Purpose/ObjectivesCancer diagnosis and treatment, including radiation therapy (RT), cause significant patient stress. Mindfulness and social support have been shown to help manage the psychological effects of cancer treatment. The objective of our study was to determine the sociodemographic and clinical factors associated with stress burden in patients undergoing RT. Materials/MethodsPatients undergoing RT for cancer at a single institution were given 3 surveys to complete at the beginning of on-treatment visit. The surveys included the Perceived Stress Scale (PSS), Medical Outcomes Study Social Support Survey (MOS), and Mindfulness Attention Awareness Scale (MAAS), which were used to measure stress, social support, and trait mindfulness, respectively. Linear regression analysis was performed to determine associations between perceived stress and age, patient sex, race and ethnicity, treatment intent, disease site, trait mindfulness, and social support. Factors significant on univariable analysis were analyzed with a multivariable analysis. ResultsA total of 93 patients completed 279 surveys during treatment at a tertiary care academic institution from July to September 2019. Median scores for PSS, MOS, and MAAS were 14.6 (range: 0-31, SD: 6.9), 4.2 (range: 0-5, SD: 1.0), and 5.1 (range: 3.1-6.0, SD: 0.8), respectively. On univariable analysis, mindfulness and social support were associated with decreased stress burden, and female sex and palliative intent were associated with increased stress burden. These factors all maintained significance on multivariable analysis. ConclusionThese results suggest measures to improve mindfulness and perceived social support, such as mindfulness meditation and psychoeducational approaches, may lessen the stress burden and improve quality of life for patients undergoing RT. Future studies should analyze the longitudinal impact of individual patient characteristics, including patient sex and treatment intent, to better understand their effects on psychological maladjustment during cancer care