Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

SIMPLE SUMMARY: The rate of recurrence remains high for lymph node negative early-stage non-small cell lung cancer that are over 2–3 cm in size following stereotactic body radiation therapy (SBRT). This is due to the increased incidence of out-of-field failures, which warrants the addition of systemic therapy. Immune checkpoint inhibitors (ICIs), a class of immunotherapy, may induce a strong distant therapeutic effect known as the “abscopal” effect. This makes them a very suitable class of drugs to be combined with SBRT when treating early lung cancer with high-risk features, such as larger tumor size. In this review, we discuss the rationale and evidence for doing so. ABSTRACT: Stereotactic body radiation therapy (SBRT) has been widely adopted as an alternative to lobar resection in medically inoperable patients with lymph-node negative (N0) early-stage (ES) non-small cell lung cancer (NSCLC). Excellent in-field local control has been consistently achieved with SBRT in ES NSCLC ≤ 3 cm in size. However, the out-of-field control following SBRT remains suboptimal. The rate of recurrence, especially distant recurrence remains high for larger tumors. Additional systemic therapy is warranted in N0 ES NSCLC that is larger in size. Radiation has been shown to have immunomodulatory effects on cancer, which is most prominent with higher fractional doses. Strong synergistic effects are observed when immune checkpoint inhibitors (ICIs) are combined with radiation doses in SBRT’s dose range. Unlike chemotherapy, ICIs can potentiate a strong systemic response outside of the irradiated field when combined with SBRT. Together with their less toxic nature, ICIs represent a very suitable class of systemic agents to be combined with SBRT when treating ES NSCLC with high-risk features, such as larger tumor size. In this review, we describe the rationale and emerging evidence, as well as ongoing investigations in this area.