[ROQs] Sarcoma Flashcards
1
Q
What is the AJCC 8th edition T classification of STS?
A
- T1: ≤ 5cm
- T2: > 5cm ≤ 10 cm
- T3: > 10 cm ≤ 15 cm
- T4: > 15 cm
2
Q
What are the AJCC 8th edition N and M classifications of STS?
A
- N
- N0: no lymph nodes
- N1: regional LN metastases - M
- M0: none
- M1: distant metastasis
3
Q
What are the AJCC 8th ed. prognostic stage groups STS?
A
- IA: T1 NO MO G1 or GX
- IB: T2,T3,4 NO MO G1 or GX
- II: T1 NO MO G2-3
- IIIA: T2 NO MO G2, G3
- IIIB: T3, T4 NO MO G2, G3
- IV: N1 or M1
Note that N1 or M1 automatically makes a pt stage IV
4
Q
What is the AJCC 8th edition TNM classification of bone sarcomas?
A
- T
– T1: ≤8cm
– T2: > 8cm
– T3: Discontinuous tumors in the primary bone - LNs
– N0: LN-
– N1: LN+ - Distant Metastases:
– M0: none
– M1a: Lung
– M1b: Bone or other distant sites
5
Q
What are the AJCC 8th ed. prognostic stage groups RP sarcomas?
A
- IA- T1 NO MO G1 or GX
- IB- T2,T3,T4 NO MO G1 or GX
- II- T1 NO MO G2-3
- IIIA- T2 NO MO G2, G3
- IIIB- T3, T4 NO MO G2, G3
– IIIB- N1 - IV: M1
6
Q
What are some common sites of metastases for retroperitoneal sarcomas?
A
- Liver
- Lungs
7
Q
What are some common histologies of RP sarcomas?
A
- Leiomyosarcoma
- Liposarcoma
- Undifferentiated STS
8
Q
Of all sarcomas, what % are RP sarcomas?
A
10-15%
9
Q
What was the pt population, randomization, and primary endpoint of NCIC pre-op vs. post-op RT for extremity STS?
A
- Pts: Extremity STS
- Randomization:
– Pre-op RT: 50 Gy
— Post-op boost of 16-20 Gy for +margins
– Post-op RT: 66-70 Gy - Endpoint: Rates of wound complications
10
Q
What were the results of NCIC pre-op vs. post-op RT for extremity STS?
A
- Pre-op vs. Post-op:
– Acute wound complications: 35% vs. 17%
– Late effects:
— Fibrosis, ≥ Gr 2: 32% vs. 48% (p=0.007)
— Edema: 15% vs. 23%
— Joint stiffness: 18% vs. 23%
– OS: 72% vs. 85% (p=0.04)
— Trial was not powered to detect this difference
11
Q
What are the adverse prognostic factors for distant recurrence in extremity STS?
A
Distant recurrence:
- Intermediate/large tumor size
- High grade
- Deep location
- Recurrent disease at presentation
- Leiomyosarcoma
12
Q
What are the adverse prognostic factors for local recurrence in extremity STS?
A
- Age (>/< 50)
- Size (>/< 5 cm)
- margins (+ vs. close vs. -)
- Grade (high vs. low)
- Previous recurrence
- Histologic subtypes
– fibrosarcoma
– malignant peripheral-nerve tumor
MSKCC Nomogram
13
Q
What is the most common sarcoma in adults?
A
- Leiomyosarcoma
- 20-25% of all STS
14
Q
Which genetic alteration is a/w leiomyosarcoma?
A
- 12q amplification including MDM2 and CDK4 genes
- Shared by well-differentiated and dedifferentiated leiomyosarcoma
15
Q
What are the different subtypes of liposarcoma?
A
- Well-differentiated/dedifferentiated liposarcoma
- Myxoid/round cell liposarcoma
- Pleomorphic liposarcoma.
16
Q
Which genetic alteration is a/w Ewing sarcoma?
A
- t(11;22) translocation
- Present in ~85%
17
Q
Which genetic alteration is a/w myxoid round cell liposarcoma?
A
t(12;16) → FUS-DDIT3 fusion gene
18
Q
Which genetic alteration is a/w RMS?
A
- t(1;13) → PAX7/FOX01 fusion
- t(2;13) → PAX3/FOX01 fusion
19
Q
Which genetic alteration is a/w alveolar soft part sarcomas?
A
t(x;17) → ASPL-TFE3 fusion gene
20
Q
Which genetic alteration is a/w synovial sarcomas?
A
t(x;18) → SS18-SSX1 fusion gene
21
Q
Which genetic alteration is a/w clear cell sarcomas?
A
- t(12;22) → ATF1-ESWR1 fusion gene
- Present in ~90% cases
22
Q
What was the pt population, randomization, and primary endpoint of the STRASS 1 trial for sarcomas?
A
- Pts:
– Sarcomas of the retroperitoneal or intraperitoneal spaces - Randomization:
– pre-op RT (50.4 Gy in 28 fx) → surgery (multi-visceral en bloc resection)
– surgery alone - Endpoint:
– Abdominal RFS
23
Q
What were the results and the official main conclusion of the STRASS 1 trial for sarcomas?
A
- Median FU 43.1 mos
- RT + surgery vs. surgery only
– 5-yr crude abdominal recurrence: 40-50% both arms
– Median abdominal RFS: 4.5 yrs vs 5 yrs (p=0.95)
– Liposarcoma 3-yr RFS: 71.6% vs. 60.4% - Conclusion: preoperative RT should not be considered a SOC treatment for RP sarcoma
24
Q
What are the main RO criticisms of the STRASS 1 trial for sarcomas?
A
- RT showed a large absolute reduction in local recurrences despite not affecting the primary endpoint. Surgery alone vs. RT + Surgery
– LR following RO/R1: 29% vs. 12%
– LR for all comers: 29% vs.15% - R1/2 margins are common in SP sarcomas, yet the trial only required 50.4 Gy RT, which is inadequate
- Tox rates in the radiotherapy plus surgery arm were unexpectedly high (77% grade 3-4) likely 2/2 poor RT protocol compliance (26% major deviation rate)
- ROs were allowed to deviate from international guidelines for RP sarcoma
- Did not require several OAR constraints
25
What is the LR rate for RP sarcomas s/p any tx?
- 5-yrs: 25%
- 8-yrs: 31%
- 10-yrs: 35%
26
When can brachytherapy monotherapy alone be considered for int/high-grade sarcoma s/p resection?
- size < 10 cm
- High-grade tumors
- -margins
## Footnote
Pisters trial (JCO 1996) showed that brachytherapy improved LC in high-grade and -margins, but NOT in +margins.
27
What doses are used for brachytherapy monotherapy alone for int/high-grade sarcoma s/p resection w/ -margins?
- LDR/PDR: 45-50 Gy
-- NCCN pref: 45 Gy
- HDR: 30-54 Gy (2-4.5 Gy fx given BID)
-- 36 Gy in 3.6 Gy BID over 10 fx
28
What doses are used for brachytherapy boost post-EBRT for int/high-grade STS s/p resection?
- LDR/PDR: 16-20 Gy
- HDR: 14-16 Gy in (2-4.5 Gy fx given BID)
29
Which sarcomas metastasize to LNs and at what rates?
- CARE (lowest to highest rates)
-- Clear cell sarcoma: 11.1%
-- Angiosarcoma: 11.1%
-- RMS: 19%
-- Epitheliod sarcoma: 20%
30
What is the expected rate of ≥ Gr 3 GI tox in RP sarcomas tx w/ pre-op RT f/b surgery?
~ 5%
## Footnote
Toronto Cross-Sectional Study
31
What is the per million incidence of RP sarcomas?
2.7 per 1 million
32
What is the 10-year survival of chondrosarcoma grade 1 s/p R0 GTR?
- ~80%
-- Grade 1 chondrosarcomas are classified by WHO as "atypical cartilaginous tumors"
-- Considered locally aggressive neoplasms and not malignant tumors
-- Rarely metastasize
33
What is the LC and median OS benefit of IORT w/ low-dose RT vs. high-dose RT in post-op per Sinderlar et al. 1993?
- IORT + LD-EBRT vs. HD-EBRT
-- LRR: 40% vs. 80% (Sig.)
-- Median OS: 45 vs. 52 mo (NS)
34
What is the rate of tumor regrowth during RT for sarcomas?
- 45%!
- Mostly happens in the first 2 weeks
35
What is the rate of tumor shrinkage during RT for sarcomas?
33%
36
Why are large margins and CBCT at least twice weekly recommended when radiating sarcomas?
Because around 45% of tumors can grow during RT, leading to underdosing if inadequate margins are used or tumor growth is not monitored w/ CBCT
37
What factors predict a higher rate of major wound complications for extremity or trunk STS s/p pre-op RT and surgery?
- Diabetes
- Tumor > 10 cm
- Tumors < 3 mm from the skin
- Use of vascular flap or STSG
| Baldini et al, 2013
38
What are the 8-yr LRR for RP liposarcomas and leiomyosarcoma?
- 8-yr LRR:
-- Leiomyosarcoma: 10%
-- Well-differentiated liposarcoma: 35%
-- Dedifferentiated liposarcoma grade 2-3: 48%
39
What is the risk of fracture after surgery and RT for extremity sarcoma?
4-8%
40
Which factors predict a higher risk of fracture after surgery and RT for extremity sarcoma?
- Sex (Fem > Male)
- Age (> 55 yrs)
- Radiation dose (50 Gy vs. 60-66 Gy)
- Compartment
- Tumor size
- Periosteal stripping
41
How is the risk of fracture after surgery and RT for extremity sarcoma related to RT dose?
5-yr risk of fracture
- 50 Gy: 0.6%
- 60-66 Gy: 7%
42
What dosimetric constraints for the bone may be used to reduce the risk of fracture?
- V40 <64%
- Dmean <37 Gy
- Dmax <59 Gy
- Avoid circumferential bone coverage with the 50 Gy IDL
43
Which syndrome is characterized by chronic lymphedema that leads to the formation of soft tissue sarcomas (STS)?
- Stewart Treves Syndrome (STS)
-- Rare
-- Soft tissue sarcoma (STS)
-- Occurs in women w/ lymphedema after breast cancer therapy
-- No effective therapy
| STS is a/w STS!
44
What kind of sarcoma is formed during Stewart Treves Syndrome (STS)?
Angiosarcoma
45
Which sarcoma has no AJCC staging system?
- Kaposi
- Use AIDS Clinical Trial Group (ACTG) TIS (tumor, immune system, systemic illness) system
46
Which adj. (or neoadj.) CHT regimen has demonstrated benefit in
- Doxorubicin ± Ifosfamide (best together)
-- LRR, Distant recurrence, and OS benefit
-- Used for pts at high risk of developing mets
--- Tumor > 5 cm
--- Int-high grade
47
What was the pt population, randomization, and primary EP of the NCI amputation vs. limb-sparing trial (Rosenberg et al. 1982)?
- Pt: High-grade extremity STS
- Randomization:
-- WLE + post-op 50 Gy + 10-20 Gy boost + adj CHT
-- Amputation + adj CHT
- Adj CHT: Doxorubicin, Cylophosphamide, MTX
- Primary EP:
48
What were the results of the NCI limb-sparing trial?
- RT vs. Amputation:
-- LR 15% vs. 0% amputation (p=0.06)
-- 5-yr DFS: 71% vs. 78% (NS)
-- 5-yr OS: 83% vs. 88% (NS)
49
What were the pt population, randomization, and primary EP of RTOG 0630 for extremity STS?
- Randomization:
-- Cohort A: Pre-op IGRT w/ CHT (arm closed early and not reported)
-- Cohort B: Pre-op IGRT w/o CHT
-- IMRT or 3DCRT allowed. 50 Gy. IMRT used in 75% of patients
- Primary EP: Late toxicities
50
What were the results and conclusions of RTOG 0630 for extremity STS?
- Results were compared to the preoperative arm of the CAN-NCIC-SR2 trial (Davis et al Radiother Oncol 2005).
-- 2-yr LC was 94%
--- All local failures were within the CTV
-- Grade 2 late toxicity (subcutaneous tissue fibrosis, joint stiffness, or edema) was 10.5% in this RTOG 0630 trial vs. 37% (P<0.001)
-- Grade 2 or greater tox:
-- FIbrosis: 5.3% vs. 31.5%
-- Stiffness: 3.5% vs. 17.8%
-- Edema: 5.3% vs 15.1%
51
What was the RT dose and how were RT volumes drawn in RTOG 0630 for extremity STS?
- Dose
-- 50 Gy in 25 fx
- Contouring
-- Grade 2/3, Size > 8 cm
--- CTV = GTV + 3 cm sup/inf + 1.5 cm radial
-- Grade 2/3, Size ≤ 8 cm
--- CTV = GTV + 2 cm sup/inf + 1 cm radial
52
When should the drain site be included in the CTV for post-op RT for extremity STS?
- Large CTV >5 cm
- Intermediate and high-grade tumors
- R1 resections
53
What are the different types of RT-induced STS?
- HALF:
1. **H**igh-grade undifferentiated pleomorphic sarcoma (26%)
2. **A**ngiosarcoma (21%)
3. **L**eiomyosarcoma (12%)
4. **F**ibrosarcoma (12%)
54
Do synovial sarcomas metastasize to LNs?
No!
55
What is the general tx paradigm for Dermatofibrosarcoma protuberans (DFSP)?
- Surgical resection w/ -margins
- Surgical resection w/ close (<1cm) or +margins → PORT
56
What is Dermatofibrosarcoma protuberans (DFSP)?
- Locally aggressive cutaneous STS
- Very rare
- ↑ local recurrence
- ↓ metastatic spread
57
Which genetic abnormality is a/w Dermatofibrosarcoma protuberans (DFSP)?
- (t(17;22) (q22;13)
- PDGTB/COL1A1 gene product
- Leads to continuous activation of the PDGF receptor b (PDGFRB), which is a tyrosine kinase.
58
What are the most common locations for Ewings sarcoma?
- Pelvis: 26%;
- Femur: 20%;
- Chest wall: 16%
-- Ribs: 10%
-- Scapula: 4%
-- Clavicle: 1.5%
-- Sternum: 0.5%
59
What are the most common locations for osteosarcoma?
- Femur (42%, with 75% of these tumors in the distal femur)
- Tibia (19%, with 80% of these tumors in the proximal tibia)
- Humerus (10% w/ 90% of these in the proximal humerus)
- Skull and jaw
- Pelvis (8%);
- Ribs (1.25%)
60
What are the absolute contraindications for the resection of RP sarcomas?
1. Spinal cord involvement
2. Distant metastases
3. Peritoneal implants
4. Involvement of the superior mesenteric vessels
5. Extensive vascular involvement (e.g. aorta)
61
Is involvement of inferior vena cava or iliac veins, a contraindication to RP sarcoma resection?
Yes, it is a relative contraindication
62
What are the OAR constraints for Pre-op RT for RP sarcomas?
1. Stomach and duodenum:
- V45 ≤ 100%, V50 < 50%, Max Dose 56 Gy
2. Small and large bowel contoured as peritoneal cavity
- V15 < 830 cm3 , V45 ≤ 195 cm3
3. Small bowel contoured as individual loops
- V15 < 120 cm3 , V55 < 20 cm3
5. Large bowel contoured as individual loops
- V60 < 20 cm3
63
What is the def. RT dose for desmoid tumors?
56 Gy in 28 fx
64
What is the characteristic protein expressed by chordomas?
- Brachyury
- It is ranscription factor protein that controls the development of notochord and mesoderm in humans
65
What is the tissue of origin of chordomas?
- Notochord remnants
- Can be found from the base-of-skull to sacral spine
66
What is the median age at dx of chrodomas?
- 60 yrs
- Base of skull chordomas present earlier
67
What proportion of chordomas arise at the base of the skull?
1/3 (clival region)
68
What proportion of chordomas arise from the sacrococcygeal region?
1/2
69
What is the general tx approach to chordomas?
Surgical resection ± RT
70
What cancers/tumors are a/w Li-Fraumeni syndrome?
- LABS
1. Leukemia
2. Adrenal Gland Cancer
3. Breast
4. Sarcoma
71
What is Gardner syndrome, and what cancers/tumors are a/w it?
1. Subtype of Familial Adenomatous Polyposis (FAP).
2. Autosomal dominant
3. Results from mutations in the APC gene on chromosome 5.
4. Multiple colon polyps
5. Cancer/tumor associations:
- Osteomas of the skull
- Fibromas
- Thyroid cancer
- Epidermoid cysts
- Desmoid tumors
72
What is Cowden Syndrome, and what cancers/tumors are a/w it?
1. aka Multiple hamartoma syndrome
2. Autosomal dominant
3. a/w PTEN mutations
4. Cancer/tumor associations:
- Benign Gl hamartomas
- Increased risk of several malignancies
-- Breast
-- Thyroid
-- Uterine
73
What is field cancerization and which sarcoma is usually a/w it?
- Def: Large areas of cells at a tissue surface or within an organ are affected by carcinogenic alterations
- a/w angiosarcoma
- poor prognosis
74
Which MRI sequence is used to delineate pre-op GTV for sarcomas?
- T1 post-contrast
75
How do you delineate CTV for RPS?
- When using 4D CT Sim
-- Geometric 1.5 cm expansion on iGTV
- When not using 4D CT Sim
-- Cephalo-caudad: 2-2.5 cm
-- Radial: 1.5-2 cm
76
What are the approaches to managing STS s/p non-oncologic resection w/ grossly + margin (R2)?
1. Preferred: Pre-op RT followed by re-resection
2. Adjuvant RT alone to a dose of 66-70 Gy, if the patient is not a further surgical candidate
3) Observation to allow the disease to 'declare' itself at which point a pre-op and surgery approach.
77
What were the findings of the NCI limb-sparing trial (Yang et al, 1998)?
- STS s/p limb-sparing surgery and -margins (1-2 cm) → observation vs. EBRT (45 Gy + 18 Gy boost to tumor bed)
-- Gross residual disease or +margins were excluded
-- Low-grade tumors LC: 60 vs. 95% (SS)
-- High-grade tumors LC: 75 vs. 100% (SS)
-- 10-yr OS ~75% (NS)
78
What is the age of dx of osteosarcoma?
- Bimodal distribution:
-- 10-24 yrs old
-- >70 yrs old
79
What are the most common sites of STS in adults?
- Lower extremity 46.4%
- Trunk 18%
- Upper extremities 13%
- Retroperitoneum 12.5%
- Head and neck 9%
- Mediastinum 1.3%
## Footnote
American college of surgeons
