MEDU-12. TREATMENT RESULTS OF CHILDREN WITH METASTATIC MEDULLOBLASTOMA ACCORDING TO C-MYC/N-MYC/Iso17q AND MGMT TUMOR STATUS. (23rd April 2019)

• Record Type: Journal Article
• Authors: Levashov, Andrey; Khochenkov, Dmitry; Stroganova, Anna; Ryzhova, Marina; Gorelyshev, Sergey; Babelyan, Stepan; Subbotina, Natalya; Daylidite, Vadmante; Zagidullina, Svetlana; Dolgopolov, Igor; Seregin, Georgy; Sidelnikov, Dmitry; Mentkevich, Georgy
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 2
• Page Start: ii105
• Page End: ii105
• Publication Date: 2019-04-23
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz036.171
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: From 2008 to 2018 forty nine patients with de novo metastatic medulloblastoma were included in trials. Median age is 7.8 years (range, 4 – 17). Children underwent adjuvant therapy arm A (like-SJMB03, n = 14) from 2008 to 2014: craniospinal radiation (CSI) 36Gy + local radiation to the tumor bed – up to 54Gy (daily fraction 1.8Gy), 4 cycles (vincristine/HD-cyclophosphamide/cisplatin) with auto stem cell rescue; arm B (n = 19) from 2014 to 2018 – induction chemotherapy (vincristine/HD-cyclophosphamide/cisplatin/etoposide +/- HD-methotrexate), CSI 24.4 (without C-MYC/N-MYC/Iso17q), other 36Gy + local - up to 54Gy, 2 cycles thiophosphamide/carboplatin +/- 5-azacitidine, with auto stem cell transplantation; arm C (n = 16) – individual treatment program (including CSI 23.4-36Gy and HD-chemotherapy). R1 status was revealed in 24 patients (49%), M2/3 in 41 (83.7%), large-cell anaplastic histological variant in 8 (16.3%), MGMT protein expression in 23 (69.7%), iso17q in 20 (48.8%), N-MYC amplification in 5 (13.5%), C-MYC amplification in 2 (4.3%). Disease-free survival (DFS) was 38.5 ± 13.5% in arm A, 65.6 ± 19.9% in B, 28.6 ± 13.8% in C (p = 0.008), a median follow-up 54.7 ± 10.2 months (A), 24.3 ± 4.2 (B), 11.9 ± 3.4 (C). DFS was 16.7 ± 14.6% in group with MGMT-positive tumor; 23.2 ± 13.8% - with iso17q-positive tumor; 33.3 ± 25.5% - with C-MYC/N-MYC -positive tumor; with CSI 23.4 Gy 73.3 ± 11.4% (a median follow-up 24.5 ± 6.4 months), 90.9 ± 8.7% (arm B, a median follow-up 28.3 ± 6.2 months), with CSI 36 Gy 29.8 ± 10.8% (a median follow-up 32.7 ± 5.7 months), p = 0.320. 9 events were revealed in arm A, 6 in B, 11 in C (p = 0.055), relapses in 12 cases, progression in 7. Treatment related mortality was 16.3% (8 children, 5 - due to septic complications, 3 – other toxicity). Chemotherapy intensification could help us to reduce CSI dose down to 23.4 Gy in some patients with metastatic disease and C-MYC/N-MYC /Iso17q - negative tumor.