Nikoghosyan et al. BMC Cancer 2010, 10:607 http://www.biomedcentral.com/1471-2407/10/607 throughout the target volume due to its dependence on various factors. RBE will be calculated for each voxel throughout the target volumes and biological optimiza- tion will be performed. The dose prescription used is related to the isoeffective dose Gy E using daily fractions of 3 Gy E and a weekly fractionation of 4-6 × 3 Gy E. For proton therapy RBE of 1.1 will be used using daily fractions of 2 Gy E and a weekly fractionation of 4-6 × 2 Gy E. Evaluation of DVH for the dose distribution will be performed with regards to assess plan quality. Maximum chiasm dose, maximum right and left optic nerves dose, maximum brain steam dose, median brain steam dose, maximum dose to spinal cord, median dose to spinal cord will be reported. Dose prescription Arm A (carbon ion therapy): Total dose to the PTV2 - 45 Gy E in 3 Gy E/d, 4-6 days a week, 15 fractions Total dose to the PTV1 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E. Arm B (proton therapy): Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E/d, 4-6 days a week, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 fractions a 2 Gy E. Dose constraints to organs at risk for both arms Dose constraints to organs at risk (OAR) are estimated considering the experience of our institution as well as the data reported by Emami et al. [19] (Table 2). Organization, Workflow and Follow-up Patient data will be collected and documented pseudo- nymously using electronic data processing (e.g. patient initials, date of birth and study number) at the study office at HIT. Table 3 presents a brief workflow. After randomisation the study number will be assigned. Table 2 Dose constraints to organs at risk OAR Eyes, temporal lobes, salivary glands, mandible and other Optic nerves and chiasm Brainstem Brainstem center Spinal cord Dose constraints as low as possible ≤ 54 Gy ≤ 54 Gy with 1% of Volume allowed to receive >54 Gy, with Dmax ≤ 60 Gy <50 Gy ≤ 45 Gy with 1% of Volume allowed to receive >45 Gy, with Dmax ≤ 50 Gy Page 5 of 9 The following study data will be collected at the study office at HIT: 1. Medical reports including pathology reports and results of staging and additional pre-treatment examinations 2. Documentation of RT (dose distributions and DVH) and position checks 3. Prescribed total target dose and fraction doses, treatment interruptions >4 days 4. Toxicity data 5. Follow-up forms 6. Trial-related documentation including severe AE (CTCAE Grad ≥ 3) will be reported immediately to the study office and the principal investigator of the study 7. The date of local recurrence (MRT or CT - mor- phological tumour progress in the former irradiated region), distant metastases or death of the patient will be reported and documented. Local recurrences will be confirmed radiologically and histologically whenever possible. At least two medical doctors (radiation oncologist and/or radiologist) will be required to judge of the recurrence or toxicity. Every patient is followed for LPFS and trial-related AEs for a time period of 8 years. Furthermore, patients will be followed for survival and locoregional recur- rences for a time period of 8 years after completion of the irradiation. The first and the second follow-up examination will be performed 4-6 weeks and 3 months after completion of RT (follow-up 1 and 2). Follow-up examinations will then be scheduled after 6 months (follow-up 3), 9-12 months (follow-up 4), and then once a year for further 6 years (follow-up 5, 6 and 7). Additional visits will be scheduled as necessary. Acute toxicity is assessed at least weekly during RT and documented at the end of the RT series, 6 weeks after completion of RT and 3 months after RT. Late toxicity will be documented in regular intervals of 6 or 12 months during the observa- tion period. All the patients will be observed for radia- tion specific acute and late AEs for the time of at least 8 years after irradiation. The maximum grade of toxicity will be determined for each patient. The Common Terminology Criteria for Adverse Events V4.0 (CTCAE V.4.0) will be used to grade acute toxicity from radiation therapy. The criteria are relevant from the 8th irradiation day until day 90, i.e. until the 1st follow-up visit. Thereafter, the RTOG/EORTC Cri- teria of Late Effects will be utilized. All acute radiation effects will be documented on an Acute Radiation Effect-Form. In addition, the AE-Form and/or SAE- Form will be filled out. RTOG/EORTC Late Morbidity