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DICKIE, HAAS, AND O’SULLIVAN
dose intensity for the given circumstance (e.g., the RPS setting
for the Sindelar trial outlined later).
Rosenberg et al randomly assigned patients to either receive
an amputation (16 patients) or limb-sparing surgery
plus adjuvant RT (27 patients). There were no local recurrences
in the amputation group, but four in the limb-sparing
group (local control 85% vs. 100%, p 0.06), with no difference
in overall survival. 37
Two subsequent trials compared conservative surgery
alone with similar surgery combined with adjuvant RT in
predominantly ESTS. The fırst study was discussed earlier,
and patients were randomly assigned to receive adjuvant
brachytherapy or surgery alone (see Types and Method of RT
Delivery, Brachytherapy). 7
Yang et al at the NCI randomly assigned 141 patients to
receive postoperative RT or not. They reported that highgrade
lesions (present in 91 patients) benefıted from adjuvant
EBRT (10-year local control rates of 78% vs. 100%; p 0.03)
as did low-grade sarcomas (present in 50 patients; 10-year
local control rates of 68% vs. 95%; p 0.067). 38 The gain in
local control by the addition of RT resulted in a substantial
and persistent reduction in joint motion. The earlier data
was recently confırmed with a median follow-up of 17.9
years. 39
The high risk of local failure following surgery has made
adjuvant RT an attractive option for RPS, but its role remains
controversial and there is a paucity of trials available.
At the National Cancer Institute, Sindelar et al
reported the prospective, randomized trial discussed earlier
(see Intraoperative Radiotherapy). In the study, 35
patients with surgically resected RPS were randomly assigned
to receive postoperative EBRT (50 to 55 Gy) versus
postoperative EBRT (35 to 40 Gy) and IORT (20 Gy). The
median follow-up was 8 years. Locoregional recurrence
was substantially lower with IORT (40% vs. 80% with external
beam alone), but with high toxicity and no survival
difference. However, only modest EBRT doses (35 to 40
Gy) delivered postoperatively without IORT resulted in
very high recurrence rates.
Withholding Adjuvant Radiotherapy
Although the benefıt of adjuvant RT is apparent in phase
III trials, guidelines and several published series also recommend
withholding RT in subsets of patients. Patients
with early-stage disease, including small size, superfıcial
location, and/or low-grade histologic subtypes are candidates.
The caveat underpinning the decision is that a resection
should be undertaken with oncologically appropriate
margins and/or intact fascial planes. 40 Such favorable presentations
do not eliminate local recurrences after surgery alone,
but the risk is low. For example, in the randomized study
from Yang et al, six of 19 low-grade cases experienced local
recurrence without RT versus one of 22 with RT (p 0.067),
but other anatomic factors (size and depth) also influence
outcome. 38,39 In two other series in which patients were selected
not to receive RT based on small size, favorable histology
of extremity/trunk STS, and wide margin resections, the
10-year local recurrence rate was 7% to 16.2% for the entire
group, and 0% to 10.6% for the subgroup after R0 surgery.
41,42 Nevertheless, recurring cases did not fare worse
with respect to disease specifıc- and overall survival compared
with similar patients without local disease recurrence.
The decision algorithm includes factors that address the ability
to salvage recurrence and the likelihood that metastasis
will not develop. Morbidity as a result of recurrent disease
management is an additional concern and not readily accounted
for.
A published nomogram based on 684 patient clinicopathologic
factors estimated the risk of local recurrence
after limb-sparing surgery without postoperative RT. 43
For example, a patient younger than age 50, with a smaller
than 5 cm high-grade extremity pleomorphic malignant
fıbrous histiocytoma resected with negative margins,
would have a 3-year local recurrence rate of less than 10%.
This patient could undergo surgery alone if the tumor location
permits potential limb salvage surgery in the event of subsequent
local recurrence. Despite the inherent bias in a retrospective
review of this nature, this nomogram shows promise as a
clinical tool for assessing the risk of local recurrence and the
need for adjuvant therapy with specifıc attention to whether RT
can be omitted.
In the management of RPS, the role of adjuvant RT is
much less clearly defıned as compared to the treatment of
ESTS. A number of large institutional studies 44,45 provide
superior results with modern and/or more aggressive surgery
alone than were obtained historically, thereby questioning
the contribution of RT in this setting. Based upon
these considerations, the European Organisation for Research
and Treatment of Cancer (EORTC) is currently
conducting a phase III, randomized study of preoperative
RT plus surgery versus surgery alone for patients with RPS
(STRASS Trial; NCT01344018). 46 This is a multi-institutional
trial addressing preoperative RT specifıcally compared with surgery
only. We await the results of this important and wellaccruing
trial that has shown a 54% global recruitment to date
and is on target for completion. 46
CONCLUSION
The local recurrence of ESTS following limb-sparing surgery
alone is in the range of 30% to 50%. In contemporary
series employing highly conformal RT including IMRT,
the addition of pre- or postoperative RT improves local
control to approximately 90% or greater with excellent
functional outcome. For RPS, the benefıt of RT has not yet
been proven, but if considered, preoperative RT seems
to be the safest process of delivery. An ongoing multiinstitutional
randomized trial should confırm its role. As
experience evolves, including a better understanding of
pathology and underlying molecular disease characteristics,
as well as imaging modalities, additional strategies
should further improve the therapeutic ratio following RT
for local control of STS in all anatomic sites.
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