1. 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 Mar;45(3):393-6.
2) Radiother Oncol Mar;54(3):
3) Int J Radiat Oncol Biol Phys Oct 1;39(3):
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, 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.