A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?

PLoS One. 2017 Feb 21;12(2):e0171559. doi: 10.1371/journal.pone.0171559. eCollection 2017.

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.

Conclusion: 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Dose Fractionation, Radiation
  • Dose-Response Relationship, Radiation
  • Female
  • Immunotherapy
  • Likelihood Functions
  • Male
  • Mice
  • Neoplasm Metastasis / physiopathology
  • Neoplasm Metastasis / radiotherapy*
  • Neoplasms, Experimental / physiopathology
  • Neoplasms, Experimental / radiotherapy*
  • Neoplasms, Experimental / therapy
  • Radiosurgery*
  • Radiotherapy Dosage
  • Research Design
  • Tumor Burden

Grants and funding

This study was supported by grant from the TOP IMPLART project (I11J10000420002) and Fondazione Umberto Veronesi Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.