Francesca Zanelli

Over the last few decades, survival among patients with lung cancer (LC) has progressively improved due to major advances in treatment strategies, particularly the introduction of immunotherapy and targeted therapies, as well as the increased detection of early-stage disease resulting from the widespread use of chest computed tomography (CT). Although the reduction in mortality, frequently achieved through effective control of the primary disease, represents a major therapeutic success, it also raises new clinical challenges, including the long-term management of cancer remission or disease stability and the competing risk of adverse outcomes related to comorbidities and treatment-related toxicities. Among these, cardiovascular (CV) complications have emerged as particularly relevant because of their frequency and prognostic impact. Within the framework of a holistic long-term management approach, increasing attention should be directed toward non-pharmacological interventions targeting lifestyle factors, particularly nutrition and physical exercise, whose role remains underestimated. These interventions may modulate chronic inflammation and immune responses, which are key drivers influencing both the effectiveness of novel anticancer therapies and the progression of cardiovascular complications. Patients with LC frequently present malnutrition and unfavorable lifestyle patterns associated with substantial physical and psychological stress, factors that may negatively affect treatment outcomes and overall prognosis. This narrative review examines the emerging role of targeted nutritional strategies and structured physical exercise as integral components of supportive care in LC, with a specific focus on their impact on cardiac metabolism, CV risk, and response to anticancer therapies, including immunotherapy.

Background: Cancer-Related Fatigue (CRF) significantly impairs physical performance and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC). The OVER-CRF study evaluated the feasibility, safety, and preliminary efficacy of a personalized pulmonary rehabilitation (PR) program combining supervised exercise and education during active treatment. Methods: Patients with stage II–III NSCLC were randomized to Early-PR (initiated at the start of anticancer therapy) or Delayed-PR (initiated three months later). The 3-month intervention included two educational sessions and eight supervised exercise sessions. The primary outcome was adherence; secondary outcomes included safety, CRF (FACIT-FS), QoL (EORTC-QLQ-C30), and physical performance (6MWT). Results: Thirty-one patients were randomized (mean age 67.4 years). Adherence was excellent (Early: 86.7%; Delayed: 91.7%), exceeding feasibility thresholds. No exercise-related adverse events occurred. At 12 months, 50% of participants showed clinically meaningful CRF improvements. While both groups improved 6MWT performance during the intervention, the Delayed-PR group demonstrated more sustained QoL improvements from T1 through T3 compared to the Early-PR group. The dropout rate (25.8%) was consistent with the existing literature. Conclusions: Personalized PR is feasible and safe for NSCLC patients undergoing multimodal therapy. While early intervention provides immediate benefits, initiation timing may influence long-term QoL trajectories. These findings support integrating exercise and education into standard oncological care pathways.

Growing evidence suggests that optimized nutritional status and regular physical activity enhance immunotherapy responsiveness by modulating immunometabolism, improving T-cell function, reducing chronic inflammation, and favorably shaping the gut microbiota. Cancer-related metabolic dysfunction and treatment-induced cardiotoxicity converge to impair both skeletal and cardiac muscle energetics, thereby limiting treatment tolerance and effectiveness. Lung cancer (LC) patients frequently present with malnutrition, systemic inflammation, sarcopenia, and pre-existing cardiovascular disease (CVD), conditions that not only compromise functional status and survival but also represent significant competing risks to oncologic outcomes. By counteracting sarcopenia and malnutrition, lifestyle interventions may also reduce immune-related adverse events (irAEs) and mitigate cardiovascular (CV) toxicity, ultimately allowing patients to sustain effective treatment intensity. This narrative review examines the emerging role of targeted nutritional strategies and structured physical exercise as integral components of supportive care in LC, with a specific focus on their impact on cardiac metabolism, CV risk, and response to anticancer therapies, including immunotherapy. In this context, exercise and appropriate dietary interventions emerge as modifiable factors capable of restoring metabolic flexibility, improving mitochondrial function, and reducing systemic inflammation. These effects are particularly relevant in patients receiving immune checkpoint inhibitors (ICIs), where metabolic health and immune competence are tightly interconnected and trained immunity may be a key issue. Finally, the review discusses future challenges and perspectives, emphasizing the impact of CVD on long-term LC survivors’ outcome and of allostatic load and financial toxicity on adherence to lifestyle interventions. The integration of personalized nutrition and exercise programs into cardio-oncology care pathways is proposed as a key strategy to enhance immunotherapy efficacy, improve cardiometabolic resilience, and translate prolonged survival into better quality of life.

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.

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.

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).