Purpose:To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular-and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

Concurrent chemotherapy and PBT to treat unresectable NSCLC afford promising clinical outcomes and rates of toxic effects compared with historical photon therapy data. Further optimization of proton therapy, particularly intensity-modulated proton therapy, is still needed.

For H&N cases studied, OAR sparing in PTV+PRV-based optimization was inferior compared to robust optimization but was superior compared to PTV-based optimization; however, target dose robustness and homogeneity were comparable in the PTV+PRV-based and PTV-based optimizations. The same pattern held for the prostate case. The authors' data suggest that the superiority of robust optimization is not due simply to its inclusion of margins for OARs, but that this is due mainly to the ability of robust optimization to compensate for perturbations in dose distributions within target volumes and normal tissues caused by uncertainties.

Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field-size effects on dose output. In the present study, we developed a pencil-beam algorithm for scanning-proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil-beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field-size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy.

Purpose The primary aim of this study was to evaluate the impact of interplay effects for intensity-modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of iso-layered re-scanning for mitigating these interplay effects. Methods and Materials Single-fraction 4D dynamic dose without considering re-scanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on moving patient described by 4D computed tomography (4DCT) during the IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase corresponding to the life span of that spot, and the final dose was accumulated to a reference CT phase by using deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected. Results The CTV prescription coverage for the 7 patients were 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53%, calculated with use of the 4D composite dose, and were 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% with use of the 1FX dynamic dose. For the 7 patients, the CTV coverage, calculated by using single-fraction dynamic dose, were 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, using maximum MU limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. Conclusions Single-fraction 4D dynamic dose without re-scanning was validated as a surrogate to evaluate the interplay effects for IMPT for lung cancer in the clinical setting. The interplay effects can be potentially mitigated by increasing the number of iso-layered re-scanning in each fraction delivery.