Pocket Oncology (Pocket Notebook Series), 1st Ed.


David B. Page and William D. Tap

Epidemiology & Etiology

• 1% of all CA w/>50 histotypes; 11K cases & 4K death annually, increasing w/more sensitive dx of GIST tumors

• STS represent a heterogeneous spectrum of malignancies w/varied genetic aberrations & clinical features

• Potentially curable if resected early; only 1:100 soft tissue tumors are malignant

• Associated w/genetic syndromes (FAP → desmoid fibromatosis; NF-1 → malignant peripheral nerve sheath tumor; LFS → rhabdomyosarcoma), radiation, lymphedema

• Radiation-associated sarcomas arise w/variable latency, generally poor prognosis

Clinical Manifestations

• Typically presents as painless mass of the extremities (60%), trunk (19%), RP (15%), HEENT (9%)

• Met generally hematogenous, frequently to lung (70%)

• Retroperitoneal & visceral primaries recur locally, less commonly to liver

• LN mets observed in clear cell, epithelioid, angiosarcoma, & rhabdomyosarcoma

• Myxoid/round cell liposarcomas may spread to RP, spine, & paraspinous tissue

Molecular Biology & Pathology

• Histotypes do not necessarily arise from mature tissue counterparts

• Associated w/either simple genetic aberrations (translocations, amp, Mts) or complex karyotype

• Complex karyotypes: Driven by derangements in p53, MDM2, pRb, p16INK4a

• Molecular/genetic analyses are reshaping tx paradigm, w/increasing sarcoma histotypes amenable to targeted therapies (see table)

Workup and Staging

• Bx: incisional or core (w/multiple specimens), ensuring resectablility of bx tract, as well as hemostasis to minimize seeding

• Imaging: CT-CAP (MRI or CT angio for nonabdominal primaries); consider PET to assess chemotherapy response; CNS imaging useful for alveolar soft part sarcoma, solitary fibrous tumor, PNET, angiosarcoma

• Staging: Controversial utility, most sited is AJCC 7th ed. 2010 staging (TNM)

• Stage IA: Tumor ≤5 cm (T1) + no nodes (N0), grade indetermined (X)-1 Stage IB: Tumor > 5 cm (T2) +N0, GX-1; Stage IIA: T1N0 + G2–3; Stage IIB: T2N0 + G2, Stage III: T2N0 + G3, or involved nodes (N1); Stage IV:Mets (M1)

• Localized tumors should be designated as superficial (T1a, above & not invading fascia) or deep (T1b, invading or below fascia)

• FISH & PCR used in molecular dx

• Nomogram available to predict 12-y sarcoma-specific death (J Clin Oncol 2002;20:791)

Localized Disease: Management

• Tx at sarcoma referral center is advised

• Wide local excision is mainstay, usu w/perioperative radiation (may consider omitting RT if >1 cm margin)

• RT: Pre-op vs. post-op RT of equivalent benefit; pre-op RT ↑ acute wound healing complications but post-op RT ↑ late complications (Curr Opin Oncol 2005;17:357)

• Consider pre-op systemic tx ± RT to downstage unresectable abdominal lesions; intra-operative RT also employed

• Adjuvant chemotherapy: Should be considered on case-by-case basis w/pt; doxorubicin-based tx considered in synovial sarcoma & myxoid/round cell liposarcoma

• Surveillance: PEx & imaging of chest & 1°, interval depends on histotype

• Oligometastatic disease: Surgical resection & other localized therapies (RT, ablation) in selected pts yield long-term survival & possibility of cure

• Rhabdomyosarcoma: Enrollment in a pediatric COG trial is favored & open to pts <50 y; adjuvant chemotherapy recommended w/RT if positive margins; selection of chemotherapy based upon risk of recurrence (low risk → vincristine + dactinomycin; high risk → vincristine + dactinomycin + cyclophosphamide) (J Clin Oncol 2009;27:5182)

Metastatic/Unresectable Disease: Management

• Observation may be considered in selected pts w/low-grade asymptomatic disease

• Response to chemotherapy a/w age <40 y, myxoid/round cell liposarcoma or synovial sarcoma histology, no bone mets, & combination chemo (Cancer 2008;112:1585)

• Clinical trials & molecularly targeted therapies (see table) should be considered

• Chemosensitivity varies by histotype & tx should be tailored appropriately. Egs of histotype tailored treatments include:

• Synovial sarcoma: Ifosfamide

• Myxoid/round cell liposarcoma: Ifosfamide; trabectedin (not yet FDA approved)

• Angiosarcoma: Paclitaxel (J Clin Oncol 2008;26:5269) or pegylated doxorubicin, VEGF-directed Rx may be considered

• Desmoid fibromatosis: NSAIDS (sulindac), low-dose IFN, doxorubicin (Cancer 2010;116:2258), imatinib, sorafenib (Clin Cancer Res 2011;17:4082)

• Uterine or GI Leiomyosarcoma: Gemcitabine + docetaxel (Ann Oncol 2010;21:supp.8)

• Solitary Fibrous Tumor/Hemangiopericytoma: Bev + temozolamide, sunitinib (J Clin Oncol 2009;27:3154)

• 1st-line Tx: Doxorubicin monotherapy is historical gold standard for STS; ifosfamide is equally efficacious but more toxic (J Clin Oncol 2007;25:3144)

• Combination regimens such as AIM (doxorubicin + ifosfamide + mesna) ↑ RR but no proven OS improvement, ↑ tox (Cochrane Database Syst Rev 2003)

• Combination chemotherapy appropriate in select pts, eg, young pts w/good PS, or pts w/sev. pain or pending bronchial obstruction

• Liposomal doxorubicin: Improved s/e profile; similar efficacy but limited head-to-head data compared to standard doxorubicin

• Pazopanib (anti-VEGF TKI): 2nd-line based upon ↑ PFS in anthracycline-experienced nonadipocytic STS (PALETTE Lancet 2012;379:1879)

• Other active chemotherapies: GEM + docetaxel, DTIC/temozolomide, vinorelbine, MTX, cisplatin, carboplatin

Kaposi Sarcoma: Management

• A/w immunodeficiency (HIV); classified & treated separately from other sarcomas

• HAART: CR in 80%; immune-constitution inflammatory syndrome (KS-IRIS) occurs in <10% & can lead to rapid progression

• Localized Tx: Resection, RT, cryotherapy, intralesional vinblastine/bleomycin, topical alitretinoin, imiquimod

• Systemic Tx: 1st-line → liposomal doxorubicin; alternatives include vinblastine ± bleomycin, paclitaxel, oral etoposide (60–90% ORR)