Biology-Guided Radiation Therapy An Evolving Treatment Paradigm

In radiation oncology, imaging guides patient selection, treatment volume delineation, and accurate treatment delivery. Therefore, improvements in radiotherapy delivery are intrinsically linked to advances in imaging technology. The advent of 3D-radiotherapy was made possible by computed tomography (CT)-based radiation treatment plan-ning, and more recently, novel magnetic resonance-guided radiation treatment has provided increasing soft tissue resolution to enable more precise anatomic target-ing.1,2 Advances in functional imaging modalities such as PET have demonstrated promise for further informing radiotherapy delivery by providing risk stratification and a means of gauging treatment response via correlation with biological activity. Indeed, early studies assessing the incorporation of PET into radiation treatment plan-ning suggested improved radiation planning (eg, incorporation of CT-subclinical dis-ease) and outcomes when combining PET with radiation.3-5 This has led to the concept of biology-guided radiotherapy (BgRT), an emerging external beam radiotherapy treatment paradigm that uses biological/molecular imaging to inform ra- diation treatment. A primary way of BgRT functions is by using imaging as a biomarker that is both prognostic and predictive of response to therapy. PET imaging is the most common modality, with the associated radiotracer being used to characterize relevant treat- ment metrics such as tumor burden/distribution, hypoxia, angiogenesis, metabolism, and proliferation.6 Functional imaging like PET can provide relevant information at several points in the radiation delivery process: before and following treatment as a prognostic indicator, as an indicator of response to therapy, during radiation to inform treatment planning and adaptation. Radiation therapy is at the cusp of integrating advanced functional imaging and treatment delivery systems and is poised to use biological information afforded by mo- lecular imaging during BgRT to deliver more effective therapies. This potentially will enable treatment of multiple disease sites simultaneously, improve motion manage- ment, decrease treatment margins, and optimize targeting of biologically active tumor. This review highlights prior applications of PET imaging to prognosticate patients and guide radiation treatment, which will be relevant as integrated BgRT develops. A sum- mary of included studies is summarized in Table 1.