Brainstem Injury in Pediatric Patients with Posterior Fossa Tumors Treated with Proton Beam Therapy and Associated Dosimetric Factors
Menée à partir de données portant sur 216 patients pédiatriques atteints d'une tumeur primitive de la fosse cérébrale postérieure traitée par protonthérapie (âge médian au traitement : 6,6 ans ; durée médiane de suivi : 4,2 ans), cette étude évalue le taux de lésions du tronc cérébral liées au traitement, puis identifie les facteurs dosimétriques associés
Background : Proton radiotherapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0-16%) than most photon series (2.2-8.6%). Here we report the incidence of brainstem injury and risk factor analysis in pediatric patients with posterior fossa (PF) primary tumors treated with proton radiotherapy at our institution. Methods : 216 consecutive patients treated between 2000-2015 were included. Dosimetry was available for all but 4 patients. Grade 2-5 late brainstem toxicity was assessed by NCI CTCAE v4.0. Results : Histologies include medulloblastoma (154, 71.3%), ependymoma (56, 25.9%), and atypical teratoid rhabdoid tumor (ATRT) (6, 2.8%). Median age at radiation: 6.6 years (range:0.5-23.1), median dose: 54 GyRBE (range:46.8-59.4) and median follow-up: 4.2 years (range:0.1-15.3) among 198 survivors. 83.3% received chemotherapy; 70.4% achieved GTR. The crude rate of injury was 2.3% in all patients, 1.9% in medulloblastoma, and 3.6%/0% in ependymoma/ATRT patients. The 5-year cumulative incidence of injury is 2.0% (95% CI:0.7-4.8%). Median (D50) brainstem dose in the whole cohort was 53.6GyRBE(range:16.5-56.8), Dmax: 55.2 GyRBE(48.4-60.5), mean: 50.4GyRBE (21.1-56.7). In the five patients with injury, median D50: 54.6GyRBE (range:50.2-55.1), Dmax: 56.2GyRBE (55.0-57.1), mean: 51.3GyRBE (45.4-54.4), and median V55: 27.4% (0-59.4). Four of five patients with injury had a brainstem Dmax in the highest quartile (≥ 55.8GyRBE; p=0.016) and a V55 in the highest tertile (>6.0%) of the cohort distribution (p=0.047). Three of 5 patients with injury were older than 6 years (age range:4.1-22.8), and 4 of 5 patients received chemotherapy and achieved GTR. Conclusions : The incidence of injury of pediatric patients with PF tumors is consistent with previous reports in the photon setting. Our data suggests that when Dmax and V55 are kept below 55.8 GyRBE and ≤6.0%, respectively that the 5-year rate of radiation brainstem injury would be <2%.