39/69 hormone replacement 9/69 Cerebrovascular events The Regression Patterns of Pediatric Optic Pathway Glioma after Proton Beam Therapy Sang Hee Youn, Hyunjung Kim, Haksoo Kim, Taehyun Kim, Jonghee Jung, and Joo-Young Kim Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang-si, Republic of Korea BACKGROUND Optic pathway gliomas comprise 1-5% of pediatric brain tumors and classically indolent low-grade astrocytoma that arises anywhere along the optic pathway. Radiotherapy (RT) plays an important role as a definitive treatment. However, the age at which chemotherapy should be used to delay RT is controversial from less than 6 years to less than 10 years. Proton beam therapy (PBT) has dosimetric benefit of reducing dose for normal brain that especially advantageous for pediatric patients who need to develop neuro-cognitive function after treatment, compared with 3D-comformal or intensity modulated photon therapy (Figure 1). Despite accumulated evidence of clinical stabilization after RT, the radiographic response of optic pathway glioma after RT is limited (Table 1). We examined the regression patterns of pediatric optic pathway glioma after PBT by measuring the cystic, and the solid volumes as well as the entire tumor volume in yearly follow-up MRIs and evaluated clinical outcomes of local control and visual outcome. Table 1. Summary of previous studies 　Author Tx. Age No. 10Y PFS 10Y OS Dose Vision Late effects Cappelli et al.1) RT 5 (3 mo -15) 69 65.5% 83% 54 Gy 18/69 improved, 29/69 stable 39/69 hormone replacement 9/69 Cerebrovascular events Grabenbauer et al. 2) RT, OP+RT 45 69% 94% 52 Gy Tao et al.3) 6.6 42 89% 100% 24.1% improved, 48.3% stable 72% new hypopituitarism 1) Ann Neurol. 1999 Mar;45(3):393-6. 2) Radiother Oncol. 2000 Mar;54(3):239-45. 3) Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):579-87. Tx., treatment; OP, operation; No., number of patients; PFS, Progression-free survival; OS, overall survival Figure 1. A comparison of dose distribution PATIENTS & METHODS A total 42 brain MRI of 7 consecutive patients (non-NF-1) treated with PBT between June 2007 and September 2016 at National Cancer Center, Korea. The chemotherapy regimen: mostly carboplatin + vincristine. Others: Vinblastine + Vincristine + 5-Fluorouricil + Cyclophosphamide + Etoposide / Procarbazine + CCNU + Vincristine / Avastin + Irinotecan / Temozolomide Patients had taken brain MRI regularly from before PBT to after PBT at 6 months, 1, 2, 3, 4 and 5 years. Prescription dose: Median 54 CGE/30 fractions (range, 50-59.4 CGE/25-33 fx) [Volume evaluation] Total tumor, cyst and solid mass area delineation and volume calculation on gadolinium enhanced T1-weighted MRI. Total tumor volume (Red-line): all the tumor Cyst volume (Orange-line): volume ≥ 0.2 cc Solid mass volume (Green-line) : contrast enhancing solid mass Software: Eclipse version 13, Varian Min-max normalization for volumes: rescaling range of values to scale the range in 0 to 1 Table 2. Patients and treatment characteristics No. % Age at diagnosis median 7 Range (9mo-11) Age at proton beam therapy (4-16) Sex Male 4 57.1 Female 3 42.9 Pathology Pilocytic astrocytoma not confirmed Initial treatment Resection + chemo Chemo alone Location of tumor Optic nerve 1 14.3 Optic chiasm 5 71.4 Optic nerve + Optic chiasm No. % Initial symptoms Decreased vision 3 42.9 Visual field cuts 1 14.3 Exophthalmos 2 28.6 EOM limitation Precocious puberty Reason of radiotherapy Intolerable of chemotherapy Tumor progression 6 85.7 Duration of chemotherapy (months) Median 25 Range (3-70) Interval after chemotherapy (months) 7 (1-44) Interval after diagnosis (months) 48 (8-71) Figure 2. An example of volume measurements RESULTS Figure 4. Cyst and solid mass volumes normalized by min-max method Figure 2. An example of patients who showed a good response after PBT Median follow-up period after PBT: 54 months (range, 30-90) Time frame of increasing cystic volume : Median 35 months (range, 25-56) Time frame of decreasing solid mass volume: Median 30 months (range, 18-65) Local control rate: 85.7% (5YR PFS 80% & 5YR OS 100%) Vision preservation: 71.4% (5 of 7 patients) We observed cystic change of tumor and increasing cystic volume in follow-up MRI after PBT. After cystic change of solid tumor, the total volume of tumor gradually decreased. *T50: the time to a 50% or greater reduction Table 3. Summary of patients outcomes Before RT After RT No Sex Age Location Pathology OP CTx VF EF Regrowth Intervention 1 M 10 ON N yes Loss* Decompression 2 F OC PA Stable 3 7 (+) 4 OC+ON Improved Local failure 5 9mo 6 VP shunt 11 yes　 Figure 3. Regression patterns of volume normalized by min-max method ON, optic nerve; OC, optic chiasm; N, not confirmed; PA, pilocytic astrocytoma; VF, visual functiona; EF, endocrine function CONCLUSION Median age of PBT 7 years (range, 4-16) and median duration of chemotherapy before referral to PBT center was 25 months (range, 3-70). PBT resulted in good local control and visual outcome. The regression patterns of pediatric optic pathway glioma after PBT involved significant cystic change. Median time to the greatest volume increase in cystic change was 35 months. Solid mass volume was gradually decreased and the time to a 50% or greater reduction (T50) was 29 months. If solid mass volume were increased, it could be suspected disease recurrence. Total volume change was variable and more slowly regression (T50=42 months). Therefore, total volume did not appropriate for evaluating response. Patients with tumor which underwent cystic change after chemotherapy by the time of radiotherapy showed severe cystic change after PBT.