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A systematic methodology review of phase I radiation dose escalation trials

2010; Elsevier BV; Volume: 95; Issue: 2 Linguagem: Inglês

10.1016/j.radonc.2010.02.009

1879-0887

Madelon Pijls-Johannesma, Ghislaine A. P. G. van Mastrigt, Steve M. Hahn, Dirk De Ruysscher, Brigitta G. Baumert, Guido Lammering, Jeroen Buijsen, Søren M. Bentzen, Yolande Lievens, Andrew Kramar, Philippe Lambin,

Radiation Therapy and Dosimetry

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.