**ATC Guidelines for the Use of IMRT (including Intra-Thoracic
Treatments)**

**May 31, 2006**

**Preamble:**

The Advanced Technology Consortium (ATC) has helped to develop general
guidelines (*Int. J. Radiat. Oncol. Biol. Phys. 59 (2004):1257-1262*)
for protocols that incorporate Intensity Modulated Radiation Therapy (
IMRT) as an option. These were communicated to all clinical trial groups
by the National Cancer Institute (NCI) and clearly stated that
respiratory motion could cause far more problems for IMRT than for
traditional treatments. The delivery of IMRT is dynamic as is the effect
of breathing motion, therefore the interplay between the two can result
in non-reproducible dose distributions due to the variability in how
subfields are added. In addition, other patient motions may have
significant effects on the summation of subfields whose intensities are
based upon a static image. Thus, extra care is required in the
acquisition of the CT datasets used in the planning process in order to
avoid motion artifacts while still being representative of the average
location of the anatomical structures. Those guidelines also explained
why accounting for heterogeneities was most important for IMRT since
heterogeneities could affect some subfields more than others and result
in localized dose distribution differences that could be clinically
significant.

The enclosed, updated version of the guidelines explicitly includes IMRT
in anatomical regions where target motion can have a significant effect,
such as intra-thoracic treatments. While these guidelines are intended
to serve only as minimal standards for NCI-supported clinical trials,
they do mandate that any protocol that requires or allows IMRT must
include the following requirements in either the initial protocol or as
an amendment if IMRT is to be subsequently allowed.

# Protocol Requirements for IMRT (including intra-thoracic lesions):

1\. The protocol must explicitly address the localization and
immobilization of both the patient and the tumor. There are several
commercially available systems that can help achieve immobilization. The
study chair and designated QA Center shall assess the adequacy of those
systems for each individual protocol. For IMRT delivery, the residual
motion after compensation techniques are applied should be explicitly
specified in the protocol. The current literature indicates that with
present-day techniques 5 mm of residual target motion is the smallest
reasonable limit for intra-thoracic anatomical structures.

2\. The protocol must require that a 3-D treatment planning volumetric
imaging study be used to define the target volumes and organs at risk
(OAR). The imaging studies need to provide an assessment of the target
volume with the patient in the treatment position, and provisions must
be made to acquire images that represent the target volume without
motion artifact. Some of the techniques that can be used for these
purposes are: spirometry, abdominal compression, 4D CT, and inspiration
and expiration scans on a fast CT scanner capable of imaging the entire
planning volume in one scan sequence for each breathing phase. The steps
taken to suppress/manage motion and achieve appropriate simulation
should be documented and submitted for review to the appropriate QA
Center.

3\. Protocols must employ the nomenclature defined in the NCI IMRT
Working Group Report (*Int. J. Radiat. Oncol. Biol. Phys. 51:880-914,
2001*) and the International Commission on Radiation Units and
Measurements (ICRU) Reports 50 and 62 for specifying: 1) the volumes of
known tumor, i.e., the gross tumor volume (GTV), 2) the volumes of
suspected microscopic spread, i.e., the clinical target volume (CTV) and
3) the marginal volumes necessary to account for setup variations and
organ and patient motion, i.e., the planning target volume (PTV). An
internal margin (IM) should be used to compensate for variation in
position, size, and shape, of the CTV during treatment. Thus the PTV for
a mobile target represents a volume that encompasses the CTV, a set-up
margin (SM) that specifically accounts for spatial uncertainties in
patient positioning and treatment delivery, as well as an IM for the
residual internal organ motion.[^1]

4\. The protocol should describe the rationale for the choice of margins
(IM and SM) to be used for expanding CTV to PTV.

5\. The protocol must require that the effects of tissue heterogeneities
be included in the dose calculations for plan evaluation, dose
prescription and MU calculations.

6\. The adequacy and accuracy of the dose algorithms for
heterogeneity-corrected dose distributions should be demonstrated by
each participating institution to the designated QA Center. The
algorithm must meet the criteria of acceptability established by the QA
Center.

7\. The protocol must provide a clear description of the prescription
dose as well as dose heterogeneity permitted in the PTV, recognizing
that dose heterogeneity will generally be greater with IMRT. The
protocol must also specify the volume to be covered by the prescription
dose (for example, the 60 Gy isodose must cover 95% of the PTV). If 3D
conformal and IMRT treatments are both allowed in a particular protocol,
the dose heterogeneity requirements for IMRT and non-IMRT patients
should be comparable.

8\. The protocol must clearly specify the organs at risk (OARs) and/or
the planning organ-at-risk volumes (PRVs) and include guidelines for
contouring each OAR/PRV. Dose constraints for each OAR/PRV must also be
specified.

9\. The GTV, CTV, PTV, OAR, PRV, and unspecified tissue (see 12. below)
must be delineated on each slice of the 3-D volumetric imaging study in
which that structure exists.

10\. The protocol must specify the procedures that should be in place
for documenting correct, reproducible positioning of patient and target.
On-board imaging to ensure reproducible positioning is acceptable.
Spatially registered volumetric imaging based on kV/MV CT is also
acceptable. As a minimum, however, the equivalent of orthogonal (AP and
lateral) digitally reconstructed radiographs (DRRs) and corresponding
orthogonal weekly portal images (film or electronic) are required.

11\. Copies of all images used to define the target and anatomical
structures, as well as the RT data (e.g. RT-structures, - dose and
-plan) should be submitted electronically to the designated QA center
for review. As a minimum, hardcopies or screen captures of the computed
dose distribution (in the coronal, axial, and sagittal planes that pass
through the center of each PTV) must be submitted. Isodose lines
superimposed upon representative slices of the 3-D volumetric imaging
study must be clear and comprehensive. Acceptable values for hot spots
and cold spots must be specified by the protocol, and images showing the
locations and magnitudes of the hot and cold spots must be submitted.
DVHs in absolute dose for the GTV, CTV, PTV, and all PRVs and OARs
specified in the protocol must be submitted for QA.

12\. A DVH in absolute dose must be submitted for a category of tissue
called "unspecified tissue" that is defined as tissue contained within
the skin, but which is not included within any other structure. This
will help ensure that the IMRT plan does not result in unintentionally
high doses in normal tissues that were not selected for DVH analysis.

13\. The treatment machine monitor units (MUs) generated by the IMRT
planning system must be independently checked prior to the patient's
first treatment. Patient specific quality assurance measurements can
suffice when the plan's delivered fluence or dose distributions are
validated quantitatively. The protocol should specify criteria for
acceptance of these measurements.

14\. Finally, before participating in a cooperative group protocol
involving IMRT, an institution must be appropriately credentialed by the
QA Center designated in the protocol.

[^1]:
    > *(ICRU Report 62 refines this definition of planning target volume
    > by introducing the concept of an Internal Margin (IM) to take into
    > account variations in size, shape, and position of the CTV in
    > reference to the patient's coordinate system using anatomical
    > reference points, and the concept of a Set-up Margin (SM) to take
    > into account all uncertainties in patient beam positioning in
    > reference to the treatment machine coordinate system. Report 62
    > defines the volume formed by the CTV and the IM as the Internal
    > Target Volume (ITV). The ITV represents the movements of the CTV
    > referenced to the patient coordinate system and is specified in
    > relation to internal and external reference points, which
    > preferably should be rigidly related to each other through bony
    > structures. The ITV concept is likely to be used mostly by
    > researchers studying internal organ motion. Note however, that the
    > introduction of the ITV concept does not change the global concept
    > and definition of the PTV as a means of accounting for geometric
    > uncertainty. In most cases, the practicing physician can skip
    > having to explicitly define the ITV. However, how the IM and SM
    > should be combined is not at all clear. Simple linear addition of
    > the two margins will generally lead to an excessively large PTV
    > that would exceed patient tolerance and not reflect the actual
    > clinical consequences. Thus, the risk of missing part of the CTV
    > must be balanced against the risk of complications due to making
    > the PTV too large. ICRU states that a quadratic approach similar
    > to that recommended by the Bureau International des Poids et
    > Mesures can be used).*
    >
    > *ICRU Report 62 introduced the concept of the planning
    > organ-at-risk volume (PRV), in which a margin is added around the
    > organ at risk (OAR) to account for that organ's geometric
    > uncertainties. The PRV margin around the critical structure that
    > must be spared is analogous to the PTV margin around the CTV. The
    > use of PRV concept is particularly important for those cases
    > involving IMRT because of the increased sensitivity of this type
    > of treatment to geometric uncertainties. The PTV and the PRV may
    > overlap, and often do so, in which case a compromise must be found
    > when weighing the importance of each in the planning process.*