Radiation Oncology/Brainstem Glioma

Epidemiology 10-20% CNS tumors in children 5% CNS tumors in adults Subtypes Diffuse brainstem glioma Usually located in the pons. Generally high grade (WHO III/IV). Locally invasive. Universally poor prognosis (median survival <1 yr). 80% brainstem gliomas. Focal brainstem glioma Located in medulla or midbrain. Low grade. Well circumscribed without local infiltration or edema. Significant proportion can have long term survival. 15-20% brainstem gliomas. Anatomy Treatment Diffuse brainstem glioma - treated with steroids and RT/temodar like a high grade astrocytoma. Hyperfractionation has been extensively studied and does not appear to benefit. Focal brainstem glioma Tectal glioma treated with CSF diversion and observation. Tegmental glioma treated with surgical resection. Dorsal exophytic focal brainstem glioma treated with surgical resection. Medullary focal brainstem glioma often treated with RT. Radiation Therapy for Diffuse Brainstem Glioma Nijmegen, Netherlands; 2009 18990510 -- "The role of hypofractionation radiotherapy for diffuse intrinsic brainstem glioma in children: a pilot study." (Janssens GO, Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):722-6. Epub 2008 Nov 5.) Prospective. 9 children, diffuse brainstem glioma. RT 39/13. Mean F/U 15 months Outcome: Median OS 8.6 months, median TTP 4.9 months; both comparable to "standard" regimens Toxicity: No Grade 3-4 Conclusion: Radical hypofractionation feasible, offers quick relief with minimal overall treatment time Harvard; 2003 (1990-96) - 12654425 -- Marcus KJ et al. "A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brainstem glioma." Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1182-5. 18 pts w/ brainstem glioma tx'd w/ etanidazole + hyperfractionated RT on dose escalation protocol. (66 Gy in 1.5 BID to 1st 3 pts, 63 Gy in 1.5 BID to next 15). 3 grade 3 toxicities (skin, 1 vomiting) Median survival 8.5 mo Conclusion: dose limiting toxicity of etanidazole in childhood pt was rash (compared to adults when it is peripheral neurophathy). POG 9239, 1999 (1992-97) - 10192340 -- Mandell LR et al. "There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy." Int J Radiat Oncol Biol Phys. 1999 Mar 15;43(5):959-64. 130 pts w/ diffuse brainstem glioma tx'd w/ concurrent cisplatin and randomized to hyperfractionated RT (117 cGy BID to 70.2 Gy) vs conventional RT (180 cGy qD to 54 Gy). OS at 1 yr was 30.9% (conventional) vs 27% (HF); OS at 2 yrs was 7.1% (conventional) vs 6.7% (HF) Median time to progression was 6 mo's (conventional) vs 5 mo's (HF). Conclusion: no benefit to hyperfractionated RT for diffuse brainstem glioma. Egypt, 2012 (2007-11) - Abstract 2012 -- Zaghloul M et al. "Hypofractionated radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): A prospective controlled randomized trial" Neuro Oncol (2012) 14 (suppl 1): i26-i32. 64 pts w/ diffuse brainstem glioma randomized to conventional RT (55.8 Gy / 1.8 Gy) vs. hyporfractionated RT (39 Gy / 3 Gy). OS at 1 yr was 36.2% (conventional) vs 41.4% (hypofractionated); OS at 2 yrs was 32.3% (conventional) vs 28.4% (hypofractionated) Median time to progression was 7.7 mo's (conventional) vs 7.0 mo's (hypofractionated). Improvement in symptoms in both arms, earlier response in hypofractionated arm. Conclusion: hypofractionated RT for diffuse brainstem glioma offers similar PFS and OS as conventional RT with faster response and less burden for patients/families/clinic