Transcript The Use of ICE therapy (Ifosfamide, Carboplatin and Etopside) and... Undifferentiated Embryonal Sarcoma

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 Children’s 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.
Introduction
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.
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 Children’s Cancer Group (CCG) Experience. Pediatric Blood and Cancer.
2005; 44: 338-347.
Physical exam:
Imaging:
Pathology:
 Decreased breath sounds RML/RLL
CT abdomen
 Large mass replacing much of the right
lobe of the liver
CT chest
 Multiple bilateral nodular masses
 Undifferentiated hepatic embryonal sarcoma.
 Mild respiratory distress
 Hepatomegaly - 8 cm
 Negative for abdominal tenderness;
splenomegaly; jaundice; scleral icterus;
lymphadenopathy.
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.
 Solid and cystic components.
 Atypical spindle/stellate cells with variable
myxoid stroma, mitotic figures and
multinucleated or giant tumor cells.
Intervention
C.
A.
complete surgical resection was accomplished.
 Additional local control was achieved with radiotherapy
 Lung metastases have resolved.
Conclusion
 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
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.
The patient received 7 cycles ICE alternating with Avastin/Irinotecan
 Following 5 cycles of therapy & significant reduction of the primary tumor
Most recently, 12 months post therapy, the patient remains in remission.
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
parenchyma’s 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.
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.
 6 patients with undifferentiated sarcoma
 Evaluable patients with refractory/recurrent sarcoma
 27% (n=26) with CR
 24% (n=23) with PR
 33% (n=32) stable disease
 Overall Survival
 1yr: 49%; 2yrs: 28%
 Responders: 1yr: 71%; 2yrs: 41% (CR: 81%, 54%)
B.
D.
Figure A, B: Chemotherapy was initiated per COG ARST0332, for nonrhabdomyosarcoma 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.
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