sarcoma Flashcards
What investigations / imaging should be done in suspected bone sarcoma
XR in two planes
MRI of whole compartment and adjacent joints
CT chest
PET-CT
Core-biopsy
Suspected Ewings - bone marrow
How is sarcoma divided
Bone - 20%
Soft tissue - 80%
In what part of the bone is osteosarcoma commonest
And in what sites of the body
Metaphysis, adjacent to growth plates
Distal femur or proximal tibia, proximal humerus
What mutations are commonly seen in osteosarcoma
TP52 & MDM2
What is needed before treatment for osteosarcoma
Fertility - consider sperm banking
GFR
Audiometry
Echo
What is the treatment regimen for osteosarcoma
And what chemotherapy regimen
Neo-adjuvant chemo - 3 cycles MAP/AP
Surgery - 2-5cm margin, and limb preservation where possible
Adjuvant chemotherapy - up to 6 cycles
If <40yrs - MAP
Methotrexate, doxorubicin and cisplatin, with macrophage stimulator mifamurtide
If >40yrs - AP
Doxorubicin and cisplatin
What is the advantage of NACT / adj chemotherapy for osteosarcoma
NACT - treats microscopic disease, facilitates surgery, allows time for prosthesis to be made. No survival advantage
Adj chemo - survival advantage
What histological response is positive after chemotherapy for osteosarcoma
High necrotic rate - >90%. A poor necrotic rate suggests treatment won’t be curative
When is radiotherapy indicated for osteosarcoma
And what regimen
Not routinely indicated as osteosarcoma is very radio-resistant
Indication:
Unresectable tumour (H&N, vertebrae and pelvis) - treat with primary RT/CRT
Post-op-RT - poor response to chemotherapy (<90%), close or positive margins
Regimen: RT +/- concurrent cisplatin.
Primary RT - 66Gy/33#
Spinal RT above L2 - 47.5/25#, due to cord tolerance
Post-op RT - 60Gy/30#
What volumes are included in primary RT for osteosarcoma
Primary RT - visible tumour on CT/MRI
What volumes are included for post-op RT
GTV-CTV margin
CTV-PTV margin
Post-op RT:
GTV – areas of risk based on pre-op imaging - reconstruct GTV on post-op planning scan
CTV – GTV +2-3cm, with inclusion of scar with 0.5-1cm margin
PTV – CTV +5-10mm
What dose of RT is given for whole lung RT for relapse following pulmonary metastatectomy for osteosarcoma
> 14yrs - 18Gy in 12#
<14yrs - 15Gy in 10#
How is metastatic osteosarcoma treated?
Depends on timing to relapse and extent
If isolated relapse, consider surgical metastatectomy, and if not suitable - RFA / SABR / cryo
If not suitable for localised treatment / disseminated disease, treat systemically
What systemic treatment is given 2nd and 3rd line for metastatic osteosarcoma
2nd line - Ifosfamide + Etoposide
3rd line - Gemcitabine + Docetaxel
What are poor prognostic factors for osteosarcoma
Raised ALP, LDH or metastases at diagnosis
Poor histological response to chemotherapy
Axial or proximal extremity tumour site
Large volume tumour
Male, >18yrs
Relapse, esp early and distant non-lung mets.
What mutation is commonly seen in Ewings sarcoma
85% have t(11;22) EWS-FLI1 translocation
10% have t(21;22) EWS-ERG translocation
What sites are typical for Ewings sarcoma
Extremity bones (50%) - femur, tibia, fibula, humerus
40% in axial skeleton - Pelvis, rib, scapula, vertebrae
What is the treatment regimen for Ewings sarcoma
NACT - VDC/IE (vincristine, doxorubicin, cyclophosphamide / ifosfamide, etoposide) - alternating every 2wks for 6wks
Followed by surgery or primary RT
Adjuvant chemotherapy - 4x VDC, followed by VC/IE alternating for four cycles
What are the radiotherapy indications for Ewings sarcoma
Primary RT - if radical surgery not feasible / too morbid
Following NACT, but before surgery - if poor response to NACT, marginal resection expected, or where a response would facilitate surgery (rib/pelvis)
Post-op RT:
Close or positive margins
Displaced pathological fracture, and not all contaminated sites removed at surgery
Poor histological response to NACT, even with negative margins
Where complete surgery is technically difficult - spine/paraspinal, rib, pelvis, H&N
Sacrum - regardless of margins or response
What are the RT doses for each indication for Ewings sarcoma
Primary RT - 55Gy/30#
Following NACT, but before surgery - 50.4/28#, or 45/25# with boost of 5.4Gy/3# if concerns about wound healing or OAR
Post-op RT: shrinking field approach - 59.4Gy/33# to tumour
Phase 1 - 54Gy/30#
Phase 2 - 5.4Gy/3# boost
What margins are applied to post-op RT for Ewings sarcoma
Post-op RT: shrinking field approach - 59.4Gy/33# to tumour
Phase 1 - 54Gy/30# - 2cm radial margin and 3-5cm sup/inf margin
Phase 2 - 5.4Gy/3# boost - 2cm radial margin and 1-2cm sup/inf
What are poor prognostic markers in Ewings sarcoma
Axial location - Up to 90% DFS for peripheral tumours, and 65% for axial tumours.
Large tumour volume
Raised serum LDH
Age >15yrs
Poor histological response to pre-operative chemotherapy
Incomplete/no surgery at the primary site
Non-pulmonary mets
What is the prognosis of Ewings sarcoma
If localised, 5-year survival 55-70%
If pulmonary mets - 20% 5YS, and <10% with non-pulmonary mets
How does a chondrosarcoma behave
What mutation is commonly present
What is the treatment
Typically locally aggressive, rather than distant spread
IDH mutations
Treated with radical surgery, or if surgery not possible, radical RT with 60Gy/30#
What can be the result of a transformed chondrosarcoma
How is it treated
Can transform / dedifferentiate into an aggressive high grade sarcoma (DCS) - commonly presents metastatic
Treated with chemotherapy as osteosarcoma (PAM / AP)
Mesenchymal variants are treated as a Ewings sarcoma
How are chordomas treated
Surgery if possible, but if not resectable, with radical RT - 70Gy/35#, considering protons if clivus.
What mutation is commonly seen in giant cell tumours of the bone
H3F3A mut.
How are spindle cell sarcomas treated
As osteosarcoma
What tumours does NF1 predispose to
Malignant peripheral nerve sheath tumours (MPNT)
Plexiform neurofibromata: 8-12% lifetime risk of malignant change
Optic gliomas
GIST
How is a soft tissue mass best investigated
US, MRI
CT staging
Biopsy at specialist centre
When can surgery alone be considered as treatment for soft tissue sarcoma
Small (<5 cm), low grade, and superficial to the fascia
When is an amputation considered for a soft tissue sarcoma
Where radical radiotherapy would cause serious radiation-induced morbidity
Where a below knee amputation would be more functional than combined surgical and radiotherapy toxicity
Recurrent disease not suitable for local resection or adjuvant RT
What is the benefit of radiotherapy for soft tissue sarcoma
No improvement in overall survival, but halves the risk of local recurrence
Pre- and post-op RT give the same outcomes, but pre-op RT has less severe side effects, but worse wound healing
What are the advantages and disadvantages of pre-op RT for soft tissue sarcoma
Advantages:
Lower dose, smaller volume, can make surgery easier as tumour becomes more fibrotic.
Disadvantages:
Worse wound healing
Increases difficulty of interpreting pathology and increased risk of wound complications
When is RT indicated for STS
Large tumeurs (>5cm)
Deep tumours
High grade - G3
Post-op if positive margins
Pre-op RT generally preferred to post-op
What are the indications for pre-op RT for STS
To increase the likelihood of an R0 resection
Radiosensitive tumours - myxoid fibrosarcoma
For tumours that are close to, but not surrounding, the neuromuscular bundle
Where a larger post-op RT volume would cause significant late toxicity
What is the RT dose for pre-op RT for STS
What are the planning volumes
50Gy/25#
GTV - tumour as seen on T1 MRI (but T2 shows oedema better)
CTV - GTV +2cm axially/radially and 5cm sup/inf, edited off bones and fascia
PTV - CTV +1cm
Where should adjuvant RT not be given to
The foot - poor functional outcome
What is the post-op RT dose for STS
How is it delivered
With what volumes / margins
60Gy/30#
Or 66Gy/33# if positive margins
Delivered as a shrinking field technique in two phases
Phase 1 - 50Gy/25#
Phase 2 - 10Gy/5# (negative margins) or 16Gy/8# (positive margins)
GTV reconstructed on post-op imaging
Phase 1: CTV = GTV +2cm axially and 4cm sup/inf, or scar +1cm, and including clips, scar, drain sites, edited off fascia and bone
Phase 2: GTV +2cm axially and sup/inf
PTV = CTV+1cm
When is primary RT indicated for a STS
And to what dose
Head and neck sarcoma - 66Gy/33#
Retroperitoneal sarcoma - 50.4Gy/28#
What is the first line systemic treatment for metastatic STS
Doxorubicin or Caelyx
Ifosfamide 2nd line
What is the adjuvant dose for retroperitoneal sarcoma, post maximal resection with positive margins
50.4Gy/28#, as two phases
45Gy/25#, followed by 5.4Gy/3# boost
What is the adjuvant RT dose to the chest wall, for phylloides tumour following mastectomy
And if pt refuses a mastectomy
50Gy/25#
If pt does not want a mastectomy - WLE and adj RT to the whole breast (50Gy/25#), with SIB to the tumour area to 60Gy
What germline mutations pre-dispose to GIST
Which mutation causes insensitivity to imatinib
cKIT and PDGFR
PDGFR-related & SHD-deficient GISTs are imatinib resistant
What other tumours does SHD deficiency lead to
Increased risk of paraganglioma or parathyroid adenoma
Where are the majority of GISTs found
Stomach and small intestine
What is the main complication of GIST
Bleeding and rupture
What is the typical treatment for GIST
Surgical resection and adjuvant imatinib if:
Size ≥5cm, high mitotic rate >50, cKIT +ve,
What are the side effects of imatinib
Oedema, rash, diarrhoea, deranged LFT
Which sarcoma is most and least likely to spread to LNs
Most - angiosarcoma
Least - liposarcoma
