In an analysis of 500 patients with postoperative external-beam radiation

retroperitoneal soft tissue therapy, intraoperative

sarcoma treated at Memorial Sloan-Kettering radiation therapy, and brachytherapy. 173
Cancer Center, Preoperative radiation
the median survival time was 103 months for therapy is feasible and well tolerated.
those who Toxic effects may be less
underwent complete resection versus 18 severe with preoperative radiation therapy
months for those who given that the tumor
underwent incomplete resection or borders are definable, the tumor displaces
observation without resection. radiosensitive viscera
165 In general, surgical resection should not away from the treatment field, and
be offered effective doses of radiation
unless radiographic evidence indicates the may be lower preoperatively.174
potential for complete Several studies have shown favorable local
resection; however, palliative surgical control rates
resection may be for intermediate- and high-grade
considered to reduce symptoms of intestinal retroperitoneal sarcoma treated
obstruction, pain, with preoperative radiation therapy and
or bleeding.168 In particular, in patients complete resection.173
with atypical lipomatous However, most studies have failed to show a
tumors, an aggressive surgical approach survival benefit.175
including incomplete This situation prompted the initiation of a
resection or debulking is justified to multicenter, randomized
palliate symptoms and may trial sponsored by the American College of
provide a potential survival benefit.169 Such Surgeons
an approach is not Oncology Group (ACOSOG) comparing surgery
justified for dedifferentiated liposarcomas to surgery
or other high-grade with preoperative radiation (ACOSOG Z9031).
retroperitoneal sarcomas because these Unfortunately,
tumors have high rates the study was closed prematurely in 2006
of distant metastasis and local recurrence. because of low patient
Adjuvant Therapy. Most studies have failed accrual. A similar study is now ongoing in
to show a survival Europe, sponsored
benefit from adjuvant chemotherapy for by the Soft Tissue and Bone Sarcoma Group
retroperitoneal (STBSG) of the
sarcoma.170-172 Because of the high rates of EORTC.
local recurrence, Current recommendations for radiation
adjuvant radiation therapy has been therapy for patients
proposed for treating microscopic with retroperitoneal sarcoma at MD Anderson
residual disease following surgical Cancer Center
resection. However, are based on disease characteristics at
the optimal technique and timing of presentation.176 For highrisk
radiation therapy have not patients, defined as those with large,
been established, and the potential high-grade tumors or
benefits of radiation therapy recurrent low-grade tumors, preoperative
must be weighed against the increased risk radiation therapy to a
of treatment-related total dose of 50 Gy followed by surgical
toxic effects. resection is considered.
Radiation treatment of retroperitoneal Postoperative radiation is discouraged
sarcomas is complex unless the resected tumor
because tumors are usually large, which bed is clearly away from dose-limiting
necessitates large structures.
treatment fields close to radiosensitive Treatment of Recurrence. Retroperitoneal
structures (e.g., bowel). sarcomas recur
Several techniques have been used, more often than extremity and trunk wall
including preoperative and ones. Retroperitoneal
leiomyosarcomas, in addition to recurring abdominal mass (38%), and abdominal pain
locally in the (21%).
tumor bed and metastasizing to the lungs, Establishing the diagnosis of a
frequently spread gastrointestinal sarcoma
to the liver. Retroperitoneal sarcomas can preoperatively is often difficult.
also recur diffusely Radiologic assessment, including
throughout the peritoneal cavity CT of the abdomen or pelvis, is sometimes
(sarcomatosis). Resection useful to determine
of recurrent retroperitoneal sarcoma is the anatomic location, size, and extent of
similar to resection of disease. Patients
recurrent extremity sarcoma. However, the with localized disease frequently present
likelihood that a with a large intraabdominal
recurrent retroperitoneal sarcoma will be mass. However, there is no radiographic
resectable declines evidence
precipitously with each recurrence. In a of regional lymph node metastases, which
large series of patients would be typical of
treated at Memorial Sloan-Kettering Cancer an adenocarcinoma of similar size and
Center, the authors anatomic location. In
were able to resect recurrent tumors in 57% patients with advanced gastrointestinal
of patients with a sarcoma, CT may demonstrate
first recurrence but only 20% of patients disseminated intra-abdominal masses with or
with a second recurrence without
and 10% of patients with a third concomitant ascites and invasion of tissue
recurrence.68 In up to planes.
25% of patients, well-differentiated Endoscopy (esophagoduodenoscopy or
retroperitoneal liposarcoma colonoscopy) has
recurs in a poorly differentiated form or become the mainstay for evaluating symptoms
recurs with areas of related to the
dedifferentiation. Dedifferentiated gastrointestinal tract. For tumors
retroperitoneal liposarcoma involving the stomach, upper
is more aggressive than its well- endoscopy with endoscopic ultrasonography
differentiated precursor and has and biopsy are
a greater propensity for distant important diagnostic tests used to
metastasis. distinguish gastrointestinal
Gastrointestinal Sarcoma sarcoma from adenocarcinoma of the stomach.
Patients with gastrointestinal sarcoma most This distinction
often present with is clinically significant because the
nonspecific gastrointestinal symptoms that extent of resection (local
are determined by excision versus gastrectomy) and the role
the site of the primary tumor. In a series of regional lymphadenectomy
from Memorial Sloan- differ for these two conditions. For
Kettering Cancer Center, early satiety and gastrointestinal sarcomas,
dyspepsia were noted lymphatic spread is not the primary route
in patients with tumors of the upper of metastasis;
gastrointestinal tract, whereas consequently, lymphadenectomy is not
tenesmus and changes in bowel habits were routinely performed as
common in patients part of resection. The general
with tumors of the lower gastrointestinal recommendation for gastrointestinal
tract.177 In a series of 80 sarcoma, based on published data and the
patients with various smooth-muscle tumors primary pattern of
of the gastrointestinal distant (vs. local) failure, is to resect
tract, Chou and colleagues178 identified the the tumor with a 2- to 4-cm
most common presenting margin of normal tissue. However, some
symptoms and signs as gastrointestinal cases may be technically
bleeding (44%), challenging because of the tumor’s
anatomic location or
size. For example, for gastric tumors of the breast, patients with radiation-
located near the gastroesophageal associated angiosarcoma
junction, achieving adequate surgical were on average 30 years older and were
margins may less likely
not be possible without a total or proximal to present with distant metastases than
subtotal gastrectomy. radiation-naive patients.
Similarly, large leiomyosarcomas arising Clinically, radiation-associated
from the stomach with angiosarcoma of the breast may
invasion of adjacent organs should be occur in the irradiated chest wall after
resected together with the mastectomy or in the irradiated
adjacent involved viscera en bloc. breast following segmental resection. The
For sarcomas of the small or large findings at presentation
intestine, segmental of a patient with cutaneous angiosarcoma
bowel resection is the standard treatment. often include
For sarcomas of the jejunum, ileum, and an expanding erythematous patch, red
colon, the tumor is excised en bloc with papular eruptions, bluishblack
the involved segment of intestine and its lesions, or bruise-like discoloration
mesentery; radical overlying an area of
mesenteric lymphadenectomy is not induration. Mammography is often
attempted. For sarcomas nonspecific, and diagnosis
originating in the rectum, the tumor requires punch or incisional biopsy.
resection technique is based Cystosarcoma phyllodes are generally not
on the anatomic location and size of the considered to
tumor. For small, low be sarcomas, because these tumors are
rectal lesions, clear margins may be thought to originate from
achievable with a transanal hormonally responsive stromal cells of the
excision. Large or locally invasive lesions breast and are usually
may require more benign. In patients with these tumors,
extensive operations for complete tumor infiltrating tumor
extirpation.179,180 margins, severe stromal overgrowth, atypia,
Breast Sarcoma and cellularity have
Sarcomas of the breast are rare tumors, all been identified as risk factors for
accounting for less than metastases.182
1% of all breast malignancies and less than As with sarcomas at other anatomic sites,
5% of all soft tissue histopathologic
sarcomas. A variety of histologic subtypes grade and tumor size are important
have been reported prognostic factors for sarcomas
within the breast, including angiosarcoma, of the breast. The likelihood of local
stromal sarcoma, recurrence increases
fibrosarcoma, and malignant fibrous as tumor size increases; tumors smaller
histiocytoma. than 5 cm are associated
Angiosarcoma of the breast accounts for with better overall survival. Local and
about 50% of all distant recurrences
sarcomas of the breast and has increasingly are more common in patients with high-grade
been associated with lesions. Complete
radiation therapy for treatment of primary excision with negative margins is the
breast cancer.10 The primary therapy. Simple
period between radiation therapy and mastectomy confers no additional benefit if
diagnosis of radiationassociated complete excision
breast sarcoma has been reported to range can be accomplished by segmental
from 3 to mastectomy. Because of low
20 years, with an incidence of 0.3% at 10 rates of regional lymphatic spread,
years and 0.5% at axillary dissection is not routinely
15 years.181 In a retrospective study of 55 indicated. Neoadjuvant chemotherapy or
patients with angiosarcoma radiation therapy
may be considered for patients with large, leiomyosarcoma.127 Doxorubicin and
high-risk tumors. trabectedin have also
Uterine Sarcoma demonstrated activity when used as first-
Sarcomas account for less than 5% of or second-line therapy.
uterine malignancies. Endometrial stromal sarcomas account for
Uterine sarcomas have been classified into approximately
four histologic subgroups: 7% to 10% of uterine sarcomas. Mitotic
uterine leiomyosarcoma, endometrial stromal count is used to classify
sarcoma, endometrial stromal sarcomas as low grade
malignant mixed mullerian tumor (<10 mitoses
(carcinosarcoma), and undifferentiated per 10 high-power fields) or high-grade
endometrial sarcoma. Five-year overall (>10 mitoses per 10
survival high-power fields). In general, low-grade
rates for patients with uterine sarcoma are tumors demonstrate
30% to 50%.183 Total an indolent clinical course, while high-
abdominal hysterectomy (TAH) is recommended grade tumors are more
for localized aggressive with a poorer prognosis. Unlike
disease. Bilateral salpingo-oophorectomy is other uterine sarcomas
mandatory only subtypes, endometrial stromal sarcomas
in endometrial stromal sarcoma. Because express progesterone
uterine sarcomas are receptors and have been found to be
rare, the benefits of adjuvant therapy responsive to
(e.g., chemotherapy, hormonal hormonal manipulation as an adjuvant
therapy) have not been adequately therapy or for treatment
evaluated. Pelvic postoperative of recurrent disease.185,186 Surgical treatment
irradiation has been studied instead in a for these tumors
randomized includes TAH and bilateral salpingo-
fashion. The results of such study have oophorectomy in premenopausal
been reported, showing women; postoperative hormone replacement
no benefit in survival in favor of therapy is
radiation therapy.184 contraindicated.187 Recurrent or advanced
Uterine leiomyosarcomas are smooth-muscle disease may respond
tumors and to antiestrogen therapy. Tamoxifen is not
account for 35% to 40% of uterine sarcomas. recommended because
Leiomyosarcoma it may be proestrogenic in this setting.
can affect women in their twenties, Malignant mixed mullerian tumor accounts
although it is more commonly for 50% of
diagnosed between 50 and 60 years of age. uterine sarcomas and arises predominantly
Standard in postmenopausal
treatment is TAH with or without ovarian women. This tumor is regarded as epithelial
preservation depending and is treated not
on the patient’s wishes and menopausal with agents typically used to treat sarcoma
status. Lymph node but with agents used
metastasis is present in less than 5% of to treat ovarian and endometrial cancers.
patients at diagnosis, and Undifferentiated endometrial sarcoma is an
lymphadenectomy is not recommended. aggressive
Adjuvant pelvic radiation malignancy that does not express estrogen
therapy can be considered for selected or progesterone
high-risk patients. receptors. It is associated with a poor
Adjuvant chemotherapy is controversial. prognosis even in patients
Gemcitabine plus presenting with localized disease. TAH with
docetaxel has been noted to be well or without preservation
tolerated and highly active, of the ovaries is recommended;
with a response rate of 53% in patients postoperative pelvic
with unresectable uterine radiation therapy may also be administered.
Systemic agents for
other soft tissue sarcomas are used for trial, patients with KIT exon 11 mutations
recurrent and/or metastatic had better response
disease. rates (83.5% vs. 47.8%) and survival than
GASTROINTESTINAL STROMAL those with KIT exon 9
TUMORS mutations or those without KIT or PDGFRA
GISTs, which account for the majority of mutation.193 These
gastrointestinal findings have subsequently been confirmed
sarcomas, have distinctive molecular in two additional
features that have been phase III trials conducted by the EORTC–
characterized over the last decade. These Italian Sarcoma
tumors share phenotypic Group–Australasian Gastrointestinal Trials
similarities with the intestinal pacemaker Group (EORTC-
cells known 62005).194,195
as the interstitial cells of Cajal 188; The most common locations for GISTs are the
interstitial cells of Cajal and stomach
GIST cells express the hematopoietic (60%) and small intestine (30%), but GISTs
progenitor cell marker can arise anywhere
CD34 and the growth factor receptor c-Kit.189 along the gastrointestinal tract.196 Gastric
Expression of the GISTs have been
c-Kit gene protein product, CD117, has shown to be associated with a more
emerged as an important favorable prognosis than
defining feature of GISTs. Using these GISTs at other sites.197 GISTs are most
diagnostic criteria, commonly diagnosed
the incidence of GIST has been estimated to by upper endoscopy and/or CT of the abdomen
be 6 to 15 cases as an incidental
per million individuals per year. 190-192 Until finding in an asymptomatic patient or in a
recently, systemic treatment for patients patient being evaluated
with unresectable or metastatic GIST was for symptoms of early satiety, abdominal
of little benefit because these tumors were pain, or gastrointestinal
resistant to conventional bleeding. GIST most frequently metastasizes
chemotherapy. Since the recognition that to the liver
KIT activation and/or abdominal cavity.
occurs in most GISTs, KIT inhibition has Radiologic Assessment
emerged as the primary FDG-PET has been reported to be useful for
treatment modality along with surgery. preoperative
Approximately 80% of GISTs have a mutation staging of GISTs because it may reveal
in the gene early metastases and
encoding the KIT receptor tyrosine kinase, establish baseline metabolic activity. PET
and 5% to 10% have has been shown
a mutation in the gene encoding the related to be highly sensitive in detecting early
PDGFRA receptor response to imatinib
tyrosine kinase; such mutations result in treatment and in predicting long-term
the expression of response in patients with
mutant proteins with constitutive tyrosine metastatic GIST. If PET is to be used for
kinase activity.1 The monitoring response to
remaining GISTs do not have a detectable therapy, baseline PET should be performed
mutation, but lack of before initiation of
a mutation does not preclude a diagnosis of treatment. Because PET is still not widely
GIST if the tumor available and because
is morphologically typical of GIST. The PET fails to detect some lesions because of
presence and type of poor glucose uptake,
KIT (exon 11 or exon 9) or PDGFRA (exon new CT-based criteria for detection of GIST
18) mutation has and for predicting
been found to predict tumor response to prognosis of GIST have also been proposed. 198
imatinib. In a phase II