273. Sarcoma Flashcards

1
Q

Bone + Soft Tissue Sarcoma

  • epi: what is the most prevalent subtype? ages, prevalence of both main categories
  • etiology
  • RF
A

Affect all ages - more as age increases (higher proportions of sarcoma in children though due to less diseases then)
80% are Soft Tissue Sarcoma (Leiomyo, pleomorphic, lipo, dermatofibro, rhabdomyo, angio)
20% are Bone Sarcoma (osteo, chondro, Ewing’s)

Most prevalent subtype: Leiomyosarcoma (then malignant fibrous histiocytoma, then liposarcoma)

Eti:
Genetic Syndromes: Li Fraumeni (p53), Retinoblastoma (Rb), Neurofibromatosis type 1 (NF1), Gardner (APC)
Li Fraumeni: sarcoma <45yo, +FamHx (1 1st degree any cancer <45yo, 1/2nd degree any cancer <45 or sarcoma at any age)

RF: Genetic, Vinyl Chloride (occupational = hepatic angiosarcoma), Herbicides (Agent Orange), RT, for soft tissue (lymphedema, HHV-8 Kaposi’s)

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2
Q

What are the key somatic genetic characteristics of sarcoma?

A

KIT (>90% GISTs) - activating mutation
PDGF (100% dermatofibrosarcoma)
RANKL (Giant Cell Tumor)
NF1 (myxofibrosarcoma, malignant peripheral nerve sheath)
CDK4, MDM2 (liposarcoma)
Ch Translocation: Synovial sarcoma, Ewing Sarcoma t(11;22), alveolar rhabdomyosarcoma

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3
Q

Soft Tissue Sarcoma

  • CP
  • Staging
  • Prognostic Features
  • key sites of mets
A

Soft tissue masses: common, benign (lipoma)
STS: variable, usually painless mass or asx
Key features: Growing, >5cm LARGE, DEEP to deep fascia, PAINFUL

Stage: T1 < 5cm, T2 > 5cm (a - superficial, b - deep)

Prognostic Factors: Stage, size, depth, grade, metastatic disease, tumor site, positive surgical margins

  • high recurrence to lung or local primary site
  • most important factor is GRADE (needed for staging)
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4
Q

Soft Tissue Sarcoma Tx

  • what is primary tx
  • tx for mets disease (specific names)
  • targeted therapy for dermatofibrosarcoma, Giant cell tumor of bone, angiosarcoma, chordoma

What is the MoA of OLARATUMAB

A

Primary: SURGERY - get R0 resection (every tumor cell) +/- either Adjuvant (controversial - no clear benefit in visceral/abd sites) or preoperative chemotx

Mets: best tx is anthracyclines (doxorubicin) and alkylating agents (ifosfamide), balance synergy and toxicity in combo tx (Gemcitabine/Docetaxal good together); metastasectomy for limited disease

Dermatofibosarcoma: IMATINIB
Giant Cell Tumor of bone: DENOSUMAB (antiRANKL)
Angiosarcoma: VEGF-inhibitor
Chordoma: EGFR inhibitor

OLARATUMAB: Anti-PGFR-alpha-inhibitor - improves survival in STS

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5
Q

Subgroups of STS

  • Liposarcoma (epi within STS, locations for well-differentiated, dedifferentiated, myxoid)
  • High Grade Myxoid (genes, pt age, tx)
  • Leiomyosarcoma (tx)
  • Synovial Sarcoma (grade, genes, tx)
A

Liposarcoma

  • 2nd most common STS
  • well and de-differentiated: Retroperitoneum
  • Myxoid, Pleomorphic: Extremities

High Grade Myxoid (Round Cell Liposarcoma)

  • t(12;16) = TLS-CHOP
  • younger pts
  • most chemo-tx sensitive subset (Doxorubicin, ifosfamide, eribulin)

Leiomyosarcoma
- Sensitive to chemo: Doxorubicin, Gemcitabine-Docetaxel, Eribulin

Synovial Sarcoma

  • high grade
  • t(X;18) = SYT-SSX1 OR SYT-SSX2 (>90%)
  • most sensitive adult sarcoma to chemo-tx esp ifosfamide
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6
Q

GIST

  • epi (highest incidence geo and age)
  • genes and effect of mutation
  • prognosis groups
  • tx
  • tx of metastatic disease
A

Epi: higher incidence in Sweden, Netherlands; Ages 50-65yo
Genes: 80-85% KIT, 5-7% PDGFRA = gain of function cause overly activated RTK
Prognosis: Favorable if KIT exon 11, Intermediate if KIT exon 9, Low response if wild-type or PDGFRA mutation
Tx: IMATINIB: occupies ATP-binding site of KIT kinase = no signaling = no survival
MAIN TX: surgery with adjuvant imatinib
Metastatic disease: NO chemotx (ineffective)
- Imatinib, then higher dose imatinib, then SUNITINIB (multi-targeted RTK-i), then REGORAFENIB (anti-angiogenic via VEGFR-2 TKi)

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7
Q

Bone Sarcomas

  • Osteosarcoma (epi/age, location, imaging, tx with specific agents)
  • Chondrosarcoma (epi, grade, growth pattern, tx)
  • Ewing’s Sarcoma (epi, grade, location, imaging, tx)
  • Staging (T1-T3)
  • Giant cell tumor of bone (benign or malignant, marker, targeted tx)
A

Osteosarcoma

  • epi: most common bone tumor, bimodal (10-20; 60-80), assoc with PAGET’s disease
  • METAPHYSIS of bone
  • Imaging: Codman triangle (periosteal rxn)
  • lytic and blastic features
  • tx: neoadjuvant +/- adjuvant chemotx + surgery
  • std chemo: Doxorubicin, Cisplatin (amount determined by % necrosis)

Chondrosarcoma

  • epi: 2nd most common bone tumor, age >60yo
  • low/intermediate grade, multinodular growth
  • no role of chemotx

Ewing Sarcoma

  • in bones of children
  • always HIGH grade
  • in DIAPHYSIS of bone, “onion skinning” pattern
  • tx: multimodal: surgery, chemo (5 drug combo), radiation, clinical trials

T1: <8cm
T2: >8cm
T3: discontinuous tumor

Giant Cell Tumor of Bone

  • benign but may metastasize
  • secrete RANKL
  • Denosumab is anti-RANK-L Ab = decreases bone destruction
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8
Q

What are the 4 most common long-term complications with sarcoma chemotherapy/radiation tx?

A
  1. Secondary malignancy
  2. Renal Tubular +/- Glomerular Dysfx
  3. Cardiomyopathy
  4. Infertility
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