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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.

Author information

Azria D1, Lapierre A1, Gourgou S1, De Ruysscher D2,3, Colinge J1, Lambin P2, Brengues M1, Ward T4, Bentzen SM5, Thierens H6, Rancati T7, Talbot CJ8, Vega A9, Kerns SL10, Andreassen CN11, Chang-Claude J12,13, West CML14, Gill CM15,16, Rosenstein BS15,16.

1 Department of Radiation Oncology, Radiobiology Unit, Biometric and Bio-informatic Divisions, Montpellier Cancer Institute (ICM), IRCM, INSERM U1194, Montpellier, France.

2 Department of Radiation Oncology, Maastricht University Medical Centre, MAASTRO Clinic, Maastricht, Netherlands.

3 Radiation Oncology, KU Leuven, Leuven, Belgium.

4 Patient Advocate, Manchester, UK.

5 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.

6 Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.

7 Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

8 Department of Genetics, University of Leicester, Leicester, UK.

9 Fundacion Publica Galega de Medicina Xenomica-SERGAS, Grupo de Medicina Xenomica-USC, IDIS, CIBERER, Santiago de Compostela, Spain.

10 Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, USA.

11 Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.

12 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

13 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

14 Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester, UK.

15 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

16 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.