Table 1.
Medulloblastoma | Germline studies | Age at Dx | Treatment | 2nd cancer | Treatment | 3rd cancer | Treatment | Outcome, time after MB, age | |
---|---|---|---|---|---|---|---|---|---|
1 | Desmoplastic/nodular MB (standard risk) Pathology: Non-amplified MCYN TP53 wildtype SHH-MB |
De novo TP53 pathologic variant from buccal swab Parents tested |
8y | Packer’s protocol (Lomustine, vincristine, cisplatin) CSI (23.4Gy) + tumor bed boost (30.6Gy) Total 54 Gys |
Myelodysplastic neoplasm with biallelic TP53 inactivation, germline TP53 LP variant, post cytotoxic therapy (Dicentric chromosome 5, 17) MB: no evidence of recurrence 17 months from MB |
Azacitidine (2 courses) Haploidentical HSCT 4 courses Conditioning regimen: • Alemtuzumab 0.6mg/kg • Fludarabine 150mg/m2 • Thiotepa 10mg/kg • Melphalan 140mg/m2 |
T-LBL, stage III MB: no evidence of recurrence 45 months from MB |
Methotrexate, asparaginase, vincristine, daunorubicin | Died from T-LBL (3rd cancer) 48 months from diagnosis 12y |
2 | Focal anaplastic features Pathology: Non-amplified MYCN TP53 mutant SHH-MB |
TP53 pathologic variant from EDTA blood Parents not tested |
9y | Packer’s protocol (Lomustine, vincristine, cisplatin) Withheld at cycle 7 due to PRES CSI (36Gy cranial + 36Gy spinal) |
Myelodysplastic neoplasm with biallelic TP53 inactivation, germline TP53 LP variant, post cytotoxic therapy (5q loss, monosomy 7, trisomy 8, 17p loss) MB: no evidence of recurrence 33 months from MB |
Double cord blood transplantation Conditioning regimen: • Cyclophosphamide 120mg/kg • Busulfan dose 12.8 mg/kg • Antithymocyte globulin 5mg/kg • Melphalan 140mg/m2 |
Died from complication of HSCT 43 months from diagnosis 13y |
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3 | Classic medulloblastoma Pathology: Non-amplified MYCN Group 3 46 months: Recurrent anaplastic medulloblastoma Variant allele 47.8%, for MUTYH protein, unknown significance |
TP53 mutation not reported from EDTA blood Parents not tested |
5y | 1. HKPHOSG PNET-CNS-2000 protocol Cisplatin, vincristine, lomustine Proton Stereotactic Body Radiation Therapy (23.4Gy) and tumor bed boost (1-1.5cm margin). Total 54 Gys 2. MEMMAT protocol Bevacizumab, thalidomide, celecoxib, fenofibrate (oral) Etoposide, cyclophosphamide (systemic) Etoposide, cytarabine (intraventricular) SBRT of recurrent lesions in left frontal region (54Gy) CAR-T cell therapy anti-GD2 |
Acute myeloid leukemia, myelodysplasia-related, post cytotoxic therapy (Monosomy 7) MB: disease progression with BM involvement 65 months from MB (18 months from relapse) |
Azacitidine, venetoclax (1 course) | Died from complications of medulloblastoma and MDS 69 months from diagnosis 11y |