869 / 1082
S853
ESTRO 36 2017
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using a threshold of 10 mmHg. Assuming a clonogenic cell
density of 10
8
per cm
3
in the CTV, the HTV doses required
to achieve 95% local control (LC) were calculated based on
a previously developed radiobiological model (Toma-Dasu
et al 2009, 2012) accounting for the dynamic tumour
oxygenation due to changes in acute hypoxia not visible in
PET images. The total doses were calculated assuming
that the treatment involves 24, 30 or 35 fractions.
Results
The non-linear conversion function and hypoxic threshold
of 10 mmHg resulted in hypoxic subvolumes identified in
five out six patients. Three out of six patients had a
hypoxic subvolume > 3cm
3
. In two of the patients, the
delineated HTV was not entirely confined within the
primary CTV. For a treatment delivered in 30 fractions,
the prescribed dose required to achieve 95% local control
for the two patients with the largest HTVs of 32.74 and
38.29 cm
3
respectively were 75.52 and 75.67 Gy, both
corresponding to an EQD2 of almost 79 Gy10. For the third
patient with a smaller HTV of only 12.37 cm
3
, the total
dose in 30 fractions for 95% LC was 72.35 Gy. If the total
dose would be delivered in 35 fractions instead, the
prescribed doses would increase with about 2.2% of the
dose prescribed in 30 fractions for all three cases. The
relative decrease in the total dose if the total dose will be
delivered in only 24 fractions is about 3.5% for all three
HTVs. For all patients and for all treatment fractionation
schemes the dose levels required for achieving 95% tumour
control probability accounting for local changes in the
oxygenation of the tumour are below the levels of dose
boosts proved to be feasible to be delivered without extra
dose burden to the OARs on a previous study carried out
on the same patients.
Conclusion
HX4-based delineation of hypoxic target volumes and
calculation of required boost doses for a predefined
tumour control probability appears to be feasible. HX4 is
thus a potentially suitable tracer for the purpose of
treatment individualisation in NSCLC.
EP-1603 Atlas of complication incidence to explore
dosimetric contributions to osteoradionecrosis
L. Humbert-Vidan
1
, S. Gulliford
2
, V. Patel
3
, C. Thomas
1
,
T. Guerrero-Urbano
4
1
Guy's & St Thomas' NHS Foundation Trust, Radiotherapy
Physics, London, United Kingdom
2
The Institute of Cancer Research and Royal Marsden NHS
Foundation Trust, Joint Department of Physics, London,
United Kingdom
3
Guy's & St Thomas' NHS Foundation Trust, Oral Surgery,
London, United Kingdom
4
Guy's & St Thomas' NHS Foundation Trust, Clinical
Oncology, London, United Kingdom
Purpose or Objective
Mandibular osteoradionecrosis (ORN) is one of the most
severe complications in patients with head and neck
cancer undergoing radiation therapy (RT). Potential risk
factors include primary tumour site and stage, radiation
dose, pre- and post-RT dental extractions and mandibular
surgery, chemotherapy, dental hygiene, smoking or
alcohol.
This pilot study aims to assess the contribution of radiation
dose to the mandible to the incidence of ORN and
investigates the effect of different risk factors using the
atlas of complication incidence (ACI) method to
summarise dose-volume histograms and toxicity data.
Material and Methods
This retrospective study included 80 patients with head
and neck cancer with a median age of 62 (range 35-86)
treated with radical IMRT. Primary tumour sites included
a majority of oropharynx cases (42), oral cavity (26),
larynx (6), paranasal sinus (4) and two unknown primary
cases. Half of the cohort had been diagnosed with ORN of
the mandible within a median follow-up time of 3.2 years
(range 1.3-5.3) from the end of RT. The toxicity endpoint
considered included ORN complication of any grading. The
other 40 patients were control cases (no ORN observed)
prospectively matched according to primary site and
treatment option (PORT or primary RT and chemotherapy
type).
For given volume v
j
and dose d
i
levels, the numerical
fraction in a cell of an ACI is composed of the number of
patients (denominator) and the number of patients with
ORN (numerator) that have a mandible percentage volume
between v
j
and v
j+1
exposed to a dose level between d
i
and
d
i+1
. Atlases were created for sub-sets of the entire cohort
to investigate the effects of pre-RT surgery,
chemotherapy, smoking or dental extractions. These risk
factors were also tested with univariate statistical
analysis. Dosimetric variables including d
max
and d
mean
were
tested with ROC analysis.
Results
A dosimetric correlation with ORN incidence was observed
in cases where treatment modality was primary RT (as
opposed to post-operative RT). An increased ORN
incidence was observed towards the large percentage
volume and high doses region of the ACI, where a large
percentage of the mandible volume had received doses of
above 40Gy as well as smaller volume percentages
receiving doses above 64Gy. A similar incidence pattern
was observed for the ACI that included smoking patients
only. The ACI for the sub-set of patients that had
undergone dental extractions pre- or post-RT also showed
a very similar incidence pattern; however, this sub-set
included very few cases.
Conclusion
The ACI analysis carried out so far has shown a dose
response in patients who received primary RT, patients
who smoked at the time of diagnosis and patients who had
dental extractions. The limited number of cases did not
allow for any conclusive statistical significance of the
logistic regression and ROC analysis results. This pilot
study will be expanded to include cases from other centres
to increase the cohort size.
EP-1604 Ion induced complex DNA damage: In silico
modelling of damage and repair using Geant4-DNA.
J.W. Warmenhoven
1
, N.T. Henthorn
1
, M. Sotiropoulos
1
,
R.I. Mackay
2
, K.J. Kirkby
1,3
, M.J. Merchant
1,3
1
University of Manchester, Division of Molecular and
Clinical Cancer Sciences, Manchester, United Kingdom
2
The Christie NHS Foundation Trust, Christie Medical
Physics and Engineering, Manchester, United Kingdom
3
The Christie NHS Foundation Trust, Manchester, United
Kingdom
Purpose or Objective
This work uses Monte Carlo simulation to assess and
understand the differences in biological response to
various radiation qualities in the context of hadron
therapy. The current clinical estimator for this is Relative
Biological Effectiveness (RBE), offering a biological dose
conversion between radiation qualities. A large variability
in reported RBE measurements implies that this parameter
does not give the full picture. This variability in RBE is a
major source of uncertainty in ion therapy treatment
planning. Recently, LET based biological effect models
have been proposed, however, among those reviewed
there are uncertainties in the behaviour of key biological