Use of Veff and iso-NTCP in the implementation of dose escalation protocols

This report investigates the use of a normal tissue complication probability (NTCP) model, 3-D dose distributions, and a dose volume histogram reduction scheme in the design and implementation of dose escalation protocols for irradiation of sites that are primarily limited by the dose to a normal tissue which exhibits a strong volume effect (e.g., lung, liver).

Plots containing iso-NTCP contours are generated as a function of dose and partial volume using a parameterization of a NTCP description. Single step dose volume histograms are generated from 3-D dose distributions using the effective-volume (Veff) reduction scheme. In this scheme, the value of Veff for each dose volume histogram is independent of dose units (Gy, %). Thus, relative dose distributions (%) may be used to segregate patients by Veff into bins containing different ranges of Veff values before the assignment of prescription doses (Gy). The doses for each bin of Veff values can then be independently escalated between estimated complication levels (iso-NTCP contours).

Given that for the site under study, an investigator believes that the NTCP parameterization and the Veff methodology at least describe the general trend of clinical expectations, the concepts discussed allow the use of patient specific 3-D dose/volume information in the design and implementation of dose escalation studies. The result is a scheme with which useful prospective tolerance data may be systematically obtained for testing the different NTCP parameterizations and models.