Practical Radiation OncologyÒ (2021) 11, 339−351
www.practicalradonc.org
Practice Guideline
Radiation Therapy for Treatment of Soft Tissue
Sarcoma in Adults: Executive Summary of an
ASTRO Clinical Practice Guideline
Kilian E. Salerno, MD,a,* Kaled M. Alektiar, MD,b Elizabeth H. Baldini, MD, MPH,c
Manpreet Bedi, MD,d Andrew J. Bishop, MD,e Lisa Bradfield, BA,f
Peter Chung, MBChB,g Thomas F. DeLaney, MD,h Andrew Folpe, MD,i
John M. Kane, III, MD,j X. Allen Li, PhD,k Ivy Petersen, MD,l John Powell, MD,m
Michael Stolten, MD,n Steven Thorpe, MD,o Jonathan C. Trent, MD, PhD,p
Maria Voermans, BS,q and B. Ashleigh Guadagnolo, MD, MPHr
a
Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland; bDepartment of Radiation Oncology,
Memorial Sloan Kettering Cancer Center, New York City, New York; cDepartment of Radiation Oncology, Dana-Farber/
Brigham and Women’s Cancer Center, Boston, Massachusetts; dDepartment of Radiation Oncology, Medical College of
Wisconsin, Milwaukee, Wisconsin; eDepartment of Radiation Oncology, UT—MD Anderson Cancer Center, Houston,
Texas; fAmerican Society for Radiation Oncology, Arlington, Virginia; gDepartment of Radiation Oncology, University
of Toronto, Princess Margaret Cancer Center, Toronto, Ontario, Canada; hDepartment of Radiation Oncology,
Massachusetts General Hospital, Boston, Massachusetts; iDepartment of Pathology and Laboratory Medicine, Mayo
Clinic, Rochester, Minnesota; jDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo,
Sources of support: This work was funded by the American Society for Radiation Oncology.
Disclosures: All task force members’ disclosure statements were reviewed before being invited and were shared with other task force members
throughout the guideline’s development. Those disclosures are published within this report. Where potential conflicts were detected, remedial measures
to address them were taken.
Elizabeth Baldini: UpToDate (royalty); Peter Chung: Boston Scientific (honoraria), Sanofi (research), Tersera and Verity Pharmaceuticals (advisory
board); Thomas DeLaney: Chordoma Foundation (medical advisory board), Best Docs (honoraria), Elsevier, GlaxoSmithKline (consultant), Oakstone
Medical Publishing, UpToDate, Wolters Kluwer Health (royalty); Andrew Folpe: Epizyme, Ultragenyx Pharmaceutical (consultant); B. Ashleigh Guadagnolo (chair): Cancer Prevention Research Institute of Texas (research); John Kane, III (Society of Surgical Oncology representative): NCCN (Sarcoma Panel vice chair); X. Allen Li: Accuray, Elekta (research, honoraria), Manteia Medical, Siemens Healthineers (research); Ivy Petersen: NRG
Oncology (committee co-chair); Kilian Salerno (vice chair and Guideline Subcommittee representative): American College of Radiology (TXIT examination committee chair, travel expenses), International Journal of Radiation Oncology, Biology, and Physics (associate senior editor); Johnson & Johnson (stock-family member); Steven Thorpe (Musculoskeletal Tumor Society (MSTS) representative): American Academy of Orthopedic Surgeons and
MSTS (committee member); Jonathan Trent (American Society of Clinical Oncology representative): Blueprint Medicine, C4 therapeutics, Deciphera,
Daichi Sankyo, Epizyme (all consultant). Kaled Alektiar, Manpreet Bedi, Andrew Bishop, Lisa Bradfield, John Powell, Michael Stolten, and
Maria Voermans (patient representative) reported no disclosures.
Disclaimer and Adherence: American Society for Radiation Oncology (ASTRO) guidelines present scientific, health, and safety information and
may reflect scientific or medical opinion. They are available to ASTRO members and the public for educational and informational purposes only. Commercial use of any content in this guideline without the prior written consent of ASTRO is strictly prohibited.
Adherence to this guideline does not ensure successful treatment in every situation. This guideline should not be deemed inclusive of all proper
methods of care or exclusive of other methods reasonably directed to obtaining the same results. The physician must make the ultimate judgment
regarding therapy considering all circumstances presented by the patient. ASTRO assumes no liability for the information, conclusions, and findings
contained in its guidelines. This guideline cannot be assumed to apply to the use of these interventions performed in the context of clinical trials. This
guideline is based on information available at the time the task force conducted its research and discussions on this topic. There may be new developments that are not reflected in this guideline and that may, over time, be a basis for ASTRO to revisit and update the guideline.
* Corresponding author: Kilian E. Salerno, MD; E-mail: kilian.salerno@nih.gov
https://doi.org/10.1016/j.prro.2021.04.005
1879-8500/Ó 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
340
K.E. Salerno et al
Practical Radiation Oncology: September−October 2021
New York; kDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin; lDepartment of
Radiation Oncology, Mayo Clinic, Rochester, Minnesota; mDepartment of Radiation Oncology, Roswell Park
Comprehensive Cancer Center, Buffalo, New York; nDepartment of Radiation Oncology, University of Rochester Medical
Center, Rochester, New York; oDepartment of Orthopedic Surgery, UC Davis Medical Center, Sacramento, California;
p
Division of Medical Oncology, Sylvester Comprehensive Cancer Center, The University of Miami Health System,
Miami, Florida; qFroedtert & Medical College of Wisconsin, Milwaukee, Wisconsin; and rDepartment of Radiation
Oncology, UT—MD Anderson Cancer Center, Houston, Texas
Received 23 March 2021; revised 29 April 2021; accepted 30 April 2021
Abstract
Purpose: This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing
of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma
(STS) in adults.
Methods: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for
management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for
sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.
Results: Multidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in
whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is
conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT
is not recommended.
Conclusions: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based
recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing
may optimize outcomes and quality of life.
Ó 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Preamble
As the leading organization in radiation oncology, the
American Society for Radiation Oncology (ASTRO) is
dedicated to improving quality of care and patient outcomes. A cornerstone of this goal is the development and
dissemination of clinical practice guidelines based on
systematic methods to evaluate and classify evidence,
combined with a focus on patient-centric care and shared
decision making. ASTRO develops and publishes guidelines without commercial support, and members volunteer their time.
Disclosure Policy—ASTRO has detailed policies and
procedures related to disclosure and management of
industry relationships to avoid actual, potential, or perceived conflicts of interest. All task force members are
required to disclose industry relationships and personal
interests, beginning 12 months before initiation of the
writing effort. Disclosures go through a review process
with final approval by ASTRO’s Conflict of Interest
Review Committee. For the purposes of full transparency, task force members’ comprehensive disclosure
information is included in this publication. The complete
disclosure policy for Formal Papers is online.
Selection of Task Force Members—ASTRO strives
to avoid bias by selecting a multidisciplinary group of
experts with variation in geographic region, gender, ethnicity, race, practice setting, and areas of expertise. Representatives from organizations and professional societies
with related interests and expertise are also invited to
serve on the task force.
Methodology—The task force uses evidence-based
methodologies to develop guideline recommendations
in accordance with the National Academy of Medicine
standards.1,2 The evidence identified from key questions
(KQs) is assessed using the Population, Intervention,
Comparator, Outcome, Timing, Setting (PICOTS)
framework. A systematic review of the KQs is completed, which includes creation of evidence tables that
summarize the evidence base task force members
use to formulate recommendations. Table 1 describes
ASTRO’s recommendation grading system.
Consensus Development—Consensus is evaluated
using a modified Delphi approach. Task force members confidentially indicate their level of agreement
on each recommendation based on a 5-point Likert
scale, from “strongly agree” to “strongly disagree.”
A prespecified threshold of ≥75% (≥90% for expert
Practical Radiation Oncology: September−October 2021
opinion recommendations) of raters who select
“strongly agree” or “agree” indicates consensus is
achieved. Recommendation(s) that do not meet this
threshold are removed or revised. Recommendations
edited in response to task force or reviewer comments are resurveyed before submission of the document for approval.
Annual Evaluation and Updates—Guidelines are
evaluated annually beginning 2 years after publication
Table 1
RT for adult soft tissue sarcoma
341
for new potentially practice-changing studies that could
result in a guideline update. In addition, ASTRO’s
Guideline Subcommittee will commission a replacement or reaffirmation within 5 years of publication.
Full-Text Guideline—The reader is encouraged to
consult the full-text guideline supplement for the supportive text, abbreviations list, and additional information on
soft tissue sarcoma because the executive summary contains limited information.
ASTRO recommendation grading classification system
ASTRO’s recommendations are based on evaluation of multiple factors including the QoE, individual study quality, and panel consensus,
all of which inform the strength of recommendation. QoE is based on the body of evidence available for a particular key question and
includes consideration of number of studies, study design, adequacy of sample sizes, consistency of findings across studies, and
generalizability of samples, settings, and treatments.
Strength of
Recommendation
Strong
Conditional
Overall QoE Grade
Definition
Benefits clearly outweigh risks and burden, or
risks and burden clearly outweigh benefits.
All or almost all informed people would make
the recommended choice.
Benefits are finely balanced with risks and
burden or appreciable uncertainty exists about
the magnitude of benefits and risks.
Most informed people would choose the
recommended course of action, but a substantial
number would not.
A shared decision-making approach regarding
patient values and preferences is particularly
important.
Type/Quality of Study
Overall QoE
Grade
Recommendation
Wording
Any
(usually high, moderate,
or expert opinion)
“Recommend/
Should”
Any
(usually moderate, low,
or expert opinion)
“Conditionally
Recommend”
Evidence Interpretation
High
2 or more well-conducted and highly generalizable The true effect is very likely to lie close to the estimate
RCTs or meta-analyses of such trials.
of the effect based on the body of evidence.
Moderate
1 well-conducted and highly generalizable
RCT or a meta-analysis of such trials OR
2 or more RCTs with some weaknesses of
procedure or generalizability OR
2 or more strong observational studies with
consistent findings.
Low
Expert Opinion*
The true effect is likely to be close to the estimate of
the effect based on the body of evidence, but it is
possible that it is substantially different.
1 RCT with some weaknesses of procedure or
The true effect may be substantially different from the
estimate of the effect. There is a risk that future
generalizability OR
1 or more RCTs with serious deficiencies of
research may significantly alter the estimate of the
effect size or the interpretation of the results.
procedure or generalizability or extremely small
sample sizes OR
2 or more observational studies with inconsistent
findings, small sample sizes, or other problems that
potentially confound interpretation of data.
Consensus of the panel based on clinical judgment
and experience, due to absence of evidence or
limitations in evidence.
Strong consensus (≥90%) of the panel guides the
recommendation despite insufficient evidence to
discern the true magnitude and direction of the net
effect. Further research may better inform the topic.
Abbreviations: ASTRO = American Society for Radiation Oncology; QoE = quality of evidence; RCTs = randomized controlled trials.
*
A lower quality of evidence, including expert opinion, does not imply that the recommendation is conditional. Many important clinical questions addressed in guidelines do not lend themselves to clinical trials, but there still may be consensus that the benefits of a treatment or diagnostic
test clearly outweigh its risks and burden.
342
K.E. Salerno et al
Introduction
Soft tissue sarcomas (STS) are potentially lethal
tumors that account for approximately 1% of adult malignancies.3 STS are comprised of many histopathologic
subtypes.4,5 These tumors can present with considerable
size and bulk and can arise anywhere in the body. Optimal patient management requires multidisciplinary input
that considers clinical, pathologic, and treatment factors.6
The primary treatment for localized STS is oncologic
resection with negative margins. Given their relatively
rare occurrence, many STS present after an unplanned
excision of a mass that is subsequently diagnosed as
STS.7 These unplanned procedures complicate options
for subsequent appropriate oncologic management.8-10
The addition of radiation therapy (RT) to surgery allows
excellent local control with surgical approaches that preserve organs and function.11-16
Questions arise regarding when RT should be used in
addition to oncologic resection and how best to sequence
surgery and RT when both are used. When multimodality
local therapy is indicated, the paradigm has evolved to
favor preoperative RT over postoperative RT. Dosing and
treatment volume considerations differ with respect to
preoperative versus postoperative RT.17,18 Advances in
external beam RT (EBRT) planning, techniques, and
onboard imaging have expanded radiotherapeutic
approaches. RT for treatment of retroperitoneal sarcoma
(RPS) remains controversial, and updated recommendations are provided to address considerations for management of this rare presentation of STS. ASTRO
commissioned this multidisciplinary task force to provide
evidence-based recommendations for 5 clinically relevant
KQs addressing the role of RT in the treatment of STS.
Methods
Task Force Composition
The task force consisted of a multidisciplinary team of
radiation, medical, orthopedic, and surgical oncologists,
a radiation oncology resident, a pathologist, a medical
physicist, and a patient representative. This guideline was
developed in collaboration with the American Society of
Clinical Oncology, the Musculoskeletal Tumor Society,
and the Society of Surgical Oncology, who provided representatives and peer reviewers.
Document Review and Approval
The guideline was reviewed by 18 official peer
reviewers and revised accordingly. The modified guideline was posted on the ASTRO website for public
Practical Radiation Oncology: September−October 2021
comment from November 2020 to January 2021. The
final guideline was approved by the ASTRO Board of
Directors and endorsed by the Canadian Association of
Radiation Oncology, European Society for Radiotherapy
and Oncology, Musculoskeletal Tumor Society, Royal
Australian and New Zealand College of Radiologists, and
the Society of Surgical Oncology.
Evidence Review
A systematic search of human subject studies retrieved
from the database Ovid MEDLINE was conducted. The
inclusion criteria required studies to involve adults (age ≥18
years), with a diagnosis of primary, localized STS involving
the extremity, superficial trunk (ie, abdominal wall, chest
wall, paraspinal musculature) or retroperitoneum, treated
with resection and RT, published in English, from January
1980 (for randomized controlled trials, meta-analyses, prospective studies) and January 1995 (for retrospective studies
and dosimetric/contouring studies) through October 25,
2019. The search was updated through September 22, 2020,
to ensure the most current evidence base, and 3 additional
studies were incorporated into the evidence tables and evaluated by the task force. Given the rarity of STS and that different qualities of evidence were available for each KQ, the
search inclusion criteria were further refined. See the full-text
guideline for the search inclusion criteria, outcomes of interest, selected Medical Subject Heading terms and key search
terms, and additional information on the search parameters.
References published in this document are representative and
not all-inclusive.
All supplementary materials, including the full-text
guideline and evidence tables (which summarize the data
used to formulate recommendations), are available at
(https://doi.org/10.1016/j.prro.2021.04.005). The full-text
guideline also includes the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) diagram showing the number of articles screened, excluded,
and included in the evidence review, and Appendix E1
(peer reviewer’s disclosure information), Appendix E2 (list
of abbreviations), Appendix E3 (literature search strategy),
and Appendix E4 (patient and provider recommendations).
Scope of the Guideline
This guideline addresses the role of RT in the treatment of adult patients with primary, operable, localized
STS of the extremity and trunk (KQs 1-4) and the complexities related to RT for RPS (KQ5) (see Table 2 in the
full-text guideline for KQs and outcomes of interest).
The guideline discusses indications for RT, and provides
dose, technique, and treatment planning recommendations. Outside the scope of this guideline are many other
important topics that may be subjects of other guidelines,
including initial evaluation and imaging; biopsy
Practical Radiation Oncology: September−October 2021
techniques for pathologic confirmation; detailed surgical
resection considerations and reconstructive options;
treatment of subsites other than extremity, trunk, and
retroperitoneum; treatment of unresectable, recurrent, or
metastatic disease; use of brachytherapy for STS; and the
role of systemic therapy (primarily used to decrease the
risk of metastases). Additionally, the integration of (neo)
adjuvant chemotherapy with surgery and RT to enhance
local control of STS or facilitate limb or organ sparing
resection is beyond the scope of this guideline. Sarcomas
arising in the setting of genetic predisposition syndromes
are not specifically addressed. Histopathologic subtypes
that were included and excluded are listed in
Appendix E3 in the full-text guideline.
KQs and Recommendations
KQ1: Indications for RT (Table 2)
See evidence tables in Supplementary Materials for
the data supporting the recommendations for KQ1.
What are the roles and indications for RT in the
treatment of extremity and superficial truncal adult
STS?
The determination of what constitutes an increased
risk of local recurrence is complex and considers clinical,
pathologic, and surgical factors. These factors include
surgical margins, grade, tumor size, anatomic location,
and histopathologic subtype. Resection margin status is
the major and most consistent factor predictive of local
recurrence.24,25 The consequences of a recurrence, effect
on functional outcome, and other potential morbidity of
future surgical salvage options are also considered when
Table 2
RT for adult soft tissue sarcoma
343
determining the role for RT. The addition of RT to surgery for STS reduces the risk of local recurrence compared with surgery alone.25,26 Selected patients at low
risk for local recurrence may be managed with surgery
alone when wide margins are obtainable.21,27-29
KQ2: Preoperative versus postoperative RT
(Table 3)
See evidence tables in Supplementary Materials for
the data supporting the recommendations for KQ2.
What are the appropriate considerations used in
determining preoperative versus postoperative RT in
the treatment of extremity and superficial truncal
adult STS?
The optimal sequencing of local therapies for an individual patient should be determined by multidisciplinary
evaluation before initiation of treatment. Preoperative
and postoperative RT result in similar local control in
combination with surgery yet differ in their risks for acute
versus late morbidity.17,34,35 In the majority of cases,
preoperative RT is preferred over postoperative RT. The
rationale for this recommendation is further discussed in
the full-text guideline. After attempted oncologic resection alone, final pathologic examination may reveal unanticipated adverse features (including inadequate margins,
invasion through fascia, higher grade disease, and infiltrative or discontinuous spread) that increase risk for local
recurrence.19,22,32,36 In such cases, postoperative RT is
recommended for local control, particularly where further
resection is not feasible.11,13,16,25 Figure 1 and Figure 2
are treatment algorithms based on the recommendations
from KQ1 and KQ2.
Roles and indications for RT in the treatment of extremity and superficial truncal adult STS
KQ1 Recommendations
Strength of
Quality of
Recommendation Evidence (refs)
1. For patients with localized STS, expert pathology and radiology review and
multidisciplinary evaluation is recommended before treatment initiation.
Strong
2. For patients with primary, localized extremity and truncal STS for whom oncologic
resection is planned, RT is recommended for those at increased risk for local recurrence.
Implementation remarks:
Assessment of risk for local recurrence is complex and incorporates multiple factors.
Potential morbidity of future surgical salvage options may also be considered when
determining the role of RT.
Strong
3. For patients with primary, localized extremity and truncal STS for whom oncologic
resection is planned and a close or microscopically positive margin is anticipated, RT is
recommended.
Strong
4. For patients with primary, localized extremity and truncal STS for whom oncologic
resection is planned, RT is not recommended for those at low risk for local recurrence.
Strong
5. For patients with primary, localized extremity and truncal STS who have had an unplanned
excision, oncologic resection is recommended, when feasible.
Strong
Abbreviations: KQ = key question; RT = radiation therapy; STS = soft tissue sarcoma.
Low
17
High
11-16
Moderate
15,19,20
Moderate
19,21,22
Low
23
344
Table 3
K.E. Salerno et al
Practical Radiation Oncology: September−October 2021
Sequence of RT and surgery for extremity and superficial truncal adult STS
KQ2 Recommendations
1. For patients with primary, localized extremity and truncal STS, the sequencing of surgery
and RT should be determined based on multidisciplinary evaluation of patient and tumor
characteristics.
Preoperative RT
2. For patients with primary, localized extremity and truncal STS, where surgery and RT
are indicated, preoperative RT is recommended over postoperative RT.
Postoperative RT
3. For patients with primary, localized extremity and truncal STS treated with initial
oncologic resection (without preoperative RT) found to have unanticipated adverse
pathologic features, postoperative RT is recommended.
4. For patients with primary, localized extremity and truncal STS, where surgery and RT
are indicated, initial oncologic resection followed by postoperative RT is conditionally
recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding,
fungating tumors), or when the risk of wound healing complications outweighs that of
late toxicity.
Following an unplanned excision
5. For patients with primary, localized extremity and truncal STS following an unplanned
excision where oncologic resection is planned and RT is indicated, preoperative RT is
recommended over postoperative RT.
6. For patients with primary, localized extremity and truncal STS following an unplanned
excision when oncologic resection is not feasible, postoperative RT is recommended.
Strength of
Recommendation
Quality of
Evidence (refs)
Strong
Moderate
17,30
Strong
Moderate
17,18,31
Strong
Moderate
13,15,32
Conditional
Expert Opinion
Strong
Moderate
17,18,33
Strong
Moderate
11,13
Abbreviations: KQ = key question; RT = radiation therapy; STS = soft tissue sarcoma.
Table 4
Dose-fractionation regimens and target volumes for EBRT in extremity and superficial truncal adult STS
KQ3 Recommendations
Radiation Dose and Fractionation
1. For patients with primary, localized extremity and truncal STS receiving preoperative RT,
5000 cGy in 25 once daily fractions is recommended.
2. For patients with primary, localized extremity and truncal STS receiving postoperative RT,
5000 cGy in 25 once daily fractions or 5040 cGy in 28 once daily fractions to CTV1 and
additional dose to a reduced volume CTV2 is recommended (see Table 5 for target volume
definitions).
Implementation remark:
Additional dose to CTV2 of 1000-1600 cGy is used for negative margins and 1600
cGy for microscopic positive margins.
Targets and OARs
3. For patients with primary, localized extremity and truncal STS receiving preoperative RT,
an anatomically constrained CTV is recommended (Table 5).
Strength of
Quality of
Recommendation Evidence (refs)
Strong
Moderate
16,17,30,37,38
Strong
Moderate
11,17,26,39-44
Strong
Moderate
17,30,37,38
4. For patients with primary, localized extremity and truncal STS receiving postoperative RT,
an initial dose to an anatomically constrained CTV1 and additional dose to a reduced
volume CTV2 is recommended (Table 5).
Strong
5. For patients receiving either preoperative or postoperative RT for primary, localized
extremity and truncal STS, volumetric contouring of the OARs and use of appropriate dose
constraints are recommended.
Strong
6. For patients with primary, localized extremity and truncal STS, elective nodal RT is not
recommended.
Strong
Moderate
17,39,45,46
Moderate
30,31,37,38,45,47,48
Moderate
17,30,37-39,45,46
Abbreviations: CTV = clinical target volume; EBRT = external beam radiation therapy; KQ = key question; OARs = organs at risk; RT = radiation
therapy; STS = soft tissue sarcoma.
Practical Radiation Oncology: September−October 2021
KQ3: Dose-fractionation regimens and target
volumes for EBRT (Table 4)
See evidence tables in Supplementary Materials for
the data supporting the recommendations for KQ3.
What are the appropriate dose-fractionation regimens
and target volumes for EBRT in the treatment of
extremity and superficial truncal adult STS?
The appropriate dose-fractionation and target volume definition differs between preoperative and postoperative RT.16,30,38 Alternative dose-fractionation
regimens exist and remain under active investigation.
Further discussion on the role for postoperative boost
and details regarding target definition, areas at risk,
and dose constraints for organs at risk are provided in
the full-text guideline.
KQ4: Appropriate RT simulation, planning, and
delivery techniques (Table 6)
See evidence tables in Supplementary Materials for
the data supporting the recommendations for KQ4.
What are the appropriate simulation, planning,
and delivery techniques for EBRT in the
treatment of extremity and superficial truncal
adult STS?
Discussion regarding the importance of immobilization for set-up reproducibility, use of bolus, and rationales for recommendations in support of intensity
modulated RT, including volumetric-modulated arc therapy, and image guidance are provided in the full-text
guideline.
KQ5: Role for RT, dose-fractionation regimens,
and treatment planning for RPS (Table 7)
See evidence tables in Supplementary Materials for
the data supporting the recommendations for KQ5.
What is the role for RT in the treatment of RPS and
what are the preferred dose regimens and treatment
planning considerations if RT is used?
Multidisciplinary evaluation should be conducted before
initiation of any treatment for patients with primary, localized RPS.6 Due to the rarity and heterogeneity of RPS,
there is a paucity of prospective data to inform the role of
RT in a multimodality treatment approach.73 The recently
published preoperative radiotherapy plus surgery versus
surgery alone for patients with primary retroperitoneal sarcoma (EORTC 62092: STRASS) trial did not show a statistically significant abdominal recurrence-free survival
benefit for the addition of RT to surgical resection.56 Post
RT for adult soft tissue sarcoma
345
Table 5 Target delineation guidelines for extremity and
superficial truncal STS target volumes30,37,45,49
Target
Delineation Guidance
Preop RT
extremity or
truncal CTV
CTV = GTV + 1.5 cm radial and 3-4 cm
longitudinal anatomically constrained
expansion with inclusion of peritumoral
edema and biopsy tract (when feasible)
CTV = GTV + 3-4 cm circumferential margins
Preop RT
with expansion of 0.5-1 cm into underlying
subcutaneous
non-involved muscle with inclusion of
tumor CTV
peritumoral edema and biopsy tract (when
feasible)
Postop RT
CTV1 = tumor bed (defined by clips/preop
extremity or
MRI) + 1.5 cm radial and 3-4 cm
truncal CTV1
longitudinal anatomically constrained
expansion + the operative field, surgical
scar, and drain sites (when feasible)
CTV2 = tumor bed (defined by clips/preop
Postop RT
MRI) + 1.5 cm radial and 2 cm
extremity or
longitudinal expansion
truncal CTV2
CTV1 = tumor bed (defined by clips/preop
Postop
MRI) + 3-4 cm circumferential margins
subcutaneous
with expansion of 0.5-1 cm into
tumor CTV1
uninvolved muscle + the operative field,
scar, and drain sites (when feasible)
CTV2 = tumor bed (defined by clips/preop
Postop
MRI) + 1.5-2 cm circumferential margins
subcutaneous
and 0.5 cm into uninvolved muscle
tumor CTV2
Extremity or
truncal PTV
expansion
PTV expansion of 0.5 cm may be used with
daily image guidance, however, >1.0 cm
may be needed without daily image
guidance.
For preop RT, dose coverage to the PTV
can be trimmed 3-5 mm from skin to
reduce wound healing complications if
achievable without unacceptable
compromise of CTV coverage and if
surgeon plans to resect overlying skin and
subcutaneous tissue38
Abbreviations: CTV = clinical target volume; GTV = gross tumor
volume; MRI = magnetic resonance imaging; preop = preoperative;
postop = postoperative; PTV = planning target volume;
RT = radiation therapy; STS = soft tissue sarcoma.
Longitudinal refers to the direction parallel to muscle fibers and
radial is perpendicular to the muscle fibers. Subcutaneous refers to
tumors not involving the the fascia.
hoc exploratory analyses were conducted to evaluate
whether specific histopathologic subtypes of RPS were
more or less likely to benefit from preoperative RT.
Although these data argue that the routine use of RT in
addition to surgery is not warranted, there may be select
patients for whom RT might provide an overall disease outcome benefit in addition to surgery. Multiple factors are
considered in determining whether RT may be beneficial
346
Table 6
K.E. Salerno et al
Practical Radiation Oncology: September−October 2021
RT simulation, planning, and delivery techniques for EBRT of extremity and superficial truncal adult STS
KQ4 Recommendations
Strength of
Quality of
Recommendation Evidence (refs)
1. For patients with primary, localized extremity and truncal STS, use of custom immobilization
for RT delivery is recommended for reproducibility of accurate patient positioning.
Strong
2. For patients with primary, localized extremity and truncal STS receiving preoperative RT,
routine use of bolus is not recommended.
Strong
3. For patients with primary, localized extremity and truncal STS receiving postoperative RT,
routine use of bolus is not recommended unless the clinical target includes subcutaneous
tissue or skin.
Strong
4. For patients with primary, localized extremity and truncal STS, IMRT, including VMAT, is
recommended to minimize dose to OARs and reduce toxicity.
Implementation remark:
3-D CRT may be preferred in certain clinical scenarios to better spare OARs or reduce
integral dose.
Strong
5. For patients with primary, localized extremity and truncal STS, daily IGRT with at least
weekly volumetric image guidance is recommended.
Strong
Moderate
47,50,51
Low
30,37
Expert Opinion
Moderate
17,30,46,52-55
Moderate
30,37,47,48,51
Abbreviations: 3-D CRT = 3-dimensional conformal radiation therapy; IGRT = image guided radiation therapy; IMRT = intensity modulated radiation
therapy; KQ = key question; OARs = organs at risk; RT = radiation therapy; STS = soft tissue sarcoma; VMAT = volumetric modulated arc therapy.
Table 7
Role for RT, dose-fractionation regimens, and treatment planning for RPS
KQ5 Recommendations
Strength of
Quality of
Recommendation Evidence (refs)
1. Due to the rarity and heterogeneity of RPS, expert pathology and radiology review as well as
multidisciplinary evaluation is recommended before treatment initiation.
Strong
2. Routine use of RT in addition to oncologic resection for patients with primary localized RPS
is conditionally not recommended.
Implementation remark:
Selective use of RT may be considered for patients at high risk of local recurrence.
Conditional
3. If RT is planned in addition to oncologic resection in patients with primary, localized RPS,
preoperative RT is recommended.
Strong
4. If preoperative RT is planned for patients with primary, localized RPS, 5000 cGy in 25 once
daily fractions or 5040 cGy in 28 once daily fractions is recommended.
Strong
5. If preoperative RT is planned for patients with primary, localized RPS, 4-D CT and
delineation of an iGTV to account for internal motion are recommended for tumors above the
iliac brim.
Strong
6. If preoperative RT is planned for patients with primary, localized RPS, an anatomically
constrained CTV or ITV, volumetric contouring of OARs, and use of appropriate dose
constraints are recommended for treatment planning (Table 8).
Implementation remark:
Before RT planning, discuss with the surgeon whether ipsilateral kidney and/or partial
liver resection is planned as this will affect OAR constraints.
Strong
7. If preoperative RT is planned for patients with primary, localized RPS, IMRT, including
VMAT, is recommended to minimize dose to OARs with the aim of reducing toxicity.
Implementation remark:
3-D CRT may be used instead of IMRT in certain clinical scenarios if it achieves similar
or better sparing of OARs or reduced integral dose.
8. If preoperative RT is planned for patients with primary, localized RPS, daily IGRT with at
least weekly volumetric image guidance is recommended.
Strong
9. Routine use of postoperative RT for patients with primary, localized RPS is not
recommended.
Implementation remark:
Selective use of postoperative RT may be considered in highly select patients including
those with high risk of local recurrence where salvage surgery would not be feasible, and
the target volume is well defined and can be treated safely.
Low
56
Moderate
15,56-62
Moderate
15,56,57,59,61,63
Moderate
56,61,64
Moderate
65,66
Moderate
56,64,65,67-70
Moderate
70,71
Strong
Moderate
66,68
Strong
Moderate
61,72
Abbreviations: 3-D CRT = 3-dimensional conformal radiation therapy; 4-D CT = 4-dimensional computed tomography; CTV = clinical target volume;
IGRT = image guided radiation therapy; iGTV = internal gross tumor volume; IMRT = intensity modulated radiation therapy; ITV = internal tumor volume;
KQ = key question; OARs = organs at risk; RT = radiation therapy; RPS = retroperitoneal sarcoma; VMAT = volumetric modulated arc therapy.
Practical Radiation Oncology: September−October 2021
RT for adult soft tissue sarcoma
347
Figure 1 Initial local management. *Multidisciplinary evaluation includes input from radiation, surgical, orthopedic, and medical
oncology, sarcoma pathology, and musculoskeletal radiology. This algorithm addresses the use of surgery and radiation for local management; recommendations for systemic therapy are beyond the scope of this guideline. yAssessment of risk for local recurrence is
complex and incorporates multiple factors. These factors include surgical margins, grade, tumor size, anatomic location, and histopathologic subtype and are further discussed in the full-text guideline. zAdverse pathologic features that increase risk for local recurrence
include inadequate margins, invasion through fascia, higher grade disease, and infiltrative or discontinuous spread and are detailed in
the full-text guideline. Abbreviations: LR = local recurrence; postop = postoperative; preop = preoperative; RT = radiation therapy;
STS = soft tissue sarcoma.
348
K.E. Salerno et al
Practical Radiation Oncology: September−October 2021
Figure 2 Local management after unplanned excision. *Multidisciplinary evaluation includes input from radiation, surgical,
orthopedic, and medical oncology, sarcoma pathology, and musculoskeletal radiology. This algorithm addresses the use of surgery and radiation for local management; recommendations for systemic therapy are beyond the scope of this guideline.
y
Assessment of risk for local recurrence is complex and incorporates multiple factors. These factors include surgical margins,
grade, tumor size, anatomic location, and histopathologic subtype and are further discussed in the full-text guideline. Abbreviations: LR = local recurrence; postop = postoperative; RT = radiation therapy; STS = soft tissue sarcoma.
Practical Radiation Oncology: September−October 2021
Table 8
RPS
Target volume definitions for preoperative RT for
Volume
Definitions
GTV
Gross tumor as determined by CT imaging
iGTV
Contour GTV incorporating internal motion (for
tumors above the iliac brim)*
CTV/ITV
Symmetric 1.5 cm expansion on iGTV with the
following edits at interfaces:
Retroperitoneal compartment, bone, liver,
kidneyy: 0 mm
Bowel and air cavity: 5 mm
Under skin surface: 3-5 mm according to
institutional preference
If tumor extends to inguinal canal, expand 3 cm
inferiorly
PTV
CTV + 5 mm (if daily IGRT with at least
weekly volumetric imaging will be performed)
CTV + 9-12 mm (if no IGRT with volumetric
imaging will be performed)
Abbreviations: CT = computed tomography; CTV = clinical target volume; IGRT = image guided radiation therapy; iGTV = internal gross
tumor volume; ITV = internal target volume; PTV = planning target
volume; RT = radiation therapy; RPS = retroperitoneal sarcoma.
*
Owing to the movement of intra-abdominal contents with respiration, motion management techniques are recommended during treatment planning for tumors above the iliac brim.
y
If kidney will be resected, no need to edit at kidney interface.
Adapted from Baldini et al.74
for RPS (eg, margin status, histopathology, age, performance status, surgical considerations, or when local failure
would be particularly morbid). In these cases, when RT is
planned, preoperative RT is preferred to postoperative RT.
Further details regarding target definition, dose constraints
for organs at risk, and treatment planning considerations
are provided in the full-text guideline.
Conclusions/Future Directions
Although surgical resection with wide margins
remains the mainstay of local management for primary,
localized STS, RT plays an important role in achieving
optimal oncologic outcomes with respect to tumor control
as well as function preservation for many patients. With
respect to treatment sequencing, tumor control outcomes
are similar for preoperative versus postoperative irradiation. What differs between the 2 sequencing approaches
are the side effects. Although preoperative RT increases
risk of a nontrivial wound complication after surgery,
this is a treatment toxicity that is temporary and remediable. Postoperative irradiation confers a higher risk of permanent, function-limiting side effects due to present,
data-supported use of higher dose and larger irradiated
volumes. Therefore, the preferred approach to sequencing
for combined modality local therapy in most cases is preoperative RT followed by surgery.
RT for adult soft tissue sarcoma
349
These guidelines reflect the evidence supporting
advanced treatment planning, on-treatment image guidance, and appropriate target volume reduction compared
with historical field margins. The RT dosing recommendations reflect decades of evidence using conventionally
fractionated regimens and corresponding favorable local
control outcomes. However, future investigations may
address whether changes to radiation dosing are feasible
with resultant improvements in patient outcomes or
improvements in quality of life. The published randomized evidence does not support the routine use of RT in
addition to surgery for management of sarcomas arising
in the retroperitoneum. For selected cases of RPS, RT
may confer additional improvement in cancer control.
For both RPS and extremity or truncal STS presentations,
multidisciplinary evaluation and discussion are critical to
determining optimal management for patients.
Acknowledgments
We are grateful to Yimin Geng, MSLIS, MS, the UT—
MD Anderson Cancer Center research medical librarian, for
her assistance with creating the search strategy for this
guideline. The task force also thanks Michael Stolten, MD
(lead resident); Cristina Decesaris, MD; Olsi Gjyshi, MD;
Rebecca Levin-Epstein, MD; Todd Pezzi, MD; Richell Van
Dams, MD; and Sara Zakem, MD for literature review
assistance. The task force thanks the peer reviewers for their
comments and time spent reviewing the guideline. See
Appendix E1 for their names and disclosures.
Supplementary Materials
Supplementary material associated with this article
can be found in the online version at doi:10.1016/j.
prro.2021.04.005.
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