Adrenal Stereotactic Body Radiation Therapy: Do Dosimetric Factors Predict for Grade 2+ Lymphopenia?

Abstract

Recent studies suggest improvement in outcomes in multiple oligometastatic tumor sites with immunotherapy (IO) and radiation therapy (RT). However, RT may induce lymphopenia that can be immunosuppressive and dosimetric consensus is lacking on parameters predicting grade ≥2 lymphopenia. In this study, we evaluated lymphopenia post receipt of stereotactic body RT (SBRT) for adrenal metastases to see if we could identify any modifiable treatment planning factors. Patients with adrenal oligometastases who were treated with conventional SBRT or MRI-guided (MRgSBRT), had absolute lymphocyte count (ALC) and white blood cell count (WBC) data available within 6 weeks before and after their radiation treatment, and had contouring data available for review were included in this IRB approved retrospective study. Lymphopenia was graded for ALC as: Grade 1 (1.0-0.8 no/ul), Grade 2 (<0.8 - 0.5 no/ul), Grade 3 (<0.5-0.2 no/ul), Grade 4 (<0.2 no/ul). The vertebral bodies (VB), at the level of the planning treatment volume (PTV) and one above and below, and the spleen were contoured. Dosimetric variables of interest included spleen and VB mean dose (Gy) as well as V2.5-20 Gy in 2.5 Gy increments. Regression analyses were used to identify dosimetric variables associated with absolute and relative difference in ALC post-SBRT. A total of 30 patients were identified with a slight male predominance (N = 17, 57%) and most commonly left adrenal (N = 17) versus right adrenal (N = 10, 33%) or bilateral metastases (N = 3, 10%). Grade 2+ lymphopenia was observed in N = 7 patients pre-SBRT (23%) and N = 17 patients post-SBRT (57%). N = 26 (87%) of the patients had previous chemotherapies and N = 17 (57%) had previous immunotherapy. Multiple primary tumor types were represented with the most common non-small cell lung cancer (N = 14, 47%), followed by melanoma (N = 4, 13%) and small cell lung cancer (N = 3, 10%). Most patients were treated with non-MRgSBRT (N = 19, 63%) vs MRgRT (N = 11, 37%) and all received SBRT in 5 fractions with median dose 50 Gy (Range: 25 - 60 Gy). The median pre-SBRT ALC was 1.13 (Range: 0.39 - 2.96) and median post-SBRT ALC was 0.72 (Range: 0.11 - 4.15). On linear regression analysis, there was no significant association between post SBRT ALC nor lymphopenia grade with splenic or vertebral body dose, treatment laterality, or SBRT dose. In this retrospective series of predominately metastatic lung cancer patients treated with adrenal SBRT, we observed high rates of post SBRT grade 2+ lymphopenia, yet no dosimetric parameter was predictive, not even for left-sided lesions. Future work includes clinical validation of these findings in a larger population, likely with multi-institutional collaboration, and further study of the investigation of the IO/RT sequencing issues in such heavily pre-treated patients.