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treated with PBS PT between 1999 and 2015. Median age
at diagnosis was 3.3 years (range, 0.3-17) and the
male/female ratio was 1.44. The median delivered dose
was 54 Gy(RBE) (range, 40–74.1). Post PT brain alterations
(white matter lesions [WML] and RN) were defined as a
new area of abnormal signal intensity on T2-weighted
images or increased signal intensity on T2-weighted
images and contrast enhancement on T1 occurring in the
brain parenchyma included in the radiation treatment
field, which did not demonstrate any abnormality before
PT. RN was graded according to the National Cancer
Institute Common Terminology Criteria for Adverse Events
v4.03 and EORTC grading systems. The median follow-up
period for the surviving patients was 49.8 months (range,
5.9-194.7).
Results
Twenty-nine (17%) patients developed RN with a median
time of 5 months (range, 1-26), the majority of them
(
n
=17; 59%) being asymptomatic (grade 1). Grade 2, 4 and
5 toxicities were observed in 8, 2 and 2 patients,
respectively. The observed toxicity reversed in a majority
of cases (
n
=18; 62%). The observed WML rate was 11%
(n=18 patients). The 5-year RN-free survival was 71%. In
univariate analysis, neo-adjuvant chemotherapy (
p
=0.025)
and hydrocephalus before PT (
p
=0.035) were significant
predictors of RN.
Conclusion
Children treated with PT demonstrated a low prevalence
(7%) of symptomatic RN. Exposure to chemotherapy before
PT and hydrocephalus as an initial symptom were
significant risk factors associated with RN in these
children/AYAs.
OC-0516 Brainstem linear energy transfer in intensity-
modulated proton therapy of paediatric brain tumours
L.F. Fjaera
1
, Z. Li
2
, K.S. Ytre-Hauge
1
, L.P. Muren
3
, D.
Indelicato
2
, Y. Lassen-Ramshad
4
, G.M. Engeseth
5
, M.
Brydøy
5
, S. Flampouri
2
, O. Dahl
5
, C.H. Stokkevåg
5
1
University of Bergen, Department of Physics and
Technology, Bergen, Norway
2
University of Florida, Department of Radiation
Oncology, Jacksonville, USA
3
Aarhus University Hospital, Department of Medical
Physics, Aarhus, Denmark
4
Aarhus University Hospital, Department of Oncology,
Aarhus, Denmark
5
Haukeland University Hospital, Department of Oncology
and Medical Physics, Bergen, Norway
Purpose or Objective
The enhanced linear energy transfer (LET) and relative
biological effectiveness (RBE) at the end of a proton track
is usually only accounted for qualitatively during
treatment planning. Intensity-modulated proton therapy
(IMPT) plans are currently optimised using dose/volume
constraints for the brainstem, but there is growing
concern about the clinical consequences of the
elevated LET surrounding a tumour volume and potentially
within nearby organs at risk. For posterior fossa tumours
invading or in close proximity to the brainstem, the
brainstem may receive an unintended increased biological
dose. The aim of this study was to investigate how various
posterior fossa tumour locations impact the LET and
biological dose distributions in the brainstem.
Material and Methods
The brainstem was contoured on CT/MRI images on a five
year old male patient with a posterior fossa tumour
treated with protons. Multiple IMPT treatment plans were
generated (in Eclipse, Varian) for different simulated
tumour locations relative to the brainstem: full overlap
between tumour and brainstem (A), half overlap (B),
juxtaposed posteriorly (C) and 1 cm posterior of the
brainstem (D). Two lateral and one posterior non-coplanar
fields were applied for all plans. The dose prescription was
54 Gy(RBE) and brainstem constraints were applied based
on published metrics to keep the risk of brainstem necrosis
<5%. All plans were optimized using a fixed RBE value of
1.1. The dose-averaged LET (LET
d
) as well as the dose-
weighted LET
d
(LET
d
x dose) were subsequently calculated
using the FLUKA Monte Carlo code. The dose-weighted