Viability of the virtual cone technique using a fixed small multi-leaf collimator field for stereotactic radiosurgery of trigeminal neuralgia.

Dosimetric uncertainties in very small (≤1.5 × 1.5 cm2 ) photon fields are remarkably higher, which undermines the validity of the virtual cone (VC) technique with a diminutive and variable MLC fields. We evaluate the accuracy and reproducibility of the VC method with a very small, fixed MLC field setting, called a fixed virtual cone (fVC), for small target radiosurgery such as trigeminal neuralgia (TGN). The fVC is characterized by 0.5 cm x 0.5 cm high-definition (HD) MLC field of 10MV FFF beam defined at 100 cm SAD, while backup jaws are positioned at 1.5 cm x 1.5 cm. A spherical dose distribution equivalent to 5 mm (diameter) physical cone was generated using 10-14 non-coplanar, partial arcs. Dosimetric accuracy was validated using SRS diode (PTW 60018), SRS MapCHECK (SNC) measurements. As a quality assurance measure, 10 treatment plans (SRS) for TGN, consisting of various arc ranges at different collimator angles were analyzed using 6 MV FFF and 10 MV FFF beams, including a field-by-field study (n = 130 fields). Dose outputs were compared between the Eclipse TPS and measurements (SRS MapCHECK). Moreover, dosimetric changes in the field defining fVC, prompted by a minute (± 0.5-1.0 mm) leaf shift, was examined among TPS, diode measurements, and Monte Carlo (MC) simulations. The beam model for fVC was validated (≤3% difference) using SRS MapCHECK based absolute dose measurements. The equivalent diameters of the 50% isodose distribution were found comparable to that of a 5 mm cone. Additionally, the comparison of field output factors, dose per MU between the TPS and SRS diode measurements using the fVC field, including ± 1 mm leaf shift, yielded average discrepancies within 5.5% and 3.5% for 6 MV FFF and 10 MV FFF beams, respectively. Overall, the fVC method is a credible alternative to the physical cone (5 mm) that can be applied in routine radiosurgical treatment of TGN.

A novel Monte Carlo (MC) dose model for small MLC fields of the cyberknife® M6TM radiosurgery system using the EGSnrc.

The multi-leaf collimator (MLC)-equipped CyberKnife® M6 radiosurgery system (CKM6) (Accuray Inc., Sunnyvale, CA) has been increasingly employed for stereotactic radiosurgery (SRS) to treat relatively small lesions. However, achieving an accurate dose distribution in such cases is usually challenging due to the combination of numerous small fields ≤ (30 × 30) mm2 . In this study, we developed a new Monte Carlo (MC) dose model for the CKM6 system using the EGSnrc to investigate dose variations in the small fields. The dose model was verified for the static MLC fields ranging from (53.8 × 53.9) to (7.6 × 7.7) mm2 at 800 mm source to axis distance in a water phantom, based on the computed doses of Accuray Precision® (Accuray Inc.) treatment planning system (TPS). We achieved a statistical uncertainty of ≤4% by simulating 30-50 million incident particles/histories. Then, the treatment plans were created for the same fields in the TPS, and the corresponding measurements were performed with MapCHECK2 (Sun Nuclear Corporation), a standard device for patient-specific quality assurance (PSQA). Results of the MC simulations, TPS, and MapCHECK2 measurements were inter-compared. An overall difference in dosimetric parameters such as profiles, tissue maximum ratio (TMR), and output factors (OF) between the MC simulations and the TPS results was found ≤3% for (53.8 × 53.9-15.4 × 15.4) mm2 MLC fields, and it rose to 4.5% for the smallest (7.6 mm × 7.7 mm) MLC field. The MapCHECK2 results showed a deviation ranging from -1.5% to + 4.5% compared to the TPS results, whereas the deviation was within ±2.5% compared with the MC results. Overall, our MC dose model for the CKM6 system showed better agreement with measurements and it could serve as a secondary dose verification tool for the patient-specific QA in small fields.

Beam characteristics of the first clinical 360° rotational single gantry room scanning pencil beam proton treatment system and comparisons against a multi-room system.

PURPOSE: The purpose of this study was to present the proton beam characteristics of the first clinical single-room ProBeam Compact™ proton therapy system (SRPT) and comparison against multi-room ProBeam™ system (MRPT). MATERIALS AND METHODS: A newly designed SRPT with proton beam energies ranging from 70 to 220 MeV was commissioned in late 2019. Integrated depth doses (IDDs) were scanned using 81.6 mm diameter Bragg peak chambers and normalized by outputs at 15 mm WET and 1.1 RBE offset, following the methodology of TRS 398. The in-air beam spot profiles were acquired by a planar scintillation device, respectively, at ISO, upper and down streams, fitted with single Gaussian distribution for beam modeling in Eclipse v15.6. The field size effect was adjusted for the best overall accuracy of clinically relevant field QAs. The halo effects at near surface were quantified by a pinpoint ionization chamber. Its major dosimetric characteristics were compared against MRPT comparable beam dataset. RESULTS: Contrast to MRPT, an increased proton straggling in the Bragg peak region was found with widened beam distal falloffs and elevated proximal transmission dose values. Integrated depth doses showed 0.105-0.221 MeV (energy sigma) or 0.30-0.94 mm broader Bragg peak widths (Rb80 -Ra80 ) for 130 MeV or higher energy beams and up to 0.48-0.79 mm extended distal falloffs (Rb20 -Rb80 ). Minor differences were identified in beam spot sizes, spot divergences, proton particles/MU, and field size output effects. High passing scores are reported for independent end-to-end dosimetry checks by IROC and for initial 108 field-specific QAs at 3%/3 mm Gamma index with fields regardless with or without range shifters. CONCLUSIONS: The author highlighted the dosimetry differences in IDDs mainly caused by the shortened beam transport system of SRPT, for which new acceptance criteria were adapted. This report offers a unique reference for future commissioning, beam modeling, planning, and analysis of QA and clinical studies.

Dosimetric Comparison of Treatment Plans Computed With Finite Size Pencil Beam and Monte Carlo Algorithms Using the InCise™ Multileaf Collimator-Equipped Cyberknife® System.

PURPOSE: InCise™ multileaf collimator (MLC) was introduced for CyberKnife® (CK) Robotic Radiosurgery System (CK-MLC) in 2015, and finite size pencil beam (FSPB) was the only available dose computation algorithm for treatment plans of CK-MLC system. The more advanced Monte Carlo (MC) dose calculation algorithm of lnCise™ was initially released in 2017 for the CK Precision™ treatment planning system (TPS) (v1.1) with new graphic processing unit (GPU) platform. GPU based TPS of the CK offers more accurate, faster treatment planning time and intuitive user interface with smart three-dimensional editing tools and fully automated autosegmentation tools. The MC algorithm used in CK TPS simulates the energy deposited by each individual photon and secondary particles to calculate more accurate dose. In the present study, the dose disparities between MC and FSPB algorithms for selected Stereotactic Ablative Radiation Therapy (SABR) CK-MLC treatment plans are quantified. MATERIALS AND METHODS: A total of 80 CK-MLC SABR plans computed with FSPB were retrospectively reviewed and compared with MC computed results, including plans for detached lung cancer (or tumors fully surrounded by lung tissues, n = 21), nondetached lung cancer (or tumor touched the chest wall or mediastinum, n = 23), intracranial (n = 21), and pancreas lesions (n = 15). Dosimetric parameters of each planning target volume and major organs at risk (OAR) are compared in terms of normalized percentage deviations (N dev). RESULTS: This study revealed an average of 24.4% overestimated D95 values in plans using FSPB over MC for detached lung (n = 21) and 14.9% for nondetached lung (n = 23) lesions. No significant dose differences are found in intracranial (0.3%, n = 21) and pancreatic (0.9%, n = 15) cases. Furthermore, no significant differences were found in Ndev of OARs. CONCLUSION: In this study, it was found that FSPB overestimates dose to inhomogeneous treatment sites. This indicates, the employment of MC algorithm in CK-MLC-based lung SABR treatment plans is strongly suggested.

In vitro Dosimetric Study of Biliary Stent Loaded with Radioactive 125I Seeds.

BACKGROUND: A novel radioactive 125I seed-loaded biliary stent has been used for patients with malignant biliary obstruction. However, the dosimetric characteristics of the stents remain unclear. Therefore, we aimed to describe the dosimetry of the stents of different lengths - with different number as well as activities of 125I seeds. METHODS: The radiation dosimetry of three representative radioactive stent models was evaluated using a treatment planning system (TPS), thermoluminescent dosimeter (TLD) measurements, and Monte Carlo (MC) simulations. In the process of TPS calculation and TLD measurement, two different water-equivalent phantoms were designed to obtain cumulative radial dose distribution. Calibration procedures using TLD in the designed phantom were also conducted. MC simulations were performed using the Monte Carlo N-Particle eXtended version 2.5 general purpose code to calculate the radioactive stent's three-dimensional dose rate distribution in liquid water. Analysis of covariance was used to examine the factors influencing radial dose distribution of the radioactive stent. RESULTS: The maximum reduction in cumulative radial dose was 26% when the seed activity changed from 0.5 mCi to 0.4 mCi for the same length of radioactive stents. The TLD's dose response in the range of 0-10 mGy irradiation by 137Cs γ-ray was linear: y = 182225x - 6651.9 (R2=0.99152; y is the irradiation dose in mGy, x is the TLDs' reading in nC). When TLDs were irradiated by different energy radiation sources to a dose of 1 mGy, reading of TLDs was different. Doses at a distance of 0.1 cm from the three stents' surface simulated by MC were 79, 93, and 97 Gy. CONCLUSIONS: TPS calculation, TLD measurement, and MC simulation were performed and were found to be in good agreement. Although the whole experiment was conducted in water-equivalent phantom, data in our evaluation may provide a theoretical basis for dosimetry for the clinical application.

Where have the organizers gone? - The growth control system as a foundation of physiology.

A model of growth control system suggests that the organizers in embryogenesis continue to exist and partially retain their function after embryogenesis. The organizers are the macroscopic singular points of the morphogen gradient and bioelectric fields. They have higher metabolic rate, higher density of gap junctions and stem cells than the surrounding tissue. The growth control model predicts that the organizers are likely to exist at the extreme points of surface or interface curvature of the body. Changes in bioelectric field at organizers precede the morphological and anatomical changes in morphogenesis and pathogenesis. Subtle perturbations at organizers can cause long lasting systemic effects. These features of organizers can be used for diagnostic and therapeutic purposes such as regenerative medicine. There is increasing evidence that acupuncture points are likely to have originated from organizers in embryogenesis. Many corollaries and predictions of the growth control model have been independently confirmed in developmental biology, physiology, as well as basic and clinical acupuncture research. This model set the first example of a truly integrative biological basis of acupuncture and conventional biomedical sciences which has met the gold standard of science with multiple confirmed predictions in both fields. The growth control system is embedded in various physiological systems and is part of the foundation of physiology and pathophysiology.

Dosimetric and radiobiological comparison of CyberKnife M6™ InCise multileaf collimator over IRIS™ variable collimator in prostate stereotactic body radiation therapy.

The impetus behind our study was to establish a quantitative comparison between the IRIS collimator and the InCise multileaf collimator (MLC) (Accuray Inc. Synnyvale, CA) for prostate stereotactic body radiation therapy (SBRT). Treatment plans for ten prostate cancer patients were performed on MultiPlan™ 5.1.2 treatment planning system utilizing MLC and IRIS for 36.25 Gy in five fractions. To reduce the magnitude of variations between cases, the planning tumor volume (PTV) was defined and outlined for treating prostate gland only, assuming no seminal vesicle or ex-capsule involvement. Evaluation indices of each plan include PTV coverage, conformity index (CI), Paddick's new CI, homogeneity index, and gradient index. Organ at risk (OAR) dose sparing was analyzed by the bladder wall Dmax and V37Gy, rectum Dmax and V36Gy. The radiobiological response was evaluated by tumor control probability and normal tissue complication probability based on equivalent uniform dose. The dose delivery efficiency was evaluated on the basis of planned monitor units (MUs) and the reported treatment time per fraction. Statistical significance was tested using the Wilcoxon signed rank test. The studies indicated that CyberKnife M6™ IRIS and InCise™ MLC produce equivalent SBRT prostate treatment plans in terms of dosimetry, radiobiology, and OAR sparing, except that the MLC plans offer improvement of the dose fall-off gradient by 29% over IRIS. The main advantage of replacing the IRIS collimator with MLC is the improved efficiency, determined from the reduction of MUs by 42%, and a 36% faster delivery time.

A computational tool for patient specific dosimetry and radiobiological modeling of selective internal radiation therapy with (90)Y microspheres.

In recent years we have witnessed tremendous progress in selective internal radiation therapy. In clinical practice, quite often, radionuclide therapy is planned using simple models based on standard activity values or activity administered per unit body weight or surface area in spite of the admission that radiation-dose methods provide more accurate dosimetric results. To address that issue, the authors developed a Matlab-based computational software, named Patient Specific Yttrium-90 Dosimetry Toolkit (PSYDT). PSYDT was designed for patient specific voxel-based dosimetric calculations and radiobiological modeling of selective internal radiation therapy with (90)Y microspheres. The developed toolkit is composed of three dimensional dose calculations for both bremsstrahlung and beta emissions. Subsequently, radiobiological modeling is performed on a per-voxel basis and cumulative dose volume histograms (DVHs) are generated. In this report we describe the functionality and visualization features of PSYDT.

B-type natriuretic peptide-guided therapy for perioperative medicine?

The recent guideline from the European Society of Cardiology and European Society of Anesthesiology recommended the use of B-type natriuretic peptide (BNP) as preoperative testing for high-risk cardiac patients undergoing non-cardiac surgery. In this article, the potential benefits, risks and details for implementing BNP testing in perioperative medicine are discussed. Review of four related lines of research including the use of BNP test for preoperative prognosis, BNP test for screening asymptomatic heart failure, BNP as prognostic test in asymptomatic, non-heart failure patients and using BNP for detecting silent myocardial ischaemia showed converging cut-off levels of BNP for risk stratification. BNP has better OR and relative risk in comparison with Revised Cardiac Risk Index (RCRI) in predicting perioperative cardiac risk. BNP-guided therapy can be low risk based on current evidence on non-surgical patients, including treating asymptomatic patients without heart failure to prevent cardiovascular complications. At present, there is lack of direct evidence supporting perioperative BNP testing. Further research with randomised controlled trials is needed to confirm the benefit of BNP-guided management. Preoperative BNP testing may be considered in patients with RCRI above 0 undergoing intermediate or high-risk surgery. BNP-guided therapy is likely a beneficial addition to perioperative medicine. Its combination with ß-blocker titration, RCRI and perioperative cardiovascular monitoring can be a major advance in reducing cardiac risk resulting in a dynamic, individualised optimisation process.

Complete response of endemic Kaposi sarcoma lesions with high-dose-rate brachytherapy: treatment method, results, and toxicity using skin surface applicators.

PURPOSE: To analyze the clinical outcome of Kaposi sarcoma skin lesions treated with high-dose-rate (HDR) brachytherapy in patients with a minimum of 2 years of followup. METHODS AND MATERIALS: Between February 2006 and July 2008, all patients with Kaposi sarcoma who received (192)Ir HDR brachytherapy using a skin surface applicator were evaluated for clinical response. Responses to treatment and toxicity were scored using standard criteria. RESULTS: Sixteen cases were collected. Treatment was delivered in four to six fractions, over a period of approximately 12 days. The specified dose ranged from 24 to 35Gy. Median followup the lesion was 41.4 months. No lesion was greater than 2cm. All patients had a complete response to treatment, with no evidence of local recurrence or tumor progression. Thirteen lesions developed Grade 1 and two lesions had Grade 2 acute skin reactions. One patient developed late skin changes with telangiectasias and hypopigmentation. CONCLUSIONS: HDR brachytherapy treatment seems to be an effective noninvasive option for patients with small cutaneous Kaposi sarcoma lesions, delivering excellent cosmesis and local control in our small series. Fewer fractions over a shorter period used in our group offer patients more convenience compared with other common regimens. Although HDR is being used more frequently for many surface applications, additional clinical studies with larger numbers of patients and longer followup are needed to confirm the general impression that it is an excellent option for many patients.

NEW MDS AND CLUSTERING BASED ALGORITHMS FOR PROTEIN MODEL QUALITY ASSESSMENT AND SELECTION.

In protein tertiary structure prediction, assessing the quality of predicted models is an essential task. Over the past years, many methods have been proposed for the protein model quality assessment (QA) and selection problem. Despite significant advances, the discerning power of current methods is still unsatisfactory. In this paper, we propose two new algorithms, CC-Select and MDS-QA, based on multidimensional scaling and k-means clustering. For the model selection problem, CC-Select combines consensus with clustering techniques to select the best models from a given pool. Given a set of predicted models, CC-Select first calculates a consensus score for each structure based on its average pairwise structural similarity to other models. Then, similar structures are grouped into clusters using multidimensional scaling and clustering algorithms. In each cluster, the one with the highest consensus score is selected as a candidate model. For the QA problem, MDS-QA combines single-model scoring functions with consensus to determine more accurate assessment score for every model in a given pool. Using extensive benchmark sets of a large collection of predicted models, we compare the two algorithms with existing state-of-the-art quality assessment methods and show significant improvement.

Prospective tests on biological models of acupuncture.

The biological effects of acupuncture include the regulation of a variety of neurohumoral factors and growth control factors. In science, models or hypotheses with confirmed predictions are considered more convincing than models solely based on retrospective explanations. Literature review showed that two biological models of acupuncture have been prospectively tested with independently confirmed predictions: The neurophysiology model on the long-term effects of acupuncture emphasizes the trophic and anti-inflammatory effects of acupuncture. Its prediction on the peripheral effect of endorphin in acupuncture has been confirmed. The growth control model encompasses the neurophysiology model and suggests that a macroscopic growth control system originates from a network of organizers in embryogenesis. The activity of the growth control system is important in the formation, maintenance and regulation of all the physiological systems. Several phenomena of acupuncture such as the distribution of auricular acupuncture points, the long-term effects of acupuncture and the effect of multimodal non-specific stimulation at acupuncture points are consistent with the growth control model. The following predictions of the growth control model have been independently confirmed by research results in both acupuncture and conventional biomedical sciences: (i) Acupuncture has extensive growth control effects. (ii) Singular point and separatrix exist in morphogenesis. (iii) Organizers have high electric conductance, high current density and high density of gap junctions. (iv) A high density of gap junctions is distributed as separatrices or boundaries at body surface after early embryogenesis. (v) Many acupuncture points are located at transition points or boundaries between different body domains or muscles, coinciding with the connective tissue planes. (vi) Some morphogens and organizers continue to function after embryogenesis. Current acupuncture research suggests a convergence of the neurophysiology model, the connective tissue model and the growth control model. The growth control model of acupuncture set the first example of a biological model in integrative medicine with significant prediction power.