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

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 (EBRT) 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 EBRT delivery modality combining 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.

Pair production tomography imaging

“…P 2 T benefits from decades of technological development of PET, which provides the energy and timing windows to remove non-pair production photon contamination. Moreover, for emission guided radiotherapy, the integration of a high energy source and a PET detector ring was recently demonstrated 33 .…”

A Century of Fractionated Radiotherapy: How Mathematical Oncology Can Break the Rules

“…Modern fractionated radiotherapy still adheres to these principles (defined hereafter as Rule One (fraction size) and Rule Two (total treatment period), respectively) established over a century ago despite drastic changes in our understanding of radiobiology [3][4][5]. The core aim of radiotherapy fractionation is the creation of a therapeutic window by leveraging differences in radiobiological principles between tumor and normal tissue.…”

The technical design and concept of a PET/CT linac for biology-guided radiotherapy

“…The RefleXion™ X1 biology-guided radiotherapy system (RefleXion Medical Inc, Hayward, CA) seeks to overcome these hurdles by enabling a tumor to communicate its present position directly to a linear accelerator. This technology combines dual imaging technologies (CT and PET) with a slice therapy linear accelerator [8] . Fundamentally, the system functions by utilizing kVCT imaging for initial patient setup and then PET detection of outgoing tumor emissions to detect the location of a tumor and respond with beamlets of radiotherapy with sub-second latency.…”