Summary Most cancer radiation therapy accelerators purchased today have gantry-mounted imagers, typically used to image the patient prior to treatment. We imaged prostate cancer patients during their treatment. Combining images with marker segmentation software and a 2- to 3-dimensional reconstruction method, we were able to measure prostate motion during the treatment to within submillimeter accuracy. Because intrafraction prostate monitoring method uses widely available clinical equipment, intratreatment prostate motion monitoring could become routine. Purpose Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiring kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced ≥3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of ≥3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.

A method for accurate dose reconstruction for moving targets with dynamic treatments was developed and experimentally validated in a variety of delivery scenarios. The method is suitable for integration into TPSs, e.g., for reconstruction of the dose delivered to moving tumors or calculation of target doses delivered with DMLC tracking.

PurposeA study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.Methods and materialsTen institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded.ResultsFor all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate.ConclusionsThe investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.

Couch and MLC tracking markedly improved the geometric and dosimetric accuracies of VMAT delivery. However, the two tracking types have different strengths and weaknesses. While couch tracking can correct perfectly for slowly moving targets such as the prostate, MLC tracking may have considerably larger dose errors for persistent target shift perpendicular to the MLC leaves. Advantages of MLC tracking include faster dynamics with better adaptation to fast moving targets, the avoidance of moving the patient, and the potential to track target rotations and deformations.

Electron capture by both bare and microsolvated small peptide dications was investigated by colliding these ions with sodium vapor in an accelerator mass spectrometer to provide insight into processes that occur on the microsecond time frame. Survival of the intact peptide monocation after electron capture depends strongly on molecular size. For dipeptides, no intact reduced species were observed; the predominant ions correspond to loss of hydrogen and ammonia. In contrast, the intact reduced species was observed for larger peptides. Calculated structures indicate that the diprotonated dipeptide ions form largely extended structures with low probability of internal ionic hydrogen bonding (i.e., charge solvation) whereas internal ionic H-bonding occurs extensively for larger peptide dications. Solvation of the peptide ions with between one to seven methanol molecules reduces the total extent of H loss even for dipeptides where intact reduced species can survive more than a microsecond after electron capture. The yield of ions corresponding to cleavage of NOC ␣ bonds (c ϩ and z ϩ· ions) does not depend strongly on peptide size but decreases with the extent of microsolvation for the dipeptide dications. H-bonding appears to play an important role for the survival of the intact reduced ions but less so for the formation of c ϩ and z ϩ· ions. Our results indicate that electron capture predominantly occurs at the ammonium groups (at least 70 to 80%), and provides important new insights into the electron capture dissociation process. (J Am Soc