Quantifying the dose accumulation uncertainty after deformable image registration in head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: Deformable image registration (DIR) facilitated dose reconstruction and accumulation can be applied to assess delivered dose and verify the validity of the treatment plan during treatment. This retrospective study used in silico deformations based on clinically observed anatomical changes as ground truth to investigate the uncertainty of reconstructed and accumulated dose in head-and-neck radiotherapy (HNRT). MATERIALS AND METHODS: A planning CT (pCT), cone beam CT (CBCT) from week one of treatment and three later CBCTs were selected for 12 HNRT patients. These images were used to generate in silico reference CBCTs and deformation vector fields (DVFs) as ground truth with B-spline DIR. Inverse consistency (IC) of voxels was assessed by determining their net displacement after successive application of the forward and backward DVF. The reconstructed dose based on demons DIR was compared to the ground truth to assess the structure-specific uncertainties of this DIR algorithm for inverse consistent and inverse inconsistent voxels. RESULTS: Overall, 98.5% of voxels were inverse consistent with the 95% level of confidence range for dose reconstruction of a single fraction equal to [-2.3%; +2.1%], [-10.2%; +15.2%] and [-9.5%; +12.5%] relative to their planned dose for target structures, critical organs at risk (OARs) and non-critical OARs, respectively. Inverse inconsistent voxels generally showed a higher level of uncertainty. CONCLUSION: The uncertainty in accumulated dose using DIR can be accurately quantified and incorporated in dose-volume histograms (DVHs). This method can be used to prospectively assess the adequacy of target coverage during treatment in an objective manner.

Dose accumulation to assess the validity of treatment plans with reduced margins in radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: Literature has reported reduced treatment toxicity in head-and-neck radiotherapy (HNRT) when reducing the planning target volume (PTV) margin from 5 to 3 mm but loco-regional control was not always preserved. This study used deformable image registration (DIR)-facilitated dose accumulation to assess clinical target volume (CTV) coverage in the presence of anatomical changes. MATERIALS AND METHODS: VMAT plans for 12 patients were optimized using 3 or 5 mm PTV and planning risk volume (PRV) margins. The planning computed tomography (pCT) scan was registered to each daily cone beam CT (CBCT) using DIR. The inverse registration was used to reconstruct and accumulate dose ( D acc ). CTV coverage was assessed using the dose-volume histogram (DVH) metric D 99 % acc and by individual voxel analysis. Both approaches included an uncertainty estimate using the 95% level of confidence. RESULTS: D 99 % acc was less than 95% of the prescribed dose D presc for three cases including only one case where this was at the 95% level of confidence. However for many patients, the accumulated dose included a substantial volume of voxels receiving less than 95% D presc independent of margin expansion, which predominantly occurred in the subdermal region. Loss in target coverage was very patient specific but tightness of target volume coverage at planning was a common factor leading to underdosage. CONCLUSION: This study agrees with previous literature that PTV/PRV margin reduction did not significantly reduce CTV coverage during treatment, but also highlighted that tight coverage of target volumes at planning increases the risk of clinically unacceptable dose delivery. Patient-specific verification of dose delivery to assess the dose delivered to each voxel is recommended.

Beta Amyloid Deposition Is Not Associated With Cognitive Impairment in Parkinson's Disease.

The extent to which Alzheimer neuropathology, particularly the accumulation of misfolded beta-amyloid, contributes to cognitive decline and dementia in Parkinson's disease (PD) is unresolved. Here, we used Florbetaben PET imaging to test for any association between cerebral amyloid deposition and cognitive impairment in PD, in a sample enriched for cases with mild cognitive impairment. This cross-sectional study used Movement Disorders Society level II criteria to classify 115 participants with PD as having normal cognition (PDN, n = 23), mild cognitive impairment (PD-MCI, n = 76), or dementia (PDD, n = 16). We acquired 18F-Florbetaben (FBB) amyloid PET and structural MRI. Amyloid deposition was assessed between the three cognitive groups, and also across the whole sample using continuous measures of both global cognitive status and average performance in memory domain tests. Outcomes were cortical FBB uptake, expressed in centiloids and as standardized uptake value ratios (SUVR) using the Centiloid Project whole cerebellum region as a reference, and regional SUVR measurements. FBB binding was higher in PDD, but this difference did not survive adjustment for the older age of the PDD group. We established a suitable centiloid cut-off for amyloid positivity in Parkinson's disease (31.3), but there was no association of FBB binding with global cognitive or memory scores. The failure to find an association between PET amyloid deposition and cognitive impairment in a moderately large sample, particularly given that it was enriched with PD-MCI patients at risk of dementia, suggests that amyloid pathology is not the primary driver of cognitive impairment and dementia in most patients with PD.

Monitoring anatomical changes of individual patients using statistical process control during head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: Reduced toxicity while maintaining loco-regional control rates have been reported after reducing planning target volume (PTV) margins for head-and-neck radiotherapy (HNRT). In this context, quantifying anatomical changes to monitor patient treatment is preferred. This retrospective feasibility study investigated the application of deformable image registration (DIR) and Exponentially Weighted Moving Average (EWMA) Statistical Process Control (SPC) charts for this purpose. MATERIALS AND METHODS: DIR between the computed tomography for treatment planning (pCT) images of twelve patients and their daily on-treatment cone beam computed tomography (CBCT) images quantified anatomical changes during treatment. EWMA charts investigated corresponding trends. Uncertainty analysis provided 90% confidence limits which were used to confirm whether a trend previously breached a threshold. RESULTS: Trends in patient positioning reproducibility occurred before the end of treatment week four in 54% of cases. Using SPC process limits, only 24% of these were confirmed at a 90% confidence level before the end of treatment. Using an a priori clinical limit of 2 mm, absolute changes in patient pose were detected in 39% of cases, of which 82% were confirmed. Soft tissue trends outside SPC process limits occurring before the end of treatment week four were confirmed in 90% of cases. CONCLUSION: Structure specific action thresholds enabled detection of systematic anatomical changes during the first four weeks of treatment. Investigation of the dosimetric impact of the observed deviations is needed to show the efficacy of SPC to timely indicate required treatment adaptation and provide a safety net for PTV margin reduction.

The dosimetric effect of electron density overrides in 3DCRT Lung SBRT for a range of lung tumor dimensions.

The combined effects of lung tumor motion and limitations of treatment planning system dose calculations in lung regions increases uncertainty in dose delivered to the tumor and surrounding normal tissues in lung stereotactic body radiotherapy (SBRT). This study investigated the effect on plan quality and accuracy when overriding treatment volume electron density values. The QUASAR phantom with modified cork cylindrical inserts, each containing a simulated spherical tumor of 15-mm, 22-mm, or 30-mm diameter, was used to simulate lung tumor motion. Using Monaco 5.1 treatment planning software, two standard plans (50% central phase (50%) and average intensity projection (AIP)) were compared to eight electron density overridden plans that focused on different target volumes (internal target volume (ITV), planning target volume (PTV), and a hybrid plan (HPTV)). The target volumes were set to a variety of electron densities between lung and water equivalence. Minimal differences were seen in the 30-mm tumor in terms of target coverage, plan conformity, and improved dosimetric accuracy. For the smaller tumors, a PTV override showed improved target coverage as well as better plan conformity compared to the baseline plans. The ITV plans showed the highest gamma pass rate agreement between treatment planning system (TPS) and measured dose (P < 0.040). However, the low electron density PTV and HPTV plans also showed improved gamma pass rates (P < 0.035, P < 0.011). Low-density PTV overrides improved the plan quality and accuracy for tumor diameters less than 22 mm only. Although an ITV override generated the most significant increase in accuracy, the low-density PTV plans had the additional benefit of plan quality improvement. Although this study and others agreed that density overrides improve the treatment of SBRT, the optimal density override and the conditions under which it should be applied were found to be department specific, due to variations in commissioning and calculation methods.