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A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease

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Summary

A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase 1 trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24–78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The10B carrier,l-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg−1 over 1 h (10 subjects), 300 mg kg−1 over 1.5 h (two subjects), or 350 mg kg−1 over 1.5–2 h (10 subjects). The pharmacokinetic profile of10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.

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Authors and Affiliations

  1. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, 02215, Boston, MA, USA

    Paul M. Busse, W. S. Kiger, Jody Kaplan, Irving Kaplan & Xing-Qi Lu

  2. Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston

    Matthew R. Palmer & Robert G. Zamenhof

  3. Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA

    Otto K. Harling, Cynthia F. Chuang, J. Tim Goorley, Kent J. Riley & Thomas H. Newton

  4. Comisión Nacional de Energía Atómica, Buenos Aires, Argentina

    Gustavo A. Santa Cruz

Authors
  1. Paul M. Busse
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  2. Otto K. Harling
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  3. Matthew R. Palmer
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  4. W. S. Kiger
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  5. Jody Kaplan
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  6. Irving Kaplan
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  8. J. Tim Goorley
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  13. Robert G. Zamenhof
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Correspondence to Paul M. Busse.

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Busse, P.M., Harling, O.K., Palmer, M.R. et al. A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease. J Neuro-Oncol 62, 111–121 (2003). https://doi.org/10.1007/BF02699938

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