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Background <p>Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas often arising in the spine, characterized by high metastatic potential and poor prognosis. While photon radiation therapy (RT) has been employed for local control, the role of proton RT in spinal MPNST remains poorly defined. Our objective is to compare treatment patterns, survival outcomes, and predictors of mortality among spinal MPNST patients treated with photon vs. proton RT.</p> Methods <p>This retrospective cohort study utilized the National Cancer Database (2004–2017) to identify patients with spinal MPNST. Demographics, tumor characteristics, treatment details, and outcomes were compared between patients receiving no radiation, photon RT, or proton RT. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Machine learning-based survival models evaluated predictive performance, feature importance, and SHAP values.</p> Results <p>Of 5,664 spinal MPNST patients, 3,264 (57.3%) received RT (photon: 97.5%; proton: 2.5%). Proton therapy recipients were younger, had smaller tumors, and more frequently received adjuvant chemoradiation (p &lt; 0.001). Proton therapy was associated with significantly improved 10-year survival (88.5% vs. 73.8%; p = 0.003) and lower long-term mortality (HR: 0.47; p = 0.024). Comorbidity burden, distant metastasis, and high biologically effective dose (BED &gt; 70&#xa0;Gy) were predictors of both short- and long-term mortality on the multivariate model. The Gradient Boosting model identified BED, CDCC score, and tumor size as the most influential predictors, with a highest AUC for 10-year mortality of 0.715.</p> Conclusion <p>Proton therapy is associated with superior long-term survival compared to photon therapy in spinal MPNST patients, particularly among the subtotal resection cohort. Radiation dose, tumor size, and comorbidity burden are strong predictors of mortality. These findings support the integration of proton therapy into treatment algorithms and emphasize the importance of individualized, risk-adapted strategies to improve survival in patients with spinal MPNST.</p>

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Comparative outcomes of proton and photon therapy in the management of malignant peripheral nerve sheath tumors

  • 期刊论文

  • 发表日期：

    2026年7月7日

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  • Taha Khalilullah,
  • Abdul Karim Ghaith,
  • Xinlan Yang,
  • Bibhas Amatya,
  • Xihang Wang,
  • Leon Fan,
  • Arman Momeni,
  • Nathan Kim,
  • Jawad Khalifeh,
  • Joshua Weinberg,
  • Tej Azad,
  • Yuanxuan Xia,
  • Maher Ghandour,
  • Allan Belzberg,
  • Kristin Redmond,
  • Yazan Alasadi,
  • Danner Butler,
  • Madison Patrick,
  • Nicholas Theodore,
  • Daniel Lubelski

摘要

Background

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas often arising in the spine, characterized by high metastatic potential and poor prognosis. While photon radiation therapy (RT) has been employed for local control, the role of proton RT in spinal MPNST remains poorly defined. Our objective is to compare treatment patterns, survival outcomes, and predictors of mortality among spinal MPNST patients treated with photon vs. proton RT.

Methods

This retrospective cohort study utilized the National Cancer Database (2004–2017) to identify patients with spinal MPNST. Demographics, tumor characteristics, treatment details, and outcomes were compared between patients receiving no radiation, photon RT, or proton RT. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Machine learning-based survival models evaluated predictive performance, feature importance, and SHAP values.

Results

Of 5,664 spinal MPNST patients, 3,264 (57.3%) received RT (photon: 97.5%; proton: 2.5%). Proton therapy recipients were younger, had smaller tumors, and more frequently received adjuvant chemoradiation (p < 0.001). Proton therapy was associated with significantly improved 10-year survival (88.5% vs. 73.8%; p = 0.003) and lower long-term mortality (HR: 0.47; p = 0.024). Comorbidity burden, distant metastasis, and high biologically effective dose (BED > 70 Gy) were predictors of both short- and long-term mortality on the multivariate model. The Gradient Boosting model identified BED, CDCC score, and tumor size as the most influential predictors, with a highest AUC for 10-year mortality of 0.715.

Conclusion

Proton therapy is associated with superior long-term survival compared to photon therapy in spinal MPNST patients, particularly among the subtotal resection cohort. Radiation dose, tumor size, and comorbidity burden are strong predictors of mortality. These findings support the integration of proton therapy into treatment algorithms and emphasize the importance of individualized, risk-adapted strategies to improve survival in patients with spinal MPNST.