Medulloblastoma Molecular Subgroup and Hyperfractionated Radiation Therapy Alone for Standard Risk Medulloblastoma : Results of the Pool Data of MSFOP 1998 and 2007 Studies

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Results of pooled data from MSFOP 98 and MSFOP 2007 studies testing hyperfractionated radiotherapy without chemotherapy in standard risk medulloblastoma on 114 evaluable patients and correlation with the new biomolecular classification in 93/114 cases. Between 12/98 and 10/01, 48 patients were included in the MSFOP 98 trial and between 10/08 and 07/13, 66 patients were included in the MSFOP 2007 observational study with the same treatment and criteria inclusion. All patients received hyperfractionated radiotherapy (36Gy- 36fraction) on craniospinal axis, boost with conformal therapy restricted to the tumor bed (68Gy- 68 fractions), and no chemotherapy. Pathologic slides were reviewed by a panel of experts .93/114 have been reclassified according the new biomolecular classification: 9 classic non-WNT/nonSHH, group 3; 28 classic non-WNT/nonSHH group 4; 22 classic non-WNT/non SHH ; 22 Classic WNT activated and 12 SHH activated. The median age of our population was 9.9 years and the sex ratio was 1.7. The mean FU is 195 months for MSFOP98 and 78 for MSFOP2007.The 5 y OS according molecular sub groups is 95% (CI95%: 72-99) for WNT activated group, 86% (CI95%:63-95) for non-WNT nonSHH sub group, 78% (CI95%:36-94) for non-WNT nonSHH, group 3sub group, 77% (CI95%:56-89) for non-WNT nonSHH, group 4 sub group, and 67% (CI95%:34-86) for the SHH activated sub group. Regarding cognitive evaluation, at last measurement for every patient, the mean Full Scale Intelligence Quotient (FSIQ) was 88 (40 – 131) with a mean interval from inclusion of 4.3 y (-0.05 – 13.17). Forty-six patients had performed two assessments or more. After a mean of 5 years (0.95 – 13.17) from inclusion, means IQ were 87 (40-131), 97 (45 - 140), 89 (50 - 111), 84 (50 - 115) and 81 (50 -111). Neurocognitive outcome of these patients is in the low average of normal range for both assessments with slowness and a late decrease of working memory over time (after 5 years of follow up). Working memory does not depend on age at diagnosis but working memory continues to decline 10 years after diagnosis The perceptual reasoning/organization index is below the verbal comprehension index measures but FSIQ remained stable with time and do not continue to decline. With time, there is an advantage of HFRT treatment for cognitive functioning (in the normal range; -0.8 DS) compared to high (35 Gys) and standard (25Gys) dose irradiation. These results confirmed that HFRT without chemotherapy could be an alternative treatment for standard risk medulloblastoma and doesn’t increase the CNS isolated relapse rate. New biomolecular classification is still prognostic in the chemotherapy naïve population.