Influence of maximum MLC leaf speed on the quality of volumetric modulated arc therapy plans.

PURPOSE: Maximum leaf speed is a configurable parameter of MLC in a treatment-planning system. This study investigated the influence of MLC on the quality of VMAT plans. METHODS: Seven MLCs with different maximum leaf speeds (1.0, 1.5, 2.25, 3.5, 5.0, 7.5, and 10 cm/s) were configured for an accelerator in treatment-planning system. Correspondingly, seven treatment plans, with the identical initial optimization parameter, were designed with the mdaccAutoPlan system. Six nasopharyngeal carcinoma (NPC) patients and nine rectal cancer patients were selected, representing complex and simple clinical circumstances. VMAT plan quality was evaluated with PlanIQTM software. The results were statistically analyzed with a one-way analysis of variance (ANOVA) and pairwise comparison tests. RESULTS: The relative changes of plan scores achieved by the seven configured accelerators, with specific maximum MLC leaf speed (MMLS) for each patient, were studied. Two apparent trends of MMLS influence on VMAT plan scores were observed: Plan scores increased with MMLS; Plan scores increased rapidly when MMLS increased from 1 to 3.5, thus the relative change of plan score decreased in this MMLS range. The stationary point of maximum MLC speed (MMSSP) is defined, for the specific MMLS when the relative changes of plan scores is first <5%, as MMLS increases from 1.0 to 10. For rectal plans, MMSSPs were 2.25 for six patients and 3.5 for the other three patients. For NPC plans, MMSSPs were 3.5 for five patients and 2.25 for one patient. CONCLUSION: This work indicates that MMLS directly influences VMAT plan quality in NPC cases and rectal cancer cases. VMAT plan quality improved conspicuously as MMLS increased from 1 to 3.5, VMAT plan quality with marginal improvement when MMLS is above 3.5.

A longitudinal evaluation of improvements in treatment plan quality for lung cancer with volumetric modulated arc therapy.

PURPOSE: To investigate planning time and number of optimizations in routine clinical lung cancer plans based on the plan quality improvements following each optimization. MATERIALS AND METHOD: We selected 40 patients with lung cancer who were treated with conventional fractionated radiotherapy (CFRT). The 40 plans (divided into two groups with one or two target volumes) were completed by 9 planners using volumetric modulated arc therapy (VMAT). A planning strategy, including technique script for each group and a planning process for data collection, was introduced. The total planning time, number of optimizations, and dose-volume parameters of each plan were recorded and analyzed. A plan quality metric (PQM) was defined according to the clinical constraints. Statistical analysis of parameters of each plan following each optimization was performed for evaluating improvements in plan quality. RESULTS: According to the clinical plans generated by different planners, the median number of optimizations of each group was 4, and the median planning time was approximately 1 h (68.6 min and 62.0 min for plans with one or two target volumes, respectively). The dose deposited in organs at risk (OARs) gradually decreased, and the PQM values gradually improved following each optimization. The improvements were significant only between adjacent optimizations from the first optimization (Opt1) to the third optimization (Opt3). CONCLUSION: Increasing the number of optimizations was associated with significantly improved sparing of OARs with slight effects on the dose coverage and homogeneity of target volume. Generally, based on the designed planning strategy, there was no significant improvement of the plan quality for more than three optimizations.

Novel multileaf collimator designs with tongues and grooves in leaf end and Monte Carlo simulations.

In this study, we proposed 2 new multileaf collimator leaf designs to eliminate leaf gaps for closed leaf pairs so that radiation leakage can be avoided. In the new designs, multi tongues and grooves were added to the conventional multileaf collimators leaf ends. Thus, when a pair of leaves closed, tongues of a leaf can enter grooves of its opposing leaf. Consequently, there would be no radiation leakage through closed leaves. One design was named finger-shaped MLC, and another design with doubled leaf end thickness was named hand-shaped MLC. Monte Carlo simulations were performed to simulate dosimetric characteristics of the new MLC designs and comparison to conventional MLCs was performed. The simulations show that for the closed field, the new designs reduce leakage dramatically. And for the open field, the finger-shaped MLC has a larger penumbra width than conventional MLC, while the penumbra for the hand-shaped MLC is comparable to that of conventional MLC. With the application of new MLC designs, it is expected to eliminate leaf gaps for MLC usage and protect normal tissues better.

A method for adjusting MLC leaf positions outside a reference region for VMAT plans in a commercial treatment planning system.

Multileaf collimators (MLC) leaf positions in a volumetric modulated arc therapy (VMAT) plan is determined from inverse treatment planning process. On the isocenter plane, leaf projections should not be set too far out of projected PTV boundary. In this study we developed an automatic method of adjusting leaf positions outside a reference region of interest (ROI) for VMAT plans generated in Pinnacle treatment planning system (TPS). The proposed method consisted of a Pinnacle script and a Python program. It checked each MLC leaf position for all control points in a VMAT arc relative to a reference ROI created by adding a small margin to PTV. For leaves opened outside the reference ROI, the method adjusted their positions to reduce dose to normal tissue while maintaining PTV coverage and satisfying leaf position constraints. The deliverability and dose accuracy of the method was verified by applying it to 15 VMAT plans which were delivered in five different linacs in our department. Dosimetric improvement of the proposed method was analyzed for another group of 16 randomly selected VMAT plans. The average gamma passing rate using a 3%/3 mm criteria for the verification group of VMAT plans was 98.3% and all passing rates were above our internal passing threshold. Dosimetric improvement was observed for the evaluation group of VMAT plans. The method can improve normal tissue protection for VMAT plans. It can be safely applied in routine clinic work.

Optimizing leaf widths for a multileaf collimator.

The multileaf collimator (MLC) is becoming a standard accessory of modern linac in shaping radiation fields. However, for a given target (projection), the radiation field shaped by an MLC has a stepwise boundary and is not identical to the desired field that exactly conforms to the target. That means there are always under-blocked and/or over-blocked areas. The total area of discrepancy depends on MLC leaf widths. The purpose of this study is to develop an optimization model for determining leaf widths so that the total area of discrepancy between MLC-shaped fields and the desired ones can be minimized. The optimization model regards leaf widths as variables, the total area of discrepancy between MLC-shaped fields and the desired fields as an objective function, and the total width of all leaves as a constraint. A problem described by the model is solved with the hybrid of a simulated annealing technique (ASA, Lester Ingber, 1993) and a gradient technique (DONLP2, P Spellucci, 2001). The performance of the optimization model was evaluated on 634 target fields continuously selected from the patient database of a treatment planning system. The lengths of these fields ranged from 3.9 to 38.7 cm and had an average of 15.3 cm. The total area of discrepancy was compared between an MLC with optimal leaf widths and a conventional MLC with the same number of leaf pairs. Optimal leaf widths were obtained for an MLC with total leaf pairs of 28, 40 and 60, respectively, which corresponded to three types of conventional MLCs. The optimal leaf width first decreases slightly and then nonlinearly increases with the distance away from the central line. Compared with the MLC with conventional leaf width arrangement, the MLCs with optimal leaf width arrangement reduced the total area of discrepancy by 11.1%, 28.6% and 25.0%, respectively. Optimizing leaf widths can either improve the conformity of MLC-shaped fields to the treatment targets when the number of leaf pairs does not change, or reduce the number of leaf pairs without sacrifice of field conformity.

Comparison of 2 methods for prediction of liver dosimetric indices in hepatocellular cancer IMRT planning.

To evaluate the performance of 2 methods predicting liver dosimetric indices for hepatocellular cancer patients treated with intensity modulated radiation therapy (IMRT). Two predicting methods were implemented to build correlation between geometric and dosimetric information of hepatocellular cancer IMRT plans. One method used Principle Component Analysis method to simplify information and Support Vector Machine (SVM) regression method to build correlation. The other method used a simple linear function to map volumes of certain regions to dosimetic indices. Thirty eight hepatocellular cancer IMRT plans were randomly selected to train the 2 methods. The effectiveness of the 2 methods was validated using another 8 plans. Liver dosimetric indices V10, V20, V30, and mean dose of the 8 plans in validation cohort were calculated using the predicting methods. The predicted indices were compared with the indices derived from the clinically accepted treatment plans. The absolute differences of V10 calculated with the SVM method and the actual values of treatment plans had a mean value of 7.87%. And the values for V20, V30, and mean dose were 4.37%, 4.41%, and 4.20%, respectively. The absolute differences of V10 calculated with the linear formulation method and the actual values of treatment plans had a mean value of 6.09%. And the values for V20, V30, and mean dose were 5.28%, 5.05%, and 5.92%, respectively. These 2 methods have similar accuracy in predicting dosimetric indices V10, V20, V30 of livers. The predicting of V30 and V20 is more accurate than the predicting of V10. The SVM method is more accurate in predicting mean liver dose.

Genomic Analyses Reveal Evidence of Independent Evolution, Demographic History, and Extreme Environment Adaptation of Tibetan Plateau Agaricus bisporus.

Agaricus bisporus distributed in the Tibetan Plateau of China has high-stress resistance that is valuable for breeding improvements. However, its evolutionary history, specialization, and adaptation to the extreme Tibetan Plateau environment are largely unknown. Here, we performed de novo genome sequencing of a representative Tibetan Plateau wild strain ABM and comparative genomic analysis with the reported European strain H97 and H39. The assembled ABM genome was 30.4 Mb in size, and comprised 8,562 protein-coding genes. The ABM genome shared highly conserved syntenic blocks and a few inversions with H97 and H39. The phylogenetic tree constructed by 1,276 single-copy orthologous genes in nine fungal species showed that the Tibetan Plateau and European A. bisporus diverged ∼5.5 million years ago. Population genomic analysis using genome resequencing of 29 strains revealed that the Tibetan Plateau population underwent significant differentiation from the European and American populations and evolved independently, and the global climate changes critically shaped the demographic history of the Tibetan Plateau population. Moreover, we identified key genes that are related to the cell wall and membrane system, and the development and defense systems regulated A. bisporus adapting to the harsh Tibetan Plateau environment. These findings highlight the value of genomic data in assessing the evolution and adaptation of mushrooms and will enhance future genetic improvements of A. bisporus.

Genome Sequencing Illustrates the Genetic Basis of the Pharmacological Properties of Gloeostereum incarnatum.

Gloeostereum incarnatum is a precious edible mushroom that is widely grown in Asia and known for its useful medicinal properties. Here, we present a high-quality genome of G. incarnatum using the single-molecule real-time (SMRT) sequencing platform. The G. incarnatum genome, which is the first complete genome to be sequenced in the family Cyphellaceae, was 38.67 Mbp, with an N50 of 3.5 Mbp, encoding 15,251 proteins. Based on our phylogenetic analysis, the Cyphellaceae diverged ~174 million years ago. Several genes and gene clusters associated with lignocellulose degradation, secondary metabolites, and polysaccharide biosynthesis were identified in G. incarnatum, and compared with other medicinal mushrooms. In particular, we identified two terpenoid-associated gene clusters, each containing a gene encoding a sesterterpenoid synthase adjacent to a gene encoding a cytochrome P450 enzyme. These clusters might participate in the biosynthesis of incarnal, a known bioactive sesterterpenoid produced by G. incarnatum. Through a transcriptomic analysis comparing the G. incarnatum mycelium and fruiting body, we also demonstrated that the genes associated with terpenoid biosynthesis were generally upregulated in the mycelium, while those associated with polysaccharide biosynthesis were generally upregulated in the fruiting body. This study provides insights into the genetic basis of the medicinal properties of G. incarnatum, laying a framework for future characterization of bioactive proteins and pharmaceutical uses of this fungus.