Thoracic Cancer最新文献

Objectives: The optimal staging system for thymic epithelial tumors (TETs) remains controversial. This study aimed to evaluate the clinical utility of the T component in the latest ninth edition of the TNM staging system.

Methods: A retrospective analysis was performed on patients diagnosed with TETs at our center from January 2001 to December 2022. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and Cox proportional hazards regression models. The predictive performance of the TNM staging systems was mainly assessed by the concordance index (C-index) and area under the receiver operating characteristic curve (AUC).

Results: Ultimately, 545 patients with TETs were included. The ninth edition TNM staging system demonstrated superior discrimination compared to the eighth edition TNM staging in RFS outcomes, particularly for T1b versus T2 patients (HR = 3.58, p = 0.014). Prognostic accuracy metrics also favored the ninth edition, with higher AUC values (RFS: 0.83 vs. 0.824; OS: 0.726 vs. 0.685) and C-index values (RFS: 0.823 vs. 0.816; OS: 0.743 vs. 0.685).

Conclusions: The ninth edition TNM staging system provides enhanced prognostic accuracy for RFS in patients with TETs compared to the eighth edition, although both editions have limitations in predicting OS. Further studies are warranted to refine staging approaches and improve patient management in TETs.

Background: This study evaluated the burden of breast cancer (BC) in Belt and Road Initiative (BRI) countries from 1990 to 2021 by age, sex, and risk factors, aiming to guide health promotion.

Methods: Data from 66 BRI countries were extracted from the Global Burden of Disease (GBD) 2021 database. Trends in age-standardized incidence (ASIR) and mortality (ASMR) were assessed using estimated annual percentage change (EAPC). Associations with the Social Development Index (SDI) and attributable risk factors were also examined.

Results: From 1990 to 2021, global ASIR rose from 21.38 to 24.56 per 100 000 (EAPC = 0.38), while ASMR declined by 0.59% annually; BRI countries showed similar trends. In 1990, Greece had the highest ASIR and Israel the highest ASMR, whereas Bangladesh and Oman had the lowest. By 2021, Lebanon reported the highest ASIR, Georgia the highest ASMR, and Mongolia and Oman the lowest. Turkey showed the largest ASIR increase (EAPC = 6.77). Both ASIR and ASMR were positively correlated with SDI. Risk factors also shifted: in 1990, major contributors were high red meat intake, high body mass index (BMI), and alcohol use; by 2021, high red meat intake, high BMI, and high fasting plasma glucose (FPG) dominated. High BMI and FPG rose markedly, whereas smoking, secondhand smoke, and alcohol use declined.

Conclusion: Although mortality has fallen, BC incidence continues to rise in BRI countries, especially in low- and middle-SDI regions. Expanded screening, improved healthcare infrastructure, and targeted interventions on modifiable risks are urgently required.

Background: To analyze the association of pathologic-complete-response (PCR) and survival after neoadjuvant concurrent chemo-radiotherapy, we evaluated a large cohort of patients with potentially resectable stage IIIA-IIIC non-small cell lung cancer (NSCLC) treated with a trimodality approach.

Methods: Consecutive patients underwent neoadjuvant induction chemotherapy, followed by concurrent chemo-radiotherapy and surgery. Patients received established imaging, and diagnostics. Leave-one-out cross-validation was employed to identify the most effective prognostic classifier.

Results: Altogether, 403 patients treated between 06/2000 and 01/2020 were included. Median follow-up was 111 months (IQR: 71-127 months). PCR was achieved in 34% (137 patients) after neoadjuvant therapy and major-pathologic response without PCR in 30% (MPR_{> 0%-≤ 10%} defined as viable cells in > 0% and ≤ 10% of the sample). PCR was significantly dependent on histology (p = 0.0005) and radiotherapy fractionation schedule (p = 0.027). PCR rates were higher for squamous than for non-squamous carcinoma with 46.2% (95% CI: 37.8%-54.7%) versus 27.3% (95% CI: 22.0%-33.2%). PCR was the most significant prognostic factor for long-term survival with an associated hazard ratio of 0.272 (0.192-0.386), while MPR was associated with a hazard ratio of 0.671 (0.498-0.905) in comparison to lesser response. Overall survival at 5/10 years with PCR was 72.9% (95% CI: 64.4%-79.6%)/ 62.8% (53.0%-71.1%)/ event-free survival at 5 years 69.5% (60.9%-76.7%). Identified through cross-validation, key prognostic features included PCR, MPR, and treatment period following ¹⁸F-FDG-PET/CT-guided staging.

Conclusions: Induction chemotherapy followed by chemo-radiotherapy results in high PCR rates. In this investigation, PCR is followed by high event-free and overall survival rates. These data warrant further investigation of chemo-radiotherapy as a significant component of neoadjuvant treatment regimens in trials combined with immunotherapy. This strategy may increase the PCR rates, particularly for patients with more advanced, potentially resectable stage III NSCLC.

Background: Osimertinib, an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), improves survival in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, a substantial proportion of patients do not proceed to subsequent therapy (ST). This study aimed to identify patient characteristics associated with ineligibility for post-osimertinib therapy.

Methods: We retrospectively enrolled patients with EGFR-mutated NSCLC who received first-line osimertinib monotherapy between January 2016 and June 2023. Patients were categorized into a ST group and a non-subsequent therapy (NST) group. Baseline characteristics, treatment outcomes, and reasons for treatment discontinuation were documented.

Results: Of 94 patients, 57 (60.6%) received ST, whereas 37 (39.4%) did not. The ST and NST groups significantly differed in age (p < 0.01) and prevalence of baseline central nervous system (CNS) metastases (24.1% vs. 54.1%, p < 0.01). The overall response rate to first-line osimertinib was similar (63.2% vs. 56.8%, p = 0.71), as was median progression-free survival (16.4 [95% confidence interval, CI: 12.4-21.4] vs. 16.1 months [95% CI: 9.8-19.3]; p = 0.24). The primary reason for not receiving subsequent treatment was deterioration in performance status, most often due to worsening pulmonary disease or CNS metastasis. In patients with baseline CNS metastasis, the main cause was also progression of CNS metastasis.

Conclusions: Advanced age and baseline CNS metastasis are significant barriers to receiving second-line therapy after osimertinib monotherapy. Alternate first-line treatment strategies may be warranted for such patients.

Background: Immune checkpoint inhibitors (ICIs) improve cancer outcomes but cause significant hepatobiliary toxicity (e.g., liver dysfunction, immune-mediated liver disease). Prior studies were limited to small samples or case reports. This study evaluated hepatobiliary toxicity, risk variations, and temporal trends for six ICIs (PD-1/PD-L1 inhibitors) via the FDA Adverse Event Reporting System (FAERS) to guide safer use.

Methods: We analyzed 18 640 061 FAERS reports (2004-2024). Disproportionality analyses (ROR, PRR, EBGM, BCPNN) detected hepatobiliary toxicity signals. A Weibull model analyzed AE timing. Logistic regression assessed effects of age, gender, and weight.

Results: PD-L1 inhibitors (Durvalumab, Atezolizumab) are associated more strongly with immune-mediated liver disease/hepatic failure (ROR = 4.28-5.07). PD-1 inhibitors (Nivolumab, Pembrolizumab) are linked more to hepatitis/liver abnormalities (ROR = 3.42-3.93). AE reports are common in males (53.32%) and patients > 65 years (43.43%), though demographics didn't alter risk (p > 0.05). Median onset: 23 days (Toripalimab liver injury) vs. 84 days (Tislelizumab autoimmune hepatitis), supporting drug-specific monitoring in the first three months.

Conclusion: Our FAERS analysis showed PD-L1 inhibitors were more associated with immune-mediated liver disease and hepatic failure, whereas PD-1 inhibitors were linked to hepatitis and liver abnormalities, underscoring the need for drug-specific monitoring.

Purpose: This study aimed to clarify the incidences and treatments of enlarged nodules detected using imaging findings during follow-up, surgical outcomes, and prognosis for patients who underwent a second surgery for primary lung cancer.

Methods: We included 236 patients who underwent a second surgery for primary lung cancer (> 2 years between first and second surgeries). Group A comprised 205 patients without nodules. Group B comprised 31 patients with nodules that had grown and metachronous lung cancer was suspected; subgroup B1 underwent surgery (23 patients) and subgroup B2 did not (8 patients).

Results: The incidences of new or enlarged intrapulmonary nodules following the second surgery were 0.0091, 0.015, 0.020, 0.024, and 0.029 after 1, 2, 3, 4, and 5 years, respectively. For the third surgery procedure, 83% of the patients underwent segmentectomy and wide-wedge resection. Ten patients (44%) experienced complications associated with the third surgery including prolonged pulmonary fistulas in 6 patients (26%). The B1 subgroup 30-day mortality rate after the third surgery was 4.3% (1/23). The 1-, 2-, 3-, 4-, and 5-year survival rates after the second surgery in subgroup B1 were 95.7%, 86.3%, 80.9%, 80.9%, and 60.0%, respectively. No significant difference was observed in prognosis between the B1 and B2 subgroups (p = 0.11).

Conclusion: Surgery can be considered effective for third primary lung cancer, notwithstanding associated complications, perioperative mortality, and prognosis.

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.