title: Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect Residual Cancer.
abstract: For many solid cancers, radiation therapy is offered as an adjuvant to surgical resection to lower rates of local recurrence and improve survival. However, a subset of patients treated with surgery alone will not have a local recurrence. Currently, there is no way to accurately determine which patients have microscopic residual disease in the tumor bed after surgery and therefore are most likely to benefit from adjuvant radiation therapy. To address this problem, a number of technologies have been developed to try to improve margin assessment of resected tissue and to detect residual cancer in the tumor bed. Moreover, some of these approaches have been translated from the preclinical arena into clinical trials. Here, we review different types of intraoperative molecular imaging systems for cancer. Optical imaging techniques like epi-illumination, fluorescence molecular tomography and optoacoustic imaging can be coupled with exogenous fluorescent imaging probes that accumulate in tumors passively via the enhanced permeability and retention effect or are targeted to tumor tissues based on affinity or enzyme activity. In these approaches, detection of fluorescence in the tumor bed may indicate residual disease. Protease activated probes have generated great interest because of their potential for leading to high tumor to normal contrast. Recently, the first Phase I clinical trial to assess the safety and activation of a protease activated probe was conducted. Spectroscopic methods like radiofrequency spectroscopy and Raman spectroscopy, which are based on energy absorption and scattering, respectively, have also been tested in humans and are able to distinguish between normal and tumors tissues intraoperatively. Most recently, multimodal contrast agents have been developed that target tumors and contain both fluorescent dyes and magnetic resonance imaging contrast agents, allowing for preoperative planning and intraoperative margin assessment with a single contrast agent. Further clinical testing of these various intraoperative imaging approaches may lead to more accurate methods for margin assessment and the intraoperative detection of microscopic residual disease, which could guide further resection and the use of adjuvant radiation therapy.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC.
authors.forename: Melodi J
authors.initials: MJ
authors.lastname: Whitley
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, MA; Department of Systems Biology, Harvard Medical School, Boston, MA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC; Department of Radiation Oncology, Duke University Medical Center, Durham, NC. Electronic address: david.kirsch@duke.edu.
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
mesh_terms: D003287:Contrast Media; D006801:Humans; D007089:Image Enhancement; D007430:Intraoperative Care / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D018365:Neoplasm, Residual; D009369:Neoplasms / Q000175:diagnosis* / Q000532:radiotherapy*; D061848:Optical Imaging / Q000379:methods*; D018714:Radiotherapy, Adjuvant
chemical_list: D003287:Contrast Media