Intensive pediatric chemotherapy regimen (PNET HR+5) in adult high-risk medulloblastoma and pineoblastoma patients

Abstract

Background: High-risk medulloblastoma (HRMB) is rare in adults. The 5-year overall survival rate is less than 60%. We present here a retrospective analysis of adults treated with an intensive pediatric chemo-radiotherapy regimen PNET HR + 5: NCT00936156.

Methods: Eighteen patients over the age of 20 (range, 20-33 years) with HRMB (n = 13), pinealoblastoma (n = 4), and central nervous system embryonal tumor (n = 1) were treated with 2 courses of carboplatin-etoposide followed by 2 courses of high-dose thiotepa (HDT) with autologous hematopoietic stem-cell rescue. A craniospinal irradiation (CSI; 36 Gy craniospinal axis then a boost of 18 Gy to the primary tumor site) was then initiated within 150 days of surgery, completed with 6 cycles of temozolomide; the axis irradiation was not mandatory for non-metastatic pinealoblastoma.

Results: We observed no progression under chemotherapy and no toxic death. Four patients received only 1 HDT. Two non-metastatic pinaloblastomas received only focal irradiation. One medulloblastoma received only 25 Gy on the axis. 56% (10/18) received 6 cycles of temozolomide. No long-term toxicity was recorded. The median time between surgery and CSI was 175 days (range, 115-250). With a median follow-up of 6.0 years (range, 2.6-9), the progression-free survival and overall survival rates for medulloblastoma were respectively 65% (95% CI: 31%-86%) and 76% (95% CI: 42%-91%) at 5 years.

Conclusions: The PNET HR + 5 regimen showed promising results in an adult population, with a meaningful improvement in progression-free survival and overall survival in patients with HRMB.

Keywords: adult medulloblastoma; high-dose chemotherapy; high-risk medulloblastoma; pinaloblastoma; thiotepa.

Figure 1.

Schematic diagram of treatment regimen administration delays in the pediatric and adult medulloblastoma cohorts compared to protocol administration recommendations. CE, carboplatin etoposide; HDT, high-dose thiotepa; CSI, craniospinal irradiation, Median D, Median time of completion in days.

Figure 2.

Kaplan–Meier curve of treatment outcome for adult medulloblastoma patients (n = 13): progression-free survival (PFS) (A) and overall survival (OS) (B) at 3 and 5 years. Individual outcomes of patients (n = 18) with medulloblastoma, pinealoblastoma, and central nervous system (CNS) embryonal tumor showing progression-free survival (PFS), overall survival (OS), and follow-up (C). No., number.