Sarcoma Flashcards
Germline mutations associated with RMS
p53 BWS (11p15 LOH) Costello (HRAS) Noonan (Ras-Mapk) NF-1 Gorlin (PTCH1) Dicer1
Name translocation seen in alveolar RMS
Pax3-FOXO1 t(2;13)
Pax7-FOXO1 t(1;13)
RMS immunohistochemical staining to differentiate from other SRBCT
myoD
myogenin
desmin
muscle specific actin
Favourable sites for IRS staging
- orbit
- non-parameningeal head and neck
- non bladder/prostate GU
- biliary tract
Who can avoid bone marrow?
- non-invasive node-negative tumor
- all NRSTS
RMS risk group classification
Low risk:
- all non-met fav-site ERMS
- non-fav site ERMS with CR
Int risk:
- all non-met ARMS
- non-fav site ERMS with PR
High risk:
- met ERMS or ARMS
Role of radiation in RMS
- local control for all but grp 1 ERMS
- starts wk 3-15 unless urgent
- 36-50.4 Gy
Prognostic factors in RMS
- Tumor stage
- Translocation status
- Extent of metastasis (<2 mets better than more)
- Site of tumor
- Age
- Extent of resection (tumor group)
Chemo responsive NRSTS
synovial sarcoma - (X; 18) translocation
undifferentiated sarcoma
infantile fibrosarcoma - (12;15) translocation
NRSTS chemo non-responsive
MPNST
Leiomyosarcoma
Aveloar soft part sarcoma
Epitheloid sarcoma
Translocations for:
- Synovial sarcoma
- Undifferentiated sarcoma
- Infantile fibrosarcoma
- Clear cell sarcoma
- t (X;18) SYT-SSX fusion
- t(4;19) CIC-DUX4 sometimes
- t (12;15) ETV6-NTRK3
- t(12;22) EWSR1-ATF1
Prognosis for RMS
Low risk 85%
Int risk 50-75%
High risk <20%
Who needs LN exploration in RMS
- clinically suspicious node
- regional node exploration for all extremity lesions
- ipsilateral retroperitoneal LN dissection for boys >10 y.o. with paratesticular tumors
Chemo used for NRSTS
Ifos/Doxo
ARST 0331 - low risk protocol
- reduce dose of cycle (4.8g/m2)
- shorter length of therapy - 22 instead of 48 wk
Same outcomes as classic VAC
ARST 0531 - int. risk protocol
VAC vs VAC/VI - same outcomes
VAC/VI had:
- less hematologic toxicity, less F&N
- lower cyclo dose (8.4 vs 16.8 g/m2)
Long term toxicity of therapy
Infertility - related to cyclo and pelvic rads
SMA - 2-3% at 30 yrs related to p53 and rads
Bone growth/atrophy - rads
Syndromes associated with NRSTS
- p53
- FAP - desmoid fibromatosis
- Rb - leiomyosarcoma
- SMARCB1 - extra-renal rhabdoid
- NF-1 - MPNST
Prognostic factors in NRSTS
- Subtype of tumor
- Stage (localized vs. metastatic)
- Group (extent of resection)
- Size (<5 cm vs. >5cm)
- Tumor grade (mitotic rate, necrosis, nuclear atypia)
NRSTS associated with HIV/immunosuppression
leiomyosarcoma
NRSTS likely to spread to LNs
Epithelioid sarcoma and clear cell sarcoma
NRSTS most common in < 1yo
Infantile fibrosarcoma and infantile hemangioperiocytoma
Osteo:
- cytogenetic abnormality
- molecula abnormalities
cytogenetics: chromothripsis, supernumary ring chromosome (parosteal)
Molecular: Rb, p53, RECQL4 (rothmund thompson syndrome)
Prognostic factors in Osteosarcoma
- stage
- number of mets
- extent of resection
- histology (parosteal, telangiectatic, fibroblastic are fav)
- extent of necrosis
- LDH/ALP
- Tumor location (axial unfav)
- size of tumor (9+ cm)
Long-term toxicity for osteo
- functional impairment from surgery
- 10% risk of anthracycline related cardiotoxicity
- 10% risk of ototoxicity
Most common translocations in Ewing’s
t(11;22) EWS-FLI1
t(21;22) EWS-ERG
t(7;22) EWS-ETV6
EWS Prognostic factors
Stage - localized vs metastatic
Primary site - extremity better than pelvis
Age
Tumor size (<8cm better)
Role of radiation in EWS
- local control for those without good surgical option that preserves function
- in addition to surgery for residual disease
Principles of therapy for NRSTS
- Surgery is critical
- everyone gets RT
- role of chemo is controversial - generally reserve for large (>5cm), high-grade or unresectable tumors.
**note if tumor is not chemo-sensitive when deciding.
List non-Ewing’s sarcoma with EWS fusion transcripts
- Desmoplastic small round cell tumor [t(11;22)(p13;q12), EWS-WT1 fusion]
- Clear cell sarcoma [EWS-ATF1 fusion; t(12;22)(q13;112)]
- Extraskeletal myxoid chondrosarcoma
- Myxoid liposarcoma [EWS-CHOP fusion; t(12;22)(q13;p11)]
Most common sites for Osteo vs EWS
Osteo: distal femur, prox tibia, prox humerus
EWS: pelvis, femur, rib
what location is most common for RMS?
head and neck is most common
followed by GU tract
how do you stage a RMS (from a classification standpoint?)
start with pre-treatment TNM to get the STAGE
then do the postoperative grouping to get GROUP
COG risk group is determined into low, intermediate or high risk based on the stage, group and histology
what group of RMS do not require radiation?
Group I ERMS
which chemotherapy agent in RMS treatment is a radiosensitizer?
Dactinomycin
what are the 3 most common locations for OS?
metaphysis of
1-distal femur
2-proximal tibia
3-proximal humerus
what are the theoretical advantages for neoadjuvant chemotherapy in OS?
- decrease in tumor-related edema and shrinkage of the tumour at the primary site to allow for better surgery
- initial chemo directed toward micromets (we know are present in 80-90% patients)
- assessment of the sensitivity of the primary tumour to chemo which has prognostic significance
what are the preliminary results of AOST0331?
this was a combined study with EURAMOS
those with good response (>90% necrosis) were randomized to MAP vs MAP plus pegylated interferon alpha 2B
those with poor response randomized to MAP or MAPIE
neither experimental arms showed a survival advantage
for relapsed OS what salvage regimens can be used
high dose ifosfamide with etoposide
Gemcitabine and docetaxel
should do full resection if able
radiation can be used for palliation
RF for NRSTS
p53 NF-1 (MPNST) FAP (desmoid-type fibromatosis) SMARCB1 (extra-renal rhabdoid tumor) RB1 (leiomyomatosis) Werner's
