Clinical Management of Sarcomas with Epithelioid Histology

1
Clinical Management of Sarcomas with Epithelioid
Histology

• Andrew J. Wagner, MD, PhD
• Center for Sarcoma and Bone Oncology
• Dana-Farber Cancer Institute
• Boston, MA

2
Heterogeneous Group of Tumors

• GIST
• Synovial Sarcoma
• Epithelioid Sarcoma
• Epithelioid Hemangioendothelioma
• Angiosarcoma
• Rhabdomyosarcoma
• Malignant Peripheral Nerve Sheath Tumor
• Alveolar Soft Part Sarcoma
• PEComa
• etc.

3
Heterogeneous Group of Tumors

• GIST
• Synovial Sarcoma
• Epithelioid Sarcoma
• Epithelioid Hemangioendothelioma
• Angiosarcoma
• Rhabdomyosarcoma
• Malignant Peripheral Nerve Sheath Tumor
• Alveolar Soft Part Sarcoma
• PEComa
• etc.

4
Epithelioid Sarcoma - Presentation

• Rare tumor of young adults
• Male predominance
• Superficial nodules or deep mass
• Proximal-type involvoing perineum/trunk

5
Epithelioid Sarcoma - Treatment

• Surgical management
• Propensity for lymph node metastases
• No evidence for benefit of lymphadenectomy
• Role of radiation?
• Limited, if any, role of systemic chemotherapy
• Role of targeted agents?
• Role of isolated limb perfusion?

6
Epithelioid Sarcoma Case Series
Baratti et al. (2007) Annals of Surgical Oncology
7
Epithelioid Sarcoma Case Series
Baratti et al. (2007) Annals of Surgical Oncology
8
Epithelioid Sarcoma - Management

• Surgery
• Wide excision (30 patients)
• Re-excision (14)
• Digit or ray amputation (5)
• Limb amputation (5)
• Regional lymphadenectomy (6)
• Adjuvant therapy
• postoperative RT (20)
• Preoperative Isolated Limb Perfusion (9)
• Ifosfamide/anthracycline-based chemotherapy (18)

9
Overall Survival
primary tumor
recurrent
10
Survival based on Local-Regional Metastasis
Without
With
11
de Vischer et al. (2006) Cancer107606
12
Epithelioid Hemangioendothelioma

• Sarcoma with vascular differentiation
• Liver, lung, bone common primary sites
• 10/30 primary hepatic sarcomas in 23 year MSKCC
  case series Weitz et al. (2007) Cancer 1091391
• Often incidental finding on chest X-ray or CT
  scan
• Ranges from very indolent course to
  angiosarcoma-like

13
Epithelioid Hemangioendothelioma
no evidence of disease at death
2 EHE each
1 died of disease at 14 months (R1) 1 alive with
disease at 24 months (R2)
Weitz et al. (2007) Cancer 1091391
14
Epithelioid Hemangioendothelioma

• When to treat?
• Progression of disease
• Symptoms
• Patient preference
• What to use?
• liposomal doxorubicin
• paclitaxel
• docetaxel
• interferon?
• liver transplantation???
• 5 year survival 70 Nissen et al. (2004) Cancer
  J. 1088

15
Epithelioid Hemangioendothelioma
5 year disease-specific survival 58
Weitz et al. (2007) Cancer 1091391
16
Epithelioid Hemangioendothelioma

• some patients die in months, whereas others
  remain alive and asymptomatic for more than 20
  years after diagnosis.

Kelly and ONeil (2005) Lancet Oncology 6813
17
Angiosarcoma

• Cutaneous angiosarcoma
• Visceral angiosarcoma
• liver, spleen, heart
• Breast angiosarcoma
• primary
• post-treatment for breast cancer
• radiation (7-15 years later)
• chronic lymphedema (Stewart-Treves syndrome)

18
patien
n

161 patients in 24 years
161
Fayette et al. (2007) Annals of Oncology 182030
19
Fayette et al. (2007) Annals of Oncology 182030
20
Median survival 42 months 5 year overall
survival 43
Fayette et al. (2007) Annals of Oncology 182030
21
Prognostic Factors
Fayette et al. (2007) Annals of Oncology 182030
22
Primary Hepatic Angiosarcoma
Weitz et al. (2007) Cancer 1091391
23
Treatment

• Complete surgical resection when possible
• Axillary node dissection NOT indicated for breast
  angiosarcoma
• Consideration of radiation/chemotherapy
• Case reports of active agents
• anthracyclines
• taxanes
• vinorelbine
• sorafenib? (DAdamo et al. ASCO 2007)
• other anti-VEGF/VEGFR2 agents?

24
Conclusions

• Rare tumors for which randomized data do not (and
  likely will not) exist
• Epithelioid sarcoma late relapses common
  questionable sensitivity to chemotherapy.
• EHE often indolent
• Angiosarcoma typically aggressive and often
  sensitive to chemotherapy, transiently
• Better molecular understanding and new
  therapeutics are needed