Data-Based Radiation Oncology: Design of Clinical Trials in the Toxicity Biomarkers Era

David Azria*, Ariane Lapierre, Sophie Gourgou, Dirk De Ruysscher, Jacques Colinge, Philippe Lambin, Muriel Brengues, Tim Ward, Soren M. Bentzen, Hubert Thierens, Tiziana Rancati, Christopher J. Talbot, Ana Vega, Sarah L. Kerns, Christian Nicolaj Andreassen, Jenny Chang-Claude, Catharine M. L. West, Corey M. Gill, Barry S. Rosenstein

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

26 Citations (Web of Science)

Abstract

The ability to stratify patients using a set of biomarkers, which predict that toxicity risk would allow for radiotherapy (RT) modulation and serve as a valuable tool for precision medicine and personalized RT. For patients presenting with tumors with a low risk of recurrence, modifying RT schedules to avoid toxicity would be clinically advantageous. Indeed, for the patient at low risk of developing radiation-associated toxicity, use of a hypofractionated protocol could be proposed leading to treatment time reduction and a cost-utility advantage. Conversely, for patients predicted to be at high risk for toxicity, either a more conformal form or a new technique of RT, or a multidisciplinary approach employing surgery could be included in the trial design to avoid or mitigate RT when the potential toxicity risk may be higher than the risk of disease recurrence. In addition, for patients at high risk of recurrence and low risk of toxicity, dose escalation, such as a greater boost dose, or irradiation field extensions could be considered to improve local control without severe toxicities, providing enhanced clinical benefit. In cases of high risk of toxicity, tumor control should be prioritized. In this review, toxicity biomarkers with sufficient evidence for clinical testing are presented. In addition, clinical trial designs and predictive models are described for different clinical situations.

Original languageEnglish
Article number83
Number of pages11
JournalFrontiers in Oncology
Volume7
DOIs
Publication statusPublished - 27 Apr 2017

Keywords

  • trial design
  • patient selection
  • biomarkers
  • radiotherapy
  • toxicity tests
  • GENOME-WIDE ASSOCIATION
  • NORMAL TISSUE-REACTIONS
  • BREAST-CANCER PATIENTS
  • TARGETED INTRAOPERATIVE RADIOTHERAPY
  • SINGLE NUCLEOTIDE POLYMORPHISMS
  • RANDOMIZED CONTROLLED-TRIAL
  • PROSTATE-CANCER
  • IN-VITRO
  • PHASE-II
  • CHROMOSOMAL RADIOSENSITIVITY

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