features were extracted. Feature selection was subsequently performed by analysis of variance (ANOVA), Spearman's correlation analysis, the Wilcoxon test, and the least absolute shrinkage and selection operator (LASSO) method. Two classification tasks were determined: Task 1, differentiating HER2 overexpression (positive) from HER2-low/zero (negative) tumors and Task 2, distinguishing HER2-low from HER2-zero tumors. To pinpoint clinicopathological markers associated with the HER2 status, univariate and multivariate logistic regression analyses were carried out. Moreover, a nomogram, integrated by key MRI radiomics features, was crafted. Model efficacy was gauged using the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy. Clinica applicability was examined via decision curve analysis (DCA).

Results: The integrated model incorporating T2WI and DCE-MRI features achieved better results than models using only one modality. In Task 1, the nomogram demonstrated good calibration and discrimination capabilities, with an area under the curve (AUC) of 0.82 and 0.80 in training and validation sets. For Task 2, the nomogram achieved an AUC of 0.88 (training) and 0.80 (validation).

Conclusions: The radiomics nomogram provides a non-invasive choice for predicting HER2 expression in BC, which may assist in personalized treatment planning.

Purpose: Dynamic changes in spleen volume (SpV) may reflect immune and hemodynamic alterations in hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic significance of SpV dynamics in patients with unresectable HCC (uHCC) treated with tislelizumab plus lenvatinib.

Methods: We retrospectively analyzed 103 patients with uHCC treated with tislelizumab plus lenvatinib between June 2021 and June 2025. SpV was measured on contrast-enhanced CT at baseline and approximately 3 months post-treatment using AI-assisted segmentation with manual correction. The absolute SpV change (ΔSpV) and monthly SpV change rate were calculated. The optimal cut-off values were identified via maximally selected rank statistics. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models.

Results: Post-treatment SpV increase was observed in 65% of patients and was associated with shorter progression-free survival (PFS). Both ΔSpV and SpV change rate were independent predictors of PFS (HR for ΔSpV: 1.005, P = 0.01; HR for change rate: 1.02, P < 0.00). Cut-off values of 23.81 cm³ (ΔSpV) and 8.24 cm³/month (change rate) significantly stratified patients into distinct PFS risk groups (11.6 vs. 25.5 months, both P < 0.05). Three-month landmark analysis revealed that a SpV change rate ≥ 8.24 cm³/month predicted significantly shorter PFS within the first 3 months (P = 0.039), while a ΔSpV ≥ 23.81 cm³ was associated with significantly poorer PFS after 3 months of treatment (P = 0.040). Baseline portal hypertension and larger tumor size correlated with greater SpV increases.

Conclusion: SpV dynamics provide a noninvasive imaging biomarker for identifying uHCC patients at elevated risk of progression during tislelizumab plus lenvatinib therapy. Incorporating these volumetric metrics into routine imaging may enhance prognostic assessment and guide risk-adapted patient management.

Background: Lung adenocarcinoma (LUAD) is a prevalent and deadly form of lung cancer. Exercise has been shown to inhibit LUAD progression, yet the underlying molecular mechanisms remain unclear. The transcription factor POU2F2 has been implicated in LUAD tumorigenesis, but its precise role and regulatory targets have not been fully elucidated.

Methods: POU2F2 expression in LUAD cell lines (HCC4006, Calu-3, NCI-H2009) and normal lung epithelial cells (BEAS-2B) was assessed by qRT-PCR and Western blot. Functional assays (CCK-8, EdU, flow cytometry, TUNEL) were performed following shRNA-mediated knockdown of POU2F2 or SPOCD1 and upregulation of POU2F2. Mechanistic studies included bioinformatics, dual-luciferase assay, ChIP, DNA pull-down, and Western blot. In vivo tumor growth was evaluated via xenograft models with Ki67 IHC.

Results: Exercise suppressed POU2F2 expression, which was otherwise elevated in LUAD cells. Knockdown of POU2F2 or its downstream target SPOCD1 reduced proliferation and increased apoptosis. Mechanistically, POU2F2 directly bound to and activated the SPOCD1 promoter, thereby enhancing PI3K/AKT pathway signaling. Rescue experiments confirmed that SPOCD1 mediates POU2F2's oncogenic effects. In vivo, POU2F2 knockdown inhibited tumor growth and Ki67 expression.

Conclusions: Exercise suppresses LUAD progression by downregulating POU2F2, thereby disrupting the POU2F2-SPOCD1-PI3K/AKT axis. This pathway plays a critical role in LUAD cell survival and may serve as a promising therapeutic target.

Key points: Exercise inhibits LUAD progression by downregulating the oncogenic transcription factor POU2F2. The POU2F2-SPOCD1 axis exerts its oncogenic function by activating the PI3K/AKT pathway. The POU2F2-SPOCD1 axis may represent a promising therapeutic target for LUAD.