Acs0308 Soft Tissue Sarcoma

© 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
3 BREAST, SKIN, AND SOFT TISSUE 8 Soft Tissue Sarcoma — 1

8 SOFT TISSUE SARCOMA
Eric Kimchi, M.D., Herbert Zeh, M.D., F.A.C.S., Yixing Jiang, M.D., Ph.D., Kevin Staveley-O’Carroll, M.D., Ph.D., F.A.C.S.

Pathologic Classification, Staging, and Prognosis
Soft tissue sarcoma (STS) is a collective term for an unusual and
diverse group of malignancies that arise from cells of the embry- STS may be broadly categorized on the basis of the tissue type
onic mesoderm. Although tissues derived from the mesoderm con- from which the tumor is believed to have originated [see Table 1].
tain approximately 75% of the cells in the human body, sarcomas Subtypes within a particular histologic category may be defined by
represent only 1% of adult tumors and 15% of pediatric tumors. means of histochemistry, flow cytometry, electron microscopy, tis-
Sarcomas may occur anywhere in the body and comprise more sue culture, and cytogenetic analysis.This more detailed classifica-
than 50 distinct histologic subtypes. Approximately 43% of STSs tion can be useful in determining which therapy is to be employed
occur in the extremities, 15% in the retroperitoneum, 10% in the for a given tumor, but it is not part of the staging system set forth
trunk, 19% in the viscera, and 13% in other locations.1 In addition, by the American Joint Commission on Cancer (AJCC) [see Tables
some sarcomas occur in the GI tract. It has been estimated that in 2 and 3], which is the one most widely employed at present. The
2007, there will be approximately 9,220 cases of sarcoma in the best indicator of a tumor’s biologic aggressiveness and metastatic
United States, with 3,560 deaths.2 STS-related mortality has been potential is its grade, regardless of its histologic type.The histolog-
quite constant over the years, indicating that relatively little ic grade is defined by the tumor’s cellularity, nuclear atypia, degree
progress has been made in the treatment of most sarcomas. of necrosis, and mitotic activity. Determining the grade of a par-
The etiology of STS is unclear and somewhat controversial. ticular specimen on the basis of these characteristics can be diffi-
Genetic factors, irradiation, chemical exposure, and lymphedema cult; as prospective reviews have shown, expert pathologists may
have all been shown to have a strong correlation with the evolution differ by as much as 40% in their assessments of specimens.15,16
of these lesions. The AJCC staging system integrates tumor grade, tumor size,
Chromosomal abnormalities associated with STS may be due depth of tissue invasion, degree of nodal involvement, and pres-
to translocations, point mutations, or deletions resulting in bal- ence or absence of metastases. It should be kept in mind that time
anced or unbalanced karyotypes. Mutations in regulatory genes, and anatomic location, in concert with tumor size and grade, help
especially p53 and RB1, are a common finding.3,4 In particular, determine the likely outcome and the type of recurrence that
persons with Li-Fraumeni syndrome, familial retinoblastoma, might be expected. Different staging variables tend to be more
Werner syndrome, Gardner syndrome, tuberous sclerosis, basal strongly related to some outcomes than to others. Tumor grade is
cell nevus syndrome, or neurofibromatosis have an increased inci- related to early recurrence, tumor size is related to late recurrence,
dence of STS (and of other tumors as well).1 and anatomic location is related to the site or sites at which metas-
Ionizing radiation has long been recognized as a factor predis- tases are found.17
posing to the development of osteosarcoma and STS. It may exert
this effect at doses as low as 8 Gy. Sarcomas arising from radiation
exposure often do not become clinically apparent until long after Clinical Evaluation and
the inciting exposure; consequently, they are frequently associated Investigative Studies
with definitive radiation treatments that lead to a long expected STS typically presents as an asymp-
survival, such as may be provided in the setting of breast cancer, tomatic mass. Such masses are fre-
cervical cancer, lymphoma, or childhood malignancies. The most quently painless and large, and they
common of the sarcomas linked with radiation exposure are often are brought to patients’ attention
osteosarcoma (accounting for 35% of radiation-related STS) and by a history of recent trauma to the
malignant fibrous histiocytomas (accounting for 22%).5 area [see Figure 1]. Approximately 38%
Chemical carcinogenesis has been linked to a variety of sarco- are larger than 10 cm at presentation, with the remaining 62%
mas. The thorium dioxide–containing contrast agent Thorotrast, about equally divided between those that are 5 cm or smaller and
vinyl chloride, and arsenic all have been conclusively shown to play those that are larger than 5 cm but not larger than 10 cm.1
a role in the development of hepatic angiosarcomas.6-8 The optimal modality for imaging a sarcoma remains a matter
Phenoxyacetic acids, chlorophenols, and dioxins, which have been of debate. Although it is accepted that for extremity lesions, mag-
used in industry and agriculture, may contribute to the genesis netic resonance imaging provides more information than comput-
of STS, but the precise causal relations are unclear and remain ed tomography, a 1997 study by the Radiology Diagnostic
controversial.9-11 Oncology Group did not find MRI to possess any significant
Chronic lymphedema occurring after lymphadenectomy or sec- advantages over CT in this setting [see Figure 2].18 Positron emis-
ondary to filarial infection is a well-documented predisposing fac- sion tomography (PET), either alone or in combination with CT
tor for the development of lymphangiosarcomas.12,13 (PET/CT), does not currently have a clearly defined role in the
The relation between trauma and sarcoma development contin- workup and diagnosis of STS, but it does appear to be useful for
ues to be highly controversial. Perhaps the best evidence for a identifying the sites of distant metastases and, in particular, for
causal connection between the two is that parturition and extrem- determining the response to adjuvant therapy in patients with gas-
ity injuries have a predilection for giving rise to desmoid tumors.14 trointestinal stromal tumors (GISTs).19


Evaluation of Suspicious Soft Tissue Mass

Patient presents with soft tissue mass
that is a potential sarcoma

Mass is > 5 cm Mass is ≤ 5 cm

Perform core-needle biopsy. Perform excisional biopsy.

Tumor is high grade Tumor is low grade Lesion is benign Tumor is high grade Tumor is low grade

Assess resectability. Completely excise tumor and Completely excise previous Completely excise previous
biopsy field to achieve a clear surgical field to achieve a surgical field to achieve a
margin, then provide adjuvant negative margin, then provide negative margin, then provide
radiation therapy (external adjuvant radiation therapy adjuvant radiation therapy
beam radiotherapy or (external beam radiotherapy (external beam radiotherapy
brachytherapy). or brachytherapy). or brachytherapy).
Look for evidence of
metastatic disease.

Tumor is unresectable or > 10 cm Tumor is resectable and ≤ 10 cm

Consider adjuvant chemoradiotherapy Completely excise tumor and biopsy field
as part of a clinical trial. to achieve a clear margin, then provide
adjuvant radiation therapy (external
beam radiotherapy or brachytherapy).
Look for evidence of metastatic disease.

No evidence of metastatic disease is apparent Metastatic disease is present

Consider adjuvant chemotherapy as part of a Consider doxorubicin-based chemotherapy.
clinical trial.


sensitivity and specificity with respect to both malignant and
Table 1 Categorization of Sarcoma by benign soft tissue masses.23-25 For most masses smaller than 5 cm,
Histologic Type* an excisional biopsy with a clear surgical margin is indicated. Fine-
needle aspiration is not a useful modality in the workup of soft tis-
Alveolar soft-part sarcoma Fibrosarcoma
sue masses, because it does not provide a large enough sample to
permit determination of histologic architecture and tumor grade.23
Desmoplastic small round cell Leimyosarcoma
tumor Liposarcoma
Epithelioid sarcoma Malignant fibrous histiocytoma Management
Clear cell sarcoma Malignant hemangiopericytoma
Chondrosarcoma, extraskeletal Malignant peripheral nerve TREATMENT MODALITIES
Osteosarcoma, extraskeletal sheath tumor
Gastrointestinal stromal tumor Rhabdomyosarcoma Surgical Therapy
Ewing sarcoma/primitive neu- Synovial sarcoma Surgery is the foundation of the
roectodermal tumor Sarcoma, NOS treatment of STS. Amputation was
once considered the only option for
* As defined by the American Joint Committee on Cancer. cure, but this view changed with the 1982 publication of the land-
NOS—not otherwise specified
mark trial carried out by Rosenberg and colleagues from the
National Cancer Institute (NCI). In this trial, 43 patients with
extremity sarcomas were randomly assigned to undergo either
Distant sites of metastases vary in accordance with the tumor amputation of the affected limb (N = 16) or limb-sparing surgery
histology and the site of the primary tumor. Extremity sarcomas (LSS) plus radiation therapy (N = 27); all patients received adju-
most commonly metastasize to the lung, whereas abdominal and vant chemotherapy. The 5-year local recurrence rate was slightly
retroperitoneal sarcomas more frequently metastasize to the liver, higher in the LSS-radiation group, though the difference was not
with the lung being a secondary site of metastatic implantation.20,21 statistically significant. The 5-year survival was nearly identical in
In addition, there are a few sarcomas that tend to metastasize to the two groups: 70% in the LSS-radiation group and 71% in the
regional lymph nodes [see Table 4].22 These differing patterns of amputation group.26 In the years since the NCI trial, LSS has
metastatic spread must be carefully considered during the initial become the standard of care. Currently, fewer than 10% of all
evaluation of sarcoma patients. patients with surgically treated extremity sarcomas resections
A mass that is larger than 5 cm, is growing, or has persisted for undergo amputation, and local recurrence rates after LSS are in the
longer than 4 weeks constitutes an indication for biopsy. In choos- range of 5% to 15%.27,28 Amputation now is usually reserved for
ing the method, location, and orientation of the biopsy, it is critical patients with extremity sarcomas that involve major vessels, nerves,
to consider possible future surgical interventions. For masses larg- or bones. Although en bloc resection with reconstruction is also
er than 5 cm, either an incisional biopsy or a core-needle biopsy possible for these types of sarcomas, long-term function is often
(CNB) is appropriate. Incisional biopsies increase the possibility of poor, and the associated morbidity tends to be high. In these cases,
tumor spread through the tissue planes of the incision. For this rea- amputation is the better option for accomplishing definitive surgi-
son, many practitioners now prefer CNB for evaluation of soft tis- cal treatment and allowing a rapid transition to rehabilitation.29
sue masses. Several studies have shown CNB to have very high Adequate surgical resection involves excising a margin of nor-
mal tissue around the tumor, along with any areas through which
Table 2 American Joint Committee on Cancer biopsies have previously been performed. Compartmental resec-
tion or resection of entire muscle groups provides no additional
TNM Classification of Soft Tissue Sarcoma benefit over wide local excision. The ideal extent of a wide local
excision has not yet been defined; however, it is usually consid-
TX No evidence of primary tumor ered that a margin of at least 1 to 2 cm, when possible, should be
T1 Tumor ≤ 5 cm the goal. Resection of STSs with negative margins is associated
T1a: superficial tumor with a 12% to 31% recurrence rate.30,31 In contrast, simple enu-
Primary tumor (T) T1b: deep tumor cleation along the pseudocapsule is associated with a 33% to 67%
T2 Tumor > 5 cm recurrence rate and should therefore be avoided.32 Frozen-sec-
T2a: superficial tumor
T2b: deep tumor

NX Regional lymph nodes cannot be Table 3 American Joint Committee on Cancer
assessed Staging System for Soft Tissue Sarcoma
Regional lymph nodes (N)
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
5-Year
MX Distant metastasis cannot be assessed Stage T N M G Survival
Distant metastasis (M) M0 No distant metastasis
M1 Distant metastasis Stage I T1a, T1b, T2a, T2b N0 M0 G1, G2 90%

GX Grade cannot be assessed Stage II T1a, T1b, T2a N0 M0 G3, G4 81%
G1 Well differentiated
Stage III T2b N0 M0 G3, G4 56%
Histologic grade (G) G2 Moderately differentiated
G3 Poorly differentiated Any T N1 M0 Any G 10–20%
Stage IV
G4 Poorly differentiated or undifferentiated Any T N0 M1 Any G


ence between the two groups. Despite the overall improvement in
local control with brachytherapy, there was no significant differ-
ence between the brachytherapy group and the no-brachytherapy
group with respect to 5-year disease-specific survival (84% and
81%, respectively). Similar results were noted when tumor grade
subsets were analyzed. The investigators concluded that
brachytherapy afforded superior local control but ultimately did
not affect disease-specific survival.
The second study was a prospective, randomized trial from the
NCI that examined adjuvant external beam radiotherapy. A total
of 91 patients with high-grade STS were randomly assigned to
receive either radiotherapy (N = 44) or no radiotherapy (N = 47)
after complete surgical excision of the sarcoma; all patients
received adjuvant chemotherapy.31 In the radiotherapy group,
there were no local recurrences, whereas in the no-radiotherapy
group, there were nine. There was no difference between the two
groups in terms of overall survival. An additional 50 patients with
low-grade sarcomas were treated according to the same protocol.
In the radiotherapy group (N = 26), there was one local recur-
Figure 1 Contrast-enhanced CT scan demonstrates a very large rence, whereas in the no-radiotherapy group (N = 24), there were
retroperitoneal liposarcoma that was resected en bloc with a por-
eight. As with the patients who had high-grade STS, there was no
tion of the left hemidiaphragm, the distal pancreas, the spleen,
difference in overall survival between the two groups. This NCI
the left half of the colon, the left kidney, the left adrenal gland,
and a portion of the duodenum. The low signal intensity in the trial, along with the MSKCC brachytherapy trial, demonstrated
mass is indicative of adipose tissue elements (arrow). that adjuvant radiotherapy effectively controlled local recurrence in
patients with high-grade STS. In addition, it demonstrated that
external beam radiotherapy was advantageous in preventing local
tion analysis may be useful when an area is thought to be a close recurrences. Unfortunately, neither study identified a means of
margin. prolonging overall survival.
Regional lymphadenectomy is not usually indicated in the treat- The third and most recent study was a prospective, randomized
ment of sarcomas, because only 2.6% of sarcomas metastasize to trial carried out by the NCI of Canada Clinical Trials
lymph nodes.33 One exception to this general rule is a case in Group/Canadian Sarcoma Group, which compared preoperative
which the tumor is in proximity to a lymph node basin. Another is and postoperative radiotherapy in patients with extremity STS.34 A
a case in which the tumor is one of the several specific subtypes total of 190 patients were randomly assigned to receive either pre-
that more commonly metastasize to the lymphatic system [see Table operative radiotherapy (N = 94) or postoperative radiotherapy (N
4]. These subtypes include rhabdomyosarcoma, epithelioid sarco- = 96). This trial was closed before completion of the planned
ma, clear cell sarcoma, synovial sarcoma, and vascular sarcoma accrual because a preliminary analysis by the data monitoring
(i.e., angiosarcoma and lymphangiosarcoma). As an alternative to committee demonstrated a significant difference in wound com-
regional lymphadenectomy for these specific sarcoma subtypes, plications between the two groups. At the time of closure, the
sentinel lymph node biopsy (SLNB) may be considered [see 3:6 median follow-up period was 3.3 years. The wound complication
Lymphatic Mapping and Sentinel Lymph Node Biopsy].22 rate in the preoperative radiotherapy group was 35%, compared
with 17% in the postoperative radiotherapy group. At the time of
Radiation Therapy the analysis, there was no difference in local control rate between
As noted [see Surgical Therapy, above], adjuvant radiation ther- the two groups (93% in both), but there was a significant differ-
apy has dramatically changed the surgical treatment of sarcomas, ence in overall survival that slightly favored the preoperative radio-
providing local control of the tumor in cases where LSS is appro- therapy group.The wound complication rate was in line with data
priate. Three distinct types of radiotherapy are currently in use: from previous preoperative radiotherapy studies and was not unex-
brachytherapy, postoperative external beam radiotherapy, and pre- pected; however, the significance of the unanticipated improve-
operative external beam radiotherapy. ment in overall survival at this early time point remains unclear.35,36
To date, only three prospective, randomized trials examining the Currently, there is no consensus on which form of radiation
utility of radiotherapy combined with surgery have been complet- therapy is best for treatment of STS. Several retrospective studies
ed.The first was a trial of adjuvant brachytherapy in STS patients suggest that small (< 5 cm) STSs that are resected with negative
that was performed at Memorial Sloan-Kettering Cancer Center margins may be treated with surgical therapy alone.37,38
(MSKCC). In this study, 164 patients were randomly assigned
during operation to receive either adjuvant brachytherapy or no Chemotherapy
further therapy after resection of an STS in an extremity or the Postoperative chemotherapy for the treatment of STS has been
superficial trunk.30 Brachytherapy consisted of 42 to 45 Gy deliv- studied in numerous prospective, randomized trials, but the small
ered over a period of 4 to 6 days.The median follow-up period was sample sizes and the various differences among the trials have
76 months.The 5-year actuarial local control rate was 82% for the made it difficult to determine how efficacious such therapy is. In
brachytherapy group and 69% for the no-brachytherapy group. In an attempt to overcome the shortcomings of these small studies,
the high-grade lesion subset, this difference in local control rates the Sarcoma Meta-analysis Collaboration performed a meta-
was maintained (89% for the brachytherapy group and 66% for analysis of 14 doxorubicin-based adjuvant trials that included a
the no-brachytherapy group) and was statistically significant; how- total of 1,568 patients.39 The median follow-up across all of the tri-
ever, in the low-grade lesion subset, there was no significant differ- als was 9.4 years. Hazard ratios were calculated for local recur-


a b

c d

Figure 2 Shown are diagnostic images obtained from a patient with a large malig-
nant fibrous histiocytoma of the right thigh. (a) Contrast-enhanced CT scan demon-
strates fine linear enhancing septations. (b) T1-weighted images are generally best
for defining anatomy and the relation of the sarcoma to the neurovascular bundle
(arrow). (c) T2-weighted images are helpful for demonstrating the heterogeneity of
the tumor with its multiple septations, as well as the tumor pseudocapsule. High
signal intensity on T2-weighted images is frequently observed in tumors that are of
myxomatous histology or have undergone necrosis. (d) Image obtained after
gadolinium infusion shows areas of low signal intensity indicative of avascular myxo-
matous or necrotic regions (*). Areas of enhancement (arrow) are indicative of
viable regions of the tumor that should be targeted for percutaneous biopsy.

rence-free interval, distant recurrence-free interval, recurrence-free all 10-year survival (from 50% to 54%) was observed in the
survival, and overall survival, which when analyzed together chemotherapy group but did not reach statistical significance;
allowed assessment of the absolute effects of treatment. A statisti- however, there was a statistically significant improvement in 10-
cally significant improvement in 10-year disease-free survival (from year overall survival (7% absolute benefit) within a subset of the
45% to 55%) was reported in the chemotherapy group. An chemotherapy group comprising 886 extremity sarcomas. Several
improvement in 10-year local disease-free survival (from 75% to trials that made use of various other chemotherapeutic agents (e.g.,
81%) was also noted in this group. A trend towards improved over- epirubicin and ifosfamide) documented modest survival benefits
that echoed the results of this very well performed meta-analysis.
Table 4 Incidence of Nodal Metastases for At present, given the uncertainty regarding its efficacy, postopera-
tive adjuvant chemotherapy for treatment of STS is probably best
Selected Sarcomas
employed in the context of appropriate clinical trials.
Preoperative adjuvant chemotherapy has several theoretical
Sarcoma Type Incidence of Nodal Metastases (%) advantages over postoperative therapy in this setting. It allows
delivery of agents through the native vasculature, permits assess-
Rhabdomyosarcoma 11–36 ment of the effectiveness of a particular treatment by means of
Epithelioid sarcoma 17–80
pathologic analysis, may facilitate treatment of micrometastases,
Clear cell sarcoma 25–50
Synovial sarcoma 2–17
and may downstage tumors or make them more amenable to sur-
Vascular sarcoma 11–40 gical treatment. Certainly, the application of this modality to the
treatment of osteosarcoma and Ewing sarcoma in the pediatric


population has met with great success. As a consequence of this early investigational phase in the United States, where TNF is not
success, several groups have performed studies aimed at deter- currently available.
mining the effects of preoperative chemotherapy in adult STS
RECURRENT SOFT TISSUE SARCOMA
patients.
A retrospective analysis of 46 patients with extremity STS at Patients with extremity STSs experience local recurrences at a
M. D. Anderson Cancer Center examined a preoperative rate of 8% to 20% despite appropriate primary resection, and those
chemotherapy regimen consisting of doxorubicin, cyclophos- with resected retroperitoneal sarcomas experience local recurrences
phamide, and dacarbazine.40 The overall tumor response rate was at a rate of 38% to 50%.47-49 These patients are often candidates for
40%. In patients who exhibited a complete, partial, or minor re-resection of the locally recurring sarcoma. A retrospective review
response, there was a statistically significant improvement in both from the Brigham and Women’s Hospital found that 67% of
disease-free survival and overall survival. Subsequently, a prospec- patients with recurrent STSs were able to undergo salvage surgery
tive trial was completed at MSKCC in which 29 patients with large with excellent long-term survival.48 Patients who have not received
(> 10 cm) high-grade stage IIIB extremity sarcomas underwent radiation therapy are candidates for preoperative or postoperative
preoperative chemotherapy (involving a regimen similar to that treatment. Those who have already received radiation therapy may
employed in the M. D. Anderson study) and were compared with be considered for brachytherapy, which has a reported 5-year actu-
historic control subjects.41 Unlike the M. D. Anderson trial, the arial control rate of 68% and a reported morbidity of 12.5%.50
MSKCC trial did not find preoperative chemotherapy to confer However, given that low-grade sarcomas do not show a significant
any survival advantage over postoperative chemotherapy or no response to brachytherapy, this modality should be reserved for
chemotherapy after resection. Given the lack of sufficient evidence treatment of high-grade sarcomas.30,51 In some instances, such as
for any survival benefit, preoperative chemotherapy may reason- when the tumor burden is disseminated or limb function cannot be
ably be considered in attempting to preserve limb function, but preserved, salvage surgery may necessitate amputation.
otherwise, its use should be limited to clinical trials.
METASTATIC DISEASE
Targeted Therapeutics
Perhaps the most interesting and exciting advances in the treat- Resectable
ment of STS are those currently being achieved in targeted thera- Pulmonary metastases are present in approximately 20% of
peutics. In particular, the characterization and targeting of the tyro- patients with trunk or extremity sarcomas.52 If the patient is med-
sine kinase receptor c-kit has generated a new approach to treating ically fit, the primary tumor is controlled, no extrathoracic disease
GISTs. Phase III trials comparing standard and high-dose imatinib is present, and the metastases are resectable, pulmonary metasta-
mesylate in the treatment of these lesions have been completed in sectomy may be attempted.53 In a retrospective study performed at
the United States and Europe.42,43 In these two trials, the progres- MSKCC, 148 of 716 patients with extremity sarcomas experi-
sion-free response rate ranged from 43% to 53%, and the estimat- enced a recurrence.52 In 135 (91%) of the 148, the lung was the
ed 2-year survival ranged from 69% to 78%. The use of imatinib only site of recurrence. Of these 135 patients, 78 (58%) were
mesylate in adjuvant and neoadjuvant settings is still evolving. Data judged to be candidates for operative management, and ultimately,
from ACOSOG-Z9000, which has finished its patient accrual, and 65 (48%) were able to undergo a complete pulmonary metasta-
from several other trials, which were still accruing patients as of sectomy.The 3-year survival in this group was 23%, and the medi-
April 2007 (ACOSOG-Z9001, EORTC 62024, SSGXVIII, an survival time was 19 months. The 3-year survival in the group
RTOG-S0132, MDACC AD03-0023), should provide some valu- that did not undergo thoracotomy was 0%.The overall 3-year sur-
able clarification in this regard.44 The initial results achieved with vival for all patients with pulmonary metastases was 11%. Large
imatinib mesylate and its therapeutic analogues have given rise to studies of resection of pulmonary metastases from STS have yield-
hopes that other similar molecules will be discovered that can be ed 3-year survival rates ranging from 23% to 54%.54-61
directed at tumor-specific targets for effective treatment of these
largely drug-resistant tumors. Unresectable
Despite adequate resection of STS
Hyperthermic Isolated Limb Perfusion and the use of adjuvant therapy, distant
Hyperthermic isolated limb perfusion is a technique that is cur- metastases may develop in as many as
rently reserved for patients in whom LSS is not a possibility. An iso- 50% of cases.1 As noted (see above), the
lated circuit is created by cannulating the inflow arterial system and tumor’s site of origin and histology
the outflow venous system of a limb and applying a proximal determine the site or sites at which
tourniquet. This isolated circuit is usually monitored by means of metastatic disease will occur.
radiolabeled albumin to identify any leakage into the systemic cir- Unfortunately, for the vast majority of
culation. A heart-lung bypass machine maintains mild hyperther- patients, the only available treatment option is systemic chemother-
mia (39° to 40° C) and oxygenation and circulates chemothera- apy. There has been considerable debate regarding the best
peutic agents in the isolated limb. chemotherapy regimen for treating metastatic sarcoma, with most of
The largest trials of this technique to date were conducted in the the controversy centering on whether it is better to employ a single
Netherlands by Eggermont and colleagues, who used tumor necro- agent or a combination of agents. Doxorubicin has been the back-
sis factor (TNF) and melphalan.45,46 A total of 246 patients with bone of most chemotherapeutic regimens, and it has proved to be as
extremity sarcomas who were not candidates for LSS underwent effective as many single-agent or combination chemotherapy regi-
one or two sessions of isolated limb perfusion. After an interval of mens with respect to recurrence rates and survival.62-65 Some com-
2 to 4 months, 76% of these patients were able to undergo a resec- bination regimens have yielded higher response rates than doxoru-
tion with a negative margin, and 71% underwent successful LSS. bicin alone, but with increased toxicity and without any improve-
This approach is very well developed in Europe, but it is still in the ment in overall survival.66,67


References

1. Brennan M, Singer S, Maki R, et al: Sarcomas of tasis in patients with liposarcoma. Cancer nation chemotherapy for adults with high grade
the soft tissues and bone. Cancer: Principles and 75:1120, 1995 soft tissue sarcoma. Cancer 73:1644, 1994
Practice of Oncology, 7th ed. DeVita VT Jr, 22. Blazer DG 3rd, Sabel MS, Sondak VK: Is there a 42. Rankin C, von Mehren M, Blanke CD, et al: Dose
Hellman S, Rosenberg SA, Eds. Lippincott role for sentinel lymph node biopsy in the man- effect of imatinib (IM) in patients (pts) with
Williams & Wilkins, Philadelphia, 2005, vol 2, p agement of sarcoma? Surg Oncol 12:201, 2003 metastatic GIST: Phase III Sarcoma Group
1581 Study S0033. J Clin Oncol 22(14 suppl):9005,
23. Barth RJ Jr, Merino MJ, Solomon D, et al: A
2. American Cancer Society: Cancer Facts and prospective study of the value of core needle biop- 2004
Figures 2007. American Cancer Society, Atlanta, sy and fine needle aspiration in the diagnosis of 43. Verweij J, Casali PG, Zalcberg J, et al:
2007 soft tissue masses. Surgery 112:536, 1992 Progression-free survival in gastrointestinal stro-
3. Cance WG, Brennan MF, Dudas ME, et al: 24. Ball AB, Fisher C, Pittam M, et al: Diagnosis of mal tumours with high-dose imatinib: ran-
Altered expression of the retinoblastoma gene soft tissue tumours by Tru-Cut biopsy. Br J Surg domised trial. Lancet 364:1127, 2004
product in human sarcomas. N Engl J Med 77:756, 1990 44. Trent JC, Benjamin RS: New developments in
323:1457, 1990 25. Heslin MJ, Lewis JJ, Woodruff JM, et al: Core gastrointestinal stromal tumor. Curr Opin Oncol
4. Latres E, Drobnjak M, Pollack D, et al: needle biopsy for diagnosis of extremity soft tis- 18:386, 2006
Chromosome 17 abnormalities and TP53 muta- sue sarcoma. Ann Surg Oncol 4:425, 1997 45. Eggermont AM, Schraffordt Koops H, Lienard
tions in adult soft tissue sarcomas. Am J Pathol 26. Rosenberg SA, Tepper J, Glatstein E, et al: The D, et al: Isolated limb perfusion with high-dose
145:345, 1994 treatment of soft-tissue sarcomas of the extremi- tumor necrosis factor-alpha in combination with
5. Nanus DM, Kelsen D, Clark DG: Radiation- ties: prospective randomized evaluations of (1) interferon-gamma and melphalan for nonre-
induced angiosarcoma. Cancer 60:777, 1987 limb-sparing surgery plus radiation therapy com- sectable extremity soft tissue sarcomas: a multi-
pared with amputation and (2) the role of adju- center trial. J Clin Oncol 14:2653, 1996
6. Falk H, Herbert J, Crowley S, et al: Epidemiology
vant chemotherapy. Ann Surg 196:305, 1982 46. Eggermont AM, de Wilt JH, ten Hagen TL:
of hepatic angiosarcoma in the United States:
27. Brennan MF, Casper ES, Harrison LB, et al: The Current uses of isolated limb perfusion in the
1964–1974. Environ Health Perspect 41:107,
role of multimodality therapy in soft-tissue sarco- clinic and a model system for new strategies.
1981
ma. Ann Surg 214:328, 1991 Lancet Oncol 4:429, 2003
7. Da Horta JS, Da Motta LC, Abbatt JD, et al:
28. Borden EC, Baker LH, Bell RS, et al: Soft tissue 47. Brennan MF: The enigma of local recurrence.
Malignancy and other late effects following
sarcomas of adults: state of the translational sci- The Society of Surgical Oncology. Ann Surg
administration of thorotrast. Lancet 32:201, 1965
ence. Clin Cancer Res 9:1941, 2003 Oncol 4:1, 1997
8. Creech JL Jr, Makk L: Liver disease among
29. Williard WC, Collin C, Casper ES, et al: The 48. Singer S, Antman K, Corson JM, et al: Long-term
polyvinyl chloride production workers. Ann NY
changing role of amputation for soft tissue sarco- salvageability for patients with locally recurrent
Acad Sci 246:88, 1973
ma of the extremity in adults. Surg Gynecol soft-tissue sarcomas. Arch Surg 127:548, 1992
9. Fingerhut MA, Halperin WE, Marlow DA, et al:
Obstet 175:389, 1992 49. Jaques DP, Coit DG, Hajdu SI, et al:
Cancer mortality in workers exposed to 2,3,7,8-
30. Pisters PW, Harrison LB, Leung DH, et al: Long- Management of primary and recurrent soft-tissue
tetrachlorodibenzo-p-dioxin. N Engl J Med
term results of a prospective randomized trial of sarcoma of the retroperitoneum. Ann Surg
324:212, 1991
adjuvant brachytherapy in soft tissue sarcoma. J 212:51, 1990
10. Kang HK, Weatherbee L, Breslin PP, et al: Soft Clin Oncol 14:859, 1996 50. Nori D, Schupak K, Shiu MH, et al: Role of
tissue sarcomas and military service in Vietnam: a brachytherapy in recurrent extremity sarcoma in
case comparison group analysis of hospital 31. Yang JC, Chang AE, Baker AR, et al: Randomized
prospective study of the benefit of adjuvant radi- patients treated with prior surgery and irradia-
patients. J Occup Med 28:1215, 1986 tion. Int J Radiat Oncol Biol Phys 20:1229, 1991
ation therapy in the treatment of soft tissue sarco-
11. Smith AH, Pearce NE, Fisher DO, et al: Soft tis- mas of the extremity. J Clin Oncol 16:197, 1998 51. Pisters PW, Harrison LB, Woodruff JM, et al: A
sue sarcoma and exposure to phenoxyherbicides prospective randomized trial of adjuvant
and chlorophenols in New Zealand. J Natl 32. Cantin J, McNeer GP, Chu FC, et al: The prob-
lem of local recurrence after treatment of soft tis- brachytherapy in the management of low-grade
Cancer Inst 73:1111, 1984 soft tissue sarcomas of the extremity and superfi-
sue sarcoma. Ann Surg 168:47, 1968
12. Stewart F, Treves N: Lymphangiosarcoma in post- cial trunk. J Clin Oncol 12:1150, 1994
mastectomy lymphedema. Cancer 1:64, 1943 33. Fong Y, Coit DG, Woodruff JM, et al: Lymph
node metastasis from soft tissue sarcoma in 52. Brennan MF: The surgeon as a leader in cancer
13. Muller R, Hajdu SI, Brennan MF: adults: analysis of data from a prospective data- care: lessons learned from the study of soft tissue
Lymphangiosarcoma associated with chronic base of 1772 sarcoma patients. Ann Surg 217:72, sarcoma. J Am Coll Surg 182:520, 1996
filarial lymphedema. Cancer 59:179, 1987 1993 53. McCormack P: Surgical resection of pulmonary
14. Fong Y, Rosen PP, Brennan MF: Multifocal 34. O’Sullivan B, Davis AM, Turcotte R, et al: metastases. Semin Surg Oncol 6:297, 1990
desmoids. Surgery 114:902, 1993 Preoperative versus postoperative radiotherapy in 54. Maruyama R, Mitsudomi T, Ishida T, et al:
15. Gaynor JJ, Tan CC, Casper ES, et al: Refinement soft-tissue sarcoma of the limbs: a randomised Aggressive pulmonary metastasectomies for syn-
of clinicopathologic staging for localized soft tis- trial. Lancet 359:2235, 2002 ovial sarcoma. Respiration 64:316, 1997
sue sarcoma of the extremity: a study of 423 35. Bujko K, Suit HD, Springfield DS, et al: Wound 55. Choong PF, Pritchard DJ, Rock MG, et al:
adults. J Clin Oncol 10:1317, 1992 healing after preoperative radiation for sarcoma of Survival after pulmonary metastasectomy in soft
16. Alvegard TA, Berg NO: Histopathology peer soft tissues. Surg Gynecol Obstet 176:124, 1993 tissue sarcoma: prognostic factors in 214 patients.
review of high-grade soft tissue sarcoma: the 36. Peat BG, Bell RS, Davis A, et al: Wound-healing Acta Orthop Scand 66:561, 1995
Scandinavian Sarcoma Group experience. J Clin complications after soft-tissue sarcoma surgery. 56. Putnam JB Jr, Roth JA: Surgical treatment for
Oncol 7:1845, 1989 Plast Reconstr Surg 93:980, 1994 pulmonary metastases from sarcoma. Hematol
17. American Joint Committee on Cancer: AJCC 37. Rydholm A, Gustafson P, Rooser B, et al: Limb- Oncol Clin North Am 9:869, 1995
Cancer Staging Manual, 6th ed. Springer-Verlag, sparing surgery without radiotherapy based on 57. Schirren J, Krysa S, Bulzebruck H, et al: Results
New York, 2002 anatomic location of soft tissue sarcoma. J Clin of surgical treatment of pulmonary metastases
18. Panicek DM, Gatsonis C, Rosenthal DI, et al: CT Oncol 9:1757, 1991 from soft tissue sarcomas. Recent Results Cancer
and MR imaging in the local staging of primary 38. Baldini EH, Goldberg J, Jenner C, et al: Long- Res 138:123, 1995
malignant musculoskeletal neoplasms: Report of term outcomes after function-sparing surgery 58. Shimizu J, Oda M, Hayashi Y, et al: Results of sur-
the Radiology Diagnostic Oncology Group. without radiotherapy for soft tissue sarcoma of gical treatment of pulmonary metastases. J Surg
Radiology 202:237, 1997 the extremities and trunk. J Clin Oncol 17:3252, Oncol 58:57, 1995
19. Vernon CB, Eary JF, Rubin BP, et al: FDG PET 1999 59. Jablons D, Steinberg SM, Roth J, et al:
imaging guided re-evaluation of histopathologic 39. Adjuvant chemotherapy for localised resectable Metastasectomy for soft tissue sarcoma: further
response in a patient with high-grade sarcoma. soft-tissue sarcoma of adults: meta-analysis of evidence for efficacy and prognostic indicators. J
Skeletal Radiol 32:139, 2003 individual data. Sarcoma Meta-analysis Thorac Cardiovasc Surg 97:695, 1989
20. Gadd MA, Casper ES, Woodruff JM, et al: Collaboration. Lancet 350:1647, 1997 60. Pogrebniak HW, Roth JA, Steinberg SM, et al:
Development and treatment of pulmonary metas- 40. Pezzi CM, Pollock RE, Evans HL, et al: Reoperative pulmonary resection in patients with
tases in adult patients with extremity soft tissue Preoperative chemotherapy for soft-tissue sarco- metastatic soft tissue sarcoma. Ann Thorac Surg
sarcoma. Ann Surg 218:705, 1993 mas of the extremities. Ann Surg 211:476, 1990 52:197, 1991
21. Cheng EY, Springfield DS, Mankin HJ: Frequent 41. Casper ES, Gaynor JJ, Harrison LB, et al: 61. van Geel AN, Pastorino U, Jauch KW, et al:
incidence of extrapulmonary sites of initial metas- Preoperative and postoperative adjuvant combi- Surgical treatment of lung metastases: the


European Organization for Research and comparison of adriamycin versus vincristine and comparative trial. A phase III, Southwest
Treatment of Cancer-Soft Tissue and Bone adriamycin, and cyclophosphamide versus vin- Oncology Group Study (7613). J Clin Oncol
Sarcoma Group study of 255 patients. Cancer cristine, actinomycin-D, and cyclophosphamide 5:851, 1987
77:675, 1996 for advanced sarcoma. Cancer 50:2757, 1982 66. Borden EC, Amato DA, Rosenbaum C, et al:
62. Santoro A, Tursz T, Mouridsen H, et al: 64. Borden EC, Amato DA, Edmonson JH, et al: Randomized comparison of three adriamycin reg-
Doxorubicin versus CYVADIC versus doxoru- Randomized comparison of doxorubicin and vin- imens for metastatic soft tissue sarcomas. J Clin
bicin plus ifosfamide in ﬁrst-line treatment of desine to doxorubicin for patients with metastat- Oncol 5:840, 1987
advanced soft tissue sarcomas: a randomized ic soft-tissue sarcomas. Cancer 66:862, 1990 67. Edmonson JH, Ryan LM, Blum RH, et al:
study of the European Organization for Research 65. Baker LH, Frank J, Fine G, et al: Combination Randomized comparison of doxorubicin alone
and Treatment of Cancer Soft Tissue and Bone chemotherapy using adriamycin, DTIC, versus ifosfamide plus doxorubicin or mitomycin,
Sarcoma Group. J Clin Oncol 13:1537, 1995 cyclophosphamide, and actinomycin D for doxorubicin, and cisplatin against advanced soft
63. Schoenfeld DA, Rosenbaum C, Horton J, et al: A advanced soft tissue sarcomas: a randomized tissue sarcomas. J Clin Oncol 11:1269, 1993

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