Correspondence www.thelancet.com/oncology Vol 17 May 2016 e173 Proton beam therapy for medulloblastoma It is heartening to read a report 1 of good functional outcomes following proton beam therapy in young patients with medulloblastoma, including the absence of many unpleasant side effects that can occur after conventional photon therapy. The authors quote UK research, 2,3 which criticises the current proton therapy treatment policy of dividing the x-ray (photon) equivalent dose by 1·1. This is done in order to compensate for the enhanced effectiveness of proton therapy caused by the greater proximity of ionisation in proton beam therapy compared with photons. 4 Radiobiological modelling studies, based on the high radiosensitivity of medulloblastoma cells, suggest a lower necessary dose reduction of 1·03–1·08 in order to maintain the same tumour control effect. A dose division by 1·1, compared with, for example, 1·05 (if correct), would incur a 4% overall change in effective dose, which could translate into a 4–8% reduction in tumour control. The number of patients required to detect such a change would be much larger than the 59 patients included in the study by Yock and colleagues, however: a minimum of several hundred and perhaps over a thousand patients might be necessary. 5 This statistical power requirement indicates the need for national and international cooperation in the conduct and analysis of such rare treatments. 4 The reported maintenance of cognitive function is important. With a predicted dose reduction for neural tissues of 1·2 or more, rather than the 1·1 used in practice, this outcome implies a sufficient reserve of cortical neural radiation tolerance compared with the dose required for tumour control. 2 The brainstem necrosis in one child is likely to be caused by a combination of the lower radiation tolerance of brainstem than cortical brain, enhanced ionisation density effects, previous surgery, and the chemotherapy regimen used. 4 Another important factor is that the meticulous treatments in Boston are given to children who may not only be fitter to travel, but are also from wealthier backgrounds, with better outcomes than those of less privileged children without such access to excellent care. I declare no competing interests. Bleddyn Jones bleddyn.jones@oncology.ox.ac.uk Gray Laboratory, CRUK/MRC Oxford Oncology Institute, University of Oxford, UK 1 Yock TI, Yeap BY, Ebb CH, et al. Long term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single arm study. Lancet Oncol 2016; 17: 287–98. 2 Jones B, Wilson P Nagano A, Fenwick J, McKenna G. Dilemmas concerning dose distribution and the influence of relative biological effect (rbe) in proton beam therapy of medulloblastoma. Brit J Radiology 2012; 85: 912–18. 3 Jones B. Patterns of failure after proton therapy in medulloblastoma. Int J Radiat Oncol Biol Phys 2014; 90: 25–26. 4 Jones B. Towards achieving the full clinical potential of proton therapy by inclusion of LET and RBE models. Cancers 2015; 7: 460–80. 5 Bentzen SM. Radiobiological considerations in the design of clinical trials. Radiotherapy & Oncol 1994; 32: 1–11. We read the recent article by Yock and colleagues 1 with great interest. We commend the authors for their study, which brings the very controversial issue of proton radiotherapy for medulloblastoma to the forefront. However, we feel caution should be exercised in adopting routine proton radiotherapy for medulloblastoma, particularly in the context of other recent studies. Our main concern pertains to the primary outcome of the study, specifically the short follow-up. Another study 2 showed that audiological toxic effects secondary to external beam irradiation are progressive, and a minimum 10 years follow-up is required to adequately assess ototoxicity. 2 The 3 year follow-up in this study should be carefully assessed, as published reports suggest that proton and photon radiotherapy show similar ototoxicity. 1 In fact, a study of intensity modulated photon radiotherapy 3 showed a prevalence of grade 3 hearing loss of 6% with low doses to the cochlea. Median doses to the cochlea with proton radiation reported by Yock and colleagues were similar to doses with intensity-modulated radiation therapy. 1 Treatment heterogeneity also confounds interpretation of this study, and carefully conducted clinical trials with uniform cisplatin dosing are required. We feel that the conclusions surrounding neurocognitive outcomes are also hampered by short follow-up times. Indeed, a recent study 4 of proton radiotherapy versus photon radiotherapy using the same modality (craniospinal radiation with tumour bed boost) showed similar changes in intelligence quotas across both radiation modalities. The study by Yock and colleagues provides a robust foundation, and we hope the authors consider reporting long-term outcomes in the coming decade. Considering the cost of proton therapy, and the state of the literature suggesting equipoise in both efficacy and side effects, we feel that a cautious approach in adopting widespread proton radiation technology for medulloblastoma is warranted. In light of the rising cost of health care in both North America and Europe, the feasibility of routine use of proton radiotherapy requires additional study. The time has now come for urgent properly controlled studies comparing proton and modern photon based radiation for medulloblastoma. We declare no competing interests. *Vijay Ramaswamy, Eric Bouffet vijay.ramaswamy@sickkids.ca Division of Haematology/Oncology, Hospital for Sick Children, Toronto ON, Canada 1 Yock TI, Yeap BY, Ebb DH, et al. Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study. Lancet Oncol 2016; 17: 287–98. 2 Bass JK, Hua CH, Huang J, et al. Hearing loss in patients who received cranial radiation therapy for childhood cancer. J Clin Oncol 2016; 34: 1248–55.