SM_273b: Sarcomas

Question 1

____ are a group of rare solid tumors arising from mesenchymal tissue

Answer 1

Sarcomas are a group of rare solid tumors arising from mesenchymal tissue

• Soft tissue sarcomas
• Bone sarcomas

Question 2

Describe soft tissue sarcomas

Answer 2

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

Question 3

Describe bone sarcomas

Answer 3

Bone sarcomas

• Most common subtypes include osteosarcoma, chondrosarcoma, and Ewing’s sarcoma

Question 4

____ is the most prevalent type of sarcoma

Answer 4

Leiomyosarcoma is the most prevalent type of sarcoma

Question 5

Describe etiology of sarcomas

Answer 5

Sarcomas

• Fat - liposarcoma
• Smooth muscle - leiomyosarcoma
• Skeletal muscle - rhabdomyosarcoma
• Nerve - MPNST
• Blood vessels - angiosarcoma
• Connective tissues - fibrosarcoma

Question 6

Sarcoma is associated with genetic syndromes: ____, ____, ____, and ____

Answer 6

Sarcoma is associated with genetic syndromes

• Li-Fraumeni (TP53 mutation)
• Retinoblastoma (RB1 gene deletion)
• NF-1 (NF1 mutation)
• Gardner (APC mutation)

Question 7

Describe Li-Fraumeni syndrome

Answer 7

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

Question 9

Describe clinical presentation and diagnosis of sarcomas

Answer 9

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

Question 10

Superficial soft tissue lesions > 5 cm and all deep-seated masses have a high risk of being a ___

Answer 10

Superficial soft tissue lesions > 5 cm and all deep-seated masses have a high risk of being a sarcoma

Question 11

Describe pathologic features and prognostic features of sarcoma

Answer 11

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

Question 12

Most important factor for prognosis of sarcoma is ___

Answer 12

Most important factor for prognosis of sarcoma is grade of tumor

Question 13

___ is primary treatment for sarcomas

Answer 13

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

Question 14

Adjuvant chemo for sarcomas is ___

Answer 14

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

Question 15

Describe treatment of metastatic soft tissue sarcomas

Answer 15

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

Question 16

____ and ____ are classic chemo drugs for metastatic sarcoma with highest response rates

Answer 16

Doxorubicin and ifosfamide are classic chemo drugs for metastatic sarcoma with highest response rates

Question 17

Combo therapy is often ___ for metastatic sarcoma

Answer 17

Combo therapy is often beneficial for metastatic sarcoma

Question 18

Sarcoma can benefit from ___

Answer 18

Sarcoma can benefit from targeted therapy

Question 19

____ is beneficial for soft tissue sarcoma

Answer 19

Olaratumab is beneficial for soft tissue sarcoma

• Promotes greater survival

Question 20

Liposarcomas are treated with ___ if well-differentiated

Answer 20

Liposarcomas are treated with surgery if well-differentiated

Question 21

High grade myxoid liposarcomas have ___

Answer 21

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

Question 22

Leiomyosarcoma is treated with ___, ___, ___, or ___

Answer 22

Leiomyosarcoma is treated with doxorubicin, DTIC, gemcitabine, or gemcitabine-docetaxel

• Also trabectedin or eribulin
• May represent a distinct phenotype

Question 23

Synovial sarcoma involves ____ or ____

Answer 23

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

Question 24

Describe treatment for soft tissue sarcoma

Answer 24

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

Question 25

GI stromal tumors often involve \_\_\_

Answer 25

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

Question 26

\_\_\_\_ and ____ are common in GI stromal tumors and are the best predictors of clinical response to imatinib mesylate

Answer 26

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

Question 27

Describe mechanism of imatinib mesylate for GI stromal tumors

Answer 27

Imatinib mesylate for GI stromal tumors 1. Occupies ATP binding pocket of the KIT kinase domain 2. Prevents substrate phosphorylation and signaling 3. Inhibits proliferation and survival

Question 28

\_\_\_ is primarily modality for GI stromal tumors with adjuvant \_\_\_

Answer 28

Surgery is primarily modality for GI stromal tumors with adjuvant imatinib

Question 29

\_\_\_ is main treatment for metastatic GI stromal tumors

Answer 29

Imatinib is main treatment for metastatic GI stromal tumors * Cytotoxic chemo is ineffective

Question 30

Describe osteosarcoma

Answer 30

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

Question 31

Osteosarcoma is treated with \_\_\_

Answer 31

Osteosarcoma is treated with doxorubicin and cisplatin

Question 32

Describe chondrosarcoma

Answer 32

Chondrosarcoma * Second most common tumor of brain * \> 60 years of age * Typically low or intermediate grade * No role for chemo * Multinodular growth pattern

Question 33

Ewing's sarcoma and PNET arise in ___ and \_\_\_

Answer 33

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

Question 34

Describe chemo for Ewing's sarcoma

Answer 34

Chemo for Ewing's sarcoma * Primary disease: vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide * Metastatic disease: vincristine / doxorubicin / cyclophospamide followed by ifosfamide / etoposide at progression

Question 35

Giant cell tumor is \_\_\_

Answer 35

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

Question 36

\_\_\_\_ is used to treat giant cell tumor of bone

Answer 36

Denosumab is used to treat giant cell tumor of bone * Inhibitory monoclonal antibody

Question 37

Describe survivorship of sarcomas

Answer 37

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