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 Ja-Ho Chou

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1737-1743
Number of pages7
JournalPediatric Blood and Cancer
Volume63
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Osteosarcoma
Bone and Bones
Neoplasms
Induction Chemotherapy
Proportional Hazards Models
Disease-Free Survival
Appointments and Schedules
Necrosis
Therapeutics
Outcome Assessment (Health Care)

Keywords

  • biomarker
  • chemotherapy
  • histologic response
  • necrosis
  • osteosarcoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)
  • Hematology
  • Oncology

Cite this

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.; Meyers, Paul A.; Provisor, Arthur J.; Schwartz, Cindy L.; Marina, Neyssa M.; Teot, Lisa A.; Gebhardt, Mark C.; Gorlick, Richard; Janeway, Katherine A.; Chou, Alexander Ja-Ho.

In: Pediatric Blood and Cancer, Vol. 63, No. 10, 01.10.2016, p. 1737-1743.

Research output: Contribution to journalArticle

Bishop, MW, Chang, YC, Krailo, MD, Meyers, PA, Provisor, AJ, Schwartz, CL, Marina, NM, Teot, LA, Gebhardt, MC, Gorlick, R, Janeway, KA & Chou, AJ-H 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
Bishop, Michael W. ; Chang, Yu Chen ; Krailo, Mark D. ; Meyers, Paul A. ; Provisor, Arthur J. ; Schwartz, Cindy L. ; Marina, Neyssa M. ; Teot, Lisa A. ; Gebhardt, Mark C. ; Gorlick, Richard ; Janeway, Katherine A. ; Chou, Alexander Ja-Ho. / 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. In: Pediatric Blood and Cancer. 2016 ; Vol. 63, No. 10. pp. 1737-1743.
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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.",
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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 Ja-Ho

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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.

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KW - histologic response

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KW - osteosarcoma

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