Immune priming by stereotactic body radiation: Dosimetric characteristics.

Abstract

85 Background: A systemic immune response to tumors after stereotactic body radiation therapy (SBRT) has been observed. The role of radiation dosimetry variables in priming an immune response is not well characterized. Methods: We analyzed radiation dosimetry variables in a patient with metastatic melanoma receiving pembrolizumab for about 1 year prior to concurrent use with Cyberknife SBRT for a symptomatic lesion in the right lower lobe of the lung. The patient received 50 Gy in 5 fractions prescribed to the 74% isodose line (using a Monte Carlo dose calculation) and developed a systemic immune response three months after this intervention. Results: We observed priming of the immune system as man ifested by radiological and clinical responses in non-irradiated cervical lymph nodes and a new persistent FDG-avid lesion on PET scan located in the base of the tongue. Given the concern for a new malignancy, the patient underwent hemi tongue base glossectomy; interestingly, this surgical specimen showed tonsillar mucosa with reactive lymphoid hyperplasia without evidence of tumor. Upon review of the CyberKnife SBRT plan, we identified that the planning target volume (PTV) was atypically under covered to 89.9% and also had a relatively high value of gross tumor volume (GTV) conformity index (CI) of 2.1. In our experience with CyberKnife plans for lung lesions, usually the PTV coverage is more than 95% and the GTV CI is less than 1.5. Other dosimetry variables had more typical values, including GTV coverage of 99.9%, PTV CI of 1.1, and both GTV and PTV homogeneity index of 1.4. Conclusions: Relatively low PTV coverage and high GTV CI were associated with immune system priming in a well-documented case of systemic responses in non-irradiated pathological and normal tissues, in the setting of concurrent immunotherapy and SBRT. Further studies are warranted to confirm this association.