Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the “one-fits-all” paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.

Thymic epithelial tumors (TETs) are rare thymic neoplasms. There are approximately 1.5 cases per million TETs per year. They are the most common anterior mediastinal tumors in adults. Due to limited activity of available treatment options novel strategies and treatment options are needed and treatment with immune checkpoint inhibitors is an attractive option. Thymic epithelial tumors have one of the lowest tumor mutational burden among all cancer in adults, but high expression of PD-L1 on tumor cells and abundant CD8+ lymphocytes provide a strong rational for implementing immune checkpoint inhibitors (ICIs) which target PD-1/PD-L1 pathway in the treatment of TETs. Few small early stage clinical trials were published so far evaluating efficacy of pembrolizumab and avelumab in thymoma and thymic carcinoma patients. Al trials showed reasonable response rates and progression-free survival. Higher PD-L1 expression was predictor of response in all trials. However, increased incidence of immune-related adverse events was seen in TET patients treated with immune checkpoint inhibitors compared to patients with other cancers. At the moment, ICIs are not standard of care for patients with TET and larger trials are needed to establish the right role of ICIs regarding efficacy and safety of these agents.

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients’ overall survival was analyzed with the Kaplan–Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV₁% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

Daily-practice challenges in oncology have been intensified by the approval of immune checkpoint inhibitors (ICI). We aimed to outline current therapy policies and management of locally advanced unresectable stage III non-small-cell lung cancer (NSCLC) in different countries. One thoracic oncologist from each of the following countries—Belgium, Croatia, Greece, Israel, the Netherlands, Norway, Poland, Portugal, Romania, Slovenia, and Switzerland—participated in an electronic survey. Descriptive statistics were conducted with categorical variables reported as frequencies and continuous variables as median and interquartile range (IQR) (StataSE-v15). EBUS (endobronchial ultrasound bronchoscopy) was used either upfront or for N2 confirmation. Resectability is still a source of disagreement; thus, decisions vary within each multidisciplinary team. Overall, 66% of stage III patients [IQR 60–75] undergo chemoradiation therapy (CRT); concurrent CRT (cCRT) accounts for most cases (~70%). Performance status is universally used for cCRT eligibility. Induction chemotherapy is fairly weighted based on radiotherapy (RT) availability. Mean time to evaluation after RT completion is less than a month; ICI consolidation is started within six weeks. Durvamulab expenditures are reimbursed in all countries, yet some limiting criteria exist (PD-L1 ≥ 1%, cCRT). No clear guidance on therapies at Durvamulab progression exist; experts agree that it depends on progression timing. Given the high heterogeneity in real-world practices, standardized evidence-based decisions and healthcare provision in NSCLC are needed.

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

Primary sarcoma of the lung is a very rare malignant tumor accounting for less than 0.5% of all lung tumors and presenting diagnostic and treatment challenge. We describe a case of a patient diagnosed with primary lung undifferentiated pleomorphic sarcoma developing subsequent peritoneal and small bowel metastases, which stand for highly unusual disease presentation. A 57-year-old male presented with extensive partially necrotic tumor in the left upper lobe (LUL) of the lung that involved LUL bronchus and extended to the visceral pleura. There was no evidence of nodal or visceral dissemination. After initial presentation, the patient was admitted to the hospital’s pulmonology department for further workup. The most likely diagnosis based on biopsy specimen was poorly differentiated sarcoma. Left pneumonectomy with mediastinal lymph node dissection was performed. The final pathohistological diagnosis (PHD) was undifferentiated pleomorphic sarcoma (UPS). Three months after lung surgery, a follow-up CT scan was done which showed a 60-mm obstructive metastatic intraabdominal lesion with small bowel infiltration and further separate peritoneal deposits. Unfortunately, an urgent surgery had to be performed as the patient developed signs of acute abdomen due to bowel perforation. Only 2 months later, the patient passed away at home. Treatment options of UPS are based on algorithms used in treatment of extremity lesions with well-established role of surgery. However, the role of perioperative chemotherapy remains equivocal with no strong evidence-based data due to the rarity of the disease. Small bowel is an unexpected metastatic site, but of significant clinical relevance.