Factors affecting Facial Asymmetry in Children Irradiated For Embryonal Rhabdomyosarcoma of the Orbit Marinka L.F. Hol, MD1; Daniel J. Indelicato, MD2; Ronny L. Rotondo, MD2; Raymond B. Mailhot Vega MD, MPH2; Haruka Uezono, MD2; Julie A. Bradley, MD2 1Amsterdam UMC, The Netherlands 2University of Florida, United States BACKGROUND AND PURPOSE MATERIALS AND METHODS 2006 to 2018: 1,657 pediatric patients treated at UF Health 17 survivors with COG group 1 stage 3 orbital ERMS MRI available at >6 months follow-up No previous treatments in the head and neck area 1 patient excluded for a tumor still largely in situ With the ongoing improvement in long-term survival among patients with paediatric embryonal rhabdomyosarcoma (ERMS), the impact of adverse late effects becomes more prominent. In patients with orbital tumors, these late effects include poor cosmesis associated with facial deformation and facial asymmetry. Our purpose was to assess orbital volume (OV) changes in patients treated for orbital ERMS and to characterize the dose effect for orbital bones. Orbital Volume Calculation PATIENTS AND TREATMENT CHARACTERISTICS OV was measured on the MRI Use: axial slice with the maximum size of lens Anterior-posterior depth: the lens to deepest part of the bony orbit Width: the most anterior part of the zygomatic bone to the posterior part nasal bone For the volume calculation, the orbit was considered a cone Radiotherapy All patients were treated to a dose of 45 GyRBE in 1.8 fractions with protons delivered in 2 sequential phases. All patients were treated with double-scattered proton plans using 2 to 3 beams per phase. Factors affecting Orbital Volume Baseline Characteristics N = 16 Age at diagnosis Mean (range) 5.4 yrs (1.1 - 9.7yrs) Follow-up time 2.9 yrs (0.8 – 3.2 yrs) Age at scan 8.4 yrs (2.3 – 12.9yrs) Sex Male Female 10 (63%) 6 (37%) Chemotherapy protocol ARST0331 D9602 RMS2005 1 (6%) 9 (56%) Patient age, orbital tumor quadrant, and the maximum radiation dose delivered to the major orbital bones (maxillary bone, frontal bone,and zygomatic bone) were recorded and correlated with orbital volume differentials. Example of left orbital hypoplasia in RMS survivor RESULTS Orbital Volume Radiation Dose-effect N=16 Radiated side Non-radiated side Statistical significance Orbital volume 11 cm3 Range: 5.3 – 17.3 cm3 12.9 cm3 Range: 7.4 – 17.9 cm3 P<0.005 N=16 Mean dose Range Correlation OV differential Frontal bone 41.9Gy 22 - 45Gy 0.32 Zygomatic bone 40.8Gy 31 - 45Gy 0.15 Maxillary bone 41Gy 27 - 45Gy 0.22 Orbital rim combined 41.25Gy 0.47 N=16 Mean difference Over 1 cm3 Over 2 cm3 Orbital volume differential 1.9 cm3 (1.0 – 4.9 ) 75% 41% Orbital Volume Differential and Time The OV differential did not correlate with age at treatment (R=-0.2, p=0.8). The OV differential moderately correlated with the amount of follow-up time (R=0.49, sig lev P=0.02), with notable volume differential observed in patients with a follow-up time over 4 years (p=0.017). The OV differential did not correlate with age at the follow-up scan (R=0.01). CONCLUSIONS Over 75% of orbital ERMS survivors will demonstrate orbital volume asymmetry. Differential in orbital volume most affected by a combined radiation dose of >40 Gy to all orbital rim bones. Isolated high radiation dose to any of the orbital rim bones did not impact orbital volume at early follow-up. These data may be used to guide treatment planning and counsel patients on expected cosmesis. Corresponding Author: Daniel J. Indelicato, MD, dindelicato@floridaproton.org