A Review of Radiotherapy-Induced Late Effects Research after Advanced Technology Treatments

Abstract

The number of incident cancers and long-term cancer survivors is expected to increase substantially for at least a decade. Advanced technology radiotherapies, e.g., using beams of protons and photons, offer dosimetric advantages that theoretically yield better outcomes. In general, evidence from controlled clinical trials and epidemiology studies are lacking. To conduct these studies, new research methods and infrastructure will be needed. In the paper, we review several key research methods of relevance to late effects after advanced technology proton-beam and photon-beam radiotherapies. In particular, we focus on the determination of exposures to therapeutic and stray radiation and related uncertainties, with discussion of recent advances in exposure calculation methods, uncertainties, in silico studies, computing infrastructure, electronic medical records, and risk visualization. We identify six key areas of methodology and infrastructure that will be needed to conduct future outcome studies of radiation late effects.

Keywords: calculation; dose; late effects; measurement; photon; proton; risk.

Figure 1

Schematic diagram of a proton therapy treatment of the spinal axis. The therapeutic dose is shown in red and unwanted stray radiation is shown in blue. The stray radiation comprises leakage radiation emanating from the treatment machine, and scatter radiation that is produced as the therapeutic radiation interacts with the patient. Figure from Ref. (26).

Figure 2

Absorbed dose D as a function of lateral distance x from the photon therapy beam. The calculated and measured absorbed dose values are normalized to the maximum therapeutic dose at the central axis D_max(CAX). The radiation fields were produced by electron linear accelerator. Figure from Ref. (38).

Figure 3

Distributions of dose and risk superposed on sagittal images of anatomy for craniospinal irradiation. (A) shows equivalent dose and (B–D) show lifetime risks of second cancer incidence based on different dose–risk relationships [LNT: linear non-threshold model, LPLA (5): linear plateau model with bending point at 5 Sv, and LEXP (5): linear exponential model with bending point at 5 Sv]. Figure from Ref. (112).