TY - JOUR
T1 - A systematic methodology review of phase I radiation dose escalation trials
AU - Pijls-Johannesma, Madelon
AU - van Mastrigt, Ghislaine
AU - Hahn, Steve M.
AU - De Ruysscher, Dirk
AU - Baumert, Brigitta G.
AU - Lammering, Guido
AU - Buijsen, Jeroen
AU - Bentzen, Soren M.
AU - Lievens, Yolande
AU - Kramar, Andrew
AU - Lambin, Philippe
PY - 2010/5
Y1 - 2010/5
N2 - Background and purpose: The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint. Materials and methods: We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients. Results: Fifty-three trials (phase I: n = 36, phase I-II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as >3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26). Conclusion: In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.
AB - Background and purpose: The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint. Materials and methods: We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients. Results: Fifty-three trials (phase I: n = 36, phase I-II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as >3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26). Conclusion: In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.
KW - Systematic review
KW - Radiotherapy and clinical trial phase I
U2 - 10.1016/j.radonc.2010.02.009
DO - 10.1016/j.radonc.2010.02.009
M3 - Article
C2 - 20338652
SN - 0167-8140
VL - 95
SP - 135
EP - 141
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 2
ER -