Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. In recent years, mortality rates have declined due to antismoking policies, earlier detection, and the advent of targeted therapies and immunotherapy, particularly for non-small cell lung cancer (NSCLC), which accounts for 85% of all cases. With improved survival, however, LC patients are increasingly exposed to competing causes of mortality, among which cardiovascular disease (CVD) is highly prevalent, affecting 30–50% of patients and contributing to nearly 30% of deaths. This burden reflects both shared risk factors and the cardiotoxic potential of radiotherapy, chemotherapy, and immunotherapy. Beyond acute adverse cardiovascular events during treatment, real-world data indicate that immune checkpoint inhibitors (ICIs) may also exert chronic cardiovascular effects, significantly accelerating the atherosclerotic process in multimorbid patients. These findings underscore the importance of accurate baseline assessment and aggressive management of cardiovascular risk factors in LC patients—particularly in the adjuvant and neoadjuvant settings, where longer survival is anticipated. Moreover, long-term monitoring should be implemented through a tailored, multiparametric strategy that integrates novel biomarkers and advanced artificial intelligence–assisted imaging techniques. Achieving this ambitious goal requires the close collaboration of a multidisciplinary team, with cardiologists playing a pivotal role. This review will address the complexity of LC patients, focusing on the interplay of cardio-immuno-metabolic factors, summarizing the cardiovascular impact of immunotherapy across metastatic, locally advanced, and perioperative settings, and outlining practical strategies for the management of these vulnerable patients.

This study assessed the incidence, mortality, and survival of lung cancer subtypes of NSCSLC (non-small-cell lung cancer), SCLC (small-cell lung cancer), and other morphologies. It is an observational epidemiological study using 7197 cases from the Reggio Emilia Cancer Registry recorded between 2001 and 2020 in males and females. The incidence of NSCLC in 5104 males indicates a significant 3% annual increase until 2013 and then a decline of −3.2% that is not statistically significant; until 2014, mortality increased significantly (3.2%), but it then decreased non-significantly (−12.1%), especially squamous cell cancer. In 2093 females, the incidence and mortality trends continued to rise significantly through 2012, and then they began to slightly decline (not statistically significant). The two-year relative survival of NSCLC increased from 32% to 38% in males and from 42% to 56% in females. SCLC in males decreased significantly both in incidence and mortality, while in women, it showed a slight increase (significantly for incidence but not for mortality). This study is important because it analyzes the decrease in lung cancer in males and the increase in females in relation to the different histotypes. Our study’s findings confirmed a decline in male incidence and death beginning in 2013. We were unable to determine if the drop in cigarette smoking and the introduction of new drugs such as EGFR in first-line therapy were responsible for the lower incidence.

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. In recent years, mortality rates have declined due to antismoking policies, earlier detection, and the advent of targeted therapies and immunotherapy, particularly for non-small cell lung cancer (NSCLC), which accounts for 85% of all cases. With improved survival, however, LC patients are increasingly exposed to competing causes of mortality, among which cardiovascular disease (CVD) is highly prevalent, affecting 30–50% of patients and contributing to nearly 30% of deaths. This burden reflects both shared risk factors and the cardiotoxic potential of radiotherapy, chemotherapy, and immunotherapy. Beyond acute adverse cardiovascular events during treatment, real-world data indicate that immune checkpoint inhibitors (ICIs) may also exert chronic cardiovascular effects, significantly accelerating the atherosclerotic process in multimorbid patients. These findings underscore the importance of accurate baseline assessment and aggressive management of cardiovascular risk factors in LC patients—particularly in the adjuvant and neoadjuvant settings, where longer survival is anticipated. Moreover, long-term monitoring should be implemented through a tailored, multiparametric strategy that integrates novel biomarkers and advanced artificial intelligence–assisted imaging techniques. Achieving this ambitious goal requires the close collaboration of a multidisciplinary team, with cardiologists playing a pivotal role. This review will address the complexity of LC patients, focusing on the interplay of cardio-immuno-metabolic factors, summarizing the cardiovascular impact of immunotherapy across metastatic, locally advanced, and perioperative settings, and outlining practical strategies for the management of these vulnerable patients.

The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts—24%) and MET exon 14 skipping mutation (11 pts—18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79–4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08–7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy.