Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate.

The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration" technique yielded the highest tumor control probability (TCP) most frequently, followed by the "bone registration" and "tattoo registration" techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (< or = 1.1 %). Reducing the margin size to 5 mm significantly degraded the TCP values of the "tattoo registration" technique in two of the five patients, where a large difference was found compared to the other techniques (< or = 11.8 %). The "CTV registration" technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the margin size seemed the only sure way to reduce the NTCP significantly, irrespective of the IGART technique employed. In escalating the dose with the iso-NTCP constraint, the largest average gain in dose was observed with the "tattoo registration" technique, followed by the "CTV registration" and "bone registration" techniques. This is attributed to the fact that in three of the five patients, the "tattoo registration" technique yielded the lowest NTCP, hence a greater window of opportunity to escalate the dose was possible with this technique. However, the variation among the five patients was also largest with the "tattoo registration" technique where, in the case of one patient, the required dose actually needed to be below the original prescription dose of 70 Gy to satisfy the iso-NTCP constraint. This was not the case with the "CTV registration" technique where positive and similar dose escalation was allowed on all five patients. Based on these data, an attractive dose escalation strategy may be to implement the "CTV registration" technique (for consistent dosimetric coverage) for daily target localization in combination with a margin reduction (for increased normal tissue sparing).