Thoracic Cancer最新文献

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.

This case highlights acquired MTAP loss during disease progression in ROS1-rearranged NSCLC. Despite persistent CD74-ROS1 fusion and absence of known resistance mutations, the patient developed CNS progression after entrectinib, underscoring the value of longitudinal genomic profiling in guiding treatment decisions.

Persistent air leaks due to alveolar pleural fistula following lung resection were a frustrating clinical condition for patients and clinicians, associated with a prolonged hospital stay and increased morbidity. Several surgical strategies have been reported over the years for the closure of alveolar fistula, but the best treatment was still debated. Herein, we reported the clinical case of a patient who experienced a persistent air leak due to alveolar-pleural fistula following thoracoscopic right upper lobectomy for the management of early lung cancer. The fistula was successfully closed by thoracoscopic application of a pleural flap and polymeric sealant. Our new strategy could turn out to be useful for surgeons when standard procedures for management of APF were unfeasible or difficult to perform. Obviously, our impression should be validated by future large studies in a prospective manner.

Background: The IMpower150 trial demonstrated the efficacy of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) therapy in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its efficacy in patients with NSCLC harboring other genetic alterations in real-world settings remains unclear. This study aimed to retrospectively evaluate the efficacy of ABCP therapy in patients with NSCLC harboring other genetic alterations.

Methods: We retrospectively analyzed 61 patients with advanced NSCLC (33 with EGFR mutations: EGFR group and 28 with other genetic alterations: other group) who received ABCP therapy between January 2019 and December 2023 at a single institution in Japan, and evaluated efficacy and toxicities.

Results: Most baseline characteristics were similar except treatment timing (p < 0.001) in both groups. The median progression-free survival (PFS) was 4.5 vs. 5.1 months (p = 0.663), and the objective response rate (ORR) was 45.5% vs. 50.0% (p = 0.77) between the EGFR and other groups. In multivariate analysis, PD-L1 expression ≥ 50% was independently associated with longer PFS (HR 0.23, p < 0.001). Grade ≥ 3 adverse events were manageable and occurred at similar rates (51.5% vs. 53.6%) between the EGFR and other groups, and discontinuation was low (9.8%). Subgroup analysis for patients with KRAS mutation (n = 14) and anaplastic lymphoma kinase (ALK) fusion (n = 6) showed trends consistent with the overall cohort.

Conclusions: ABCP therapy demonstrated efficacy and manageable toxicity in NSCLC patients in both groups. Notably, those with high PD-L1 expression (≥ 50%) may derive greater PFS benefit. Further confirmation in larger prospective trials is warranted.

Introduction: Lung cancer accounts for 9% of all cancer diagnoses in Australia with a 5-year survival rate of 26%. Small cell lung cancer (SCLC) is a more aggressive subtype of lung cancer, representing 15% of all lung cancer cases and a 5-year survival of 11.1%. This study aims to assess the extent of guideline concordant treatment (GCT) delivery for SCLC in Victoria, identify patient, clinical, and hospital factors influencing GCT receipt, and evaluate its impact on survival.

Methods: Data were obtained from the Victorian Lung Cancer Registry (VLCR) in Victoria, Australia (n = 1769). Descriptive statistics were used to summarie patient and disease characteristics by treatment type, including GCT, non-GCT, and no/declined treatment. Statistical analyses included multiple logistic regression, Cox regression, and Kaplan-Meier survival estimates.

Results: 78.1% received GCT, 10.5% received non-GCT, and 11.5% had no treatment. Older age, poor performance status, and advanced cancer stage were associated with a lower likelihood of receiving GCT. Patients who received stage-specific GCT had a 60% lower mortality risk compared to those who received non-GCT treatment.

Conclusion: This study highlights significant variation in the receipt of guideline concordant treatment for SCLC, with older age, poorer performance status, and advanced cancer stage reducing the likelihood of GCT. Given the survival benefits associated with GCT, addressing barriers to its delivery is essential to improving outcomes for SCLC patients in Victoria.

Objective: This study evaluates the effectiveness and safety of C-arm cone beam CT (CBCT)-guided microcoil localization combined with uniportal video-assisted thoracoscopic surgery (VATS) for the management of small, difficult-to-localize ground-glass opacities (GGOs) and sub-solid nodules in the lungs.

Methods: We retrospectively analyzed data from 13 patients with single, small, peripheral, non-subpleural GGOs or SSN. All patients underwent successful microcoil localization using CB-CT guidance followed by uniportal VATS resection. A microcoil was positioned partly in the lung parenchyma and partly in the extra-pleural space to assist in intraoperative localization. We evaluated the rate of correct microcoil placement and the technical success of the resection.

Results: Microcoil placement was successfully performed in all patients, with an average procedure time of 28.8 ± 10.8 min. The mean nodule size was 9.9 ± 5.4 mm, and 76.9% of the nodules were classified as ground-glass opacities. No intraparenchymal bleeding was observed, and four patients (30.8%) experienced pneumothorax, all of which were self-limited and required no intervention or coil repositioning. The uniVATS resection success rate was 100%.

Conclusion: CBCT-guided microcoil localization, with partial placement of the coil in the extra-pleural space, proved to be a highly effective technique for the localization and resection of small pulmonary nodules. The procedure demonstrated high accuracy, minimal complications, reduction of procedural time, and short hospital stays. Intraoperative fluoroscopy was never necessary, with a high reduction in radiation exposure for the patient and the operator. Further studies with larger populations and longer follow-ups are needed to validate these findings.

Trastuzumab deruxtecan (T-DXd) significantly improves outcomes in HER2-positive or low metastatic breast cancer (MBC), but systematic documentation of its myotoxicity is lacking. A 45-year-old woman with HER2-low MBC and normal body composition (BMI 22.9 kg/m², visceral adipose area [VAT] 69.1 cm²) developed T-DXd myopathy. She experienced dysphagia, Grade III myalgia, and creatine kinase (CK) peak of 1755 U/L, with MRI confirming lumbar subcutaneous edema and paraspinal muscle swelling. T-DXd was discontinued. Supportive therapy included hydration, urine alkalization by sodium bicarbonate, glutathione, and magnesium isoglycyrrhizinate. By Day 8, CK decreased to 539 U/L with myalgia improvement. After 13 days off therapy, CK rebounded to 1735 U/L with Grade III myalgia, which resolved upon reinitiating support. This case report presents the first documented instance of severe T-DXd-related myopathy in a patient with normal body composition. The observed case outcomes suggest that the combination of glutathione and magnesium isoglycyrrhizinate could potentially reduce CK levels and alleviate T-DXd-associated muscle pain. However, the observed clinical efficacy is based on an individual case. Extrapolation of these clinical outcomes requires large-scale randomized controlled trials with rigorous covariate adjustment.

Sublobar resection is gaining popularity for the treatment of early stage lung adenocarcinoma, often presenting as a ground glass nodule on CT. Ground glass nodules are, however, a heterogeneous group of lesions, and they are too often equated with in situ or lepidic pattern adenocarcinoma. Many of these lesions actually harbor high grade micropapillary pattern and display spread through air spaces (STAS) on histology; features that are associated with increased recurrence following sublobar resection. Post hoc analysis of the impact of STAS in the JCOG0802 and CALGB140503 trials is currently ongoing and has yet to be published. This brief report aims to raise awareness of these pertinent issues that should be considered when approaching the management of early stage lung adenocarcinoma.

This review presents a comprehensive overview of recent advancements and clinical applications of three-dimensional (3D) reconstruction technology in thoracic surgery, with a focus on lung cancer surgery. The widespread adoption of chest computed tomography (CT) screening has increased the detection rates of early-stage lung cancers, facilitating a transition from traditional lobectomy to parenchymal-sparing sublobar resections, such as segmentectomy, which demand higher anatomical precision. 3D reconstruction technology significantly improves tumor localization, as well as vascular and bronchial visualization, thereby enhancing surgical accuracy and safety. Its key applications encompass preoperative planning, intraoperative navigation, real-time localization, vascular and airway visualization, and postoperative pulmonary function assessment, collectively contributing to improved surgical outcomes and patient prognosis. Recent innovations in artificial intelligence have streamlined and automated the reconstruction process, leading to reduced operative times and increased accuracy. However, challenges persist, including image quality limitations, algorithm robustness, and limited high-quality clinical evidence. Future integration with emerging technologies such as virtual reality and augmented reality holds promise for achieving personalized, intelligent thoracic surgical procedures. This review aims to systematically evaluate the clinical value of 3D reconstruction technology and explore its future development directions.

Objectives: Timely discovery and adequate patient management are crucial in non-small cell lung cancer (NSCLC) since long-term survival is only achievable in early-stage disease. In our study, we aimed to elucidate the effects of time to surgery on survival and to assess the impact of the COVID-19 pandemic on elapsed time until surgery.

Methods: In total, 2536 Caucasian NSCLC patients who underwent curative-intent lung resection surgery were included in this study. 1 month, 2 months, 77 days, and 91.06 days between CT-based diagnosis and surgery were evaluated as possible cut-off values for worse outcome. Survival curves were estimated by Kaplan-Meier plots, and the differences between groups were compared using the log-rank test. Multivariate analysis was performed using a Cox regression model.

Results: Patients with time-to-surgery ≥ 2 months had significantly impaired overall survival (OS) (vs. those with < 2 months; p = 0.002). In our multivariate model, time-to-surgery (p = 0.011), age (p = 0.02), diabetes mellitus (p = 0.02), disease stage (p = 0.0001) and vascular invasion (p < 0.001) all had a significant impact on OS. Importantly, during the COVID-19 pandemic, the elapsed time between diagnosis and surgery increased with a median of 12 days, resulting in a significant delay in time-to-surgery compared to the pre-pandemic period (p < 0.001). Post hoc tests showed, however, that there were no significant differences in time-to-surgery concerning the major waves of COVID-19 infections.

Conclusions: Time-to-surgery is an independent predictor of long-term survival in surgically treated NSCLC. In general, the COVID-19 pandemic caused a significant delay in the elapsed time until surgery, but the specific COVID-19 waves had no significant impact on time-to-surgery.