High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases: Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008

Research output: Contribution to journalArticlepeer-review

Standard

High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases : Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008. / Dirksen, Uta; Brennan, Bernadette; Le Deley, Marie Cécile; Cozic, Nathalie; Van Den Berg, Henk; Bhadri, Vivek; Brichard, Bénédicte; Claude, Line; Craft, Alan; Amler, Susanne; Gaspar, Natalie; Gelderblom, Hans; Goldsby, Robert; Gorlick, Richard; Grier, Holcombe E.; Guinbretiere, Jean Marc; Hauser, Peter; Hjorth, Lars; Janeway, Katherine; Juergens, Heribert; Judson, Ian; Krailo, Mark; Kruseova, Jarmila; Kuehne, Thomas; Ladenstein, Ruth; Lervat, Cyril; Lessnick, Stephen L.; Lewis, Ian; Linassier, Claude; Marec-Berard, Perrine; Marina, Neyssa; Morland, Bruce; Pacquement, Hélène; Paulussen, Michael; Randall, R. Lor; Ranft, Andreas; Le Teuff, Gwénaël; Wheatley, Keith; Whelan, Jeremy; Womer, Richard; Oberlin, Odile; Hawkins, Douglas S.

In: Journal of Clinical Oncology, Vol. 37, No. 34, 01.01.2019, p. 3192-3202.

Research output: Contribution to journalArticlepeer-review

Harvard

Dirksen, U, Brennan, B, Le Deley, MC, Cozic, N, Van Den Berg, H, Bhadri, V, Brichard, B, Claude, L, Craft, A, Amler, S, Gaspar, N, Gelderblom, H, Goldsby, R, Gorlick, R, Grier, HE, Guinbretiere, JM, Hauser, P, Hjorth, L, Janeway, K, Juergens, H, Judson, I, Krailo, M, Kruseova, J, Kuehne, T, Ladenstein, R, Lervat, C, Lessnick, SL, Lewis, I, Linassier, C, Marec-Berard, P, Marina, N, Morland, B, Pacquement, H, Paulussen, M, Randall, RL, Ranft, A, Le Teuff, G, Wheatley, K, Whelan, J, Womer, R, Oberlin, O & Hawkins, DS 2019, 'High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases: Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008', Journal of Clinical Oncology, vol. 37, no. 34, pp. 3192-3202. https://doi.org/10.1200/JCO.19.00915

APA

Dirksen, U., Brennan, B., Le Deley, M. C., Cozic, N., Van Den Berg, H., Bhadri, V., Brichard, B., Claude, L., Craft, A., Amler, S., Gaspar, N., Gelderblom, H., Goldsby, R., Gorlick, R., Grier, H. E., Guinbretiere, J. M., Hauser, P., Hjorth, L., Janeway, K., ... Hawkins, D. S. (2019). High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases: Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008. Journal of Clinical Oncology, 37(34), 3192-3202. https://doi.org/10.1200/JCO.19.00915

Vancouver

Author

Dirksen, Uta ; Brennan, Bernadette ; Le Deley, Marie Cécile ; Cozic, Nathalie ; Van Den Berg, Henk ; Bhadri, Vivek ; Brichard, Bénédicte ; Claude, Line ; Craft, Alan ; Amler, Susanne ; Gaspar, Natalie ; Gelderblom, Hans ; Goldsby, Robert ; Gorlick, Richard ; Grier, Holcombe E. ; Guinbretiere, Jean Marc ; Hauser, Peter ; Hjorth, Lars ; Janeway, Katherine ; Juergens, Heribert ; Judson, Ian ; Krailo, Mark ; Kruseova, Jarmila ; Kuehne, Thomas ; Ladenstein, Ruth ; Lervat, Cyril ; Lessnick, Stephen L. ; Lewis, Ian ; Linassier, Claude ; Marec-Berard, Perrine ; Marina, Neyssa ; Morland, Bruce ; Pacquement, Hélène ; Paulussen, Michael ; Randall, R. Lor ; Ranft, Andreas ; Le Teuff, Gwénaël ; Wheatley, Keith ; Whelan, Jeremy ; Womer, Richard ; Oberlin, Odile ; Hawkins, Douglas S. / High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases : Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 34. pp. 3192-3202.

Bibtex

@article{3e1ac205e0264ea6ad40bc454026f5a8,
title = "High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases: Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008",
abstract = "PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.",
author = "Uta Dirksen and Bernadette Brennan and {Le Deley}, {Marie C{\'e}cile} and Nathalie Cozic and {Van Den Berg}, Henk and Vivek Bhadri and B{\'e}n{\'e}dicte Brichard and Line Claude and Alan Craft and Susanne Amler and Natalie Gaspar and Hans Gelderblom and Robert Goldsby and Richard Gorlick and Grier, {Holcombe E.} and Guinbretiere, {Jean Marc} and Peter Hauser and Lars Hjorth and Katherine Janeway and Heribert Juergens and Ian Judson and Mark Krailo and Jarmila Kruseova and Thomas Kuehne and Ruth Ladenstein and Cyril Lervat and Lessnick, {Stephen L.} and Ian Lewis and Claude Linassier and Perrine Marec-Berard and Neyssa Marina and Bruce Morland and H{\'e}l{\`e}ne Pacquement and Michael Paulussen and Randall, {R. Lor} and Andreas Ranft and {Le Teuff}, Gw{\'e}na{\"e}l and Keith Wheatley and Jeremy Whelan and Richard Womer and Odile Oberlin and Hawkins, {Douglas S.}",
year = "2019",
month = jan,
day = "1",
doi = "10.1200/JCO.19.00915",
language = "English",
volume = "37",
pages = "3192--3202",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "34",

}

RIS

TY - JOUR

T1 - High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases

T2 - Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008

AU - Dirksen, Uta

AU - Brennan, Bernadette

AU - Le Deley, Marie Cécile

AU - Cozic, Nathalie

AU - Van Den Berg, Henk

AU - Bhadri, Vivek

AU - Brichard, Bénédicte

AU - Claude, Line

AU - Craft, Alan

AU - Amler, Susanne

AU - Gaspar, Natalie

AU - Gelderblom, Hans

AU - Goldsby, Robert

AU - Gorlick, Richard

AU - Grier, Holcombe E.

AU - Guinbretiere, Jean Marc

AU - Hauser, Peter

AU - Hjorth, Lars

AU - Janeway, Katherine

AU - Juergens, Heribert

AU - Judson, Ian

AU - Krailo, Mark

AU - Kruseova, Jarmila

AU - Kuehne, Thomas

AU - Ladenstein, Ruth

AU - Lervat, Cyril

AU - Lessnick, Stephen L.

AU - Lewis, Ian

AU - Linassier, Claude

AU - Marec-Berard, Perrine

AU - Marina, Neyssa

AU - Morland, Bruce

AU - Pacquement, Hélène

AU - Paulussen, Michael

AU - Randall, R. Lor

AU - Ranft, Andreas

AU - Le Teuff, Gwénaël

AU - Wheatley, Keith

AU - Whelan, Jeremy

AU - Womer, Richard

AU - Oberlin, Odile

AU - Hawkins, Douglas S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

AB - PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

UR - http://www.scopus.com/inward/record.url?scp=85075814144&partnerID=8YFLogxK

U2 - 10.1200/JCO.19.00915

DO - 10.1200/JCO.19.00915

M3 - Article

C2 - 31553693

AN - SCOPUS:85075814144

VL - 37

SP - 3192

EP - 3202

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 34

ER -