soft tissue sarcoma-what is the role of radiation
DESCRIPTION
A short presentation on briefly about management outline and details of Radiation therapy in soft tissue sarcomas.TRANSCRIPT
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MANAGEMENT OF SOFT TISSUE SARCOMA
Dr Sanudev Sadanandan V PSenior RegistrarDept of Radiation OncologyBaby Memorial Hospital
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Contents Introduction Etiology & Presentation Investigation,Staging,Pathological
classification Management -Surgery -Radiotherapy -Chemotherapy Retroperitoneal sarcoma Follow up Prognostic factors Summary
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Introduction
mesenchymal neoplasms
Adult <1%
paediatric neoplasms 15%
Incidence in United states 11280 cases in 2012
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Introduction
Can occur at any site Extrimities 43% Visceral 19% Retroperitoneal 15% Trunk/thoracic 10% Other 13%
Lower extremity > trunk > upper extremity > H&N .
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Etiological factors Genetic mutations-NF-1, RB, Gardner’s
syndrome, LF syndrome
Radiation exposure (osteosarcoma, angiosarcoma)
Chronic lymphoedema- Angiosarcoma
Chemical exposure eg. arsenic, polyvinyl chloride (hepatic angiosarcoma)
Infections eg. HHV-8: Kaposi’s Sarcoma
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WHO PATHOLOGICAL CLASSICATION 2002
Adipocytic tumors-Liposarcoma Chondro osseous tumor-CS/OS
Fibroblasic/myofibroblastic tumor Undifferentiated tr
Fibrohystiocytic tr-MFH 1.Synovial2.Epitheloid3.Alveolar soft part sa4.Clear cell sarcoma5.Extraskeletal myxoid chondrosarcoma6.Extraskeletal Ewings/PNET7.Desmoplastic small round cell tr8.Extrarenal rhabdoid tr9.Undifferentiated sarcoma/NOS
Smooth muscle -Leiomyosarcoma
Skeletal muscle-RMS
Vascular-AS
Periferal n-Malignan peripheral nerve sheath tr
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EXTREMITY SOFT TISSUE SARCOMA
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Presentation
Asymptomatic mass-MC
Pain - 33%
Paraneoplastic symptoms eg. Fever
Nodal swellings -Rare
Features of Metastasis –Cough, Dyspnoea, Hemoptysis (10%)
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INVESTIGATION
ESSENTIAL Routine inv
MRI Scan +/- CT Scan
CT Chest
True cut Biopsy/Incision Biopsy
OTHER USEFUL INV IN SELECTED SITUATIONS
Abdominopelvic CT Scan-AS,LMS,ES,M/RC-LS
MRI Total spine-M/RC LS
MRI/CT Brain- AS,Alveolar softpart
PET CT
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STAGING
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MANAGEMENT
ONCO PATHOLO
GISTIMAGEOL
OGIST
SURGICAL ONCOLOGISTORTHOPEDIC ONCOLOGIST
RADIATION ONCOLOGIST MEDICAL
ONCOLOGIST
MULTIDISCIPLINARY
TEAM
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STAGE WISE MANAGEMENT
IA LG SX--FOLLOW UP
IB LG SX ONLY if margin adequate
SX –PORT if close/positive margin
IIA Resectable without functional loss
SX—PORT
IIB,III Resectable without fuctional loss
SX ---PORT
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Synchronous Stage IV
Single organ ,limited tumor bulk, amenable to complete resection
Disseminated
Primary tr mx +Metastatectomy/SBRT +/- CT +/-RT
Palliation + BSC
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SURGERY
First intervention
Most effective treatment to ensure cure.
Function preservation
Adequate Oncologic clearance
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SURGERY
BIOPSY-TRU CUT/OPEN-EXPERIENCED SURGEON-NO VIOLATION OF FASCIAL PLANES-NEEDLE TRACK & SCAR TO BE EXCISED AT THE TIME OF DEFINITIVE SURGERY
*WIDE EXCISIONWITH NEGATIVE MARGINS
*LIMB SALVAGE SURGERY
Minimum margin 1 cm
Close <1 cm margin
AMPUTATION -GROSS TOTAL RESECTION IS EXPECTED TO RENDER LIMB NON FUNCTIONAL
-AT PATIENT PREFERENCE
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PATHOLOGIC ASSESSMENT HISTOPATHOLOGY REPORT
Organ/site/Sx Status of Margin
Primary Diagnosis-WHO
Depth of tumor
Status of LN
Size of tumor Other studies IHC/EM Molecular genetics
Grade-NCI-Histo/Loc/Necrosis -FNCLCC-diff/mito count/necro
Additional Mitotic rate Vascular invasion inflamatory infiltrate
Necrosis +/-,Type,% TNM Stage.
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RADIOTHERAPY
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INDICATIONS-PORT
1.All deep seated tumors
2.All high grade tumors ,size>5cm
3.Intermediate grade tumor size >5cm
4.Repeated margin positivity
5.Tumor >5cm superficial
6.Close margin Intermediate/High grade
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INDICATIONS-PREOP RT
Unresectable disease
Resectable disease but resection will lead to significant functional loss
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PREOP RT PORT
Treatment volume smaller-No need to cover operated field
Treatment volume larger
Reduce seeding during surgery More seeding
Tumor regression and better resectability
Decreased risk of recurrence
Less toxic More toxic
No hypoxia-Blood supply uninterrupted
Hypoxia in tumor bed may adversely affect oucome
Disadv-Poor wound healing -No complete HPR
Adv-Complete HPR available
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RADIOTHERAPY PLANNING
Positioning & Immobilisation
Planning CT Scan 3-5 mm cuts with iv contrast
Co register Preoperative MRI /CT
3DCRT/IMRT preferred
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RADIOTHERAPY PLANNING
GTV –contour tumor in preop MRI –T1C
CTV ---Initial GTV + Margin to encompass
microscopic spread
---Surgical Scar/Drain sites/Surgical clips
---GTV to CTV Margin 3 cm longitudinally (RTOG)
1.5 cm laterally
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CTV-PTV Margin 5-10 mm
OAR & Constraints—Depends on primary site.
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Example Case
55-year-old male with a large high-grade round cell liposarcoma in right distal thigh. Clinical stage (AJCC 7th edition) III T2bN0M0G3.
The MRI of right distal thigh showed a large well circumscribed heterogeneous, multiloculated mass located within the posterior thigh.
The tumor measured 14.8 cm in craniocaudal
dimension, 7.8 cm in AP dimension, and 11.3 cm in maximal medial-lateral dimension.
Simulation CT images were fused with those from the diagnostic thigh MRI
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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GTV→
←CTV
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Brachytherapy
Surgical resection + Frozen section
Place tumor bed clips
HDR tube placed at 1cm spacing
Target vol –Tumor + 2cm margin
Planning-Paris system
Load on POD4/D5
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IORT
Surgical resection + Frozen section
TV= Tumor with 2 cm margin
Electrons/photons
Single sitting
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DOSE-PORT
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PREOP RT
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TrialsTrial Results
Pisters et al 160 extremity & trunk Randomized to BT/Obs 42–45 Gy over 4–6d)
BT-LC for high-grade lesions (65–90%), but not for LG.
No difference in DSS /DM.
NCI (Yang et al. 1998):rct
140 ,extremity sarcoma, WLE. LG to obs vs. PORTHG post-op CT vs.post-op chemo-RT. RT = large field to 45 Gy → boost to 63 Gy.
RT increased LC for low-grade (60% vs. 95%) and high-grade (75% vs. 100%).
No difference in OS /DMFS
NCI (Rosenberg et al. 1982):
43 , HG STS ,extremity
WLE + PORT vs. amputation alone. RT = 45–50 Gy to compartment with boost to 60–70 Gy.
No difference in LC, OS, or DFS.
Chemo decreased LR and increased DFS (60% vs. 90%) and OS (75% vs. 95%).
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Pre-op or Post-op RT
NCIC (O’Sullivan et al. 2002; Davis et al. 2005):
190 patientswith extremity STS randomized pre-op RT (50 Gy) vs. post-opRT (66 Gy). If +margins, pre-op got 16 Gy boost..
No difference LC /DM /PFS
Preop-woundhealingPORT-late fibrosis
Pollack et al. (1998): post-op RT(60–66 Gy) Vs pre-op RT (50 Gy) before excision or reexcision..
No difference in LC
presenting with gross disease, best LC with pre-op RT (88% vs.67%)
presenting after excision -immediate reexcision and post-op RT (LC 91% vs.72%).
wound-healing --pre-op
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IORT
Oertel et al. (2006):
n=153 primary or recurrentextremity STS limb-sparing surgery + IORT 10–20 Gy → post-op EBRT 36–50 Gy.
Five-year OS 77%, DMFS48%, and LC 78%. IORT dose >15 Gy improved LC, but EBRT <45 or 45 Gy not significant for LC. Acute wound-healing toxicity.-High
NCI (Sindelar et al. 1993):
N=35 ,resectable retroperitoneal STS randomized to surgery + IORT 20 Gy → post-op 35–40 Gy vs. surgery → post-op 50–55 Gy.
No difference in 5-yearOS (35%), nonsignificant increase in LC ,IORTincreased neuropathy if >15 Gy.
Alektiar et al. (2000):
primary or recurrent retroperitoneal STS surgery + IORT 12–15 Gy →post-op EBRT 45–50 Gy.
5-year OS 55%, DMFS 80%, LC 62%, 10% neuropathy
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BENEFIT OF PORT
Enucleation-80% recurrence
WE with negative margin- 30%
WE with negative margin and PORT-5%
Adjuvant radiotherapy improves local control without benefit in Overall survival
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Toxicities
Hair loss Skin telangictasia Skin fibrosis Lymphoedema ORN Pathological # Radiation induced 2nd malignancies
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CHEMOTHERAPY
Indications 1. Adjuvant HG extrimity sarcoma Tumor size >5 cm
2.Neoadjuvant Unresectable disease
3.Palliative To palliate symptomatic mets
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Regimen ADR 60mg/m2 IV D1 IFOSFAMIDE 1.3gm/m2 IV D1-D3 q3weekly
x 6 cycle
2nd line Doce+Gem,Pazopanib
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Benefit in adjuvant setting Metaanalysis ( Pervaiz et al. 2008):
N=1,953 resectable STS
WLE ± RT ---observation vs. adjuvant doxorubicin-based chemo.
Chemo improved LC (absolute 4%), DMFS (9%), RFS (10%), and OS (6%).
Specifically doxorubicin/ifosfamide improved LC (absolute 5%, not significant), DMFS (10%), RFS (12%), and OS (11%).
No trial of pre-op vs. post-op chemo.
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MANAGEMENT OF RETROPERITONEAL SARCOMA
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34% of all STS
MC- liposarcoma (40%), leiomyosarcoma (25%), malignant peripheral nerve sheath tumour and fibrosarcoma
MC visceral STS -GIST, leiomyosarcoma and desmoid tumour
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Presentation
Asymptomatic mass Pain Gastrointestinal bleeding Incomplete obstruction Neurological symptoms due to
invasion of neurovascular structures
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Imaging
CT-abdomen Also allows evaluation of the liver,
the most common site of metastasis
Staging
No official staging system The same grading system applies as
for extremity STS
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Diagnosis
Laparotomy with open biopsy CT guided biopsy has a limited role
only Only if: - unresectable tumour - doubtful diagnosis - neoadjuvent chemotherapy
considered
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Treatment
Surgery -The mainstay of treatment
Chemotherapy principles are the same as for extremity STS
Radiotherapy
-High morbidity and mortality due to radiosensitivity of surrounding organs
-Intensity-modulated radiation showing promising results
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prognosis Adverse factors for local recurrence:
+ margins >50 years age deep location fibrosarcoma type including desmoid, malignant peripheral nerve sheath tumors.
Adverse factors for distant metastasis:
high-grade (at 5 years, <10% for low-grade, 50% for high grade)
increasing size deep location, leiomyosarcoma or malignant peripheral nerve sheath tumor high Ki-67.
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Follow up
H&P
CXR/CT Chest 3-6 mon x 2-3 yr 6monthly x 2yr Annual
Baseline and periodic imaging of primary site
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Recurrence Local relaspse-Work up
Metastasis Single organ &Limited tumor bulk- Metastatectomy+/-CT/RT Ablation
Isolated Node-Nodal dissection+/- RT/CT
Disseminated mets-Palliation
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Survival
StageI extrimity 5-year LC 90–100%, OS 90%
II–III extremity ~5-year LC 90%, OS 80% for stage II, 60% for stage III. For recurrence, amputation salvages ~75%
Stage IV EXTRIMITY Limited mets~5-year OS ~25%.Disseminated ~5-year OS 10%
Retroperitoneal ~5-year LC 50%, DM20–30%, OS 50%
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Take home message STS are hterogeneous neoplasms
Management of STS requires multidisciplinary tumor boards and close collaboration between specialists.
Surgery is the most important form of treatment
Radiotherapy helps to improve local control.
Chemotherapy can be utilised in selected situations in adjuvant/Neoadjuvant treatment.
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References
NCCN V2.2014
Textbook of Radiotherapy planning –Dobbs
Textbook of Radiation Oncology-Leibel Philips,Perez
RTOG Sarcoma contouring guideline
Online resources
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THANK YOU