Understanding the Treatment Strategies of Intracranial Germ Cell Tumors: Focusing on Radiotherapy

Abstract

Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients.

Keywords: Biology; ICGCT; Intracranial germ cell tumor; Proton beam therapy; Radiotherapy.

Fig. 1. Unusual sites of germ cell tumors in the brain. A : T2-axial (left) and T2-sagittal (right) magnetic resonance images show a nodular mass (arrow) in the posterior aspect of medulla. B : Pre-treatment images of a subtle patch streaky lesion involving the right internal capsule. Left : T2 image, Right : nodular contrast enhancement of the right basal ganglia. C : A solid and cystic mass in the right lenticular nucleus area before treatment (left) and 5 years after radiotherapy (right). D : Germinoma of the left basal ganglia. Subtle patchy lesion visible mainly in T2-weighted and fluid-attenuated inversion recovery images with no contrast enhancement in the left basal ganglia before treatment (left) and 2 years after treatment (right). The biopsy site is seen at the left basal ganglia in both scans. E : A huge mass in right basal ganglia with mass effect. The mass did not show any contrast enhancement before treatment (left) or 2 years after treatment (right). F : Huge germinoma involving bilateral basal ganglia, which shows contrast enhancement and peritumor edema. Top left and top right : pre-treatment axial T2 and coronal T1 images with contrast enhancement, Bottom left : axial T2 image 3 years after proton beam therapy, Bottom right : coronal T1 image with contrast enhancement. Magnetic resonance imaging 3 years after treatment shows a residual cystic lesion in the right basal ganglia, with white matter changes in the left frontal periventricular area.

Fig. 2. Sample treatment plan for craniospinal irradiation showing dose distributions. A : Sagittal view of 3-dimensional conformal radiation therapy (3D-CRT). B : Axial view of 3D-CRT. C : Sagittal view of proton beam treatment (PBT). D : Axial view of PBT. Yoon M, Shin DH, Kim J, Kim JW, Kim DW, Park SY, et al. Int J Radiat Oncol Biol Phys 81 : 637-646, 2011 with permission.

Fig. 3. A : Radiation dose distribution for whole ventricle (WV) irradiation. Comparison of 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) passive scattering proton beam therapy (PS-PBT), and spot scanning proton beam therapy (SS-PBT). Thick pink lines are planning target volume (PTV) for the WV. The blue, green, and yellow lines represent the 10 Gy, 15 Gy, and 29.1 Gy isodose lines, respectively. B : Dose-volume histogram of the normal brain and both temporal lobes for WV irradiation, including the pineal gland tumor bed. The prescribed (100%) doses are 30.6 Gy for 95% volume of the WV PTV.

Fig. 4. Dose distribution of primary site irradiation to tumors arising in the pineal gland (A), suprasellar (B), and basal ganglia (C), with their pre-chemotherapy magnetic resonance imaging. The thick red lines represent planning target volumes (PTV) to the primary tumor sites. The thick blue and green lines represent 10 Gy and 15 Gy isodose lines, respectively. The prescribed doses are 30.6 Gy at 95% volume of the PTV.