Medulloblastoma: optimizing care with a multidisciplinary approach

Figures & data

Table 1 Maintenance strategy from trial HIT’91

	Surgery	–		RT-CT						–						CT
Week	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	19	23	27	31	35	39	43
Chemotherapy	–	–		V	V	V	V	V	V	–						A	A	A	A	A	A	A	A
Radiotherapy	–	–		CSI	CSI	CSI	CSI	b	b	–						–

Notes: “–” indicates no treatment during this period. Data from von Hoff et al.⁶⁵

Abbreviations: A, lomustine, vincristine, and cisplatin; b, boost to the posterior fossa to 55.2 Gy (20 Gy given in 10 fractions) and to metastatic sites to 50 Gy; CSI, craniospinal irradiation (35.2 Gy given in 22 fractions); CT, chemotherapy; RT, radiotherapy; V, vincristine.

Table 2 Prognostic classification for pediatric medulloblastomas according to molecular subgroups

	5-year overall survival	Molecular profile
Very high risk	<50%	• Metastatic group 3 • SHH group with TP53 mutation
High risk	50%–75%	• Metastatic or MYCN amplified SHH group • Metastatic group 4
Standard risk	76%–90%	• Localized SHH group without TP53 mutation or MYCN amplification • Group 3 without MYC amplification • Group 4 without loss of chromosome 11
Low risk	>90%	• Localized WNT group • Localized group 4 with loss of chromosome 11

Note: Data from Ramaswamy et al.^5,6

Table 3 Overview summary of current molecular understanding of medulloblastoma

Predominant age group	WNT	SHH	Group 3	Group 4
	Children	Infants, Adults	Infants	Children
Outcome	Very good 5-year OS >95%	Infants good Others intermediate 5-year OS 70%	Poor Children: 5-year OS 58% Infants: 5-year OS 45%	Intermediate 5-year OS 75%–90%
Pattern of relapse	Local or metastatic (rare)	Local	Metastatic	Metastatic
Histology	Classic	Desmoplastic/nodular	Classic, large cell/anaplastic (40%)	Classic
Predominant genetic alterations	CTNNB1 mutation	PTCH1, SMO, TERT, SUFU, TP53 mutation, GLI2, MYCN amplification	SMARCA4 mutation, MYC, OTX2 amplification, GFI1 enhancer activation	KDM6A mutation, SNCAIP duplication, MYCN, CDK6 amplification
Cytogenetic aberrations	Monosomy 6		Isochrome 17q, 1q gain, 7 gain, 8 p loss, 8q gain, 10q loss, 12q gain, 16q loss, 18 gain	Isochrome 17q, X loss, 7 gain, 8 p loss, 1àq loss, 12q gain, 18 gain
Therapeutic prospects	Dose decrease of RT and CT	SMO inhibitor (vismodegib) BET inhibitors CDK4/6 inhibitor (ribociclib) MET inhibitor (foretinib)	Palbociclib HDAC + PI3K inhibitor BET inhibitors	NFkB
Ongoing clinical trials	NCT01878617 NCT02724579 NCT02212574	NCT03434262 NCT01601184 NCT00939484 NCT01239316

Abbreviations: OS, overall survival; RT, radiotherapy; CT, chemotherapy; BET, bromodomain.

von HoffKHinkesBGerberNULong-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT’91Eur J Cancer20094571209121719250820

 PubMed Web of Science ®Google Scholar

RamaswamyVRemkeMBouffetERisk stratification of childhood medulloblastoma in the molecular era: the current consensusActa Neuropathol2016131682183127040285

 PubMed Web of Science ®Google Scholar

RamaswamyVRemkeMAdamskiJMedulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients?Neuro Oncol201618229129725605817

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