Soft tissue sarcoma, surgery based ppt

1. Soft Tissue Sarcomas
October 12, 2018

2. Introduction
 Rare: only 8300 new cases annually in U.S.
 3900 die annually from STS
 Mesodermal origin

3. Location and Type

5.  Sarcomas are malignant tumors that arise from
skeletal
 and extra-skeletal connective tissue, mesenchymal
cells
 including:
  adipose tissue
  bone
  cartilage
  smooth muscle including vascular smooth muscle
  skeletal muscle

10. Dermatofibrosarcoma

11.  64 y/o male with increasing abdominal girth

12. Liposarcoma

13. Etiology
 h/o Radiation therapy increases grade of tumors and
risk for metastasis
 Chemical exposure
 Thorotrast, vinyl chloride, arsenic for hepatic angiosarcoma
 Genetic syndromes
 Neurofibromatosis – nerve sheath tumors
 Familial gastrointestinal stromal tumor syndrome – KIT
mutation
 Skin hyperpigmentation, uticaria, cutaneous mast cell dx

14.  Neurofibromatosis is a disease that usually runs
in families and is characterized by
 many neurofibromas (benign tumors that form in
nerves under the skin and in other
 parts of the body). It is also known as von
Recklinghausen disease. It is caused by a
 defect (mutation) in a gene called NF1. About
5% of people with neurofibromatosis
 will develop a malignant peripheral nerve sheath
tumor in a neurofibroma

15.  Gardner syndrome is a disease caused by
defects in the gene APC. People with this
 syndrome get many polyps in the colon (and
intestines) and have a high risk of
 getting colon cancer. It also causes
musculoaponeurotic fibromatosis (also called
 desmoid tumors). Some experts consider
desmoid tumors a slow-growing (low-grade)
 type of fibrosarcoma.

16.  Li-Fraumeni syndrome is caused by inherited
defects in the gene TP53. People
 affected by this syndrome have a high risk of
cancer, such as breast cancer, brain
 tumors, and sarcomas. People with this
syndrome are sensitive to the cancer-causing
 effects of radiation— if their cancer is treated
with radiation, they have a very high
 chance of developing a new cancer in the part of
the body that received the radiation

17.  Retinoblastoma is an eye cancer of children
that can be caused by inherited defects in
 the gene RB1. Children with the inherited
form of retinoblastoma also have an
 increased risk of developing bone or soft
tissue sarcomas

18.  Werner syndrome is caused by defects in the gene
RECQL2. Children with this syndrome have problems like
those seen in the elderly. These include clogged heart
arteries (arteriosclerosis) which can lead to heart attacks,
cataracts, and skin changes.
 They also have an increased risk of cancer, including soft
tissue sarcomas.
 · Gorlin syndrome, also called nevoid basal cell
carcinoma syndrome, is caused by defects in the PTC
gene. People with this syndrome have a high risk of
developing

19.  Immunohistochemistry
 Cytogenetics
 Fluorescent in situ hybridization (FISH)
 Reverse transcription polymerase chain
reaction (RT-PCR):

20. Classification
 Soft tissue and bone
 viscera (gastrointestinal, genitourinary, and gynecologic organs)
 nonvisceral soft tissues (muscle, tendon, adipose, pleura, and
connective tissue)
 By differentiation (usually with IHC staining)
 adipocytic tumors
 fibroblastic/myofibroblastic tumors
 fibrohistiocytic tumors
 smooth muscle tumors
 pericytic (perivascular) tumors
 primitive neuroectodermal tumors (PNETs)
 skeletal muscle tumors
 vascular tumors
 osseous tumors
 tumors of uncertain differentiation

23.  (i) increasing in size,
 (ii) size >5 cm,
 (iii) deep to the deep fascia,
 (iv) painful.
 (v) > 6 weeks duration

26. Biopsy
 Most present as painless mass leading to delayed
diagnosis as lipoma or hematoma
 Core needle biopsy guided by palpation or by image
guidance if not palpable
 Few cases of tumor seeding with closed biopsy so some
recommend tattooing site for later excision with specimen
 Excisional biopsy for superficial small lesions if
needle biopsy non-diagnostic
 Incision biopsy
 Longitudinal incision without tissue flaps with meticulous
hemostasis to prevent tumor seeding in hematomas
 Send biopsy fresh and orientated

28. Tumor seeding after biopsy

29. Imaging
 MRI
 For extremity masses
 Gives good delineation between muscle, tumor and
blood vessels
 CT for abdominal and retroperitoneal
 PET
 May help determine high vs. low grade
 May be helpful in recurrences

30. MRI
sagittal & axial

32. STAGING

35. Staging
 AJCC/UICC Staging System for Soft Tissue Sarcomas
 T1: <5cm
– T1a: superficial to muscular fascia
– T1b: Deep to muscular fascia
 T2: >5cm
– T2a: superficial to muscular fascia
– T2b: Deep to muscular fascia
 N1: Regional nodal involvement
 Grading
– G1: Well-differentiated
– G2: Moderately differentiated
– G3: Poorly differentiated
– G4: Undifferentiated

36. Staging
Stage IA G1,2 T1a,b N0 M0
Stage IB G2,2 T2a,b N0 M0
Stage IIA G3,4 T1a,b N0 M0
Stage IIB G3,4 T2a N0 M0
Stage III G3,4 T2b N0 M0
Stage IV Any G Any T N1 M1
**Does not take into account extremity vs. visceral
Staging system predicts survival and risk of metastasis, but not local recurrence

38. Survival by stage

39. Relative risk for recurrence and
survival
 Age >50 years 1.6
 Local recurrence at presentation 2.0
 Microscopically positive margin 1.8
 Size 5.0–10.0 cm 1.9
 Size > 10.0 cm 1.5
 High-grade 4.3
 Deep location 2.5
 Local recurrence 1.5

41. Surgery
 Limb-sparing vs amputation
 Comparison study with post-op radiation in limb sparing
showed no difference in survival
 Amputation still may be indicated for
neurovascular or bone involvement

42. EXCISION

53. Resection
 Arbitrary 2 cm margin if no plan for post-op
radiotherapy
 Negative margins may be adequate for post-
op radiation therapy
 Presence of positive margins increases local recurrence
by 10-15%
 No need for lymph node dissection as only 2-
3% have nodal metastasis

57. Radiotherapy
 Postoperative radiotherapy is recommended
following surgical resection of the primary
tumour for the majority of patients with high-
grade tumours, and for selected patients with
large or marginally excised, low-grade
tumours
 The recommended dose for postoperative
radiotherapy is 60–66Gy; in 2Gy per fraction

58. Perioperative radiotherapy
 Pre-operative radiotherapy is advantageous
in termsof long-term functional outcome with
equivalent rates of disease control when
compared with postoperative radiotherapy.
 There is however an increased risk of
postoperative wound complications.
 The recommended dose for pre-operative
radiotherapyis 50Gy, in 2Gy per fraction.

60. Adjuvant chemotherapy
 not routinely recommended
 but could be considered in situations where
 it may contribute to local disease control, for
example, where proximity to sensitive vital
structures precludes giving an adequate
dose of radiotherapy
 or in the case of an R1 resection and a
further wideexcision cannot be performed.

61. Chemotherapy
 Standard first-line treatment is single doxorubicin
75 mg/m2 every 3 weeks.
 Ifosfamide at a dose of 9–10 g/m2 may be used first line if
anthracyclines are contraindicated and maybe an option
for second-line therapy, other options
 could be considered according to the histology.
 Additional second-line agents include dacarbazine,
trabectedin and the combination of gemcitabine
+docetaxel. Reported response rates are in the range
of 5–25%.

62. Adjuvant radiotherapy
 Small, low grade tumors resected with 2 cm
margins may not require radiation
 Improves local control but not survival
 Whether improved local control leads to
improved survival is controversial

63. Local recurrence with post-op
brachytherapy

64. Pre-op or post-op radiation?
 Some avoid pre-op use because of
increased wound complications (although
this is debatable)
 RCT looking at wound complication rate pre-op vs post-
op radiation showed 35% vs 17%
 Risk confined to lower extremity
 Conclusions: pre-op may be better for upper extremity
and head & neck because of equal wound complication
risk and benefit of lower radiation doses to more vital
tissues

65. Pre-op vs post-op radiotherapy

66. Chemotherapy
 Can improve local control, but not survival
 Doxorubicin and ibosfamide have response
rates of 20%
 Use only in advanced disease
 Combination with radiation or neoadjuvant
therapy are controversial
 Hypothermic isolated limb perfusion may be
used for palliation

67. Treatment of Recurrence
 20-30% of STS patients will recur
 More common in retroperitoneal and head &
neck high grade tumors because hard to get
clear margins
 38% for retroperitoneal
 42% for head and neck
 5-25% for extremity
 After re-resection recurrence is 32% for
extremity and much higher for visceral

68. Metastatic disease
 Lung most common site of mets, but visceral
often go to liver
 Median survival from development of
metastatic disease is 8-12 months
 Resection of pulmonary mets can give 5 year
survival of 32% if all mets can be removed
 >3 mets is poor prognosticator

69. Retroperitoneal Sarcomas
 15% of all sarcomas
 Liposarcoma 42% and leiomyosarcoma 26%
 CT scan can show cystic/solid/necrotic components and
relation to surroundings
 CXR to r/o mets, chest CT if CXR abnormal
 Biopsy not necessary unless suspect a lymphoma or germ cell
tumor or plan preop chemo or radiation
 En bloc resection is standard treatment
 bowel prep
 assess bilateral kidney function
 50-80% need organ resection
 78% of primary lesions can be completely resected

70. Survival after resection of primary
retroperitoneal sarcoma

71. Prognosis for retroperitoneal
sarcomas
 5 year survival after complete resection of
54-65%
 Drops to 10-36% if incompletely resected
 Recurrence occurs in 46-59% of completely
resected tumors

72. Radiation or chemotherapy for
retroperitoneal sarcomas
 Radiation
– GI and neurotoxicities limit delivery of sufficient
doses
– May improve local control
– Recommended for use only in clinical trials given
lack of data either way
 Chemotherapy
– Use for recurrent, unresectable or metastatic
disease

73. Case #2
• 49 y/o female with GERD undergoing EGD

74. GIST
 Separate subtype of sarcoma defined by expression
of c-Kit (CD117)
 Surgery: complete resection without local or regional
lymphadenectomy
 Very resistant to traditional chemotherapy
 Gleevec (imantinib mesylate)
 c-Kit is constitutively active tyrosine kinase receptor
 Drug is tyrosine kinase inhibitor used in CML
 Initial studies showed 54% response rates
 Two RCTs currently looking at adjuvant treatment

75. GIST

76. GIST

77. Extremity sarcomas
MFH
Synovial sarcoma

78. Breast sarcomas
 1% of all breast neoplasms
 Wide excision with negative margins
 No clear role for adjuvant radiotherapy

79. Sarcoma after mastectomy

80. Vascular sarcomas
 Angiosarcoma, hemangiosarcoma,
lymphangiosarcoma, hemangiopericytoma
 Key points:
 Hepatic angiosarcoma – thorotrast, vinyl chloride,
arsenic
 Stewart Treve’s – lymphangiosarcoma in chronic
lymphedema
 High risk for bleeding during excision
 No clear role for chemo or radiation