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
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,2 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
1. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–289.
2. Editorials. Prevention is as good as a cure. Nature. 2016;539:467.
3. Verellen D, De Ridder M, Linthout N, Tournel K, Soete G, Storme G. Innovations in image-guided radiotherapy. Nat Rev Cancer. 2007;7(12):949–960.
4. Dawson LA, Sharpe MB. Image-guided radiotherapy: rationale, benefits, and limitations. Lancet Oncol. 2006;7(10):848–858.
5. Dawson LA, Jaffray DA. Advances in image-guided radiation therapy. J Clin Oncol. 2007;25(8):938–946.
6. Swerdlow AJ, Higgins CD, Smith P, et al. Second cancer risk after chemotherapy for Hodgkin’s lymphoma: a collaborative British cohort study. J Clin Oncol. 2011;29(31):4096–4104.
7. Berrington de Gonzalez A, Curtis RE, Kry SF, et al. Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol. 2011;12(4):353–360.
8. Brenner DJ, Hall EJ. Computed tomography-an increasing source of radiation exposure. N Engl J Med. 2007;357:2277–2284.
9. Brenner DJ, Doll R, Goodhead DT, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci U S A. 2003;100(24):13761–13766.
10. Moul JW. Radiotherapy: secondary malignancies after prostate cancer treatment. Nat Rev Clin Oncol. 2010;7:249–250.
11. Huq MS, Fraass BA, Dunscombe PB, et al. The report of Task Group 100 of the AAPM: Application of risk analysis methods to radiation therapy quality management. Med Phys. 2016;43(7):4209.
12. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.
13. National Lung Screening Trial Research Team, Church TR, Black WC, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368(21):1980–1991.
14. Evans WP. Breast cancer screening: successes and challenges. CA Cancer J Clin. 2012;62:5–9.
15. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106–1114.
16. Smith RA, Andrews K, Brooks D, et al. Cancer screening in the United States, 2016: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2016;66(2):96–114.
17. Humphrey LL, Deffebach M, Pappas M, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive services task force recommendation. Ann Intern Med. 2013;159(6):411–420.
18. Myers ER, Moorman P, Gierisch JM, et al. Benefits and harms of breast cancer screening: a systematic review. JAMA. 2015;314(15):1615–1634.
19. Siegel RL, Ward EM, Jemal A. Trends in colorectal cancer incidence rates in the United States by tumor location and stage, 1992-2008. Cancer Epidemiol Biomark Prev. 2012;21(3):411–416.
20. Aberle DR, Abtin F, Brown K. Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial. J Clin Oncol. 2013;31(8):1002–1008.
21. Berrington de González A, Kim KP, Knudsen AB, et al. Radiation-related cancer risks from CT colonography screening: a risk-benefit analysis. AJR Am J Roentgenol. 2011;196(4):816–823.
22. Mullenders L, Atkinson M, Paretzke H, Sabatier L, Bouffler S. Assessing cancer risks of low-dose radiation. Nat Rev Cancer. 2009;9(8):596–604.
23. Asha S, Curtis KA, Grant N, et al. Comparison of radiation exposure of trauma patients from diagnostic radiology procedures before and after the introduction of a panscan protocol. Emerg Med Australas. 2012;24(1):43–51.
24. Kritsaneepaiboon S, Jutiyon A, Krisanachinda A. Cumulative radiation exposure and estimated lifetime cancer risk in multiple-injury adult patients undergoing repeated or multiple CTs. Eur J Trauma Emerg Surg. 2018;44(1):19–27.
25. Calabrese EJ. Origin of the linearity no threshold (LNT) dose-response concept. Arch Toxicol. 2013;87(9):1621–1633.