Introduction: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. Methods: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. Results: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. Conclusion: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.
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