title: A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?
abstract: BACKGROUND
  Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR). In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence. In this work we introduce a new dose-response relationship based on relevant publications concerning preclinical models with regard to delivered dose, fractionation schedule and occurrence of biological effects on non-irradiated tissue, abscopal effects.
  
  
  METHODS
  We reviewed relevant publications on murine models and the abscopal effect in radiation cancer research following PRISMA methodology. In particular, through a log-likelihood method, we evaluated whether the occurrence of abscopal effects may be related to the biologically effective dose (BED). To this aim, studies accomplished with different tumor histotypes were considered in our analysis including breast, colon, lung, fibrosarcoma, pancreas, melanoma and head and neck cancer. For all the tumors, the α / β ratio was assumed to be 10 Gy, as generally adopted for neoplastic cells.
  
  
  RESULTS
  Our results support the hypothesis that the occurrence rate of abscopal effects in preclinical models increases with BED. In particular, the probability of revealing abscopal effects is 50% when a BED of 60 Gy is generated.
  
  
  CONCLUSIONS
  Our study provides evidence that SABR treatments associated with high BEDs could be considered an effective strategy in triggering the abscopal effect, thus shedding light on the promising outcomes revealed in clinical practice.
authors.affiliation: Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Raffaella
authors.identifier: http://orcid.org/0000-0002-5678-6861
authors.initials: R
authors.lastname: Marconi
authors.affiliation: Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Strolin
authors.affiliation: Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.|Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bossi
authors.affiliation: Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Strigari
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007167:Immunotherapy; D016013:Likelihood Functions; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000532:radiotherapy*; D009374:Neoplasms, Experimental / Q000503:physiopathology / Q000532:radiotherapy* / Q000628:therapy; D016634:Radiosurgery; D011879:Radiotherapy Dosage; D012107:Research Design; D047368:Tumor Burden