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Radiation Therapy Oncology Group (RTOG) Consensus Panel Atlas
of Musculoskeletal Anatomy (CAMAS) for Soft Tissue Sarcoma of the
Lower Extremities.
Steven Eric Finkelstein, Jesse M. Shulman, Andrea Trotti, George Douglas Letson, Jamie
Caracciolo, Tom Delaney, William Kraybill, Barry Eisenberg, Kalid Alektiar, Jeff
Michalski, and Dian Wang
Abstract
Purpose/Objective(s): With the increasing use of advanced techniques in
radiation therapy, there is an increasing need for fast, useful radiologic
correlation with surgical anatomy. Accordingly, our purpose is to develop
deformable imaging capability for the Radiation Therapy Oncology Group
(RTOG) consensus panel atlas of musculoskeletal anatomy (CAMAS) for
planning 3D conformal and intensity-modulated external beam radiotherapy
(IMRT) for soft tissue sarcoma (STS) of the lower extremities.
Materials/Methods: CAMAS structures contoured on CT and MRI images of
lower extremities were examined and reviewed by sarcoma experts (radiation
oncologists, surgeons, radiologists). A consensus meeting achieved agreement
about radiologic correlation with anatomy. A deformable registration algorithm is
under development to transform the CAMAS atlas to the patient specific planning
volume thereby providing detailed anatomical segmentations within the patient
space.
Results: Definitions of musculoskeletal anatomy to be employed as guidelines
for pre-operative therapy of sarcoma were achieved. Detailed contouring
guidelines of lower extremity anatomic compartments (uniquely characterized by
critical structures) / joints (including knee) / normal tissue structures are
delineated and transformed to the patient specific planning volume.
Conclusions: CAMAS helps facilitate a common system of communication and
reporting to enhance standards of contouring, treatment, and follow-up response
evaluation with the potential of deformable registration to transform the atlas into
the patient specific planning volume. This report further enhances definition of
musculoskeletal anatomy / normal tissue structures for planning 3D conformal
and IMRT of STS.
Introduction
Intensity-modulated radiotherapy (IMRT) enables delivery of complex
radiation therapy (RT) plans that previously could not be accomplished with
conventionally planned two- to four-field techniques or more sophisticated threedimensional (3D) conformal RT (3D-CRT). The advent of IMRT provides an
opportunity to spare critical normal anatomic tissue. For patients receiving
radiation for sarcomas, normal structures may be better protected with IMRT
than other conformal techniques as demonstrated by dosimetric investigations [16]. Use of IMRT has also been associated with reduced acute toxicity for
sarcoma [7, 8]. A clear understanding of targets as well as organs at risk (OAR)
is critical to the use of IMRT. Treatment with IMRT demands much more detailed
knowledge of target structures and OAR than conventionally planned techniques.
Indeed, IMRT utilizes customized treatment planning based on an individual's
anatomy.
This atlas was produced by a consensus panel of 11 radiation oncologists,
surgeons, and radiologists (S.E.F, A.T., G.D.L., J.C.,T.D., D.K., W.K., B.E., K.A.,
J.M., and D.W.) designated by the Sarcoma Committee of the Radiation Therapy
Oncology Group (RTOG). The formation of this panel was motivated, in part, by
a desire to improve contouring for cases enrolled on RTOG 0630 (A Phase II
Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue
Sarcomas of the Extremity) [9]. This is a phase II study to evaluate the effect of
preoperative image-guided radiotherapy (IGRT) on the reduction of late radiation
morbidity, patterns of failure, impact of late radiation morbidity on limb function
and physical ability, quality of life (QOL), and sexuality. Correlative biomarker
studies including gene expression profiling are included in the study to identify a
molecular signature that predicts late radiation morbidity, poor QOL, local failure,
and distant failure. It is important to note that this single arm phase II study is not
intended to resolve the debate discussed above regarding the sequence of
radiotherapy and surgery [9].
This report provides the recommendations of this consensus panel and
serves as a template for the definition of normal tissue structures to be used in
planning for sarcoma.
Methods and Materials
For the RTOG 0630 trial, there is extensive detail describing gross tumor
volume (GTV) and clinical target volume (CTV). GTV is defined to include
enhancing tumor on contrast-enhanced (gadolinium-based contrast agents) T1weighted magnetic resonance (MR) images. CTV for intermediate to high grade
tumors ≥ 8 cm is defined as GTV plus surrounding peritumoral edema seen as
increased signal intensity on T2-weighted MR images plus 3 cm in the
longitudinal (proximal and distal) directions. If this causes the field to extend
beyond the anatomic compartment, the field can be shortened to extend up to
the end of the compartment. The radial margin should be 1.5 cm including any
portion of the tumor not confined by an intact fascial barrier, bone, or skin
surface. The CTV for all other tumors is defined as GTV plus 2 cm including
suspicious edema in the longitudinal directions. If this causes the field to extend
beyond the compartment, the field can be shortened to extend up to the end of
compartment. The radial margin should be 1 cm including any portion of the
tumor not confined by an intact fascial barrier, bone, or skin surface. The PTV is
defined as CTV plus 5 mm. Skin surfaces should not be contoured in CTV or
PTV unless these are involved by gross tumor. Incisional biopsy scar is not
recommended to be contoured as CTV if it will be resected after radiation
treatment.
Multiple discussions were held to define organs at risk for the purpose of
this atlas. In the RTOG 0630 trial, there are no agreed upon definitions on what
constitutes OAR volumes. Details with respect to constraints are limited to the
following: every effort should be made to avoid treating the full circumference of
an extremity; avoid treating the anus, vulva and/or scrotum; avoid treating skin
over areas commonly traumatized such as the knee or shin; and avoid treating
the femoral head and neck. If the tumor is close to an OAR, less than 50%
volume of the anus and/or vulva should receive 3000 cGy; less than 50% volume
of testis should receive 300 cGy if the patient prefers to reserve fertility; and less
than 5% of the femoral head or neck should receive 60 Gy. Less than 50% of
any joint (including the knee) should receive 50 Gy. Less than 50% of kidney
volumes should receive 1400 cGy. No more than 50% of a longitudinal stripe of
skin and subcutaneous tissue of an extremity should receive 2000 cGy. This
stripe of normal tissue is contoured at the discretion of treating radiation
oncologist. Full prescription dose to skin of areas commonly traumatized should
be avoided. No more than 50% of normal weight-bearing bone within the
radiation field should receive 50 Gy except when the tumor invades the bone,
when there is greater than 25% circumferential involvement of the bone, or when
the bone will subsequently be resected at surgery. For any other normal tissue
structures, no radiation dose more than the established TD5/5 limit should be
given.
Consensus definition of compartmental anatomy was achieved upon
review of representative sets of computed tomography (CT) and magnetic
resonance imaging (MRI) scans of the lower extremity. A sample set of CT and
MRI images was utilized to generate CAMAS. CAMAS was analyzed and
reviewed by sarcoma experts including radiation oncologists, surgeons, and
radiologists. A consensus meeting and conference calls were arranged to reach
an agreement about anatomic and radiological correlation. Anatomic contours
were reviewed by the group during formal consensus conference calls and in
meetings in Philadelphia, PA. General consensus regarding OAR was obtained
and the lead author has presented the panel with final modified contouring
images.
Institutional review board approval was submitted for this study and exempted.
Results
Compartmental Anatomy of the Thigh
The thigh is separated into three anatomic compartments: anterior,
posterior, and medial. The fascia lata surrounds the thigh musculature forming
the superficial border of the three muscular compartments. The anterior
compartment contains the quadriceps muscle, consisting of the rectus femoris,
vastus medialis, vastus lateralis, and vastus intermedius muslces; the tensor
fascia lata; the iliopsoas muscle; the sartorius muscle; and the iliotibial band
(Powerpoint slides 2-44 ). The sartorius muscle is generally classified as an
anterior structure as it travels from the anterior superior iliac spine to the medial
aspect of the proximal tibia. The anterior compartment is separated from the
medial and posterior compartments by the medial and lateral intermuscular septa
(fascia). The medial compartment consists of the adductor musculature,
including the adductor longus, brevis, and magnus muscles, and the gracilis
muscle. The medial compartment is separated from the posterior compartment
by intermuscular fascia. The posterior compartment contains the
semitendinosus, semimembranosus, and biceps femoris muscles, collectively
referred to as the hamstring muscles.
With respect to neurovascular structures, the femoral nerve travels deep
to the inguinal ligament within the fascia of the iliopsoas muscle to enter the
thigh. The femoral artery and vein course more medially within the femoral
sheath of the femoral triangle of the inguinal region and are thus
extracompartmental structures in the proximal thigh (Powerpoint slides 2-22).
The femoral artery continues distally between the quadriceps and adductor
muscles and travels through the adductor canal formed by the fascia between
the anterior and medial compartments (Powerpoint slides 22-44). After passing
through the adductor hiatus within the adductor magnus muscle in the distal
thigh, the femoral artery becomes the popliteal artery in the posterior and distal
aspect of the thigh. The sciatic nerve enters the thigh posteriorly between the
gluteus maximus and adductor magnus muscles and continues in the posterior
compartment between the adductor magnus muscle and hamstring musculature.
Compartmental Anatomy of the Leg
The leg is comprised of three compartments: anterior, lateral, and
posterior (Powerpoint slides 45-87). The deep crural fascia of the leg invests the
muscular compartments and attaches to the tibia medially. The anterior
intermuscular septum separates the anterior compartment from the lateral
compartment. The posterior intermuscular septum separates the lateral
compartment from the posterior compartment. The interosseous membrane
separates the anterior compartment from the posterior compartment, and more
specifically, from the deep posterior compartmental musculature. The transverse
intermuscular septum separates the musculature of the posterior compartment
into superficial and deep muscle groups.
The anterior compartment of the leg contains the extensor musculature
including the tibialis anterior, extensor digitorum longus, extensor hallucis longus,
and peroneus tertius muscles (Powerpoint slides 45-87). The anterior tibial
artery and vein are located anterior to the interosseous membrane within the
anterior compartment. The deep peroneal nerve, a branch of the common
peroneal nerve originating in the lateral compartment, crosses into the anterior
compartment and descends to the ankle with the anterior tibial artery and vein.
The posterior compartment is comprised of deep and superficial muscle
groups. The deep muscles include the flexor digitorum longus, tibialis posterior,
flexor hallucis longus, and popliteus muscles. Laterally, the peroneal artery and
vein are found between the flexor hallucis longus and tibialis posterior muscles.
Medially and posteriorly, the posterior tibial artery and vein and the tibial nerve lie
deep to the transverse intermuscular septum. The superficial muscles include the
soleus, medial and lateral heads of the gastrocnemius, and plantaris (merely a
long tendon throughout much of the lower leg) muscles which serve to dorsiflex
the ankle.
The lateral compartment contains the peroneus longus and brevis
muscles as well as the common peroneal nerve proximally. The common
peroneal nerve divides into the deep peroneal nerve which enters the anterior
compartment and the superficial peroneal nerve which descends along the
anterior intermuscular septum.
Organs at Risk (OAR) - Constraints
Several general recommendations by the consensus panel were
incorporated into CAMAS. The group believed that it is paramount that dose–
volume histograms (DVH) be as consistent from one contourer to the next.
When applicable:
1) Less than 50% volume of the anus and vulva should receive 3000 cGy;
2) Less than 50% volume of the testis should receive 300 cGy if the patient
prefers to reserve fertility;
3) Less than 5% of the femoral head/neck should receive 60 Gy;
4) Less than 50% of any joint (including hip, knee and ankle) should receive 50
Gy;
5) No more than 50% of a longitudinal stripe of skin and subcutaneous tissue of
an extremity should receive 2000 cGy. This stripe of normal tissue is contoured
at the discretion of treating radiation oncologist;
6) Full prescription dose to skin over areas commonly traumatized (e.g., the knee
or shin) should be avoided. No more than 50% of normal weight-bearing bone
within the radiation field should receive 50 Gy except when the tumor invades the
bone, when there is greater than 25% circumferential involvement of the bone, or
when the bone will be removed at subsequent surgical resection following
radiation.
There is no special requirement for skin dose limit. However, for IMRT of
sarcoma, skin surface (5-mm thickness) including scar from incisional biopsy is
not included in CTV or PTV and is not bolused for IMRT unless the biopsy scar is
not subsequently resected following radiotherapy. For any other normal
structures, radiation dose should not exceed established TD5/5 limits.
Discussion
Research into the potential benefits of IMRT in the treatment of extremity
sarcomas has only recently been undertaken. Current standard pre-operative
recommendations for conventional external beam RT are 50 Gy with a 5-cm
longitudinal (superior-inferior) margin and a 2-cm radial margin. A combination of
conservative surgery and radiotherapy has previously been shown to achieve
excellent local control in sarcoma patients following margin negative surgery.
However, radiation therapy may contribute to late radiation morbidity, physical
disability, and reduced quality life [13-18]. In the recent Canadian phase III
study, patients that received postoperative radiation therapy had increased rates
of grade 2 or greater fibrosis (48% vs. 31.5%), increased edema (23% vs.
15.1%), and joint stiffness (23% vs.17.8%) [13]. These late effects correlated with
significantly lower physical function. Although late effects were lower in the
preoperative cohort, they were still substantial totaling 64.4% (31.5% with
fibrosis, 15.1% with lymphedema, and 17.8% with joint stiffness) at 2 years
following treatment. Additionally, field size was predictive of higher rates of late
effects. Therefore, decreasing the field volume may translate into reduced late
radiation toxicities in the treatment of sarcoma.
Recently, image-guided radiotherapy (IGRT) technologies such as imageguided intensity modulated radiotherapy (IG-IMRT) have emerged [1-5]. IMRT is
able to deliver a highly conformal dose to the gross disease planning target
volume and high risk subclinical disease regions, while dose to surrounding
critical structures such as the adjacent normal tissue, bone, testis, spinal cord,
kidney and ovary is minimized. Recent studies have demonstrated the
dosimetrical and technical advantages of IG-IMRT in terms of dose conformality
to tumors and volume reduction to normal tissues, which in turn may result in
improved clinical outcomes, reduction of side effects, and improved quality of life.
In addition, daily pre-treatment imaging and position adjustment prior to radiation
therapy may prove to be another key factor to successful tumor radiotherapy
[3,6].
Sarcoma patients may be afforded unique benefit from IGRT technologies
for several reasons. Firstly, as sarcoma patients are often not in a rigid
immobilization device during radiotherapy, set up error can be significant when
treating sarcomas of certain sites. Secondly, a large field size is often required
for conventional radiotherapy of sarcoma [7]. It is conceivable that improved
techniques of delivering radiotherapy that decrease radiation dose to critical
surrounding tissues may in turn reduce late radiation toxicity.
Use of IMRT in the treatment of sarcoma has tremendous potential for
reducing these toxicities while allowing for these higher radiation doses to the
gross tumor volume. With IMRT, radiation dose to the normal structures is
reduced as compared to conventional 2D and more sophisticated 3D treatment
planning. Small pilot series show IMRT in this population to be well tolerated,
with most patients experiencing only mild to moderate acute symptoms.
Moreover, the use of IMRT has not compromised elective target coverage as
locoregional control in these reports appears favorable, albeit with limited followup.
One of the significant hurdles facing implementation of IMRT sarcoma has
been the complexity of target and elective lymphatic definition. Standardization
of clinical target volume definition will not only provide an important basis for the
prospective study of IMRT for extremity sarcomas in a multi-institutional setting,
but will also establish contouring guidelines for the radiation oncology community
if IMRT proves efficacious in reducing normal tissue toxicities while not
compromising outcome. The CAMAS RTOG sarcoma contouring consensus
panel demonstrated good concordance in their CTV definitions. This may be
expected when considering that the panel members are physicians who
specialize in the delivery of radiation therapy for these rare malignancies.
Conclusion
This is the first report of the Radiation Therapy Oncology Group CAMAS
sarcoma atlas. The guidelines and images should serve as a template for the
definition of OAR to be used in planning for sarcomas of the extremity. This atlas
has assisted as a contouring guideline for the prospective IMRT trial RTOG 0630
(A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft
Tissue Sarcomas of the Extremity) and future prospective trials. In this study,
particular attention will be paid to the patterns of local recurrence to ensure that
these CTV consensus panel recommendations as well as the use of IMRT for the
management of sarcomas of the extremity are appropriate.
Acknowledgments
S.E.F. and D.W. co-wrote the manuscript. This work was supported by RTOG
U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115 NCI grants. The
contents are the sole responsibility of the authors and do not necessarily
represent official views of the National Cancer Institute. Advanced Technology
QA Consortium supported by National Institutes of Health/National Cancer
Institute U24 Grant CA81647.
Conflict of interest: none.
Reprint requests to: Steven Eric Finkelstein, M.D. ([email protected])
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Power Point slides on RTOG website:
2-22 Axial CT scan through the proximal thigh demonstrating compartmental
anatomy. The anterior compartment (light blue) contains the sartorius (green),
rectus femoris, vastus medialis, vastus intermedius, and vastus lateralis muscles.
The medial compartment (orange) contains the adductor longus, gracilis,
adductor brevis , and adductor magnus muscles. The semitendinosus occupies
the posterior compartment at this level. The gluteus maximus is not considered a
posterior compartment structure. The femoral artery, nerve, and vein are
considered extracompartmental structure as they through the adductor canal.
23-44. Axial CT through the distal thigh demonstrating compartmental anatomy.
At this level, the anterior compartment (light blue) contains the sartorius vastus
medialis, vastus intermedius, and vastus lateralis muscles and the quadriceps
tendon. The medial intermuscular septum and femur (pink) separate the anterior
compartment from the medial (orange) and posterior (purple) compartments. The
gracilis (Gr) muscle is seen in the medial compartment. The posterior
compartment contains the long and short heads of the biceps femoris,
semitendinosus , and semimembranosus muscles. Distal to the adductor canal,
the popliteal artery and vein join the sciatic nerve as the posterior compartmental
neurovascular bundle.
45-87 Axial CT demonstrating compartmental anatomy of the leg. The anterior
compartment (blue) contains the tibialis anterior, extensor hallucis longus, and
extensor digitorum longus muscles. The anterior intermuscular septum and
lateral intermuscular septum are the anterior and posterior boundaries of the
lateral compartment (yellow-green) which contains the peroneus longus and
brevis muscles. The fibula (purple), tibia (green), and interosseous membrane
separate the anterior compartment from the posterior compartment deep which
contains the tibialis posterior, flexor hallucis longus, and flexor digitorum longus
muscles. The peroneal artery and vein are located laterally in this compartment.
The posterior compartment (superficial) contains the gastrocnemius and soleus
muscles.