Thoracic Cancer最新文献

Main problem: The treatment and prognosis of lung adenocarcinoma (LUAD) remain challenging. The study aimed to identify prognostic genes and construct a prognostic model for LUAD.

Methods: After identifying malignant alveolar type II (AT2) cells using InferCNV, we applied CytoTRACE, pseudo-time analysis, Mendelian randomization (MR), and univariate Cox regression analysis to identify prognostic genes. A prognostic model was then developed using an optimized subset of these genes, selected through the least absolute shrinkage and selection operator (LASSO) algorithm. Further analyses included Gene Ontology enrichment analysis and the construction of a protein-protein interaction (PPI) network.

Results: Pseudo-time analysis identified 3526 dynamically expressed genes during malignant AT2 cell dedifferentiation. Subsequent multi-omics integration refined the gene selection, yielding four prognostic genes for the final predictive model. The resulting model achieved area under the receiver operating characteristic (ROC) curve (AUC) values of 0.649, 0.675, and 0.654 for predicting 1, 2, and 3-year overall survival (OS) in the training set, respectively, and was successfully validated in two external cohorts at the corresponding time points. Moreover, survival analysis demonstrated that patients in the high-risk group had significantly poorer OS than those in the low-risk group, both in the training set and the validation sets (p < 0.01).

Conclusions: The study developed a novel signature based on genes dynamically expressed during malignant AT2 cell dedifferentiation, capable of predicting the prognosis of LUAD patients, and offered four accurate prognostic biomarkers (ADM, MARK4, PARVA, and RPS6KA1).

Pleomorphic carcinoma is a rare, aggressive subtype of non-small cell lung cancer (NSCLC). Invasion into the left atrium and dissemination to cerebral arteries are exceptionally uncommon, and the role of cardiopulmonary bypass (CPB)-assisted resection remains debated. We report two surgically treated cases with left atrial invasion. Case 1: A 57-year-old man underwent left lower lobectomy with partial atrial resection under CPB. One month later, he developed subarachnoid hemorrhage caused by rupture of a cerebral aneurysm secondary to metastasis; histology of the aneurysmal wall confirmed carcinoma. He remains recurrence-free at 21 months. Case 2: A 62-year-old woman underwent extended left upper lobectomy with partial atrial resection under CPB. Although adrenal metastasis was suspected radiologically, pathological confirmation was lacking preoperatively; surgery was pursued because of symptomatic disease and atrial involvement. She developed postoperative cerebral infarction and rapid adrenal progression and died at 4 months despite chemotherapy. These cases illustrate both the technical feasibility of CPB-assisted atrial resection and the aggressive biology of pleomorphic carcinoma, including atypical vascular metastasis to cerebral arteries. Careful staging, patient selection, and early multidisciplinary planning (thoracic surgery, cardiac surgery, neurosurgery, oncology, and radiology) are essential. Surgery can be justified in selected patients with atrial invasion; however, pleomorphic histology portends poor outcomes and unusual metastatic tropism. Vigilant postoperative surveillance and integration of systemic therapy are required.

Background: The role of wedge resection in the treatment of non-small cell lung cancer (NSCLC) with solid components ≤ 2 cm remains controversial. This study compared the efficacy of wedge resection with that of segmentectomy in these patients.

Materials and methods: This real-world retrospective study included NSCLC patients who underwent wedge resection or segmentectomy at Beijing Chao-Yang Hospital, Capital Medical University, from January 2018 to December 2020. Patient data were retrospectively reviewed. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to minimize baseline disparities. Survival outcomes, including overall survival (OS), recurrence-free survival (RFS), and lung cancer-specific survival (LCSS), were examined via Cox proportional hazards modeling.

Results: A total of 640 patients were enrolled (wedge resection: 295; segmentectomy: 345). After IPTW, no difference in baseline characteristics was observed between the two groups. Additionally, long-term outcomes did not significantly differ between the groups. However, compared with segmentectomy, wedge resection was associated with a shorter operation duration (p < 0.001), less intraoperative blood loss (p < 0.001), fewer complications (p < 0.001), and shorter postoperative stay (p = 0.047). In the subgroup with a consolidation-to-tumor ratio (CTR) > 0.25, segmentectomy resulted in longer OS (p = 0.046), LCSS (p = 0.036) as well as higher 5-year OS (p = 0.045), 5-year RFS (p = 0.023), and 5-year LCSS (p = 0.015).

Conclusion: Wedge resection is an optimal choice for patients with NSCLC ≤ 2 cm, especially for patients with Ground-Glass Opacity (GGO) dominant tumors. However, segmentectomy is more appropriate when the CTR is > 0.25.

Targeted therapy is the standard treatment for driver-mutated lung cancer, but its efficacy in multiple primary lung cancers (MPLCs) remains limited due to significant inter-lesional molecular heterogeneity. We present a case of synchronous MPLC with 34 bilateral pulmonary nodules. The dominant right upper lobe lesion was an EGFR L858R-mutated adenocarcinoma that responded to osimertinib, while other nodules progressed. Switching to chemoimmunotherapy induced regression of all lesions, enabling surgical resection. Postoperative pathological analysis revealed two resected lesions with discordant molecular profiles-one EGFR-mutated and one driver-negative. Despite adjuvant therapy, the patient developed early recurrence as non-small cell lung carcinoma-not otherwise specified with no driver mutation and died within 6 months post-radiotherapy. This case highlights the limitations of single-agent targeted therapy in MPLC, challenges the assumption that driver-negative lesions typically follow an indolent course, and supports early chemotherapy-based systemic combination strategies to address the significant molecular heterogeneity in MPLC.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Although chemotherapy remains a cornerstone in the treatment of advanced NSCLC, local ablative strategies such as microwave ablation (MWA) have emerged as promising adjunctive therapies. However, the survival benefits of combining MWA with chemotherapy remain uncertain. This meta-analysis aims to evaluate the efficacy and safety of microwave ablation combined with chemotherapy compared to chemotherapy alone in patients with advanced NSCLC. A comprehensive search was conducted in MEDLINE, EMBASE, and Cochrane Library through January 2025. Eligible studies included randomized controlled trials or observational studies comparing MWA associated with chemotherapy versus chemotherapy alone in patients with advanced NSCLC. The primary outcome was progression-free survival (PFS); secondary outcomes included partial remission (PR) rate and adverse events (AE). Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) were pooled using random-effects models. Individual patient data (IPD) were reconstructed from Kaplan-Meier curves to perform a one-stage survival meta-analysis. Four studies comprising 483 patients were included. MWA associated with chemotherapy significantly improved PFS (HR 0.408; 95% CI 0.24-0.49; p < 0.001; I² = 53.3%). No significant differences were found for PR (RR 0.74; 95% CI 0.37-1.50; p = 0.41) or AE (RR 1.08; 95% CI 0.86-1.36; p = 0.49). Sensitivity analyses confirmed the robustness of the findings. MWA combined with chemotherapy significantly improves PFS in advanced NSCLC without increasing toxicity.

Background: We previously reported the short-term real-world effectiveness and safety of first-line atezolizumab combined with chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). This study provides an updated analysis of the effectiveness, prognostic factors, and subsequent treatment patterns in first-line immunochemotherapy.

Methods: This prospective multicenter observational study enrolled patients with ES-SCLC, diagnosed at seven university hospitals throughout Korea, between June 2021 and August 2022. Primary outcomes were 1-year overall survival (OS) and progression-free survival (PFS), whereas secondary outcomes included OS, objective response rate, disease control rate, second progression-free survival, and safety, evaluated based on established clinical guidelines.

Results: A total of 100 ES-SCLC patients (median age, 69 years) were enrolled, with a median follow-up duration of 26.0 months. The median PFS and OS were 6.2 and 17.1 months, respectively, with a 1-year OS rate of 62.5%. Favorable prognostic factors for OS included partial response (PR) and stable disease (SD) as the best responses (SD: hazard ratio (HR), 0.79; PR: HR, 0.38) and a longer platinum-free interval (HR 0.84). Brain radiotherapy significantly improved OS in patients with brain metastases, whereas thoracic radiotherapy during first-line treatment tended to prolong survival in patients who responded to systemic treatment. Patients receiving second-line treatment after progression presented a significantly longer OS than did those receiving only best supportive care.

Conclusion: This study outlined the real-world effectiveness and safety of first-line atezolizumab immunochemotherapy for ES-SCLC patients over an extended follow-up, noting that local treatment and post-progression therapy were associated with improved survival.

Background: The distress thermometer (DT) is an effective tool for identifying distress among cancer patients worldwide. Our study objective is to evaluate the prevalence and severity of distress in lung cancer patients by using DT.

Methods: A total of 153 lung cancer patients were retrospective enrolled at the Lung Cancer Center of Peking Union Medical College Hospital. Participants completed three assessments: the clinical characteristics, the associated problem list (PL) scale and the DT.

Results: At a DT cut-off score of ≥ 4, 56.2% of lung cancer patients had significant distress, which was related to the number of PL items symptoms. Sleep (55.6%), fatigue (51.0%), and pain (47.7%) were the most commonly reported issues. Univariate logistic regression analysis revealed that a DT score ≥ 4 was significantly associated with most of the PL items, such as housing, child care, insurance, transportation, dealing with children and relatives, loneliness, depression, nervousness, sadness, worry, loss of interest in usual activities, sleep, memory/concentration, bathing, appearance, change in urination, fatigue, breathing, diarrhea, indigestion, constipation, eating, dizziness, pain, mouth sores, nausea, sexual issues, dry nose, tingling in hands/feet, and physical activity restrictions. However, multivariate regression analysis identified only the following as independent predictors of significant distress in patients with lung cancer: insurance, transportation, depression, sleep, mouth sores, and dry nose.

Conclusion: This study recommends using the DT for screening lung cancer patients, and the involvement of the social services and psycho-oncology at the time of initial diagnosis and treatment.

The KRAS G12D mutation is a highly prevalent oncogenic driver in pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. Unlike other KRAS variants, G12D lacks a reactive site; therefore, it is considered "undruggable" and exhibits a propensity to activate the PI3K/AKT pathway while fostering an immunosuppressive microenvironment. This review summarizes recent breakthroughs in inhibitor design that are reshaping the therapeutic landscape for KRAS G12D. Significant progress has been made in the development of small-molecule inhibitors: non-covalent inhibitors (e.g., MRTX1133) exploit ionic interactions (salt bridges) with the mutant aspartic acid residue to achieve high affinity and selectivity; novel covalent strategies are emerging, including strain-release alkylation and tri-complex inhibitors (e.g., RMC-9805). Alternative modalities such as Proteolysis Targeting Chimeras (PROTACs), peptide inhibitors, and monobodies are also discussed. The article further evaluates the status of candidate drugs currently in clinical trials and addresses the critical challenges of acquired resistance, which may arise through secondary mutations or bypass signaling pathways. Finally, it emphasizes future directions, including the optimization of drug delivery via nanoparticles and the implementation of combination therapies to enhance efficacy and achieve durable clinical responses.

Background: Intentional pulmonary segmentectomy via minimally invasive surgery is now commonly used to treat early stage non-small cell lung cancers smaller than 2 cm. The main challenge of this procedure lies in identifying the intersegmental plane (ISP). Two primary methods are used: the method of inflation-deflation (MID) and indocyanine green (ICG) fluorescence.

Methods: This prospective, single-center study included 196 patients who underwent minimally invasive segmentectomy between January 2022 and December 2024. The ISP was identified using both MID and ICG injection. Patients were divided into two groups based on whether the discrepancy between the two methods was ≤ 10 mm or > 10 mm, in order to identify factors associated with discordance.

Results: A discrepancy > 10 mm was observed in 41.3% of cases (n = 81). Factors significantly associated with this discordance included pleuropulmonary adhesions (OR = 4.61; p = 0.032), complex segmentectomies (OR = 2.36; p = 0.027), and bronchial variations (OR = 3.72; p = 0.011). ICG visualization of the ISP was rated satisfactory or very satisfactory (score ≥ 2) in 88.8% of cases. No significant differences were observed in postoperative outcomes, complications, or resection margin quality.

Conclusion: ICG proves to be a reliable and reproducible method for ISP visualization, though it has limitations in certain clinical situations. It remains a valuable tool, especially during the learning phase or in cases of anatomical uncertainty, and should be adapted to each patient's anatomy, the type of segmentectomy, and the surgeon's experience.