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International Dosimetry Exchange for Boron Neutron Capture Therapy
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International Dosimetry Exchange for Boron Neutron Capture Therapy

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Presentation at 13th International Symposium on Neutron Capture Therapy

Presentation at 13th International Symposium on Neutron Capture Therapy

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  • Perception: BNCT has been around for a long time and does not work
  • Stress that limited resources can be best used to advance clinical aims of BNCT.

International Dosimetry Exchange for Boron Neutron Capture Therapy International Dosimetry Exchange for Boron Neutron Capture Therapy Presentation Transcript

  • GLOBALLY ADVANCING BNCT: COLLECTIVE ANALYSES OF CLINICAL OUTCOMES Kent J. Riley Radiation Monitoring Devices Boston, MA USA [email_address] Research Affiliate Massachusetts Institute of Technology 13 th International Congress on Neutron Capture Therapy 3rd November, 2008
  • BNCT: A research endeavor
    • Multidisciplinary: Expertise required from several disciplines.
    • Complex: Multiple dose components behaving differently from photon radiotherapy. Conformity via binary compound targeting instead of beam tailoring.
    • Intensive Effort: Steep learning curves in all aspects of the project; multiple regulatory agencies and inter-organizational coordination.
    • Clinical programs successfully organized around the world and hundreds of patients safely irradiated.
    • Remains a research endeavor, but now with many active clinical centers.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • Achievements in BNCT
    • Developed necessary scientific infrastructure
      • Neutron beams, boron quantification, measuring absorbed dose, treatment planning systems.
      • Identified critical areas – improved tumor targeting with new boron compounds and/or administration techniques.
    • Clinical trials implemented at 10 different centers in North and South America, Europe and Asia.
      • About 600 irradiations so far with approximately 10-100 cases at each facility.
    • Trials have been safely conducted with some success.
      • Tumor response realized for at least some patients.
      • Good quality of life for most with therapeutic outcome comparable to established therapy.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy View slide
  • Near Term Prospects
    • Irradiations are still a major event, requiring the better part of a day for medical staff.
    • This limitation practically restricts caseloads at most centers to tens of patients per year.
    • New centers are being planned and may come online in the near future but the same limitations are faced because of the complexity of therapy.
    • Competition in medical research is high and agencies adopt a conservative approach.
    • These problems and perceptions will remain unless we can show clear and dramatic breakthroughs.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy View slide
  • A ‘New’ Strategy
    • Patient statistics must be significantly increased to facilitate definitive comparisons with other modalities.
    • New centers should be able to continue where others have left off to avoid needlessly repeating previous work and conserve limited resources.
    • The worldwide clinical infrastructure in BNCT needs to be engaged to collectively advance the modality.
    • Collective analyses of BNCT trial data can be a first step toward these aims.
    • Cooperations are not new and have already been successful in BNCT.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • Informal Cooperation
    • Initial trials - Drs. Sweet & Hatanaka
        • The Japanese program sustained BNCT for two decades
    • Beam design
        • Workshop in the late 80’s promoted epithermal beam development
    • Radiobiology
        • Coderre RBEs used in many trials
    • Treatment planning
        • NCTPlan – MIT, Rez, Petten
        • bnct_rtpe & SERA – BNL, Espoo, Studsvik, Petten
    • Recent trials
        • Brookhaven experience translated to Studsvik
    • Plus many others …
    3rd November, 2008 13th International Congress on Neutron Capture Therapy 3rd November, 2008
  • A More Formal Collaboration
    • Standardization is desirable, but not a pre-requisite.
      • Practices can evolve over time and standards emerge as experience is gained.
      • ICRU not yet ready to support this effort.
    • Many similarities exist between the various facilities and protocols.
      • Beams, compounds, infusions, all similar to BNL program.
    • First-order analyses can provide valuable insight and help prioritize refinements.
    • Coordinated collaborative ventures are effective.
      • The International Dosimetry Exchange is an example that has benefited the participants and BNCT.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • The International Dosimetry Exchange
    • Purpose: Enable combination of clinical data from different centers conducting BNCT trials.
    • Exchanges
      • Within USA (MIT  BNL )
      • USA/Europe
        • MIT  Finland, Sweden, The Netherlands, Czech Republic
        • Finland  USA (MIT & BNL)
        • Czech Republic  USA (MIT)
      • Europe/Japan
        • Finland  Kyoto University & Japan Atomic Energy Agency
        • Czech Republic  Japan Atomic Energy Agency
      • USA/Argentina
        • MIT  Bariloche
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • Depth Profiles in 7 Beams 13th International Congress on Neutron Capture Therapy 3rd November, 2008
  • What is 10 Gy?
    • Treatment planning output normalized to a common set of corresponding (MIT) measurements.
    • Dose specification: peak weighted dose in brain using factors applied in protocols of the respective clinical centers.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy 10.0 MIT 11.3 Petten Center Dose (Gy) Brookhaven 7.6 Espoo 10.9 Studsvik 13.2 Petten (BSH) 8.9 Rez (BSH) 11.0
  • Recent Examples
    • Miyatake et al. J. Neuro-oncol. 2008
    • 22 cases of recurrent malignant glioma.
    • In Recursive Partitioning Analysis (classes 3+7), MST for BNCT is larger than other trials, but confidence intervals overlap.
    • Referring to the median survival for all patients: “ We are not sure whether this result is reliable, as this is the result from a small series from a single institute. ”
    • Henriksson et al. Radiother. Oncol. 2008
    • 30 cases of malignant glioma.
    • Maximum Studsvik brain dose 15.4 Gy comparable to BNL reported dose of 14.8 Gy.
    • Higher than expected incidence of neurological symptoms attributed to tumor size.
    • Renormalized maximum doses (Gy): BNL 11.3 Studsvik: 20.1
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • The Initiative
    • We are now ready to proceed with collective analyses.
    • Assess normal tissue tolerance, as measured by adverse events, etc.
    • Clinical centers devote a small fraction of their resources toward collective clinical analyses.
      • Contribute data
      • Re-calculate treatment plans
      • Analyze results, advance protocol designs
    • Perform analyses to include Japanese centers
      • Data are perhaps already available from earlier measurements performed by other participants in the IDX.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • Benefits
    • The results would:
      • Facilitate broader understanding of BNCT in the radiotherapy community.
      • Provide proven results for comparing against other radiotherapy modalities.
    • Follow-on Initiatives
      • Aid new centers beginning trials: improved safety, increased participation.
      • Help implement new, possibly joint protocols.
    • Increased communication between groups
      • Encourages further collective analyses and better coordination of efforts.
    3rd November, 2008 13th International Congress on Neutron Capture Therapy
  • Acknowledgements
    • ICNCT-13 Organizers and Program Committee
    • Participants and collaborators at facilities around the world.
    • US Department of Energy – sponsored much of the International Dosimetry Exchange
    • Otto Harling and Peter Binns (MIT)
    • Stead Kiger (Harvard-BIDMC)
    13th International Congress on Neutron Capture Therapy 3rd November, 2008
  • Dialogue
    • Centers are understandably reluctant to contribute data.
      • What factors are involved in this?
      • Can these be overcome?
    • Structure – control of information
    • Logistics of managing/distributing data
    • Publications - sharing academic credit
    • Commercial interests
    • Financial support for effort
    3rd November, 2008 13th International Congress on Neutron Capture Therapy