New perspectives on inoperable early-stage lung cancer management: Clinicians, physicists, and biologists unveil strategies and insights

This work provides a comprehensive overview of the current landscape of lung cancer, emphasizing the global significance of the disease and the challenges associated with its diagnosis and treatment. The authors highlight the prevalence of lung cancer, with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCC) being the predominant histological subtypes. Advanced-stage diagnosis is common due to the asymptomatic nature of the disease, leading to a systemic treatment approach involving chemotherapy and radiotherapy.The authors discuss the evolution of treatment strategies, with a focus on the emergence of targeted therapies for advanced-stage NSCLC. A panel of predictive biomarkers, both DNA-based (e.g., EGFR, BRAF, KRAS) and RNA-based (e.g., ALK, ROS1, RET, MET), is highlighted as crucial for molecular analysis in diagnostic specimens. While advanced NSCLC patients benefit from targeted therapy, early-stage patients may undergo surgery followed by adjuvant cisplatin-based chemotherapy or stereotactic body radiotherapy (SBRT). The work emphasizes the importance of screening programs for early detection, with a particular focus on the Italian Lung Cancer Screening Network (RISP). RISP aims to recruit high-risk individuals for screening using low-dose computed tomography (LDCT) and implements primary prevention interventions, such as smoking cessation support. The program's objectives include reducing lung cancer mortality, developing a recruitment system for suitable candidates, and integrating radiological, clinical, and molecular data for individual risk profiling. The review also delves into the perspectives of clinicians, physicists, and biologists in the management of lung cancer. Clinicians focus on risk stratification and treatment options, physicists discuss the role of medical physicists in SBRT, and biologists explore precision medicine, biomarkers, and challenges inearly detection.The comparison between surgery and SBRT for early-stage NSCLC patients is discussed, emphasizing the efficacy of SBRT as a non-invasive approach for patients ineligible for surgery. The authors also touch upon ongoing trials addressing the clinical performance of SBRT in comparison to surgery and the challenges posed by preexisting treatment preferences. The physicist's perspective emphasizes the role of medical physicists in lung SBRT, covering aspects from treatment planning to quality assurance. The importance of radiation physics expertise, advanced imaging techniques, image-guided radiation therapy (IGRT), and adaptive radiotherapy is highlighted. Customized models for tumor control and toxicity evaluation, derived from dosimetric analysis, contribute to treatment optimization and patient care. The biologist's viewpoint explores precision medicine in advanced NSCLC treatment, emphasizing the role of somatic alterations as predictive biomarkers. Challenges in early detection are discussed, and the ideal screening tool is proposed to integrate radiological, pathological, and clinical data. Various blood-derived biomarkers and diagnostic assays, such as EarlyCDT-Lung, Nodify XL2, and miRNA-based signatures, are presented as potential tools for early-stage lung cancer detection. In conclusion, the review underscores the multidisciplinary approach required for effective lung cancer management. Advances in early detection, personalized treatment, and the integration of technology and biomarkers offer hope for improving outcomes and reducing the global burden of lung cancer.