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R E S E A R C H Open Access
Quality assurance of the SCOPE 1 trial in
oesophageal radiotherapy
Lucy Wills
1,5*
, Rhydian Maggs
1,5
, Geraint Lewis
1,5
, Gareth Jones
1,5
, Lisette Nixon
3
, John Staffurth
4,5
,
Tom Crosby
2
and on behalf of the SCOPE 1 trial management group and collaborators
Abstract
Background: SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A
comprehensive radiotherapy trials quality assurance programme was launched with two main aims:
1. To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol
compliance and thereby enable their participation in the trial.
2. To support the trial’s clinical outcomes by ensuring the consistent planning and delivery of radiotherapy
across all participating centres.
Methods: A detailed information package was provided and centres were required to complete a benchmark case in
which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form
were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme
continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was
requested in order to gather information about each centre’s equipment and techniques relating to their trial
participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus.
During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1
community in response to common areas of concern using bulletins.
Results: 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the
issues which have arisen throughout this process and present details of the benchmark case solutions, centre
questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8–67.
8cm
3
; and PTV volumes 221.9–513.3 cm
3
. For the dose distributions associated with these volumes, the percentage
volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.
0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial.
Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a
result of their participation in the SCOPE1 trial.
(Continued on next page)
* Correspondence: lucy.wills@wales.nhs.uk
1
Department of Medical Physics, Velindre Cancer Centre, Cardiff CF14 2TL, UK
5
National Radiotherapy Trials QA (RTTQA) Group, Velindre Cancer Centre,
Cardiff CF14 2TL, UK
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Wills et al. Radiation Oncology (2017) 12:179
DOI 10.1186/s13014-017-0916-7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
(Continued from previous page)
Conclusions: The SCOPE 1 QA programme outcomes lend support to the trial’s clinical conclusions. The range of patient
planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present
in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for
increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of
minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource
for this to be addressed within future trials. As indicated in questionnaire responses, theQAexerciseasawholehas
contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of
elements of the protocol.
Trial registration: The SCOPE1 trial is an International Standard Randomized Controlled Trial, ISRCTN47718479.
Keywords: SCOPE 1 clinical trial, Radiotherapy, Quality assurance, Oesophageal cancer, Radiotherapy planning variation
Background
Definitive chemo-radiotherapy (dCRT) has an increas-
ingly recognised role in the primary management of
oesophageal cancer. SCOPE 1 was the largest multicen-
tre trial of dCRT in localised oesophageal cancer in the
UK, recruiting 258 patients from 36 centres. The trial
investigated the addition of Cetuximab to standard
radiotherapy (RT) plus cisplatin/fluoropyrimidine treat-
ment [1], yet the phase II primary endpoint of 24 week
treatment failure-free rate was not met and the trial
closed on the basis of futility. Toxicity rates were higher
in the dCRT + Cetuximab arm. Importantly however,
survival rate in the standard dCRT arm is to our know-
ledge superior to any previous published multi-centre
study [2]. More specifically, loco-regional recurrence
was low in comparison to other studies and compromise
in ability to give full RT dose associated with poor out-
come, thereby suggesting the importance of RT [2]. It
has been further proposed that the SCOPE QA
programme was a crucial component to the successful
outcomes seen in the cRT only arm [2].
The radiotherapy schedule was identical in both arms
of the trial (50Gy in 25 fractions over 5 weeks). The
minimum requirement was for a 3D–conformal plan
using contrast enhanced computed tomography (CT)
with a minimum slice thickness of 3 mm to achieve the
dose volume criteria in Table 2. The GTV was to be out-
lined with contrast enhanced diagnostic CT and endo-
scopic ultrasound, PET-CT was optional. Generation of
the PTV from the GTV was to be done in accordance
with the protocol (described in Table 1 and illustrated in
Fig. 1). Verification of isocentre position and external
patient contour was a requirement that could be man-
aged according to the participating centre’s local
protocols.
In order to support a trial’s clinical outcomes a Radio-
therapy Trials Quality Assurance (RTQA) programme
should provide evidence for adherence to the protocol
thereby reducing the variation in RT planning and deliv-
ery to each recruited patient [3–5]. It requires good
communication with participating centres, suitable infra-
structure and software tools for analysis and sufficient
man-power and expertise. Because of known variations
in technique in oesophageal RT planning prior to
SCOPE1 [6], the QA exercise aimed to ensure treatment
delivery consistent with the SCOPE1 trial protocol [see
Additional file 1] and evidence based best practice whilst
assisting centres to adapt their RT techniques to enable
their participation in the trial, and to provide ongoing
support to RT centres throughout the UK.
The RTQA programme was implemented by the
National RTTQA (Cardiff group) [7] which includes
physicists, clinicians and radiographers at Velindre
Cancer Centre in collaboration with a trial management
team at the Wales Cancer Trials Unit (WCTU) based at
Cardiff University. The methodology and results of the
QA programme are described in this paper.
Method
Preparation of information for participating centres
Early collaboration between lead clinicians and QA
physicists during the protocol development provided a
basis for effective QA later in the trial. Areas of develop-
ment which took place at this stage are summarised in
Table 1. Detailed information concerning these topics
were included as part of a pre-trial information package
(CD-ROM) aimed at assisting centre’s acceptance into
the trial. This contained the SCOPE1 protocol, a ‘RT
planning and delivery’document [see Additional file 2],
examples of three compliant case studies (upper, mid
and lower third) and software to enable their review
(‘GUINESS’(MSS Medical Software Solutions)) Two trial
launch meetings organised by the trial co-ordinators
(WCTU) were held in 2007. Presentations on the RT
planning technique and the QA processes were made by
members of the team.
Pre-trial quality assurance
The ‘GUINESS’visualisation platform, and subsequent
versions (packaged as ‘VODCA’
1
–Visualisation and
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Organisation of Data for Cancer Analysis) was used for
analysis of submitted benchmark cases.
Benchmark case requirements, analysis and feedback
For the benchmark case: an anonymised CT series was
provided by the QA team which was common to all
centres. The selected case included two elements which it
was hoped would be challenging and thereby provide a
suitable test of trial procedures and communication chan-
nels. Firstly the GTV length (8 cm) approached the upper
allowable limit of the SCOPE patient entry criteria
(10 cm): it was expected that plan dose volume objectives
might not be achieved for all cases, prompting dialogue
and checking procedures for data reporting. Secondly the
GTV was close to the spinal cord, requiring application of
a discretionary modification to the posterior part of the
CTV as described in the ‘RT planning and delivery’
document.
Outlining review
Outlining review was performed in part by an experi-
enced treatment planning dosimetrist (LW) who
assessed the OARs, the superior and inferior target ex-
tents with respect to the reference standard, the applied
margins and the suitability of water density structures
applied to correct for IV contrast (if used). The GTV
was assessed qualitatively by the Chief Investigator (TC)
by comparison to the reference standard. Images and/or
description of any areas of outlining disagreement were
fed back to each centre individually in the form of a
written report.
Planning review
Plan quality was assessed with respect to the SCOPE1
protocol requirements (Table 2, columns 1–3) and the
International Commission on Radiological Units and
Measurements (ICRU) reports [8, 9]. The dose volume
objectives for the trial were based on a review of existing
literature [10] and our own centre’s experience (at that
time) of using a ‘pencil beam’/‘type a’[11] dose calcula-
tion algorithm. During the early months of the trial, the
need for greater clarity of plan criteria for centres using
‘type b’algorithms was identified. A retrospective
planning study was performed which concluded that the
same OAR dose volume objectives should apply for both
‘type a’and ‘type b’algorithms [12]. The study also
proposed a measure for individualised PTV coverage
with accounted for the proportion of the PTV overlap-
ping lung tissue (readily calculable in treatment planning
systems) according to
V95%≥99−0:4%PTVoverlap½ð1Þ
Where ‘V95%’is the volume of the PTV receiving 95%
of the prescribed dose and ‘%PTVoverlap’is the percent-
age of the volume of the PTV in lung tissue. Following
this piece of work, the plan assessment form was up-
dated and an E-mail bulletin was sent to participating
and prospective centres which summarised the findings.
QA of plan reporting
Benchmark case PAFs were checked to ensure that the
requirements for reporting had been correctly inter-
preted and the recorded values agreed with an independ-
ent evaluation using VODCA. Having passed this aspect
of protocol compliance, the centre’s PAFs were then
used for real time checking of on-trial plan suitability by
the QA team prior to treatment.
QA of centre processes
A facility questionnaire was distributed in order to con-
firm compliance with aspects of the RT protocol which
could not be determined from the benchmark case
Table 1 Summarised QA Team input to the development of trial documentation
Topic Items included in the pre-trial CR-ROM
Patient
preparation
Descriptions of ‘best practice’for patient immobilisation and acquisition of the planning scan, administration of intravenous (IV)
contrast and subsequent handling of contrasted images in the treatment planning system.
Structure
delineation
Written and pictorial descriptions of the method for planning target volume (PTV) generation from the gross tumour volume
(GTV) via the consecutive stages of clinical target volume (CTV), (‘CTVA’and ‘CTVB’). Margin sizes were adopted from local
practice [28], with multiple CTV stages formalised to correctly account for sub-clinical spread of disease along the line of the
oesophagus, radially and below the level of the gastro-oesophageal junction (GOJ). In addition, a method
for discretionary posterior modification of CTVB where close to the spinal cord was included.
Dose-volume
criteria
Dose volume histogram (DVH) requirements (Table 2, column 1) for use with different types of dose calculation algorithms,
namely ‘type a’and ‘type b’[11]. For ‘type b’, this required an investigative planning study [12], summarised later.
A plan assessment form (PAF) [see Additional file 3] to maximise correct data return.
Deviation levels for target coverage and OAR doses
Single phase
planning
An illustrated planning guide including four problem examples. Use of a single phase plan, which had been shown to deliver
lower heart doses than a widely used two phase approach using a ‘lung sparing’anterior-posterior pair followed by a ‘cord
sparing’three field arrangement [29,30] was mandated. Since this was not exclusively used in the UK at the time of the trial
launch [6] the planning guide sought to assist with this transition, where required.
Treatment
verification
An illustrated description of suitable pre-treatment and/or on-treatment verification processes aimed at ensuring accurate reproduction
of the planned isocentre position and to manage significant changes to the patient’s external anatomy subsequent to planning.
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analysis, including immobilisation, pre-treatment checks
and on-treatment verification. The questionnaire also
sought to establish the extent to which centres were
changing their practice in order to comply with trial
requirements so that help could be offered if needed, and if
participation in the trial had led to changes to local practice
outside the trial.
On-trial QA of clinical cases
Centres were required to send both a completed PAF and
the anonymised full DICOM data, consisting of the planning
CT images, structure set, plan and calculated dose for every
patient. The upfront QA aims were firstly for every PAF to
be checked as soon as received with respect to the dose vol-
ume objectives by trained trial management staff and for a
QA physicist to be informed of any deviations from proto-
col. Secondly, for full retrospective individual case reviews to
be performed by a QA physicist for the first clinical case
from each centre, and a 10% sample from each centre there-
after. These were done using VODCA and / or CERR [13].
CERR (Computational Environment for Radiotherapy
Research) is an open source application for viewing and ana-
lyzing RT data, written in MATLAB (MATLAB and Statis-
tics Toolbox, The MathWorks, Inc., Natick, Massachusetts,
United States). Reference was made to the centre’s bench-
mark case report in order to check for the successful reso-
lution of any deviations noted and where issues were raised
for on-trial cases, the RTQA team fed back to the centre
andendeavoredtoassessafurthercasefromthesame
centre to confirm resolution of the relevant aspects.
Feedback and ongoing QA support
Written reports were provided detailing benchmark and
subsequent patient case outcomes. Moreover dialogue
was frequently engaged in between physics and/or
clinical personnel enabling centres to access support
throughout the trial.
Selected results
Issues arising from both the benchmark case and the
on-trial QA are summarised in Table 3 by topic and
frequency.
Benchmark case results and feedback
The results here include data from 36 RT centres in the
UK who submitted full benchmark cases. Nine of these
centres did not recruit to the SCOPE l trial, yet their
results are included in the benchmark case analysis.
Where the results relate to target outlining, 54 investiga-
tors are included owing to submissions of outlines from
additional clinicians from the 36 centres.
Target generation
The average GTV was 47.1cm
3
(SD 8.6cm
3
,range29.8–
67.8cm
3
). The reference standard GTV was 37.4cm
3
.The
average PTV was 378.2cm
3
(SD 47.7cm
3
, range 221.9–
513.3 cm
3
). The reference standard PTV was 333.1cm
3
.Fig-
ure 2 shows the most commonly occurring minor issues
Table 2 Dose volume objectives, deviations, and benchmark case results (data for 36 cases)
Structure & Dose Volume Objective Minor Deviation Major Deviation Range
Achieved
Number of
Deviations
Type a algorithm:
PTV V95% > 99.0%
PTV deviations were not pre-classified but reviewed individually 98.6–100.0% 4 deviations
(98.6, 98.8, 98.9, 98.9%)
Type a algorithm:
PTV point minimum dose >93.0%
86.5–96.5% 2 deviations
(86.5, 92.7%)
Type b algorithm:
PTV V95% > 99.0% - [0.4 x % PTVoverlap]
92.4–99.3% no deviations
ICRU maximum dose <107% 120% > max > 107% max >120% 103–108% 2 minor deviations
(108, 108%)
Heart V40Gy < 30.0% 50% > V40Gy > 30% V40Gy > 50% 16.1–33.0% 1 minor deviation
(33.0)
Liver V30Gy < 60.0% 70% > V30Gy > 60% V30Gy > 70% 0.0–4.2% no deviations
Combined lung V20Gy < 25.0% 35% > V20Gy > 25% V20Gy > 35% 20.4–33.5% 18 minor deviations
(6 of which >30%)
Spinal cord PRV D1cc < 40.0Gy N/A D1cc >40Gy 34.2–41.5Gy 2 major deviations
(40.1, 41.5)
Table 3 Summary of QA feedback
Topic Percentage of benchmark
cases requiring feedback
Percentage of on-trial
cases requiring feedback
Outlining of GTV 72% N/A
Target margins 39% 16%
Outlining of OARs 50% 64%
Cord PRV margin 33% 36%
Treatment Plan 22% 10%
Completion of
the PAF
69% 42%
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highlighted to clinicians in transverse delineation of the
GTV. GTV outlining has also been studied in greater detail
as part of a sub-study by Gwynne et al. [14].
OAR outlining
The radiotherapy procedures document described the
superior level to which the heart should be outlined and
included illustrations. Ten centres did not include three
or four of the most superior expected slices. In five cases
centres lung outlines included parts of the bronchi or
trachea. Twelve centres had generated the cord PRV in
only the transverse directions omitting to include a lon-
gitudinal margin as would be necessary to fully account
for positional uncertainty.
Dose volume results
Summarised dose volume results for the submitted
benchmark cases are presented in Table 2 with the cor-
responding dose volume objectives and deviation levels.
Major deviations were seen for the cord PRV dose in
two cases. For each, following discussions, the centres
were accepted to the trial on the understanding that
cord PRV doses would be maintained to the 40Gy level
where possible and that any deviations would be
reported on the PAF for review prior to the patient start-
ing treatment. For the greater of these deviations
(D1cc = 41.5Gy) the QA team suggested an alternative
solution, which when explored at the centre, also failed
to meet the cord objective. However, the QA team was
satisfied with the centre’s approach and level of engage-
ment with the protocol so no further action was
required. This case and others highlighted, as the
analysis of benchmark cases progressed, the difficulty of
assessing plans produced on a range of planning systems
for a benchmark case which had not been pre-outlined.
This is discussed later.
The range of heart and lung doses achieved are pre-
sented in Figs. 3 and 4 as a function of the PTV size, the
minor and major deviation thresholds are also shown.
Figure 5 shows the achieved PTV V95% with respect
to the target level of 99% where planned using a type a
algorithm. The target was not met in four plans: three
cases (within 0.2% of the target) were attributed to a
minor discrepancy between VODCA’s calculated result
and the planning system used at the centre; the devi-
ation in the final case (98.6%) was deemed acceptable
since the consultant had given justification. Figure 6
shows the achieved PTV V95% for type b plans with re-
spect to the target level, individually calculated using eq.
(1): there were no deviations. As shown in Table 2 there
were two deviations against a second PTV objective
(point minimum dose >93.0%). These were associated
with deliberate and justified compromises to a small sec-
tion of the PTV in order to keep the cord PRV to within
tolerance. However, following the previously mentioned
planning study which resulted in the adoption of eq. (1)
[12], it was evident that this objective was inappropriate
for use with type b planning and the objective was
removed entirely from the SCOPE 1 reporting require-
ments as a matter of simplification.
Planning
For eight plans the QA team offered one or more
suggestions as to how the dose distributions could be
improved upon and a revised plan was requested. An
example case is shown in Fig. 7.
Fig. 1 Target generation stages for SCOPE1
Fig. 2 Examples of differences in interpretation of the GTV from the reference standard. In each image the reference standard is shown in yellow. a
shows the unnecessary inclusion of the azygos vein; bis an example of the unnecessary inclusion of tissues surrounding the tumour; cshows the
incorrect inclusion of the whole bronchus; and dshows a case where the anterior part of the oesophageal wall had not been included in the GTV
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Radiotherapy processes
Only 23 QA questionnaires were returned, some of these
were from centres who did not recruit yet their results are
included as the questionnaire explored changes to stand-
ard practice regardless of recruitment to SCOPE 1. The
completed questionnaires represented 24 of 36 recruiting
centres (including satellites), which contributed 161
patients (62%) to the trial. This level of response is
discussed later. For all of the returned questionnaires
centres demonstrated full compliance with procedures in
relation to patient immobilisation, pre-treatment checks
and on-treatment verification to at least the minimum
standard as described in the protocol.
Centres underwent varying levels of adaptation to com-
ply with the protocol. When asked if SCOPE had changed
standard practice at the centre, 15 of the 23 centres who
returned questionnaires (65%) stated that it had.
On-trial QA
Two hundred fifty-eight patients were recruited to the
trial from 36 centres (27 RT centres having completed a
benchmark case and nine satellites of these). Retrospect-
ive individual case reviews (using full DICOM data) of
the first patient from each centre were proposed. Owing
to resourcing constraints, not all of the reviews were
conducted around the time of the patient’s treatment.
Indeed a proportion of the reviews were done
retrospectively following the completion of the trial.
DICOM data was available for 30 of 36 intended first pa-
tient reviews. For three centres the first patient data
were not available, yet a subsequently recruited patient
was able to be reviewed. The remaining three centres
each recruited a single patient, yet no DICOM data was
received and a full review could not be conducted.
Target generation
A review was undertaken for all 33 cases with available
DICOM data (as above: thirty first cases and three later
cases where no DICOM data was available for the
centres’first case.).
It was possible to measure GTV length for 32 of the
33 cases. The Mean (SD) GTV length was 6.1 cm
(2.0 cm), range = 2.3 to 9.9 cm). All were within the
protocol limit of 10 cm. For 20 cases the GTV length
recorded on the PAF and the length from the DICOM
data were able to be compared: there was agreement for
12 cases, the largest discrepancy in the others was
1.3 cm. For all these discrepancies, the GTVs were
quoted as being longer on the PAF than what was
measured in VODCA. This is discussed later.
CTVB margins were determinable from DICOM for
32 plans. The superior and inferior margins were correct
(2.0 cm or 2.1 cm) for 29 of the 32 having DICOM data.
For the remaining three, the superior margin was within
Fig. 3 Heart V40Gy vs. PTV size for benchmark cases
Fig. 4 Lung V20Gy vs. PTV volume for benchmark cases
Fig. 5 PTV coverage for benchmark case solutions planned with
‘type a’algorithms (n= 22)
Fig. 6 PTV coverage for benchmark solutions planned with ‘type b’
algorithms (n= 14)
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one slice (0.3 cm) of the protocol specification. The
radial margin was correctly applied in all except one case.
PTV margins were correctly applied for 32 of the 33
cases reviewed. In one case superior and inferior
margins of only 0.5 cm (instead of 1 cm) had been
applied. Mean (SD) PTV volume was 314.7cm
3
(112.4cm
3
) in the range 141.9 to 591.5cm
3
.
On-trial results
A review was undertaken for all of the 33 cases with
available DICOM data.
Twenty-one centres’plans included 1 or more minor
deviations from the protocol in respect of outlining of
OARs. The most common outlining deviations were in-
clusion of bronchi (11) and trachea (5) in the lung,
under outlining the heart superiorly (12), and omitting
to include a sup-inf element of the cord PRV margin
(11). In one case no cord PRV had been generated.
Dose volume results
A major deviation was associated with the non-
generation of a cord PRV in one case. When created
retrospectively, the PRV dose was found to exceed
the protocol limits; this was the only on-trial instance
of a major deviation from protocol. The error was
reported back and was resolved for the centres’
second patient.
Nineteen plans used a type a algorithm and 14 used
type b. Of the type a plans, two plans failed to
achieve PTV V95% > 99%, yet were deemed to have
been fully optimised. PTV coverage results for the
type b plans are shown in Fig. 8. All centres had
correctly calculated the individualised PTV V95%
objective in accordance with the eq. (1). Three plans
did not achieve the coverage target. In one case (case
number 1 in Fig. 8) the low result was justified by
the presence of significant air of the trachea and
bronchi within the PTV. The remaining two (cases
numbered 7 and 8 in Fig. 8) occurred prior to the
outcome of the investigative study when centres had
no specific guidance as to the acceptability of
coverage of the 95% isodose, it was thought in these
cases that the coverage at the superior or inferior ex-
tremes of the target region might have been improved
by further optimisation. This is discussed later.
On-trial support & commonly occurring on-trial planning
issues
Two common themes emerged from discussions with the
QA team. Firstly there was uncertainty as to the
acceptability of dose distributions achieved using ‘type b’
algorithms. Initially advice was given on a case by case
basis where, in the absence of specific requirements for
PTV coverage and of detailed experience of every treat-
ment planning system (a common issue for RTQA), defer-
ence was generally made to local knowledge and expertise.
Following the publication by the QA team of the previ-
ously mentioned comparative study on this topic [12], and
the circulation of a bulletin giving definitive advice, quer-
ies of this nature were eliminated. The second area of
interest concerned solutions for planning when the targets
were in very close proximity to the spinal cord. In re-
sponse, a bulletin was circulated which summarised best
practice and presented an optimisation solution. Addition-
ally IMRT solutions, where proposed by participating
centres, were permitted and quality assurance of these
techniques was achieved with the assistance of colleagues
in the wider national QA group.
Discussion
Overview
The pre-trial QA programme fulfilled a primary QA
objective: it ensured that collaborating personnel in indi-
vidual centres had read and understood the protocol and
that centres had the necessary resources in place to
deliver RT in accordance with the trial. The on-trial QA
was to some extent limited by availability of resource at
the QA centre. Our discussion herein focuses on areas
which, with hindsight and more comprehensive resour-
cing may have been done differently to improve the
Fig. 7 Example of a benchmark plan improvement via the QA process:
Adjustment of the lateral beam orientations of the submitted plan (a)
to better avoid the spinal cord PRV, allowed an increase in the
contribution from the anterior and posterior beams, thereby enabling
a greater level of lung sparing at the 20Gy dose level (b)
Fig. 8 PTV coverage for reviewed on-trial cases planned with ‘type
b’algorithm (n = 14)
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completeness of QA data, or increase the efficiency of
analysis in the context of this particular clinical trial.
Benchmarking with pre-outlined cases
Ability to advise centres on the optimality of their
benchmark case solution can be limited owing to differ-
ences in treatment planning systems and compounded
by variations in target delineation. This problem can be
lessened by providing both a non-outlined benchmark
case to test outlining accuracy and a pre-outlined bench-
mark case to test planning to standardised geometry.
Dosimetric results for the latter can be more easily com-
pared to an expected outcome. This methodology is
noted by Ibbott et al. [3] and now used by the RTTQA
group where warranted, according to a tiered system of
RT complexity as described by Bekelman et al. [15].
Whilst differences due to planning system and algorithm
would remain, it may not be unreasonable, given the
extent of collaboration within national RTTQA at time
of writing, to explore these variations prospectively for
an RTQA programme. The use of a single benchmark
case for both outlining and planning in SCOPE1 does
however reveal the effect of differences in GTV outlining
on the eventual dose distribution as presented above.
Recommendations for future trials QA
The pre-trial QA processes did not eliminate the recur-
rence of inconsistencies from protocol seen in benchmark
cases, particularly in the outlining of OARs (where incon-
sistencies increased). This could be due to insufficient
training and dissemination within centres of the outcomes
and recommendations of the QA exercise and may point
to the need for more rigorous processes at recruiting cen-
tres (an individual patient checklist, for example). More
recent development in on-line real-time and timely retro-
spective outlining and plan review will also address this
[14, 16]. The implications of these minor inconsistencies
are unlikely to have any impact on the SCOPE 1 clinical
conclusions in our opinion. Indeed, an upfront, risk
assessed approach, to identify aspects of the treatment de-
livery chain which are likely to affect the ability to answer
the trial question, such as is recommended by Ibbott et al.
[3] can be applied in order to rationalise the use of QA
resource.
The variation in GTV outlining of the benchmark case,
quantified by Gwynne et al. [14] demonstrated the pres-
ence of a range of both methodology and precision
applied for this treatment site. Within the SCOPE 1 QA
process, each investigator was provided with comments
from the CI: effectively they participated in an external
audit of their GTV definition. Feedback such as this had
not been commonly available elsewhere within clinical
practice and was a first in oesophageal RT in the UK.
However, improvements in the process were identified as
follows: the SCOPE 1 reference standard was based on the
interpretation two individuals (the CI and a radiologist).
The need for a more robust reference standard became a
point of discussion throughout the QA cycle as alternative
legitimate clinical interpretations were observed in bench-
mark solutions. Variation in target delineation is a widely
known and universal issue in RT [17–20], the need for
‘consensus guidelines’with dissemination and training, is
re-emphasised here. This approach is being widely incor-
porated into trials QA systems and RT more generally
[21–24].
In our comparison of outlined GTV length against
that quoted on the PAF, discrepancies were seen, always
in the same direction (PAF GTV longer than VODCA
GTV). This could be attributed to the method of meas-
urement used by centres: if the operator were to use a
software measure tool placed along a sectional recon-
struction of the CT series the value measured would
always be equal to or longer than the length calculated
based on the longitudinal coordinates of the extents of
the GTV. This is because the organ may lie at a diagonal
to the longitudinal. Furthermore, up to one slice thick-
ness may be added if the operator interprets the length
to be ‘the number of slices outlined multiplied by the
slice thickness.’In this case the operator is assuming
that each slice is representative of a volume of patient
rather than a 2-dimensional level. In the absence of
knowledge of exactly how each operator interpreted the
value of GTV length requested on the PAF, this uncer-
tainty remains. Future studies should therefore define
how lengths, if needed, are to be calculated, or request
the raw data (slice positions) in order to enable a
calculation of the parameter.
The return rate of the QA questionnaire was poor
(53% of recruiting centres), despite encouragement from
WCTU at various stages throughout the trial. It was
intended to serve a dual purpose: firstly to check that
elements of practice at each centre met trial criteria, and
secondly to assess the impact of the trial on changes to
standard practice. For the latter reason the questionnaire
was not made a pre-requisite to centre recruitment.
Rather, centres were given time to reflect on any changes
that had been introduced into standard practice. The
result of not mandating a response to the questionnaire
prior to recruitment may have contributed to a loss of
momentum of its return. With this hindsight, it would
have been better not to combine the two aspects, instead
to require a response before centres were given QA
approval. Notwithstanding a disappointing return, the
responses, as summarised earlier, indicate that quality
and consistency of practice across the UK increased as a
result of SCOPE1. In addition, outside of oesophageal
RT, the description of heart delineation for SCOPE1 has
Wills et al. Radiation Oncology (2017) 12:179 Page 8 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
been used, with permission, in subsequent trial protocols
for the Fast-Forward [25] and I-START [26] trials.
Reflections on the PTV coverage target for type b
algorithms and future use
The investigative planning study [12] provided a
standard for PTV coverage. The benefit of this piece of
work is demonstrated here as all of the type b deviations
for PTV coverage according to the criteria suggested by
the study, occurred prior to its outcome. This suggests
that the guidance, once issued, provided greater clarity
as to the acceptability of distributions, enabling planners
to persist with the optimization process until at least the
suggested minimum had been achieved. For future trials,
if conducted with access to improved optimisation
techniques, a higher standard of PTV coverage could be
specified simply by adjustment of the multiplier
(currently 0.4) within the formula.
Conclusions
The benchmark case successfully identified and advised
participating centres of the areas of their RT technique
which were inconsistent with the SCOPE 1 protocol in
advance of recruitment. On-trial QA revealed no more
than a single major deviation (relating to cord PRV dose)
for patients treated within SCOPE 1, thereby supporting
the clinical conclusions. However, for recruited patients
there did appear to be repetitions of minor inconsisten-
cies of technique, revealed retrospectively, highlighting
the need for sufficient QA systems and resource to
ensure a continuous feedback process throughout the
progress of an RT trial. The range of patient planning
outcomes for the benchmark case is illustrative of the
potential variation in oesophageal treatments at the out-
set of the trial, which are largely due to differences in
interpretation of the GTV, despite the presence of a proto-
col. This supports the case for increasingly detailed defin-
ition of practice by means of consensus protocols, training
and peer review. Further exercises in oesophageal RT QA
may in the future be able to draw comparisons to this
piece of work. The QA exercise as a whole has facilitated
greater consistency of oesophageal RT in the UK via the
widespread adoption into standard practice of many
elements of the protocol, and has contributed, in part, to
wider collaboration in UK Oesophageal radiotherapy [27].
Endnotes
1
http://www.vodca.ch/
Additional files
Additional file 1: SCOPE1 Trial Radiotherapy Protocol. (PDF 988 kb)
Additional file 2: SCOPE1 Trial Radiotherapy Procedures Document.
(PDF 2300 kb)
Additional file 3: SCOPE1 Trial Plan Assessment Form. (PDF 165 kb)
Abbreviations
CT: Computed tomography; CTV: Clinical target volume; dCRT: Definitive
chemo-radiation; DVH: Dose volume histogram; GTV: Gross tumour volume;
IMRT: Intensity modulated radiotherapy; IV: Intravenous; OAR: Organ at risk;
PAF: Plan assessment form; PRV: Planning risk volume; PTV: Planning tumour
volume; QA: Quality assurance; RT: Radiotherapy; RTQA: Radiotherapy trials
quality assurance; VMAT: Volumetric modulated arc therapy; WCTU: Wales
cancer trials unit
Acknowledgements
We acknowledge the support and guidance of the National Radiotherapy
Trials QA Group.
Funding
The SCOPE1 trial was funded by Cancer Research UK (CRUK: A72569),
sponsored by Velindre NHS Trust and Co-orientated by the Wales Cancer
Trials Unit, Cardiff University.
Availability of data and materials
The SCOPE1 protocol, RT planning and delivery document, and plan
assessment form are available in the supplementary files of this published
article. The datasets generated and analysed within the SCOPE1 QA
programme are available from the corresponding author in anonymised
format on reasonable request.
Authors’contributions
LW: Analysis of data and writing the manuscript, contribution to design and
implementation of RTQA procedures and documents including design of
dosimetric criteria, planning technique, pre trial QA reports. RhM:
Contribution to RTQA procedures, analysis of on-trial data and contribution
to manuscript writing. GL: contribution to manuscript writing. GJ: Analysis of
on trial data, LN: Contribution to SCOPE 1 Trial Management including
documentation finalisation, QA procedures, data collation. JS: Clinical QA lead
for SCOPE1, supervision of the QA programme, critical review of the
manuscript. TC: Chief investigator for SCOPE1, overall supervision of the
trial, critical review of the manuscript. All authors have read and approve
the final manuscript.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Department of Medical Physics, Velindre Cancer Centre, Cardiff CF14 2TL,
UK.
2
Department of Clinical Oncology, Velindre Cancer Centre, Cardiff CF14
2TL, UK.
3
Wales Cancer Trials Unit, Centre for Trials Research, Cardiff
University, Cardiff CF14 1YS, UK.
4
School of Medicine, Cardiff University,
University Hospital Wales, Cardiff CF14 4XN, UK.
5
National Radiotherapy Trials
QA (RTTQA) Group, Velindre Cancer Centre, Cardiff CF14 2TL, UK.
Received: 10 August 2017 Accepted: 2 November 2017
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