The development of a histopathologically different tumor other than the primary neoplasm is known as secondary neoplasm. Secondary neoplasms might occur at the time of the treatment as well as many years after primary treatment
5. CNS toxicity is a rare but serious complication of radiotherapy and its mechanism is still not clarified. Currently, despite well known early and late complications, radiotherapy is an essential treatment with good prognosis and high survival rates for many oncological patients. Radiotherapy and chemotherapy associated late-term side effects become an important issue in life expectancy of oncological patients. Three decades ago, the incidence of secondary neoplasms was 6% of all malignities but today this ratio reaches up to 16%
5. However, close follow-up of surviving patients is also thought to contribute this increased ratio. It is suggested that the development of a secondary neoplasm has a multifactorial etiology involving gene-environment and gene to gene interactions
5.
It is well known that radiotherapy and anti-cancer treatments are major causal factors for secondary tumors following primary pediatric and adult malignites. Depending on organ sensitivity, ionising radiation may cause many cancer types. Exposure to radiation at younger age is the greatest risk factor for secondary neoplasms. The risk of secondary neoplasm following radiotherapy increases with proportion to the length of period after exposure and the amount of radiation delivered5. Bhati et al reported that secondary brain tumors are more frequently seen in patients who are treated and diagnosed at early ages for primary tumors and develope after a latent-period of 9-10 years following cranial radiotherapy6. Additionally, a report including 14361 pediatric cancer cases showed that 116 cases developed a CNS tumor secondary to radiotherapy. It was emphasized in this study that gliomas developed in 9 years, whereas meningiomas developed in 17 years after primary diagnosis6. The report also showed that chemotherapy has no effect on secondary CNS tumor development after radiotherapy. The incidence of secondary malignities were linearly increased depending to radiotherapy dose delivered for primary tumor7. It was reported that cumulative glioma incidence was 2.7% in 15 years follow-up of patients who underwent radiotherapy for pituitary adenoma8. Ron et al reported that among over 10.000 patients exposed to radiotherapy for tinea pedis, glioma incidence was 2.6 times higher than the patients who were not exposed to radiotherapy9. In our pediatric case, radiotherapy was given to the patient at same time with chemotherapy and the tumor secondary to radiotherapy developed in only 11 months after radiotherapy. We think that the development of a secondary brain tumor in this pediatric patient may be related to high radiation sensitivity of neuronal tissue at early age.
Currently, the maximum radiation dose to cerebral paranchyma is calculated as 1.8-1.9 gray/day (Gy) and a total dose of 45-60 Gy. Despite these radiation dose limits, the side-effect ratio was reported as 3-5%, which is still remarkably high. Moreover, some publications reported side-effect in up to %24 of the patients10. Tumor secondary to radiotherapy was detected at a very early period in our case, despite a total radiotherapy dose within safe limits. We also think that early development of secondary tumor may be linked to additional exposure to chemotherapy at pediatric age.
The incidence of secondary neoplasms increase due to high survival rates obtained with intense anti-cancer treatments for primary tumors. Long term follow-up of patients is very important especially by pediatric patients with a history of radiotherapy, since secondary tumors are the second cause of death in surviving patients with primary tumors. We suggest that aggressive radiotherapy protocols may be avoided in patients with good prognostic tumor characteristics for the prevention of secondary tumors, and the incidence, mortality and morbidity of secondary tumors may decrease dramatically as a result of this theraphy algorithm.
Acknowledgements: The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest: All authors declare that they have no conflict of interest.