SM_273b: Sarcomas Flashcards
____ are a group of rare solid tumors arising from mesenchymal tissue
Sarcomas are a group of rare solid tumors arising from mesenchymal tissue
- Soft tissue sarcomas
- Bone sarcomas
Describe soft tissue sarcomas
Soft tissue sarcomas
- Include fat, muscle, nerve and nerve sheath, blood vessel, and other connective tissue tumors
- Most common subtypes include leiomyosarcoma, pleomorphic sarcoma / malignant fibrous histiocytoma, liposarcoma, dermatofibrosarcoma, rhabdomyosarcoma, angiosarcoma, and malignant peripheral nerve sheath tumors
Describe bone sarcomas
Bone sarcomas
- Most common subtypes include osteosarcoma, chondrosarcoma, and Ewing’s sarcoma
____ is the most prevalent type of sarcoma
Leiomyosarcoma is the most prevalent type of sarcoma
Describe etiology of sarcomas
Sarcomas
- Fat - liposarcoma
- Smooth muscle - leiomyosarcoma
- Skeletal muscle - rhabdomyosarcoma
- Nerve - MPNST
- Blood vessels - angiosarcoma
- Connective tissues - fibrosarcoma
Sarcoma is associated with genetic syndromes: ____, ____, ____, and ____
Sarcoma is associated with genetic syndromes
- Li-Fraumeni (TP53 mutation)
- Retinoblastoma (RB1 gene deletion)
- NF-1 (NF1 mutation)
- Gardner (APC mutation)
Describe Li-Fraumeni syndrome
Li-Fraumeni syndrome
- Patient has been diagnosed with a sarcoma at a young age: below 45
- First-degree relative has been diagnosed with any cancer at a young age: below 45
- Another first-degree or second-degree relative has been diagnosed with any cancer at a young age (below 45) or with a sarcoma at any age
Describe clinical presentation and diagnosis of sarcomas
Clinical presentation and diagnosis of sarcomas
- Soft tissue masses are common and usually benign
- Variable: heterogeneous based on sites of origin
- Soft tissue of extremities and trunk wall: mass, generally painless or asymptomatic
- Malignant if: increasing in size, > 5 cm in size, deep to deep fascia, painful
Superficial soft tissue lesions > 5 cm and all deep-seated masses have a high risk of being a ___
Superficial soft tissue lesions > 5 cm and all deep-seated masses have a high risk of being a sarcoma
Describe pathologic features and prognostic features of sarcoma
Pathologic features and prognostic features of sarcoma
- Core needle biopsy
- Fine needle aspiration inadequate
- Tumor size, tumor size, tumor depth, tumor grade, histologic subtype, increasing age, metastatic disease at presentation, tumor site, and positive surgical margins
Most important factor for prognosis of sarcoma is ___
Most important factor for prognosis of sarcoma is grade of tumor
___ is primary treatment for sarcomas
Surgery is primary treatment for sarcomas
- R0 resection is required
- Adjuvant radiation to site of primary tumor for all soft tissue sarcomas of extremities / trunk > 5 cm
- No clear role for radiation in abdominal or visceral sarcomas
Adjuvant chemo for sarcomas is ___
Adjuvant chemo for sarcomas is controversial
- May shrink but not eliminate microscopic metastatic disease
- Not beneficial for soft tissue sarcomas arising from visceral or abdominal sites
- Patients with specific subtypes benefit: synovial sarcoma, high-grade myxoid / round cell liposarcoma
Describe treatment of metastatic soft tissue sarcomas
Treatment of metastatic soft tissue sarcomas
- Anthracyclines and alkylating agents yield best response rates
- Gemcitabine-docetaxel are synergistic combo
- Single agent therapy may be useful as combo therapy because doxorubicin and ifosfamide are not synergistic
____ and ____ are classic chemo drugs for metastatic sarcoma with highest response rates
Doxorubicin and ifosfamide are classic chemo drugs for metastatic sarcoma with highest response rates
Combo therapy is often ___ for metastatic sarcoma
Combo therapy is often beneficial for metastatic sarcoma
Sarcoma can benefit from ___
Sarcoma can benefit from targeted therapy
____ is beneficial for soft tissue sarcoma
Olaratumab is beneficial for soft tissue sarcoma
- Promotes greater survival
Liposarcomas are treated with ___ if well-differentiated
Liposarcomas are treated with surgery if well-differentiated
High grade myxoid liposarcomas have ___
High grade myxoid liposarcomas have t(12;16) or t(12;22) translocations
- TLS or ERSR1 coupled with CHOP
- Most chemotherapy sensitive liposarcoma subtype: doxorubicin, ifosfamide, trabectedin, eribulin
Leiomyosarcoma is treated with ___, ___, ___, or ___
Leiomyosarcoma is treated with doxorubicin, DTIC, gemcitabine, or gemcitabine-docetaxel
- Also trabectedin or eribulin
- May represent a distinct phenotype
Synovial sarcoma involves ____ or ____
Synovial sarcoma involves t(X;18) SYT-SSX1 (biphasic) or SYT-SSX2 (monophasic)
- Biphasic has better prognosis
- Among most sensitive adult sarcoma to chemotherapy especially to ifofsfamide regimens
- High grade
Describe treatment for soft tissue sarcoma
Soft tissue sarcoma treatment
- Stage I: surgery w/ wide excision ± radiation
- II and III: surgery with wide excision ± pre or postop RT ± chemo, or RT or chemo/RT or chemo if unresectable
- IV: metastectomy for limited disease, single or combination anthracycline-based chemotherapy
GI stromal tumors often involve ___
GI stromal tumors often involve gene mutations that cause malignant transformation
- KIT, PDGFRA
- Gain of function mutation result in abnormal constitutively activated RTKs: ligand independent mitogenic activity, stimulation of downstream signaling pathways
____ and ____ are common in GI stromal tumors and are the best predictors of clinical response to imatinib mesylate
KIT and PDGFRA are common in GI stromal tumors and are the best predictors of clinical response to imatinib mesylate
- KIT exon 11: favorable
- KIT exon 9: intermediate response
- Wild-type or PDGFRRA D842V: low response
- Exon 9 mutations are biologically more aggressive relative to other genotypes
Describe mechanism of imatinib mesylate for GI stromal tumors
Imatinib mesylate for GI stromal tumors
- Occupies ATP binding pocket of the KIT kinase domain
- Prevents substrate phosphorylation and signaling
- Inhibits proliferation and survival
___ is primarily modality for GI stromal tumors with adjuvant ___
Surgery is primarily modality for GI stromal tumors with adjuvant imatinib
___ is main treatment for metastatic GI stromal tumors
Imatinib is main treatment for metastatic GI stromal tumors
- Cytotoxic chemo is ineffective
Describe osteosarcoma
Osteosarcoma
- Peaks of incidence at age 10-20 and age 60-80: associated with Paget disease
- Arise in metaphysis of the bone
- Codman triangle: periosteal reaction
- Characterized by lytic and blastic features
- Neoadjuvant and/or adjuvant chemotherapy is standard care
Osteosarcoma is treated with ___
Osteosarcoma is treated with doxorubicin and cisplatin
Describe chondrosarcoma
Chondrosarcoma
- Second most common tumor of brain
- > 60 years of age
- Typically low or intermediate grade
- No role for chemo
- Multinodular growth pattern
Ewing’s sarcoma and PNET arise in ___ and ___
Ewing’s sarcoma and PNET arise in bones of children and commonly soft tissues in adults
- Always considered high grade
- Infiltrative onion skinning pattern in affecting shaft of bone
- Surgery, chemo, and radiation multimodal is standard of care
Describe chemo for Ewing’s sarcoma
Chemo for Ewing’s sarcoma
- Primary disease: vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide
- Metastatic disease: vincristine / doxorubicin / cyclophospamide followed by ifosfamide / etoposide at progression
Giant cell tumor is ___
Giant cell tumor is tumor composed of malignant stromal cells that secrete receptor activator of NFkB RANKL ligand and recruit multinucleated osteoclast like cells that result in bone lysis
____ is used to treat giant cell tumor of bone
Denosumab is used to treat giant cell tumor of bone
- Inhibitory monoclonal antibody
Describe survivorship of sarcomas
Sarcomas survivorship
- 1-2% treated with doxorubicin and ifosfamide develop symptomatic cardiomyopathy and 5-10% develop renal tubular / glomerular dysfunction with risk related to cumulative dose received
- Infertility is most often related to aklylating agent exposure and affects post-pubescent males more often than females
