Thoracic Cancer最新文献

Anatomical variation of the pulmonary vessels poses challenges to thoracoscopic lung resection and may be associated with an increased risk of intraoperative bleeding and damage to pulmonary circulation. Herein, we reported a rare and dangerous variation as the partial anomalous venous drainage of the right upper lobe into the superior vena cava in a patient undergoing thoracoscopic lobectomy for management of lung cancer of right upper lobe. The preoperative identification of such variation by 3D computed tomography scan allowed to plan a safe and accurate resection, and to prepare additional strategies for overcome unexpected intraoperative bleeding. No intraoperative and/or postoperative complications were observed. Chest drainage was removed on postoperative day two and patient discharged the day after. At 3 months follow up, the patient was well without recurrence.

In early-stage lung cancer, lung function appears to be less compromised after segmentectomy than lobectomy, though the advantage seems modest. We aimed to re-assess postoperative lung function in surgical patients, with a particular focus on the diffusion capacity for carbon monoxide (DL_CO). We evaluated all patients who underwent either lobectomy or segmentectomy for T1a-c lung cancer at our center between March 2016 and March 2023. From January to June 2024, patients who had undergone segmentectomy, along with a matched cohort of patients who had undergone lobectomy, were invited for a repeat lung function evaluation. Patients were matched 1:1 based on age, sex, surgical approach, year in which the procedure was performed, and tumor location. Lung function testing data including DL_CO were then compared to preoperative measures. During the study period, 480 patients received a lobectomy, and 97 received a segmentectomy. Complete lung function evaluation for the study was available for 52 patients (26 matched pairs). The median time from lung resection to repeat spirometry was 35 months. A modest reduction of lung function measures was observed in the segmentectomy group. Conversely, all lung function measures, including DL_CO, were significantly impaired in the lobectomy group. In early-stage lung cancer, patients who perform segmentectomy demonstrated better long-term lung function preservation compared to those who underwent lobectomy. Whenever feasible, segmentectomy should be considered the procedure of choice for early-stage lung cancer patients.

Introduction: To evaluate the impact of antibiotic (ATB) exposure on the outcome of chemoimmunotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC).

Methods: In this multicenter retrospective study, 132 patients with ES-SCLC who received chemoimmunotherapy were included from three hospitals in China. Patients receiving ATB within 30 days prior to initiating ICI therapy (p-ATB) and those receiving concurrent ICI therapy until cessation (c-ATB)were compared to those who did not (n-ATB). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs) were assessed. To avoid immortal time bias, c-ATB was analyzed as a time-dependent covariate in the Cox proportional hazards model.

Results: Among the 132 patients, 25 were included in the p-ATB group and 26 in the c-ATB group, while 81 patients were categorized in the n-ATB group. Multivariate analysis revealed no significant differences in PFS (aHR = 1.028, 95% CI: 0.666-1.589, p = 0.900) and OS (aHR = 0.957, 95% CI: 0.549-1.668, p = 0.877) between the p-ATB and n-ATB groups. Similarly, p-ATB had no significant impact on ORR (p = 0.510) or irAEs (p = 0.516). The use of c-ATB had no significant effect on either PFS (aHR: 1.165, 95% CI: 0.907-1.497; p = 0.232) or OS (aHR: 1.221, 95% CI: 0.918-1.624; p = 0.171) by multivariate analysis.

Conclusions: p-ATB has no significant impact on PFS, OS, ORR, or the incidence of irAEs in ES-SCLC patients receiving chemoimmunotherapy. Similarly, c-ATB does not seem to affect PFS or OS.

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, with cisplatin (DDP) resistance being a significant challenge in its treatment. Histone deacetylase 1 (HDAC1) has been implicated in the regulation of NSCLC progression; however, its role in the resistance of NSCLC to DDP remains unclear.

Methods: The mRNA levels of HDAC1, ubiquitin specific peptidase 5 (USP5), and Rab interacting lysosomal protein (RILP) were analyzed by quantitative real-time polymerase chain reaction. The protein expression of HDAC1, multidrug resistance protein 1 (MRP1) and RILP was detected by western blotting assay or immunohistochemistry assay. The IC₅₀ value of DDP was determined using a cell counting kit-8 assay, while cell proliferation, apoptosis, and invasion were assessed using 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, and trans well invasion assay, respectively. Cancer stem-like cell properties were analyzed by a sphere formation assay. The interaction between USP5 andHDAC1 was investigated using MG132 assay and co-immunoprecipitation (Co-IP).RILP acetylation was analyzed by a Co-IP assay. A xenograft mouse model assay was employed to study the in vivo effects of HDAC1 silencing on DDP sensitivity.

Results: HDAC1 expression was upregulated in DDP-resistant NSCLC tissues and cells. Silencing HDAC1 enhanced the sensitivity of NSCLC cells to DDP, inhibited cell proliferation, invasion, and the formation of microspheres and induced cell apoptosis. USP5 was found to deubiquitinate and stabilize HDAC1 in DDP-resistant NSCLC cells. Moreover, HDAC1 overexpression reversed the effects induced by USP5 silencing. HDAC1 also sensitized Rab-interacting lysosomal protein (RILP) acetylation in DDP-resistant NSCLC cells, and RILP upregulation counteracted the effects of HDAC1 overexpression in DDP-resistant NSCLC cells. HDAC1 silencing also improved the sensitivity of tumors to DDP in vivo.

Conclusion: USP5-dependentstabilization of HDAC1 contributed to cisplatin resistance and the malignancy of NSCLC by diminishing the levels of RILP acetylation, which suggested that targeting the HDAC1-USP5axis might represent a novel therapeutic strategy for overcoming DDP resistance in NSCLC patients.

Introduction: First-line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR-tyrosine kinase inhibitor (TKI) is often performed after first-line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR-TKI rechallenge after first-line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR-TKI rechallenge with another TKI.

Methods: This multicenter prospective observational study enrolled patients with EGFR-mutated NSCLC who received first-line osimertinib and another EGFR-TKI as second- or third-line treatment between September 2018 and August 2020.

Results: Fifty-three patients received rechallenge with another EGFR-TKI in the second-line (n = 38, 71.7%) or third-line (n = 15, 28.3%) setting. The primary reason for first-line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR-TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real-world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR-TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis.

Conclusion: EGFR-TKI rechallenge with another TKI is well tolerated in patients with EGFR-mutated NSCLC. Thus, it may be a useful treatment option after first-line osimertinib failure, especially after osimertinib discontinuation due to toxicity.

Objective: Stereotactic ablative radiotherapy (SABR) is renowned for its high local control (LC) rates. Nonetheless, for tumors that are either large in volume or in close proximity to critical organs at risk, the application of SABR to the entire tumor becomes impractical. This study aims to evaluate the efficacy and safety of partial SABR boost before conventional radiotherapy (P-SABR) for the treatment of large (> 5 cm) unresectable stage III nonsmall cell lung cancer (NSCLC).

Methods: From April 2014 to January 2024, 44 patients with > 5 cm unresectable T3-4N0-3M0 stage III NSCLC were analyzed. The median diameter was 9 cm (5.2-22.7 cm). The P-SABR plan is combined with a partial SABR boost part and a conventional fractionated radiotherapy (CFRT) part. In the partial SABR boost plan, the prescription dose for planning target volume (PTV) was 1.8-3 Gy per fraction over 3-4 fractions, and the artificially delineated gross tumor boost volume (GTVb) within GTV received a simultaneously integrated SABR dose (6 or 8 Gy per fraction). In the following CFRT plan, the median dose for the entire PTV was 54 Gy in 22 fractions. For the synthetic P-SABR plan, the median cumulative dose delivered to the PTV was 62.1 Gy, while the median cumulative dose to the GTVb was escalated to 78 Gy.

Results: The median follow-up time was 36 months (95% CI, 14.6-57.4 months). The LC rates at 1 and 2 years were 90.2% and 76.8%, respectively. The median OS was 47.0 months (95% CI, 16.8-77.2 months) and 15.0 months (95% CI, 6.0-24.0 months) for the chemoradiotherapy and radiotherapy groups, respectively. Univariate analysis showed that P-SABR combined with immunotherapy was associated with significantly longer OS (HR, 0.163; 95% CI, 0.038-0.704). Only one (2.3%) patient experienced grade 3 acute pneumonitis.

Conclusions: The P-SABR treatment has shown a high rate of LC and tolerable toxicity in patients with large unresectable stage III NSCLC.

Background: Schlafen 11 (SLFN-11) has been identified as a sensitizer of tumor cells to DNA-damaging agents. However, the relationship between SLFN-11 expression and clinical outcomes in patients with small cell lung cancer (SCLC) remains unexplored. Thus, we aimed to evaluate the impact of SLFN-11 expression on survival in patients with limited-stage (LS) SCLC.

Methods: We conducted a retrospective review of data from patients pathologically diagnosed with LS-SCLC post-surgery between January 2008 and December 2018. SLFN-11 expression was assessed using immunohistochemistry in tissue microarrays and scored using a histology (H)-score (range: 0-300).

Results: Overall, 86 patients were included in the analysis with a median H-score of 43 for SLFN-11 expression. Among the patients, 44 had high SLFN-11 expression (provisionally defined as H-score ≥ 43). No significant differences in clinical profiles were observed between the two groups (high and low SLFN expression). The median survival durations were not reached (NR; 95% confidence interval [CI]: 65.1 months to NR) and 33.5 months (95% CI: 24.2 months to NR) for patients with high and low SLFN-11 expression, respectively (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.81; p = 0.012). Among patients who relapsed post-surgery (n = 21), the median survival durations were 22.0 (95% CI: 7.6-44.9 months) and 8.1 (95% CI: 1.8-24.6 months) months in patients with high and low SLFN-11 expression, respectively (HR: 0.22, 95% CI: 0.06-0.84; p = 0.026).

Conclusions: High SLFN-11 expression is associated with relatively longer survival in patients with LS-SCLC in both those undergoing surgery and those who have relapsed.

This illustrates the outcomes of patients with esophageal cancer undergoing neoadjuvant concurrent chemoradiation and esophagectomy, specifically focusing on those who develop new-onset atrial fibrillation (NOAF). Statistically significant findings (p < 0.05, dark red) increased mortality and ventricular fibrillation, as well as trends of (p > 0.05, light red) myocardial infarction and pericardial effusion among NOAF patients. The data emphasize the significant cardiovascular risks associated with NOAF in this population.

Background: Existing studies have shown that transferrin receptor (TfR) is highly expressed on the surface of lung cancer cells, and nanoparticles (NPs) have been widely used as delivery vehicles. The aim of this study was to investigate the effect of the targeted delivery of Fe₃O₄ NPs modified with transferrin (Tf) compared with photothermal treatment for lung cancer.

Methods: The morphology and properties of Fe3O4 NPs modified with Tf were tested by internal morphological characterization experiments including transmission electron microscopy, particle size meter infrared spectrometer and other experiments. The delivery of materials was investigated by cell proliferation and apoptosis experiments, and western blot experiment was used to detect yes-associated protein 1(YAP1) protein expression changes after delivering miR-15a-5p. In addition, animal models were constructed to further explore the targeting properties of the material.

Results: The results demonstrated that the nanomaterial has good stability and targeting properties. Meanwhile, we also discovered that the miR-15a-5p carried by NPs can inhibit cell growth after its entry to the lung cancer cells. The effect became more evident when the nanomaterials were assisted with laser therapy, as verified by in vivo and in vitro experiments. In terms of the related mechanism, miR-15a-5p inhibited YAP1 expression, which affected cell proliferation and apoptosis.

Conclusion: In this study, Fe3O4 NPs modified with Tf delivered miR-15a-5p in combination with photothermal therapy for lung cancer. In future research, the targeted delivery of Tf and the photothermal synergy of nanomaterials will provide a theoretical basis for cancer treatment.