gms | German Medical Science

48th Meeting of the Particle Therapy Co-Operative Group

Particle Therapy Co-Operative Group (PTCOG)

28.09. - 03.10.2009, Heidelberg

A model-based strategy to assess indications for proton radiotherapy

Meeting Abstract

  • J. Langendijk - Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands
  • M. Verheij - Radiation Oncology, Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
  • P. Lambin - Radiation Oncology, MAASTRO/Maastricht University Medical Center, Maastricht, The Netherlands
  • M. Pijls-Johannesma - Radiation Oncology, MAASTRO/Maastricht University Medical Center Groningen, Maastricht, The Netherlands
  • F. R. Ubbels - Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands
  • P. C. Levendag - Radiation Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
  • C. A. Marijnen - Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
  • G. de Bock - Epidemiology, University Medical Center Groningen, Groningen, The Netherlands

PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09ptcog121

doi: 10.3205/09ptcog121, urn:nbn:de:0183-09ptcog1211

Published: September 24, 2009

© 2009 Langendijk et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Introduction: The last 2 years, there is a profound discussion around the question whether or not proton beam therapy should be clinically introduced as the standard of care for specific indications without having this confirmed by RCT's. This debate arises in particular from the situation when protons are introduced primarily with the aim to reduce the dose to critical organs and thus to prevent side effects. We developed an alternative methodology to assess the potential benefit of protons over photons. This 3-step strategy will be used by the national authorities in the Netherlands to select the most solid indications for proton radiotherapy.

Methods: Step 1: The basic principle in the development of new radiation delivery techniques is the existence of validated relationships between dose distributions in critical organs and the probability of radiation-induced side effects (i.e. NTCP). In general, the NTCP will increase with increasing dose and increasing volume that receives a certain dose.

Step 2: With respect to reduction of side effects, the potential benefit of proton therapy is mainly based on the assumption that this new technique results in a further optimized dose distribution, referring to an at least equivalent dose to the target volume with a lower radiation dose to critical organs. Subgroups must be identified from studies, in which the dose distributions that can be achieved with the new technique will be compared with the current standard in the same cohort of patients. These kinds of studies are referred to as planning comparative studies. The added value of protons can only be justified in case of straightforward comparisons with photons, meaning that the reference technique should at least include the most advanced and currently available photon techniques. Moreover, for a proper design of in-silico studies it is important to define clear endpoints, i.e., the most relevant DVH-parameters following from NTCP-modelling studies, and to use these parameters with properly chosen dose constraints for treatment planning optimisation for all techniques included in the analysis.

Step 3: The final step will be to determine to what extent optimised physical dose distributions will translate into a clinically relevant beneficial effect, using the combination of data from existing NTCP-models and planning comparative studies. This last step is crucial as not all differences in dose distribution will translate in similar reductions of NTCP-values, depending on the baseline value on the X-axis and the shape of the NTCP-curve.

Discussion and conclusion: This model-based strategy can be used to estimate the percentage of patients in specific populations of patients and to assess whether an individual patient will benefit from protons instead of photons. The indications resulting from this methodology are referred to as model-based indications.