Patients are usually treated supine in a custom-made immobilization device. All patients should undergo CT simulation and for all patients the diagnostic MRI should be co-registered with the CT images. The target volume for radiotherapy is then contoured on MRI. The gross target volume is almost always best defined on T2-weighted or FLAIR MRI (maximum extent of disease). The margin for the clinical target volume is 1–1.5 cm, anatomically constrained by bone and sometimes too by the tentorium. The planning target volume will be technique- and institution specific. Although these days more sophisticated techniques such as IMRT are commonly used, 2D or 3D techniques may also be very acceptable, especially if to do so reduces the preparation time and so the delay to the start of treatment. The radiotherapy dose is typically 54–55.8 Gy given in 30–31 daily fractions of 1.8 Gy over 6 weeks. Alternative fractionation schedules have been extensively investigated in patients with DIPG. Hyperfractionated radiotherapy using fraction sizes of 1–1.26 Gy given twice a day to higher total doses of up to 78 Gy in an attempt to improve tumor control was tested in series of studies in North America in the 1980s and 1990s. There was no evidence of benefit and at the highest doses levels of 76–78 Gy considerable morbidity such as protracted use of steroids and vascular events was observed (Freeman 1996). Accelerated radiotherapy using conventional fraction size of 1.8 Gy given twice a day to total doses of 48.6–50.4 Gy over a shorter overall treatment time of approximately 3 weeks theoretically reduces the opportunity for tumor repopulation. While outcome in a British study was not improved, treatment was well tolerated and considered advantageous in that the patient and family spends less time in/near to the hospital (Lewis et al. 1997). Hypofractionated radiotherapy has been given with the goal of achieving equivalent tumor control with fewer hospital visits. When compared with conventional radiotherapy in previously treated patients and in one prospective randomized study, hypofractionated radiotherapy using doses of 39–45 Gy given once daily with fraction sizes of 3 Gy appeared safe and equally effective and thus could be considered an acceptable option given the shorter overall treatment time of less than 3 weeks and lesser burden for patients and families (Janssens et al. 2013; Negretti et al. 2011; Zaghloul et al. 2014).

Chemotherapy has no established role in the treatment of newly diagnosed DIPG. Two randomized phase III trials as well as many phase I/II studies using chemotherapy and/or biological agents concurrent with standard radiotherapy, e.g., cisplatinum, VP-16, temozolomide, topotecan, gadolinium texaphrin, have all failed to show any improvement in outcome (Hargrave et al. 2006). Nimotuzumab, an anti-EGFR monoclonal antibody, appears somewhat more promising with a very high response rate of 96% and a median time to progression of 8.5 months when given in combination with Vinorelbine and radiotherapy (Massimino et al. 2014).