Radiation-induced lung injury (RILI) occurs in up to 30% of thoracic radiotherapy (RT) cases and is a major limiting factor of dose escalation to achieve tumor control and improve survival. RILI can be separated into two phases: an early inflammatory phase and a late fibrotic phase. Imaging has the potential to provide a helpful understanding of RILI for diagnosis, monitoring and treatment. Current clinical imaging methods rely on anatomical imaging and occasionally incorporate functional imaging. With the advent of molecular imaging, specific targeted probes can be designed to image RILI at every stage of the process. Molecular imaging is still in its infancy and most new RILI imaging techniques are still under development. This chapter summarizes the different imaging methods used clinically for RILI imaging and explores new developments for the future of RILI management.
TopIntroduction
Lung cancer 5-year survival rates remain very low (15%) and is the leading cause of cancer deaths in the world. During the course of treatment, about 50% of cancer patients will undergo radiation therapy (RT) (Bentzen, 2006). RT uses ionizing radiation to kill tumor cells via DNA and cellular damage and treat cancer. RT dose escalation would improve tumor control but is limited by normal tissue toxicity. Like all cancer therapies, radiotherapy involves the risk of developing side effects that could impair the quality of life of patients and lead to severe complications. However, unlike chemotherapy, the side effects of radiotherapy are localized in the organs or tissues that have been irradiated. There is a fine balance, or therapeutic window, between achieving cure or tumor control and reducing adverse effects or toxicities associated with radiotherapy. Radiation-induced lung injury (RILI) occurs in up to 30% of patients who received thoracic irradiation. This primarily includes patients treated for lung cancer, but also includes breast, esophageal cancer or lymphoma patients (Bentzen, 2006; Kong, Haken, Eisbruch, & Lawrence, 2005).
The dose delivered to treat the tumor is limited by side effects, acute and late, to surrounding normal tissue. Imaging has the potential to monitor such effects to allow for potential prevention or mitigation strategies in a patient specific manner
(Robbins et al., 2012). Imaging can be used to diagnose patients that are at risk of developing side effects early in the course of treatment when it is still possible to change or adapt treatment or add drugs to mitigate those. Having an imaging tool to detect adverse effects allows for monitoring the response of the patient to mitigating agents or validating newly developed treatment options.
Current clinical practice focuses on anatomical imaging for diagnosis and monitoring of RILI. RILI is a complex process comprising of a myriad of molecular players acting over time to develop functional lung impairments and radiological evidence of disease. Functional lung tests are used to assess the overall lung capacity but lack spatial resolution. Functional imaging techniques can also be used to map lung function for RT avoidance or treatment monitoring. With the advent of molecular imaging and the development of targeted imaging probes, it becomes possible to gain insight into RILI at the molecular level. Most molecular imaging methods for RILI imaging, although promising, are currently being developed and are not yet routinely implemented in the clinic.
This chapter aims to review the current status of RILI imaging and highlight future developments with the potential to improve the diagnosis, monitoring and management of RILI clinically.