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
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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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The demarcation between good and poor response varied between studies, corresponding to 90-98% tumour necrosis in the resection specimen.
“With differences in percentages ascribed to each, the demarcation between good and poor response varied between studies (90-98% tumour necrosis in the resection specimen) 117 .”
From Osteosarcoma (2022) · cites this paper as [117]
Prognosis improvement seems linear with increasing necrosis, with some studies setting the good/poor cut-off between grades 2 and 3 and others between grades 3 and 4.
“The improvement in prognosis seems linear with increasing necrosis, with some studies setting the cut-off point between good and poor between grades 2 and 3, whereas others have set it between grades 3 and 4.”
From Osteosarcoma (2022) · cites this paper as [117]
A study confirmed that pathological response to treatment predicts prognosis in osteosarcoma after neoadjuvant chemotherapy.
“This study validates the prognostic significance of pathological treatment response in osteosarcoma following neoadjuvant chemotherapy.”
From Osteosarcoma (2022) · cites this paper as [117]
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Tararykova, A. A., Valiev, A. K., Kononets, P. V., Charchyan, E. R., Kabardaev, R. M., Fedorova, A. V., Batyrova, G. S., Shin, A. R., & Козлов, Н. А. (2023) · Bone and soft tissue sarcomas tumors of the skin · doi:10.17650/2219-4614-2023-15-4-56-63
Impact of Postoperative Radiotherapy on Survival in Primary Osteosarcoma: A Population-Based StudyPreprint
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Srinivasan, S., & Kanwar, V. S. (2025) · Springer eBooks · doi:10.1007/978-3-031-76882-8_29
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- Authors
- Bishop, M. W., Chang, Y., 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.
- Affiliations
- St. Jude Children's Research Hospital (US)
- University of Southern California (US)
- Memorial Sloan Kettering Cancer Center (US)
- Memorial Health University Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Lucile Packard Children's Hospital (US)
- Boston Children's Hospital (US)
- Children's Hospital at Montefiore (US)
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
- Corresponding author
- Bishop, Michael W.
- ORCID
- Venue
- Pediatric Blood & Cancer
- Publisher
- Wiley
- Published
- 2016-04-29
- Volume
- 63
- Issue
- 10
- Pages
- 1737-1743
- ISSN
- 1545-5009 (ISSN-L)
- 1545-5017
- PMC
- PMC5136499
- OpenAlex
- W2344321498
- Cited by
- 52
- References
- 34
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 3 · 2020: 6 · 2019: 4 · 2017: 4 · 2016: 3
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pediatric Blood & Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (U10CA098543, U10CA180886, U10CA098413, U10CA180899)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- osteosarcoma, histological response, tumor necrosis, prognostic factors, induction chemotherapy, event-free survival, surgical resection, pediatric bone tumors, Children's Cancer Group
- MeSH terms
- Adolescent, Adult, Bone Neoplasms, Child, Child, Preschool, Female, Humans, Infant, Male, Prognosis, Retrospective Studies, Osteosarcoma, Proportional Hazards Models, Treatment Outcome, Induction Chemotherapy
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