MANAGEMENT OF SOFT TISSUE SARCOMA

Dr Sanudev Sadanandan V PSenior RegistrarDept of Radiation OncologyBaby Memorial Hospital

Contents Introduction Etiology & Presentation Investigation,Staging,Pathological

classification Management -Surgery -Radiotherapy -Chemotherapy Retroperitoneal sarcoma Follow up Prognostic factors Summary

Introduction

mesenchymal neoplasms

Adult <1%

paediatric neoplasms 15%

Incidence in United states 11280 cases in 2012

Introduction

Can occur at any site Extrimities 43% Visceral 19% Retroperitoneal 15% Trunk/thoracic 10% Other 13%

Lower extremity > trunk > upper extremity > H&N .

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

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

EXTREMITY SOFT TISSUE SARCOMA

Presentation

Asymptomatic mass-MC

Pain - 33%

Paraneoplastic symptoms eg. Fever

Nodal swellings -Rare

Features of Metastasis –Cough, Dyspnoea, Hemoptysis (10%)

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

STAGING

MANAGEMENT

ONCO PATHOLO

GISTIMAGEOL

OGIST

SURGICAL ONCOLOGISTORTHOPEDIC ONCOLOGIST

RADIATION ONCOLOGIST MEDICAL

ONCOLOGIST

MULTIDISCIPLINARY

TEAM

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

Synchronous Stage IV

Single organ ,limited tumor bulk, amenable to complete resection

Disseminated

Primary tr mx +Metastatectomy/SBRT +/- CT +/-RT

Palliation + BSC

SURGERY

First intervention

Most effective treatment to ensure cure.

Function preservation

Adequate Oncologic clearance

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

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.

RADIOTHERAPY

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

INDICATIONS-PREOP RT

Unresectable disease

Resectable disease but resection will lead to significant functional loss

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

RADIOTHERAPY PLANNING

Positioning & Immobilisation

Planning CT Scan 3-5 mm cuts with iv contrast

Co register Preoperative MRI /CT

3DCRT/IMRT preferred

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

CTV-PTV Margin 5-10 mm

OAR & Constraints—Depends on primary site.

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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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

IORT

Surgical resection + Frozen section

TV= Tumor with 2 cm margin

Electrons/photons

Single sitting

DOSE-PORT

PREOP RT

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%).

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

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

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

Toxicities

Hair loss Skin telangictasia Skin fibrosis Lymphoedema ORN Pathological # Radiation induced 2nd malignancies

CHEMOTHERAPY

Indications 1. Adjuvant HG extrimity sarcoma Tumor size >5 cm

2.Neoadjuvant Unresectable disease

3.Palliative To palliate symptomatic mets

Regimen ADR 60mg/m2 IV D1 IFOSFAMIDE 1.3gm/m2 IV D1-D3 q3weekly

x 6 cycle

2nd line Doce+Gem,Pazopanib

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.

MANAGEMENT OF RETROPERITONEAL SARCOMA

34% of all STS

MC- liposarcoma (40%), leiomyosarcoma (25%), malignant peripheral nerve sheath tumour and fibrosarcoma

MC visceral STS -GIST, leiomyosarcoma and desmoid tumour

Presentation

Asymptomatic mass Pain Gastrointestinal bleeding Incomplete obstruction Neurological symptoms due to

invasion of neurovascular structures

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

Diagnosis

Laparotomy with open biopsy CT guided biopsy has a limited role

only Only if: - unresectable tumour - doubtful diagnosis - neoadjuvent chemotherapy

considered

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

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.

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

Recurrence Local relaspse-Work up

Metastasis Single organ &Limited tumor bulk- Metastatectomy+/-CT/RT Ablation

Isolated Node-Nodal dissection+/- RT/CT

Disseminated mets-Palliation

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%

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.

References

NCCN V2.2014

Textbook of Radiotherapy planning –Dobbs

Textbook of Radiation Oncology-Leibel Philips,Perez

RTOG Sarcoma contouring guideline

Online resources

THANK YOU