[ROQs] Sarcoma Flashcards
What is the AJCC 8th edition T classification of STS?
- T1: ≤ 5cm
- T2: > 5cm ≤ 10 cm
- T3: > 10 cm ≤ 15 cm
- T4: > 15 cm
What are the AJCC 8th edition N and M classifications of STS?
- N
- N0: no lymph nodes
- N1: regional LN metastases - M
- M0: none
- M1: distant metastasis
What are the AJCC 8th ed. prognostic stage groups STS?
- 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
What is the AJCC 8th edition TNM classification of bone sarcomas?
- 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
What are the AJCC 8th ed. prognostic stage groups RP sarcomas?
- 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
What are some common sites of metastases for retroperitoneal sarcomas?
- Liver
- Lungs
What are some common histologies of RP sarcomas?
- Leiomyosarcoma
- Liposarcoma
- Undifferentiated STS
Of all sarcomas, what % are RP sarcomas?
10-15%
What was the pt population, randomization, and primary endpoint of NCIC pre-op vs. post-op RT for extremity STS?
- 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
What were the results of NCIC pre-op vs. post-op RT for extremity STS?
- 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
What are the adverse prognostic factors for distant recurrence in extremity STS?
Distant recurrence:
- Intermediate/large tumor size
- High grade
- Deep location
- Recurrent disease at presentation
- Leiomyosarcoma
What are the adverse prognostic factors for local recurrence in extremity STS?
- Age (>/< 50)
- Size (>/< 5 cm)
- margins (+ vs. close vs. -)
- Grade (high vs. low)
- Previous recurrence
- Histologic subtypes
– fibrosarcoma
– malignant peripheral-nerve tumor
MSKCC Nomogram
What is the most common sarcoma in adults?
- Leiomyosarcoma
- 20-25% of all STS
Which genetic alteration is a/w leiomyosarcoma?
- 12q amplification including MDM2 and CDK4 genes
- Shared by well-differentiated and dedifferentiated leiomyosarcoma
What are the different subtypes of liposarcoma?
- Well-differentiated/dedifferentiated liposarcoma
- Myxoid/round cell liposarcoma
- Pleomorphic liposarcoma.
Which genetic alteration is a/w Ewing sarcoma?
- t(11;22) translocation
- Present in ~85%
Which genetic alteration is a/w myxoid round cell liposarcoma?
t(12;16) → FUS-DDIT3 fusion gene
Which genetic alteration is a/w RMS?
- t(1;13) → PAX7/FOX01 fusion
- t(2;13) → PAX3/FOX01 fusion
Which genetic alteration is a/w alveolar soft part sarcomas?
t(x;17) → ASPL-TFE3 fusion gene
Which genetic alteration is a/w synovial sarcomas?
t(x;18) → SS18-SSX1 fusion gene
Which genetic alteration is a/w clear cell sarcomas?
- t(12;22) → ATF1-ESWR1 fusion gene
- Present in ~90% cases
What was the pt population, randomization, and primary endpoint of the STRASS 1 trial for sarcomas?
- 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
What were the results and the official main conclusion of the STRASS 1 trial for sarcomas?
- 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
What are the main RO criticisms of the STRASS 1 trial for sarcomas?
- 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
What is the LR rate for RP sarcomas s/p any tx?
- 5-yrs: 25%
- 8-yrs: 31%
- 10-yrs: 35%
When can brachytherapy monotherapy alone be considered for int/high-grade sarcoma s/p resection?
- size < 10 cm
- High-grade tumors
- -margins
Pisters trial (JCO 1996) showed that brachytherapy improved LC in high-grade and -margins, but NOT in +margins.
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
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)
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%
What is the expected rate of ≥ Gr 3 GI tox in RP sarcomas tx w/ pre-op RT f/b surgery?
~ 5%
Toronto Cross-Sectional Study
What is the per million incidence of RP sarcomas?
2.7 per 1 million
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
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)
What is the rate of tumor regrowth during RT for sarcomas?
- 45%!
- Mostly happens in the first 2 weeks
What is the rate of tumor shrinkage during RT for sarcomas?
33%
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
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
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%
What is the risk of fracture after surgery and RT for extremity sarcoma?
4-8%
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
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%
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
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!
What kind of sarcoma is formed during Stewart Treves Syndrome (STS)?
Angiosarcoma
Which sarcoma has no AJCC staging system?
- Kaposi
- Use AIDS Clinical Trial Group (ACTG) TIS (tumor, immune system, systemic illness) system
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
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:
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)
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
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%
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
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
What are the different types of RT-induced STS?
- HALF:
1. High-grade undifferentiated pleomorphic sarcoma (26%)
2. Angiosarcoma (21%)
3. Leiomyosarcoma (12%)
4. Fibrosarcoma (12%)
Do synovial sarcomas metastasize to LNs?
No!
What is the general tx paradigm for Dermatofibrosarcoma protuberans (DFSP)?
- Surgical resection w/ -margins
- Surgical resection w/ close (<1cm) or +margins → PORT
What is Dermatofibrosarcoma protuberans (DFSP)?
- Locally aggressive cutaneous STS
- Very rare
- ↑ local recurrence
- ↓ metastatic spread
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.
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%
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%)
What are the absolute contraindications for the resection of RP sarcomas?
- Spinal cord involvement
- Distant metastases
- Peritoneal implants
- Involvement of the superior mesenteric vessels
- Extensive vascular involvement (e.g. aorta)
Is involvement of inferior vena cava or iliac veins, a contraindication to RP sarcoma resection?
Yes, it is a relative contraindication
What are the OAR constraints for Pre-op RT for RP sarcomas?
- Stomach and duodenum:
- V45 ≤ 100%, V50 < 50%, Max Dose 56 Gy - Small and large bowel contoured as peritoneal cavity
- V15 < 830 cm3 , V45 ≤ 195 cm3 - Small bowel contoured as individual loops
- V15 < 120 cm3 , V55 < 20 cm3 - Large bowel contoured as individual loops
- V60 < 20 cm3
What is the def. RT dose for desmoid tumors?
56 Gy in 28 fx
What is the characteristic protein expressed by chordomas?
- Brachyury
- It is ranscription factor protein that controls the development of notochord and mesoderm in humans
What is the tissue of origin of chordomas?
- Notochord remnants
- Can be found from the base-of-skull to sacral spine
What is the median age at dx of chrodomas?
- 60 yrs
- Base of skull chordomas present earlier
What proportion of chordomas arise at the base of the skull?
1/3 (clival region)
What proportion of chordomas arise from the sacrococcygeal region?
1/2
What is the general tx approach to chordomas?
Surgical resection ± RT
What cancers/tumors are a/w Li-Fraumeni syndrome?
- LABS
1. Leukemia
2. Adrenal Gland Cancer
3. Breast
4. Sarcoma
What is Gardner syndrome, and what cancers/tumors are a/w it?
- Subtype of Familial Adenomatous Polyposis (FAP).
- Autosomal dominant
- Results from mutations in the APC gene on chromosome 5.
- Multiple colon polyps
- Cancer/tumor associations:
- Osteomas of the skull
- Fibromas
- Thyroid cancer
- Epidermoid cysts
- Desmoid tumors
What is Cowden Syndrome, and what cancers/tumors are a/w it?
- aka Multiple hamartoma syndrome
- Autosomal dominant
- a/w PTEN mutations
- Cancer/tumor associations:
- Benign Gl hamartomas
- Increased risk of several malignancies
– Breast
– Thyroid
– Uterine
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
Which MRI sequence is used to delineate pre-op GTV for sarcomas?
- T1 post-contrast
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
What are the approaches to managing STS s/p non-oncologic resection w/ grossly + margin (R2)?
- Preferred: Pre-op RT followed by re-resection
- 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.
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)
What is the age of dx of osteosarcoma?
- Bimodal distribution:
– 10-24 yrs old
– >70 yrs old
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%
American college of surgeons
