SOFT TISSUE SARCOMAS


Soft tissue sarcoma comprises a group of relatively rare but anatomically and
histologically diverse neoplasms. These tumors share a common embryonic origin,
arising primarily from tissues derived from the mesoderm, with the notable exception of
neurosarcomas, primitive neuroectodermal tumors (PNET) and possibly Ewing sarcomas,
which are thought to arise from tissues of ectodermal origin.

Despite the fact that the skeleton and somatic soft tissue account for as much as 75% of
total body weight, neoplasms of the soft tissues are comparatively rare, accounting for
1% of adult malignancies and 15% of pediatric malignancies.


No specific etiologic agent is identified in the overwhelming majority of patients with
soft tissue sarcoma. There are a number of recognized associations between specific
environmental factors and subsequent development of sarcoma. Exposure to
environmental toxins has been limited with development of this specific sarcoma:
mesothelioma (asbestos) and hepatic angiosarcoma (thorotrast and vinyl chloride).
Ionizing radiation has been indicated as a cause of sarcoma arising in soft tissue and
bone. The latent period averages approximately 10 years but ranges between 2 and 30
years, and the prognosis is usually poor. The association of lymphodema and
lymphangiosarcoma is well rcognized, as is Stewart Treves syndrome. The epidemiologic
relationship between the development of soft tissue sarcoma and inherited syndromes
associated with predisposition to sarcoma has been appreciated for more than two
decades and these include Li-Fraumemi syndrome, neurofibromatosis, tuberous sclerosis,
basal cell nevus syndrome and Gardener syndrome. Pediatric patients with familial
retinoblastoma have a 13 q chromosomal deletion and an increased incidence of
osteosarcoma and other second primary neoplasms including soft tissue sarcoma.
Sarcomas rarely develop from preexisting benign soft tissue tumors.


A number of sarcomas have been found to have consistent chromosomal abnormalities,
which in many cases may be diagnostic. These abnormalities may be important in the
pathogenesis of malignant transformation. Those cytogenetic abnormalities identified in
sarcoma are as follows:

Soft Tissue Sarcoma                                                                Page 1 of 20
Management Guidelines

                             Sarcoma                     Cytogenetic Findings
                            Bone sarcomas                          13q14
                            Osteosarcoma                   t(11;22)(q24;q11.2-12)
                            Ewing sarcoma

                           Visceral sarcomas                  t(12:14) and 7q
                        Uterine leiomyosarcoma

                    Soft tissue sarcomas
                        Synovial cell                      t(X;18)(p11.2;;q11.2)
                       Neuroblastoma                          del(1)(p32p36)
                   Liposarcoma (myxoid)                    t(12;16)(q13-14;p11)
                          Embryonal                                Trisomy 2q
                           Alveolar                           t(2;13)(q35-37;q14)
               Malignant fibrous histiocytoma              lq11,3p12,11p11,19p13
              Malignant peripheral nerve tumor              t(11;22)(q24;q11.2-12)
            Extraskeletal myxoid chondrosarcoma          t(9;15;22)(q31;q15;q12.2)
                     Peripheral primitive                   t(11;22)(q24;q11.2-12)
                  Neurorectodermal tumor


A thorough understanding of clinicopathological factors known to have an impact on
outcome is essential in formulating a treatment plan for patients with soft tissue sarcoma.
Prognostic factors having an impact on both the rate of development of distant metastasis
and disease related mortality includes histologic grade, deep location and size of 5 cm or
greater. Analysis of factors influencing postmetastasis survival demonstrated that age at
metastasis of 60 years or older, interval from initial presentation to the development of
metastasis and metastasis to site(s) other than one lung are unfavorable prognostic


There are approximately 70 different histological types of soft tissue sarcomas. Most
sarcomas are classified according to normal cell type they mimic. The cell type is not part
of prognostic staging system so these are usually grouped under the heading of soft tissue
sarcoma for the purpose of treatment. All subsets with the following pathology will be
treated with the same policies of treatment both for surgical, adjuvant and advanced

           - Fibrosarcoma
           - Malignant Fibrous Histiocytoma
           - Liposarcoma
           - Leiomyosarcoma
           - Hemangiosarcoma

Soft Tissue Sarcoma                                                                  Page 2 of 20
Management Guidelines
           - Dermatofibrosarcoma Protuberans
           - Synovial sarcoma
           - Malignant schwannoma
           - Soft tissue alveolar sarcoma
           - Clear cell sarcoma
           - Epithelioid sarcoma

One of the pathologic hallmarks of the tissue sarcoma, distinguishing it from carcinoma,
is the tendency of sarcoma to spread by hematogenous means. Lymph node metastases
are uncommon in sarcoma.


In case of carcinoma, there is well defined relationship between tumor size, regional
lymph node involvement and prognosis. However, few soft tissue sarcoma metastasize to
regional lymph nodes; thus staging by classic TNM approach does not accurately reflect
prognosis of most patients. Histologic grade is the most important determinant of
outcome in soft tissue sarcoma. Histologic grading is based on subjective interpretation
by pathologist of a number of light microscopic histopathologic criteria including
cellularity, cellular pleomorphism mitotic activity and necrosis. With the realization that
histological grade was of such clinical significance, grade was incorporated into
American Joint Committee on Cancer (AJCC) staging system. The nodal and distant
metastasis criteria have been retained from classic term staging approach but essentially
does not contribute to the staging of Stage I, II, III.

                             SARCOMA STAGING SYSTEM

Stage                           Description
0                               Tumor grade                  Grade Cannot be assessed
                                GX                           Well differentiated
                                G1                           Moderately differentiated
                                G2                           Poorly differentiated
                                G3                           Undifferentiated
T                               Primary tumor size
                                TX                           Primary size cannot be assessed
                                TO                           No evidence of tumor
                                T1                           Tumor size ≤ 5 cm
                                T2                           Tumor size > 5 cm
N                               Regional lymph node status
                                NX                           Regional nodes cannot be assessed
                                NO                           No regional lymph node metastasis
                                N1                           Regional lymph node metastasis
M                               Distant metastasis
                                MX                           Presence of distant metastasis cannot
                                MO                           be assessed
                                M1                           No distant metastasis
                                                             Distant metastasis

Soft Tissue Sarcoma                                                                            Page 3 of 20
Management Guidelines
          Stage              G                  T                 N                  M
             IA             G1                  T1                N0                 MO
              IB            G1                  T2                N0                 MO
             IIA            G2                  T1                N0                 MO
             IIB            G2                  T2                N0                 MO
            IIIA           G3, G4               T1                N0                 MO
            IIIB           G3, G4               T2                N0                 MO
            IVA            Any G               Any T              N1                 MO
            IVB            Any G               Any T             Any N               M1


Initial Workup

       1. Histopathology review by KFSH&RC Pathologist
       2. History and physical examination
       3. CBCD and screening profile
       4. CXR and CT scan of lung
       5. CT scan or preferably MRI of primary tumor bearing area
       6. If the lesion abuts bone, a bone scan should be obtained to help determine whether
          there is periosteal invasion or reaction.

PRIMARY THERAPY                     Stage I, II and III (High and Low Grade)

Treatment options include:

1. Surgery

       The recommended surgical treatment for resectable tumors is radical excision with
       negative tissue margins of at least 2 cm or more in all directions.

       If tumors cannot be completely resected, surgical debulking is generally
       recommended followed by radiation therapy.

2. Radiation Therapy

       Tumors which are completely resected with negative margins of 2 cm in all directions
       and classified as low grade, generally do not require radiation therapy.

       High grade tumors or tumors in which a high likelihood of residual disease is thought
       to be present or when margins are known to be less than 2 cm in diameter require
       post-operative radiation therapy. Generally, the entire surgical bed with a 3-4 cm
       margin in each direction is radiated to a central dose of 4,500 cGy in 25 fractions over
       5 weeks. This is followed by a boost to the area of original tumor volume, which is

Soft Tissue Sarcoma                                                                       Page 4 of 20
Management Guidelines
       treated to a central dose of 1,800 cGy in 9 fractions over 2 weeks for a total dose of
       6,300 cGy. The doses and field arrangements may be modified depending on the
       actual location of the tumor, the presence of critical and normal tissues etc. CT
       planning is used whenever appropriate.

       Unresectable tumors should be considered for radical radiation therapy. A dose of at
       least 6,000 cGy in 6 weeks should generally be delivered and CT planning is usually

Role of Adjuvant Chemotherapy

This is a most contentious issue in the management of soft tissue sarcoma. Several
prospective randomized trials have examined the role of adjuvant chemotherapy with
doxorubicin either as single agent or in combination with other cytotoxic drugs. The
majority of these studies accrued in small numbers of patients and did not demonstrate
either a metastasis free or an overall survival benefit for adjuvant chemotherapy. There is
wide inter-study variability among the numerous trials, including differences in
therapeutic regimens, drug doses, sample site, tumor site and histologic grade. Although a
metaanalysis of 15 prospective randomized trials suggests a treatment benefit in favor of
adjuvant chemotherapy, inherent flaws and bias in analyzing published data from
disparate studies render any conclusions unreliable. It is, therefore, our policy at present
at KFSH&RC not recommend systemic adjuvant chemotherapy outside the clinical trial.

Neoadjuvant Chemotherapy

In some situations chemotherapy may be used prior to surgery to convert unresectable
tumor to one that can be adequately resected with limb/organ preservation. This treatment
may be followed by postoperative radiation therapy. We will use the combination of
ifosfamide and adriamycin in this situation. The doses will be as follow

Ifosfamide 2000 mg/m2 iv as per out patient protocol with mesna X 4 days
Adriamycin 50 mg/m2 iv X 1 day

Stage IVA               Soft tissue sarcoma

Stage IVA sarcomas are tumors that have metastatic involvement of regional lymph
nodes but have not spread to distant organs. Local control of primary tumor is best
obtained by resection with negative margins, lymphadenectomy and postoperative
radiation therapy.

Stage IVB

Stage IVB sarcomas are those that have distant metastasis most commonly to the lung. In
20-30% of the cases of soft tissue sarcoma with only lung metastasis can still be cured
with aggressive treatment of the primary tumor and resection of the pulmonary

Soft Tissue Sarcoma                                                                    Page 5 of 20
Management Guidelines
Metastasis. The primary tumor in these cases should be treated as Stage II and III

For patients with unresectable pulmonary metastases or widespread desseminated disease
palliation may be provided by radiation therapy to the primary tumor and systemic


The goal of systemic chemotherapy is only palliation and, therefore, it is offered to
patients with symptoms. The criteria for the use of chemotherapy is as follows:

       - Symptomatic metastatic disease
       - Histological proof of STS
       - Normal bone marrow reserve
       - Normal cardiac function
       - Normal hepatic function

Treatment Plan

Adriamycin 60-75 mg/m2 IVP
Courses to be repeated every three weeks
Evaluation of response after 2nd cycle
If progressive disease - off chemotherapy

If response to chemo - continue the treatment for maximum of six- eight cycles (depend
on the dose)

Ewing Sarcoma

The pathologic process currently known as Ewing sarcoma was described as early as
1866 by Lücke. It became more widely known in 1921 as James Ewing described the
condition as endothelial myeloma, a lesion of perivascular endothelial origin. A number
of cell types have been proposed as the cell of origin. In addition to pericystic cells, these
include mesenchymal myeloid, retiartum, neuroepithelial and primitive multipotential
cells. Ewing sarcoma is one of the recognized small round cell tumor variants.
Commonly sophisticated immunochemistry, electron microscopy and cytogenetic and
molecular Ewing sarcoma from other small round cell neoplasms such as neuroblastoma,
embryonal rhabdomyosarcoma, osteomyelitis, small cell osteosarcoma and non-Hodgkins
lymphoma. Primitive neurorectodermal tumors and Ewing sarcoma represent a biologic
spectrum of the same tumor. Greater than 90% of these tumors are characterized by an
11:22 translocation.

Soft Tissue Sarcoma                                                                     Page 6 of 20
Management Guidelines

Ewing sarcoma is the third most commonly primary sarcoma of bone, comprising
approximately 10% of all primary bone tumors. Males are slightly more affected than
females. The peak incidence is at 10-14 years. Ewing sarcoma is distinctly rare in blacks
and uncommon in Chinese.

The most common sites for primary lesion are pelvic bones, femur, humerus and ribs.
Ewing sarcoma occurs less commonly at non-bone primary sites, a presentation that has
historically been termed extra-osseus Ewing sarcoma. However, the morphologic and
biologic characteristics of Ewing sarcoma developing in soft tissue appears to be
indistinguishable from those of tumors developing at bone sites and currently the
treatment is the same for these tumors.

Prognostic Factors

Two important prognostic factors are the site of the primary tumor and whether disease is
metastatic. Studies suggest that more than 50% of patients without metastatic disease
may have long-term disease free survival, compared to only 20-30% for patients who
present with metastatic disease. Patients with distal extremity tumor and primary tumors
arising in the jaw, skull, face, vertebra, clavicle and scapula have had better prognosis
than patients with proximal extremity, rib and pelvic/sacral primary tumors.

Chemotherapy induced necrosis in the primary tumor has been shown to be a statistically
significant prognostic factor for disease free and overall survival.


    Patients will be treated with VAIA chemotherapy as per outpatient protocol. The
dosages are as follows:

               Vincristine 1.5 mg/m2 IVP
*              Adriamycin 20 mg/m2 IVP day 1, 2, 3
               Ifosfamide 2000 mg/m2 (1 hour infusion) on days 1, 2, 3
               Mesna 2000 mg/m2 (24 hour) on days 1, 2, 3, 4
               Actinomycin D 0.5 mg/m2 on days 1, 2, 3

• (Alternate Actinomycin D and adriamycin)

       -       Evaluation will be done after 4 cycles and 8 cycles of chemotherapy. After
               completion of 4 cycles of this chemo, decision for local therapy will be made, ie
               surgery - v- radiotherapy. After local therapy, patient will receive 10 more cycles
               of the same chemotherapy. Patient will receive total of 14 cycles of chemotherapy
               (4 cycles before local therapy and 10 cycles after local therapy. If local therapy is
               radiation therapy then chemotherapy will be continued during radiation therapy

Soft Tissue Sarcoma                                                                           Page 7 of 20
Management Guidelines
               and actinomycin or adriamycin will be omitted for the duration of radiation


Section of Radiation Oncology and KFSH&RC treat patients on the conventional
fractionalization of the EICESS 92 protocol. This goes for both definitive radiation
therapy of inoperable lesions and post-operative radiation therapy.

Radiation Therapy Technique:

For patients with lesions of the extremities, moulding is elective, depending on site of the
disease and reproducability of the treatment position.

The initial treatment volume is the compartment corresponding to the tumor at the time of
diagnosis. However, the epiphysis of a long bone distally from the tumor may be spared
as long as the five-centimeter safety margin can be assured. This is particularly applicable
to patients who are still growing. The compartmental dose is 4,500 cGy in 25 fractions
over 5 weeks. Six MV x-rays are typically used and an opposing pairs technique is
generally applied, either AP-PA or opposing laterals if possible. Great care should be
taken to avoid soft tissue and skin at least on one side of the extremity first from the
tumor to avoid subsequent lymphodema. In addition, a boost is given to the remaining
tumor delivering 1,000 cGy in 5 fractions with a 2 cm margin.

For lesions of the trunk, pelvis, scapula and chest wall, CT planning will be used and the
target volumes will be the same as stated above.

Pulmonary Radiation

Patients who present with initial lung metastases but no bony metastases and who obtain
complete remission on chemotherapy should have consolidation radiation therapy to the
lungs. A central dose of 1,800 cGy in 12 fractions over two and half weeks is given to the
entire lung.

Likewise selected patients who develop isolated lung metastases in the follow-up period
may be considered for whole lung radiation with a boost to the gross metastases if this is
considered technically feasible.

Salvage Chemotherapy

Patients who failed initial chemotherapy , 2nd line VIP chemotherapy will be offered
dosage of VIP chemotherapy as follows:

               Etoposide 75 mg/m2 iv days 1 - 5
               Ifosfamide 1200 mg/m2 iv days 1 - 5
               Cisplatin 20 mg/m2 iv days 1 - 5

Soft Tissue Sarcoma                                                                   Page 8 of 20
Management Guidelines
               To be repeated every 4 weeks

                        This salvage chemotherapy will be continued until disease progression or
                        maximum of 6 cycles
                        Patient who failed salvage chemotherapy should be referred to palliative care


Osteosarcoma is the most common primary malignant bone tumor. It presents with
bimodal age distribution with the 1st peak occurring during childhood and adolescence
and the 2nd peak occurs 6th decade of life. It is a high grade, malignant, spindle cell tumor
o the bone characterized by the production of osteoids by malignant cell stroma. In
children, 80% of these tumors arise from the bones around the knee. Prior to 1970s,
treatment of localized osteosarcomas consisted of amputation, with an overall survival
rate of 5-20% at 2 years. Pulmonary metastasis usually occurred within 9 months and
were responsible for patients death. The introduction of effective chemotherapeutic
agents allowed a change in the approach to treatment of osteosarcomas. The beneficial
role of adjuvant chemotherapy in patients with osteosarcoma is now proven and disease
free survival at 2 years have increased to 60%. Moreover introduction of neoadjuvant
chemotherapy allowed more conservative links salvage surgery in 50% - 80% of patients
without compromising a patient’s chance of survival by delaying surgery.

Cellular Classification

The World Health Organization’s histologic classification of bone tumors separate
osteosarcoma into central (medullary) and surface (peripheral) tumors and recognizes a
number of subtypes within each group.

               Central (Medullary):

               a. conventional central osteosarcoma
               b. telangiectatic osteosarcoma
               c. intraosseous well differentiated (low grade) osteosarcoma
               d. small round-cell osteosarcoma

               Surface (Peripheral)

               a. Parosteal (juxta cortical) well differentiated (low grade) sarcoma
               b. Peristeal osteosarcoma - low intermediate grade
               c. High grade surface osteosarcoma

The most common pathologic type is conventional osteosarcoma. Recognition of
intraosseous well differentiated osteosarcoma and parosteal osteosarcoma is important
because these are associated with a favorable prognosis and can be successfully treated
with radical excision of the primary tumor.

Soft Tissue Sarcoma                                                                            Page 9 of 20
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(a) Localized (Operable) Osteosarcoma

       1.Biopsy proven osteosarcoma of long bones of an extremity (reviewed by
         KFSH&RC pathologist.
       2. Untreated non-metastatic..
       3. Chemotherapy planned to start within 4 weeks of biopsy.
       4. Neutrophile >1.5x109 and Plt _ 100,000.
       5. GFR > 60 ml/min.
       6. Serum bilirubin <20 µmol/L.
       7. Normal cardiac function.

Pre-Treatment Assessments

       1. History and physical examination
       2. X-ray of affected limb
       3. CT or MRI of affected limb
       4. Chest x-ray
       5. Chest CT
       6. Bone scan with x-rays of abnormal bones
       7. Alkaline phosphatase, LDH
       8. CBCD, serum creatinine, urea, calcium, magnesium, albumin and GIT


               Adriamycin 37.5 mg/m2 X 2 days
               Cisplatin 50 mg/m2 X 2 days

               Above chemo will be repeated every 3 weeks as out patient. Patient will receive 3
               cycles preoperative and 3 cycles postoperative.

Radiation Therapy for Osteogenic Sarcoma

Radiation therapy of osteogenic sarcoma and chondrosarcoma is generally palliative.
Lesions that require palliative radiation therapy will be treated by 1800 cGy in 3 fractions
or 2000 cGy in 5 fractions or another similar regimen.

Definitive radiation therapy can be considered for unresectable lesions in the absence of
distal metastasis, if this is warranted by the circumstances of the case. For such lesions a
shrinking field technique will be used and the known tumor will be treated to a dose of
6,600 – 7,000 cGy, depending on size and location and the presence of critical normal
tissues. For lesions in unfavorable locations (spine, base of skull), a palliative dose of
5000 cGy in 5 weeks will represebt tge maximum tolerated dose.

Soft Tissue Sarcoma                                                                       Page 10 of 20
Management Guidelines
Postoperative radiation therapy for known microscopic residuals following combination
chemotherapy and radical surgery can be considered in selected cases. A dose of 6,500 –
7,000 cGy should be given if circumstances permit.

(b) Metastatic Disease

Patient with metastatic disease or not eligible for the protocol and, therefore, will be
treated with Adriamycin and Cisplatin as outpatient.

                        Adriamycin 37.5 mg/m2 x 2 days
                        Cisplatin 50 mg/m2 x 2 days

(c) Treatment of recurrent disease in patients previously exposed to Adriamycin/
Platinum regimen or pooor histologic response to initial chemotherapy

These patients will be treated with salvage chemotherapy including combination of
Etoposide and ifosfamide. After two cycles, if there is no response than patient will be
referred to palliative care. Patient will receive three cycles of same chemotherapy for
poor histologic response. Dosage is as follows:

                        Etoposide 150 mg/m2 x 3 days
                        Ifosfamide 2.4 g/m2 x 3 days

Soft Tissue Sarcoma                                                                        Page 11 of 20
Management Guidelines

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents.
It arises from striated muscle progenitor cells found throughout the body. It is a curable
disease in the majority of children who receive optimal therapy, multimodal therapy
(chemotherapy, radiation therapy and surgery). Refinements in tumor staging and better
supportive care have significantly improved the outcome among patients with
rhabdomyosarcoma, with long-term survival rates approaching 70%.

Rhabdomyosarcoma is part of the spectrum of tumors encompassed in Li-Fraumeni

Cellular Classification

Rhabdomyosarcoma can be divided into several histologic sub-sets: embryonal, botryoid,
spindle cell, alveolar, pleomorphic.

The embryonal subtype is the most frequently observed histologic subtype in children.
Tumor with embryonal histology typically arise in head and neck region or in the
genitourinary tract, although they may occur at any primary site.

Botryoid tumor represents 10% of all rhabdomyosarcoma cases and arises under the
mucosal surface of body orifices such as the vagina, bladder and noses.

The spindle cell variant of embryonal rhabdomyosarcoma is the most frequently observed
at paratesticular site.

Alveolar subtype accounts for 20% of rhabdomyosarcoma with an increased frequency of
this subtype noted in adolescents and in patients with primary sites involving extremities,
trunk, perineum, and perirectal region.

Pleomorphic rhabdomyosarcoma occurs predominantly in patients age 30 – 50 years and
is rarely seen in children.


The identification of prognostic variables is crucial to understanding the behavior of
rhabdomyosarcoma as well as planning therapy. The most important prognostic factor
appears to be extent of disease or clinical group at the initiation of chemotherapy.

The primary site of disease is also an important prognostic variable. Thus, orbital and
extremity primary tumors are often recognized at an earlier stage than are deep-seated
tumors. The location of primary also influences the probability of primary surgical
extpiration as well as the tolerance of subsequent radiotherapy.

Soft Tissue Sarcoma                                                                  Page 12 of 20
Management Guidelines
Diagnostic and Staging Evaluation:

       1.) History and physical exam
       2.) Histologic diagnosis
       3.) CBCD
       4.) Renal and hepatic profile
       5.) Urinalysis before each cycle of chemotherapy
       6.) MRI or CT Scan of primary lesion
       7.) CT chest, abdomen and pelvis
       8.) Bone marrow biopsy and aspirate
       9.) Bone Scan
       10.) CSF cytology for parameningeal lesion.

Staging System:

Favorable prognostic groups have been identified by Intergroup Rhabdomyosarcoma
studies and treatment plans have been designed based on assignment of patients to
different groups based on prognosis. The definitions of the clinical groups on IRS I-III
studies are given below:

Clinical Group I

Group I has localized disease that is completely resected with no regional nodal
involvement. Approximately 13% of all patients are in this group.

Clinical Group II

Group IIA has grossly resected tumor with microscopic residual disease, but no regional
nodal involvement. Group IIB has regional disease with involved nodes, with complete
resection and no residual disease. Group IIC has regional disease with involved nodes,
grossly resected, but with evidence of microscopic residual and/or histologic involvement
of the most distal regional node (from primary site). Approximately 20% of all patients
are in this group.

Clinical Group III

Group III has incomplete resection (or biopsy only) of the primary site and therefore has
gross residual disease. Approximately 48% of all patients are in this group.

Soft Tissue Sarcoma                                                                Page 13 of 20
Management Guidelines
Clinical Group IV

Group IV has distant metastatic disease present at the time of diagnosis. Approximately
18% of all patients are in this group.


Stage    Sites                   T                         Size           N              M
1.    Orbit                  T1 or T2                     a or b      N0, or N1, or N2   M0
      Head & Neck
      (excluding parameningeal)
          Non Prostate

2              Bladder/Prostate         T1or T2            a              N0 or Nx       M0
               Cranial Paramenigeal
               Other (include trunk,
               retroperitoneum, etc)

3              Bladder/Prostate         T1 or T2           a             N1              M0
               Extremity                                   b          N0 or N1 or Nx     M0
               Cranial Parameningeal
               Other (includes trunk,
               retroperitoneum, etc.)

4              All                      T1 or T2           a or b     N0 or N1           M1


Tumor –

               T(site)1-     confined to anatomic site of origin
               (a)           ≤5 cm in diameter in size
               (b)           >5 cm in diameter in size
               T(site)2-      extension and/or fixation to surrounding tissue
               (a)           ≤5 cm in diameter in size
               (b)           >5 cm in diameter in size

Regional Nodes -

               No            regional nodes not clinically involved
               N1            regional nodes clinically involved by neoplasm
               Nx            preclude lymph node evaluation

Soft Tissue Sarcoma                                                                       Page 14 of 20
Management Guidelines
Metastasis –
       Mo                       no distant metastasis
       M1                       metastasis present

Brief definition for each stage is given below:

Stage I:                Favorable localized disease involving the orbit or head and neck
                        (excluding parameningeal sites), or nonbladder/nonprostate genitourinary

Stage II:               Localized disease of any unfavorable primary site not included in the stage
                        I category. Primary tumors must be less than 5 cm in diameter, and there
                        must be no regional nodal involvement.

Stage III:              Localized disease of any unfavorable primary site not included in the stage
                        I category. These patients differ from stage II patients by having primary
                        tumors greater than 5 cm and/or regional nodal involvement.

Stage IV:               Metastatic disease at diagnosis.


Local Therapy

               1. Complete resection with negative margins at diagnosis: no further local
               2. Microscopic residual disease: local radiation therapy
               3. Gross residual disease: give chemotherapy first and assess the response after 3
                  cycles. Score response to neoadjuvant chemotherapy as CR, PR, NR or
                  disease progression. If tumor is amenable to surgery, tumor should be resected
                  and tumor bed biopsied, otherwise all patients should receive radiation


Stage I

a.) Patient with completely resected paratesticular or orbital tumor: pulse intensive
    VA for 24 weeks.

b.) Patients with orbital disease with microscopic or gross residual disease will be
    treated with pulse intensive VA for 24 weeks, plus local radiation therapy.

c.) All other Stage I patients will be treated like Stage II.

Soft Tissue Sarcoma                                                                          Page 15 of 20
Management Guidelines
Stage II, III

a.) All these patients will be treated with V1A (vincristine, ifosfamide and actinomycin
    D) every three weeks for a total of 12 cycles.

b.) Radiation therapy to the primary tumor will be initiated at week 9 with cycle #3 of

c.) Patients with parameningeal disease, radiation therapy will be started at day #1 of
    cycle 1 chemotherapy.

Stage IV

Patient with metastatic disease will be treated with VIA. If there is a response, continue
the same chemotherapy for a maximum of 12 cycles.

Radiation Therapy for Rahbdomyosarcoma

Radical radiation therapy is indicated where radical surgery cannot be applied. All such
patients should be planned using CT. The initial target volume will receive 4,500 cGy
in 25 fractions over 5 weeks and a boosted volume of 900 cGy in 5 fractions depending
on tumor size, anatomical location and the presence or absence of critical or normal

Recurrent Disease or Disease Progression

Patients will be treated with cisplatin/carboplatin and etoposide. Evaluate the response
after two cycles. If partial or complete response, continue chemotherapy until
maximum response or toxicity.

Soft Tissue Sarcoma                                                                   Page 16 of 20
Management Guidelines
                                       Road Map/Flow Sheet
                                         Stage II and III

Eligibility Criteria:

I:             Orbit, head & neck (non parameningeal),
               GU (non bladder, non prostate) with FH and
               Node positive.

II:            Bladder/prostate, extremity parameningeal,
               Trunk: <5cm, node negative, FH.

               (week)        Treatment*
               (0)           VCR ________________, A _____________, I______________
               (1)           VCR ________________
               (2)           VCR ________________
               (3)           VCR ________________, A _____________, I______________
               (4)           VCR________________
               (5)           VCR ________________
               (6)           VCR ________________, A _____________, I _______________
               (7)           VCR ________________
               (8)           VCR _____________________________surgical/XRT evaluation
               (9)           VCR _________________, A ____________, I _______________
               (12)          VCR _________________, A* ___________, I _______________
               (15)          VCR _________________, A* ___________, I _______________
               (18)          VCR _________________, A ____________, I _______________
               (21)          VCR _________________, A ____________, I _______________
               (24)          VCR _________________, A ____________, I _______________
               (27)          VCR _________________, A ____________, I _______________
               (30)          VCR _________________, A ____________, I _______________
               (33)          VCR _________________, A ____________, I _______________
               (36)          VCR _________________, A ____________, I _______________

Doses:          VCR 1.5mg/m2 IV day 1 (top dose 2.0mg)
                ACTD 0.015mg/kg IV x 5 days (top dose 0.5mg)
                Ifosfamide 1.8gm/mv IV x 5 days with mesna
* Omit ACTD if receiving XRT
* If there is complete surgical resection - No XRT

Soft Tissue Sarcoma                                                             Page 17 of 20
Management Guidelines

       1. Deyrub AT, Weiss SW, Grading of soft tissue sarcomas: the challenge of
          providing precise information in an imprecise world. Histopathology 2006, 48:42.
       2. Brown, FM, Fletcher, CD. Problems in grading soft tissue sarcomas. Am J Clin
          Pathol 2000; 114 Suppl:S82.
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