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Purpose <p>High-dose ifosfamide (HD-IFO) remains an effective regimen for advanced bone and soft tissue sarcomas, but predictors of long-term benefit are poorly defined. This study evaluated clinical outcomes and prognostic factors using machine learning-assisted modeling in sarcoma patients treated with HD-IFO at a high-volume academic center.</p> Methods <p>We retrospectively analyzed 26 patients with histologically confirmed bone or soft tissue sarcoma who received HD-IFO (≥ 12&#xa0;g/m<sup>2</sup> per cycle) between 2015 and 2025. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared across RECIST response categories using log-rank testing. Prognostic factors were identified using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with leave-one-out cross-validation. The top three variables were entered into multivariable logistic regression to estimate odds ratios (ORs) for OS &gt; 24&#xa0;months.</p> Results <p>Median PFS and OS from start of HD-IFO was 6.6&#xa0;months (95% CI 4.4–9.8) and 24.7&#xa0;months (95% CI, 14.7–34.2), respectively. Patients with progressive disease (PD) had significantly shorter OS than those with partial response (PR; <i>p</i> = 0.0047) or stable disease (SD; <i>p</i> = 0.0485). LASSO identified intervention prior to progression, prior tumor control ≥ 12&#xa0;months, and absence of metastases as the strongest predictors for OS &gt; 24&#xa0;months. In multivariable analysis, intervention prior to progression (OR 24.18, 95% CI 1.81–1001.27, <i>p</i> = 0.037) and prior tumor control ≥ 12&#xa0;months (OR 25.39, 95% CI 2.1–1008.9, <i>p</i> = 0.030) independently predicted OS &gt; 24&#xa0;months.</p> Conclusion <p>HD-IFO provides durable disease control in selected sarcoma patients, particularly those with sustained prior tumor control and intervention prior to progression.</p>

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Long-term benefit from high-dose ifosfamide in sarcoma depends on sustained prior control and timely intervention: a machine learning analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月8日

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  • Michael Hoberger,
  • Romy L. Zuber,
  • Anton Burkhard-Meier,
  • Dorit Di Gioia,
  • Vindi Jurinovic,
  • Michael Völkl,
  • Sinan E. Güler,
  • Markus Albertsmeier,
  • Alexander Klein,
  • Hans Roland Dürr,
  • Nina-Sophie Schmidt-Hegemann,
  • Thomas Knösel,
  • Wolfgang G. Kunz,
  • Michael von Bergwelt-Baildon,
  • Lars H. Lindner,
  • Luc M. Berclaz

摘要

Purpose

High-dose ifosfamide (HD-IFO) remains an effective regimen for advanced bone and soft tissue sarcomas, but predictors of long-term benefit are poorly defined. This study evaluated clinical outcomes and prognostic factors using machine learning-assisted modeling in sarcoma patients treated with HD-IFO at a high-volume academic center.

Methods

We retrospectively analyzed 26 patients with histologically confirmed bone or soft tissue sarcoma who received HD-IFO (≥ 12 g/m2 per cycle) between 2015 and 2025. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared across RECIST response categories using log-rank testing. Prognostic factors were identified using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with leave-one-out cross-validation. The top three variables were entered into multivariable logistic regression to estimate odds ratios (ORs) for OS > 24 months.

Results

Median PFS and OS from start of HD-IFO was 6.6 months (95% CI 4.4–9.8) and 24.7 months (95% CI, 14.7–34.2), respectively. Patients with progressive disease (PD) had significantly shorter OS than those with partial response (PR; p = 0.0047) or stable disease (SD; p = 0.0485). LASSO identified intervention prior to progression, prior tumor control ≥ 12 months, and absence of metastases as the strongest predictors for OS > 24 months. In multivariable analysis, intervention prior to progression (OR 24.18, 95% CI 1.81–1001.27, p = 0.037) and prior tumor control ≥ 12 months (OR 25.39, 95% CI 2.1–1008.9, p = 0.030) independently predicted OS > 24 months.

Conclusion

HD-IFO provides durable disease control in selected sarcoma patients, particularly those with sustained prior tumor control and intervention prior to progression.