This document provides information on the management of soft tissue sarcoma, including epidemiology, pathology, etiology, clinical manifestations, diagnosis, staging, prognostic factors, and treatment options. It discusses that soft tissue sarcomas most commonly occur in the extremities, with the three most common histologic types being undifferentiated pleomorphic sarcomas, liposarcomas, and leiomyosarcomas. The mainstay of treatment is surgery, with the goal of wide excision and negative margins. For high grade tumors, radiation therapy is often recommended pre- or post-operatively to improve local control. Treatment requires a multidisciplinary approach and careful consideration of tumor factors, margins, and functional outcomes

1. MANAGEMENT OF
SOFT TISSUE
SARCOMA
1
Dr. Sachin. S,
Junior Resident.
Dept. of Radiotherapy/Radiation medicine
SSH, IMS, BHU

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4. EPIDEMIOLOGYAND PATHOLOGY
 Extremity - 60% (lower extremity, 45%, upper extremity,
15%)
 Trunk - 15% to 20%
 Retroperitoneum - 10% to 15%
 Head and neck - 9%-abdominal (16%),
 65% high grade and 35% low grade.
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5. EPIDEMIOLOGYAND PATHOLOGY
 The three most-common histologic types (adults):
1. undifferentiated pleomorphic sarcomas (previously known as malignant
fibrous histiocytoma),
2. liposarcomas,
3. leiomyosarcomas.
 Children: embryonal rhabdomyosarcoma
 Young adults: synovial sarcoma
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6. ETIOLOGY
 Environmental:
1. Radiation exposure
2. chemical exposures
3. immunosuppression;
4. Chronic lymphedema (Stewart-Treves syndrome); and
5. Viruses (HIV, HHV type 8).
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7. ETIOLOGY
 Genetic:
1. Li-Fraumeni syndrome
2. Werner syndrome
3. Neurofibromatosis type 1, associated with malignant peripheral
nerve sheath tumors
4. Familial adenomatous polyposis (Gardner syndrome): a/w
abdominal desmoid tumors
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8. CLINICAL MANIFESTATIONS
 most common - painless mass
 pain - origin from or invasion of neurovascular structures.
 Erythema and warmth.
 Large slow growing, restricted joint mobility
 Skin changes
 Signs of neuro-vascular compromise
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9. HISTORY & EXAMINATION
• Duration, pain
• Change in size and rate of change
• Local or systemic symptoms associated,
• Neurofibromas and Café-au-lait spots
• H/o radiation exposure
• Family H/o STS
• All soft-tissue masses deep to the fascia should be considered sarcoma
until proven otherwise.
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10. DIAGNOSTIC WORKUP – Primary site +
Sites of potential metastatic spread
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• CBC, RFT, LFT, FBS, Viral markers, 2D ECHO, ECG-12 leads
• MRI > CT (extremities, trunk, head and neck)
• Core biopsy > incisional biopsy/FNAC

11. MRI vs CT
• T1- weighted MRI:
• excellent definition of anatomic relation between tumor & adjacent
structures.
• T2-weighted MRI:
• tumor and associated edema.
• Peritumoral edema can contain malignant cells
• MRI :
• arterial wall invasion,
• fascial enhancement of muscle, and
• definition of tumor spiculations into the adjacent fat and along biopsy tract.
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12. SITE BASED IMAGING
• Extremities, trunk, head and neck:
1. Primary site: MRI > CT
2. Lung metastasis:
a) Chest X-ray for low-grade and small (<5cm) high-grade lesions
b) CT chest for all others
• Retroperitoneal/ Intra-abdominal: CT > MRI
• Abdominal/Pelvic: CT or MRI
• Central Nervous System (CNS): MRI > CT
• Total spine MRI
• Regional lymph node basin: CT or PET/CT
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13. BIOPSY
• Performed by or in presence of the operating surgeon and radiation
oncologist
• CT-guided core biopsy:
• accurate, safe, and expeditious.
• Incisional biopsy:
• accurate and acceptable, but more invasive.
• subsequent definitive resection in mind.
• Tumor cells can potentially seed an incision, thereby necessitating
removal of skin incisions at the time of surgical resection.
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14. BIOPSY
• Biopsy should not transgress an uninvolved compartment or
joint
• much more radical resection.
• subsequent loss of function,
• LR, and death.
• FNAC for recurrent disease, no enough tissue to establish an
initial diagnosis.
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19. WHO CLASSIFICATION OF STS
SUBGROUPS
• Benign
• Intermediate, locally aggressive (e.g., desmoid fibromatosis);
• Intermediate, rarely metastasizing (e.g., plexiform fibrohistiocytic
tumor);
• Malignant.
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Diagnostic algorithm – Soft
tissue sarcoma

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TNM Classification of STS of
extremities and trunk
except Kaposi’s sarcoma,
fibromatosis (desmoid
tumor), and sarcoma arising from
the dura mater, brain, and
parenchymatous organs

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T1, Grade 1

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T2-4, Grade 1

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T1, Grade 2/3

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T2, Grade 2/3

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T 3-4, Grade 2/3

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Any T, any Grade,
N1 or M1

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STS – Head & Neck

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STS – Abdomen & Thoracic visceral organ

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STS - Retroperitoneum

31. NODAL SPREAD
• Rare in STS, except
• SCREAM:
• Synovial sarcoma
• Clear cell sarcoma
• Rhabdomyosarcoma
• Epitheloid cell sarcoma
• Angiosarcoma cutaneous
• Malignant fibrocystic sarcoma
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32. PROGNOSTIC FACTORS
• AJCC TNMG stage
• High grade
• Tumor size and site
• Histologic subtype
• Older age at presentation
• Positive resection margins
• Bone or neurovascular invasion
• Gender and race
• Lymph node involvement
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33. TREATMENT – A
MULTIDISCIPLINARY APPROACH
• Pathologists
• Radiologists
• Surgeons
• Surgical oncology
• Orthopedics
• Reconstructive surgery
• Radiation oncologists
• Medical oncologists
• Medical physicists
• Physical therapists
• Social workers.
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34. TREATMENT GOALS
• Complete eradication of tumor
• Optimal function preservation
• Minimal treatment related toxicities.
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35. TREATMENT OPTIONS
• Surgery – mainstay
• Marginal resection or excisional biopsy
• Wide resection
• Radical resection or amputation.
• Pre-op or post-op Radiotherapy
• EBRT
• Brachytherapy
• SBRT/SRS
• Neo-adjuvant or adjuvant Chemotherapy
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36. MARGINAL RESECTION
• Removal of the tumor & pseudocapsule.
• “shell-out” or “whoops”
• LR rates: 50% to 93% - microscopic tumor cells beyond the
pseudocapsule.
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37. RADICAL RESECTION / AMPUTATION
• Removal of all of the muscles & neurovascular structures
within the compartment or amputation.
• LR rates: 0% to 18%
- acceptable,
- but cost of loss of limb (or loss of an entire compartment) is high.
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38. WIDE EXCISION
• Conservative surgery (CS) / limb-sparing surgery / function sparing
surgery.
• Preserves good function (limb salvage)
• Moderately high LR rates: 25% to 60%
• Current standard of care:
• High-grade STS - Wide resection/CS combined with pre- or
postoperative radiation therapy (RT).
• Low-grade STS of the extremity and trunk - wide excision alone.
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PRIMARY THERAPY FOR EXTREMITY STS
Surgery :
 Limb-sparing surgery - mainstay treatment for extremity STS.
 Aim :
1. R0 resection or planned close or microscopically positive margins
2. Biopsy site should be excised en bloc with the definitive surgical specimen.
3. Surgical clips placed to mark the periphery of the surgical field - guide
potential future RT.
4. The drains should exit the skin close to the edge of the surgical incision

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42. SURGERY ALONE
 Low grade, negative margins
T1 and Superficial or subcutaneous
 Widely excised
 Margin >/=1cm or less if an intervening fascial barrier present
 Surgical plane should transverse normal tissue outside the reactive tumor zone
 Tumor locations amenable to limb-sparing salvage surgery for recurrence
 Patient willingness to comply with appropriate follow-up
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 Amputation vs Conservative surgery + RT
No significant difference in OS/DFS and LR rates
 Amputation should be considered only –
 tumor involves several compartments or invades major nerves (thigh STS
involving both sciatic and femoral nerves).
 distal lower extremity lesion - below-knee amputation prosthesis may
provide better functional outcome than a limb damaged by tumor, extensive
surgery, and RT

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 Benefit of adjuvant RT in terms of local control:
Trial from MSKCC - CS + BRT vs CS alone.
Trial from NCI - CS vs CS + EBRT.
 Both trials showed improved local control with the addition of RT
 BRT - not recommended for low-grade STS.
 BRT as monotherapy - only for high-grade tumors resected with negative margins.
 Positive margins – EBRT + BRT

45. POST OP RT
Start RT within 4-6 weeks of surgery.
 High risk of local recurrence after surgical resection –
i. tumor size >5cm
ii. lesions deep to or invading superficial fascia
iii. high grade tumors
iv. narrow or positive surgical margins
v. local recurrence after prior surgery
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46. POST OP RT FOR LOW GRADE TUMOURS
 Positive resection margins
 Locally recurrent disease following initial treatment with surgery alone
 Tumor location that would not be amenable to subsequent salvage surgery.
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47. PRE-OP V/S POST-OP RT
Pre op RT Post op RT
Lower dose (50 Gy) Higher dose (60-66 Gy)
Smaller field size Larger field size
Reduced fibrosis, edema, bone
fractures
Increased fibrosis, edema and bone
fractures
Easy target volume definition Difficult
Less informative pathology Complete specimen available
Reduced treatment time and cost Increased treatment time and cost
No hypoxia – good efficacy Hypoxia – reduced efficacy
Increased wound complications (35%) Wound complication risk (17%)

48. MODALITY OF RT
 EBRT alone- Conventional/3DCRT/IMRT/IGRT/Proton
 Perioperative Brachytherapy alone
 EBRT + BT
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49. CONVENTIONAL EXTERNAL RADIATION
 AP/PA or B/L fields
 Positioning of extremity
 upper extremity – supine with arm abducted away from the body with supination
or pronation of arm determined by location of tumor.
 “swimmer position,” - prone with arm extended above head.
 leg - ipsilateral leg should be straight, and contralateral leg separated to create a
gap.
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 proximal leg - contralateral leg can be in a frog-leg position with support under the
knee.
 proximal tumors - the genitalia should be pulled to the contralateral side (using
mesh).
 should consider sperm banking to preserve fertility.
 the patient must be immobilized in a reproducible fashion.

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The “swimmer position” is often an
ideal position for treating STS of the
hand, forearm, or distal upper arm

52.  Tattoo placement, protocol for
extremities - 3 anterior tattoos and 3
lateral tattoos.
 3 anterior tattoos: 15 to 20 cm
apart in the same sagittal plane and
at each point, an additional lateral
mark is placed in the same axial
plane
 6 tattoo points are all placed in a
stable anatomical location
52
Anterior view of the lower leg
tumor showing placement of
tattoos at isocenter and about 15
to 20 cm apart in the same

53. • Dosing guidelines
• Spare 1cm thickness to receive <20 Gy
• 3D CRT – part of limb can be entirely excluded
• IMRT – some low dose is almost always received (<20Gy preferable)
• Joint dose < 40-45 gy
• Avoid full thickness bone radiation
• V40 <64%, Dmean <37Gy, Dmax <59Gy
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 Recommended mean femoral neck dose of <40 Gy
 V40 <64%

55. • Renal DTPA if one kidney will be compromised
• IMRT > 3D-CRT
• Target coverage
• Conformal dose distribution
• reduction in sparing of circumferential margin at soft tissues bone interface
• Dose painting IMRT
• IGRT – smaller treatment fields, potential dose escalation with
sparing of normal tissues
• Adaptive radiation therapy – Myxoid liposarcoma respond
dramatically to radiation
• SBRT
• Particle beam : protons, photons, carbon
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56. 3DCRT/IMRT
Isodose distribution for a patient with STS of
thigh treated with A: 3DCRT, B: IMRT
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PRE OP RT CTV
 Sarcoma case without peritumoral
edema.
 CTV = GTV with 1.5 cm radial and
4 cm cranio-caudal margin
 Radially CTV need not expand
beyond surface of bones and fascia,
unless invaded

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 Sarcoma case with peritumoral
edema,
 CTV = GTV with 1.5 cm radial and 4
cm cranio-caudal margin
 radially CTV need not expand beyond
surface of bones and fascia, unless
invaded
 CTV - manually edited (bold dashed
line) to encompass edema zone in both
transverse and coronal planes.
 PTV = CTV with 1 cm margin in all
directions (vary by institutional
protocols)

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POST OP RT CTV
 Phase I – preop GTV
 CTV = GTV with 1.5 cm radial and 4 cm
cranio-caudal margin
 includes all visible clips, drain sites and
surgical scar
 radially CTV need not expand beyond
surface of bones and fascia, unless
involved with tumor at surgery
 PTV = CTV with 1 cm margin in all
directions (vary by institutional protocols)

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 Phase II
 CTV - same as phase I except 2cm
cranio-caudal margin
 PTV = CTV with 1 cm margin in all
directions (vary by institutional
protocols)

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DOSE
 Pre op RT 50 Gy @ 1.8-2 Gy (no concurrent chemotherapy)
 +ve margins after surgery, a post-op external beam RT boost of 16 to 20 Gy
( 1.8- to 2-Gy fractions)
 total dose – post op
 R0 : 60 Gy @ 1.8-2 Gy
 R1 : 64-66 Gy @ 1.8-2 Gy
 R2 : 66-70 Gy @ 1.8-2 Gy

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COMPLICATIONS
 ACUTE TOXICITY –
 dermatitis,
 problems with wound healing,
 localized alopecia,
 fatigue, nausea, bowel irritability, or esophagitis

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COMPLICATIONS
 LATE TOXICITY –
 subcutaneous fibrosis
 joint stiffness
 edema
 peripheral neuropathy
 bone fracture
decreased muscle strength
pain.

64. INDEPENDENT PREDICTORS FOR
WOUND COMPLICATIONS
• Tumor size >10 cm
• Tumor proximity to skin surface
• Vascularized flap closure
• Diabetes mellitus
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65. BRACHYTHERAPY
 Localized radiation with maximum sparing of surrounding normal tissues
 radio biologically better
 short and convenient
 small rate of complications
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68. BRACHYTHERAPY
 intra op
 nylon catheters are placed in target
area of operative tumor bed
 spaced at 1-1.5 cm interval
 2 cm cranio-caudal and 1-2 cm radial
margin around tumor
 treatment usually starts 4-5 days after
surgery
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(a) Operative cavity - catheters were placed perpendicular to the wound, spaced 1-1.5
cm apart in parallel.
(b) CTV was constructed with a tumor bed expansion of >/= 2 cm craniocaudally and >/=
1 cm lateral to tumor bed

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 Catheter entry point - at least 1cm away from wound incision
 Fix catheter to tumor bed by –
 sutures (vicryl)
 anchor button to skin
 keep drain on top of brachy catheters and remove after completion of brachy
 Avoid –
 Penetrating blood vessels during catheter placement
 direct catheter contact with bones and nerves

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 CT Simulation preferred – on D4-5
 If CT not available, Orthogonal X-Rays
 check that wound has begun to heal, not infected, drains are working well, flap
has been taken up well
CTV is reconstructed using pre op imaging and clips in post op scans

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 V100 >/= 90-95% (ideal 95%)
 V150 </=50-40% (ideal 40%)
 D90 >/=90-100% (ideal 100%)
 Dose to skin should be less than 2/3rd of prescription dose
 Loading dose should be >/= 0.5 cm from skin surface
 OARs should get <100% of prescription dose, unless it is at high risk of tumor
involvement

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TREATMENT PRESCRIPTION
 At 0.5 cm from depth of catheter, up to 1cm can be used after consideration of doses
to OARs and RT doses
 >1 cm not recommended because of increased risk of late complications
 BT Monotherapy :
i. LDR/PDR (45 Gy)
ii. HDR (30-50 Gy) in 2- to 4-Gy bid fractions
 IORT + EBRT :
EBRT 45-50 Gy/ 1.8-2 Gy per fraction + 10-20 Gy IORT
 EBRT 45-50 Gy/ 1.8-2 Gy per fraction +
i. 15 to 25 Gy LDR BT boost or
ii. 12 to 20 Gy HDR BT boost ( 2- to 4-Gy bid fraction)
for a total of 65 Gy

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TREATMENT DELIVERY
 Catheter position, tumor bed geometry (seroma/hematoma) and wound healing
should be checked before starting treatment
 with immediate reconstruction and BT monotherapy – start after PO D5
 With BT Boost – can start on PO D2-4
 If wound breakdown or infection – delay BT

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76. Limitations –
 Large target volume
 Restriction of catheter placement because of bone or visceral organs
 site where good catheter geometry is difficult to achieve – around shoulder
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77. BRACHYTHERAPY BOOST
 EBRT +BT = LCR – 77-100%, Grade 3 toxicity – 27-30%
 when target volume/ volume at risk cannot adequately be covered with BT alone
(i.e. OAR restriction, atypical geometry, skin ulceration)
 high risk of recurrence –
 tumor > 10 cm
 positive margin
 recurrent disease
 Advantage of adding EBRT to BT –
 safely escalate dose to a large clinical volume with cumulative RT doses - >60 Gy
(45-50 Gy EBRT +15-20 Gy BT)
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78. BRACHYTHERAPY BOOST
Advantages:
 RT starts in immediate post op period controlling tumor repopulation
 In perioperative period, tissues less hypovascular/fibrosed –than in the
postoperative period - RT more effective
 BT catheters in contact with tumor bed giving higher RT doses to potential areas
of microscopic disease
 can safely treat STS abutting neurovascular structures
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Chemotherapy for Non-Metastatic Extremity STS (Stage III – locally
advanced)
 Neoadjuvant chemotherapy
 Adjuvant chemotherapy
 Combined radiation and chemotherapy

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NEOADJUVANT CHEMOTHERAPY
 advantages over adjuvant :
 early initiation of systemic therapy,
 Micrometastatic disease addressed
 Favourable response – less radical surgery
 an unfavorable response - need of more therapy;
 enhanced drug delivery and more efficacy

81. CHEMOTHERAPY
• Doxorubicin based CTH – IA / MAID
• Concurrent options: Doxorubicin, Ifosfamide, Gemcitabine,
Temozolamide
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Retroperitoneal Sarcoma
 large at presentation with a median size of 17 cm.
 nonspecific abdominal pain, anorexia, and weight loss.
 Metastasis to the lungs and to the liver may occur
 initial assessment : CT of chest, abdomen, and pelvis.
 Core biopsy with image guidance - preferred
 optimal primary treatment - en bloc excision of the tumor with adjacent involved
viscera and a margin of uninvolved tissue
 Adjuvant RT could be recommended, but the benefits, are uncertain.
 Chemotherapy has not shown benefit

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Retroperitoneal STS

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Retroperitoneal Sarcoma….
 no randomized trials have compared surgery with surgery and radiation
 The typical pattern of relapse is more local than distant suggesting a role for
adjuvant RT.
 no prospective randomized trials supports its role, and the toxicity is not minimal.
 If RT is to be used, preoperative RT of 45 Gy to 50 Gy is preferred over postoperative
RT.
 dose escalation can be done through IORT, dose 10-15 Gy
 target to be treated with IORT is mainly the posterior structures (paraspinal tissues
and vessels) where surgeons have difficulty obtaining wide negative margins.

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