Clinical trial of proton craniospinal irradiation for leptomeningeal metastases Journal Article


Authors: Yang, T. J.; Wijetunga, N. A.; Yamada, J.; Wolden, S.; Mehallow, M.; Goldman, D. A.; Zhang, Z.; Young, R. J.; Kris, M. G.; Yu, H. A.; Seidman, A. D.; Gavrilovic, I. T.; Lin, A.; Santomasso, B.; Grommes, C.; Piotrowski, A. F.; Schaff, L.; Stone, J. B.; DeAngelis, L. M.; Boire, A.; Pentsova, E.
Article Title: Clinical trial of proton craniospinal irradiation for leptomeningeal metastases
Abstract: BACKGROUND: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). RESULTS: We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. CONCLUSION: Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Keywords: proton radiation; leptomeningeal metastases; craniospinal irradiation
Journal Title: Neuro-Oncology
Volume: 23
Issue: 1
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2021-01-01
Start Page: 134
End Page: 143
Language: English
DOI: 10.1093/neuonc/noaa152
PUBMED: 32592583
PROVIDER: scopus
PMCID: PMC7850116
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Zhigang Zhang
    315 Zhang
  2. Andrew D Seidman
    288 Seidman
  3. Robert J Young
    156 Young
  4. Suzanne L Wolden
    481 Wolden
  5. Yoshiya Yamada
    407 Yamada
  6. Helena Alexandra Yu
    160 Yu
  7. Christian Grommes
    81 Grommes
  8. Mark Kris
    766 Kris
  9. T. Jonathan Yang
    101 Yang
  10. Debra Alyssa Goldman
    132 Goldman
  11. Adrienne Boire
    45 Boire
  12. Jacqueline Blair Stone
    19 Stone
  13. Andrew Lee Lin
    29 Lin
  14. Lauren Rhea Schaff
    18 Schaff