Lung cancer in young patients is rare and has unique clinicopathological features. However, the molecular features of lung cancer in these patients are unclear. In this study, we aimed to describe the molecular features and outcomes of lung adenocarcinoma in patients aged ≤35 years. A total of 89 patients aged ≤35 years with pathologically diagnosed lung adenocarcinoma were retrospectively evaluated. Mutations in 59 cancer-associated genes and fusions of ALK and ROS1 were analyzed to understand the molecular features of young patients with lung adenocarcinoma. The clinicopathological characteristics and prognosis of each patient were reviewed. Of the 89 young patients, 25 (28.1%) were male, 9 (10.1%) were smokers, and the median age was 32 years (range, 18–35 years). The authors analyzed 59 genes and a total of 6 mutations and 2 fusion genes were detected. These genes were distributed among 60 patients, 12 of which had two or more mutations. ERBB2 mutations were most common (24.7%), followed by EGFR mutation (21.3%), ALK fusion (16.9%), TP53 mutation (9.0%), BRAF mutation (3.4%), PIK3CA mutation (1.1%), CTNNB1 mutation (1.1%), and ROS1 fusion (1.1%). EGFR, ERBB2, and TP53 mutations, gene abnormalities, and ALK fusions all had significant correlations with histopathological differentiation (P < 0.01). ALK fusions and EGFR mutations conferred a significantly worse prognosis than did ERBB2 mutations and tumors that contained no mutations or fusions (P < 0.01). The molecular features of lung adenocarcinoma in young patients are different from those of common adenocarcinoma, and the main driver genes are closely correlated with tumor differentiation and prognosis.

Background. Most patients with small-cell lung cancer (SCLC) have extensive-stage (ES) disease with a poor prognosis. Immunotherapy has shown good therapeutic effects in the treatment of ES-SCLC. We performed a real-world retrospective study to evaluate the safety and efficacy of PD-L1 inhibitors plus chemotherapy in patients with ES-SCLC. Method. A total of 224 patients diagnosed with ES-SCLC between March 2017 and April 2021 were included, of which 115 received only etoposide-platinum (EP) chemotherapy,and 109 received programmed cell-death ligand 1 (PD-L1) inhibitors and EP. Results. Immune checkpoint inhibitors (ICIs) plus platinum were associated with a significant improvement in overall survival (OS), with a hazard ratio (HR) of 0.60 (95% CI, 0.42–0.85; ); median OS was 19 months in the ICIs plus EP group vs. 12 months in the EP group. The median progression-free survival (PFS) was 8.5 and 5.0 months, respectively (HR for disease progression or death, 0.42; 95% CI, 0.31–0.57; ). Male patients <65 years old, Stage IV, PS 0-1, without liver and brain metastasis had a better OS in the ICIs plus EP group than the EP group. The PFS and OS in the durvalumab plus chemotherapy group were insignificantly longer than that of the atezolizumab plus chemotherapy group. Any adverse effects (AEs) of grade 3 or 4 occurred in 50 patients (45.9%) in the ICIs plus EP group and 48 patients (41.7%) in the EP alone group. The most common immune-related AEs (irAEs) were immune hypothyroidism events (17.1%, 7/41), immune dermatitis (9.8%, 4/41), and immune pneumonia (9.8%, 4/41) in the durvalumab plus platinum-etoposide group. Immune liver insufficiency (10.3%, 7/68) and immune hypothyroidism (8.8%, 6/68) were the most common irAEs in the atezolizumab plus platinum-etoposide group. Conclusion. This study shows that adding PD-L1 inhibitors to chemotherapy can significantly improve PFS and OS in patients with ES-SCLC and demonstrates its safety without additional AEs.

Pulmonary nuclear protein in testis (NUT) carcinoma is a rare and aggressive malignancy that often exhibits clinical and pathological features overlapping with other thoracic malignancies, posing significant challenges for accurate diagnosis and leading to poor treatment outcomes. We conducted a retrospective analysis of five patients diagnosed with pulmonary NUT carcinoma between 2020 and 2023. Comprehensive clinical, imaging, histopathological, and molecular data and survival outcomes were collected. The cohort included three females and two males, with a median age of 44 years. Clinical features commonly involved centrally located masses with mediastinal invasion. Distant metastases to bones, pleura, and lungs were confirmed in 60% of cases. Diagnostic confirmation was achieved through NUT protein positivity via IHC and FISH rearrangements in all five patients. RNA sequencing identified BRD3-NUTM1 fusions in 60% (3/5) patients. Chemotherapy was employed as the initial treatment strategy but showed limited efficacy in advanced stages. Among two patients undergoing surgical resection, better outcomes were achieved in the patient receiving adjuvant therapy with overall survival (OS) exceeding 36 months. Immunotherapy demonstrated limited benefit, likely attributable to low PD-L1 expression and an immunologically “cold” tumor microenvironment. Despite multimodal treatment approaches, three out of five patients in advanced pulmonary NUT carcinoma died to the disease, with OS ranging from 6 to 15 months. Advanced molecular techniques are critical for diagnosing pulmonary NUT carcinoma, but survival outcomes remain poor. Surgical resection with adjuvant therapy offers better outcomes for early-stage patients, while chemotherapy and immunotherapy show limited efficacy in metastatic cases due to the tumor’s aggressive behavior. Early detection and innovative therapies are essential for improving outcomes.