Frontiers in Oncology最新文献

Glioneuronal tumor with ATRX alteration, kinase fusion, and anaplastic features (GTAKA) is a rare pathological subtype of the central nervous system, with currently limited research available. This case report details a 37-year-old woman who developed a new intracranial tumor 22 years after initial treatment (surgical resection and adjuvant radiotherapy) for a WHO grade 2 astrocytoma. The new lesion was histopathologically diagnosed as GTAKA, a distinct glioneuronal tumor entity, following which the patient received adjuvant radiotherapy with concomitant temozolomide chemotherapy. Although this pathological type is rare, the immunohistochemical and molecular findings, combined with the therapeutic approach in this case, contribute to a deeper understanding of the disease.

Introduction: To evaluate the safety and efficacy of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) in patients with pulmonary dysfunction.

Methods: A retrospective study was conducted involving 1,635 patients who underwent MWA between January 2018 and December 2024. The observation group consisted of 42 patients with moderate-to-severe pulmonary dysfunction, defined as maximal voluntary ventilation (MVV) < 70% or forced expiratory volume in one second (FEV₁) < 60%. The control group included 106 patients with normal lung function. The primary study endpoints were postoperative complications and length of hospitalization, while the secondary endpoint was progression-free survival (PFS).

Results: The observation group had a median follow-up time of 25.5 months and a median survival period of 39 months, with 1-year and 3-year survival rates of 94.9% and 68.7%, respectively. The control group had a median follow-up time of 22 months and a median survival period of 44 months, with 1-year and 3-year survival rates of 98.1% and 72.3%, respectively. The median length of hospitalization was 6 days in both groups. The incidence of adverse reactions was 42.86% in the observation group and 33.96% in the control group, with no statistically significant difference between the two groups (p > 0.4099). In the observation group, statistically significant differences were identified with respect to smoking history, emphysema, and severe pulmonary dysfunction (p < 0.05). Univariate analysis indicated that patients with FEV₁ (percentage of predicted value) < 55% and FEV₁/VC < 70 were more prone to postoperative complications; however, multivariate analysis revealed no statistically significant differences.

Discussion: MWA represents a safe, effective, and potential alternative therapeutic option for patients with stage I NSCLC and moderate-to-severe pulmonary dysfunction.

Background: Bevacizumab, a VEGF-A inhibitor widely used in ovarian cancer, is associated with kidney adverse effects ranging from mild proteinuria to thrombotic microangiopathy (TMA). However, the longitudinal course, reversibility, and spectrum of kidney-limited injury remain under-characterized.

Case report: We describe three patients with ovarian cancer who developed proteinuria during prolonged bevacizumab therapy, including one with biopsy-proven kidney-limited glomerular microangiopathy. Proteinuria emerged after 6 to 12 months of exposure in all cases. Kidney function remained preserved throughout treatment. All three patients discontinued bevacizumab, after which proteinuria consistently improved. Two patients experienced complete resolution within 3 to 6 months, and one showed marked reduction to dipstick 1 plus by three months. Kidney biopsy in one case revealed double-contour basement membrane changes and subendothelial electron-dense deposits, confirming kidney-limited TMA without systemic microangiopathic findings.

Conclusion: These cases illustrate the characteristic time course of bevacizumab-induced kidney toxicity, highlight the reversibility of proteinuria following drug discontinuation, and demonstrate that bevacizumab can induce kidney-limited TMA in the absence of systemic microangiopathic features. Multidisciplinary management is essential to balance oncologic benefit with kidney safety.

Objective: To present two cases of primary ovarian squamous-cell carcinoma (POSCC) and describe a comprehensive review and analysis of the published related literature.

Methods: We reviewed the medical records of two patients with POSCC who underwent optimal debulking surgery followed by systemic chemotherapy at Nanjing Drum Tower Hospital. We also reviewed published case reports and case series describing POSCC, focusing on histogenesis, diagnostic approaches, current therapeutic modalities, and prognosis associated with this condition.

Results: The median age at diagnosis of patients with POSCC was 53.4 years. Few patients were diagnosed at an early stage (stage I, 19.71%), and tumor stage had a significant prognostic effect (p = 0.0081). However, the difference in survival between advanced stages (stage III and stage IV) was small and not statistically significant. Most patients underwent hysterectomy and bilateral salpingo-oophorectomy, and omentectomy and lymphadenectomy improved survival outcomes in patients with advanced-stage disease.

Conclusion: Primary ovarian squamous-cell carcinoma is a rare and challenging type of ovarian cancer, and its prognosis remains extremely poor. Aggressive multimodal treatment may include surgery, systemic chemotherapy, and targeted therapies.

Direct drug delivery encompasses minimally invasive methods for the local administration of therapeutics and is already widely applied in diseases affecting the liver, eyes, peritoneum, breast, joints, coronary arteries, and brain. In oncology, localized approaches such as intratumoral injections, implantable depots, inhalable aerosols, and image-guided procedures allow controlled drug release at tumor sites with high selectivity. Given its large surface area, rich vascularization, and anatomical accessibility, the respiratory system provides an ideal setting for direct delivery strategies across a range of respiratory diseases. Among these, lung cancer, the leading cause of cancer-related deaths worldwide, is characterized by high molecular heterogeneity, making it particularly suitable for targeted gene-silencing and replacement therapies at specific oncogenic drivers. Advances in genomics and transcriptomics increasingly support the potential of gene therapy, especially RNA-based therapeutics and gene-editing technologies, to selectively silence or correct oncogenic mutations. In patients with unresectable or recurrent disease, where therapeutic precision is crucial, the combination of direct pulmonary drug delivery and RNA-based therapies offers a powerful synergy: anatomical precision, reduced systemic toxicity, and molecular selectivity targeting tumor-specific alterations. Unlike previous reviews, this work provides an integrated perspective that bridges findings from orthotopic in vivo studies on siRNA nanomedicine with emerging clinical evidence, underscoring direct pulmonary delivery as a central strategy in precision medicine for lung cancer. By critically examining advanced delivery technologies, the review considers both their potential advantages and the scientific and technical challenges that remain in the clinical translation of siRNA for lung cancer. Moreover, by highlighting how direct pulmonary administration can overcome these challenges, it underscores the transformative potential of siRNA therapeutics in lung cancer and the need for sustained, high-intensity collaboration between scientists and clinicians to advance RNA-based therapies in thoracic oncology.

Lung cancer remains one of the malignancies with the highest incidence and mortality rates worldwide, and its treatment continues to pose significant challenges. Metabolic reprogramming, as one of the hallmarks of cancer, supports the abnormal growth, proliferation, invasion, and drug resistance of cancer cells by altering glucose, lipid, and amino acid metabolic pathways, providing both energy and biosynthetic precursors. It has thus become a critical focus in lung cancer research. Circular RNAs (CircRNAs), owing to their unique closed-loop structure and high stability, play important roles in regulating tumor metabolism and progression. This review systematically summarizes the molecular mechanisms through which CircRNAs drive metabolic reprogramming in lung cancer, including the regulation of key metabolic enzymes, influence on metabolism-related signaling pathways, remodeling of the tumor microenvironment, and mediation of epigenetic modifications. Furthermore, CircRNAs demonstrate great potential in clinical applications for lung cancer, not only as biomarkers for early diagnosis and prognostic evaluation but also as promising therapeutic targets. Leveraging their stability and low immunogenicity, the development of CircRNA-based vaccines and targeted delivery systems has opened new avenues for lung cancer immunotherapy. However, challenges remain in the synthesis of CircRNAs, understanding their in vivo metabolism, and achieving multi-target synergistic interventions, which warrant further investigation. This review provides a theoretical foundation for in-depth exploration of the metabolic regulatory network in lung cancer and the development of precise therapeutic strategies, while also highlighting the broad prospects of CircRNAs in translational medicine. We conducted a literature search across databases including PubMed up to 2025, focusing on keywords related to circRNA, lung cancer, and metabolic reprogramming. Ultimately, 161 relevant references were included in this narrative review.

Introduction: This study aimed to comprehensively analyze the dosimetric parameters, plan complexity, gamma passing rates (GPRs), and most importantly, the beam-on time (BOT) of stereotactic body radiotherapy (SBRT) for small-volume inoperable early-stage centrally-located non-small-cell lung cancer (NSCLC) at a radiotherapy center. The analysis was based on both single-arc (SA) and dual-arc (DA) VMAT techniques under the deep inspiration breath hold (DIBH) scenario.

Methods: We retrospectively selected 24 cases of small-volume inoperable early-stage centrally-located NSCLC treated with SBRT under the DIBH scenario at our institution between March 2021 and June 2024. The redesigned SA-VMAT plans (SA plans) adopted the same prescription dose of 50 Gy/5 fractions and flattening-filter free (FFF) beam as the original DA-VMAT plans (DA plans). The 2-group plans (i.e., the SA and DA plans) were normalized to cover 95% of the planning target volume (PTV) and 99% of the gross tumor volume (GTV) by the prescription dose. The evaluation factors included PTV parameters (D_98%, D_2%, HI, CI, and R_50%), organs at risk (OARs), plan complexity (segments and MUs), GPRs, and BOT.

Results: The SA technique consistently yielded superior plans. Among the PTV parameters, the SA plans were superior to the DA plans in D_98%, D_2%, and HI (all p < 0.05), whereas the CI and R_50% of the 2-group plans were comparable (all p > 0.05), and the SA plans had an increase in the ipsilateral PBT D_max (p < 0.05). Otherwise, the differences between other OARs were insignificant (all p > 0.05). The SA plans had reduced complexity, with mean segments and mean MUs decreasing by 18.82% and 8.15%, respectively (all p < 0.001); the GPRs did not differ significantly under the three acquisition parameters (all p > 0.05). The mean BOT was reduced by 19.70% in SA plans (p < 0.001).

Discussion: The SA plans significantly shortened the BOT while maintaining comparable plan quality, thereby improving comfort for patients with small-volume inoperable early-stage centrally located NSCLC under the DIBH scenario. Future studies should accumulate more patient data to evaluate the long-term clinical outcomes of SA plans.

Alterations involving the mitogen-activated protein kinase (MAPK) pathway are central drivers of pediatric and adult low-grade gliomas (LGGs), with BRAF fusions representing a dominant oncogenic mechanism in pilocytic astrocytoma. While KIAA1549::BRAF remains the most prevalent fusion, an expanding repertoire of alternative fusion partners continues to refine the molecular landscape of MAPK-driven gliomas and has important therapeutic implications. Here, we report a previously unrecognized ASAP1::BRAF fusion identified in a young adult with a World Health Organization grade 1 temporal lobe pilocytic astrocytoma, highlighting both its biological plausibility and potential relevance for targeted therapy. A 31-year-old female presented with new-onset seizures and underwent gross total resection of a well-circumscribed, partially cystic left temporal lobe tumor. Histopathological and immunohistochemical findings were consistent with pilocytic astrocytoma, demonstrating low proliferative activity and absence of high-grade features. Comprehensive molecular profiling using RNA-based next-generation sequencing revealed an in-frame ASAP1 exon 29::BRAF exon 9 fusion, preserving the intact C-terminal BRAF kinase domain while eliminating N-terminal regulatory regions. No additional pathogenic variants were detected. To substantiate the structural authenticity of the fusion, deep learning-based breakpoint validation using FusionAI was performed, yielding a high fusion probability score and supporting a bona fide genomic rearrangement rather than an RNA-sequencing artifact. Genomic feature annotation demonstrated enrichment of repetitive elements, regulatory regions, and chromatin accessibility features flanking the breakpoint, consistent with known mechanisms of fusion gene formation. Functionally, the ASAP1::BRAF fusion is predicted to emphasize constitutive MAPK pathway activation via dimer-dependent BRAF signaling, analogous to canonical BRAF fusions and mechanistically distinct from BRAF V600E mutations. Clinically, BRAF fusion-driven tumors are typically resistant to first-generation BRAF inhibitors but may be sensitive to MEK inhibitors or emerging type II RAF inhibitors that effectively target RAF dimers. Although no adjuvant therapy was required following complete resection, documentation of this fusion provides a rational framework for future molecularly guided treatment should disease recurrence occur. This case expands the spectrum of oncogenic BRAF fusion partners in LGG and underscores the importance of integrated RNA-based diagnostics and computational validation in precision neuro-oncology.

Primary intracranial myxofibrosarcoma (MFS) is an exceedingly rare mesenchymal malignancy, with only a few cases reported. We report a 34-year-old male with a right frontal lobe MFS who subsequently developed two non-contiguous recurrences in the right temporal and left frontal lobes. Histopathological examination revealed a stepwise progression from low- to intermediate- to high-grade disease, accompanied by progressively increasing Ki-67 labeling indices. Notably, the pattern of spatially separate recurrences suggests the possibility of cerebrospinal fluid-mediated dissemination. This case highlights the aggressive and heterogeneous nature of intracranial MFS and underscores the importance of long-term, comprehensive follow-up to detect recurrences, particularly at non-contiguous sites.