Radiotherapy (RT), along with surgery and chemotherapy, is an important cancer treatment. Although there are no accurate statistics for childhood cancer alone, a previous study reported that more than half of patients receive RT during the course of their illness .
RT is an essential component of cancer treatment, including childhood cancer. It is used in combination with surgery and chemotherapy to improve the chances of survival and local tumor control. However, due to growing tissue, children are more sensitive to radiation-induced adverse effects and the risk of developing secondary malignancies. In the last decades, survival after childhood cancer has increased considerably, and now is about 80% five years after diagnosis . Therefore, sophisticated radiation techniques are used to minimize long-term sequelae and improve the quality of life of childhood cancer survivors.
The excellent survival outcomes of childhood cancer patients undergoing RT are accompanied by serious side effects. One of the most serious side effects of RT in childhood cancer patients is growth and developmental delays . Abnormal gonadotropin secretion and early puberty have been observed in 25 to 50% of patients who survive medulloblastoma and GH deficiency has been reported in 40-80% of cases. Hypothyroidism has been reported in varying proportions of patients, ranging from 8% to 60% .
Other serious side effects include gastrointestinal dysfunction, pulmonary and cardiac abnormalities, neurocognitive defects, infertility, and secondary cancers . A study comparing more than 300 pediatric brain tumor survivors with a group of similar healthy individuals found that cancer survivors were 10 times less likely to be employed and 28 times less likely to be able to drive a car. There is a report that described the cumulative risk of secondary cancer varies from 1.7% to 13%. A retrospective study of cancer survivors found a 20% reduction in fertility among women who received RT below the diaphragm .
The principle of RT for childhood cancer is to tailor treatment intensity according to the individual risk profile. Advanced RT technologies may be used to spare important organs at risk (OARs) and decrease the risk for late normal tissue damage while still achieving the primary goal of local tumor control. Achieving highly conformal dose distributions is especially important for childhood cancer patients who are being treated with curative intent or who have long life expectancies following therapy. Continuous advances in radiation technology have improved the conservation of surrounding tissues. Thus, using modern, precise techniques or seeking treatment in the direction of omitting RT, if possible, is recommended. The use of RT to treat childhood cancers has declined for several decades . RT is a very important component of multimodal therapy strategies, particularly in the treatment of solid tumors of the central nervous system or bones and soft tissue. RT could be restricted to higher-risk patients with other tumors, such as lymphoma, neuroblastoma, or Wilms tumor .
Currently, most centers in Korea are implementing photon-based three-dimensional conformal RT (3DCRT) and intensity-modulated RT (IMRT) using X-rays. IMRT is recommended in most cases to reduce risk or the magnitude of side effects from treatment. However, 3DCRT is also an acceptable option.
Unlike conventional photon therapy, proton beam therapy (PBT) does not use high-energy electromagnetic waves but charged particles, namely hydrogen ions (protons). These physical characteristics make protons particularly attractive for tumors requiring high doses and malignancies where sparing of OARs is critical to avoid late effects. PBT for pediatric patients may be particularly beneficial in reducing in late toxicities, such as growth disturbances and second malignancies . Although its availability and distribution are still limited compared to other techniques, there has been sustainable progress in recent years, and it is being increasingly used in many countries. There are two PBT facilities in Korea; one began proton therapy in 2007, and the other began in 2015. Since then, no other PBT facilities have been opened so far in 2023.
Carbon ion RT (CIRT) is also an option, but it is considered an experimental treatment for most tumors, including childhood cancers. There is limited evidence supporting its use, and large randomized clinical trials comparing CIRT with other radiation modalities are lacking. CIRT has been reluctantly used for the treatment of pediatric tumors due to the fear of severe adverse events and/or the concern of an increased risk of second malignancies. The few available reports with short follow-ups did not report any second malignancies. Although the dosimetric advantages are clear, the current evidence supporting CIRT is level 2b, at best, without any randomized phase III clinical trial comparing carbon beams with any other radiation modality . Due to the limited number of CIRT centers globally and financial issues related to insurance coverage and treatment reimbursement, designing such trials is challenging. The CIRT facility in Korea began treating patients in April 2023. As of June 2023, only adult prostate cancer is being treated with CIRT. Photon beam RT (including IMRT) and proton therapy have been implemented for pediatric tumors. CIRT has not yet been implemented for all kinds of cancers.
IMRT and PBT have been implemented for pediatric tumors, but the implementation of CIRT has not been as widespread. PBT may be considered for patients with better prognoses, and IMRT is a viable option in most cases to reduce treatment side effects.
The authors have no conflict of interest to declare.