Normal tissue damage: its importance, history and challenges for the future

Abstract

Sir Oliver Scott, a philanthropist and radiation biologist and, therefore, the epitome of a gentleman and a scholar, was an early Director of the BECC Radiobiology Research Unit at Mount Vernon. His tenure preceded that of Jack Fowler, with both contributing to basic, translational and clinical thought and application in radiation across the globe. With respect to this review, Fowler's name in particular has remained synonymous with the use of models, both animal and mathematical, that assess and quantify the biological mechanisms that underlie radiation-associated normal tissue toxicities. An understanding of these effects is critical to the optimal use of radiation therapy in the clinic; however, the role that basic sciences play in clinical practice has been undergoing considerable change in recent years, particularly in the USA, where there has been a growing emphasis on engineering and imaging to improve radiation delivery, with empirical observations of clinical outcome taking the place of models underpinned by evidence from basic science experiments. In honour of Scott and Fowler's work, we have taken this opportunity to review how our respective fields of radiation biology and radiation physics have intertwined over the years, affecting the clinical use of radiation with respect to normal tissue outcomes. We discuss the past and current achievements, with the hope of encouraging a revived interest in physics and biology as they relate to radiation oncology practice, since, like Scott and Fowler, we share the goal of improving the future outlook for cancer patients.

Modeling radiation-induced lung injury: lessons learned from whole thorax irradiation

“…However, there is considerable patient heterogeneity, with some patients appearing asymptomatic, while others develop chronic respiratory insufficiency (Fajardo et al 2001). In the most recent decades, refinements in clinicians' ability to shape the radiation field, application of stereotactic body radiotherapy (SBRT) and altered fractionation protocols have managed to reduce the volume of exposed normal tissue while applying smaller dose fractions rather than a large single dose, thereby reducing the risk of pulmonary toxicity and their relative frequency (Williams and Newhauser 2018). However, despite these improvements, pulmonary radiation toxicity still exists and radiation oncologists must balance the need to deliver an effective dosing regimen to the appropriate volume of tissue, while minimizing radiation toxicity in the surrounding normal tissue (Emami et al 1991).…”

Evolution of the Supermodel: Progress in Modelling Radiotherapy Response in Mice

“…Mouse tissues have similar turnover rates and organisational structures to human tissues and so develop similar pathologies in terms of early and late occurring radiation toxicities. Normal tissue injuries involve a complex series pathogenic cascade, which affects tissue homeostasis and is dependent on immune status, vascular integrity, cytokine signalling and oxidative stress levels [40,42]. A particularly important consideration in the context of assessing the translational power of mice in modelling normal tissue responses is the functional similarity of the immune system and features of response to challenge.…”

Three discipline collaborative radiation therapy (3DCRT) special debate: The United States should build additional proton therapy facilities

“…Numerous computational studies have predicted lower risks of second cancers and other radiogenic late effects in long‐term survivors who receive proton therapy compared with photon therapy . More generally, there is increasing impetus to reduce radiogenic toxicities in normal tissues, a challenging task common to all types of external beam radiotherapy. Decreased off‐target dose may also engender increased preservation of the immune compartment leading to improved tumor control …”