Thoracic Cancer最新文献

Introduction: The promising therapeutic outcomes of neoadjuvant chemoimmunotherapy (NCIT) in locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by multiple phase II clinical trials and are widely used in clinical practice. However, there are some cases, such as clinical T3N+ stage, that achieve poor tumor regression after receiving NCIT, reflecting the insufficient efficacy of NCIT for advanced T-type tumors. It may be necessary to add concurrent radiotherapy to further improve the local control effect of tumor, but it also means higher adverse events and immune suppression when irradiating tumor-draining lymph nodes. Nevertheless, node-sparing radiotherapy can enhance the effect of NCIT with fewer adverse effects, which has been applied to other solid tumors. The aim of this study was to evaluate the safety and efficacy of NCIT combined with node-sparing radiotherapy for clinical T3N+ locally advanced ESCC (CINSREC trial).

Methods: Forty eligible patients with pathologically confirmed ESCC of clinical T3N + M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel + carboplatin, q3w × 2 cycles) and node-sparing radiotherapy (41.4 Gy/23 times) treatment. The primary end point of this study is the pathological complete response rate. The secondary end points include major pathological response rate, adverse events, 2-year overall survival, and disease-free survival.

Discussion: This is the first prospective clinical trial to investigate the safety and efficacy of NCIT combined with node-sparing radiotherapy for clinical T3N+ locally advanced ESCC. We hypothesize that this promising strategy can provide a better pCR rate and acceptable safety.

Trial registration: ClinicalTrial.gov: NCT06965829.

Background: Antibody-drug conjugates (ADCs) have demonstrated promising efficacy in several prospective clinical studies, offering new possibilities for the treatment of non-small cell lung cancer (NSCLC). Consequently, understanding the toxicity profile associated with ADCs is of critical importance.

Methods: A comprehensive search was performed across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies on ADC monotherapy in NSCLC. Data extraction prioritized treatment-related adverse events (TRAEs), drug-related adverse events (AEs), or treatment-emergent adverse events (TEAEs). Incidences were pooled using a random-effects model.

Results: Thirteen studies including 1566 NSCLC patients were analyzed. The pooled incidence of all-grade TRAEs was 93.67%. Grade ≥ 3 TRAEs occurred in 38.74%, and serious TRAEs in 15.89%. Discontinuation and mortality rates were 9.52% and 0.63%. Hematologic toxicity was common among grade ≥ 3 TRAEs. Additionally, 20 fatal TRAEs were mainly associated with respiratory toxicity. Subgroup analysis for adverse events of special interest (AESIs) showed that Trastuzumab deruxtecan was more likely to cause grade ≥ 3 pneumonitis or interstitial lung disease (ILD), while TROP2-targeted ADCs were prone to high-grade stomatitis and ocular toxicity.

Conclusion: The overall incidence of TRAEs with ADC monotherapy in NSCLC is high, but most are Grade 1 or 2 and overall safety is manageable. Importantly, fatal TRAEs were mainly respiratory in this study, requiring clinical vigilance. Grade ≥ 3 AESIs should also be closely monitored.

Registration: This study was registered at INPLASY (ID: INPLASY2023120046).

Background: In metastatic non-small cell lung cancer (NSCLC) patients receiving first-line immune checkpoint inhibitors (ICIs), the real-world progression patterns and subsequent treatment outcomes remain controversial.

Methods: We retrospectively analyzed patients with stage IV NSCLCs treated with first-line immunotherapy between January 2017 and June 2023. Clinico-demographic and treatment data were obtained from an electronic medical record system. Progression patterns were categorized by: (1) Progression in different organs; (2) Progression in existing or new lesions; and (3) Oligoprogression versus systemic progression. Survival was assessed using the Kaplan-Meier method and Cox proportional hazards models.

Results: Among 157 patients, 67.5% experienced systemic progression, and 49.0% had progression in existing lesions. The most common organs with progression were the lung (81.5%), lymph nodes (35.0%), and pleural effusion (24.2%). Median post-progression survival (PPS) was superior in oligoprogression versus systemic progression (22.4 vs. 10.9 months, p = 0.012). Patients with extrapulmonary progression (8.2 vs. 22.9 months, p < 0.001) or progression in new lesions (9.6 vs. 25.3 months, p = 0.029) showed decreased PPS. In multivariate Cox regression, ECOG PS of 2-4 (HR: 2.26, p = 0.003), tumor stage of IVB (HR: 1.74, p = 0.013), and extrapulmonary progression (HR: 2.05, p = 0.002) were associated with decreased PPS. Subsequent treatments containing ICIs improved survival compared to regimens without ICIs (29.0 vs. 11.3 months, p = 0.004), particularly in patients with systemic progression (19.3 vs. 9.2 months, p = 0.013).

Conclusion: Most metastatic NSCLCs on first-line immunotherapy experienced systemic progression. Oligoprogression and progression only in existing lesions showed better prognoses, whereas extrapulmonary progression indicated worse survival. Subsequent ICI-containing treatments had improved survival.

Radiation-induced lung injury (RILI) can be caused by thoracic tumor radiotherapy. Qingdi mixture (QDM) has been routinely used in preventing RILI during tumor radiotherapy. However, the molecular mechanisms of QDM remain to be fully elucidated. Initially, we employed network pharmacology to identify potential therapeutic targets and their related signaling pathways. Secondly, molecular docking was applied to validate the interactions between the QDM components and hub targets. Furthermore, we retrospectively collected clinical data from RILI patients who received basic therapy combined with QDM. To investigate the therapeutic potential, we established both in vitro RILI cell models and in vivo murine models. We elucidated the molecular mechanisms of QDM's protective effects against RILI. The network pharmacology results showed that 157 common targets were identified for RILI. Enrichment analysis indicated that NF-κB, JAK-STAT, and necroptosis signaling pathways were involved in the QDM treatment of RILI. The molecular docking results indicated that ligands from multiple compounds exhibited strong interactions with inflammatory cytokines, including IL-6, IL-1α, IL-4, and so on. The therapeutic efficacy of QDM was verified by clinical observation of patients with RILI. In vitro experiments demonstrate that QDM promotes cell proliferation after radiation therapy. Meanwhile, in vivo experiments showed that QDM reduced inflammatory factor levels and enhanced the therapeutic effects of basic treatment. Finally, the western blot experiments were conducted to verify the activation of the NF-κB signaling pathway, as predicted by network pharmacology. This study demonstrated that QDM effectively alleviates RILI and holds promise for broad clinical application.

Diffuse pulmonary meningotheliomatosis (DPM) is a rare lung condition characterized by widespread meningothelial-like nodules and may radiologically mimic metastatic or granulomatous disease. We report a 2019-onset case of a 44-year-old woman with incidentally detected, bilateral 1-2-mm pulmonary micronodules on screening CT. Laboratory tests and pulmonary function were normal. Owing to the minute, peripheral distribution of the nodules, bronchoscopic biopsy was not feasible, and diagnostic video-assisted thoracoscopic wedge resection was undertaken. Histology showed spindle-to-ovoid cells in whorled arrangements without atypia or mitoses. Immunohistochemistry revealed diffuse vimentin positivity and negativity for epithelial and neuroendocrine markers (EMA, cytokeratin AE1/AE3, SMA, chromogranin). Postoperative brain MRI showed no intracranial lesion. The patient has remained asymptomatic without radiologic progression over 3 years. This case underscores DPM as an uncommon yet important differential diagnosis of diffuse pulmonary micronodules and highlights the need for histopathologic confirmation when bronchoscopic sampling is impracticable. Where available, PR and SSTR2A immunostains may further support the diagnosis.

Hypertrophic pulmonary osteoarthropathy is a rare paraneoplastic syndrome affecting < 1% of patients with non-small cell lung cancer, characterized by clubbed fingers, periosteal proliferation, and arthritis. Although symptoms improve after treatment, objective functional recovery has not previously been reported. We present a 52-year-old male heavy smoker with right upper lobe adenocarcinoma and hypertrophic pulmonary osteoarthropathy causing profound grip strength impairment (5/2 right/left kilogram-force (kgf)). Genetic testing identified the KRAS G12C mutation. The patient underwent right upper lobectomy after which his arthralgia resolved immediately and grip strength recovered progressively (16/12 kgf, postoperative day 3; 40.9/32.9 kgf, 3 months), reaching normal adult levels. Periosteal changes initially persisted but resolved by 1 year. This case provides the first objective documentation of functional recovery in a patient with hypertrophic pulmonary osteoarthropathy, suggesting that impaired grip strength may be caused by joint inflammation and edema affecting bone-tendon attachments, rather than by muscle weakness alone. The KRAS G12C mutation may contribute to the development of hypertrophic pulmonary osteoarthropathy through upregulation of vascular endothelial growth factor via the Raf pathway. This case provides valuable insights into the pathophysiology of hypertrophic pulmonary osteoarthropathy and confirms that functional impairment is reversible with appropriate treatment.

Background: Second-generation anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and brigatinib, are widely used in patients with ALK-positive non-small cell lung cancer (NSCLC) who develop resistance or progress on crizotinib. However, real-world data comparing their efficacy and safety remain limited. This multicenter, prospective cohort study compared the clinical outcomes of alectinib and brigatinib in this setting.

Methods: Patients with stage IV ALK-positive NSCLC who progressed on crizotinib were enrolled and treated with either brigatinib or alectinib. The primary endpoint was the progression-free survival (PFS) rate.

Results: Sixty patients were included (brigatinib, n = 34; alectinib, n = 26). Median follow-up durations were 26.5 and 30.0 months. Disease progression or death occurred in 50.0% (brigatinib) and 46.2% (alectinib), respectively. The 3-year PFS was 51.5% (brigatinib) vs. 62.1% (alectinib), with no significant difference at 5 years (40.0% vs. 42.5%; p = 0.260). Overall response rates were similar (58.8% vs. 46.2%; p = 0.475). However, intracranial outcomes appeared more favorable with alectinib: the 3-year intracranial PFS was 70.5% vs. 31.7% (p = 0.023), and intracranial ORR was 94.4% vs. 64.3% (p = 0.028). More patients in the brigatinib group had prior whole-brain radiotherapy (21.4% vs. 5.6%), while radiosurgery was more frequent in the alectinib group (55.6% vs. 35.7%). Treatment discontinuation rates due to adverse events were comparable between the two groups.

Conclusions: In crizotinib-refractory ALK-positive NSCLC, systemic efficacy was not significantly different between brigatinib and alectinib; however, alectinib was associated with more favorable intracranial PFS and ORR, which may be partly explained by differences in prior brain-directed local treatments.

Objective: Although uniportal video-assisted thoracoscopic surgery (uVATS) is increasingly adopted for early-stage lung cancer, long-term survival data comparing different forms of anatomic resection remain limited. This study aimed to evaluate the long-term oncologic outcomes-specifically, 5-year disease-free survival (DFS) and overall survival (OS)-of patients with clinical stage I non-small cell lung cancer (NSCLC) who underwent uVATS segmentectomy or lobectomy. Secondary outcomes included perioperative parameters and complication rates.

Method: We conducted a retrospective analysis of patients with clinical stage I NSCLC who underwent uVATS anatomical resection (lobectomy or segmentectomy) between January 2014 and December 2020. The primary endpoints were 5-year DFS and OS, while the secondary endpoints included operative time, drainage duration, hospital stay, conversion rates, and postoperative complications.

Results: A total of 386 patients with clinical stage I NSCLC underwent uVATS anatomical resection, with 280 receiving lobectomy and 106 undergoing segmentectomy. The 5-year DFS and OS rates did not significantly differ between segmentectomy and lobectomy for patients with pathological stage IA tumors. Segmentectomy was associated with a shorter drainage duration. The overall conversion rate to multiple-port VATS or thoracotomy was 1.8%, with no 30-day surgical mortality observed. Prolonged air leaks were the most common complication.

Conclusion: uVATS anatomical resection is an effective treatment option for clinical stage I NSCLC, offering comparable long-term survival outcomes for segmentectomy and lobectomy in selected patients. Further prospective studies are warranted to confirm these findings and optimize patient selection.

Background: Uncommon EGFR mutations, including G719X, L861Q, S768I, and compound mutations, present therapeutic challenges due to limited prospective evidence and variable drug sensitivity. Although later-generation (i.e., second- and third-) EGFR-TKIs have shown benefit in some subtypes, real-world data is limited.

Methods: We retrospectively analyzed patients with advanced or recurrent NSCLC harboring uncommon EGFR mutations diagnosed between 2014 and 2019 at Keio University Hospital and affiliated hospitals. Clinical data were updated through May 2023. EGFR mutations were detected using commercial assays. Common mutations and exon 20 insertions were excluded unless coexisting as compound mutations. Survival outcomes were estimated using the Kaplan-Meier method and compared by log-rank test; hazard ratios were calculated using the Cox proportional hazards model. Swimmer plots depicted treatment duration by subtype and EGFR-TKI agents.

Results: Among 35 patients, G719X was the most frequently detected mutation, followed by L861Q and S768I. In addition to these single mutations, various compound mutations involving combinations of G719X, L861Q, S768I, and other rare variants were also observed. While first-generation EGFR-TKIs were frequently used initially, 71% of patients eventually received a later-generation EGFR-TKI. These patients had significantly longer OS (47.7 vs. 15.5 months; p = 0.0177). Multivariate analysis identified non-use of later-generation EGFR-TKIs, liver metastases, and poor performance status as independent poor prognostic factors. Afatinib showed favorable treatment duration in G719X and compound mutations.

Conclusions: Later-generation EGFR-TKIs were associated with improved outcomes in patients with uncommon EGFR mutations, with afatinib showing favorable treatment duration in G719X and compound subtypes.