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 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) 2 nd most common primary bone tumor in children, male : female ratio of 1.6 to 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 5- year 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 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. muti- system mets is 29%, 19%, 8% respectively Chemotherapy

Treatment options in metastatic or recurrent ES 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 Gy irradiation Currently, many protocols reserve WLI for patients with pulmonary metastases who are poor chemotherapy responders Whole Lung Irradiation

Treatment options in metastatic or recurrent ES 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. Surgery

Briccoli et al, European Journal of Cancer Surgery Retrospective review of 496 patients with ES treated at a single institution in Italy between 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 non- op 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 ( ) 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: ( )

Letourneau et al, Journal of Pediatric Surgery, 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.

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