Adaptor protein-3 produces synaptic vesicles that release phasic dopamine.

The burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. At many synapses, however, high firing rates deplete synaptic vesicles (SVs), resulting in synaptic depression that limits release. What accounts for the increased release of dopamine by stimulation at high frequency? We find that adaptor protein-3 (AP-3) and its coat protein VPS41 promote axonal dopamine release by targeting vesicular monoamine transporter VMAT2 to the axon rather than dendrites. AP-3 and VPS41 also produce SVs that respond preferentially to high-frequency stimulation, independent of their role in axonal polarity. In addition, conditional inactivation of VPS41 in dopamine neurons impairs reinforcement learning, and this involves a defect in the frequency dependence of release rather than the amount of dopamine released. Thus, AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine.

Combining CRISPR-Cas9 and brain imaging to study the link from genes to molecules to networks.

Receptors, transporters, and ion channels are important targets for therapy development in neurological diseases, but their mechanistic role in pathogenesis is often poorly understood. Gene editing and in vivo imaging approaches will help to identify the molecular and functional role of these targets and the consequence of their regional dysfunction on the whole-brain level. We combine CRISPR-Cas9 gene editing with in vivo positron emission tomography (PET) and functional MRI (fMRI) to investigate the direct link between genes, molecules, and the brain connectome. The extensive knowledge of the Slc18a2 gene encoding the vesicular monoamine transporter (VMAT2), involved in the storage and release of dopamine, makes it an excellent target for studying the gene network relationships while structurally preserving neuronal integrity and function. We edited the Slc18a2 in the substantia nigra pars compacta of adult rats and used in vivo molecular imaging besides behavioral, histological, and biochemical assessments to characterize the CRISPR-Cas9-mediated VMAT2 knockdown. Simultaneous PET/fMRI was performed to investigate molecular and functional brain alterations. We found that stage-specific adaptations of brain functional connectivity follow the selective impairment of presynaptic dopamine storage and release. Our study reveals that recruiting different brain networks is an early response to the dopaminergic dysfunction preceding neuronal cell loss. Our combinatorial approach is a tool to investigate the impact of specific genes on brain molecular and functional dynamics, which will help to develop tailored therapies for normalizing brain function.

Synaptic vesicle glycoprotein 2C enhances vesicular storage of dopamine and counters dopaminergic toxicity.

Dopaminergic neurons of the substantia nigra exist in a persistent state of vulnerability resulting from high baseline oxidative stress, high-energy demand, and broad unmyelinated axonal arborisations. Impairments in the storage of dopamine compound this stress because of cytosolic reactions that transform the vital neurotransmitter into an endogenous neurotoxicant, and this toxicity is thought to contribute to the dopamine neuron degeneration that occurs Parkinson's disease. We have previously identified synaptic vesicle glycoprotein 2C (SV2C) as a modifier of vesicular dopamine function, demonstrating that genetic ablation of SV2C in mice results in decreased dopamine content and evoked dopamine release in the striatum. Here, we adapted a previously published in vitro assay utilising false fluorescent neurotransmitter 206 (FFN206) to visualise how SV2C regulates vesicular dopamine dynamics and determined that SV2C promotes the uptake and retention of FFN206 within vesicles. In addition, we present data indicating that SV2C enhances the retention of dopamine in the vesicular compartment with radiolabelled dopamine in vesicles isolated from immortalised cells and from mouse brain. Further, we demonstrate that SV2C enhances the ability of vesicles to store the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) and that genetic ablation of SV2C results in enhanced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced vulnerability in mice. Together, these findings suggest that SV2C functions to enhance vesicular storage of dopamine and neurotoxicants and helps maintain the integrity of dopaminergic neurons.

Stereotactic body radiotherapy with volumetric intensity-modulated arc therapy and flattening filter-free beams: dosimetric considerations.

PURPOSE: The present study comparatively evaluates the impact of energy-matched flattening filter-free (FFF) photon beams with different energy levels on the physical-dosimetric quality of lung and liver stereotactic body radiotherapy (SBRT) treatment plans. METHODS: For this purpose, 54 different lung and liver lesions from 44 patients who had already received SBRT combined with volumetric modulated arc therapy (VMAT) were included in this retrospective planning study. Planning computed tomography scans already available were used for the renewed planning with 6 MV, 6 MV-FFF, 10 MV, and 10 MV-FFF under constant planning objectives. The treatment delivery data, dosimetric distributions, and dose-volume histograms as well as parameters such as the conformity index and gradient indices were the basis for the evaluation and comparison of treatment plans. RESULTS: A significant reduction of beam-on time (BOT) was achieved due to the high dose rates of FFF beams. In addition, we showed that for FFF beams compared to flattened beams of the same energy level, smaller planning target volumes (PTV) require fewer monitor units (MU) than larger PTVs. An equal to slightly superior target volume coverage and sparing of healthy tissue as well as organs at risk in both lung and liver lesions were found. Significant differences were seen mainly in the medium to lower dose range. CONCLUSION: We found that FFF beams together with VMAT represent an excellent combination for SBRT of lung or liver lesions with shortest BOT for 10 MV-FFF but significant dose savings for 6 MV-FFF in lung lesions.

Tolerance of radiotherapy with concomitant glofitamab in diffuse large B cell lymphoma: a case report.

Glofitamab, an anti-CD20 antibody, is approved as a third-line treatment for relapsed or refractory (r/r) diffuse large-cell B lymphoma (DLBCL), achieving a complete response in nearly 40% of patients. This humanized IgG1 bispecific monoclonal antibody binds to CD20 on malignant B lymphocytes and to CD3 on cytotoxic T cells. This dual binding forms an immunological synapse, activating T lymphocytes and leading to the lysis of tumor cells. Salvage radiotherapy is also effective for r/r DLBCL, but its combination with systemic treatments like glofitamab may increase radiation-induced toxicity. We report the first case of a patient with r/r DLBCL receiving concurrent salvage radiotherapy and glofitamab. A 68-year-old female diagnosed with stage IV DLBCL underwent initial treatment with R-CHOP, then Car-T cell therapy, followed by glofitamab for recurrence. Upon early metabolic progression detected by 18FDG-PET/CT, salvage radiotherapy was administered to the refractory site concurrently with glofitamab. The patient experienced mild para-spinal pain post-radiotherapy but no other significant toxicities. Three months post-treatment, she showed a complete metabolic response with no radiotherapy toxicity, as evidenced by PET-CT, and no signs of radiation pneumonitis. This case indicates that combining glofitamab with salvage radiotherapy is tolerable and suggests potential efficacy, warranting further investigation in prospective studies for r/r DLBCL.

In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson's disease.

Humans accumulate with age the dark-brown pigment neuromelanin inside specific neuronal groups. Neurons with the highest neuromelanin levels are particularly susceptible to degeneration in Parkinson's disease, especially dopaminergic neurons of the substantia nigra, the loss of which leads to characteristic motor Parkinson's disease symptoms. In contrast to humans, neuromelanin does not appear spontaneously in most animals, including rodents, and Parkinson's disease is an exclusively human condition. Using humanized neuromelanin-producing rodents, we recently found that neuromelanin can trigger Parkinson's disease pathology when accumulated above a specific pathogenic threshold. Here, by taking advantage of this newly developed animal model, we assessed whether the intracellular build-up of neuromelanin that occurs with age can be slowed down in vivo to prevent or attenuate Parkinson's disease. Because neuromelanin derives from the oxidation of free cytosolic dopamine, we enhanced dopamine vesicular encapsulation in the substantia nigra of neuromelanin-producing rats by viral vector-mediated overexpression of vesicular monoamine transporter 2 (VMAT2). This strategy reduced the formation of potentially toxic oxidized dopamine species that can convert into neuromelanin and maintained intracellular neuromelanin levels below their pathogenic threshold. Decreased neuromelanin production was associated with an attenuation of Lewy body-like inclusion formation and a long-term preservation of dopamine homeostasis, nigrostriatal neuronal integrity and motor function in these animals. Our results demonstrate the feasibility and therapeutic potential of modulating age-dependent intracellular neuromelanin production in vivo, thereby opening an unexplored path for the treatment of Parkinson's disease and, in a broader sense, brain ageing.

Stereotactic body radiation therapy for prostate cancer: a dosimetric comparison of IMRT and VMAT using flattening filter and flattening filter-free beams.

This retrospective study was performed to evaluate plan quality and treatment delivery parameters of stereotactic body radiation therapy (SBRT) for prostate cancer. The study utilized different isocentric modulated techniques: intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using 6 MV flattening filter (FF) and 10 MV flattening filter-free beams (FFF). Fifteen retrospective prostate cancer patients were selected for this study. Sixty plans were created with an SBRT-prescribed dose of 36.25 Gy delivered in five fractions. Planning target volume (PTV) coverage, plan quality indices, doses delivered to organs at risk (OARs), and treatment delivery parameters were compared for all plans. It turned out that VMAT plans, particularly those using the FFF beam, provided superior target conformality and a steeper dose gradient as compared to IMRT plans. Additionally, VMAT plans showed better OARs sparing compared to IMRT plans. However, IMRT plans delivered a lower maximum dose to the target than VMAT plans. Importantly, the VMAT plans resulted in reduced treatment delivery parameters, including beam on time (BOT), monitor unit (MU), and modulation factor (MF), compared to IMRT plans. Furthermore, a statistically significant difference was observed in BOT and mean body dose between FF and FFF beams, with FFF beams showing superior performance. Considering all results, VMAT using 10 MV (FFF) is suggested for treating prostate cancer patients with SBRT. This offers the fastest delivery in addition to maintaining the highest plan quality.

Impact of flattening filter-free beams on remaining volume at risk in lung cancer treatment.

Modern radiotherapy machines offer a new modality, like flattening filter-free beam (FFF), which is used especially in stereotactic body radiation therapy (SBRT) to reduce treatment time. The remaining volume at risk (RVR) is known as undefined normal tissue, and assists in evaluating late effects such as carcinogenesis. This study aimed to compare the effects of flattening and un-flattened beams on RVR in lung cancer treated by conventional doses using volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT). Twenty-three lung cancer patients with a prescribed dose of 60 Gy delivered in 30 fractions were selected retrospectively. Four treatment plans were generated for each case (VMAT FF, VMAT FFF, IMRT FF and IMRT FFF). Mean doses to RVR and volumes that received low doses (V15Gy, V10Gy and V5Gy) were introduced as RVR evaluation parameters. Variance percentage comparison between flattening filter (FF) and FFF for the RVR evaluation parameters gave 2.38, 1.10, 1.80 and 2.22 for VMAT, and 1.73, 1.18, 1.62 and 1.81 for IMRT. In contrast, VMAT and IMRT RVR evaluation parameters resulted in variance percentage differences of 10.29, 5.02, - 8.84 and - 4.82 for FF, and 11.18, 4.96, - 8.59 and - 4.48for FFF. It is concluded that in terms of RVR evaluation parameters, FFF is clinically beneficial compared to FF for RVR, due to the decrease in mean RVR dose and low-dose irradiated RVR volume. Furthermore, VMAT is preferred in the mean RVR dose and V15Gy, while IMRT is better in V10Gy and V5Gy for RVR.

Exploring feasibility criteria for stereotactic radiosurgical treatment of multiple brain metastases using five linac machines.

PURPOSE: This study aimed to find descriptors that correlates with normal brain dose to determine the feasibility of performing fractionated stereotactic radiosurgery (SRS) for multiple brain metastases (BMs) using five linac machines. METHODS: Thirty-two patients with 1-30 BMs were enrolled. Treatment plans were created using TrueBeam, Novalis Tx, TrueBeam Edge, Halcyon, and Tomotherapy linacs. The sum of all planning target volumes (PTVs) was defined as PTVall, and the brain region excluding PTVall was defined as normal brain. The total surface area (TSA) of the PTV was calculated from the sum of the surface areas of the equivalent spheres for each PTV. Volumes receiving more than 5, 12, and 18 Gy (V5Gy, V12Gy, and V18Gy, respectively) were used for evaluation of normal brain dose. Correlations between normal brain dose and each tumor characteristic (number, PTVall, and TSA) were investigated using the Spearman rank correlation coefficient. RESULTS: Correlations between each characteristic and normal brain dose were statistically significant (p < 0.05) across all machines. The correlation coefficients between each characteristic and V18Gy for the five machines were as follows: tumor number, 0.39-0.60; PTVall, 0.79-0.93; TSA, 0.93-0.99. The fit equations between TSA and V18Gy exhibited high coefficients of determination, ranging from 0.92 to 0.99 across five machines. CONCLUSION: This study devised fractionated SRS plans using for 1-30 BMs across five linac machines to find descriptors for determining SRS feasibility based on normal brain dose. TSA proved to be a promising descriptor of SRS feasibility for treating multiple BMs.

Dosimetric impact of MLC positional errors on dose distribution in IMRT.

Optimizing the positional accuracy of multileaf collimators (MLC) for radiotherapy is important for dose accuracy and for reducing doses delivered to normal tissues. This study investigates dose sensitivity variations and complexity metrics of MLC positional error in volumetric modulated arc therapy and determines the acceptable ranges of MLC positional accuracy in several clinical situations. Treatment plans were generated for four treatment sites (prostate cancer, lung cancer, spinal, and brain metastases) using different treatment planning systems (TPSs) and fraction sizes. Each treatment plan introduced 0.25-2.0 mm systematic or random MLC leaf bank errors. The generalized equivalent uniform dose (gEUD) sensitivity and complexity metrics (MU/Gy and plan irregularity) were calculated, and the correlation coefficients were assessed. Furthermore, the required tolerances for MLC positional accuracy control were calculated. The gEUD sensitivity showed the highest dependence of systematic positional error on the treatment site, followed by TPS and fraction size. The gEUD sensitivities were 6.7, 4.5, 2.5, and 1.7%/mm for Monaco and 8.9, 6.2, 3.4, and 2.3%/mm (spinal metastasis, lung cancer, prostate cancer, and brain metastasis, respectively) for RayStation. The gEUD sensitivity was strongly correlated with the complexity metrics (r = 0.88-0.93). The minimum allowable positional error for MLC was 0.63, 0.34, 1.02, and 0.28 mm (prostate, lung, brain, and spinal metastasis, respectively). The acceptable range of MLC positional accuracy depends on the treatment site, and an appropriate tolerance should be set for each treatment site with reference to the complexity metric. It is expected to enable easier and more detailed MLC positional accuracy control than before by reducing dose errors to patients at the treatment planning stage and by controlling MLC quality based on complexity metrics, such as MU/Gy.

The delivery assessment for small targets on Halcyon radiotherapy system - Measured and calculated dose comparison.

BACKGROUND: With the ever-increasing requirements of accuracy and personalization of radiotherapy treatments, stereotactic radiotherapy (SRT) with volumetric modulated arc therapy (VMAT) on O-ring Halcyon radiotherapy system could potentially provide a fast, safe, and feasible treatment option. PURPOSE: The purpose of this study was to assess the delivery of Halcyon VMAT plans for small targets. METHODS: Well-defined VMAT-SRT plans were created on Halcyon radiotherapy system with the stacked and staggered dual-layer MLC design for the film measurement set-up and the target sizes and shapes designed to emulate the targets of the stereotactic treatments. The planar dose distributions were acquired with film measurements and compared to a current clinical reference dose calculation with AcurosXB (v18.0, Varian Medical Systems) and to Monte Carlo simulations. With the collapsed arc versions of the VMAT-SRT plans, the uncertainty in dose delivery due to the multileaf collimator (MLC) without the gantry rotation could be separated and analyzed. RESULTS: The target size was mainly limited by the resolution originated from the design of the MLC leaves. The results of the collapsed arc versions of the plans show good consistency among measured, calculated, and simulated dose distributions. With the full VMAT plans, the agreement between calculated and simulated dose distributions was consistent with the collapsed arc versions. The measured dose distribution agreed with the calculated and simulated dose distributions within the target regions, but considerable local differences were observed in the margins of the target. The largest differences located in the steep gradient regions presumably originating from the deviation of the isocenter. CONCLUSIONS: The potential of the Halcyon radiotherapy system for VMAT-SRT delivery was evaluated and the study revealed valuable insights on the machine characteristics with the delivery.

Feasibility of determining external beam radiotherapy dose using LuSy dosimeter.

INTRODUCTION: Radiation dose measurement is an essential part of radiotherapy to verify the correct delivery of doses to patients and ensure patient safety. Recent advancements in radiotherapy technology have highlighted the need for fast and precise dosimeters. Technologies like FLASH radiotherapy and magnetic-resonance linear accelerators (MR-LINAC) demand dosimeters that can meet their unique requirements. One promising solution is the plastic scintillator-based dosimeter with high spatial resolution and real-time dose output. This study explores the feasibility of using the LuSy dosimeter, an in-house developed plastic scintillator dosimeter for dose verification across various radiotherapy techniques, including conformal radiotherapy (CRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS). MATERIALS AND METHODS: A new dosimetry system, comprising a new plastic scintillator as the sensing material, was developed and characterized for radiotherapy beams. Treatment plans were created for conformal radiotherapy, IMRT, VMAT, and SRS and delivered to a phantom. LuSy dosimeter was used to measure the delivered dose for each plan on the surface of the phantom and inside the target volumes. Then, LuSy measurements were compared against an ionization chamber, MOSFET dosimeter, radiochromic films, and dose calculated using the treatment planning system (TPS). RESULTS: For CRT, surface dose measurement by LuSy dosimeter showed a deviation of -5.5% and -5.4% for breast and abdomen treatment from the TPS, respectively. When measuring inside the target volume for IMRT, VMAT, and SRS, the LuSy dosimeter produced a mean deviation of -3.0% from the TPS. Surface dose measurement resulted in higher TPS discrepancies where the deviations for IMRT, VMAT, and SRS were -2.0%, -19.5%, and 16.1%, respectively. CONCLUSION: The LuSy dosimeter was feasible for measuring radiotherapy doses for various treatment techniques. Treatment delivery verification enables early error detection, allowing for safe treatment delivery for radiotherapy patients.

Evaluating AAPM-TG-218 recommendations: Gamma index tolerance and action limits in IMRT and VMAT quality assurance using SunCHECK.

PURPOSE: This study aimed to improve the safety and accuracy of radiotherapy by establishing tolerance (TL) and action (AL) limits for the gamma index in patient-specific quality assurance (PSQA) for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) using SunCHECK software, as per AAPM TG-218 report recommendations. METHODS: The study included 125 patients divided into six groups by treatment regions (H&N, thoracic and pelvic) and techniques (VMAT, IMRT). SunCHECK was used to calculate the gamma passing rate (%GP) and dose error (%DE) for each patient, for the planning target volume and organs at risk (OARs). The TL and AL were then determined for each group according to TG-218 recommendations. We conducted a comprehensive analysis to compare %DE among different groups and examined the relationship between %GP and %DE. RESULTS: The TL and AL of all groups were more stringent than the common standard as defined by the TG218 report. The TL and AL values of the groups differed significantly, and the values for the thoracic groups were lower for both VMAT and IMRT. The %DE of the parameters D95%, D90%, and Dmean in the planning target volume, and Dmean and Dmax in OARs were significantly different. The dose deviation of VMAT was larger than IMRT, especially in the thoracic group. A %GP and %DE correlation analysis showed a strong correlation for the planning target volume, but a weak correlation for the OARs. Additionally, a significant correlation existed between %GP of SunCHECK and Delta4. CONCLUSION: The study established TL and AL values tailored to various anatomical regions and treatment techniques at our institution. Establishing PSQA workflows for VMAT and IMRT offers valuable clinical insights and guidance. We also suggest developing a standard combining clinically relevant metrics with %GP to evaluate PSQA results comprehensively.

Total scalp irradiation: A study comparing multiple types of bolus and VMAT optimization techniques.

PURPOSE: To investigate bolus design and VMAT optimization settings for total scalp irradiation. METHODS: Three silicone bolus designs (flat, hat, and custom) from .decimal were evaluated for adherence to five anthropomorphic head phantoms. Flat bolus was cut from a silicone sheet. Generic hat bolus resembles an elongated swim cap while custom bolus is manufactured by injecting silicone into a 3D printed mold. Bolus placement time was recorded. Air gaps between bolus and scalp were quantified on CT images. The dosimetric effect of air gaps on target coverage was evaluated in a treatment planning study where the scalp was planned to 60 Gy in 30 fractions. A noncoplanar VMAT technique based on gEUD penalties was investigated that explored the full range of gEUD alpha values to determine which settings achieve sufficient target coverage while minimizing brain dose. ANOVA and the t-test were used to evaluate statistically significant differences (threshold = 0.05). RESULTS: The flat bolus took 32 ± 5.9 min to construct and place, which was significantly longer (p < 0.001) compared with 0.67 ± 0.2 min for the generic hat bolus or 0.53 ± 0.10 min for the custom bolus. The air gap volumes were 38 ± 9.3 cc, 32 ± 14 cc, and 17 ± 7.0 cc for the flat, hat, and custom boluses, respectively. While the air gap differences between the flat and custom boluses were significant (p = 0.011), there were no significant dosimetric differences in PTV coverage at V57Gy or V60Gy. In the VMAT optimization study, a gEUD alpha of 2 was found to minimize the mean brain dose. CONCLUSIONS: Two challenging aspects of total scalp irradiation were investigated: bolus design and plan optimization. Results from this study show opportunities to shorten bolus fabrication time during simulation and create high quality treatment plans using a straightforward VMAT template with simple optimization settings.

Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

A four-dimensional dynamic conformal arc approach for real-time tumor tracking: A retrospective treatment planning study.

PURPOSE: For many thoracic tumors, patient respiration can introduce a significant amount of variability in tumor position that must be accounted for during radiotherapy. Of all existing techniques, real-time dynamic tumor tracking (DTT) represents the most ideal motion management strategy but can be limited by the treatment delivery technique. Our objective was to analyze the dosimetric performance of a dynamic conformal arc (DCA) approach to tumor tracking on standard linear accelerators that may offer similar dosimetric benefit, but with less complexity compared to intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). METHODS: Ten patients who previously received free-breathing VMAT for lung cancer were retrospectively analyzed. Patient 4D-CT and respiratory traces were simultaneously acquired prior to treatment and re-planned with DCA and VMAT using the Eclipse v15.6 Treatment Planning System with gated, deep inspiration breath hold (DIBH), and motion encompassment techniques taken into consideration, generating seven new plans per patient. DTT with DCA was simulated using an in-house MATLAB script to parse the radiation dose into each phase of the 4D-CT based on the patient's respiratory trace. Dose distributions were normalized to the same prescription and analyzed using dose volume histograms (DVHs). DVH metrics were assessed using ANOVA with subsequent paired t-tests. RESULTS: The DCA-based DTT plans outperformed or showed comparable performance in their DVH metrics compared to all other combinations of treatment techniques while using motion management in normal lung sparing (p < 0.05). Normal lung sparing was not significantly different when comparing DCA-based DTT to gated and DIBH VMAT (p > 0.05), while both outperformed the corresponding DCA plans (p < 0.05). Simulated treatment times using DCA-based DTT were significantly shorter than both gating and DIBH plans (p < 0.05). CONCLUSIONS: A DCA-based DTT technique showed significant advantages over conventional motion encompassment treatments in lung cancer radiotherapy, with comparable performance to stricter techniques like gating and DIBH while conferring greater time-saving benefits.

Off-isocentric VMAT technique for breast cancer: Effective dose reduction to organs at risk and its applicability based on patient anatomy.

PURPOSE: This study aims to explore the off-isocentric volumetric modulated arc therapy (offVMAT) technique for breast cancer and determine its applicability based on patient anatomical parameters. METHODS: We retrospectively analyzed 44 breast cancer patients with varied lymph node involvement using different arc designs. Off-isocentric techniques were benchmarked against previously published arc techniques: classic arcs (clVMAT), tangential arcs (tVMAT), and split arcs (spVMAT). During optimization, target coverage was made for all plans as close as possible to the criteria D99% > 95% and Dmax < 110% of the prescribed dose. A novel patient categorization, based on anatomical parameters (auxiliary structures) rather than lymph node involvement, is introduced. This categorization considers the volume of ipsilateral organs at risk (OARs) adjacent to the target. A binary regression model was developed on these anatomical parameters. It predicts the likelihood of offVMAT (P[offVMAT]) achieving better criteria. RESULTS: Using the regression model, patients were divided into two groups: P(offVMAT) > 0.5 and P(offVMAT) < 0.5. For the P(offVMAT) > 0.5 group, most tVMAT plans are unable to achieve the clinical objectives. Comparing offVMAT with spVMAT, offVMAT exhibited better dose parameters for the heart (V20, V10, and D2 are 7.1, 2.4, and 1.5 times lower respectively), ipsilateral lung (V20, V10, V5 and the mean dose are 1.4, 1.3, 1.2, and 1.2 times lower respectively). The average doses to the contralateral side are consistent. In the P(offVMAT) < 0.5 group, the tVMAT technique showed increased doses at medium and high levels, yet reduced doses in contralateral OARs compared to spVMAT and offVMAT. spVMAT showed lower doses in the contralateral lung relative to the offVMAT technique, while clVMAT trailed in both groups. Validation of the model yielded a 90% accuracy rate. CONCLUSIONS: The new off-isocentric breast planning technique effectively reduces doses to ipsilateral OARs, maintaining acceptable contralateral mean doses. This technique has an advantage over other techniques for patients with intricate anatomies. It is evaluated using anatomical parameters, which are also used to build binary regression model, which shows the dependence of anatomical parameters on whether offVMAT is preferred for individual patients. Also, such anatomical parameters provide a more objective and precise comparison between different planning techniques.

Multi-planner validation of RapidPlan knowledge-based model for volumetric modulated arc therapy in prostate cancer.

PURPOSE: To investigate the performance of a model-based optimization process for volumetric modulated arc therapy (VMAT) applied to prostate cancer patients with the multi-planner. METHODS AND MATERIALS: The 120 prostate plans for VMAT treatment were entered into the database system of the RapidPlan (RP) knowledge-based treatment planning. The treatment planning data for each plan was used to create and train the RP model. Twelve prostate cancer cases were selected and were used for planning by a manual of 12 planners based on the clinical protocol for dose constraints. Then, the treatment plans for each patient were compared with the RP model plans and analyzed with Wilcoxon tests. RESULTS: On average, the RP models can estimate comparable doses among all planner plans and clinical plans for the PTV, which Dmax , D95% , D98% , HI, and CI were used to evaluate. For the normal organ doses of the bladder, rectum, penile bulb, and femoral head, all RP model plans showed comparable or better dose sparing than all planner plans and clinical plans. Moreover, the average planning time of the RP model was faster than manual plans by about two times. The RP model can significantly reduce the variation dose of the normal organs compared with the manual plans among the planners. CONCLUSION: The automated plans of the RP model might benefit from further fine-tuning of the dose constraints of the normal organs, although both procedure plans are acceptable and fulfill the clinical protocol goals so that the RP model can enhance the efficacy and quality of plans.

Influence of dose calculation algorithms on the helical diode array using volumetric-modulated arc therapy for small targets.

BACKGROUND: For patient-specific quality assurance (PSQA) for small targets, the dose resolution can change depending on the characteristics of the dose calculation algorithms. PURPOSE: This study aimed to evaluate the influence of the dose calculation algorithms Acuros XB (AXB), anisotropic analytical algorithm (AAA), photon Monte Carlo (pMC), and collapsed cone (CC) on a helical diode array using volumetric-modulated arc therapy (VMAT) for small targets. MATERIALS AND METHODS: ArcCHECK detectors were inserted with a physical depth of 2.9 cm from the surface. To evaluate the influence of the dose calculation algorithms for small targets, rectangular fields of 2×100, 5×100, 10×100, 20×100, 50×100, and 100×100 mm2 were irradiated and measured using ArcCHECK with TrueBeam STx. A total of 20 VMAT plans for small targets, including the clinical sites of 19 brain metastases and one spine, were also evaluated. The gamma passing rates (GPRs) were evaluated for the rectangular fields and the 20 VMAT plans using AXB, AAA, pMC, and CC. RESULTS: For rectangular fields of 2×100 and 5×100 mm2, the GPR at 3%/2 mm of AXB was < 50% because AXB resulted in a coarser dose resolution with narrow beams. For field sizes > 10×100 mm2, the GPR at 3%/2 mm was > 88.1% and comparable for all dose calculation algorithms. For the 20 VMAT plans, the GPRs at 3%/2 mm were 79.1 ± 15.7%, 93.2 ± 5.8%, 94.9 ± 4.1%, and 94.5 ± 4.1% for AXB, AAA, pMC, and CC, respectively. CONCLUSION: The behavior of the dose distribution on the helical diode array differed depending on the dose calculation algorithm for small targets. Measurements using ArcCHECK for VMAT with small targets can have lower GPRs owing to the coarse dose resolution of AXB around the detector area.

Impact of setup errors on the robustness of linac-based single-isocenter coplanar and non-coplanar VMAT plans for multiple brain metastases.

PURPOSE: Patient setup errors have been a primary concern impacting the dose delivery accuracy in radiation therapy. A robust treatment plan might mitigate the effects of patient setup errors. In this reported study, we aimed to evaluate the impact of translational and rotational errors on the robustness of linac-based, single-isocenter, coplanar, and non-coplanar volumetric modulated arc therapy treatment plans for multiple brain metastases. METHODS: Fifteen patients were retrospectively selected for this study with a combined total of 49 gross tumor volumes (GTVs). Single-isocenter coplanar and non-coplanar plans were generated first with a prescribed dose of 40 Gy in 5 fractions or 42 Gy in 7 fractions to cover 95% of planning target volume (PTV). Next, four setup errors (+1  and +2 mm translation, and +1° and +2° rotation) were applied individually to generate modified plans. Different plan quality evaluation metrics were compared between coplanar and non-coplanar plans. 3D gamma analysis (3%/2 mm) was performed to compare the modified plans (+2 mm and +2° only) and the original plans. Paired t-test was conducted for statistical analysis. RESULTS: After applying setup errors, variations of all plan evaluation metrics were similar (p > 0.05). The worst case for V100% to GTV was 92.07% ± 6.13% in the case of +2 mm translational error. 3D gamma pass rates were > 90% for both coplanar (+2 mm and +2°) and the +2 mm non-coplanar groups but was 87.40% ± 6.89% for the +2° non-coplanar group. CONCLUSION: Translational errors have a greater impact on PTV and GTV dose coverage for both planning methods. Rotational errors have a greater negative impact on gamma pass rates of non-coplanar plans. Plan evaluation metrics after applying setup errors showed that both coplanar and non-coplanar plans were robust and clinically acceptable.