Biomed Imaging Interv J 2007; 3(1):e2
© 2007 Biomedical Imaging and
Initial experience in treating lung cancer with helical tomotherapy
S Yartsev1,*, PhD,
AR Dar1,2, MD, FRCPC,
E Wong1,2, PhD, FCCPM,
G Bauman1,2, MD, FRCPC,
J Van Dyk1,2, MSc, FCCPM
1 London Regional Cancer Program, London Health
Sciences Centre, London, Ontario, Canada
2 The University of Western Ontario, London, Ontario, Canada
Helical tomotherapy is a new form of image-guided radiation
therapy that combines features of a linear accelerator and a helical computed
tomography (CT) scanner. Megavoltage CT (MVCT) data allow the verification and
correction of patient setup on the couch by comparison and image registration
with the kilovoltage CT multi-slice images used for treatment planning. An
84-year-old male patient with Stage III bulky non-small cell lung cancer was
treated on a Hi-ART II tomotherapy unit. Daily MVCT imaging was useful for
setup corrections and signaled the need to adapt the delivery plan when the
patient�s anatomy changed significantly. � 2006 Biomedical Imaging and
Intervention Journal. All rights reserved.
Keywords: Image-guided adaptive radiotherapy; helical tomotherapy; megavoltage CT; lung cancer
Helical tomotherapy is a radiotherapy technique that
combines the geometry of a diagnostic helical Computed Tomography (CT) scanner
with the capability to deliver highly conformal radiation dose distributions in
an intensity-modulated fashion [1,2]. The same linac is also used for obtaining
MVCT images prior to actual daily fractionated treatment. There are at least
two major benefits provided by such imaging: i) a correction of setup errors [3-5]
which is especially important in cases where rigid immobilisation is difficult
or internal motion is common (i.e. extracranial sites such as thorax/abdomen,
some lung cancer patients have difficulty in keeping their arms up even in a
vac-loc immobilisation device, mostly because of arthritis in the shoulders)
and ii) a modification of the treatment itself based on information obtained
from MVCT images. The latter feature, often referred to as image-guided adaptive
radiotherapy, has already been discussed in the literature [6-10]. Ramsey et al.
have done a retrospective treatment planning study and concluded that weekly
plan adjustment of tomotherapy plans may reduce the absolute volume of
ipsilateral lung receiving 20 Gy by 17-23% in lung cancer patients [6,10].
Kupelian et al. have observed a gradual reduction of the gross tumour
volume (GTV) ranging from 0.6-2.3% per day in their non-small-sell lung cancer
patients treated on the tomotherapy unit [7-9]. In this communication, we
describe a clinical case where treatment plan was modified after 22 fractions
and various options to perform adaptive radiotherapy were discussed based on
information provided by a daily MVCT imaging. In particular, we assess the
clinical significance of modifications made to radiation delivery plans
prompted by changes in GTV revealed by MVCT images during fractionated lung
cancer treatment on the tomotherapy unit.
METHODS AND MATERIALS
An 84-year-old male patient presented with symptomatic left
upper lobe and hilar mass, Stage III bulky non-small cell lung cancer without
atelectasis. A kilovoltage CT (kVCT, Philips Brilliance Big Bore, 3 mm slice
thickness, 120 kVp, 300 mAs/Slice) image (Figure 1) was taken 17 days before the start
of treatment and the radiation oncologist (ARD) outlined two targets (gross
tumour volume (GTV) and mediastinal nodes) and the following sensitive structures:
lungs, esophagus, spinal cord, heart. Planning target volumes (PTV) were
created by a 12 mm 3D margin around GTV (PTV Lung) and around mediastinal nodes
(PTV Nodes). Doses of 60 Gy to PTV Lung and 50 Gy to PTV Nodes in 30 fractions
were prescribed. The helical tomotherapy plan based on this anatomy (plan 1:
field slice thickness 2.5 cm, pitch 0.286, expected beam-on time 465 s per
fraction) was approved for treatment.� All treatments were preceded by daily
MVCT imaging (Figure 2). The MVCT study was used for two reasons: a) to correct
for inter-fraction changes of the patient�s position (Figure 3) on the couch by
co-registration of the MVCT study with the kVCT study used for treatment (Figure
4), and b) to assess variations in tumour size and/or positioning inside the
patient. MVCT images for all treatment days were transferred to the planning
station and GTV were contoured on all of them. The variation of the GTV with
time is presented in Figure 5. The error bars were determined by outlining the
maximum and minimum imaginable GTVs on MVCT studies made on Day 1 and Day 43 of
treatment. After 15 fractions, the MVCT images showed a tumour size reduction of
70%. However, the radiation oncologist decided to continue the treatment
according to Plan 1 until delivery of 44 Gy in 22 fractions to ensure
sterilisation of a sub-clinical microscopic disease of the initial target. A
repeat kVCT study (Figure 6) was performed and a new plan with new structure
outlines to reflect the anatomy changes (Plan 2: beam-on time 388 s) was
applied for the remaining eight fractions. To test the clinical significance of
the margin choice we have created another set of target outlines (Figure 7) with
a 0.5 cm margin around GTVs.
Figure 1 Axial slice of kVCT study made
17 days before treatment start date. This was used for the
creation of treatment Plan 1.
Figure 2 30 images corresponding
to 30 fractions of treatment. Reduction of tumour volume is
Figure 3 Daily setup shifts
determined from MVCT/kVCT registration.
Figure 4 Registration
screen on the operating station used for automatic and/or
manual alignment of the MVCT images (upper left and green
colour on the central frame) with the planning kVCT images
(lower left and white colour on the central frame).
Figure 5 GTV reduction
during the treatment showing three distinct phases.
Figure 6 Axial slice of
kVCT study made 39 days after treatment start date. This study,
with the 3D margin around GVT of 1.2 cm was used for the creation
of treatment Plan 2.
Figure 7 Axial slice of
kVCT study made 39 days after treatment start date. This study
with the 3D margin around GVT of 0.5 cm was used for the creation
of treatment Plan 3.
Subsequent follow-ups after four and eight months showed (by
physical examination and diagnostic kVCT with contrast) moderate radiation
pneumonitis (Grade 2) that resolved with fibrosis. The patient follow up
continued for 11 months with no evidence of cancer recurrence.
RESULTS AND DISCUSSION
Sensitive structures tolerance dose criteria  were met
in all three plans as shown in the dose-volume histograms (DVH) for plans 1, 2,
and 3 in Figures 8 (a), (b), and (c), respectively. The full dose was delivered
to the primary target and the nodes without any side effects. The PTV was
reduced to 769 cm3 in Plan 1 to 386 cm3 in Plan 2 and to
193 cm3 in Plan 3. The calculated mean lung dose was 16.3 Gy
according to Plan 1, 10.4 Gy in Plan 2, and 7.9 Gy in Plan 3.� The planned dose
distribution according to Plan 1 is shown in Figure 9. We note high conformity
of the 60 Gy isodose line to the PTV contour. If this plan would have been
delivered 39 days after the start of the treatment when the tumour size has been
significantly reduced (Figure 5), a large region of healthy lung tissue would
have been irradiated as shown in Figure 10. However, Plan 2 (adapted for the
changing tumour size) delivers the prescription dose quite comfortably on Day 39
(Figure 11), with no irradiation to healthy lung tissue due to a lower mean lung
dose of 10.4 Gy. Clinically, there is a possibility to reduce the margin around
GTV after delivery of 44 Gy because the microscopic disease spread which
defines the margin of PTV to CTV should be eliminated by this dose. In this
case, we can use quite a tight margin for generating the PTV, because set-up
errors are under control by the registration process shown in Figure 4. Our
calculations with the plan with such a tighter margin (Plan 3) gave a dose
distribution presented in Figure 12 with superior lung tissue sparing and a mean
lung dose of only 7.9 Gy.
Figure 8 (a) Dose volume histogram of
Plan 1. Colour code: black: GTV; red: PTV; violet: PTV Nodes;
blue: left lung; light blue: right lung; yellow: spinal cord;
brown: oesophagus, (b) dose volume histogram of Plan 2, (c)
dose volume histogram of Plan 3.
Figure 9 (a) Dose distribution
((a) axial and (b) sagittal views) as calculated by Plan 1
on the kVCT image used for this plan. (c) Colour code for
Figure 10 (a) Dose distribution
((a) axial and (b) sagittal views) which would have been produced
by radiation fluence of Plan 1 in the patient on 39th day
of the treatment. (c) Colour code for isodose lines.
Figure 11 (a) Dose distribution
((a) axial and (b) sagittal views) produced by radiation fluence
of Plan 2 in the patient on 39th day of treatment. (c) Colour
code for isodose lines.
Figure 12 (a) Dose distribution
((a) axial and (b) sagittal views) which would have been produced
in the patient on 39th day of treatment if radiation fluence
of Plan 3 is used. (c) Colour code for isodose lines.
In this case, there were at least three phases in tumour
reduction, with initial phase of ca. 10 fractions (or 20 Gy with delivery of 2
Gy per fraction) when tumour reduction of 1.6% per day was noted. After this
dose there was a rather rapid reduction in tumour size, of more than 5% per day
which continued for three weeks until 40 Gy was administered. Finally, there was
a slow reduction in tumour volume at 0.5% per day which probably continued when
the treatment was finished at 60 Gy. The possible mechanisms for such a three
phase reduction include an initial accumulation of radiation damage in Phase 1
before a radiosensitive Phase 2 of rapid reduction due to re-oxygenation occurs,
while in Phase 3 cell death is counterbalanced by repopulation. Such a
hypothesis requires verification in larger number of patients and correlation
with histology or non-invasive information about tumour metabolism by PET/SPECT.
The combined usage of kVCT and MVCT studies allowed high
quality kVCT images for precise radiation dose calculations on tomotherapy
planning station for both initial and adapted plans, while MVCT scans were used
for accurate patient setup and monitoring of tumour evolution. MVCT has
sufficient image quality for verification of daily treatment delivery allowing
for plan adaptation according to tumour response. It can be used to
quantitatively measure tumour response during radiotherapy. Furthermore, daily
imaging provides data necessary for an optimal choice of GTV to PTV margin
based on values for setup corrections and tumour dynamics.
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|Received 10 June 2006; received in revised form 19 October 2006; accepted 23 November 2006
Correspondence: Department of Physics and Engineering,
London Regional Cancer Program, London Health Sciences Centre,
790 Commissioners Road East, London, Ontario, Canada N6A
4L6. Tel.: +1-5196858600; Fax.: +1-5196858658;
Please cite as: Yartsev S, Dar AR, Woodford
C, Wong E, Bauman G, Van Dyk J,
Initial experience in treating lung cancer with helical tomotherapy, Biomed Imaging Interv J 2007; 3(1):e2
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