SEOUL NATIONAL UNIVERSITY HOSPITAL

- SNUH Research Team Tracks 160 Patients for an Average of 13.1 Years... 10-Year Overall Survival Rate Reaches 88.6%

- Secondary Malignancies and Other Fatal Complications Emerge After a Mean Latency of 17.6 Years... Chemotherapy Combined With Reduced-Extent, Reduced-Dose Radiotherapy Shows Preventive Effect

 

[Photo] Intracranial germinoma in the pineal region (brain midline), circled in yellow

 

A study has revealed that intracranial germinoma, a pediatric brain tumor with a good prognosis and a 10-year survival rate of 88.6%, can cause fatal complications, such as secondary malignancies, even decades after apparent cure. To prevent these long-term adverse effects, the study found that long-term follow-up beyond 20 years is essential, along with treatment strategies combining chemotherapy with reduced-extent, reduced-dose radiotherapy.

On July 28, a research team composed of Professor Emeritus Kyu-Chang Wang (currently at the National Cancer Center), Professors Seung-Ki Kim and Kyung Hyun Kim of the Department of Pediatric Neurosurgery at Seoul National University Hospital, Professor Emeritus Il-Han Kim of the Department of Radiation Oncology, and Professor Young-Bo Shim of the Department of Critical Care Medicine at Kangbuk Samsung Hospital announced the results of a study that followed 160 patients treated for intracranial germinoma between 1983 and 2013 for an average of 13.1 years.

Intracranial germinoma is a brain tumor that primarily occurs in children, adolescents, and young adults; it is a germ cell tumor that develops in the pineal or suprasellar region of the brain. The mean age of the study subjects at diagnosis was 15.6 years, with males (77.5%) being overwhelmingly the majority. Although the prognosis is favorable due to responsiveness to chemotherapy and radiotherapy, concerns regarding long-term adverse effects—such as secondary malignancies, endocrine abnormalities, and neurological deficits—have been consistently raised because treatment is often administered at a young age.

The analysis showed that overall survival (OS) rates at 5 and 10 years post-treatment were favorable, at 93.8% and 88.6%, respectively. The cumulative incidence of recurrence (CIR) of the original tumor plateaued at 5.6% five years after treatment and did not increase further. Additionally, 88.5% of patients maintained a good functional status (KPS ≥ 60) even after 10 years.

 

[Figure 1] Recurrence in patients with intracranial germinoma plateaued after 5 years of treatment, whereas secondary malignancies continued to increase over the long term.

 

In contrast, the cumulative incidence of secondary malignancies—new cancers arising after treatment—did not stop at 0.6% at 5 years and 2.1% at 10 years, but showed a continuously increasing trend over decades following treatment. In fact, the 14 patients who developed secondary malignancies were diagnosed at a mean of 17.6 years after their initial treatment; glioblastoma was the most common, followed by meningioma in 3 patients and astrocytic glioma in 2. Notably, 11 of these 14 patients had received their initial radiation therapy during their teenage years, highlighting the need for special vigilance regarding radiation exposure during the growth period.

Furthermore, 9 of the 31 total deaths were attributable to radiation-induced malignancies that developed after treatment, and the overall survival rate showed a pattern of further decline starting approximately 20 years after treatment, reflecting the aftermath of these late complications.

A wide range of long-term complications was also observed. Some 19.5% of patients required hormone replacement therapy, and among those who developed radiation-induced vasculopathy (2.5%), some progressed to moyamoya syndrome and underwent cerebral revascularization surgery. Notably, a substantial number of patients also experienced psychiatric problems (5.0%), including depression and suicide, indicating the need for comprehensive survivor care that addresses mental health alongside physical illness.

Regarding treatment methods, the group of patients who received chemotherapy combined with reduced-extent, reduced-dose radiotherapy showed superior outcomes compared to the group that did not receive chemotherapy. When chemotherapy was combined, the mean radiation dose to the primary tumor was 45.9 Gy, significantly lower than the 52.1 Gy given to those who did not receive chemotherapy. This is interpreted not as a direct effect of the chemotherapy agents themselves, but as a combined effect resulting from reduced radiation exposure. As a result, overall survival improved significantly without an increase in recurrence, and daily functional status was better preserved. However, the research team added that, given the study spanned multiple treatment eras, the impact of evolving treatment strategies on long-term prognosis must also be considered.

 

[Figure 2] The patient group who received chemotherapy (blue) showed better survival probability (left) and a higher probability of maintaining a KPS score ≥ 60 (right), even though the extent and dose of radiation were reduced.

 

Professor Seung-Ki Kim of Seoul National University Hospital (co-first author) stated, "Intracranial germinoma is a tumor with a very high chance of cure, but secondary malignancies and complications can occur even decades after treatment," adding, "A long-term survivor management system spanning over 20 years that monitors both physical and mental health, along with follow-up studies spanning generations, is necessary."

Meanwhile, this study was supported by the SNUH Kun-hee Lee Child Cancer & Rare Disease Project and was published in the latest issue of the international neuro-oncology journal Neuro-Oncology Advances.

 

[From left] Professor Emeritus Kyu-Chang Wang (currently at the National Cancer Center), Professor Seung-Ki Kim, and Professor Kyung-Hyun Kim of the Department of Pediatric Neurosurgery at Seoul National University Hospital; Professor Emeritus Il-Han Kim of the Department of Radiation Oncology; and Professor Young-Bo Shim of the Department of Intensive Care Medicine at Kangbuk Samsung Hospital.