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Surgical Management of
Pulmonary Metastases in
Pediatric Patients with Ewing
Sarcoma
Kevin Hug
Case Presentation
• SM is a previously healthy 18 y/o M
• FHx: Stage IV tongue cancer in F and prostate cancer in
maternal GF.
• Intermittent L hip pain, for 1 year, worse over previous 2
months. Describes “tingling” in anterior thigh and
inability to participate in running sports for 2 months
CT Pelvis
• Operative biopsy is performed revealing Ewing
Sarcoma
Ewing Sarcoma
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Part of the Ewing family of tumors along with primitive
neuroectodermal tumors (PNET)
Malignant small, round blue cell tumors
Classically, 11;22 chromosomal translocation (FLI1/EWS fusion gene)
Other translocations are t(21;22) and t(7;22)
2nd most common primary bone tumor in children, male : female ratio
of 1.6 to 1
250 cases are diagnosed in the US per year
Ewing Sarcoma
• Most common locations are pelvis, long bone
diaphyses, and scapula
• Plain film imaging: lytic, classic finding of “onion skin”
periosteal reaction. Permeative appearance.
• Isolated 5-year survival
is 70%. Metastatic 5year survival is <20%
• Metastases primarily to
the lungs, bone, bone
marrow
CT Thorax
• Innumerable tiny 2-4 mm lower lung nodules
scattered in both lung fields predominantly in the
lower lobes. No other evidence for metastatic
disease
Thoracoscopic wedge
biopsies, LLL x 2
Treatment options in metastatic
or recurrent ES
Chemotherapy
• In contrast to localized disease, modern chemotherapy
is limited to extending progression free survival
• Overall Survival (OS) of patients with metastatic disease
remains at 25%.
• OS in isolated pulmonary mets vs. osseous mets vs. mutisystem mets is 29%, 19%, 8% respectively
Treatment options in
metastatic or recurrent ES
Whole Lung Irradiation
• Controversial and co-morbid therapy, but multiple
studies show increased survival
• German/European Intergroup Cooperative Ewing’s
Sarcoma Studies (CESS) showed a benefit in disease
free survival and recommended 18-20 Gy irradiation
• Currently, many protocols reserve WLI for patients
with pulmonary metastases who are poor
chemotherapy responders
Treatment options in
metastatic or recurrent ES
Surgery
• Multiple studies have suggested aggressive
pulmonary resection for metastatic osteosarcoma
• Osteosarcoma and ES have similar presentations,
but arise from different cell types and have different
biological characteristics
• This practice in ES is less well studied and perhaps
more controversial.
Briccoli et al, European Journal of
Cancer Surgery
• Retrospective review of 496
patients with ES treated at a
single institution in Italy
between 1972-97
• All patients were treated
with chemotherapy (5
different protocols)
• Matched 24 operative
patients to 34 non-operative
patients by age, gender,
tumor location, disease-free
interval
Briccoli et al, European Journal of
Cancer Surgery
• Mean disease-free interval was 30.3 months in nonop group and 37.4 months in operative group
• Mean 5 year survival in non-op vs. op groups was
24.2% vs. 55.8% (P = 0.02)
Letourneau et al, Journal of
Pediatric Surgery, 2011
• Retrospective review, patients < 21 y/o treated at a
single institution (1990-2006)
• 80 patients identified, 31 with pulmonary mets
• Groups: resection alone (5), radiation alone (3),
radiation and resection (3), chemotherapy alone (11)
• Authors do not describe how the treatment decisions
were made.
Letourneau et al, Journal of
Pediatric Surgery, 2011
• Hazard ratio, lung resected vs not resected:
15.11 (2.63-86.78)
Letourneau et al, Journal of
Pediatric Surgery, 2011
• 5-year survival:
Radiation, no resection: 0%
No radiation, no resection: 0%
Radiation and resection: 65%
Resection only: 80%
Discussion
• The small sample size, multivariate care strategies,
and major selection biases make these studies
suspect.
• Given the long term f/u of these studies, these
procedures were all done with thoracotomies. Due
to the reduced morbidity of thoracoscopy, this
moderately life-prelonging procedure begins to
appear more favorable
• Higher level clinical studies are likely not feasible,
but tumor biology plays a large role in determining
which patients may benefit from metastasectomy
and can be studied further.
References
[1] Ludwig JA. Ewing sarcoma: historical perspectives, current state-of-the-art, and opportunities for targeted
therapy in the future. Curr OpinOncol 2008;20:412-8.
[2] Cotterill SJ, Ahrens S, Paulussen M, et al. Prognostic factors in Ewing's tumor of bone: analysis of 975 patients
from the European intergroup cooperative Ewing's sarcoma study group. JClinOncol 2000;18:3108-14.
[3] Subbiah V, Anderson P, Lazar AJ, et al. Ewing's sarcoma: standard and experimental options. Curr Treat
Options Oncol 2009;10:126-40.
[4] Harting MT, Blakely ML, Jaffe N, et al. Long term survival after aggressive resection of pulmonary metastases
among children and adolescents with osteosarcoma. J Pediatr Surg 2006;41:194-9.
[5] Briccoli A, Rocca M, Ferrari S, et al. Surgery for lung metastases in Ewing's sarcoma of bone. Eur J Cancer Surg
2004;30:63-7.
[6] Miser J, Goldsby R, Chen Z, et al. Treatment of metastatic Ewing's sarcoma/primitive neuroectodermal tumor
of bone: evaluation of increasing the dose intensity of chemotherapy—a report from the Children's Oncology
Group. Pediatr Blood Cancer 2007;49:894-900.
[7] Tronc F, Conter C, Marec-Berard P, et al. Prognostic factors and longterm results of pulmonary
metastasectomy for pediatric histologies. Eur J Cardiothorac Surg 2008;34:1240-6.
[8] Karnak I, Emin Senocak M, Kutluk T, et al. Pulmonary metastases in children: an analysis of surgical spectrum.
Eur J Pediatr Surg 2002;12: 151-8.
[9] Paulussen M, Ahrens A, Craft J et al. Ewing’s tumors with primary lung metastases: survival analysis of 114
(European Intergroup) Cooperative Ewing’s sarcoma studies patients. J Clin Oncol 1998; 16: 3044-52.
[10] Spunt S, McCarville B, Kun L et al. Selective use of whole-lung irradiation for patients with Ewing sarcoma
family tumors and pulmonary metastases at the time of diagnosis. J Ped Heme/Onc 2001; 23: 93-8.
[11] Letourneau P, Shackett B, Xia L, et al. Resection of pulmonary metastases in pediatric patients with Ewing
sarcoma improves survival. J Pediatr Surg 2011; 46:332-35