Nowadays, although the selection criteria for re-irradiation remain poorly defined and vary across centers, a careful second course of irradiation might provide a symptomatic and survival benefit in special patients. A single institutional experience shows that thoracic re-irradiation with conventional RT appears to deliver a meaningful survival benefit in new primary or recurrent lung cancer with low target volume (PTV <300cc).88 Re-irradiation also may be considered an option for recurrent or new primary cancer of the head and neck, rectum, breast, cervix, or other sites in carefully selected patients using a variety of techniques and fractionation schedules, providing good local control rates while toxicity remains acceptable.89–94 Despite a paucity of large randomized studies, re-irradiation has been adopted in different clinical scenarios by many institutions, and the role of contemporary methods, such as IGRT, remains an area of active investigation in re-irradiation. Regardless of these aspects, careful attention to RT planning and delivery is critical to optimize the outcomes, so the corresponding guidelines are beginning to emerge for certain indications.

In recent years, enormous advances in RT have been achieved, for instance, introducing particle therapy into clinical routine, or the development of MRI-guided radiotherapy.95,96 These high-energy particle beams can often achieve excellent disease control while delivering minimal radiation dose to healthy tissue near cancer targets, offering a significantly lower second cancer incidence rates than photons. In a ROCOCO in silico clinical trial, a reduction in mean dose to OARs is also demonstrated using particle therapy compared to photons in the re-irradiation of patients with squamous cell carcinoma of the head and neck.97 However, due to the high cost of the particle therapy facility, the cost/benefit ratio is being debated. MRI provides the gold standard for defining soft tissue structures during RT planning, and the use of MRI-guided treatment delivery is providing a further argument for an MRI-only workflow, which will eliminate setup and registration error while also reducing workload and strain on the patient, especially additional radiation in the RT workflow. But the dosimetric errors in an MRI-only RT workflow need to be considered due to the specific geometric distortion from MRI.98

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This review describes the cancer risks in numerous processes of IGRT, including screening and diagnosis, contouring and planning, targeting and delivery, and follow-up care and re-irradiation. Although we do not know the exact mechanism and dose–response relationship for radiation-induced malignancy, enormous advances in IGRT will help clinicians better understand the technology and the process in general and have an effect on individualized RT guidelines and strategies for cancer risk reduction, improving safe RT delivery and patient treatment outcomes. This review only describes external beam radiation therapy, and it is conceivable that brachytherapy faces a similar challenge. In the future, we believe that utilizing artificial intelligence (AI) to translate and combine all data sources into knowledge will enable health care to move to individualized, high-quality, and safe cancer treatments.


This study was supported by the National Natural Science Foundation of China under grant number 11575038.


The authors report no conflicts of interest in this work.

Fu Jin,1 Huan-Li Luo,1 Juan Zhou,Ya-Nan He,1 Xian-Feng Liu,1 Ming-Song Zhong,1 Han Yang,1 Chao Li,1 Qi-Cheng Li,1 Xia Huang,1 Xiu-Mei Tian,1 Da Qiu,1 Guang-Lei He,1 Li Yin,1 Ying Wang11Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing, People’s Republic of China; 2Forensic Identification Center, College of Criminal Investigation, Southwest University of Political Science and Law, Chongqing, People’s Republic of China 


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