Knowledge-based planning using pseudo-structures for volumetric modulated arc therapy (VMAT) of postoperative uterine cervical cancer: a multi-institutional study.

BACKGROUND: The aim of this study was to investigate the performance of the RapidPlan (RP ) using models registered pseudostructures, and to determine how many structures are required for automatic optimization of volumetric modulated arc therapy (VMAT) for postoperative uterine cervical cancer. MATERIALS AND METHODS: Pseudo-structures around the PTV were retrospectively contoured for patients who had completed treatment at five institutions. For 22 common patients, plans were generated with a single optimization for models with two (RP_2), four (RP_4), and five (RP_5) registered structures, and the dosimetric parameters of these models were compared with a clinical plan with several optimizations. RESULTS: Most dosimetric parameters showed no major differences between each RP model. In particular, the rectum Dmax, V50Gy, and V40Gy with RP_2, RP_4, and RP_5 were not significantly different, and were lower than those of the clinical plan. The average proportions of plans achieving acceptable criteria for dosimetric parameters were close to 100% for all models. Using RP_2, the average time for the VMAT planning was reduced by 88 minutes compared with the clinical plan. CONCLUSION: The RapidPlan model with two registered pseudo-structures could generate clinically acceptable plans while saving time.

A Clinical Evaluation of American Brachytherapy Society Consensus Guideline for Bulky Vaginal Mass in Gynecological Cancer.

OBJECTIVES: American Brachytherapy Society (ABS)-recommended interstitial brachytherapy (IBT) should be considered for bulky vaginal tumor thicker than 5 mm. The aim of this study was to evaluate the ABS consensus guideline for patients with severe vaginal invasion based on our long-term follow-up results. METHODS/MATERIALS: The study included 7 patients with vaginal cancer and 14 patients with cervical cancer invading to the lower vagina. Based on prebrachytherapy magnetic resonance imaging findings, patients received intracavitary brachytherapy (ICT) for vaginal tumors 5 mm or less or IBT for vaginal tumors less than 5 mm. Nine patients received ICT and the remaining 12 patients received IBT. For dosimetric comparison, an experimental recalculation as the virtual IBT for patients actually treated by ICT, and vice versa, was performed. RESULTS: The 5-year local control rate for all tumors was 89.4%. No differences in local control between ICT- and IBT-treated groups were observed (P = 0.21). One patient experienced a grade 3 rectal complication. There were no significant differences in the CTV D90 and rectum D2cc between the 2 groups (P = 0.13 and 0.39, respectively). In the dosimetric study of ICT-treated patients, neither the actual ICT plans nor the experimental IBT plans exceeded the limited dose for organs at risk, which were recommended in the guideline published from the ABS. In the IBT-treated patients, D2cc for bladder and rectum of the experimental ICT plans was significantly higher than for the actual IBT plans (P < 0.001 and <0.001, respectively), and 11 experimental ICT plans (92%) exceeded the limited dose for bladder and/or rectum D2cc. CONCLUSIONS: Tumor control and toxicity after selected brachytherapy according to vaginal tumor thickness were satisfactory; IBT instead of ICT is recommended for patients with vaginal tumor thickness greater than 5 mm to maintain bladder and/or rectum D2cc.

[Optimal parameter decision method in VMAT for lung tumors with respiratory motions].

When performing lung cancer treatments using volumetric modulated arc therapy (VMAT) technique, dose error related to respiratory motion of tumors and multi leaf collimator (MLC) movement may occur. The dose error causes daily dose variation in multiple fractionations irradiation. The purpose of this study is to verify the influence of the respiratory motion and the MLC movement on the daily dose variation, and to confirm the feasibility of deciding robust planning parameter against the dose variation. We prepared 5 VMAT plans for imitating lung tumor in thorax dynamic phantom. Dose calculations of these plans were done taking into account the respiratory motions. We examined the relation between dose variation and two parameters that were number of respiration in an arc and MLC gap width. We presented the relationship between the dose variation and each parameters using regression analysis, and we could derive the approximation formula for estimating the dose variation using these parameters. We could estimate dose variation in another VMAT plans using the approximation formula and another plans parameters. By confirming dose variation in planning procedure using this estimation method, we may decide planning parameter taking the dose variation into account. So, we could establish the estimation method to decide adequate planning parameters in VMAT.

Management of the baseline shift using a new and simple method for respiratory-gated radiation therapy: detectability and effectiveness of a flexible monitoring system.

PURPOSE: In respiratory-gated radiation therapy, a baseline shift decreases the accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness of audio-feedback and audio-visual feedback in correcting the baseline shift in the breathing pattern of the patient has been demonstrated previously. However, the baseline shift derived from the intrafraction motion of the patient's body cannot be corrected by these methods. In the present study, the authors designed and developed a simple and flexible system. METHODS: The system consisted of a web camera and a computer running our in-house software. The in-house software was adapted to template matching and also to no preimage processing. The system was capable of monitoring the baseline shift in the intrafraction motion of the patient's body. Another marker box was used to monitor the baseline shift due to the flexible setups required of a marker box for gated signals. The system accuracy was evaluated by employing a respiratory motion phantom and was found to be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the effectiveness of this flexible and independent system in gated treatment was investigated in healthy volunteers, in terms of the results from the differences in the baseline shift detectable between the marker positions, which the authors evaluated statistically. RESULTS: The movement of the marker on the sternum [1.599 +/- 0.622 mm (1 SD)] was substantially decreased as compared with the abdomen [6.547 +/- 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the baseline shifts for the sternum [-0.136 +/- 0.868 (2 SD)] were in better agreement with the nominal baseline shifts than was the case for the abdomen [-0.722 +/- 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and detected using the monitoring system, which could acquire the movement of the marker on the sternum. The baseline shift-monitoring system with the displacement-based methods for highly accurate respiratory-gated treatments should be used to make most of the displacement-based gating methods. CONCLUSIONS: The advent of intensity modulated radiation therapy and volumetric modulated radiation therapy facilitates margin reduction for the planning target volumes and the OARs, but highly accurate irradiation is needed to achieve target coverage and OAR sparing with a small margin. The baseline shifts can affect treatment not only with the respiratory gating system but also without the system. Our system can manage the baseline shift and also enables treatment irradiation to be undertaken with high accuracy.

General ion recombination effect in a liquid ionization chamber in high-dose-rate pulsed photon and electron beams.

Liquid ionization chambers (LICs) are highly sensitive to dose irradiation and have small perturbations because of their liquid-filled sensitive volume. They require a sensitive volume much smaller than conventional air-filled chambers. However, it has been reported that the collection efficiency has dependencies on the dose per pulse and the pulse repetition frequency of a pulsed beam. The purpose of this study was to evaluate in detail the dependency of the ion collection efficiency on the pulse repetition frequency. A microLion (PTW, Freiburg, Germany) LIC was exposed to photon and electron beams from a TrueBeam (Varian Medical Systems, Palo Alto, USA) linear accelerator. The pulse repetition frequency was varied, but the dose per pulse was fixed. A theoretical evaluation of the collection efficiency was performed based on Boag's theory. Linear correlations were observed between the frequency and the relative collection for all energies of the photon and electron beams. The decrease in the collected charge was within 1% for all the flattened photon and electron beams, and they were 1.1 and 1.8% for the 6 and 10 MV flattening filter-free photon beams, respectively. The theoretical ion collection efficiency was 0.990 for a 10 MV flattened photon beam with a dose rate of 3 Gy·min-1. It is suggested that the collected charge decreased because of the short time intervals of the beam pulse compared with the ion collection time. Thus, it is important to correctly choose the pulse repetition frequency, particularly when flattening filter-free mode is used for absolute dose measurements.

Prognostic factors associated with the accuracy of deformable image registration in lung cancer patients treated with stereotactic body radiotherapy.

We evaluated the accuracy of an in-house program in lung stereotactic body radiation therapy (SBRT) cancer patients, and explored the prognostic factors associated with the accuracy of deformable image registrations (DIRs). The accuracy of the 3 programs which implement the free-form deformation and the B-spline algorithm was compared regarding the structures on 4-dimensional computed tomography (4DCT) image datasets between the peak-inhale and peak-exhale phases. The dice similarity coefficient (DSC) and normalized DSC (NDSC) were measured for the gross tumor volumes from 19 lung SBRT patients. We evaluated the accuracy of DIR using gross tumor volume, magnitude of displacement from 0% phase to 50% phase, whole lung volume in the 50% phase image, and status of tumor pleural attachment. The median NDSC values using the NiftyReg, MIM Maestro and Velocity AI programs were 1.027, 1.005, and 0.946, respectively, indicating that NiftyReg and MIM Maestro programs had similar accuracy with an uncertainty of < 1 mm. Larger uncertainty of 1 to 2 mm was observed using the Velocity AI program. The NiftyReg and the MIM programs provided higher NDSC values than the median values when the gross tumor volume was attached to the pleura (p <0.05). However, it showed a different trend in using the Velocity AI program. All software programs provided unexpected results, and there is a possibility that such results would reduce the accuracy of 4D treatment planning and adaptive radiotherapy. The unexpected results may be because the tumors are surrounded by other tissues, and there are differences regarding the region of interest for rigid and nonrigid registration. Furthermore, our results indicated that the pleural attachment status might be an important predictor of DIR accuracy for thoracic images, indicating that there is a potentially large dose distribution discrepancy concerning 4D treatment planning and adaptive radiotherapy.

Dose warping performance in deformable image registration in lung.

PURPOSE: It is unclear that spatial accuracy can reflect the impact of deformed dose distribution. In this study, we used dosimetric parameters to compare an in-house deformable image registration (DIR) system using NiftyReg, with two commercially available systems, MIM Maestro (MIM) and Velocity AI (Velocity). METHODS: For 19 non-small-cell lung cancer patients, the peak inspiration (0%)-4DCT images were deformed to the peak expiration (50%)-4DCT images using each of the three DIR systems, which included computation of the deformation vector fields (DVF). The 0%-gross tumor volume (GTV) and the 0%-dose distribution were also then deformed using the DVFs. The agreement in the dose distributions for the GTVs was evaluated using generalized equivalent uniform dose (gEUD), mean dose (Dmean), and three-dimensional (3D) gamma index (criteria: 3mm/3%). Additionally, a Dice similarity coefficient (DSC) was used to measure the similarity of the GTV volumes. RESULTS: Dmean and gEUD demonstrated good agreement between the original and deformed dose distributions (differences were generally less than 3%) in 17 of the patients. In two other patients, the Velocity system resulted in differences in gEUD of 50.1% and 29.7% and in Dmean of 11.8% and 4.78%. The gamma index comparison showed statistically significant differences for the in-house DIR vs. MIM, and MIM vs. Velocity. CONCLUSIONS: The finely tuned in-house DIR system could achieve similar spatial and dose accuracy to the commercial systems. Care must be taken, as we found errors of more than 5% for Dmean and 30% for gEUD, even with a commercially available DIR tool.

Three-month stability of delay and probability discounting measures.

Psychopharmacologists are interested in delay and probability discounting because the tendency to discount the value of future and uncertain rewards has been linked with drug dependency. However, relatively little is known about the long-term stability of discounting measures typically studied in clinical psychopharmacology. To evaluate the stability of discounting over a 3-month period, the authors compared points of subjective equality (indifference points) with those collected from the same subjects 3 months earlier. Seven delay periods, ranging from 1 week to 25 years, and 7 probability values, ranging from .95 to .05, were assessed in an undergraduate sample (n=22, delay discounting; n=18, probability discounting). The authors examined both differential stability (stability of individual differences) and absolute stability (stability of the group mean) of delay and probability discounting measures as well as their respective indifference points. The results demonstrate that standard delay and probability discounting parameters (e.g., hyperbolic k and area under the curve) had both differential stability and absolute stability across 3 months. Moreover, most indifference points in the delay and probability discounting tasks demonstrated both differential and absolute stability. All together, these results suggest that delay and probability parameters are stable enough to predict future behavior, such as substance abuse. Additional findings indicated that a hyperbolic function fitted the data better than an exponential function and that delay and probability discounting parameters were not significantly correlated.

[Examination of formula for enhanced dynamic wedge factors in symmetric and asymmetric fields].

We proposed a formula for the enhanced dynamic wedge (EDW) factor in the half-field (HF) that combined the formula proposed by Liu et al. in 1998 and their formula in 2003. When the EDW was used for irradiation to the tangent line of the HF breast, the values calculated by our formula and the measured values were consistent within 0.5%. We showed that our proposed formula was useful, easy to use, and more accurate than the conventional formula. The purpose of this study was to examine the available range of the wedge factor of symmetrical and asymmetric EDW calculated by our formula. As a result of the examination, the values calculated by our formula and the measured values were consistent within 2% except for highly asymmetric EDW. We created a spreadsheet to calculate the wedge factor easily and accurately. We will examine the reason why the calculated and measured values were greater than 2%, and improve our formula so that it can be used in a wider range.

Discounting delayed and probabilistic monetary gains and losses by smokers of cigarettes.

RATIONALE: Nicotine dependence has been associated with impulsivity and discounting delayed/uncertain outcomes. OBJECTIVES: This study had two main objectives: (1) to examine the relationship between the number of cigarettes consumed per day and the degree to which delayed and uncertain monetary gains and losses are discounted by smokers, and (2) to determine the relationship between the estimated dose of nicotine intake per day and the degree to which four types of discounting occur. METHODS: Twenty seven habitual smokers and 23 never smokers participated in this experiment. They were required to choose between immediate and delayed monetary rewards (or losses), or between guaranteed and probabilistic rewards (or losses). RESULTS: The degree to which delayed monetary gains were discounted was significantly and positively correlated with both the number of cigarettes smoked and the estimated dose of nicotine intake per day. Conversely, there was no relationship between smoking and the remaining three types of discounting. Also, mild smokers in our sample did not differ from never smokers in discounting monetary gains or losses. CONCLUSIONS: In general, our results suggest that both the frequency of nicotine self-administration, as well as the dosage, are positively associated with greater delay discounting of gains. One neuropsychopharmacological explanation for this effect is that chronic nicotine intake may induce neuroadaptation of the neural circuitry involved in reward processing.

Interpersonal trust and social stress-induced cortisol elevation.

A neuroendocrine correlate of interpersonal trust is relatively unknown. We investigated the relationship between an interpersonal trust-related personality (General Trust Scale) and cortisol elevation induced by social stress in 20 men. Spearman's rank order correlation analysis revealed a significant negative correlation between social stress-induced cortisol elevation and General Trust Scale. The present results indicate subjects with higher degrees of interpersonal trust have lower levels of neuroendocrine response to social stress.

Anxiety, reactivity, and social stress-induced cortisol elevation in humans.

OBJECTIVES: Traditionally, it has been hypothesized that highly anxious/emotionally reactive subjects may have exaggerated social stress response. We examined the relationship between self-reported anxiety, emotional reactivity, and social stress response. METHODS: We investigated the relationship between personality scales of trait-state anxiety, subjective autonomic reactivity, and salivary cortisol levels before and after social stress exposure (Trier Social Stress Test) in 20 men. RESULTS: Significant positive correlations between anxiety, subjective autonomic reactivity, and basal cortisol levels were observed, while neither anxiety nor subjective autonomic reactivity was correlated with social stress-induced cortisol elevation. CONCLUSIONS: The present results indicate (i) subjects with higher degrees of trait anxiety/subjective autonomic reactivity have higher basal cortisol levels, and (ii) in contrast to the traditional view, anxious personality is not strongly associated with exaggerated cortisol response to social stress.