Failure-probability driven dose painting

Abstract

Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.

Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). The total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose-response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.

Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%-91%) as compared to the observed TCP of 70%.

Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.

Figure 1

(Left) Estimated dose–response curves based on the observed recurrence pattern and the actuarial risk of local recurrence following complete clinical response after five years. The circles show the partial control probabilities with the current prescription. (Right) The optimized mean physical doses to the target structures in 20 HNSCC patients versus the current clinical plans.

Figure 2

Optimized tumor control probability vs maximum dose constraint. The 85 Gy maximum tolerated dose from the Ghent experience (Ref. 9) capture the vast majority of the potential for improvement in TCP. The curves are smoothed to remove a part of a jitter on the order of 0.5% TCP from the optimizer.

Figure 3

Clinical dose plan (left) and the realization of the optimal dose prescription (middle). The doses to the central target volumes are substantially increased with the optimized prescription. The parotids appear to be better spared with the dose painted plan. This is, however, mostly an effect of the updated technique (VMAT versus IMRT) and largely the same sparing of the parotids can be achieved by replanning the clinically used dose prescription with a VMAT technique (right). See also Fig. 4.

Figure 4

(Left) Mean physical doses to the salivary gland structures with the dose painted plans versus the delivered plans (upper) or reoptimized VMAT plans with standard prescription (lower) in 20 patients. (Right) Normal tissue complication probability for the salivary gland structures (Refs. 15, 16, 17). The models presented on submandibular toxicity is for stimulated flow (Ref. 16) and in the multivariate model of sticky saliva we assumed, for illustration, a patient of age 60 and same dose to sublingual glands as for the submandibular glands (Ref. 17).