Style E 36 by 54

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The Use of ICE therapy (Ifosfamide, Carboplatin
and Etopside) and Avastin/Irinotecan to Treat
Undifferentiated Embryonal Sarcoma Alison Chase
DO, Asneha Iqbal MD, Sharad Salvi MD, Ammar
Hayani MD, Rebecca McFall MD, Jason Canner
DO Department of Pediatrics, Department of
Hematology/Oncology, Advocate Hope Childrens
Hospital, Oak Lawn, IL,
Abstract
Diagnosis
Review of Literature
Pachera, S. Nishio, H. Takahashi, Y. et al.
Undifferentiated Embryonal Sarcoma of the Liver
case report and literature survey. Journal
Hepatobiliary Pancreatic Surgery, 15 536-544,
2008.
Background Undifferentiated embryonal sarcoma is
the third most common type of hepatic malignancy
in children. Current management consists of
multiple agent chemotherapy, most often
Doxorubicin and Ifosfamide although, this
aggressive disease traditionally shows a limited
response to chemotherapy making surgical
resection imperative. Metastatic and
non-responsive disease has poor overall survival
with inadequate treatment options. To our
knowledge this is the first report of successful
salvage chemotherapy using a combination of ICE
therapy (Ifosfamide, Carboplatin, and Etoposide),
alternating with Avastin and Irinotecan.
Design/Method We describe a case of a nine-year
old male diagnosed with an undifferentiated
embryonal sarcoma of the liver. The patient
presented with two weeks of right upper quadrant
abdominal pain, fatigue and fevers. Review of
systems was notable for weight loss and night
sweats. Exam was significant for hepatomegaly and
decreased breath sounds at the right lung.
Evaluation with a computed tomography scan
confirmed a large mass replacing the right lobe
of the liver with bilateral metastatic nodules
within the lungs. Biopsy confirmed the diagnosis.
Following high risk tumor stratification,
chemotherapy was initiated using Doxorubicin and
Ifosfamide per COG ARST0332. Due to disease
progression, standard therapy was discontinued
and a regimen of ICE alternating with Avastin and
Irinotecan was initiated. Partial response of the
primary tumor with near resolution (VGPR) of lung
metastases allowed for complete surgical
resection. The patient is currently in
remission. Conclusion Undifferentiated embryonal
sarcoma of the liver is known to be aggressive.
Although we have had some success with localized
disease, metastatic and non-responsive tumors
have poor outcomes. A novel regimen using ICE
alternating with Avastin and Irinotecan may
enhance chemosensitivity allowing for tumor
resection and improved survival. This
combination should be considered when traditional
therapy is unsuccessful.

• Summary
• n 51
• Initial therapy
• Combination sarcomatous thearpy
• 35 patients surgical resection
• 20/35 alive
• All patients w/o resection DOD
• 2 patients received radiotherapy
• 33 patients evaluable/follow-up
• 16 tumor recurrence
• 4/16 alive

Van Winkle, P. Angiolillo, A. Krailo, M et al.
Ifosfamide, Carboplatin, and Etoposide (ICE)
Reinduction Chemotherapy in a Large Cohort of
Children and Adolescents WithRecurrent/Refractory
Sarcoma The Childrens Cancer Group (CCG)
Experience. Pediatric Blood and Cancer. 2005 44
338-347.

• 6 patients with undifferentiated sarcoma
• Evaluable patients with refractory/recurrent
  sarcoma
• 27 (n26) with CR
• 24 (n23) with PR
• 33 (n32) stable disease
• Overall Survival
• 1yr 49 2yrs 28
• Responders 1yr 71 2yrs 41 (CR 81, 54)

Introduction

• Physical exam
• Decreased breath sounds RML/RLL
• Mild respiratory distress
• Hepatomegaly - 8 cm
• Negative for abdominal tenderness
• splenomegaly jaundice scleral icterus
• lymphadenopathy.

• Pathology
• Undifferentiated hepatic embryonal sarcoma.
• Solid and cystic components.
• Atypical spindle/stellate cells with variable
• myxoid stroma, mitotic figures and
• multinucleated or giant tumor cells.

• Imaging
• CT abdomen
• Large mass replacing much of the right
• lobe of the liver
• CT chest
• Multiple bilateral nodular masses

Hepatic tumors account for 0.5-2 of all
primary pediatric malignancies. Embryonal
sarcoma is the third most common following
hepatoblastoma and hepatocellular carcinoma.
It is a rare, rapidly growing, aggressive
malignant tumor that typically occurs in children
ages 5-10 yrs old. The common presentation is an
abdominal mass with pain. Nausea, anorexia or
fever may also be seen. Historically,
embryonal sarcomas have a poor prognosis,
particularly because the tumor is often
chemoresistant. Chemotherapy alone provides no
evidence of cure unfortunately, surgical
resection is not achievable in greater than 60
of liver tumors, due to the size and/or location.
Current management consists of a multi-modality
approach using chemotherapy and radical surgical
resection if possible. Radiation has had limited
success due to the normal liver parenchymas
maximum-tolerated dose. Chemotherapy for an
embryonal sarcoma, grouped with
non-rhabdomyosarcoma soft tissue sarcoma (NRSTS),
is currently based on COG ARST0332 (Ifosfamide
and Doxorubicin). For tumors that are not
responding or progressive on standard therapy,
there are limited options. We suggest ICE
regimen (Ifosfamide, Carboplatin, and Etoposide),
most commonly used in the treatment of recurrent
lymphomas or sarcomas, alternating with Avastin
and Irinotecan as salvage therapy.

• The patient received 7 cycles ICE alternating
  with Avastin/Irinotecan
• Following 5 cycles of therapy significant
  reduction of the primary tumor complete surgical
  resection was accomplished.
• Additional local control was achieved with
  radiotherapy
• Lung metastases have resolved.
• Most recently, 12 months post therapy, the
  patient remains in remission.

Intervention
Conclusion
C.
A.

• Surgical resection continues to be the primary
  modality offering cure. Neoadjuvant therapy
  often is necessary to decrease tumor size and
  treat metastasis.
• A chemotherapy regimen of ICE alternating with
  Avastin and Irinotecan should be considered with
  refractory or recurrent embryonal sarcoma of the
  liver.

Case Presentation
A 9 yr old Hispanic male, with unremarkable past
medical history, was admitted for complaints of
abdominal pain, fatigue and fevers for a duration
of 2 weeks. Pain originally started in the right
upper quadrant and became persistent, localized
to the right flank. Low grade fevers were noted
before bed and in the early morning associated
with night sweats. During this time, there was
an eleven pound weight loss. Patient denied
nausea, emesis or persistent diarrhea. Eight
days prior to admission, the patient was
diagnosed with influenza and conjunctivitis, and
treated with antibiotics. Persistent symptoms
prompted further evaluation. Labs revealed a
microcytic anemia and elevated LDH. Chest x-ray
revealed a right-sided mass occupying lesion with
severe hepatomegaly.
D.
B.
References

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Figure A, B Chemotherapy was initiated per COG
ARST0332, for non-rhabdomyosarcoma tumors, with
Doxorubicin and Ifosfamide.
Figure C, D Due to disease progression, therapy
was changed to salvage therapy with ICE regimen
(Ifosfamide, Carboplatin, and Etoposide)
alternating with Avastin and Irinotecan.