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Results
Almost 50% of the patients had tumour motion amplitudes
of less than 5mm. For these patients, the simulated dose
degradation per fraction was much smaller than for
patients with larger motion amplitudes, with 2% versus 12
% average absolute reduction of the V95 (p<0.01), and an
average increase in absolute V107 of 2% vs 9% (p<0,01). In
no patient case studied was the minimum dose in the
target degraded to below 80% of the prescribed dose, and
rarely increased above 120%. Simulating a 33-fraction
treatment, the mean reduction of the V95 was below 1%
for patients with motion amplitudes below 5mm, while for
patients with larger motion, V95 was degraded on average
by 4% with worst case scenarios of 4% versus 19% (p<0.01),
cf. Fig. 1. V107 had an average increase of about 0% and
1% (n.s.), with worst case values of 5% and 15%. The
additional analysis of one patient case with a repeated CT
revealed a large increase of tumour motion by about 5mm
during treatment, resulting in a large dose degradation
and partial miss of the target (V95<70%), cf. Fig. 2.
Conclusion
Motion amplitude is an indicator of dose degradation
caused by the interplay effect. Fractionation reduces the
dose degradation to such an amount that rescanning might
be unnecessary for patients with a small tumour motion
less than 5mm. Patients with larger tumour motion should
not be treated without any kind of motion mitigation
technique (e.g. rescanning , gating or breath hold) to
prevent tumour underdosage persisting through to the end
of fractionated treatment. Furthermore, the tumour
motion needs to be assessed during treatment for all
patients to quickly react to possible changes in motion
which might require a treatment adaptation.
Proffered Papers: Lung
OC-0139 Induction of pulmonary hypertension may
explain early mortality after thoracic radiotherapy
P. Van Luijk
1
, T.M. Gorter
2
, T.P. Willems
3
, R.P. Coppes
1
,
J. Widder
1
, J.A. Langendijk
1
1
University Medical Center Groningen, Department of
Radiation Oncology, Groningen, The Netherlands
2
University Medical Center Groningen, Department of
Cardiology, Groningen, The Netherlands
3
University Medical Center Groningen, Department of
Radiology, Groningen, The Netherlands
Purpose or Objective
Studies of primary or postoperative radiotherapy for
thoracic tumours, such as for lung and oesophageal
cancer) suggest increased early post-treatment mortality
with escalated dose (e.g. RTOG0617, INT0123). This
increase in mortality is largely unexplained and is not due
to currently-recognized cardiac and pulmonary toxicities.
We have previously shown in rats that thoracic irradiation
can also lead to pulmonary hypertension (PH) secondary
to endothelial cell loss and pulmonary vascular
remodelling (1). PH is a progressive and lethal disease that
might explain the early mortality after thoracic
radiotherapy. However, since detection of PH requires
specialized diagnostics, PH has not been assessed in RT
patients so far. Therefore, the main objective of this first-
in-human translational study was to test the hypothesis
that thoracic radiotherapy can induce PH.
Material and Methods
Patients with locally advanced NSCLC undergoing standard
concurrent chemoradiotherapy (60 Gy in 5 weeks) were
included
in
this
prospective
cohort
study
(clinicaltrials.gov; NCT02377934). Since PH typically
decreases pulmonary arterial blood flow (PAF) and
acceleration time (PAcT), these were measured using
cardiac MRI before and at 6 and 12 weeks after
radiotherapy. To establish treatment dependence,
changes in PAF and PAcT were tested for correlation with
mean dose to the lungs.
Results
PAF was reduced by 0.5-0.6 l/min in individual (left/right)
lungs receiving >15 Gy. The reduction in PAF was
significantly correlated with mean radiation dose to that
lung (p=0.04 and p<0.01 at 6 and 12 weeks after
radiotherapy, respectively). In addition, in patients
receiving >15 Gy mean dose to their total lung volume,
PAcT was decreased by 30-40 ms, and this reduction in
PAcT again was correlated with dose (p=0.03 and p=0.07
at 6 weeks and 12 weeks after radiotherapy respectively).
Both hemodynamic changes are strong indicators for PH.
Therefore, these results indicate that PH occurs in
patients treated with thoracic radiotherapy.
Conclusion
In line with our preclinical data we found that thoracic
radiotherapy may induce pulmonary hypertension, which
might in turn explain observed early mortality in patients
treated with thoracic radiotherapy. Additional
investigations are needed to characterise the incidence
and clinical impact of radiotherapy-induced PH and to
develop prevention and treatment strategies to
ameliorate its consequences in terms of quality of life and
survival of these patients.