While the majority of patients with diffuse intrinsic pontine glioma (DIPG) experience symptomatic improvement following radiation therapy (RT), long term survival is virtually nonexistent. Dose escalation attempts encompassing essentially every type of RT method have failed to improve median survival and several approaches have been met with increased toxicity. Historic dose threshold studies suggest doses greater than 45Gy may result in improved survival; however, dose response to symptom change in DIPG is unknown. A total of 110 consecutive patients with clinically and/or pathologically diagnosed DIPG treated at a single institution from 2006 to 2014 were retrospectively reviewed. Two patients required intubation throughout RT and were excluded from analysis. The presence and severity of neurological symptoms related to cranial neuropathy (CN), cerebellar signs (CS), and long tract signs (LTS), the triad of clinical symptoms in DIPG, were subjectively scored prior to start of RT and at each weekly therapy visit during RT. The baseline and weekly corticosteroid use, the use of concurrent systemic therapy, and presence of CSF shunt placement were recorded. The incidence and rate of change of each symptom category was evaluated through descriptive statistics. Kaplan Meier product limit method was used to estimate progression-free and overall survival. The median age at time of RT was 6.2 years (range, 2.1 – 17.6 years). One year progression-free and overall survival estimates were 13.5% (95% CI, 8.3%-21.9%) and 36.8% (95% CI, 28.7%-47.2%), respectively. A total of 96 (88.9%) patients received concurrent systemic therapy during RT. Ninety patients (83.3%) were treated on a prospective clinical trial. The median RT dose was 54Gy (range, 42-55.8 Gy). Prior to start of RT, 95.3%, 76.9%, and 72.2% of patients experienced neurologic symptoms related to CN, CS, and LTS, respectively, while the triad of deficits was noted in 57.4% of patients. Near the completion of RT, symptomatic improvement related to CN, CS, and LTS was noted in 85.4%, 87.9%, and 80.8% of patients, respectively. Corticosteroids were required for 85% of patients prior to RT and 53.7% near completion of RT. The median (range) doses prior to RT and near completion were 8mg/day (1-16mg/day) and 1.75mg/day (0.25-16mg/day), respectively. The median RT dose to symptomatic improvement was 16.2 Gy (CN), 21.6 Gy (CS) and 19.8 Gy (LTS), with the majority of patients improved by 20Gy. Of those patients with baseline symptoms, 6-8% of patients experienced progressive neurologic symptoms at a cumulative dose of 36Gy. This descriptive analysis suggests that low cumulative doses of RT provide neurologic improvement as measured by clinical assessment of common deficits in patients with DIPG. Incorporation of validated neurologic symptom assessment into prospective clinical trials for DIPG should be considered to address the impact of altering RT parameters on neurologic symptom palliation.
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Dec 1, 2018
Bartlomiej Tyzo + 8
Open Access