A Retrospective Comparative Analysis of Outcomes and Prognostic Factors in Adult and Pediatric Patients with Osteosarcoma
Bibliographic record
Abstract
Osteosarcoma is the most common primary bone malignancy in both children and adults. Despite introduction of intensive multimodal treatment with chemotherapy and surgery, outcomes are still poor, especially for patients with metastatic disease and adults. Hence, there is an ongoing need for better prognostic markers and outcome data to inform management decisions in both the adult and pediatric setting. Here, we retrospectively analyzed 112 patients with bone osteosarcoma treated at two large adult and pediatric tertiary academic centers between 1989 and 2019. Patients were divided into an adult (≥18 years) and pediatric (<18 years) cohort for comparison. Our aim was to evaluate predictors of outcomes in pediatric and adult patients, with a specific focus on the role of methotrexate when added to a combination of doxorubicin-cisplatin; the prognostic value of tumor necrosis after neoadjuvant chemotherapy; and outlining any differences in outcomes between adults and pediatric patients that could inform clinical management. Adult patients treated with methotrexate-doxorubicin-cisplatin and those treated with doxorubicin-cisplatin had similar 5-year PFS (26%, 95%CI: 45.5%–10% vs. 50%, 95%CI: 69.6%–26.2%, p = 0.1) and 5-year OS (63%, 95%CI: 82%–34%, vs. 78%, 95%CI: 90.6%–52.6%, p = 0.5). In the adult cohort, there was no difference between patients with ≥90% necrosis and <90% necrosis in either 5-year PFS (42%, 95%CI: 71.1%–11.3% vs. 38%, 95%CI: 57.7%–18.2%, p = 0.4) or 5-year OS (85%, 95%CI: 97.8%–33.4% vs. 56%, 95%CI: 76.8%–27.6%, p = 0.4). In the pediatric cohort, compared to patients with <90% necrosis, those with ≥90% necrosis had significantly better 5-year PFS (30%, 95%CI: 49.3%–14.1% vs. 55%, 95%CI: 73.9%–38.5%, p = 0.003) and 5-year OS (64%, 95%CI: 80.8%–41.1% vs. 78%, 95%CI: 92%–60.9%, p = 0.04). Adult and pediatric patients had similar 5-year OS (69%, 95%CI: 83.2%–49.8% vs. 73%, 95%CI: 83.2%–59.3%, p = 0.8) and 5-year PFS (37%, 95%CI: 52.4%–22.9% vs. 43%, 95%CI: 56.2%–30.4% p = 0.3) even though the proportion of patients with ≥90% necrosis after neoadjuvant chemotherapy was higher for children compared to adults (60.3% vs. 30%, OR: 3.54, 95%CI: 1.38–8.46, p = 0.006). In conclusion, in adult patients, the addition of methotrexate to doxorubicin and cisplatin did not correlate with a significant survival benefit, questioning the therapeutic value of methotrexate overall. Our study confirms the prognostic utility of percent tumor necrosis after neoadjuvant chemotherapy in pediatric patients but not in adult patients. Lastly, this is one of the few reported studies where patients with osteosarcoma younger and older than 18 years had similar PFS and OS.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".