Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee

Michael W. Bishop; Yu Chen Chang; Mark D. Krailo; Paul A. Meyers; Arthur J. Provisor; Cindy L. Schwartz; Neyssa M. Marina; Lisa A. Teot; Mark C. Gebhardt; Richard Gorlick; Katherine A. Janeway; Alexander J. Chou

doi:10.1002/pbc.26034

Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee

Michael W. Bishop, Yu Chen Chang, Mark D. Krailo, Paul A. Meyers, Arthur J. Provisor, Cindy L. Schwartz, Neyssa M. Marina, Lisa A. Teot, Mark C. Gebhardt, Richard Gorlick, Katherine A. Janeway, Alexander J. Chou

Pediatrics

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31 Scopus citations

Abstract

Background: The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery. Methods: Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan–Meier methodology. Results: Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1). Conclusion: We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.

Original language	English (US)
Pages (from-to)	1737-1743
Number of pages	7
Journal	Pediatric Blood and Cancer
Volume	63
Issue number	10
DOIs	https://doi.org/10.1002/pbc.26034
State	Published - Oct 1 2016

Keywords

biomarker
chemotherapy
histologic response
necrosis
osteosarcoma

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/pbc.26034

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Bishop, M. W., Chang, Y. C., Krailo, M. D., Meyers, P. A., Provisor, A. J., Schwartz, C. L., Marina, N. M., Teot, L. A., Gebhardt, M. C., Gorlick, R., Janeway, K. A., & Chou, A. J. (2016). Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee. Pediatric Blood and Cancer, 63(10), 1737-1743. https://doi.org/10.1002/pbc.26034

Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee. / Bishop, Michael W.; Chang, Yu Chen; Krailo, Mark D. et al.
In: Pediatric Blood and Cancer, Vol. 63, No. 10, 01.10.2016, p. 1737-1743.

Research output: Contribution to journal › Article › peer-review

Bishop, MW, Chang, YC, Krailo, MD, Meyers, PA, Provisor, AJ, Schwartz, CL, Marina, NM, Teot, LA, Gebhardt, MC, Gorlick, R, Janeway, KA & Chou, AJ 2016, 'Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee', Pediatric Blood and Cancer, vol. 63, no. 10, pp. 1737-1743. https://doi.org/10.1002/pbc.26034

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title = "Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee",

abstract = "Background: The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery. Methods: Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan–Meier methodology. Results: Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1). Conclusion: We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.",

keywords = "biomarker, chemotherapy, histologic response, necrosis, osteosarcoma",

author = "Bishop, {Michael W.} and Chang, {Yu Chen} and Krailo, {Mark D.} and Meyers, {Paul A.} and Provisor, {Arthur J.} and Schwartz, {Cindy L.} and Marina, {Neyssa M.} and Teot, {Lisa A.} and Gebhardt, {Mark C.} and Richard Gorlick and Janeway, {Katherine A.} and Chou, {Alexander J.}",

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T2 - A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee

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AU - Chang, Yu Chen

AU - Krailo, Mark D.

AU - Meyers, Paul A.

AU - Provisor, Arthur J.

AU - Schwartz, Cindy L.

AU - Marina, Neyssa M.

AU - Teot, Lisa A.

AU - Gebhardt, Mark C.

AU - Gorlick, Richard

AU - Janeway, Katherine A.

AU - Chou, Alexander J.

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N2 - Background: The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery. Methods: Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan–Meier methodology. Results: Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1). Conclusion: We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.

AB - Background: The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery. Methods: Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan–Meier methodology. Results: Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1). Conclusion: We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.

KW - biomarker

KW - chemotherapy

KW - histologic response

KW - necrosis

KW - osteosarcoma

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Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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