Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously
Abstract
Radiotherapy is employed in the treatment of over 50% of cancer patients. However, this therapy approach is limited to mainly treating localized disease. In 1953, Mole described the remarkable abscopal effect, whereby, localized radiotherapy of a patient’s primary tumor might engender regression of cancer at distant sites, which were not irradiated. Current consensus is that if the abscopal effect can be efficaciously leveraged, it would transform the field of radiation oncology, extending the use of radiotherapy to treatment of both localized and metastatic disease. A close examination of the literature on the abscopal effect proffers a disruptive new hypothesis for consideration in future clinical trials. This hypothesis is that generating a subcutaneous human tumor autograft as the primary tumor may be a more efficacious approach to prime the abscopal effect. Following the preclinical data, the merits and demerits of such an approach are examined in this article.
Keywords: abscopal effect, radiotherapy, immunoadjuvants, metastasis,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388832/
Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously
Re: Following the Preclinical Data: Leveraging the Abscopal Effect More Efficaciously
Throughout the treatment, patients should be monitored closely for their response. The treatment site or the autograft can be easily measured for its response to radiotherapy. Imaging modalities, like CT and PET, can be used to assess the abscopal response. As reported by Golden et al., significantly lower neutrophil to lymphocyte ratio is presented in patients who have abscopal responses (
. Other methods, like T cell trafficking (27), may also be useful for treatment monitoring.
Conclusion
Given the significant body of preclinical work showing the effectiveness of subcutaneous models in generating the abscopal effect, more preclinical studies designed to better assess the risks of generating subcutaneous autografts in clinical trials should first be considered to provide more data. Such studies could involve comparison with orthotopic tumor models. If the use of subcutaneous autografts is further justified by such data and validated, the impact of such an approach would be significant. It would further extend the use of radiotherapy to the treatment of both local and metastatic disease. Metastasis accounts for over 90% of all cancer-associated suffering and death, hence, such an approach would be of great benefit to many cancer patients.
. Other methods, like T cell trafficking (27), may also be useful for treatment monitoring.Conclusion
Given the significant body of preclinical work showing the effectiveness of subcutaneous models in generating the abscopal effect, more preclinical studies designed to better assess the risks of generating subcutaneous autografts in clinical trials should first be considered to provide more data. Such studies could involve comparison with orthotopic tumor models. If the use of subcutaneous autografts is further justified by such data and validated, the impact of such an approach would be significant. It would further extend the use of radiotherapy to the treatment of both local and metastatic disease. Metastasis accounts for over 90% of all cancer-associated suffering and death, hence, such an approach would be of great benefit to many cancer patients.
Debbie