Protocols Are Given in Chronological Order for Each Group

Text 1.

Protocols are given in chronological order for each group

Older Children (> 3 years)

PNET III [1] – intensive chemotherapy prior to craniospinal radiotherapy 56Gy/35Gy

SIOP-HIT PNET IV [2] – for M0 standard risk, radiotherapy (RT) randomised between 56Gy/23.4Gy conventional RT and hyperfractionated RT, followed by Packer chemotherapy

POG 9031 [3] – for metastatic, chemotherapy (cisplatin and etoposide) followed by 56Gy/40Gy conventional radiotherapy and then a consolidation chemotherapy regime (vincristine and cyclophosphamide)

CCLG HART – for metastatic, hyperfractionated accelerated radiotherapy followed by Packer chemotherapy.

CCLG High Risk Guildelines – based on the Milan Protocol [4] – chemotherapy, hyperfractionated craniospinal radiotherapy and high dose thiotipa chemotherapy

Younger Children (< 3 years)

CCLG Infant PNET - Chemotherapy (vincristine, carboplatin, cyclophosphamide) then focal radiotherapy

Headstart II [5] – multi-agent chemotherapy and radiotherapy depending on response

Headstart III – multi-agent chemotherapy and radiotherapy depending on response.

Packer Chemotherapy refers to a 6 weekly schedule with vincristine, cisplatin and lomustine.

Protocol references

[1] Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, Lucraft H, Gilbertson R, Tait DM, Walker DA, Pizer BL, Imeson J, Lashford LS; International Society of Paediatric Oncology; United Kingdom Children's Cancer Study Group. Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study.J Clin Oncol. 2003 Apr 15;21(8):1581-91.

[2] Lannering B, Rutkowski S, Doz F, Pizer B, Gustafsson G, Navajas A, Massimino M, Reddingius R, Benesch M, Carrie C, Taylor R, Gandola L, Björk-Eriksson T, Giralt J, Oldenburger F, Pietsch T, Figarella-Branger D, Robson K, Forni M, Clifford SC, Warmuth-Metz M, von Hoff K, Faldum A, Mosseri V, Kortmann R. Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial. J Clin Oncol. 2012 Sep 10;30(26):3187-93.

[3] Tarbell NJ, Friedman H, Polkinghorn WR, Yock T, Zhou T, Chen Z, Burger P, Barnes P, Kun L High-risk medulloblastoma: a pediatric oncology group randomized trial of chemotherapy before or after radiation therapy (POG 9031).. J Clin Oncol. 2013 Aug 10;31(23):2936-41

[4] Gandola L, Massimino M, Cefalo G, Solero C, Spreafico F, Pecori E, Riva D, Collini P, Pignoli E, Giangaspero F, Luksch R, Berretta S, Poggi G, Biassoni V, Ferrari A, Pollo B, Favre C, Sardi I, Terenziani M, Fossati-Bellani F. Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol. 2009 Feb 1;27(4):566-71

[5] Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, McCowage GB, Diez B, Allen JC, Gopalan A, Cornelius AS, Termuhlen A, Abromowitch M, Sposto R, Finlay JL. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols. Pediatr Blood Cancer. 2008 Jun;50(6):1169-75.

Figure 1.