Combining Radiation, Immunotherapy: An Emerging Challenge for Oncology Nursing

There remain significant unknowns that require careful study, however. Issues of acquired tumor cross-resistance may emerge over time, for example. Durable remission rates for patients treated with immune checkpoint inhibitors for non-small cell lung cancer (NSCLC) remain low (20% or less of patients treated), though the development of predictive biomarkers may in the future help identify which patients are most likely to benefit.¹² The hope, bolstered by early research data, is that together, immunotherapy and radiotherapy can more effectively kill tumor cells than either treatment modality alone — possibly even systemically, and not just in irradiated tissues — and that early signs of synergy will be validated in well-designed clinical studies, allowing optimization of dosing, timing, sequencing, and combinatorial strategies.^3,9-12 

With increasing rates of patient co-exposures to these treatment modalities and the development of rational, empirically supported combination regimens, oncology nurses will face an increasingly complex management task with patients who must be closely monitored for toxicities.^2,3 In small cohorts of patients administered immune checkpoint inhibition for NSCLC, followed by thoracic radiotherapy, severe toxicities, and patient deaths have been reported.^12,13

Radiotherapy and Antitumor Immunity

A connection between tumor radiosensitivity and antitumor immune competence has been recognized in laboratory mice for close to 40 years, with higher radiation doses needed to control tumors in immunosuppressed animals than in immunocompetent ones.² With the development of cancer immunotherapy agents, isolated case studies and phase 1 and phase 2 clinical data on interleukin-2 (IL-2) with radiotherapy were reported in 2012 that together suggested possible synergies between radiotherapy and immunotherapies.^2,8-12

Case reports have described patients treated with ipilimumab, a monoclonal antibody that targets the CTLA-4 immune checkpoint pathway, and radiation.^2,8,9 A phase 1 clinical study suggested that in a small cohort of patients, stereotactic body radiotherapy plus high-dose IL-2 for patients with skin and kidney cancer yielded higher tumor response rates than had been previously reported for IL-2 alone.¹¹

Radiotherapeutic tumor control outside of irradiated target volumes (the so-called abscopal radiotherapy response) is thought to be rare in part because of tumors’ immunosuppressive microenvironments, providing a rationale for the combination of immunomodulating agents with radiation.^5,12-14 Indeed, preclinical experiments strongly suggest that immuno-radiotherapy can induce systemic abscopal antitumor responses, and that PD-L1 immune checkpoint blockade can reverse acquired radioresistance.^12-16 Radiotherapy might also allow effective use of immunotherapy against malignancies such as prostate cancer against which immunotherapies have not yet shown convincing efficacy, and more meaningful progression-free survival times among patients with brain metastases.^17-21