title: The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant.
abstract: BACKGROUND
  Recently, immunologic responses to localized irradiation are proposed as mediator of systemic effects after localized radiotherapy (called the abscopal effect). Here, we give an overview of both preclinical and clinical data about the abscopal effect in particular and link them with the immunogenic properties of radiotherapy.
  
  
  METHODS
  We searched Medline and Embase with the search term "abscopal", "(non-targeted irradiation) OR (non-targeted radiotherapy)" and "distant bystander" from 1960 until July, 2014. Only papers that cover radiotherapy in an oncological setting were selected and only if no concurrent cytotoxic treatment was given. Targeted immune therapy was allowed.
  
  
  RESULTS
  Twenty-three case reports, one retrospective study and 13 preclinical papers were selected. Eleven preclinical papers used a combination of immune modification and radiotherapy to achieve abscopal effects. Patient age range (28-83years) and radiation dose (median total dose 32Gy) varied. Fractionation size ranged from 1.2Gy to 26Gy. Time to documented abscopal response ranged between less than one and 24months, with a median reported time of 5months. Once an abscopal response was achieved, a median time of 13months went by before disease progression occurred or the reported follow-up ended (range 3-39months).
  
  
  CONCLUSIONS
  Preclinical data points heavily toward a strong synergy between radiotherapy and immune treatments. Recent case reports already illustrate that such a systemic effect of radiotherapy is possible when enhanced by targeted immune treatments. However, several issues concerning dosage, timing, patient selection and toxicity need to be resolved before the abscopal effect can become clinically relevant.
authors: KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, University Hospitals Leuven, Department of Radiation Oncology, B-3000 Leuven, Belgium. Electronic address: kobe.reynders@med.kuleuven.be.
authors: Kobe
authors: K
authors: Reynders
authors: Institute of Cancer Sciences, University of Manchester, Christie NHS Foundation Trust, Manchester Academic Health Sciences Centre, Wilmslow Road, Withington M20 4BX, United Kingdom.
authors: Tim
authors: T
authors: Illidge
authors: Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville 8006, Australia.
authors: Shankar
authors: S
authors: Siva
authors: Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Joe Y
authors: JY
authors: Chang
authors: KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, University Hospitals Leuven, Department of Radiation Oncology, B-3000 Leuven, Belgium.
authors: Dirk
authors: D
authors: De Ruysscher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000532:radiotherapy*
keywords: Abscopal effect; Immune therapy; Irradiation; Radiotherapy