NcXHF

INDICATIONS FOR ADJUVANT RADIATION FOR SOFT TISSUE SARCOMAS
STS IMRT, indicating the need for reliable on-board imaging
to detect target volume changes. 24
TIMING AND SCHEDULING OF RADIOTHERAPY: THE
“WHEN” COMPONENT
The two most common methods of EBRT delivery are preoperatively
or postoperatively. Postoperative delivery is associated
with increased limb fıbrosis, edema, joint stiffness, and
bone fractures. Preoperative RT results in an increased rate of
acute wound complications. 6
Several studies have reported the late morbidities following
pre- and postoperative RT in extremity STS. Long-term
follow-up of patients treated in the Canadian Sarcoma Group
NCIC trial (SR2) showed that, of 129 patients evaluable for
late toxicity, 48.2% in the postoperative group compared
with 31.5% in the preoperative group had grade 2 or greater
fıbrosis (p 0.07). 25 Edema was more frequently seen in the
postoperative group (23.2% vs. 15.5%), as was joint stiffness
(23.2% vs. 17.8%). Patients with these complications had
lower function scores (all p values 0.01) on the Toronto
Extremity Salvage Score and the Musculoskeletal Tumor
Society Rating Scale. Field size predicted greater rates of
fıbrosis (p 0.002) and joint stiffness (p 0.006), and
marginally predicted edema (p 0.06). Acute wound
healing complications were twice as common with preoperative
compared with postoperative RT. The increased
risk was almost entirely confıned to the lower extremity
(43% associated with preoperative vs. 21% with postoperative
timing; p 0.01).
The influence of time interval between preoperative EBRT
and surgery on the development of wound complications in
extremity sarcoma has been studied. Although the interval
had little influence, the data still suggest that the optimal interval
to reduce potential wound complications was 4 or 5
weeks between RT and surgery. 26
Although toxicity is a known accompaniment of the
combination of EBRT and surgery, these problems and
considerations do not preclude the use of RT in the management
of ESTS. In fact, the gain in local control is at least
as large as the benefıt of adjuvant RT in breast conserving
therapy for invasive breast cancers. 27 Furthermore, for highgrade
sarcomas, a survival benefıt has been suggested. 28
Whether a radiation therapy boost is needed following preoperative
RT and surgery with positive resection margins has been
questioned in a retrospective review of 216 patients with ESTS;
52 received preoperative RT (50 Gy) alone and were compared
with 41 who received preoperative RT with a postoperative
boost (generally 16 Gy). A portion of the population did not receive
radiotherapy at all, or received post-operative RT and were
excluded (123 of 216 patients). Patients who received the postoperative
boost had lower 5-year local recurrence-free rates
(73.8% vs. 90.4% for preoperative RT only), indicating that
the postoperative boost provides no obvious advantage. 29
A similar study of 67 patients yielded almost identical
results. 30 These results suggest that a benefıt from a delayed
postoperative boost following preoperative RT and
surgery is at best debatable, and the increased risk and
challenges of managing later RT morbidity (e.g., radiationinduced
fractures) resulting from the higher radiation doses involved
should be considered.
Finally, preoperative EBRT may be particularly suited to
the management of RPS. Its potential role was mentioned
briefly in the discussion of IORT because of the way these
approaches evolved. Radiotherapy delivered to an in situ
tumor has the advantages of treating a well-defıned and
undisturbed tumor volume where the tumor also acts as a
tissue-expander to displace small bowel and other radiosensitive
viscera from the radiation volume. Preoperative
external beam radiotherapy for RPS was associated with
minimal acute toxicity in two prospective clinical trials
from the Princess Margaret Hospital and The University
of Texas MD Anderson Cancer Center 31,32 with no increase
in wound healing complications. Long-term follow-up of
both trials combined indicated that preoperative radiotherapy
may be associated with favorable local control and overall
survival. 33 This has been further addressed in the very
long-term follow-up of the PMH study. 34
The minimal early toxicity reports of preoperative EBRT were
further confırmed in an additional trial where only one of 20
patients experienced gastrointestinal toxicity of grade 2 or
greater and one additional patient experienced leucopenia during
the EBRT phase. 35 Additional toxicity manifesting later 35,36
included a 33% severe postoperative complication rate and may
relate to the subsequent IORT phase. This underlines the importance
of prospective data collection in addressing complex
toxicity reporting from sequential phases of adjuvant local
therapy that is diffıcult to interpret in retrospective studies
such as those reported earlier from the Mayo Clinic and
MGH. 15,16 In such retrospective studies where toxicity is
reported remotely (often years later), only aggregated toxicities
can realistically be reported, since differential toxicities
from separate treatments are generally neither
defıned nor attributed distinctly at the time of occurrence.
RATIONALE FOR THE USE OF RT: THE “WHY”
COMPONENT
Adjuvant Radiotherapy
Even in large, deep seated, intermediate- to high-grade sarcomas,
the combination of limb sparing surgery with RT permits
more conservative surgical resections and results in high
local control results of approximately 90%. 6,17 The gain
should be balanced against the costs. The scope of this domain
is broad and includes RT treatment planning and delivery,
patient expenses including travel and work leave, and
the cost to health care when managing acute and late
radiation-induced morbidities.
To fully appreciate the role of RT in STS, it is also informative
to reflect on the outcome in randomized trials of patients
in whom RT was either not applied or was of only moderate
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