Gökce Yavuz

Introduction: Upfront surgery is standard of care for resectable early-stage EGFRmut non-small cell lung cancer (NSCLC). However, lymph node upstaging—defined as pathological nodal status exceeding clinical nodal staging—significantly impacts prognosis and adjuvant treatment decisions. This study aims to determine the rate of nodal upstaging and identify associated predictive factors in EGFRmut NSCLC undergoing upfront surgery.Materials and Methods: Patients with EGFRmut NSCLC who underwent upfront resection between January 2014 and December 2023 were identified from a prospectively maintained database. Data on patient demographics, preoperative imaging and mediastinal staging, tumor characteristics, and final pathological results were collected and analyzed. Univariable and multivariable models were used to identify predictors of nodal upstaging, with significance set at p < 0.05. A multivariable logistic regression model was developed and validated externally.Results: Among 107 patients, 74 (69.2%) were female and the mean age was 67.3 years. 27 patients (25.2%) had pathological nodal upstaging. On multivariable analysis, higher SUVmax of the primary tumor (OR 1.22, 95% CI: 1.04–1.42, p = 0.015) and purely solid lesions (consolidation-to-tumor ratio = 1.0) (OR 10.98, 95% CI: 2.72–44.3, p < 0.001) were independent predictors of nodal upstaging. The model demonstrated a sensitivity of 92.3%, specificity of 77%, a positive predictive value of 58.5%, and a negative predictive value of 96.6%.Conclusion: Pathological nodal upstaging occurs frequently in resectable EGFRmut NSCLC. Higher primary tumor SUVmax and purely solid CT appearance independently predict nodal upstaging and may improve preoperative risk stratification for mediastinal staging and treatment planning.

Objectives: Thoracic sarcomas are a heterogeneous group of rare mesenchymal tumors. This study aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) in patients undergoing resection of primary thoracic soft tissue and bone sarcomas. Methods: We retrospectively reviewed patients with primary intrathoracic or chest wall sarcomas who underwent surgical resection between 2005 and 2020. Eighty-four patients were included: 60 with soft tissue sarcoma and 24 with bone sarcoma. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors for PFS and OS. Results: The most common histological subtypes were chondrosarcoma (19%) and undifferentiated pleomorphic sarcoma (17.8%). Overall, 54.8% of patients were female, and the mean age was 55.7 years (SD 17.9). Neoadjuvant and adjuvant therapies were primarily administered in intermediate- (G2) and high-grade (G3) tumors. Median OS was 28.4 months. On multivariate analysis, high tumor grade (G3 vs. G1–2) independently predicted worse PFS (HR 3.21, 95% CI 1.34–7.68; p = 0.01) and OS (HR 4.40, 95% CI 1.56–12.41; p = 0.01). Larger tumor size (HR 1.09, 95% CI 1.03–1.15; p = 0.001) and incomplete resection (HR 12.21, 95% CI 2.56–58.34; p = 0.002) were independently associated with worse OS, while lung metastases at diagnosis independently predicted worse PFS (HR 4.89, 95% CI 1.21–19.69; p = 0.03). Conclusions: Histological grade is the strongest independent predictor of survival in resected thoracic sarcoma. Surgery alone appears adequate for low-grade sarcomas, whereas multimodal treatment strategies seem particularly relevant for patients with higher-grade sarcomas.

Introduction: Acute rejection is a significant risk factor for developing chronic lung allograft dysfunction. Current monitoring tools, transbronchial biopsies and HLA antibody determination, have limitations in detecting acute rejection. This study aims to explore the potential utility of donor-derived cell-free DNA (ddcfDNA) as a non-invasive biomarker for detecting acute rejection in lung transplant recipients (LTR).Methods: We developed a molecular method based on digital droplet PCR to determine the total amount and the proportion of ddcfDNA. Using blood samples collected sequentially post-transplant from a cohort of 81 LTR, we compared median levels of %ddcfDNA in patients with acute cellular rejection (ACR), antibody-mediated rejection (AMR), infection, or decline in pulmonary function (FEV₁).Results: Median %ddcfDNA levels were significantly higher in groups with ACR (1.92% [0.70%, 2.30%], p=0.0006), AMR (1.27% [0.34%, 2.29%], p=0.0009), isolated lymphocytic bronchiolitis (0.54% [0.23%, 2.18%], p=0.03), and infection or prolonged ventilation over 30 days (0.50% [0.22%, 2.35%], p=0.005) versus stable allograft function group (0.26% [0.09%, 0.60%]). %ddcfDNA levels were also elevated in patients with FEV1 loss compared to those with stable or improving FEV1 after 12 months (1.98% vs. 1.36%, p=0.04). An optimal cut-off of 0.73% for %ddcfDNA was calculated to detect ACR and AMR with 80% specificity and 68% sensitivity.Discussion: %ddcfDNA is a promising biomarker for identifying allograft injury due to acute rejection in LTR and could be a valuable tool for monitoring allograft health.

The aim of this study was to evaluate the diagnostic accuracy of integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of suspected or proven lung cancer, and to investigate potential risk factors for false negative and false positive HMLN metastases. We retrospectively analyzed 162 consecutive patients with suspected or pathologically proven non-small cell lung cancer (NSCLC). The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficacy of 18F-FDG-PET/CT. Univariate and multivariate analyses were conducted to detect risk factors of false positives and false negatives. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of integrated 18F-FDG-PET/CT in detecting HMLN metastases were 59.1% (26/44), 69.1% (65/94), 47.3% (26/55), 78.3% (65/83), and 65.9% (91/138), respectively. The ROC curve showed an area under the curve (AUC) of 0.625 (95%-CI 0.468–0.782). The incidence of false negative and false positive HMLN metastases was 21.7% (18/83) and 52.7% (29/55), respectively. Our data shows that integrated 18F-FDG-PET/CT staging provides lower specificity and sensitivity. This confirms the ESTS guideline on lymph node staging for PET-positive HMLN. Yet it advocates more invasive staging even for PET-negative HMLN.

Introduction: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation.Methods: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19).Results: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES.Conclusion: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.