Frontiers in Oncology最新文献

Objective: Cervical cancer faces significant pathological diagnosis challenges including pathologist shortages, subjective interpretation, and inconsistent detection rates. This systematic review evaluates AI technology's application status, development level, and key challenges in cervical cancer pathological diagnosis.

Methods: A systematic literature review across three databases (PubMed/MEDLINE, Scopus, Web of Science) covering January 2015 to August 2025. Search terms included "artificial intelligence," "cervical cancer," "pathological diagnosis," "histopathology," "machine learning," and "deep learning." Studies involving AI applications in cervical cancer pathological diagnosis were included, encompassing histopathological, immunohistochemical, and molecular pathological diagnoses. Animal studies, cytological screening, and genomic analyses unrelated to pathological diagnosis were excluded.

Results: From 1,847 identified articles, 56 studies were included. AI technology demonstrated substantial potential in histopathological image analysis, diagnostic support systems, and accuracy validation. Deep learning architectures, particularly convolutional neural networks, achieved 92-98% diagnostic accuracy while reducing processing time from 8-15 minutes to 1-3 minutes per case. However, significant implementation challenges persist including standardization issues, limited clinical validation, and substantial infrastructure costs.

Conclusion: AI technology shows broad application prospects in cervical cancer pathological diagnosis, potentially alleviating pathologist shortages and improving diagnostic standardization. The technology particularly suits cervical cancer prevention in resource-limited regions, supporting global elimination goals, though standardization and validation challenges require addressing before widespread clinical implementation.

Aim: Breast cancer is the most prevalent form of cancer among females and carries a substantial societal impact. DSN1, a component of the MIS12 complex, plays a critical role in centromere assembly, distribution, and stability. While DSN1's role in tumors has been investigated, its specific function in breast cancer remains unclear.

Methods: First, we utilized bioinformatics techniques to explore DSN1 expression in breast cancer and conducted functional enrichment and correlation analyses. Subsequently, we assessed the clinical relevance of DSN1 through immunohistochemistry. Furthermore, we examined how DSN1 affects the growth of breast cancer cells by conducting CCK8 and colony formation tests. Cell cycle and apoptosis changes were assessed using flow cytometry. Moreover, we examined key genes related to cell cycle and apoptosis to further elucidate the underlying mechanisms. Finally, we screened potential drugs targeting DSN1 by drug sensitivity and molecular docking analyses.

Results: Bioinformatics analysis revealed that DSN1 is highly expressed in breast cancer, making it a potential diagnostic marker. Functional enrichment analysis indicated that the DSN1- overexpressed group was enriched in cell proliferation-related pathways. Cellular experiments confirmed that DSN1 promotes breast cancer proliferation by affecting cell cycle pathways, involving key molecules such as CCNB1, CCND1, CKD1, CDK4, and CDK6. Drug sensitivity analysis showed that the DSN1 high expression group was resistant to drugs such as Epirubicin, Cyclophosphamide, Ribociclib, and Palbociclib, but relatively sensitive to tamoxifen and lapatinib.

Conclusions: DSN1 contributes to breast cancer progression by modulating cell cycle pathways, making it a potential diagnostic and therapeutic target with clinical applicability.

Introduction: Glioblastoma is the most common malignant brain tumor. Standard treatment involves surgical resection with radiotherapy and chemotherapy, but tumors in deep or eloquent brain regions often limit surgical options. Laser interstitial thermal therapy (LITT) and photodynamic therapy (PDT) have emerged as minimally invasive alternatives.

Materials and methods: This systematic review followed PRISMA 2020 guidelines. Study quality was assessed using the Newcastle-Ottawa Scale, ROBINS-I, and RoB 2 tools. Data extraction included tumor characteristics, survival outcomes, quality of life, treatment response, and complications.

Results: A total of 1,468 records were identified; after screening and eligibility assessment, 11 studies involving patients aged 16-86 were included. LITT was found to be safe and effective for recurrent glioblastoma, with 12-month survival rates up to 65%, particularly in patients with small, deep-seated tumors and high Karnofsky scores. PDT, when combined with gross total resection, reduced postoperative edema and improved survival but was associated with higher rates of distant recurrence.

Discussion: LITT and PDT are promising minimally invasive strategies for glioblastoma management, each with distinct mechanisms and clinical roles. LITT is most beneficial for deep-seated, unresectable tumors and may enhance tumor immunogenicity. PDT, though limited by shallow light penetration, effectively eliminates residual tumor cells post-resection and may reduce local recurrence. However, variability in patient selection, tumor features, and treatment protocols across studies limits direct comparison. Adverse events, while generally manageable, require close monitoring. Current evidence supports the adjunctive use of both therapies, but large-scale randomized trials are needed to confirm efficacy, standardize protocols, and explore combinations with immunotherapy.

Conclusion: LITT and PDT are safe and effective adjunct therapies for glioblastoma patients, improving survival and reducing complications in selected patients. LITT mostly benefits patients with small, deep, or unresectable tumors, while PDT enhances outcomes when combined with gross total resection. Further large-scale trials are needed to optimize their use and refine patient selection.

Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis, particularly in patients with extensive-stage disease (ES-SCLC). Although the incorporation of immune checkpoint inhibitors (ICIs) into first-line chemotherapy has modestly improved survival, long-term disease control remains rare. Central airway obstruction (CAO), a common complication of advanced SCLC, often leads to respiratory failure and interruption of systemic therapy, further compromising outcomes. We report the case of a 65-year-old man diagnosed with ES-SCLC based on endobronchial ultrasound-guided transbronchial needle aspiration. The patient initially responded to platinum-etoposide chemotherapy but experienced treatment interruption during the COVID-19 pandemic, followed by recurrent malignant airway obstruction and respiratory failure. Repeated bronchoscopic interventions, including tumor debulking, airway stent placement, electrocautery, laser therapy, and cryotherapy, were performed to restore airway patency and stabilize respiratory function, thereby enabling the resumption and continuation of systemic antitumor therapy. Subsequently, chemotherapy combined with the programmed cell death protein-1 (PD-1) inhibitor serplulimab was initiated, followed by maintenance immunotherapy. After local bronchoscopic ablation, transient elevations in circulating inflammatory cytokines, including interleukin-6 and interleukin-8, were observed, suggesting systemic immune activation. The patient achieved sustained partial remission, with preserved airway patency and good general condition. At five years after initial diagnosis, the patient remains alive with stable disease and without severe treatment-related adverse events. This case highlights the potential role of integrating bronchoscopic local interventions with systemic chemotherapy and immunotherapy to enable durable disease control and long-term survival in selected patients with ES-SCLC complicated by central airway obstruction.

Introduction: Glioma stem cells (GSCs) have been implicated in radio- and chemotherapeutic resistance of glioblastoma (GBM). Therapeutic targeting of GSCs has shown promise in immunocompromised rodent models but have not been translated into effective therapies for human patients. These failures underscore the translational limitations of rodent models and highlight the need for complementary models that accurately and reliably predict therapeutic translation for human HGG. Spontaneous canine high-grade gliomas (HGGs) may provide a complementary translational model for human therapeutic development. While described in canine HGGs, little is known about canine glioma stem cell biology.

Methods: Here, we evaluated cellular metabolism, cytosine modifications, gene expression, and functional tests of malignancy to interrogate differences between canine high-grade astrocytoma-derived glioma stem-cell like cells (GSLC) and a traditional non-stem cell glioma cell line following exposure to hypoxia.

Results: Hypoxia increased oxygen consumption rates in GSLCs and augmented features of malignancy in GSLCs. We observed variable cytosine modifications and mRNA expression across cell lines, and our data did not correlate cytosine modification patterns with oxygen consumption capacity following hypoxia. However, we did demonstrate a positive correlation between up-regulated genes in human GBM GSCs and hypomethylation of orthologous canine genes following hypoxia.

Discussion: Together, these data support that hypoxia enhances distinct stem-like traits in canine astrocytoma GSLCs, similar to human GSCs.

Objective: To evaluate the advantages and disadvantages of single-field versus multi-field optimization in the clinical implementation of pencil beam scanning (PBS) proton lattice radiotherapy (LRT).

Methods: LRT proton plans were created retrospectively for 12 patients with head-and-neck, thoracic, or abdominal bulky tumors, averaging a gross tumor volume (GTV) of 1011.1 cc (between 333 cc and 3546 cc). The plans were developed in the RayStation treatment planning system (version 2023B), adhering to established consensus guidelines for prescription dose and planning goals. For each plan, 6-8 vertices with an average diameter of 1.4 cm were positioned approximately 3.5 cm apart. The prescription was 18 Gy to each vertex and 3 Gy to the GTV. Single-field optimization (SFO) and multi-field optimization (MFO) techniques were employed. The dosimetric parameters of GTV Dmean, D95%, generalized equivalent uniform dose (gEUD a=-10), vertex D90%, peak-to-valley dose ratio (PVDR), and skin D1% were used for plan quality assessment. Plan robustness was also investigated by comparing dose metrics between the nominal and second worst-case scenarios in the robust analysis.

Results: For all 12 patients, both SFO and MFO plans achieved a PVDR close to 4 across the three treatment sites. No significant differences in primary dose metrics were observed between SFO and MFO plans, except for skin D1%, which was reduced by an average of 25% in the MFO plans (p<0.05). Robustness evaluation indicated larger deviations in PVDR, GTV Dmean, and skin D1% between nominal and second worst-case scenarios for MFO plans compared to SFO (p<0.05).

Conclusion: Both SFO and MFO techniques can be reliably implemented with current proton beam quality standards and advanced treatment planning algorithms. While SFO offers better plan robustness in maintaining the originally optimized metrics under various treatment-related uncertainties, MFO enhances the ability to spare critical organs.

Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive malignancy, with a poor prognosis and limited therapeutic options, particularly in advanced stages with brain metastases. Long-term survival in metastatic LCNEC is exceedingly uncommon.

Case presentation: We report a case of a 32-year-old female diagnosed with stage IV pulmonary LCNEC in 2015. Over a 10-year disease course, she underwent a comprehensive, multimodal treatment approach, including chemotherapy, targeted therapy, two craniotomies, whole-brain radiotherapy, and resection of pelvic metastases. Serial imaging revealed prolonged stability of pulmonary lesions and dynamic control of brain metastases. Longitudinal monitoring of pro-gastrin-releasing peptide (PRO-GRP) levels showed a strong correlation with tumor progression. Molecular profiling identified RB1 and SDHD copy number loss, among other alterations. The patient remains alive 115 months after diagnosis and over 50 months after initial brain metastasis, representing one of the longest documented survivals in metastatic LCNEC.

Conclusion: This case demonstrates that prolonged survival in stage IV LCNEC with brain metastases is possible through individualized multimodal therapy and close longitudinal monitoring. It underscores the potential value of molecular profiling and biomarkers like PRO-GRP in treatment planning and disease tracking.

Introduction: Tracheal adenoid cystic carcinoma (ACC) is a rare malignancy with a slow but relentless course. Surgical resection is the standard treatment, but in cases where surgery is not feasible, definitive radiotherapy serves as an alternative approach.

Case description: We report the case of a 55-year-old female patient diagnosed with unresectable ACC of the left main bronchus near the carina. Due to the high surgical risk of pneumonectomy with carinal reconstruction, the patient was treated with definitive intensity-modulated radiation therapy (IMRT) using a simultaneous integrated boost technique. A total dose of 69 Gy in 30 fractions was delivered. The patient tolerated the treatment well without significant acute or late complications. Follow-up imaging demonstrated a durable local response, with near-complete remission of the primary tumor. Ten years post-treatment, the patient remains free of local recurrence, with slow-progressing pulmonary metastases under surveillance.

Conclusion: This case highlights the potential of definitive IMRT using a hypofractionated dose scheme in achieving long-term local control for unresectable tracheal ACC.

Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized cancer treatment, yet its application remains limited by high costs, safety concerns, and challenges in solid tumors. Natural killer (NK) cells offer a promising alternative due to their innate tumor-killing capacity, diverse cell sources, lower risk of graft-versus-host disease and cytokine release syndrome, and potential for "off-the-shelf" production. This review synthesizes recent advances in CAR-NK, focusing on NK-specific CAR engineering strategies, preclinical models across hematological and solid malignancies, and the latest clinical trials up to 2025. We highlight distinctive CAR-NK optimization approaches, such as integration of Fc-binding domains, cytokine armoring, and strategies to overcome tumor microenvironment mediated resistance, that distinguish CAR-NK from CAR-T platforms. Key challenges, including insufficient in vitro expansion, manufacturing scalability barriers, in vivo persistence, and the immunosuppressive effects of the tumor microenvironments (TME), as well as their corresponding potential technical solutions, are critically analyzed. By integrating the latest translational insights, this review aims to provide a forward-looking perspective on CAR-NK as a next-generation immunotherapeutic modality.