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

• Published in: International journal of radiation oncology, biology, physics Vol. 95; no. 1; pp. 30 - 36
• Main Authors: Widder, Joachim, MD, PhD, van der Schaaf, Arjen, PhD, Lambin, Philippe, MD, PhD, Marijnen, Corrie A.M., MD, PhD, Pignol, Jean-Philippe, MD, PhD, Rasch, Coen R., MD, PhD, Slotman, Ben J., MD, PhD, Verheij, Marcel, MD, PhD, Langendijk, Johannes A., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016
• Subjects: ANIMAL TISSUES; Biomarkers; DRUGS; Evidence-Based Medicine; Hematology, Oncology and Palliative Medicine; Humans; Models, Theoretical; NEOPLASMS; Neoplasms - radiotherapy; Netherlands; Organ Sparing Treatments - methods; Organs at Risk - radiation effects; Patient Selection; Photons - therapeutic use; Precision Medicine - methods; Probability; PROTON BEAMS; Proton Therapy - adverse effects; Proton Therapy - methods; Radiation Dosage; Radiation Injuries - etiology; Radiation Injuries - prevention & control; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Randomized Controlled Trials as Topic; Netherlands
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2015.10.004

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.