The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

Joachim Widder*, Arjen van der Schaaf, Philippe Lambin, Corrie A. M. Marijnen, Jean-Philippe Pignol, Coen R. Rasch, Ben J. Slotman, Marcel Verheij, Johannes A. Langendijk

*Corresponding author for this work

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Abstract

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be tested in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.
Original languageEnglish
Pages (from-to)30-36
JournalInternational Journal of Radiation Oncology Biology Physics
Volume95
Issue number1
DOIs
Publication statusPublished - 1 May 2016

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