A Case Report of the Clinico-radiologic Challenges of Assessing Treatment Response after Stereotactic Radiation of Oligometastases Preceded by Immunotherapy: Pseudoprogression, Mixed Response Patterns, and Opportunities for Precision Radiation.

As immunotherapy continues to translate to the clinic and is combined with existing modalities, such as radiation therapy, novel treatment response patterns have been observed which complicate conventional clinical assessment and management. Herein, we describe a case study of a patient with non-small cell lung cancer treated initially with definitive chemoradiation who subsequently developed oligorecurrent disease which was managed with nivolumab and then comprehensive salvage stereotactic radiation. Serial radiographic assessment had shown worsening at these limited sites of disease after initiating immunotherapy, improvement after radiation, and then heterogeneous response behavior across sites during longer-term follow-up. Given the dual effects ablative radiation may have in the context of global immune checkpoint inhibition, both cytotoxic and synergistic immune-related, assessment of treatment response to such treatment is complicated. Such assessment is further complicated by novel immunotherapy response phenomena, e.g. pseudoprogression, which are being uncovered and are not fully characterized. Current clinical and radiologic assessment strategies are inadequate to interrogate and discern between immunomodulation-influenced response behavior and further diagnostic innovation is warranted to meet the needs of evolving clinical practice in the era of immunotherapy.