2. All are true except
A. soft tissue comprises of mesenchymal
derivatives like fat, fibrous tissue, muscles,
cartilage, blood vessels and lymphatics
B. soft tissue sarcoma includes tumor arising
from mesodermal derivatives alone
C. though soft tissue contributes to large portion
of our dry tissue weight, it accounts only 1% of
all neoplasm
D. all STS develops de novo from adult cells
3.
4. All are true except
A. soft tissue comprises of mesenchymal
derivatives like fat, fibrous tissue, muscles,
cartilage, blood vessels and lymphatics
B. soft tissue sarcoma includes tumor arising
from mesodermal derivatives alone
C. though soft tissue contributes to large portion
of our dry tissue weight, it accounts only 1% of
all neoplasm
D. all STS develops de novo from adult cells
5. INTRODUCTION
• Soft tissue - includes supportive tissue of various
organs and the non epithelial, extra skeletal
structures exclusive of lympho hematopoietic
tissues
• non osseous soft tissues account for 75% of dry
TBW
• primary neoplasm of these connective tissues
are rare, accounting for 1% of adult and 15% of
pediatric malignancies
6. Tissue of origin
• Histologic, morphologic, experimental &
immunohistochemical data suggests, sarcomas
arise from primitive, multipotential
mesenchymal cells (MESODERM), which in the
course of neoplastic transformation
differentiate along one or more cell lines
• except malignant peripheral nerve sheath
tumors, Ewing’s Sa which are neuroectodermal
in origin
7. • Except for MPNST in NF1, STS do not seem to
result from progression or dedifferentiation of
a benign STT, they arise de novo
8. • HISTIOGENESIS IS NOT DEFINABLE except for
– subcutaneous lipoma
– leiomyoma
• Develops from sites that are devoid of adult
counterpart, ex:
– Liposarcoma develops from area that lacks
adipose tissue
– Rhadomyosarcoma develops from area that lacks
voluntary muscles
9. All are true except
A. STS incidence increases with increasing age
B. benign soft tissue tumors are more common
than malignant soft tissue tumors
C. synovial sarcoma arises from synovium
D. Rhabdomyosarcoma is more common in
children
E. Neuroma is a benign tumor of nerve
elements
10.
11. All are true except
A. STS incidence increases with increasing age
B. benign soft tissue tumors are more common
than malignant soft tissue tumors
C. synovial sarcoma arises from synovium
D. Rhabdomyosarcoma is more common in
children
E. Neuroma is a benign tumor of nerve
elements
12. INCIDENCE
• 1.4 and 5.0 cases / lakh population
– 1 – 2 /lakh at 15 years of age
– 6/lakh at 49 years of age
– 20/lakh at 80 years of age
• < 1% of overall human burden of malignant
tumors
• Mortality rate - 40% of the newly diagnosed
cases per year
13. EPIDEMIOLOGY
• Median age 65 years
• 2nd to 4th decades translocation-associated
sarcomas
• 5th to 6th decades in the complex sarcoma
types
14. Age & STS
• Benign : malignant STS = > 100 : 1
• Rhabdomyosarcoma, hemangioma,
neurofibroma, alveolar sarcoma - seen more
frequently in children and young adults.
• Synovial sarcoma arises in young adults.
• Malignant fibrous histiocytoma and
liposarcoma generally occur in older adults
15. SYNOVIAL SARCOMA
• Two kinds of cells - spindle or sarcomatous cell
& epithelial cells
• unique t(X;18)(p11;q11) chromosomal
translocation
• human multi potent mesenchymal stem cell
malignancy resulting from dysregulation of
self-renewal and differentiation capacities
driven by SS18-SSX fusion protein.
16. SYNOVIAL SARCOMA
• 8% of all soft tissue sarcomas
• 15–20% of cases in adolescents and young
adults
• peak of incidence is before the 30th birthday
• Males > females (1.2 : 1)
• Arises near the large joints of arm & leg
• documented in brain, prostate, and heart too
19. Risk factors for the development of soft tissue
sarcoma include all of the following except:
• A. Retinoblastoma
• B. Li-Fraumeni syndrome
• C. von Hippel-Lindau syndrome
• D. Lymphedema
• E. External beam radiation
20.
21. Risk factors for the development of soft tissue
sarcoma include all of the following except:
• A. Retinoblastoma
• B. Li-Fraumeni syndrome
• C. von Hippel-Lindau syndrome
• D. Lymphedema
• E. External beam radiation
22. A 51-year-old man has worked for 10 years in a factory
producing plastic pipe. He has noted weight loss, nausea, and
vomiting worsening over the past 5 months. On examination
he is afebrile. There is generalized muscle wasting. His sr. ALP-
405 U/L with AST 67 U/L, ALT 55 U/L, and TB- 1.2 mg/dL. An
abdominal CT scan reveals a 12 cm right liver lobe mass. Liver
biopsy reveals a neoplasm composed of spindle cells forming
irregular vascular channels. The cells demonstrate vimentin
+ve & cytokeratin negativity . What is the tumor? Its probable
etiology
A Benzene
B Cyclophosphamide
C Asbestos
D Vinyl chloride
26. Li-Fraumeni syndrome
• autosomal dominant
• germline mutation of the p53 tumor suppressor
gene, which is located on chromosome 17p13
• Includes
– soft tissue sarcoma (12% – 21%)
– breast cancer,
– osteosarcoma,
– brain tumors,
– acute leukemia,
– adrenocortical carcinoma, and germ cell tumors
• Before 45yrs of age
27. FAP
• AD
• Germline mutations in APC gene – chr 5q21
• Colorectal polyps
• Desmoid tumors (7.5% to 16%)
33. True statements?
A. radiation induced STS arises from the tumor
bed
B. they are low grade tumors
C. they are associated with better prognosis as
they are highly responsive to chemotherapy
D. Stewart Treves syndrome is a radiation
induced sarcoma
36. Prior radiation
• STS – m/c radiation associated tumor both in
general population and cancer susceptibility
syndromes
• Seen in survivors of
– Breast cancer
– Lymphoma
– Genito urinary tumors
– Head and neck cancer
38. Radiation
• Site : close to vicinity of radiotherapy fields
• Incomplete damage in normal tissues may
result in mutagenic response and disorganized
proliferation that can eventually trigger tumor
induction
• Poor prognosis (ex: PMFH 5yr DFS 44% vs
66%)
– Younger age of exposure
– Exposure to chemotherapy
– histology
39. • Post irradiation sarcomas are associated with
high-grade lesions,
• less responsive to chemotherapy than their de
novo counterparts
40. Lymphedema
• STEWART TREVES SYNDROME :
– lymphangiosarcoma in a post mastectomy post
irradiated lymphedematous arm
– 0.07% of patients undergoing ALND
– NOT A RADIATION INDUCED SARCOMA (cancer
develops both inside and outside the irradiated
field)
– Latency period of 10yrs after initial therapy
– Average survival – 19 months
• FILARIASIS
41. Lymphedema & STS
• Blocked lymphatics stimulates growth factors
and cytokines – proliferation of vessels and
lymphatics
• edematous tissue results in a regional immune
deficiency that enables mutant cells to escape
recognition by the host's immune surveillance
43. Trauma
• Controversial
• No proven causal relationship has been
proved yet
• An injury may be merely the factor that draws
attention to the presence of a mass, rather
than being a causative factor
• Rare exceptions include dermatofibrosarcoma
arising in a burn scar or fibrosarcomas arising
at old orthopaedic fracture sites or in the
surgical scars of patients with Gardner's
syndrome.
44. Infections
• Viral factors
– avian sarcoma virus, (Rous virus)
– HIV, HHV-8 being implicated in Kaposi's sarcoma.
• It is unclear, however, whether Kaposi's
sarcoma is caused by the virus alone or by a
combination of viral effect and immunologic
suppression (probably the latter).
45. Foreign body
• Rare human cases have also been described,
involving surgical implants, plastic, bullets,
surgical sponges, bone wax, or Teflon-Dacron
prostheses.
• The largest study was done by Engel* and
colleagues, who looked at the rate of sarcoma
in thousands of women with breast implants
but did not find a statistically significant
increase
* Human breast sarcoma and human breast implantation: a time trend analysis based on
SEER data (1973-1990).Engel A, Lamm SH, Lai SH,J Clin Epidemiol. 1995 Apr; 48(4):539-44
46. False statement?
A. most common site of STS is extremity
B. most common STT is lipoma
C. most common STS is liposarcoma
D. most common STS of extremity is
liposarcoma
E. most common STS of viscera is GIST
F. most common STS of retroperitoneum is
liposarcoma
63. Tumors with limited metastatic
potential
• desmoid,
• atypical lipomatous tumor (also called well
differentiated liposarcoma),
• dermatofibrosarcoma protuberans,and
• solitary fibrous tumor.
64. Tumors with an intermediate risk of
metastatic spread
• large myxoid component and include myxoid
liposarcoma myxofibrosarcoma,
• extraskeletal myxoid chondrosarcoma.
66. • Histologic type is an important prognostic
factor
– Ex: increase in myogenic differentiation increases
risk of metastasis
• low-grade lesions < 15% chance of metastasis
• high-grade lesions > 15% chance of metastasis
67. • Which is the most common route of
metastasis for STS?
• What is the most common site of metastasis
for a STS in lower limb?
72. • What are the clinical presentation of an
extremity STS?
73. clinical presentation-extremity STS
• painless mass
• 33% complain of pain (indicates poor prognosis)
• pain - often the first complaint in patients with
MPNST, which tend to spread along nerve
bundles
• rapidly growing or aggressive tumor subtypes
are more likely to be painful
• systemic symptoms such as fever, weight loss,
or malaise (uncommon)
• tumor impingement on bone or neurovascular
bundles produces pain, edema, and swelling
74. • Of the patients who present with pain, about
half eventually undergo amputation
• Rapidly increasing size
• sudden appearance of a new large mass
• sudden appearance of pain, particularly in a
lesion that was previously painless, suggests
malignancy
75. Clinical presentation - intra abdominal
sarcoma
• Asymptomatic abdominal mass
• Pain
• GI bleeding
• Obstruction
• Neurological symptoms due to invasion of
retroperitoneal invasion/ pressure
• Weight loss(uncommon)
76. • Which kind of lesion hints towards
malignancy?
77. • tumor larger than 5 cm
• located deep to the deep fascia
• rapidly growing, change in color
• painful or tender
• occurring in older individuals
78. A 27-year-old woman in excellent health has a routine health
maintenance examination. No h/o trauma. A 2 cm firm, rounded mass is
palpable beneath the skin of the left forearm. She has no difficulty using
the arm and there is no associated pain with the mass, either in
movement or on palpation. No associated LNP. The overlying skin
appears normal. The mass does not change in size over the next year.
Which of the following neoplasms is she most likely to have?
A Metastatic carcinoma
B Melanoma
C abscess
D Lipoma
E hematoma
79.
80. A 27-year-old woman in excellent health has a routine health
maintenance examination. No h/o trauma. A 2 cm firm, rounded mass is
palpable beneath the skin of the left forearm. She has no difficulty using
the arm and there is no associated pain with the mass, either in
movement or on palpation. No associated LNP. The overlying skin
appears normal. The mass does not change in size over the next year.
Which of the following neoplasm is she most likely to have?
A Metastatic carcinoma
B Melanoma
C abscess
D Lipoma
E hematoma
83. DD for RP STS
• Pseudocyst of pancreas
• Cystic lesions of pancreas
• Mesentric cyst
• Aortic aneurysm
• Secondary RP lymph node deposits
• RP hematoma
• RP abscess, cold abscess
• PCKD, renal malignancies and cysts
84. A 37-year-old woman has developed a 6-cm mass
on her anterior thigh over the past 10 months.
The mass appears to be fixed to the underlying
muscle, but the overlying skin is movable. Which
of the following is the most appropriate next step
in her management?
A. AK amputation
B. Excisional biopsy
C. Incisional biopsy
D. Bone scan
E. Abdominal CT
85.
86. A 37-year-old woman has developed a 6-cm mass
on her anterior thigh over the past 10 months. The
mass appears to be fixed to the underlying muscle,
but the overlying skin is movable. Which of the
following is the most appropriate next step in her
management?
A. AK amputation
B. Excisional biopsy
C. Incisional biopsy
D. Bone scan
E. Abdominal CT
87. A 50-year-old man has felt vague abdominal discomfort for the
past 4 months. There is no history of altered bowel and bladder
habits. On physical examination he has no generalized
lymphadenopathy, no organomegaly or free fluid is present.
Bowel sounds are present. A non ballottable retro peritoneal lump
of size 20 cm occupying the right lumbar region found on further
examination. A stool specimen tested for occult blood is negative.
Which of the following neoplasms is this man most likely to have?
What is the next logical step of investigation?
A Melanoma
B Adenocarcinoma
C Lymphoma
D Liposarcoma
90. A 50-year-old man has felt vague abdominal discomfort for the
past 4 months. There is no history of altered bowel and bladder
habits. On physical examination he has no generalized
lymphadenopathy, no organomegaly or free fluid is present.
Bowel sounds are present. A non ballottable retro peritoneal lump
of size 20 cm occupying the right lumbar region found on further
examination. A stool specimen tested for occult blood is negative.
Which of the following neoplasms is this man most likely to have?
What is the next logical step of investigation?
A Melanoma
B Adenocarcinoma
C Lymphoma
D Liposarcoma
92. IMAGING before BIOPSY
• all imaging studies prior to any biopsy,
because :
• it is impossible to accurately place a biopsy site
that will be consistent with future limb salvage
procedures without detailed information about
the lesion and its relationship to the normal
anatomy that is now distorted by the mass
• biopsy inherently causes hemorrhage, edema
and other changes that can interfere with
interpretation of any subsequent imaging
93. MRI
• imaging of choice for primary extremity
sarcoma
• enhances the contrast between tumor &
adjacent structures & provides excellent
three-dimensional definition of fascial planes
• MRI accurately defines tumor size, multiplicity,
and location
• superior soft tissue contrast resolution
• better delineation of neurovascular bundle
94. MRI
• T1 weighted image – for disease extent
• T2 weighted image – for peritumoral edema
95.
96.
97.
98.
99. Drawbacks of MRI
• Cannot reliably predict histologic diagnosis
and biologic behavior unlike PET CT
• Cannot be used in pts. with pacemakers, other
metallic implants that would generate a lot of
magnetic interference
• air-tissue interface and motion artifacts -
degrades MRI quality
• Lengthy time of study
100. CT SCAN
• For the primary intra abdominal and chest
sarcoma, a spiral CT scan is preferable over MRI
• with spiral CT - both primary and metastasis
can be assessed in a single study
• bone involvement (though rare) and
calcification is better appreciated in CT
101. • CT is a predominantly anatomic imaging
modality.
• It is limited in the differentiation of subtle soft
tissue differences.
• CT plays mainly a complementary role to MRI
in evaluation of the extent of tumor.
103. METASTASIS
• Extremities :
– Low grade /small superficial high grade – CXR
– High grade/deep lesions – CT chest
• Intra abdominal sarcoma : CT
• CT chest less sensitive for pulmonary
metastasis < 1cm in size
• Identifies only 60% lesions < 6mm
104. METASTASIS
• CT chest adds little clinical benefit when risk
for pulmonary metastasis is low
• In pts. In whom CXR are difficult to interpret
due to scarring , emphysema – CT chest is
indicated
105. • What is the role of PET CT in metastatic work
up?
106. Role of PET
• standard uptake value ( SUV) in 18 F fluoro
deoxyglucose (FDG) PET has been associated
with histo pathological grade, cellularity,
mitotic activity, MIB labeling index, and p53
overexpression and hence grade
• PET assessment of proliferation with the
thymidine analogue 3 ' -deoxy-3 ' (18F) fluoro
thymidine correlated significantly with tumor
grade and was superior to traditional FDG-PET
for the grading of sarcoma
107. Role of PET CT in metastasis
• PET is an alternative for CT showing suspicious
pulmonary lesions and lesions < 1cm
108. • What is the role of PET CT in monitoring
tumor response?
109. Role of PET CT in monitoring of tumor
response
• primary extremity sarcomas, the association with
outcome after treatment with neoadjuvant
chemotherapy was stronger for PET response
than for radiologic tumor size changes
• Similar results have been found for pediatric
sarcomas.
• early prediction of chemo sensitivity in pts. with
STS who received NACT and has been found to
have an accuracy of 83 % and a PPV for
responders of 92 %
111. Drawbacks of PET CT
• PET though sensitive lacks specificity
• Low grade sarcoma & certain high grade
tumors like round cell sarcoma are not FDG
avid
• False positive in benign conditions like
granulomatous inflammation
112. • Bone scans have no role in the preoperative
investigation of a soft tissue sarcoma
113. • Is pre operative biopsy a must for abdominal
sarcoma?
114. • What is indication for biopsy in truncal STS?
115. Role of biopsy in TRUNCAL STS
• Usually diagnosis is clear without biopsy
• FNA biopsy and CT guided core biopsy limited
role in routine diagnosis
• Pre operative biopsy is only indicated in
– patients with distant metastasis
– tumor is unresectable (planning to start
neoadjuvant CT/RT to downstage the disease)
117. • Is pre op biopsy a must for extremity
sarcoma?
118. Diagnostic biopsy in extremity STS
• Recommended prior to definitive treatment in
all lesions
– Deep seated lesions
– Superficial lesions > 5cm except subcutaneous
lipoma
• any soft-tissue mass in an adult that is
enlarging (even if asymptomatic), is larger
than 5 cm, or persists beyond 4 to 6 weeks
should be biopsied
121. • Which is better, incisional or core cut or
FNAC?
122. INCISIONAL BIOPSY
• Excisional biopsy > incisional biopsy > core cut
biopsy > frozen section
• should be performed at centres where pt is
planned to get operated
• Incision should be placed along the axis of limb
• Incision should be placed such that the entire
tract can be excised along with the tumor
during definitive surgery
• No tissue flaps to be raised
• Complete hemostasis to be achieved
123. ROLE OF CORE CUT BIOPSY
• Accuracy lower than incisional biopsy
• Easy to perform, low cost, low complication
rate, can be repeated readily
• Tumor characteristics can be identified pre op
– Histologic type
– Histologic grade
– Immunohistochemistry
– Cytogenetics
• Enables planning of optimal treatment plan &
extent of surgery
124. FROZEN SECTION
• Only for diagnosis of malignancy intra
operatively (unsuspected pre operatively)
• Not accurate for subtypes and grade
126. ROLE OF FNAC
• Only for confirmation of recurrence rather
than primary diagnosis
• Limited sampling
• Lack of tissue architecture
• Difficult molecular diagnostic studies
• Not representative
• Difficult in grading and subtyping
129. AJCC staging
• Correlates for stage and disease specific
survival for extremity sarcoma
• Does not adequately correlate for intra
abdominal sarcoma
131. Changes in AJCC 7th edition
• Excludes:
– GIST
– Desmoid tumor
– Kaposi sarcoma
– Infantile fibrosarcoma
• Adds:
– Angiosarcoma
– Extraskeletal Ewing’s sarcoma
– Dermatofibrosarcoma protuberans
• Reclassifies N1 from stage 4 to 3
• 4 grade to 3 grade system
132. Primary Tumor (T)
• TX Primary tumor cannot be assessed
• T0 No evidence of primary tumor
• T1 Tumor 5 cm or less in greatest dimension
• T1a Superficial tumor
• T1b Deep tumor
• T2 Tumor more than 5 cm in greatest dimension
• T2a Superficial tumor
• T2b Deep tumor
136. Grading systems
• National Cancer
Institute grading system
• Comprises of
– Histology
– Necrosis
– Mitosis/HPF
• Federation Nationale
des Centres de Lutte
Contre le Cancer
(FNCLCC) grading
system
• Comprises of
– Tumor differentiation
– Mitotic count
– Tumor necrosis
138. • histologic grade is determined by assessment
of several features:
• (1) degree of cellularity,
• (2) cellular pleomorphism or anaplasia,
• (3) mitotic activity,
• (4) degree of necrosis, and
• (5) expansive or infiltrative and invasive
growth
141. DEFINITION
• Superficial is defined as lack of any
involvement of the superficial investing
muscular fascia in extremity or trunk lesions
• Deep is defined as partly or completely within
one or more muscle groups, deep to fascia
within the extremity.
• Intra thoracic, intra-abdominal,
retroperitoneal, and visceral lesions are
considered to be deep lesions
144. Prognostic factors
• Age >50yrs
• Size > 8cm
• Vascular invasion
• Local infiltration
• Deep location
• High grade tumors
• Recurrent disease
• Non lipomatous histology
145. Clinical course
• clinical course depends on
– histology
– aggressiveness of the original tumor
• varies between the major histologic categories
& also among individual lesions of the same
type.
146. • How will you treat a patient with stage 1 STS?
147.
148. • Surgery with intent to obtain negative margin
• Surgery is definitive if margins are > 1cm,
fascial plane is intact
• If margins < 1cm, fascial plane is breached –
re resection is necessary
Stage 1
149. • How will you treat a patient with stage 2 or 3
STS?
150. Stage 2 & 3
• Pre op chemoradiation increases:
– OS
– DFS
– LOCAL CONTROL RATES
• To be considered in high grade tumors (>8 –
10 cm)
• Post operative ERBT improves local control in
patients with high grade lesions
151. • How will you manage patient with regional
lymphadenopathy?
152. Lymph node disease
• Radical lymphadenectomy – long term survival
benefit ( median survival 4.3 vs 16.3 months)
when compared with control
• regional nodal involvement is an important
prognosticator of survival
• patients with multiple positive nodes, a single
lymph node, and distant metastatic disease all
have similar survival
153. • What is the treatment approach for
unresectable STS?
154. Unresectable disease
• Primarily RT / CRT/ CT
then
• If resectable –
– surgery
– f/b RT (if not previously irradiated) with/without post
op CT
• If unresectable / resectable with adverse
functional outcomes
– Asymptomatic: observation
– Symptomatic: CT/ palliative surgery/ amputation/ best
supportive care/ induction into trial
155. Regional limb therapy
• Isolated limb perfusion/ isolated limb infusion
can be considered as limb saving procedures
in unresectable intermediary / high grade STS
• TNF alpha
• Melphalan
• Doxorubicin
• Dactinomycin
156. • How will you treat a stage 4 metastatic
disease ?
157. Stage 4 – synchronous metastatic dis
• Poor prognosis
• No DF interval
• Clinical trial is one of the preferred treatment
158. LIMITED METASTASIS
• Limited organ
• Limited tumor bulk- amenable to local therapy
are managed in line with stage 2 or 3 disease
159. DISSEMINATED METASTASIS
• If asymptomatic: watchful waiting is a
reasonable option (esp. for minimal tumor
bulk , ex: sub centrimetric pulmonary nodule)
• Symptomatic : palliative RT/ Surgery/ CT
• Ablation procedures – RFA / cryotherapy
160. • What is the recommended surveillance
protocol after treatment?
161. surveillance
H & P IMAGING
STAGE 1 every 3 to 6 months for
2 to 3 yrs and then
annually
chest imaging
every 6 to 12
months
STAGE
2 , 3, 4
every 3 to 6 months for 2 to 3 yrs
then every 6 months for next 2 years
and then annually
162. • What is the role of surgery in STS ?
• Which is the preferred surgical approach ?
Limb saving or amputation?
163. Aim of surgery
• minimizing local recurrence,
• maximizing function, and
• Improving overall survival
164. ROLE OF SURGERY- extremity sarcoma
• surgery remains the principal therapeutic
modality in soft tissue sarcoma, the extent of
surgery required, along with the optimum
combination of radiotherapy and
chemotherapy, remains controversial.
165. Limb sparing surgery
• Wide en bloc resection
• obtain a 1- to 2-cm margin of uninvolved
tissue in all directions
• most extensive resection is clearly
amputation.
• This should be only rarely indicated in soft
tissue sarcoma because limb-sparing
operations are possible in at least 95 % of
patients with extremity sarcoma.
166. Limb saving procedure vs amputation
• The issue of amputation versus limb-sparing
surgery for extremity lesions has been
addressed by a prospective, randomized trial
at the NCI with well over 10 years' follow-up .
• Limb sparing surgery with RT for high grade
STS showed local recurrence of 15% and no
difference in OS & DFS as compared to
amputation
167. • The limiting factor for LSS(limb saving surgery)
is usually neurovascular or, occasionally, bony
juxtaposition.
• very few STS invades bone directly , bone
resection is rarely needed
• Few STS involve the skin, and so major skin
resection should be limited.
168. • What is the contra indication for limb saving
surgery?
169. Contraindications for limb sparing
surgery
• margin-free resection is impossible and/or
when radiation therapy is risky
• if major vessels and nerves are involved at the
site where resection would critically
compromise function
172. Only surgery
• surgery alone (adequate wide excision with a
good 1 cm cuff of surrounding fat and muscle)
can be done in
– subcutaneous or intramuscular high-grade sarcoma
smaller than 5 cm
– low-grade sarcoma of any size
• low-grade histologic types (atypical lipomas and
well-differentiated liposarcoma of the
extremities), margins < 1cm is enough(minimal
surrounding margin) , provided excision is
complete
173. • Sarcomas tend to expand and compress tissue
planes, which produces a pseudo capsule
comprising normal tissue interlaced with tumor
tissue.
• When surgical resection does not include the
plane of tissue adjacent to the pseudo capsule,
the local recurrence rates are between 33 and
66%.
• Wide local resection with a margin of normal
tissue surrounding the tumor is associated with
better results; local recurrence rates of
approximately 10 to 30%
177. • Positive surgical margin is a strong predictor of
local recurrence for patients with extremity
STS
• Risk of patient to develop local recurrence
with positive margin is 3.76 times than those
with negative margin (6yr follow up – 38% vs
12%)
178. Role of surgery – intra abdominal
sarcoma
• OS , DFS , Median survival time depends upon
– complete surgical resection (preferably R0)
– grade of the lesion
• RP sarcomas are large, making it difficult to
obtain adequate margins of resection
• mandates a multi modality treatment:
combined chemotherapy and radiotherapy as
a neoadjuvant to surgery.
• Surgery remains the mainstay of treatment
179. • proximity of normal organs such as small bowel,
large bowel, kidney, and liver makes delivery of
therapeutic doses of radiation therapy either
difficult or impossible
• retroperitoneum is a site that may be particularly
suited to preoperative radiotherapy for sarcoma,
because the tumor has frequently displaced
bowel from the target volume
• Postoperatively, in contrast, loops of bowel are
frequently tethered or fixed within the target
area.
180. • The most common histologic types
encountered in the retroperitoneal location
(well-differentiated liposarcoma,
dedifferentiated liposarcoma,
leiomyosarcoma, and MPNST) are typically not
very responsive to conventional
chemotherapy, and chemotherapy has never
been shown to improve survival
181. • What are the particulars or details you will
ensure in a pathological report after STS
surgery?
182. Pathological assessment of Sa
specimens
• Organ , site and operative procedure
• Primary diagnosis (WHO nomenclature)
• Depth of tumor (superficial/deep)
• Size of tumor
• Histologic grade(atleast low / high grade)
• Necrosis (+/-, micro/macroscopic, %)
• Status of margin (uninvolved, involved, close)
183. Pathological assessment of Sa
specimens
• Status of lymph nodes (site, no. examined, no. of
+ve nodes,)
• Results of ancillary study(electron microscopy,
IHC, cytogenetics)
• Additional tumor factors of potential clinical
value (mitotic rate, vascular invasion,character of
tumor margin- well circumscribed/ infiltrative,
inflammatory infiltrate – type & extent)
• TNM stage
184. • What is the indication for adjuvant
radiotherapy?
185. Role of radiation
• adjuvant radiation therapy should be added to
the surgical resection to reduce the probability
of local failure for :
– deep,
– greater than 5 cm,
– high grade sarcomas
– if the excision margin is close,
• with extra muscular involvement
• local recurrence would necessitate amputation
• the sacrifice of a major neurovascular bundle
186. Goals of adjuvant RT
• enhance local control
• preserve function
• achieve acceptable cosmesis by contributing
to tissue preservation
187. • What are the various RT modalities applicable
in STS?
189. ERBT
POST OP RT
• allows for sterilization of microscopic nests of
residual disease without the need to postpone
surgery
• enhance local control compared to conservative
surgery alone.
• Though adjuvant RT results in
– significantly worse limb strength
– edema
– Loss of range of motion
• these deficits were often transient and had few
measurable effects on activities of daily life or
global quality of life.
191. Post op RT
• Advantage : entire pathology specimen & final
margins are available for pathologic analysis,
helping to determine the need for further
therapy.
• Limitation : is that the target is less precisely
defined, and therefore volume is larger and dose
is higher, resulting in greater late tissue morbidity
• More hypoxic tissue – radiobiological
disadvantage
• High incidence of delayed toxicity(irreversible)
193. Preoperative EBRT
• treatment volume well defined
• blood supply is intact
• intact vascular supply and relative absence of
actively proliferating tumor clonogens and radio
resistant hypoxic cells decrease the dose needed
compared to post op RT(radiobiological advantage)
• Reduced treatment time
• Tumor down staging
• irradiation increases the risk of acute wound
complications upon surgery(reversible)
195. Pre op RT Post op RT
Local control 93% 92%
Metastatic free
relapse survival
67% 69%
5yr overall survival 73% 67%
5yr cause specific
survival
78% 73%
196. Time Pre op RT Post op RT
6 wks Inferior function, worst
body pain score
3 – 12
months
No difference in pain rating
scores
2 year • deteriorating late
tissue sequale
(fibrosis & edema)
• increased bone
fracture
197.
198.
199.
200.
201. • What is IMRT? What are its advantage? When
is it indicated?
202. IMRT
• IMRT may be particularly applicable to
complex anatomic volumes such as
retroperitoneal sarcoma juxtapositioned to
liver or paraspinal lesions, for which conformal
avoidance of liver or of kidney and spinal cord
is necessary.
• Avoidance of bone is also possible and may
reduce the risk of the radiation-induced
fracture of weight- bearing bone
203. • Superiority of IMRT over conventional EBRT
due to a reduction in late toxicity(bone
fracture)
• the 5-year local control rate for IMRT in one
study was very similar to those with
conventional EBRT in both arms of the trial
that compared preoperative to postoperative
radiotherapy
208. • RT is not a substitute for definitive surgical
resection with negative margins and re
resection to negative margins is preferable
• Pre op dose is 50Gy
• Post op RT is recommended for all patients
with positive margins
209. Post op RT in patients with positive
margins who received pre op RT
R1 R2
ERBT 16 – 18 Gy 20 – 26Gy
BRACHYTHERAPY LDR – 16 TO 26Gy HDR -14 TO 24Gy
IORT 10 – 12.5Gy 15Gy
210. Post op RT in patients with positive
margins who has not received pre op
RT
• ERBT – 50 Gy irrespective of R1 / R2 in 25 fractions
• IORT – 10 – 16 f/b 50Gy ERBT
• ERBT is delivered to target tissue after surgical;
healing is complete after 3 – 8 weeks to allow
acute radiation changes to subside
• Conventional fractionation is usually 1.8 to 2 Gy
per day
• The optimal radiation margin is not well defined: a
margin of 5 to 7 cm is standard, but some centers
advocate wider margins for tumors larger than 15
cm
216. BRT
• BRT is an attractive approach because patients
usually complete all their treatment in about 2
weeks compared to 6 to 7 weeks with EBRT
• The rapid dose fall-off with BRT usually spares
more normal tissue than EBRT, except when
precision techniques such as IMRT are used.
• Drawback : unlike in postoperative irradiation,
no attempts are made to treat large margins
or to include the scar and the drainage site
218. • Of importance, the catheters are loaded no
sooner than the sixth postoperative day to
allow enough time for wound healing.
• most commonly used isotope
– low-dose-rate 192Ir
– high-activity 125I is occasionally used in young
patients or to protect the gonads.
• High-dose rate 192Ir has been advocated to
take advantage of its radiation safety and
dose-optimization capabilities
219. When not to omit RT
• positive surgical margin of resection(even for
smaller lesions < 5cm)
• Whether pt. had prior unplanned excision
(i.e., excision without adequate preoperative
staging or consideration of the need to
remove normal tissue around tumor)
220. Unplanned resection
• An intralesional or an unplanned microscopically
positive margin is associated with high recurrence
rates, despite adjuvant radiation therapy
• patients who have undergone previous surgery
with +ve margins should receive preoperative
radiation and a complete resection of the
previous surgical bed if this is feasible.
• Even with this aggressive treatment, these
patients still have inferior outcomes,
underscoring the importance of appropriate
diagnosis and management by the initial treating
physician.
221. • patients with positive margins, radiotherapy
reduces the risk of recurrence compared to no
adjuvant treatments, although their 5 -year
local recurrence rates continue to be higher
than those of patients with negative margins.
• Surgery with negative margin is the standard
of care
222. • What is the role of chemotherapy?
• What is the chemotherapeutic agent of
choice?
• What is the most common regimen used?
223. Role of chemotherapy
• anthracyclines are the agents most active against
metastatic sarcoma
• A question that remains unanswered is the timing
of chemotherapy with respect to surgery and
radiation.
• Chemotherapy was started within 10 weeks of
surgery if radiation was used or within 6 weeks if
no radiation was used
• Preoperative chemotherapy has been very
successful in the management of predominantly
pediatric sarcomas such as Ewing sarcoma and
osteo sarcoma.
224. Advantages of NACT
• makes subsequent surgery easier
• potentially treats micro metastatic disease early
before acquisition of resistance (before surgery
the primary vasculature is still intact for) drug
delivery
• Preoperative chemotherapy response can guide
postoperative treatment based on pathologic
review of the tissue response after chemotherapy
• In experimental models, preoperative
chemotherapy eliminates a postoperative surge
in growth of metastases noted after resection of
primary tumors
225. • Doxorubicin-most active at doses of 75 mg/m2
@ 48- to 96-h continuous infusion
• Ifosfamide - 10 g/m2 or higher when
administered as a 2- to 3-h infusion has a
greater efficacy as opposed to a 24-h infusion
226. CT response rates
• response rates according to histology
– malignant fibrous histiocytoma (MFH) 69%,
– synovial sarcoma 88%,
– unclassified sarcomas 60%,
– non-GI–leiomyosarcomas 50%,
– liposarcomas 56%,
– angiosarcomas 83%,
– neurogenic sarcomas 40%,
– other miscellaneous histologies 45%
• Hence, sensitivity to chemotherapy depends on the
histologic type of sarcoma underscores the importance
of proper histologic diagnosis in determining prognosis
227. Various modalities
• Intra venous CT
– Single agent
– Combination therapy
• Intra arterial CT
• Hyperthermia and limb perfusion
• Combined chemoradiotherapy
– MAID(doxorubicin,ifosfamide,mesna,dacarbazine)
interdigitated with two 22 Gy courses of radiation (11
fractions each)
• Concurrent chemotherapy and definitive
radiotherapy for unresectable STS
228. • How will you manage a patient with recurrent
STS?
229. RECURRENCE
• Difficult to treat
• More likely to recur
– Due to prior contamination of field
– Intrinsically aggressive tumor biology
• Factors:
– Size
– timing
230. • Repeat resection is the treatment of choice for
locally recurrent soft tissue sarcoma in almost
any site that is amenable to low-morbidity
surgical resection.
• When surgical resection can be achieved, then
adjuvant radiation therapy should be
considered in the vast majority of patients
with recurrent disease.
231. RP Sa recurrence
• Isolated local recurrence is most common following
complete resection of a primary retroperitoneal
liposarcoma .
• Retroperitoneal recurrences are often detected on
routine screening with imaging, or patients may present
with pain or nonspecific symptoms.
• After workup to determine the extent of disease,
patients with isolated local recurrence should be
carefully evaluated for re-resection.
• As current chemotherapy is ineffective for the majority
of patients with liposarcoma and toxicity limits
adequate dosing by radiation therapy, complete surgical
resection remains the most effective treatment
modality.
232. RP Sa recurrence
• Despite aggressive operative management, patients
with a local recurrence growth rate greater than 1 cm
per month had poor outcomes that were similar to
those of patients who were not treated with resection.
• Only patients with local recurrence growth rates of less
than 0.9 cm per month had improved survival following
aggressive resection of the local recurrence.
• Based on these results, for patients presenting with
asymptomatic local recurrence and growth rates equal
to or exceeding 1cm per month, the recommendation
now is treatment with systemic chemotherapy or novel
targeted therapy trials.
233. RP Sa recurrence
• Surgery is only considered in this subgroup if they
develop symptoms, such as obstruction or bleeding,
that do not respond to medical management.
• If the local recurrence growth rate is less than 1 cm per
month, immediate surgery is recommended for all
symptomatic patients and for asymptomatic patients
whose local recurrence is impinging on critical
structures (particularly if further growth may result in
the need to sacrifice critical organs) or has a solid
appearance on CT scan (suspicious for
dedifferentiation)
234. RP Sa recurrence
• Debulking, however, has limited overall value
in terms of long-term survival of patients with
recurrent lesions.
235. • A 68-year-old male being treated with
anticoagulants for atrial fibrillation presented
with a soft tissue mass.
• mass was managed as a spontaneous
hematoma with percutaneous drainage for
several months.
236. • After the lesion became fungating , MR
images were obtained. Subsequent biopsy
confirmed malignant fibrous histiocytoma. A
partial hemipelvectomy was performed and
systemic staging investigations identified
metastatic lung lesions.
