Journal of thoracic disease最新文献

Background: The efficacy of first-line immune checkpoint inhibitor (ICI)-based therapy remains to be established for patients with advanced non-small cell lung cancer (NSCLC) harboring specific driver mutations for which effective first-line targeted therapies are unavailable. This study aims to examine the outcomes of first-line ICIs for advanced NSCLC with gene alterations in China and explore predictive factors of survival in this cohort.

Methods: This retrospective study analyzed pathologically diagnosed advanced NSCLC with KRAS, insensitive EGFR, HER2, MET, BRAF, RET, NTRK, or non-driver gene alterations that received first-line ICIs at Peking Union Medical College Hospital (PUMCH) in China between January 2017 and June 2023. Clinical, genomic, and serological information before first-line treatment was collected from an electronic medical database. Best overall response, progression-free survival (PFS), and overall survival (OS) were evaluated.

Results: There are 138 patients enrolled, including 96 with driver gene alterations and 42 with non-driver alterations. Driver gene alterations were insensitive EGFR (n=14), KRAS (n=45), HER2 (n=8), MET (n=2), BRAF (n=11), RET or NTRK (n=5), and concurrent driver genes (n=11). The objective response rate (ORR) was 44.9%, the median PFS was 11.3 months, and the median OS was 24.4 months. Survival was similar among different gene alteration subgroups. However, those with KRAS [14.6 months, 95% confidence interval (CI): 9.7-not reached (NR)] had longer PFS, while EGFR (7.97 months, 95% CI: 6.13-NR) and MET (7.4 months, 95% CI: not calculable) showed an inferior PFS. Programmed death ligand 1 (PD-L1) ≥50% was a consistent protective factor in univariate [hazard ratio (HR) 0.402, 95% CI: 0.196-0.827, P=0.01] and multivariate (HR 0.409, 95% CI: 0.186-0.903, P=0.03) Cox regression models, and PFS varied significantly among patients with PD-L1 <1%, 1-49%, and ≥50% (7.97 vs. 11.27 vs. 11.77 months, P=0.04). In KRAS mutant NSCLC, patients with KRAS G12C mutations exhibited longer PFS (19.9 vs. 10.3 months, P=0.71) and OS (NR vs. 14.2 months, P=0.36) compared to non-G12C mutations. Similarly, KRAS mutant patients with TP53 co-mutation had numerically prolonged PFS (25.9 vs. 10.5 months, P=0.16) and OS (NR vs. 20.4 months, P=0.06), compared to those without TP53 co-mutation.

Conclusions: Among different gene alteration subgroups for advanced NSCLC, the efficacy of first-line ICIs did not differ with statistical significance, with high PD-L1 expression as a predictive factor for better survival. In KRAS mutant patients, KRAS G12C mutation or TP53 co-mutation might indicate improved survival.

Background: Evidence supporting the efficacy of adjunctive corticosteroid therapy in human immunodeficiency virus (HIV)-negative patients with Pneumocystis jirovecii pneumonia (PJP) who present with respiratory failure is increasing. However, the optimal dosing regimen remains uncertain. Our study aimed to evaluate the effectiveness of high-dose versus low-dose adjunctive corticosteroid therapy in this population.

Methods: This retrospective cohort study included HIV-negative patients diagnosed with PJP who received adjunctive corticosteroid therapy in Zhongnan Hospital of Wuhan University from June 2018 to March 2023. Patients were categorized into high-dose group (≥1 mg/kg/day of prednisone equivalent) and low-dose group (<1 mg/kg/day). The risk was estimated by the time-dependent Cox regression analyses with inverse probability of treatment weighting (IPTW). Subgroup analysis focused on patients with respiratory failure.

Results: Ultimately, 120 HIV-negative PJP patients were included (high-dose, n=72; low-dose, n=48). The overall 30- and 90-day mortality rates were 30.8% and 41.7%, respectively. No significant differences were observed in 30-day mortality (P=0.80 before analysis; P=0.62 after analysis) and 90-day mortality (P=0.86 before analysis; P=0.97 after analysis) between the two groups before and after IPTW analysis. Results in the respiratory failure subgroup were consistent with the overall findings.

Conclusions: In conclusion, low-dose adjunctive corticosteroid therapy may be adequate for treating HIV-negative PJP.

Background: Thymectomy is a cornerstone in the management of thymic epithelial tumors and myasthenia gravis (MG). While minimally invasive techniques like video-assisted thoracoscopic surgery (VATS) have gained prominence, robotic-assisted thoracoscopic surgery (RATS) has emerged as a technically advanced alternative. However, comparative long-term oncological outcomes between RATS and VATS remain underexplored. This review aims to compare RATS and VATS thymectomy regarding long-term outcomes, perioperative results, and cost.

Methods: A systematic review was conducted following PRISMA guidelines, with a protocol registered in PROSPERO (CRD420251126351). PubMed/MEDLINE, Web of Science, and Cochrane Library were searched for comparative studies reporting long-term outcomes (≥12 months follow-up) of RATS versus VATS thymectomy. Risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: Three retrospective cohort studies (430 patients: 181 RATS, 249 VATS) were included. No significant differences were found in long-term oncological outcomes: 5-year progression-free survival (RATS 87.7% vs. VATS 90.6%, P=0.504) and overall survival (87.7% vs. 92.2%) were comparable. Recurrence and reoperation rates were low and similar between groups. In MG patients, RATS was associated with a higher rate of complete stable remission (26% vs. 18%, P=0.06) and was an independent predictor of remission (hazard ratio: 0.472, P=0.049). Perioperatively, RATS demonstrated advantages including lower conversion rates (3% vs. 15%, P=0.03), shorter operative time (median 100 vs. 120 min, P=0.039), and reduced hospital stay (mean 1.3 vs. 2.4 days, P=0.01). Complication rates were similarly low. However, RATS was significantly more costly (¥68,122 vs. ¥37,886, P<0.001).

Conclusions: RATS and VATS thymectomy yield equivalent long-term oncological outcomes. RATS offers superior perioperative recovery and may enhance neurological remission in MG patients, but at a significantly higher cost. The choice of technique should consider clinical context, surgeon expertise, and economic factors.

Background: The severity of interstitial lung disease (ILD) is frequently linked to poorer outcomes and reduced quality of life in connective tissue disease-associated ILD (CTD-ILD) patients. The purpose of this study is to investigate the utility of artificial intelligence (AI)-based quantitative high-resolution computed tomography (HRCT) analysis in assessing the prognosis of patients with CTD-ILD.

Methods: This retrospective study included 116 CTD-ILD patients who underwent HRCT scans. Patients were stratified into mild, moderate, and severe groups based on pulmonary function test (PFT) results. Differences in the 17 AI parameters across the three groups were evaluated using one-way analysis of variance (ANOVA) followed by least significant difference (LSD) post hoc pairwise comparisons. The Spearman rank correlation test was employed to examine the association between the 17 AI parameters and pulmonary function grades. Overall survival rates were compared using Kaplan-Meier analysis and ANOVA. Univariate analysis and Cox proportional-hazards regression were used to assess the association between AI-derived parameters and prognosis.

Results: The 17 AI parameters exhibited significant variations across the three groups. Among them, three pulmonary volume parameters were negatively correlated with lung function, while fourteen pulmonary parenchymal involvement parameters were positively correlated with pulmonary function. Significant differences in overall survival rates were observed among the mild, moderate, and severe groups. Univariate analysis revealed that there were 12 indicators showing significant differences between the survival group and the death group. The Cox proportional-hazards regression revealed that the two most important factors were left lung volume and the percentage of disease components ≤-751 Hounsfield units (HU), which were protective factors and risk factors for overall survival rate, respectively.

Conclusions: The quantitative HRCT analysis based on AI can be used to evaluate patients with CTD-ILD and is correlated with overall survival rate.

Background: There is significant value in predicting and better assessing patients who are at risk of post-surgery upstaging in lung cancer. The objective of this study is to review patients who were upstaged following resection and evaluate their clinical and demographic data to elucidate which factors portend an increased risk of pathologic upstaging at our institution (the Thomas Jefferson University Hospital).

Methods: A retrospective review of institutional data was performed between 2011 and 2023. Patients with stage I-II non-small cell lung cancer (NSCLC) were included. Patients were excluded if they received neoadjuvant systemic therapy, including chemotherapy and/or immunotherapy, and were excluded if they received pre-operative mediastinoscopy or endobronchial ultrasound (EBUS). Kaplan-Meier analysis was utilized with log-rank testing to examine 5-year overall survival and progression-free survival. A logistic regression model was built to evaluate whether certain clinical or demographic factors affect the odds of being upstaged.

Results: A total of 371 patients met the inclusion criteria. Male sex, primary tumor standardized uptake value (SUV) >8, pre-operative biopsy, and having 10-13 lymph nodes explored were all associated with increased odds of being upstaged. Squamous cell histology was associated with lower odds of upstaging compared to adenocarcinoma. Patients who had their tumor detected via a screening computed tomography (CT) scan had a trend towards a decreased odds of upstaging compared to symptomatic and incidentally found tumors.

Conclusions: Male gender, primary tumor SUV >8, having a preoperative biopsy, and having 10-13 lymph nodes explored were associated with increased odds of being upstaged. This analysis provides patients and clinicians with valuable data regarding upstaging early-stage lung cancers, which could be used to guide multidisciplinary teams in making more informed decisions regarding resection and the use of perioperative systemic therapy.

Background: Retrospective studies indicate that morning chemotherapy enhances efficacy and reduces side effects in non-small cell lung cancer (NSCLC). However, the role of infusion timing for pemetrexed plus platinum (AP) chronotherapy remains unclear. This study evaluates the impact of AP administration time on efficacy and safety in advanced NSCLC.

Methods: We retrospectively analyzed 132 advanced NSCLC patients receiving AP chemotherapy at Guangdong Second Provincial General Hospital from 2018 to 2023. Based on previous research, patients were grouped into morning (AM; infusion before 2:00 PM, n=58) and afternoon (PM; n=74) groups. Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors Criteria V.1.1. The primary endpoint was progression-free survival (PFS), with safety profile serving as the secondary endpoint. All adverse events (AEs) were identified and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0.

Results: The AM group showed significantly longer PFS than the PM group (24.0 vs. 14.0 months, P=0.04). Subsequent subgroup analysis in the AP cohort favored the AM group across all major subgroups for PFS treatment effect. Furthermore, the analysis of adverse reactions revealed similar incidences of any treatment-emergent adverse events (TEAEs) in both AM and PM (AM 86.21% vs. PM 86.49% in AP cohort), and grade ≥3 TEAEs (AM 31.03% vs. PM 21.62% in AP cohort). The most common AEs were anemia, leukopenia, and neutropenia. Univariate and multivariate analyses indicated that the infusion time of AP chemotherapy (P=0.03) was an independent prognostic factor for NSCLC.

Conclusions: AP treatment administered in the morning may enhance PFS in advanced NSCLC. This suggests that chrono-chemotherapy (CCT) could potentially enhance the efficacy of individualized chemotherapy in advanced NSCLC.

Background: Thoracoscopic surgery has become the standard approach for many thoracic conditions. Despite its advantages, postoperative pain remains a significant cause of complications. Liposomal bupivacaine (LB), an extended-release local analgesic, has been introduced to enhance recovery. This meta-analysis of randomized controlled trials (RCTs) compares the efficacy of LB vs. non-liposomal local anesthetics in patients undergoing thoracoscopic surgery.

Methods: We systematically searched PubMed, the Cochrane Library, Embase, and Web of Science for RCTs published from the inception of each database to November 2025. The risk of bias of the included studies was evaluated with the Cochrane Risk of Bias 1 (RoB 1) tool, and the quality of evidence was graded using the GRADE system. The primary outcome was postoperative opioid consumption at 24 hours, measured in morphine milligram equivalents (MMEs). Secondary outcomes included opioid consumption at 48 hours, 72 hours, and during total hospitalization; pain scores assessed using the visual analogue scale (VAS) at 24 hours, 48 hours, 72 hours, and over the entire hospitalization period; length of hospital stay (LOS); and time to first ambulation. Data were synthesized using Review Manager (RevMan; version 5.4).

Results: Nine RCTs involving 915 patients were included. Compared to the control group, LB significantly reduced opioid consumption at 24 hours [mean difference (MD) =-1.83; 95% confidence interval (CI): -2.42, -1.24; P<0.001], 48 hours (MD =-2.22; 95% CI: -2.78, -1.66; P<0.001), and 72 hours (MD =-1.73; 95% CI: -2.21, -1.25; P<0.001). Pain scores were also significantly lower in the LB group at 24 hours (MD =-0.99; 95% CI: -1.57, -0.41; P<0.001) and 48 hours (MD =-0.42; 95% CI: -0.77, -0.06; P=0.02), but the difference was not statistically significant at 72 hours (MD =-0.41; 95% CI: -0.95, 0.13; P=0.14). No significant differences were found in total opioid consumption, pain scores over the entire hospitalization period, LOS, or time to first ambulation.

Conclusions: LB provides superior short-term analgesia but does not improve functional recovery outcomes compared to non-liposomal local anesthetics.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease which affects 3 million people worldwide. Our previous study confirmed that isoforskolin (ISOF) can improve the status of the mouse with pulmonary fibrosis (PF). This study aimed to explore the effect of ISOF on linear ubiquitin chain assembly complex (LUBAC) in the cell model of PF induced by transforming growth factor-β1 (TGF-β1).

Methods: The fibrosis of mice lung fibroblasts (MLGs) were stimulated by TGF-β1 to establish a PF cell model. ISOF (0.5 and 1.0 µmol/L) was administrated as treatment drug in cell model, while pirfenidone (PFD; 10 µmol/L) and dexamethasone (DXM; 25 µmol/L) were administrated as control drug. In addition, HOIP inhibitor-8 (HOIPIN-8), the inhibitor of LUBAC, was also administrated. The PF model of mice was established by intratracheal instillation of bleomycin (BLM). Meanwhile, the expressions of LUBAC subunits [shank-associated RH domain interaction protein (SHARPIN), heme oxidation IRP2 ubiquitin ligase 1L (HOIL-1L), and HOIL-1L interacting protein (HOIP)], gasdermin D (GSDMD), and interleukin-1beta (IL-1β) were detected by western blot.

Results: The expression of LUBAC was increased in the cell model, while attenuated with 24 h administration of ISOF 0.5 or 1.0 µmol/L (P<0.05), and the inhibitor of LUBAC. Meanwhile, the expression of GSDMD and IL-1β increased in the cell model, while attenuated with the administration of ISOF 1.0 µmol/L and inhibitor of LUBAC (P<0.05). Moreover, the expression of LUBAC, GSDMD, and IL-1β was inhibited by PFD or DXM in the cell model. The expressions of LUBAC, GSDMD and IL-1β increased in mice with PF, while decreased after intervention with ISOF, PFD, and DXM.

Conclusions: LUBAC is involved in PF and inhibited by ISOF. In addition, ISOF may ameliorate PF by inhibiting the LUBAC/GSDMD/IL-1β cascades. Accordingly, LUBAC may be a potential therapeutic target for PF.