Robust optimization is not sufficient to account for anatomical changes in bilateral head and neck intensity-modulated proton therapy

Purpose/Objective
Robust optimization in proton therapy considers uncertainties in patient setup and particle range during the plan optimization. In general, however, anatomical changes occurring during the treatment course, potentially causing a degradation of the plan quality, are neglected. The aim of this study was to quantify the influence of these changes on the dose distribution for patients with bilateral head and neck cancer (HNC).

Material/Methods
Datasets from 20 HNC patients, consisting of a planning CT and weekly control CTs (cCT), were analyzed. Intensity-modulated proton therapy (IMPT) plans with minimax robust optimization were calculated, accounting 3 mm and 3.5% for setup and range uncertainty, respectively. Prescribed doses to the low- and high-risk clinical target volume (CTV) were 57 and 70 Gy(RBE), respectively, delivered in 33 fractions. The organs at risk (OAR) spinal cord, brainstem, parotid glands, larynx, pharyngeal constrictor and esophageal inlet muscle were considered for plan optimization. Weekly cumulative doses, taking the anatomical variations of the cCTs into account, were compared with the nominal plan.
When a reduction in target coverage and/or increased dose to OARs was detected, a plan adaptation was performed on the cCT where the dose degradation was observed. Furthermore, for these patients an additional robust plan was calculated, taking also anatomical changes from the first two cCTs into account in the robust optimization. It was evaluated if a subsequent plan adaptation would still be necessary.

Results
Nominal plans fulfilled the clinical specifications of D98% ≥ 95% of the prescribed dose to the CTVs (range 96.58-98.81% for low-risk CTV and 96.83-98.76% for high-risk CTV). During the treatment course, anatomical changes lead to reduced weekly cumulative D98% values in five patients (25%; minimum 90.17% for low-risk CTV and 89.19% for high-risk CTV). Doses in OARs remained below the clinical constrains during the treatment course. One treatment adaptation was performed for each of these five patients, which allowed a target coverage improvement (range 97.68-99.72% for low-risk CTV and 95.89-98.46% for high-risk CTV). Total cumulative doses including adaptation were acceptable (range 96.67-98.37% for low-risk CTV and 95.11-97.39% for high-risk CTV, see Figure 1a).
The results for the more sophisticated robust plan, considering the first two cCTs, were diverse: whereas plan adaption became obsolete in one patient, the total cumulative dose would, without adaptation, still have been below clinical constraints in another (Figure 1b and 2).

Conclusion
In a substantial number of patients, robust optimization only is not sufficient to account for anatomical changes occurring during the treatment course, resulting in severe target coverage degradation. Assessment of the cumulative weekly doses allowed detection of target coverage loss. The importance of frequent in-treatment imaging is underlined.