Radiation and immune checkpoint inhibitors in the treatment of oligometastatic non-small-cell lung cancer: a practical review of rationale, recent data, and research questions

Abstract

The combined use of stereotactic ablative radiotherapy (SABR) and immune checkpoint inhibitors (ICIs) is an emerging treatment paradigm for oligometastatic non-small-cell lung cancer (NSCLC). Recent phase I and II trial data suggest that SABR to multiple metastases in addition to ICI use is safe and effective with promising progression-free survival and overall survival signals. There is great interest in capitalizing on combined immunomodulation from these two modalities for the treatment of oligometastatic NSCLC. Ongoing trials seek to validate the safety, efficacy, and preferred sequencing of SABR and ICI. This narrative review of the role of SABR when combined with ICI in oligometastatic NSCLC discusses the rationale for this bimodality treatment, summarizes recent clinical trial evidence, and proposes key principles of management based on the available evidence.

Keywords: immune checkpoint inhibitors; immunotherapy; non-small-cell lung cancer; oligometastasis; stereotactic ablative radiotherapy.

Figure 1.

Synchronous oligometastatic disease. A patient with oligometastatic lung cancer at diagnosis with three metastases receives systemic therapy as well as SABR to all gross sites of disease. SABR, stereotactic ablative radiotherapy.

Figure 2.

Metachronous oligometastatic disease. A patient with localized lung cancer at diagnosis received local treatment and eventually develops OMD with three new metastatic deposits. The patient then receives systemic therapy as well as SABR to all gross sites of disease. *Note that although some patients will receive systemic therapy for metachronous OMD in addition to SABR, others will receive local therapies only (e.g. SABR and/or surgery). OMD, oligometastatic disease; SABR, stereotactic ablative radiotherapy.

Figure 3.

Proposed management principles for treatment of oligometastatic disease with SABR and ICIs. (1) Careful patient selection; (2) caution with concurrent SABR and ICI; (3) ablate all sites of disease; and (4) minimize toxicity. ICI, immune checkpoint inhibitor; OAR, organ at risk; RT, radiation therapy; SABR, stereotactic ablative radiotherapy.