Heiko Enderling, PhD
The combination of radiation and immunotherapy is currently enjoying unprecedented attention as a treatment strategy for patients with metastatic cancer. Clinical case studies and proof-of-principle clinical trials report on systemic, abscopal responses to the combination of focal irradiation and immunotherapy in patients who were progressing on immunotherapy alone.1 However, individualized treatment plans to optimally exploit the synergy between immunotherapy and radiotherapy remain elusive due to high intra- and inter-patient heterogeneity and a myriad of possible radiation fractionation protocols, immunotherapy agents, and scheduling options.
As a first step toward developing quantitative models, we recently developed a mathematical framework to simulate the systemic dissemination of T cells activated in response to focal therapy.2 Model simulations suggest that metastatic sites within individual patients do not participate equally in immune surveillance and thus are likely to exhibit different systemic responses after local irradiation. We hypothesized that such a model could help identify patient-specific radiation treatment targets that have a high likelihood of inducing abscopal effects. Such targeted treatment strategies would be then worthy of validation in a prospective clinical trial. In a subsequent commentary, this model was critically discussed, with a focus on complex biology that was not incorporated in the model.3 Here we discuss the raised concerns in light of the purpose and applicability of the mathematical model. We echo the need for clinical validation.
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