Table 3. Clinical trial results of high-risk medulloblastoma.
| Study | No. of patients | Cohort | Study outcome | Radiation dose (Gy) | Chemotherapy | Survival |
|---|---|---|---|---|---|---|
| POG 9031 [42] | 224 | 3–21 yrs, T3b/T4 disease at time of surgery or M+ or R+ | Randomized trial, pre-RT vs. post-RT CT; prognostic factor of response to pre-RT CT | M0–1 CSI 35.2/PF 53.2 M2–3 CSI 40/PF 54.4 Spinal or brain meta 44.8 |
Randomized CDDP, VP pre or post RT; maintenance with CPM/VCR | Pre-RT CT arm 5-yr EFS 66% (CR or PR 73% vs. not CR or PR 56% after pre-RT CT [p=0.1]) Post-RT CT arm 5-yr EFS 70% |
| SIOP PNET-3 [44] | 68 | 3–16 yrs, M2-3 | Non-randomized trial, outcome treated with PNET-3 pre-RT CT | CSI 35/PF 55 | Pre-RT VCR, VP, alternating CBP/CPM alter (total 4 cycles) | 5-yr EFS 34.7% |
| SJMB-96 [45] | 48 | R+ or M1–M3 | Non-randomized trial, 5-yr EFS | CSI for M0–1 36/M2–3 39.6/TB 55.8/meta 50.4 | TPT before RT; CDDP, CPM, VCR + SCR (4 cycles) | 5-yr EFS 70% |
| HART [46] | 33 | ≥3 yrs, M+ | Non-randomized trial, efficacy and toxicity of a HART regimen delivered after intensive sequential CT | CSI 39/TB 60 (HART regimen) | Pre-RT MTX, VP, CPM, CBP/2 cycles of thiotepa & SCR (not in CR before CSI) or 6 cycles of CCNU, VCR (CR before CSI) | 5-yr PFS 72% (CR or PR 3-yr PFS 94%, not CR or PR 3-yr PFS 61% after pre-RT CT [p=0.04]) |
| HIT 2000 [50] | 123 | 4–21 yrs, M+ | Non-randomized trial, outcome analysis by clinical risk factors, methylation/genetic subgroup status, and other biologic parameters | HF CSI 40/PF +20/spinal meta +10/supratentorial meta +28 | Pre-RT CPM, VCR, MTX, CBP, VP, intraventricular MTX (2 cycles); maintenance with CDDP, CCNU, VCR (4 cycles) | 5-yr EFS 62% |
| COG 99701 [43] | 161 | R+, M+ or supratentorial PNET | Phase I/II trial | CSI 36/PF +19.8 | VCR, CBP during RT; maintenance with CPM, VCR +/- CDDP | 5-yr EFS 77% for M1, 50% for M2, 67% for M3 |
| COG ACNS0332 [25] | 294 | R+, M+, LC/A histology | Randomized trial, 1) CBP concurrently with RT, 2) isotretinoin 12 cycles | CSI 36/PF 55.8 | VCR/randomized CBP during RT; CDDP/CPM/VCR (6 cycles) | 5-yr EFS 62.9% CBP 66.4% vs. No CBP 59.2% (p=0.11) Group 3: CBP 73.2% vs. No CBP 3.7% (p=0.047) |
| PNET HR +5 [47] | 51 | 5–20 yrs, R+, M+, MYC/N amplification LC/A histology | Non-randomized trial, 3-yr PFS, molecular characteristics associated with PFS | CSI 36 (if R+ alone 23.4)/TB 54 | Pre-RT CBP, VP (2 cycles); high dose thiotepa + SCR (2 cycles); maintenance with TMZ 6 cycles | 3-yr PFS 78%, 5-yr PFS 76% |
| SJMB-03 [40] | 103 | 3–21 yrs, M+, not GTR | Non-randomized trial, 5-yr PFS | CSI 36–39.6, boost 55.8–59.4 | VCR, CDDP, CPM + SCR (4 cycles) | 5-yr PFS 56.7% |
R+ means greater than 1.5 cm3 of residual tumor after surgery, M+ means M1-4 disease by modified Chang staging classification. RT, radiotherapy; CT, chemotherapy; CSI, craniospinal irradiation; PF, posterior fossa; CDDP, cisplatin; VP, etoposide; CPM, cyclophosphamide; VCR, vincristine; EFS, event free survival; CR, complete remission; PR, partial remission; TB, tumor bed; HART, hyperfractionated accelerated radiotherapy; TPT, topotecan; SCR, stem cell rescue; MTX, methotrexate; CCNU, lomustine; HF, hyperfractionated; CBP, carboplatin; PFS, progression-free survival; TMZ, temozolomide