title: Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group.
abstract: Flow cytometry and RT-PCR can detect occult Ewing sarcoma cells in the blood and bone marrow. These techniques were used to evaluate the prognostic significance of micrometastatic disease in Ewing sarcoma.
  
  
  
  Newly diagnosed patients with Ewing sarcoma were enrolled on two prospective multicenter studies. In the flow cytometry cohort, patients were defined as "positive" for bone marrow micrometastatic disease if their CD99(+)/CD45(-) values were above the upper limit in 22 control patients. In the PCR cohort, RT-PCR on blood or bone marrow samples classified the patients as "positive" or "negative" for EWSR1/FLI1 translocations. The association between micrometastatic disease burden with clinical features and outcome was assessed. Coexpression of insulin-like growth factor-1 receptor (IGF-1R) on detected tumor cells was performed in a subset of flow cytometry samples.
  
  
  
  The median total bone marrow CD99(+)CD45(-) percent was 0.0012% (range 0%-1.10%) in the flow cytometry cohort, with 14 of 109 (12.8%) of Ewing sarcoma patients defined as "positive." In the PCR cohort, 19.6% (44/225) patients were "positive" for any EWSR1/FLI1 translocation in blood or bone marrow. There were no differences in baseline clinical features or event-free or overall survival between patients classified as "positive" versus "negative" by either method. CD99(+)CD45(-) cells had significantly higher IGF-1R expression compared with CD45(+) hematopoietic cells (mean geometric mean fluorescence intensity 982.7 vs. 190.9; P < 0.001).
  
  
  
  The detection of micrometastatic disease at initial diagnosis by flow cytometry or RT-PCR is not associated with outcome in newly diagnosed patients with Ewing sarcoma. Flow cytometry provides a tool to characterize occult micrometastatic tumor cells for proteins of interest. Clin Cancer Res; 22(14); 3643-50. ©2016 AACR.
authors: Department of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, California.
authors: Kieuhoa T
authors: KT
authors: Vo
authors: Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC.
authors: Jeremy V
authors: JV
authors: Edwards
authors: Division of Experimental Medicine Core Immunology Laboratory, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, California.
authors: C Lorrie
authors: CL
authors: Epling
authors: Division of Experimental Medicine Core Immunology Laboratory, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, California.
authors: Elizabeth
authors: E
authors: Sinclair
authors: Division of Hematology/Oncology, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
authors: Douglas S
authors: DS
authors: Hawkins
authors: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
authors: Holcombe E
authors: HE
authors: Grier
authors: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
authors: Katherine A
authors: KA
authors: Janeway
authors: Department of Pediatric Hematology/Oncology, Center for Children's Cancer Research, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors: Phillip
authors: P
authors: Barnette
authors: Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Elizabeth
authors: E
authors: McIlvaine
authors: Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Mark D
authors: MD
authors: Krailo
authors: Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Donald A
authors: DA
authors: Barkauskas
authors: Department of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, California.
authors: Katherine K
authors: KK
authors: Matthay
authors: Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Richard B
authors: RB
authors: Womer
authors: Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.
authors: Richard G
authors: RG
authors: Gorlick
authors: Center for Childhood Cancer and Blood Disorders at Nationwide Children's Hospital and the Division of Hematology, Oncology, and BMT at The Ohio State University, Columbus, Ohio.
authors: Stephen L
authors: SL
authors: Lessnick
authors: Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Crystal L
authors: CL
authors: Mackall
authors: Department of Pediatrics, UCSF Benioff Children's Hospital, University of California, San Francisco School of Medicine, San Francisco, California. steven_dubois@dfci.harvard.edu.
authors: Steven G
authors: SG
authors: DuBois
mesh_terms: D000071443:12E7 Antigen / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D061206:Neoplasm Micrometastasis / Q000473:pathology*; D011446:Prospective Studies; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D000071443:12E7 Antigen; D017526:Receptor, IGF Type 1; D017493:Leukocyte Common Antigens