Outcome of Therapies for Pineal Region Tumors in Children

Outcome After Surgery

• Long-term outcome: After surgical resection of the tumor, long-term outcome depends largely on tumor histology, as well as evolving modalities of adjuvant therapy. Given the range of histology and outcomes for pathology of the pineal region, stereotactic biopsy for tissue diagnosis of pineal region tumors may be necessary. Patients with benign tumors of the pineal region do well after total surgical resection without the need for adjuvant therapy (87). For patients with malignant tumors, gross total resection in some cases may be associated with a more favorable prognosis.
• Germinomas: Pineal germinomas are not surgical lesions because of their extreme sensitivity to radiation and chemotherapy.  The role of surgery in treating patients with germinomas is limited to the histological confirmation and control of hydrocephalus (87). 
• Teratomas: The cure rate after total removal of a mature teratoma is extremely high in the senior author’s experience, with large case series reporting rates of up to 92% 5-year progression-free survival and 98% overall survival (53, 58).
• Astrocytomas: A recent study using the SEER database reported an overall survival rate for patients with pineal region astrocytomas of 61% ± 9.3% (2).
• Papillary tumors of the pineal region: Patients with this tumor have 5-year overall and progression-free survival rates reported at 27% and 73%, respectively (26).Local recurrence after resection and adjuvant therapy is common.
• Pineal parenchymal tumors: A surgical cure may be achieved for patients with pineocytoma, with 5-year survival rates ranging from 86–100%(56). For patients with pineoblastomas, some studies have shown a trend toward higher survival rates after maximum surgical resection, but these results did not reach statistical significance (72, 75, 88).  Other authors have demonstrated that the extent of pineoblastoma resection has no effect on outcome in patients treated with postoperative radiation and chemotherapy (39). Currently, the 5-year overall survival rate for patients with pineoblastomas is estimated to be 58% (56).

Outcome After Nonsurgical Treatments

• Germinomas: Patients with pure germinomas have an excellent prognosis after radiation therapy, with survival rates of 80–100% (11, 19, 27, 35, 49, 95, 98). However, despite the radiosensitivity of germinomas, up to 10% of patients experience recurrence (61, 91, 95).  This may occur due to inadequate initial radiation, the growth of radioresistant cells, or extraneural metastases through a CSF shunt.   Adjuvant chemotherapy can reduce the necessary radiation field and treat CSF dissemination, even via a shunt to the peritoneal cavity. Its use in one study led to an 84% 5-yearsurvival rate. Patients with multifocal germinomas or elevated ?-HCG (indicating differentiation in the tumor and perhaps relative radiotherapy resistance) are considered high risk and require radiation and chemotherapy (4, 14, 60, 77). As there is growing evidence of germinoma chemosensitivity, chemotherapy may become a dominant therapeutic modality for this tumor in the future (60).
• Malignant NGGCTs: Patients with malignant NGGCTs respond poorly to radiation therapy alone, and there is growing evidence of chemosensitivity of these tumors (6).  One study found a 62% 5-year survival rate when chemotherapy was used with radiation (6). Survival rates for patients with NGGCTs remains poor compared to those for patients with germinomas.
• Pineal parenchymal tumors: Children with pineoblastomas have a poor prognosis due to the high frequency of CSF dissemination and young age at diagnosis.  Long-term recurrence-free survival is very uncommon after either postoperative radiation therapy or adjuvant stand-alone chemotherapy.  Despite similar multimodality therapy after surgical resection for medulloblastomas, the prognosis for children with pineoblastomas and other supratentorial PNETs remains far worse (72). Aggressive radiation therapy plus adjuvant chemotherapy has been shown to provide improved recurrence-free survival rates, but the latent effects of ionizing radiation on the growing CNS are a serious concern (31, 39).