Adjuvant Therapies for Supratentorial Primitive Neuroectodermal Tumors in Children

The treatment of supratentorial PNETs requires a multimodal approach.  Consequently, adjuvant treatment with radiation with or without chemotherapy is always considered. The plan for each patient is determined by a multidisciplinary oncology team and put into action if parents agree. Patients will be followed periodically by the oncology team and the neurosurgeon, according to the patterns of practice in individual centers.

If chemotherapy is to be used, a central venous access line is inserted during the initial hospitalization to allow easier administration of chemotherapeutic drugs.

Radiation

Most patients with supratentorial PNETs who are older than 3 years receive postoperative radiotherapy to the tumor bed and to the craniospinal axis. The rationale for the use of radiotherapy is based on the intermediate radiosensitivity of embryonal tumors.

• Improved survival: Three trials that studied children with supratentorial embryonal tumors showed that overall survival and event-free survival were worse when radiotherapy was delayed (12, 13) or suppressed (8). Furthermore, two recent and separate analyses of patients with supratentorial PNETs determined that radiation therapy was the only significant factor associated with improved survival (1, 14).
• Craniospinal radiotherapy is strongly recommended because of the propensity of supratentorial PNETs to disseminate along CSF pathways.
• Protocols based on medulloblastoma experience: The radiation protocols for supratentorial PNETs are based on inferences from the medulloblastoma literature. The standard regimen for patients with a supratentorial PNET is a radiation dose of 4680–6000 cGy to the primary site and 2700–4000 cGy to the cranial and spinal fields.

Chemotherapy

Currently there is no universal agreement regarding the standard or best therapy for supratentorial PNETs. Because of the rarity of the disease, the use of adjuvant combination chemotherapy shown to be effective in the treatment of medulloblastomas has been applied to supratentorial PNETs.

• Vincristine and nitrosourea: Treatment with vincristine/nitrosourea combined with either prednisone or cisplatin has resulted in a progression-free survival (PFS) rate of 45% at 3 years (8, 10).
• High-dose chemotherapy with bone marrow rescue: The Head Start I and II results in patients with supratentorial PNET have recently been reported (17). Forty-three patients who underwent maximal safe surgical resection were treated with five cycles of etoposide, cyclophosphamide, vincristine, and cisplatin, with methotrexate added for patients with disseminated disease. In patients who responded or who had stable disease, consolidation myeloablative chemotherapy and autologous stem cell rescue were performed. The 5-year event-free survival and overall survival rates were 39% and 49%, respectively. It is important to note that 60% of the survivors in this study never had radiation therapy.
• Alternative approaches, such as preirradiation chemotherapy with ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine increased the risk of early disease progression (16).
• Postponing radiation with chemotherapy: Although there is evidence that radiation confers a survival benefit in supratentorial PNET, the results of the Head Start experience suggest that it may be reasonable to defer radiation in the younger child (under 3 years of age, and perhaps even under 5 years).
• Treating recurrent disease with chemotherapy: A national study by the Children’s Cancer and Leukemia Group (U.K.) suggests that there may be little or no benefit for supratentorial PNET relapse after radiation (20). However, a recent literature review of relapsed supratentorial PNETs points to a possible benefit among younger children (under 3 years) to whom no radiation therapy had been given (21).