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

Kieuhoa T. Vo, Jeremy V. Edwards, C. Lorrie Epling, Elizabeth Sinclair, Douglas S. Hawkins, Holcombe E. Grier, Katherine A. Janeway, Phillip Barnette, Elizabeth McIlvaine, Mark D. Krailo, Donald A. Barkauskas, Katherine K. Matthay, Richard B. Womer, Richard G. Gorlick, Stephen L. Lessnick, Crystal L. Mackall, Steven G. DuBois

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Experimental Design: 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. Results: The median total bone marrow CD99? CD45 ô percent was 0.0012% (range 0%-1.10%) inthe 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)3643-3650
Number of pages8
JournalClinical Cancer Research
Volume22
Issue number14
DOIs
StatePublished - Jul 15 2016

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Ewing's Sarcoma
Flow Cytometry
Polymerase Chain Reaction
Bone Marrow
Somatomedin Receptors
Bone Marrow Diseases
Multicenter Studies
Blood Cells
Neoplasms
Research Design
Fluorescence
Prospective Studies
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Vo, Kieuhoa T.; Edwards, Jeremy V.; Epling, C. Lorrie; Sinclair, Elizabeth; Hawkins, Douglas S.; Grier, Holcombe E.; Janeway, Katherine A.; Barnette, Phillip; McIlvaine, Elizabeth; Krailo, Mark D.; Barkauskas, Donald A.; Matthay, Katherine K.; Womer, Richard B.; Gorlick, Richard G.; Lessnick, Stephen L.; Mackall, Crystal L.; DuBois, Steven G.

In: Clinical Cancer Research, Vol. 22, No. 14, 15.07.2016, p. 3643-3650.

Research output: Contribution to journalArticle

Vo, KT, Edwards, JV, Epling, CL, Sinclair, E, Hawkins, DS, Grier, HE, Janeway, KA, Barnette, P, McIlvaine, E, Krailo, MD, Barkauskas, DA, Matthay, KK, Womer, RB, Gorlick, RG, Lessnick, SL, Mackall, CL & DuBois, SG 2016, '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', Clinical Cancer Research, vol. 22, no. 14, pp. 3643-3650. https://doi.org/10.1158/1078-0432.CCR-15-2516
Vo, Kieuhoa T. ; Edwards, Jeremy V. ; Epling, C. Lorrie ; Sinclair, Elizabeth ; Hawkins, Douglas S. ; Grier, Holcombe E. ; Janeway, Katherine A. ; Barnette, Phillip ; McIlvaine, Elizabeth ; Krailo, Mark D. ; Barkauskas, Donald A. ; Matthay, Katherine K. ; Womer, Richard B. ; Gorlick, Richard G. ; Lessnick, Stephen L. ; Mackall, Crystal L. ; DuBois, Steven G. / 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. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 14. pp. 3643-3650.
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abstract = "Purpose: 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. Experimental Design: 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. Results: The median total bone marrow CD99? CD45 {\^o} percent was 0.0012{\%} (range 0{\%}-1.10{\%}) inthe 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). Conclusions: 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.",
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T2 - A report from the children's oncology group

AU - Vo, Kieuhoa T.

AU - Edwards, Jeremy V.

AU - Epling, C. Lorrie

AU - Sinclair, Elizabeth

AU - Hawkins, Douglas S.

AU - Grier, Holcombe E.

AU - Janeway, Katherine A.

AU - Barnette, Phillip

AU - McIlvaine, Elizabeth

AU - Krailo, Mark D.

AU - Barkauskas, Donald A.

AU - Matthay, Katherine K.

AU - Womer, Richard B.

AU - Gorlick, Richard G.

AU - Lessnick, Stephen L.

AU - Mackall, Crystal L.

AU - DuBois, Steven G.

PY - 2016/7/15

Y1 - 2016/7/15

N2 - Purpose: 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. Experimental Design: 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. Results: The median total bone marrow CD99? CD45 ô percent was 0.0012% (range 0%-1.10%) inthe 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). Conclusions: 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.

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