Predictors of subclinical nodal involvement in clinical stages I and II non-small cell lung cancer: Implications in the inoperable and three-dimensional dose-escalation settings

Purpose: When mediastinal lymph nodes are clinically uninvolved in the sett ing of inoperable non-small cell lung cancer, whether conventional radiatio n techniques or three-dimensional dose-escalation techniques are used, the benefit of elective nodal irradiation is unclear. Inclusion of the clinical ly negative mediastinum in the radiation portals increases the risk of lung toxicity and limits the ability to escalate dose. This analysis represents an attempt to use clinical characteristics to estimate the risk of subclin ical nodal involvement, which may help determine which patients are most li kely to benefit from elective nodal irradiation. Methods: From 1987 to 1990, 346 patients undergoing complete resection of n on-small cell lung cancer underwent a preoperative computed tomographic sca n revealing no clinical evidence of N2/N3 involvement. Multivariate regress ion and regression tree analyses attempted to define which patients were at highest risk for subclinical mediastinal involvement (N2) and which patien ts were at highest risk for subclinical N1 and/or N2 involvement (N1/N2). I mmunohistochemical data suggest that the conventional histopathologic techn iques used during this study somewhat underestimate the true degree of lymp h node involvement; therefore, a third end point was also evaluated: N1 inv olvement and/or N2 involvement and/or local-regional recurrence (N1/N2/LRR) . Results: Regression analyses revealed that the following factors were indep endently associated with a high risk of more advanced disease: positive pre operative bronchoscopy (NZ, p = 0.02; N1/N2, p < 0.0001; N1/N2/LRR, p < 0.0 01) and tumor grade 3/4 (N1/N2/LRR, p < 0.01). A regression tree analysis w as then used to separate patients into risk groups with respect to N1/N2/LR R. Conclusion: In inoperable non-small cell lung cancer, the patients for whom mediastinal radiation therapy mag most likely be indicated are those with a positive preoperative bronchoscopy, especially with large (> 3 cm) primar y tumors. (C) 1999 Elsevier Science Inc.