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Review
. 2021 Jan 1;94(1117):20200873.
doi: 10.1259/bjr.20200873. Epub 2020 Oct 30.

Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer

Shervin M Shirvani  1 , Calvin J Huntzinger  1 , Thorsten Melcher  1 , Peter D Olcott  1 , Yevgen Voronenko  1 , Judy Bartlett-Roberto  1 , Samuel Mazin  1
Affiliations
Review

Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer

Shervin M Shirvani et al. Br J Radiol. .

Abstract

The emerging biological understanding of metastatic cancer and proof-of-concept clinical trials suggest that debulking all gross disease holds great promise for improving patient outcomes. However, ablation of multiple targets with conventional external beam radiotherapy systems is burdensome, which limits investigation and utilization of complete metastatic ablation in the majority of patients with advanced disease. To overcome this logistical hurdle, technical innovation is necessary. Biology-guided radiotherapy (BgRT) is a new external beam radiotherapy delivery modality combining positron emission tomography-computed tomography (PET-CT) with a 6 MV linear accelerator. The key innovation is continuous response of the linear accelerator to outgoing tumor PET emissions with beamlets of radiotherapy at subsecond latency. This allows the deposited dose to track tumors in real time. Multiple new hardware and algorithmic advances further facilitate this low-latency feedback process. By transforming tumors into their own fiducials after intravenous injection of a radiotracer, BgRT has the potential to enable complete metastatic ablation in a manner efficient for a single patient and scalable to entire populations with metastatic disease. Future trends may further enhance the utility of BgRT in the clinic as this technology dovetails with other innovations in radiotherapy, including novel dose painting and fractionation schemes, radiomics, and new radiotracers.

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Figures

Figure 1.
Figure 1.
Comparison of imaging modalities with respect to molecular sensitivity and spatial resolution (Adapted from Tichauer et al). PET, Positron emission tomography; SPECT, single photon emission computed tomography.
Figure 2.
Figure 2.
The RefleXion™ X1 Biology-guided radiotherapy machine.
Figure 3.
Figure 3.
Just as the LTS PET images, Xt, sum to the full PET image X, the derived partial fluences sum to the complete intended fluence. LTS, limited-time-sampled; PET, positron emmision tomography. BTZ, biology-tracking zone.
Figure 4.
Figure 4.
Steps in BgRT delivery which occur every 100 ms. BgRT, biology-guided radiotherapy; BTZ, biology-tracking zone; LTS, limited-time-sampled; PET, positron emmision tomography.
Figure 5.
Figure 5.
Closing the feedback loops using temporal monitoring of biological signals.
See this image and copyright information in PMC

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References

    1. Hellman S. Weichselbaum Rr. Oligometastases. J Clin Oncol 1995; 13: 8–10. - PubMed
    1. Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, et al. . T-Cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 2017; 545: 60–5. doi: 10.1038/nature22079 - DOI - PMC - PubMed
    1. Stewart EL, Tan SZ, Liu G, Tsao M-S. Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations-a review. Transl Lung Cancer Res 2015; 4: 67–81. doi: 10.3978/j.issn.2218-6751.2014.11.06 - DOI - PMC - PubMed
    1. Oxnard GR, Arcila ME, Chmielecki J, Ladanyi M, Miller VA, Pao W. New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer. Clin Cancer Res 2011; 17: 5530–7. doi: 10.1158/1078-0432.CCR-10-2571 - DOI - PMC - PubMed
    1. Tang C, Wang X, Soh H, Seyedin S, Cortez MA, Krishnan S, et al. . Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res 2014; 2: 831–8. doi: 10.1158/2326-6066.CIR-14-0069 - DOI - PMC - PubMed

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