Adjuvant radiation therapy

With radiation therapy alone, using a craniospinal radiation dose of 35 Gy with a boost to the posterior fossa of 55 Gy, 5-year EFS rates range between 50% and 65% in patients with nondisseminated disease.[80,118]

The minimal dose of craniospinal radiation needed for disease control is unknown. Attempts to lower the dose of craniospinal radiation therapy to 23.4 Gy without chemotherapy have resulted in an increased incidence of isolated leptomeningeal relapse.[123] One series attempted to treat children with WNT-activated tumors using focal radiation therapy alone, without CSI. The study showed an unacceptable incidence of neuroaxial failure with the omission of up-front CSI.[124]Lower doses and boost volume of craniospinal radiation were evaluated in a COG study (NCT00085735). Children aged 3 to 7 years were randomly assigned to receive a craniospinal radiation dose of either 18 Gy or 23.4 Gy, as well as whole posterior fossa versus limited target volume boost to the tumor bed.[59][Level of evidence A1]Analysis according to molecular subgroups demonstrated that children with group 4 medulloblastoma who received 18 Gy of craniospinal radiation therapy had poorer EFS than those who received 23.4 Gy. This was not demonstrated in the other molecular subgroups, although the study was not sized for molecular subgroup analysis.[59] Craniospinal radiation dose reduction to 18 Gy is currently being investigated in WNT medulloblastoma patients (NCT02724579), the molecular subgroup with the best prognosis.

The minimal dose of craniospinal radiation needed for disease control is unknown. Attempts to lower the dose of craniospinal radiation therapy to 23.4 Gy without chemotherapy have resulted in an increased incidence of isolated leptomeningeal relapse.[123] One series attempted to treat children with WNT-activated tumors using focal radiation therapy alone, without CSI. The study showed an unacceptable incidence of neuroaxial failure with the omission of up-front CSI.[124]Lower doses and boost volume of craniospinal radiation were evaluated in a COG study (NCT00085735). Children aged 3 to 7 years were randomly assigned to receive a craniospinal radiation dose of either 18 Gy or 23.4 Gy, as well as whole posterior fossa versus limited target volume boost to the tumor bed.[59][Level of evidence A1]Analysis according to molecular subgroups demonstrated that children with group 4 medulloblastoma who received 18 Gy of craniospinal radiation therapy had poorer EFS than those who received 23.4 Gy. This was not demonstrated in the other molecular subgroups, although the study was not sized for molecular subgroup analysis.[59] Craniospinal radiation dose reduction to 18 Gy is currently being investigated in WNT medulloblastoma patients (NCT02724579), the molecular subgroup with the best prognosis.

Results revealed that 18 Gy of CSI was inferior to 23.4 Gy of CSI (5-year EFS rate of 82.6% ± 4.2% and OS rate of 85.8% for patients who received 23.4 Gy vs. EFS rate of 71.9% ± 4.9% and OS rate of 77.9% ± 4.9% for patients who received 18 Gy).

The minimal dose of craniospinal radiation needed for disease control is unknown. Attempts to lower the dose of craniospinal radiation therapy to 23.4 Gy without chemotherapy have resulted in an increased incidence of isolated leptomeningeal relapse.[123] One series attempted to treat children with WNT-activated tumors using focal radiation therapy alone, without CSI. The study showed an unacceptable incidence of neuroaxial failure with the omission of up-front CSI.[124]Lower doses and boost volume of craniospinal radiation were evaluated in a COG study (NCT00085735). Children aged 3 to 7 years were randomly assigned to receive a craniospinal radiation dose of either 18 Gy or 23.4 Gy, as well as whole posterior fossa versus limited target volume boost to the tumor bed.[59][Level of evidence A1]Analysis according to molecular subgroups demonstrated that children with group 4 medulloblastoma who received 18 Gy of craniospinal radiation therapy had poorer EFS than those who received 23.4 Gy. This was not demonstrated in the other molecular subgroups, although the study was not sized for molecular subgroup analysis.[59] Craniospinal radiation dose reduction to 18 Gy is currently being investigated in WNT medulloblastoma patients (NCT02724579), the molecular subgroup with the best prognosis.

The 5-year EFS rate was 82.5% for patients who received radiation therapy targeting the tumor bed, compared with 80.5% for patients who received posterior fossa radiation therapy. Therefore, radiation therapy targeting the tumor bed was not inferior to posterior fossa radiation therapy (hazard ratio, 0.97; 94% upper confidence interval, 1.32).

The SIOP-PNET-4 (NCT01351870) study compared daily radiation therapy (1.8 Gy fractions with 23.4 Gy to the neuraxis and a 30 Gy boost to the posterior fossa) with twice-per-day radiation (1 Gy fractions with 36 Gy and a 24-Gy boost to the posterior fossa).[125]

The SIOP-PNET-4 (NCT01351870) study compared daily radiation therapy (1.8 Gy fractions with 23.4 Gy to the neuraxis and a 30 Gy boost to the posterior fossa) with twice-per-day radiation (1 Gy fractions with 36 Gy and a 24-Gy boost to the posterior fossa).[125]

With a median follow-up of 7.8 years, the 10-year OS was not significantly different between the two radiation groups.

The SIOP-PNET-4 (NCT01351870) study compared daily radiation therapy (1.8 Gy fractions with 23.4 Gy to the neuraxis and a 30 Gy boost to the posterior fossa) with twice-per-day radiation (1 Gy fractions with 36 Gy and a 24-Gy boost to the posterior fossa).[125]

Long-term side effects were not reported in this study.

If chemotherapy is added after radiation therapy, 23.4 Gy of craniospinal radiation therapy has been shown to be an effective dose.[94,125-127] Lower doses are being evaluated.

Although the standard boost in medulloblastoma is to the entire posterior fossa, failure data patterns reveal that radiation therapy to the tumor bed instead of the entire posterior fossa is equally effective and may be associated with reduced toxicity.[128,129]; [59][Level of evidence A1]