Sarcoma Flashcards
what are the two broad categories of sarcoma
soft tissue sarcoma (80%)
bone sarcoma (20%)
classification of sarcoma
- numerous different types
- various tools used to define them
biological behaviour
tissue of origin
grade
frequently require review by international specialists
sarcoma location
9% H&N
25% GI tract
15-20% retroperitoneum/intra-abdominal
60% arms or legs
risk factors
- probably arise de novo
- multifactorial including exposure to radiation, chemotherapy, carcinogens, chronic lymphoedema, HIV/HSV8 (Kaposi’s), around 10% genetic
clinical presentation
- usually slow growing painless lumps
- mean time before attending GP 4 months
- symptoms related to site of tumour
- metastases unusual at presentation
can be very easily mistaken for number of non-cancerous conditions
warning signs that a lump in soft tissue might be a sarcoma
- measures >4cm - the side of a golf ball
- is getting bigger
- lies deep to fascia
- is non tender (but pain occasionally)
- is in the leg, arm or back
spread of sarcoma
direct
- occasionally with skip areas
- generally extend along tissue planes
regional LN
- involvement infrequent
- around 5-10% (1st site of metastases) except rhabdomyocin sarcoma, epithelioid sarcoma, vascular sarcomas
- more common with increasing grade: G1 0%, GII 2.5%, GIII 12%
direct metastases
- uncommon at presentation
- often present later in disease course - related to grade and size of tumour
- 1st site usually lung (70-80%)
diagnosis
- complete history and physical examination
- bloods: FBC, U/E, LFT
- Biopsy
-> crucial
-> incisional (open), core, FNA or exceptionally total excision
-> must be performed by experienced surgeons
-> must be carefully planned - to be incorporated within later operative bed - Imaging
-> plain films, ultrasound, MRI (soft tissue extent) and CT (bone destruction, lymph nodes)
-> CT thorax
-> role of PET/CT is unclear
-> bone scan is not usually helpful for initial staging (except primary bone tumours)
staging
AJCC 6th Edition (2002)
T1 <5cm a - superficial, b - deep
T2 >5cm a- superficial, b - deep
stage IA/B | T1a-b T2a-b | Grade 1-2
stage IIA/B | T1a-b T2a | Grade 3
stage III | T2b | Grade 3
poor prognostic factors
for local stage:
- increased size of tumour
- deep vs superficial location
- high grade
- symptoms at presentation
- retroperitoneum vs extremities
- R1-2 (micro/macro incomplete) vs R0 (complete) resection
- increased age of patient
Treatment
surgical resection is only potentially curative therapy
- sole treatment for superficial low grade tumours <= 5cm
- aims of surgery: total en bloc excision of 1deg without cutting through tumour
- most important surgical variable that influences local control is presence or absence of tumour cells at surgical margin
- occasionally amputation is only option
RT and chemo (given before or after surgery) are aimed at:
1. marking a sarcoma easier to remove
2. reducing the risk of the sarcoma coming back in the area it started
3. reducing the risk of the sarcoma travelling to other organs
palliative treatment
- when a sarcoma is not curable and the aim of treatment is to alleviate the symptoms it is causing
- most frequently achieved by:
RT
chemo
non-chemo medication
psychological support
impact of RT
- reduces risk of local relapse
- no impact on survival
- QoL and limb function depend on good local control
role of RT
adjuvant RT improves local control
- Yang (1998) 141 Pts EBRT vs no EBRT (64% high grade). HG LR 0% vs 22% (p = 0.0001). LG LR (p = 0.003)
- Pisters (1996) 164 Pts Brachy vs none. LR 18% vs 31% at 5 years (p=0.04)
permits limb sparing
indications for RT in localised soft tissue sarcoma
- intermediate and high grade tumours
- tumour >= 5cm
- deep tumours (deep to fascia)
- ‘close’ resection margins
- microscopically positive resection margins, if further surgery not possible
- low grade tumours, if marginally resected and further resection at relapse will be difficult
timing of RT
- given alone
palliation (inoperable)
occasionally -> long term control - pre-op
5 weeks treatment centred on gross tumour - post-op
6-6.5 weeks treatment
2 phases
need to treat operative bed
RT scheduling (pre vs post-op)
only one randomised phase III trial (O’ Sullivan 2002)
190 Pts. median follow up 6.9 years. pre-op 50Gy/25# (+16Gy boost if margin +ve) vs, post-operative (66Gy/33#)
1st end point: wound complication rate
2nd end point: late complications/function/QoL
- no difference in LR, regional/distant failure rate, PFS
- trial closed before completion
-> wound complication rate in pre-op arm (35% vs 17%)
-> lower extremity > upper (43% vs 5%) - increased late effects in post-op arm
-> tissue oedema/fibrosis
-> impaired function
-> fractures
target volume (pre-op)
Single phase (50Gy/25#)
Proximal/distal margins: 2-4cm proximal and distal to site of disease
radical margins: 2cm or up to bone, interosseous membrane, major fascial plane
aim to spare corridor (around 1/3 limb circumference) of normal tissue (lymphatic drainage)
GTV defined using T1W MRI but with oedema included (T2W images)
RT target volume (post-op)
Phase I (50Gy/25#/5 weeks)
proximal/ distal margins: >= 4cm proximal and distal to site of original disease - ideally to include scar/drain sites i.e. potential sites of contamination
radical margins: 2cm or up to bone, interosseous membrane, major fascial plane
>2cm if plane has been violated
aim to spare corridor of normal tissue (lymphatic drainage)
Phase II (10-16Gy/5-8#/1-1.5 weeks)
proximal/distal margins: >= 2cm proximal and distal to site of original disease
radical margins: 2cm or up to bone, interosseous membrane, major fascial plane
>2cm if plane has been violated
aim to spare corridor of normal tissue (lymphatic drainage)
late normal tissue toxicity
subcutaneous fibrosis
joint
oedema
generally all greater in post-op arm compared to pre-op complications
RT-induced bone fractures
- morbidity significantly higher than normal fracture (around 20%)
- lower limb > upper limb
- delayed union
- multiple operations
- increased infection rate
–> endoprosthetic replacement or amputation - limited RT dose volumetric data
late bone toxicity
retrospective Princess Margaret Hospital study (Dickie 2009) (6% fracture rate)
21 patient plans (24 fractures) treated 1995-2004
matched (2:1) to non-fracture cohort
risk of radiation induced fracture significantly reduced if:
- maximum dose <60Gy
- mean dose <38Gy
- % of bone irradiated to >=40Gy is <66%
minimising toxicity
- optimising volume increasing conformality
- role of IMRT
-> offers potentially less normal tissue morbidity
-> two recent prospective phase II trials: RTOG 0630 trial (Wang 2011), Princess Margaret Hospital trial (Dickie 2010)
-> both specifically assess effect of IMRT on the reduction of late toxicity - optimising volume - better immobilisation
-> customised device
summary
- RT decreased LR if given before/after limb sparing surgery soft tissue sarcomas
- late normal toxicity has significant impact on QoL
- minimising irradiated volume essential: conformal techniques, clinical trials, better immobilisation
