Sinoatrial Node Irradiation in Patients Undergoing Definitive Stereotactic Body Radiation Therapy (SBRT) for Central Lung Cancers

Abstract

The clinical consequences of sinoatrial node (SAN) and atrioventricular node (AVN) irradiation in patients undergoing thoracic stereotactic body radiation therapy (SBRT) remains unclear. We examined the relationship between SAN and AVN dose with survival outcomes in patients with central non-small cell lung cancer (NSCLC) tumors. A single-institutional retrospective review of patients with primary NSCLC undergoing definitive SBRT for centrally located tumors from February 2007 to December 2021 was performed. Central tumors were defined as within 2 cm of the proximal airway, mediastinum, great vessels, or spinal cord whereas ultracentral tumors were directly abutting any of the above structures. All patients underwent five-fraction SBRT to a total dose of 50 to 60 Gy. The SAN and AVN were contoured in accordance with a published contouring atlas and the maximum dose (Dmax) and mean dose (Dmean) for each structure were calculated. Sequential log rank testing between the 50th and 90th percentiles was used to identify potential cutoff values for the corresponding dosimetric parameters and non-cancer associated survival. Among 93 eligible patients, the median age was 72.5 years (Inter-Quartile Range [IQR], 66.6-78.3), median follow up was 32.4 months (IQR, 13.0-49.6), and 48 patients were female (52%). There were 49 ultracentral tumors (53%) and the median planning target volume (PTV) was 31.0 cc (IQR, 18.0-53.3). The median SAN Dmax and Dmean were 95 cGy (IQR, 37-1,072) and 58 cGy (IQR, 26-641), respectively. The median AVN Dmax and Dmean were 45 cGy (IQR, 19-506) and 34 cGy (IQR, 15-160), respectively. Candidate cutoff values for SAN Dmax and Dmean were 1,309 cGy and 814 cGy, respectively. No significant cutoff values were identified for either AVN parameter. Kaplan-Meier analysis for the proposed SAN Dmean constraint was significantly associated with overall (p = 0.016) and non-cancer associated survival (p = 0.028). The SAN Dmax constraint was significantly associated with only overall survival (p = 0.029). In a multivariate model, the SAN Dmean cutoff significantly correlated with both overall (Hazard Ratio [HR] 2.1 [1.13-3.78], p = 0.019) and non-cancer associated survival (HR 2.39 [1.12-5.10], p = 0.025) whereas the SAN Dmax cutoff was only significantly associated with overall survival (HR 1.95 [1.03-3.68], p = 0.041). SAN Dmax and Dmean were associated with significantly worse overall survival using cut-off values of 1,309 cGy and 814 cGy, respectively. SAN dose should be considered in radiation planning and further study on the consequence of SAN irradiation during SBRT is warranted.