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

TY - JOUR

T1 - Data-Based Radiation Oncology: Design of Clinical Trials in the Toxicity Biomarkers Era

AU - Azria, David

AU - Lapierre, Ariane

AU - Gourgou, Sophie

AU - De Ruysscher, Dirk

AU - Colinge, Jacques

AU - Lambin, Philippe

AU - Brengues, Muriel

AU - Ward, Tim

AU - Bentzen, Søren M

AU - Thierens, Hubert

AU - Rancati, Tiziana

AU - Talbot, Christopher J

AU - Vega, Ana

AU - Kerns, Sarah L

AU - Andreassen, Christian Nicolaj

AU - Chang-Claude, Jenny

AU - West, Catharine M L

AU - Gill, Corey M

AU - Rosenstein, Barry S

PY - 2017/4

Y1 - 2017/4

N2 - 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.

AB - 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.

KW - Journal Article

KW - Review

U2 - 10.3389/fonc.2017.00083

DO - 10.3389/fonc.2017.00083

M3 - SCORING: Review article

C2 - 28497027

VL - 7

SP - 83

JO - FRONT ONCOL

JF - FRONT ONCOL

SN - 2234-943X

ER -