Thoracic Cancer最新文献

Introduction: Despite advances in lung cancer management, it remains the leading cause of cancer-related deaths. Low-dose computed tomography (LDCT) screening has increased detection of small, difficult-to-palpate lung lesions.

Materials and methods: This retrospective study at Chang Gung Memorial Hospital (2014-2022) evaluated the feasibility of image-guided segmentectomy (I-segmentectomy) using indocyanine green (ICG) for lesion localization and intersegmental plane navigation.

Results: A total of 260 patients with 266 pulmonary lesions were enrolled in the study cohort, with 122 lesions undergoing image-guided segmentectomy (I-segmentectomy). After propensity score matching, lesions resected using the I-segmentectomy method provided appropriate resection margins and margin-to-tumor ratios, particularly for lesions larger than 1 cm. Additionally, operation times were shorter with I-segmentectomy. Survival analysis showed no significant differences in disease-free and overall survival; although I-segmentectomy maintained a 100% survival rate.

Conclusion: Overall, I-segmentectomy with dual ICG fluorescence imaging is a feasible, safe, and effective method for ensuring adequate resection margins in difficult-to-discern lung lesions. Further prospective studies are necessary to validate these findings and assess long-term outcomes.

Background: Sortilin-1 (SORT1) has been implicated in the pathogenesis of various malignancies, but its role in non-small cell lung cancer (NSCLC) remains to be elucidated.

Methods: Immunohistochemistry was employed to assess the expression of SORT1 in cancerous tissues compared to adjacent non-cancerous tissues. NSCLC cell lines, including A549, H1299, and PC-9, underwent treatment with miR-146a mimics or SORT1 small interfering RNA (siRNA), followed by evaluations of cell viability, migration, invasion, and apoptosis using cell counting kit-8, transwell assays, and scratch wound assays. Additionally, bioinformatic methods were employed to predict miR-146a target genes, which were subsequently validated through dual-luciferase reporter assays.

Results: SORT1 was significantly elevated in NSCLC tissues compared to adjacent non-cancerous counterparts. Downregulation of SORT1 inhibited proliferation, invasion, migration of tumor cell lines and promoted apoptosis. Moreover, SORT1 was a direct target of miR-146a. MiR-146a modulated tumor cell proliferation, migration, invasion, and apoptosis by suppressing SORT1 expression.

Conclusion: These results suggest that miR-146a plays a critical role in the pathogenesis of NSCLC by targeting SORT1, highlighting its potential as a therapeutic target for NSCLC.

Background: Chemotherapy combined with immunotherapy has emerged as a pivotal neoadjuvant strategy for resectable locally advanced non-small cell lung cancer (NSCLC). However, several problems urge to be resolved, including suboptimal pathologic complete response(pCR)/major pathologic response (MPR). Microwave ablation (MWA) exerts direct tumoricidal effects through thermal coagulation while releasing tumor-associated antigens to remodel the local immune microenvironment. In patients with advanced NSCLC, MWA combined with chemotherapy or immunotherapy has shown prolonged overall survival (OS).

Methods: This study investigated the neoadjuvant therapeutic strategy combining MWA with chemotherapy and immunotherapy for optimizing neoadjuvant treatment strategies of stage IIB-IIIB NSCLC. We evaluated the pCR, MPR, R0 resection rate, and incidence of grade ≥ 3 adverse events in patients following surgical resection, aiming to improve surgical outcomes and survival.

Results: This study confirmed the safety and feasibility of a neoadjuvant therapeutic strategy combining MWA with chemotherapy and immunotherapy in patients with NSCLC. The study was a single-center retrospective analysis (n = 8), demonstrating a pCR rate of 50%, an MPR rate of 62.5%, an R0 resection rate of 100%, with no increase in grade ≥ 3 adverse events.

Conclusions: In this retrospective analysis, the neoadjuvant therapeutic strategy combining MWA with chemotherapy and immunotherapy preliminarily demonstrates safety and feasibility in resectable stage IIB-IIIB NSCLC, while showing potential to improve pCR and MPR rates. Furthermore, the integration of MWA may propose a novel treatment approach for optimizing neoadjuvant therapy. Prospective multicenter clinical trials are required to further validate the safety and feasibility, as well as its impact on long-term survival benefits.

ALK fusions are well-established oncogenic drivers in lung cancer, typically resulting in ALK activation through dimerization mediated by partner proteins. However, alternative mechanisms of ALK activation have also been reported. We herein report an 80-year-old man with metastatic lung adenocarcinoma, who initially tested negative for ALK rearrangement using a polymerase chain reaction-based assay. RNA-based hybrid capture targeted sequencing later identified an EML4-ALK fusion transcript in which EML4 exon 15 and ALK intron 19 were fused. This resulted in a stop codon being retained in the unspliced ALK intron 19, preventing fusion protein translation. However, immunohistochemistry revealed overexpression of ALK, suggesting the existence of alternative translation initiation sites in exon 20 or downstream. The patient showed a marked response to alectinib therapy. This case underscores the importance of using multiple methods to detect actionable gene fusions and to ensure appropriate targeted therapy selection.

Introduction: Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, faces challenges such as drug resistance and tumor heterogeneity. N4-acetylcytidine (ac4C) is an important RNA modification involved in cancer progression, but its role in lung adenocarcinoma remains unclear.

Methods: This study analyzed transcriptomic and single-cell RNA sequencing data from public databases to investigate the expression and clinical significance of ac4C-related genes in lung adenocarcinoma. Ten machine learning algorithms were applied to develop and validate an ac4C-related gene signature (ARGSig) for prognosis prediction across multiple independent cohorts.

Results: Cells with high ac4C activity showed increased intercellular communication and activation of tumor-associated pathways. The ARGSig model effectively stratified patients by survival outcomes and predicted sensitivity to immune checkpoint inhibitors and chemotherapy agents.

Conclusion: ac4C modification and its related genes play a critical role in lung adenocarcinoma development. The ARGSig model provides a promising molecular tool for prognosis evaluation and personalized treatment guidance in lung adenocarcinoma patients.

Background: Sarcopenia is associated with poor outcomes of various cancers treated with immune checkpoint inhibitors. Durvalumab is the standard of care for patients with locally advanced (LA) non-small cell lung cancer (NSCLC) after chemoradiation therapy (CRT). However, the effect of sarcopenia on the efficacy and safety of durvalumab in patients with LA-NSCLC remains unclear.

Methods: This single-center retrospective study was conducted between 2018 and 2021. Body composition indices were measured using computed tomography scans taken at the third lumbar vertebra before and after CRT. The cutoff values were set based on the change ratios for each index before and after CRT. Tumor response, survival, and the efficacy and safety of durvalumab were compared between patients who showed skeletal muscle loss and those who did not.

Results: Among 153 eligible patients (median age: 65 years; 74.5% men), skeletal muscle index (SMI) significantly decreased during CRT. With the threshold set at a -10% change in SMI, no significant difference in objective response rate (ΔSMI ≤ -10% vs. ΔSMI > -10%: 76.6% vs. 75.7%, p = 1.000), progression-free survival (hazard ratio [HR], 0.99, p = 0.983), overall survival (HR 1.04, p = 0.909), or the frequency of immune-related adverse events (44.9% vs. 44.2%, p = 1.000) was observed between the two groups.

Conclusions: Although muscle loss during CRT is common, it does not compromise the efficacy or safety of subsequent durvalumab therapy in patients with LA-NSCLC. Future studies are needed to delineate sarcopenia criteria specific to LA-NSCLC and assess interventions, including rehabilitation and pharmacotherapy.

Background: Studies indicated that afatinib combined with angiogenesis inhibitor may achieve promising efficacy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.

Methods: This is a multicenter, Phase II trial to explore the efficacy and safety of afatinib plus bevacizumab at first-line setting for EGFR-mutant NSCLC patients. The primary end point was progression-free survival (PFS). The secondary end point included objective response rate (ORR), disease control rate (DCR) and safety.

Results: Between July 11, 2020 and November 11, 2021, 54 treatment-naïve NSCLC patients were enrolled in the afatinib plus bevacizumab combination cohort. Meanwhile, 81 NSCLC patients with EGFR mutations treated with first-line afatinib monotherapy were retrospectively collected. The median follow-up time was 26.6 months. No significant difference in PFS was observed between the afatinib plus bevacizumab combination cohort and the afatinib monotherapy cohort (14.5 vs. 12.2 months, HR 0.87, p = 0.15), confirmed by propensity score matching (PSM) analysis. Patients with pleural metastasis (HR 0.56, 95% CI: 0.32-0.98, p < 0.05) and uncommon EGFR mutations (HR 0.61, 95% CI: 0.25-1.47, p = 0.05) experienced longer PFS in the combination cohort. ORR in the combination cohort is more favorable than in the afatinib monotherapy cohort (77.8% vs. 42.0%, p < 0.05). Diarrhea was the most common treatment-related adverse events (TRAEs). 11.1% (6/54) patients had grade ≥ 3 TRAEs when treated with afatinib plus bevacizumab.

Conclusion: Afatinib combined with bevacizumab is well tolerated with moderate efficacy among patients with NSCLC, which might be a prospective strategy for patients with uncommon EGFR mutations and pleural metastasis.

Trial registration: www.chictr.org.cn.

Background: This study aims to explore clinical outcomes and safety of neoadjuvant immunotherapy combined with chemotherapy in limited-stage small cell lung cancer (SCLC), providing insights for upcoming clinical trials.

Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings, updated through 10 February 2025. Pathological complete response (pCR) rate and major pathological response (MPR) rate were calculated as the major assessments for the clinical outcomes. The incidences of the rate of R0 resection and treatment-related severe adverse events (tr-SAE) were considered as the primary outcomes for assessing the safety. Subgroup analyses were conducted according to neoadjuvant therapy cycle and study type.

Results: A total of 114 patients from 6 studies were included. The meta-analysis results suggested that the pooled rates of pCR and MPR were 35% [95% confidence interval (CI) 14-56] and 49% (95% CI 18-80) in LS-SCLC patients. In terms of safety, most patients achieved R0 surgical resection [95% (95% CI 85-100)] and the pooled incidence of tr-SAE was 44% (95% CI 13-76). Meanwhile, all studies reported that there were no deaths during the perioperative period. Subgroup analysis suggests that more than two neoadjuvant therapy cycles may be associated with better clinical outcomes.

Conclusions: In conclusion, the current research findings demonstrate that neoadjuvant immunotherapy has shown promising clinical efficacy and acceptable safety in SCLC. These results provide valuable reference for upcoming clinical trials regarding the optimal neoadjuvant strategy and potential beneficiary populations.

Background: With advancements in medical devices, more hospitals are incorporating the digital chest drainage (DCD) system into postoperative care. Although some studies have suggested that the DCD system provides accurate information and shortens hospital stays compared with the traditional chest drainage (TCD) system, the effect of the DCD system on quality of life remains unclear. This study investigated whether the digital chest drainage system improves postoperative outcomes and quality of life.

Methods: This single-center, prospective, randomized controlled trial initially included 362 patients. After exclusion and randomization, 128 and 125 patients were included in the DCD and TCD groups, respectively. Wearable devices were used to measure sleep duration and walking distance after surgery. Primary outcomes included postoperative recovery and quality of sleep and rehabilitation.

Results: Both groups had similar baseline characteristics. In terms of postoperative outcomes, the DCG group had shorter durations of chest tube insertion and hospital stays than the TCD group did. We noted no significant differences in postoperative pulmonary complications or extended hospitalizations exceeding 1 week between the groups. Regarding physiological changes, the DCD group had a longer sleep duration during the first 2 days after surgery. Furthermore, the number of walking steps after surgery was higher in the DCD group.

Conclusion: The DCD system provides precise information that can help surgeons in decision-making, potentially shortening the postoperative course and reducing the need for postoperative chest x-rays. Furthermore, the DCD system can enhance postoperative recovery by improving sleep quality and ambulation.