Thoracic Cancer最新文献

Background/objectives: Thoracostomy and pleurodesis are the mainstay of management for malignant pleural effusions (MPEs). However, pleurodesis may not be effective for patients with MPEs and non-expandable lungs. Intrapleural chemotherapeutic agents such as hypotonic cisplatin are reportedly useful for treating MPEs with expandable lungs; however, their efficacy in patients with non-expandable lungs remains unclear. We aimed to analyze the efficacy and safety of intrapleural administration of hypotonic cisplatin in patients with MPEs and non-expandable lungs.

Methods: We retrospectively analyzed patients with MPEs of thoracic malignancies who were administered intrapleural hypotonic cisplatin. We investigated the changes in drained fluid volume, radiological outcomes at 4 weeks, thoracentesis-free survival, and adverse events. Between June 2009 and September 2022, 62 patients with MPEs received 69 administrations of hypotonic cisplatin.

Results: The most frequent primary site was the lungs (90.3%), and the mean drained fluid volume per day decreased by 65% (95% confidence interval [CI] 58%-72%) after intrapleural hypotonic cisplatin administration. At 4 weeks post-administration, MPE volumes decreased in 33 (53.2%) patients, remained unchanged in 22 (35.4%), and increased in seven (11.3%), based on frontal plane chest radiographs. The median thoracentesis-free survival was 456 days (95% CI, 122-842 days), the 30-day thoracentesis-free survival rate was 86.1%, and the 90-day survival rate was 70.8%. In total, 37 patients (59.7%) were censored. The most frequent adverse event was pleural empyema, observed in four patients.

Conclusions: Intrapleural hypotonic cisplatin administration decreased or stabilized pleural effusion and may be useful for suppressing MPE with non-expandable lungs.

Clinicaltrials: gov identifier: E23-0003.

This review has been written with the intention of explaining to the patients with ALK-positive lung cancer, and to their families, friends, carers and medical teams, in simple terms, the fundamentals, and the current state of knowledge of this particular type of cancer. The review begins with basic facts about lung anatomy and lung cancer, then explains general principles of how cell proliferation is regulated at the molecular level. The coverage of the molecular events underlying the development of ALK-positive lung cancer and principles of targeted therapies then follows. The review concludes with an analysis of various therapeutic approaches to treat ALK-positive lung cancer. The Supporting Information section contains additional advanced information illustrating specific points of interest.

Background: In certain types of solid tumors, nuclear factor of activated T cell 5 (NFAT5) plays critical roles in tumor development and progression. However, the subtle regulatory mechanism of NFAT5 in particularly lung cancer has not been well characterized.

Methods: In this report, we measured the levels of interleukin-8 (IL8) in NSCLC cell lines. The target gene of IL8 was verified by ChIP assay and Luciferase reporter assay. Moreover, the function and regulatory mechanism of IL8 in the progression of cancer were further investigated.

Results: ELISA assay showed that IL8 was significantly downregulated in NFAT5 silencing PC9 cells and HCC827 cells. NFAT5 silencing caused inhibiting effects on proliferation, migration, and invasion in NSCLC cell lines. Further analysis indicated that IL8 was a direct target gene of NFAT5, evidenced by the direct binding of NFAT5 to the promoter of IL8. Elevated IL8 further enhanced the activation of the canonical NF-κB pathway.

Discussion: Our findings provide new insight into the mechanism of NSCLC progression. NFAT5 promotes cell growth and motility by regulating IL8 directly in NSCLC cell lines. Elevated IL8 expression causes enhancement of the NF-κB signaling pathway partially through autocrine or paracrine effects. These findings provide a possible mechanism of the inflammatory environment on lung cancer progression.

Objective: This study aimed to evaluate the short-term clinical outcomes of subxiphoid approach thoracoscopic surgery (SATS) versus lateral intercostal approach thoracoscopic surgery (LIATS) for anterior mediastinal tumors.

Methods: Clinical data from patients who underwent video-assisted thoracoscopic surgery for anterior mediastinal tumors between April 1, 2020 and December 31, 2023 were analyzed. Patients were stratified into two cohorts according to the surgical approach used: the SATS group (n = 679) and the LIATS group (n = 461). Intraoperative and postoperative outcomes were compared between the two groups.

Results: A total of 1140 patients were included in the statistical analysis after screening and assessment. After propensity score matching, a total of 417 SATS patients were matched with 417 LIATS patients. In the analysis of the outcomes, the LIATS group had a shorter operation time than the SATS group (p < 0.001). There were no statistical differences in Numeric Rating Scale (NRS) pain scores on Postoperative Day 1 (p = 0.113), Day 2 (p = 0.189), or Day 3 (p = 0.462). Postoperative atelectasis was more common in the SATS group than in the LIATS group (p = 0.025). There were no perioperative deaths.

Conclusions: The SATS did not demonstrate significant improvements in postoperative pain compared with the LIATS. However, the LIATS was associated with shorter operative time in the overall cohort.

Cancer cachexia is a multifactorial syndrome characterized by progressive weight loss, muscle wasting, and systemic inflammation. Early identification of individuals at risk for cachexia is essential for timely intervention, yet a universally accepted definition of the "at risk" stage remains lacking. Building on the Asian Working Group for Cachexia (AWGC) framework, we propose that the presence of any one of the five components-low BMI (< 21 kg/m²), weight loss ≥ 2% over 3-6 months, anorexia, low handgrip strength, or elevated CRP levels-may indicate vulnerability to cachexia. We evaluated the prognostic value of this definition in a cohort of 364 patients with palliative cancer. The patients were categorized into three groups: non-cachectic, at risk, and cachectic. Survival analyses demonstrated significant differences across groups (p = 0.005), with the median overall survival not reached in the non-cachectic group, 381 days in the at-risk group, and 157 days in the cachectic group. While low BMI and weight loss were not associated with survival in patients with edema, they became evident in those without edema (HR = 1.54 and 1.58), highlighting the confounding role of fluid retention in anthropometric assessment. Anorexia, low handgrip strength, and elevated CRP levels independently predicted poor prognosis in both full and non-edematous cohorts. These findings support the clinical relevance of an "at risk" category based on AWGC components, especially in patients without edema. This simple and pragmatic definition may facilitate the early identification of patients who could benefit from supportive interventions before cachexia becomes refractory.

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.