MDB-04. LONG-TERM OUTCOME OF THE MILANO STRATEGY FOR HIGH-RISK MEDULLOBLASTOMA, INCLUDING THE IMPACT OF MOLECULAR SUBTYPE
Maura Massimino, Chiara Dossena, Francesco Minasi, Francesco Barretta, Francesca Romana Buttarelli, Veronica Biassoni, Matilde Oriani, Elisabetta Schiavello, Marica Ficorilli, Olga Nigro, Bianca Pollo, Manila Antonelli, Vittoria Donofrio, Marco Maggioni, Marcel Kool, Emilia Pecori, Sabina Vennarini, Francesca Gianno, olga nigro, Alessandra Erbetta, Luisa Chiapparini, Roberto Luksch, Elena Barzanò, Cristina Meazza, Marta Podda, Filippo Spreafico, Monica Terenziani, Luca Bergamaschi, Andrea Ferrari, Michela Casanova, Stefano Chiaravalli, Giovanna Gattuso, Simon Bailey, Piergiorgio Modena, Loris De CeccoAbstract
BACKGROUND
Since 2008 we have been using the same strategy as for M+ medulloblastoma for all other high-risk subgroups(LC/A histology,TP53 mutations,and/or MYC/MYCN amplification).
METHODS
After surgery,patients >3-year-old received staging/histo-biological revision and sequential HD-methotrexate,HD-VP16,HD-Cyclo,HD-Carbo.HART-CSI,in two daily 1.3 Gy-fractions/5-days-a-week, reached doses tailored to age and pre-radiation response to chemotherapy:31.2 Gy under 10 years-old if CR+PR or no metastases,39 Gy in other/older patients.Boosts to posterior fossa/residual M+ deposits were given reaching total doses of 59.7–60 Gy and 9 Gy,respectively and avoided if metastatic nodules very big or patients very young.Two courses of high-dose thiotepa were delivered in case of not-optimal response after pre-RT phase and in all M0 patients either in pre/post-RT phase.Subgrouping was obtained through IHC and methylation EPICv2.0 in rescued samples.
RESULTS
Patients were 89,median age 8.8 years,64 males,median fup 136 months. OS/PFS/EFS at 5/15-years were 75.9/66.5%,71.1/69.8%,68.2/65.3%,respectively; 6/28 fatal events were not correlated to medulloblastoma relapse(four 2nd tumors).Sex,age below 10/over 15 years, post-sugical residues,histological subtype(#24 LC/A,#57 classic,#7 nodular-desmoplastic),MYC amplification(#17),CSI dose reduction(#31),absence of boosts(#16),use of myeloablative courses(#45),presence/absence of metastases(#77 M+) did not impact prognosis.Patients progressing after pre-HART chemotherapy(#14) and SD+PD after HART(# 10) did significantly worse(P<0.001)with 1/0 survivors, respectively.Subgrouping done in 44/89 patients so far,showed significant worse PFS/EFS for patients with SHH-tumors(#11, 2 with constitutional Tp53-mutations) vs. groups3 and 4(11 and 22 patients, respectively).Patients younger than 10 had worse response to CT and less boosts (P=0.03 in both) but could receive lower CSI-doses if stratified according to CT-response.
CONCLUSIONS
This strategy, partly adopted in the ongoing SIOPE protocol, confirmed satisfying results in all high-risk categories; SHH tumors appeared the most aggressive in this context.