NEW WINE IN AN OLD BOTTLE? DOSE ESCALATION UNDER DOSE-VOLUME CONSTRAINTS: A MODEL OF CONFORMAL THERAPY OF THE PROSTATE

In this issue Lee ef al. (5 ) report that rectal toxicity can be moderated in high-dose therapy of the prostate by reducing the volume of the rectal wall irradiated to a high dose. In their study, 257 patients were treated to isocenter doses in the range of 75 Gy, 88 of whom had rectal shielding blocks added to the lateral fields for the last 10 fractions of a four-field plan. The estimated dose reduction to the anterior rectal wall was 4-5 Gy. This approach reduces the observed rectal Grade 2-3 morbidity from 30 out of 137 (22%) to 6 out of 88 (7%). An unstated implication of this approach is that the dose to the posterior of the prostate is also reduced. This article and other recent work addresses the need to clarify the nature of dose escalation in the application of conformal therapy. Similar to Lee et al. (5)) we have long been aware of the need for dose-volume constraints in escalating the dose to the prostatic target. The “classical” approach uniformly increases the dose to the entire planning target volume (PTV ) until the adjacent organs reach their tolerance level. An alternative approach escalates the dose to almost all of the PTV, while a minor volume of tissue adjacent to a critical normal organ may receive a somewhat lower dose to accommodate the dose-volume constraints of a critical organ. One consequence of this latter strategy is the possibility of delivering a higher mean target dose than would have otherwise been possible. Furthermore, it has been theoretically argued in a model of tumor response by Brahme (3) that-with confined target dose heterogeneity-the mean, rather than the minimum, target dose is the sine qua non of local control. Although this strategy, within limits, may meet the goals of dose escalation in prostate cancer, its validity needs to be tested in prospective studies. In our dose escalation studies for prostate cancer we have adapted the latter approach incorporating two essential features. The first is the use of nonuniform margins around the clinical target volume (CTV) to account for treatment uncertainties: 6 mm adjacent to the rectum and 10 mm elsewhere. An additional margin is added to the beam aperture to account for penumbra. The second is the use of rectal dose-volume data as a constraint on dose escalation. Based upon an analysis of rectal toxicity and rectal wall DVH in our patients, and using other published data (2), we estimated that 75 Gy to 30% of the rectal wall would keep the rate of KTOG Grade 2 rectal complications below 10%. In order to escalate to a prescribed dose of 8 1 Gy we treat the prostate uniformly to as high a dose as possible (72 Gy) and then use a conformal plan with tight margins for an additional 9 Gy such that the composite dose distribution carries less than 30% of the rectal wall to 75 Gy. Detailed DVH calculations in a random sample of 10 (of 44) patients demonstrates that the PTV isocenter dose was increased to 86.7 Gy and the mean dose to 84.8 Gy. The dose inhomogeneity might best be expressed by noting that for the PTV the percent volume receiving 78 Gy (VT8cy) is 96% and the VW+ is 89.5%; while for the CTV the VT8cy is 99.5% and the V8,cy is 95.7%-that is, 4% of the CTV ranges in dose between 78 and 8 1 Gy (unpublished data). Thus, this technique produces high mean and isocenter doses with the exception of a transition zone between the posterior of the prostate and the anterior rectal wall. A full description of the technique and the dosimetry will be forthcoming. This strategy of constrained dose escalation, using the technique discussed above, was implemented by us in 44 patients with Stages T2c and T3 prostate cancer treated to a prescribed dose of 81 Gy. Three patients (7% ) developed late Grade 2 rectal toxicity within a median followup time of 21 months. No higher grade toxicities have been observed (unpublished data). Encouraged by the apparent lack of toxicity, we are beginning a phase II