Thoracic Cancer最新文献

Entrectinib, a first-generation TRK inhibitor, is effective in NTRK fusion-positive non-small cell lung cancer (NSCLC) but commonly induces significant weight gain. We describe the case of a 42-year-old patient with metastatic NTRK-positive NSCLC undergoing entrectinib who participated in a two-year, supervised exercise program. The intervention included twice-weekly aerobic and resistance training aligned with international exercise-oncology guidelines. Adherence was high (91.6%), and no exercise-related adverse events occurred. Despite an initial 13 kg weight gain over 9 months, split between fat and lean mass, subsequent fat loss (~3.5 kg) occurred while lean mass was preserved. This case suggests that prolonged, structured exercise is a safe and feasible strategy to attenuate entrectinib-associated metabolic effects and support physical function during targeted therapy in advanced NSCLC.

Background: Immune checkpoint inhibitors (ICIs) significantly impact advanced non-small cell lung cancer (NSCLC) management, but predictive biomarkers for elderly patients remain controversial. This study aimed to assess peripheral immune cells as biomarkers for predicting ICI efficacy in elderly NSCLC patients.

Methods: This was an ambispective, observational study enrolling patients aged ≥ 65 years with advanced NSCLC treated with first-line ICI ± chemotherapy from January 2023 to August 2024 at Beijing Chest Hospital. Peripheral immune cell subsets were analyzed by flow cytometry at baseline and dynamically during treatment. Associations between clinical characteristics, immune cell profiles, and outcomes were assessed using Kaplan-Meier analysis, Cox regression, and Wilcoxon tests.

Results: A total of 34 patients were included in this study. Objective response rate and disease control rate were 41.2% and 97.1%, respectively. Median progression-free survival (PFS) was 10.3 months, while median overall survival (OS) was not reached. Patients responding to ICIs had significantly higher baseline percentages of CD3⁺ T cells, CD3⁺CD8⁺Perforin⁺ T cells, and CD3⁺CD8⁺Granzyme B⁺ T cells. Higher baseline absolute counts of CD3⁺ T cells and CD3⁺CD8⁺ T cells were also significantly associated with longer OS. Post-treatment increases in the percentage of CD3⁺Perforin⁺ T cells were associated with significantly longer OS (up vs. down: not reached vs. 15.1 months, p = 0.034).

Conclusions: Peripheral cytotoxic T cell subsets may serve as promising biomarkers for predicting the efficacy of ICIs in elderly NSCLC patients. Dynamic monitoring of immune cell profiles could further enhance prognostic accuracy.

Background: Lung cancer, representing a predominant form of pulmonary malignancy, demonstrates significant disease burden and poor clinical outcomes. Circular RNAs (circRNAs) have emerged as critical regulators in various cancers, including lung cancer. However, the specific roles and mechanisms of circRNAs in lung cancer remain largely unexplored.

Methods: Differential circRNA expression was analyzed using GEO datasets GSE101586 and GSE112214. CircFUT8 was prioritized for its upregulation in lung cancer tissues. In vitro and in vivo functional experiments evaluated its effects on cell proliferation, apoptosis, migration, and invasion. RNA pull-down, immunofluorescence, and western blotting assessed interactions with ENO1. Macrophage polarization was examined via cocultures and flow cytometry.

Results: CircFUT8 (hsa_circ_0003028) was significantly upregulated in lung cancer tissues, correlating with advanced stages and poor prognosis. It enhanced lung cancer cell proliferation, migration, and invasion while inhibiting apoptosis in cellular and animal models. Mechanistically, circFUT8 directly binds ENO1 to form an RNA-protein complex, promoting M2 macrophage polarization. Silencing circFUT8 reversed these effects by suppressing ENO1 and M2 polarization, inhibiting tumor progression. Moreover, ENO1 promotes TNF signaling through glycolytic metabolites.

Conclusions: Our findings highlight the critical role of circFUT8 in lung cancer progression through its regulation of M2 macrophage polarization via interaction with ENO1. The findings suggest that circFUT8 may serve as both a diagnostic marker and a promising therapeutic target in lung cancer management. This study first identified the regulating oncogenic role of circFUT8 in lung cancer progression and the microenvironment.

Pericardial metastases are common in advanced cancers but often remain undetected due to subtle symptoms. Photon-counting CT (PCT) offers improved spatial resolution and contrast-to-noise ratio (CNR) compared with conventional CT (CCT), potentially enhancing diagnostic performance. In this retrospective single-center study, patients diagnosed with pericardial metastases by transthoracic echocardiography (TTE) between April and September 2025, who underwent both unenhanced and contrast-enhanced chest CT were included. After Propensity Score Matching (PSM), two groups were established: the PCT group (n = 11; reconstructions at 0.4 and 1 mm) and the CCT group (n = 22). Diagnostic sensitivity, image quality, and radiation dose were assessed, with TTE as the reference standard. PCT-0.4 mm demonstrated the highest overall sensitivity (91.5%) and small-lesion sensitivity (88.9%), followed by PCT-1 mm (87.2% and 83.3%) and CCT-1 mm (86.1% and 78.6%). Although not statistically significant, PCT showed consistently better lesion detection. The PCT-0.4 mm group showed higher standardized CNR versus CCT-1 mm (Tukey-Kramer p = 0.021) but not versus PCT-1 mm (p = 0.641); overall one-way ANOVA p = 0.020, whereas SNR did not differ among groups (ANOVA p = 0.18). Radiation exposure was significantly lower with PCT than CCT (ED: 11.7 ± 3.9 vs. 20.6 ± 6.6 mSv; p < 0.001). Compared with the 1-mm CCT reconstruction, the 0.4-mm PCT showed a trend toward improved detection of both overall and small pericardial metastases, enhanced image quality, and reduced radiation dose, highlighting its potential clinical value in managing pericardial metastases.

Objective: To compare the predictive value of the estimated dose of radiation to immune cells (EDRIC) with conventional dosimetric parameters for survival in elderly patients with stage III unresectable NSCLC after chemoimmunotherapy and radiotherapy.

Methods: We conducted a retrospective study of elderly patients (≥ 65 years) treated at two institutions. Patients were stratified by median EDRIC, mean lung dose (MLD), mean heart dose (MHD), and mean body dose (MBD). Survival was analyzed using Kaplan-Meier, Cox regression, and ROC curves.

Results: Baseline characteristics were well-balanced across dosimetric parameter subgroups (all p > 0.05). The median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 23.9 months and 46.0 months, respectively. EDRIC ≥ 6.4 Gy was associated with worse PFS (p = 0.019) and OS (p = 0.011), while MLD, MHD, and MBD showed no prognostic significance (all p > 0.05). Multivariate analysis identified EDRIC ≥ 6.4 Gy as an independent predictor of worse PFS (HR = 1.852, p = 0.049) and OS (HR = 2.289, p = 0.048). Age ≥ 70 years was also independently associated with poorer OS (HR = 2.870, p = 0.011). ROC analysis demonstrated superior predictive performance of EDRIC over conventional parameters for 1-, 2-, and 3-year PFS and OS, with particularly outstanding discrimination for 12-month OS (AUC = 0.93).

Conclusion: EDRIC shows potential in predicting survival for elderly stage III unresectable NSCLC patients, with 6.4 Gy as a potential threshold for personalized radiotherapy optimization. These findings require prospective validation.

Background: The molecular landscape of thymic epithelial tumors has been partially elucidated. GTF2I mutation drives the pathogenesis in approximately 50% of tumors; however, the key molecular aberrations in the other cases remain unclear.

Methods: We designed a panel including the most frequently mutated genes in thymic epithelial tumors and sequenced tumor and normal DNA from 70 patients prospectively accrued at a single institution in the Thymogene trial. Moreover, 19 neoplastic samples were dissociated to isolate tumor cells using flow cytometry.

Results: GTF2I mutations were the most common, being present in 41% of patients. GTF2I mutations were prevalent in type A and AB thymomas, in Stage I-II tumors, and in patients without myasthenia gravis. The unique pattern of mutually exclusive and co-occurring mutations suggests a distinct pathogenesis for thymomas with and without GTF2I mutation. In 39% of patients, no mutations were found in the 77 genes evaluated. The absence of epithelial cells in some dissociated tumors highlights the challenge of identifying mutations in a subset of thymic epithelial tumors that lack the GTF2I mutation. Mutational signatures, including COSMIC 1, 19, and 25, were enriched, possibly linked to 5'-methylcytosine deamination and the effects of chemotherapy.

Conclusions: GTF2I mutations drive the growth of a significant portion of thymic epithelial tumors, often in conjunction with other gene mutations. Somatic mutations are not commonly found in many GTF2I wild-type tumors, where the underlying genomic abnormalities remain elusive, even when using a dedicated tool for sequencing thymic epithelial tumors.

Objective: To evaluate the effect of postoperative adjuvant immune checkpoint inhibitor (ICI) therapy on survival outcomes in resectable non-small cell lung cancer (NSCLC) patients who received neoadjuvant chemoimmunotherapy.

Methods: A retrospective cohort study was conducted at Zhongshan Hospital, Fudan University, from January 2019 to June 2024, including resectable NSCLC patients treated with neoadjuvant chemotherapy combined with ICIs. Pathological responses were assessed, and event-free survival (EFS) and overall survival (OS) were compared between patients who received postoperative adjuvant ICI therapy and those who did not.

Results: Among the 186 patients included, 106 received adjuvant ICI therapy, while 80 did not. No significant differences in EFS or OS were observed between the two groups in patients who achieved pathological complete response (pCR) or major pathological response (MPR) (EFS: p = 0.282, OS: p = 0.330). In contrast, patients who did not achieve pCR or MPR experienced a significant improvement in EFS with adjuvant ICI therapy (p = 0.004). An AI-based decision tree model developed to predict the need for postoperative adjuvant immunotherapy demonstrated strong performance, with an accuracy of 85% and an area under the curve (AUC) of 0.82. Key predictors identified by the model included pathological response, age, clinical stage, and PD-L1 expression.

Conclusions: Postoperative adjuvant ICI therapy significantly improves EFS in resectable NSCLC patients, especially in those without pCR or MPR. However, its effect on OS remains uncertain. These findings highlight the importance of personalized treatment strategies, with adjuvant ICI offering greater benefits for patients with incomplete pathological responses.

Background: Thymoma is a rare thymic epithelial tumor, and its prognostic factors remain not fully elucidated. This study aimed to identify simple, practical preoperative predictors of prognosis, focusing on tumor dimensions assessed by computed tomography (CT).

Methods: We retrospectively analyzed 181 patients who underwent complete or partial resection for thymoma between 2004 and 2022. Tumor size was assessed by measuring the maximum transverse and craniocaudal dimensions on preoperative CT. Freedom from recurrence (FFR) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were constructed: Model A included only preoperative variables, while Model B additionally incorporated postoperative factors (e.g., TNM stage classification and histology).

Results: During a median follow-up of 96 months, the 5- and 10-year FFR rates were 78.4% and 71.4%, and the corresponding OS rates were 96.5% and 87.3%, respectively. In multivariate analysis, TNM stage classification and preoperative steroid pulse therapy were significantly associated with FFR, whereas no variables were significantly associated with OS. Model A demonstrated good discriminatory ability (C-index = 0.839), which improved only modestly after including postoperative factors in Model B (C-index = 0.867). In the steroid-excluded cohort (N = 148), the craniocaudal tumor dimension emerged as a significant predictor of FFR (p = 0.027).

Conclusions: The craniocaudal tumor dimension measured on preoperative CT was consistently associated with recurrence and may reflect prognostic information embedded within the pathological TNM classification. This easily measurable parameter could complement TNM-based evaluation in preoperative risk assessment and surgical decision-making for thymoma.

Background: Lung cancer remains a leading cause of cancer mortality globally, with particulate matter pollution (PMP) identified as a critical environmental risk. This study analyzes long-term trends in age-standardized mortality (ASMR) and disability-adjusted life-year rates (ASDR) for PMP-attributable lung cancer, with projections to 2030.

Method: Using Global Burden of Disease data, we evaluated temporal trends across age, sex, and Sociodemographic Index (SDI) regions through age-period-cohort and Bayesian models.

Result: Global Trends: PMP-related ASMR/ASDR declined significantly over the study period, while ambient PMP (APMP)-attributable rates increased, contrasting with household air pollution (HAP)-related declines. Age and Sex Disparities: Mortality burden shifted toward older populations, with APMP-related deaths rising sharply in the elderly. Males exhibited faster declines in PMP/HAP-related mortality, whereas females faced steeper increases in APMP-attributable risks. SDI variations: High-middle SDI regions consistently had the highest PMP-related mortality, with ASMR trends reflecting industrialization phases. Projections: PMP-related burdens are expected to rise globally, driven by aging populations and persistent pollution in middle-SDI regions.

Conclusion: The escalating burden in vulnerable populations demands urgent interventions, including air quality improvement, tobacco control, and enhanced screening, Notably, China consistently exhibited the world's highest PMP-attributable lung cancer ASMR (13.6 per 100 000 in 1990, declining to 10.1 per 100 000 in 2021). Future strategies must integrate gender-specific risk mitigation and environmental-genetic assessments to address disparities.

Thymoma is a rare malignant tumor originating from the thymus epithelium. In recent years, immune checkpoint inhibitors have become an indispensable treatment for cancer. However, the efficacy and adverse events of immunotherapy for thymoma have not been widely evaluated. A 53-year-old Chinese man who was diagnosed with metastatic B2 thymomas since March 2023. He received chemotherapy plus anlotinib for four cycles since May 5, 2023, and underwent radiotherapy from May 23, 2023 to June 30, 2023. However, the treatment was not satisfactory. Thus, we detected PD-L1 expression in tumors; immunohistochemical examination on the tumor revealed a high PD-L1 expression in 60% of tumor cells. He presented symptoms of palpitation, gasping, fatigue, diplopia, and eyelid ptosis. Additionally, he was found to have significantly elevated levels of serum cardiac troponin, creatine kinase, creatine kinase isoenzymes, N-terminal pro brain natriuretic peptide, and anti-acetylcholine receptor antibody. He was eventually diagnosed with immune-related myocarditis and myasthenia gravis. Finally, the patient was discharged after treatment with glucocorticoids, immunoglobulin, and pyridostigmine. Although immune checkpoint inhibitors have achieved similar anti-tumor effects in thymomas as in other solid tumors, they may be closely associated with serious immune-related adverse events, so special caution is required when using immune checkpoint inhibitors in thymoma patients.