Determining optimal clinical target volume margins based on microscopic extracapsular extension of metastatic nodes in patients with non-small-cell lung cancer after chemotherapy or chemotherapy combined with immunotherapy.

Background: No standard has been established for the clinical target volume (CTV) margins of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) receiving chemotherapy or chemotherapy combined with immunotherapy followed by radiotherapy. This study aimed to discuss the CTV range of NSCLC after chemotherapy or chemotherapy combined with immunotherapy by observing the microscopic extent of tumor spread beyond the LN capsule.

Methods: We retrospectively analyzed the data of 240 patients with stage II and III NSCLC who underwent surgery without neoadjuvant therapy, with neoadjuvant chemotherapy (NAC), or with NAC combined with immunotherapy (NACI). We measured the maximal distance of extracapsular extension (ECE) using a digital microscope, analyzed the correlation between clinicopathological features and ECE distance, and determined the CTV margins of metastatic LN under different treatment methods.

Results: The ECE distance differed significantly among the three groups (p < 0.001). We determined appropriate margin widths based on a 5% error risk as 3.00, 2.30, and 1.40 mm for direct surgery, NAC, and NACI, respectively. Multivariate analysis revealed that the ECE of metastatic LN correlated with the treatment methods and LN size.

Conclusion: The existing CTV delineation standards may increase the radiation toxicity of patients. We believe that different CTV margins should be used for LN in patients with NSCLC receiving different treatments. To ensure 95% coverage of ECE, the gross tumor volume of untreated, chemotherapy-treated, and chemotherapy combined with immunotherapy-treated patients should be expanded by 3.00, 2.30, and 1.40 mm, respectively, to obtain the CTV.