Lung cancer poses a global health challenge and stands as the leading cause of cancer-related deaths worldwide. However, its incidence, mortality, and characteristics are not uniform across all regions worldwide. Understanding the factors contributing to this diversity is crucial in a prevalent disease where most cases are diagnosed in advanced stages. Hence, prevention and early diagnosis emerge as the most efficient strategies to enhance outcomes. In Western societies, tobacco consumption constitutes the primary risk factor for lung cancer, accounting for up to 90% of cases. In other geographic locations, different significant factors play a fundamental role in disease development, such as individual genetic predisposition, or exposure to other carcinogens such as radon gas, environmental pollution, occupational exposures, or specific infectious diseases. Comprehensive clinical and molecular characterization of lung cancer in recent decades has enabled us to distinguish different subtypes of lung cancer with distinct phenotypes, genotypes, immunogenicity, treatment responses, and survival rates. The ultimate goal is to prevent and individualize lung cancer management in each community and improve patient outcomes.

Introduction: Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer. Methods: Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C). Results: From January to June 2021, 20 patients were enrolled in Cohort A; median age was 70.5 years (range 33–87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (4/7 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue ( p = 0.10). Mean time from referral to treatment initiation was significantly shorter in cohort A at 32.6 days (SD 13.1) versus 62.2 days (SD 31.2) in cohort B and 61.5 days (SD 29.1) in cohort C, both p < 0.0001. Conclusion: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC can lead to faster molecular results and shorten time to treatment even with smaller DNA panels. An expansion study using comprehensive NGS plasma testing with faster turnaround time is ongoing (NCT04862924).

Immunotherapy using immune checkpoint modulators has revolutionized the oncology field, emerging as a new standard of care for multiple indications, including non-small cell lung cancer (NSCLC). However, prognosis for patients with lung cancer is still poor. Although immunotherapy is highly effective in some cases, not all patients experience significant or durable responses, and further strategies are needed to improve outcomes. Therapeutic cancer vaccines are designed to exploit the body’s immune system to activate long-lasting memory against tumor cells that ensure tumor regression, with minimal toxicity. A unique feature of cancer vaccines lies in their complementary approach to boost antitumor immunity that could potentially act synergistically with immune checkpoint inhibitors (ICIs). However, single-line immunization against tumor epitopes with vaccine-based therapeutics has been disappointingly unsuccessful, to date, in lung cancer. The high level of success of several recent vaccines against SARS-CoV-2 has highlighted the evolving advances in science and technology in the vaccines field, raising hope that this strategy can be successfully applied to cancer treatments. In this review, we describe the biology behind the cancer vaccines, and discuss current evidence for the different types of therapeutic cancer vaccines in NSCLC, including their mechanisms of action, current clinical development, and future strategies.

Background: Geographical variations in the frequency of oncogenic driver alterations in non-small cell lung cancer (NSCLC) are observed worldwide, likely influenced by genetic and environmental factors. Radon, a leading cause of lung cancer in nonsmokers, may influence NSCLC’s molecular profile. Objectives: This study aims to explore the potential correlation between estimated indoor radon concentrations and the frequency of driver alterations in NSCLC across Europe. Design: Ecological study of European countries with available data on indoor radon exposure (estimated mean levels and the proportion (%) of dwellings with concentrations >200 and >400 Bq/m ³ ), and frequency of NSCLC actionable genomic alterations ( EGFR , ALK ) from PubMed articles and meeting abstracts with sample size >100 patients. Methods: We retrospectively analyzed NSCLC molecular data and radon exposure levels from European countries. Radon data, including the mean and proportion (%) of dwellings with concentrations >200 and >400 Bq/m ³ , were sourced from the European Commission Report 2005. NSCLC molecular alteration frequency ( EGFR , ALK ) was extracted from PubMed articles with sample sizes >100 patients. The correlation between molecular alteration frequencies and country-specific radon data were assessed. Results: Data on radon exposure and EGFR / ALK frequency were available for 21 European countries. Five countries had mean radon levels >100 Bq/m ³ , and eight countries had ⩾3% of dwellings with concentrations >400 Bq/m ³ . The median frequency of EGFR mutations and ALK fusions was 11.3% (range 7%–18.1%) and 4.1% (range 3.4%–12%), respectively. A positive correlation was found between estimated ALK -fusion frequency and the percentage of dwellings with >400 Bq/m ³ ( r = 0.72, p = 0.001). No correlation was found between EGFR mutation frequency and radon exposure. Conclusion: We found a positive correlation between estimated ALK fusion frequency in NSCLC and the proportion of dwellings exceeding 400 Bq/m ³ radon exposure in 21 European countries. Further research is needed to explore the potential influence of radon and other environmental factors on NSCLC with driver alterations.