The Determination of the Biocompatibility of New Compositional Materials, including Carbamide-Containing Heterocycles of Anti-Adhesion Agents for Abdominal Surgery.

Due to traumatic injuries, including those from surgical procedures, adhesions occur in over 50% of cases, necessitating exclusive surgical intervention for treatment. However, preventive measures can be implemented during abdominal organ surgeries. These measures involve creating a barrier around internal organs to forestall adhesion formation in the postoperative phase. Yet, the effectiveness of the artificial barrier relies on considerations of its biocompatibility and the avoidance of adverse effects on the body. This study explores the biocompatibility aspects, encompassing hemocompatibility, cytotoxicity, and antibacterial and antioxidant activities, as well as the adhesion of blood serum proteins and macrophages to the surface of new composite film materials. The materials, derived from the sodium salt of carboxymethylcellulose modified by glycoluril and allantoin, were investigated. The research reveals that film materials with a heterocyclic fragment exhibit biocompatibility comparable to commercially used samples in surgery. Notably, film samples developed with glycoluril outperform the effects of commercial samples in certain aspects.

Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer.

PURPOSE/OBJECTIVE: Definitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT. MATERIAL/METHODS: This was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS. RESULTS: 117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5-89.2) and 46% (95% CI 36.5-57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%. CONCLUSION: Partial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Monte Carlo investigation of dose distribution of uniformly and non-uniformly loaded standard and notched eye plaques.

To investigate the effect of using non-uniform loading and notched plaques on dose distribution for eye plaques. Using EGSnrc Monte Carlo (MC) simulations, we investigate eye plaque dose distributions in water and in an anatomically representative eye phantom. Simulations were performed in accordance with TG43 formalism and compared against full MC simulations which account for inter-seed and inhomogeneity effects. For standard plaque configurations, uniformly and non-uniformly loaded plaque dose distributions in water showed virtually no difference between each other. For standard plaque, the MC calculated dose distribution in planes parallel to the plaque is narrower than the TG43 calculation due to attenuation at the periphery of the plaque by the modulay. MC calculated the dose behind the plaque is fully attenuated. Similar results were found for the notched plaque, with asymmetric attenuation along the plane of the notch. Cumulative dose volume histograms showed significant reductions in the calculated MC doses for both tumor and eye structures, compared to TG43 calculations. The effect was most pronounced for the notch plaque where the MC dose to the optic nerve was greatly attenuated by the modulay surrounding the optic nerve compared to the TG43. Thus, a reduction of optic nerve D95% from 14 to 0.2 Gy was observed, when comparing the TG43 calculation to the MC result. The tumor D95% reduced from 89.2 to 79.95 Gy for TG43 and MC calculations, respectively. TG43 calculations overestimate the absolute dose and the lateral dose distribution of both standard and notched eye plaques, leading to the dose overestimation for the target and organs at risk. The dose matching along the central axis for the non-uniformly loaded plaques to that of uniformly loaded ones was found to be sufficient for providing comparable coverage and can be clinically used in eye-cancer-busy centers.

Practice-based training strategy for therapist-driven prostate MR-Linac adaptive radiotherapy.

Purpose: To develop a practice-based training strategy to transition from radiation oncologist to therapist-driven prostate MR-Linac adaptive radiotherapy. Methods and materials: In phase 1, 7 therapists independently contoured the prostate and organs-at-risk on T2-weighted MR images from 11 previously treated MR-Linac prostate patients. Contours were evaluated quantitatively (i.e. Dice similarity coefficient [DSC] calculated against oncologist generated online contours) and qualitatively (i.e. oncologist using a 5-point Likert scale; a score ≥ 4 was deemed a pass, a 90% pass rate was required to proceed to the next phase). Phase 2 consisted of supervised online workflow with therapists required no intervention from the oncologist on 10 total cases to advance. Phase 3 involved unsupervised therapist-driven workflow, with offline support from oncologists prior to the next fraction. Results: In phase 1, the mean DSC was 0.92 (range 0.85-0.97), and mean Likert score was 3.7 for the prostate. Five therapists did not attain a pass rate (3-5 cases with prostate contour score < 4), underwent follow-up one-on-one review, and performed contours on a further training set (n = 5). Each participant completed a median of 12 (range 10-13) cases in phase 2; of 82 cases, minor direction were required from the oncologist on 5 regarding target contouring. Radiation oncologists reviewed 179 treatment fractions in phase 3, and deemed 5 cases acceptable but with suggestions for next fraction; all other cases were accepted without suggestions. Conclusion: A training stepwise program was developed and successfully implemented to enable a therapist-driven workflow for online prostate MR-Linac adaptive radiotherapy.

Quantifying uncertainties associated with reference dosimetry in an MR-Linac.

BACKGROUND: Magnetic resonance (MR)-guided radiation therapy provides capabilities to utilize high-resolution and real-time MR imaging before and during treatment, which is critical for adaptive radiotherapy. This emerging modality has been promptly adopted in the clinic settings in advance of adaptations to reference dosimetry formalism that are needed to account for the presence of strong magnetic fields. In particular, the influence of magnetic field on the uncertainty of parameters in the reference dosimetry equation needs to be determined in order to fully characterize the uncertainty budget for reference dosimetry in MR-guided radiation therapy systems. PURPOSE: To identify and quantify key sources of uncertainty in the reference dosimetry of external high energy radiotherapy beams in the presence of a strong magnetic field. METHODS: In the absence of a formalized Task Group report for reference dosimetry in MR-integrated linacs, the currently suggested formalism follows the TG-51 protocol with the addition of a quality conversion factor kBQ accounting for the effects of the magnetic field on ionization chamber response. In this work, we quantify various sources of uncertainty that impact each of the parameters in the formalism, and evaluate their overall contribution to the final dose. Measurements are done in a 1.5 T MR-Linac (Unity, Elekta AB, Stockholm, Sweden) which integrates a 1.5 T Philips MR scanner and a 7 MVFFF linac. The responses of several reference-class small volume ionization chambers (Exradin:A1SL, IBA:CC13, PTW:Semiflex-3D) and Farmer type ionization chambers (Exradin:A19, IBA:FC65-G) were evaluated throughout this process. Long-term reproducibility and stability of beam quality, TPR 10 20 ${\mathrm{TPR}}_{10}^{20}$ , was also measured with an in-house built phantom. RESULTS: Relative to the conventional external high energy linacs, the uncertainty on overall reference dose in MR-linac is more significantly affected by the chamber setup: A translational displacement along y-axis of ± 3 mm results in dose variation of < |0.20| ± 0.02% (k = 1), while rotation of ± 5° in horizontal and vertical parallel planes relative to relative to the direction of magnetic field, did not exceed variation of < |0.44| ± 0.02% for all 5 ionization chambers. We measured a larger dose variation for xy-plane (horizontal) rotations (< |0.44| ± 0.02% (k = 1)) than for yz-plane (vertical) rotations (< ||0.28| ± 0.02% (k = 1)), which we associate with the gradient of kB,Q as a function of chamber orientation with respect to direction of the B0 -field. Uncertainty in Pion (for two depths), Ppol (with various sub-studies including effects of cable length, cable looping in the MRgRT bore, connector type in magnetic environment), and Prp were determined. Combined conversion factor kQ × kB,Q was provided for two reference depths at four cardinal angle orientations. Over a two-year period, beam quality was quite stable with TPR 10 20 ${\mathrm{TPR}}_{10}^{20}$ being 0.669 ± 0.01%. The actual magnitude of TPR 10 20 ${\mathrm{TPR}}_{10}^{20}$ was measured using identical equipment and compared between two different Elekta Unity MR-Linacs with results agreeing to within 0.21%. CONCLUSION: In this work, the uncertainty of a number of parameters influencing reference dosimetry was quantified. The results of this work can be used to identify best practice guidelines for reference dosimetry in the presence of magnetic fields, and to evaluate an uncertainty budget for future reference dosimetry protocols for MR-linac.

MR-linac daily semi-automated end-to-end quality control verification.

PURPOSE: Adaptive radiation therapy (ART) on the integrated Elekta Unity magnetic resonance (MR)-linac requires routine quality assurance to verify delivery accuracy and system data transfer. In this work, our objective was to develop and validate a novel automated end-to-end test suite that verifies data transfer between multiple software platforms and quantifies the performance of multiple machine subcomponents critical to the ART process. METHODS: We designed and implemented a software tool to quantify the MR and megavoltage (MV) isocenter coincidence, treatment couch positioning consistency, isocenter shift accuracy for the adapted plan as well as the MLC and jaw position accuracy following the beam aperture adaptation. Our tool employs a reference treatment plan with a simulated isocenter shift generated on an MR image of a readily available phantom with MR and MV visible fiducials. Execution of the test occurs within the standard adapt-to-position (ATP) clinical workflow with MV images collected of the delivered treatment fields. Using descriptive statistics, we quantified uncertainty in couch positioning, isocentre shift as well as the jaw and MLC positions of the adapted fields. We also executed sensitivity measurements to evaluate the detection algorithm's performance. RESULTS: We report the results of 301 daily testing instances. We demonstrated consistent tracking of the MR-to-MV alignment with respect to the established value and to detect small changes on the order of 0.2 mm following machine service events. We found couch position consistency relative to the test baseline value was within 95% CI [-0.31, 0.26 mm]. For phantom shifts that form the basis for the plan adaptation, we found agreement between MV-image-detected phantom shift and online image registration, within ± 1.5 mm in all directions with a 95% CI difference of [-1.29, 0.79 mm]. For beam aperture adaptation accuracy, we found differences between the planned and detected jaw positions had a mean value of 0.27 mm and 95% CI of [-0.29, 0.82 mm] and -0.17 mm and 95% CI of [-0.37, 0.05 mm] for the MLC positions. Automated fiducial detected accuracy was within 0.08 ± 0.20 mm of manual localization. Introduced jaw and MLC position errors (1-10 mm) were detected within 0.55 mm (within 1 mm for 15/256 instances for the jaws). Phantom shifts (1.3 or 5 mm in each cardinal direction) from a reference position were detected within 0.26 mm. CONCLUSIONS: We have demonstrated the accuracy and sensitivity of a daily end-to-end test suite capable of detecting errors in multiple machine subcomponents including system data transfer. Our test suite evaluates the entire treatment workflow and has captured system communication issues prior to patient treatment. With automated processing and the use of a standard vendor-provided phantom, it is possible to expand to other Unity sites.

Impact of intrafraction changes in delivered dose of the day for prostate cancer patients treated with stereotactic body radiotherapy via MR-Linac.

Purpose: The purpose of this study is to evaluate the impact of intrafraction pelvic motion by comparing the adapted plan dose (APD) and the computed delivered dose of the day (DDOTD) for patients with prostate cancer (PCa) treated with SBRT on the MR-Linac. Methods: Twenty patients with PCa treated with MR-guided adaptive SBRT were included. A 9-field IMRT distribution was adapted based on the anatomy of the day to deliver a total prescription dose of 3000 cGy in 5 fractions to the prostate plus a 5 mm isotropic margin. Prostate, bladder, and rectum were re-contoured on the MR-image acquired during treatment delivery (MRBO). DDOTD was computed by propagating the dose from the daily adapted plan generated during treatment onto the MRBO. Results: Target coverage was met for all fractions, however, computed DDOTD was significantly less than the APD (p < 0.05). During an average treatment of 53 min, mean bladder volume increased by 116%, which led to a significant decrease in the DDOTD bladder D40% (p < 0.001). However, DDOTD to bladder 5 cc was significantly higher (p < 0.001) than APD. Rectum intrafraction changes were observed based on a volume change of -20% to 83% and presence of significant dose changes from APD to DDOTD for rectum D20% (p < 0.05) and D1cc (p < 0.0001). Conclusions: Intrafraction motion observed during prostate SBRT treatment on the MR-Linac have dosimetric impacts on both the target and organs at risk. Post-treatment computation using DDOTD may inform adaptation beyond anatomic changes in subsequent treatment fractions to best capitalize on MR-Linac technology and widen the therapeutic index of SBRT for PCa.

Photon versus proton whole ventricular radiotherapy for non-germinomatous germ cell tumors: A report from the Children's Oncology Group.

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

Dosimetric comparison of MR-guided adaptive IMRT versus 3DOF-VMAT for prostate stereotactic radiotherapy.

INTRODUCTION: To compare the dosimetry of prostate stereotactic radiotherapy (SBRT) delivered by adaptive intensity modulated radiotherapy (A-IMRT) and 3 degree of freedom volumetric modulated arc therapy (3DOF-VMAT). METHODS & MATERIALS: Twenty-five prostate patients treated with High Dose Rate (HDR) brachytherapy followed by SBRT were included (fifteen with hydrogel spacer in place for treatment). Interfraction changes in the volume of prostate, rectum and bladder were measured. Fractional dose to these structures was estimated for A-IMRT and 3DOF-VMAT for comparison against the corresponding reference dose and between each other. RESULTS: Clinically acceptable dose was delivered to prostate in all 125 fractions through A-IMRT and 3DOF-VMAT. A-IMRT was better than 3DOF-VMAT in reducing dose to 1 cm3 of rectum. Conversely, 3DOF-VMAT was superior in sparing 50% and 20% of rectum. When comparing the reference and delivered dose, there was no significant difference for Bladder D5cm3 for either technique. However, rectum in the high dose region benefited more from A-IMRT by being irradiated to a lower than reference dose in more fractions than 3DOF-VMAT. Hydrogel spacer reduced the rectal dose and was associated with a smaller deviation from reference dose for rectum D50% for A-IMRT. CONCLUSIONS: Despite the presence of large interfraction organ volumes changes, clinically acceptable dose was delivered to the prostate by both systems. A-IMRT facilitated a greater rectal sparing from the high dose region than 3DOF-VMAT. Further reduction in rectal dose could be achieved by hydrogel spacer to displace the rectum, or by adaptation delivered by VMAT.

Design and feasibility of a flexible, on-body, high impedance coil receive array for a 1.5 T MR-linac.

The lack of radiation-attenuating tuning capacitors in high impedance coils (HICs) make HICs an interesting building block of receive arrays for MRI-guided radiotherapy (MRIgRT). Additionally, their flexibility and limited channel coupling allow for low-density support materials, which are likely to be more radiation transparent (radiolucent). In this work, we introduce the use of HICs in receive arrays for MRIgRT treatments. We discuss the design and show the dosimetric feasibility of a HIC receive array that has a high channel count and aims to improve the imaging performance of the 1.5 T MR-linac. Our on-body design comprises an anterior and posterior element, which each feature a [Formula: see text] channel layout (32 channels total). The anterior element is flexible, while the posterior element is rigid to support the patient. Mockups consisting of support materials and conductors were built, irradiated, and optimized to minimize impact on the surface dose (7% of the dose maximum) and dose at depth ([Formula: see text]0.8% under a single conductor and [Formula: see text]1.4% under a conductor crossing). Anatomical motion and the use of multiple beam angles will ensure that these slight dose changes at depth are clinically insignificant. Subsequently, several functional, single-channel HIC imaging prototypes and a 5-channel array were built to assess the performance in terms of signal-to-noise ratio (SNR). The performance was compared to the clinical MR-linac array and showed that the 5-channel imaging prototype outperformed the clinical array in terms of SNR and channel coupling. Imaging performance was not affected by the radiation beam. In conclusion, the use of HICs allowed for the design of our flexible, on-body receive array for MRIgRT. The design was shown to be dosimetrically feasible and improved the SNR. Future research with a full array will need to show the gain in parallel imaging performance and thus acceleration.

Monte Carlo simulations of out-of-field surface doses due to the electron streaming effect in orthogonal magnetic fields.

The out-of-field surface dose contribution due to backscattered or ejected electrons, focused by the magnetic field, is evaluated in this work. This electron streaming effect (ESE) can contribute to out-of-field skin doses in orthogonal magnetic resonance guided radiation therapy machines. Using the EGSnrc Monte Carlo package, a phantom is set-up along the central axis of an incident 10 [Formula: see text] 10 cm2 7 MV FFF photon beam. The phantom exit or entry surface is inclined with respect to the magnetic field, and an out-of-field water panel is positioned 10 cm away from, and centered on, the isocenter. The doses from streaming backscattered or ejected electrons, for either a 0.35 T or 1.5 T magnetic field, are evaluated in the out-of-field water panel for surface inclines of 10, 30, and 45°. The magnetic field focuses electrons emitted from the inclined phantom. Dose distributions at the surface of the out-of-field water panel are sharper in the 1.5 T magnetic field as compared to 0.35 T. The maximum doses for the 0.35 T simulations are 23.2%, 37.8%, and 39.0% for the respective 10, 30, and 45° simulations. For 1.5 T, for the same angles, the maximum values are 17.1%, 29.8%, and 35.8%. Dose values drop to below 2% within the first 1 cm of the out-of-field water phantom. The phantom thickness is an important variable in the magnitude of the ESE dose. The ESE can produce large out-of-field skin doses and must be a consideration in treatment planning in the MRgRT work-flow. Treatments often include multiple beams which will serve to spread out the effect, and many beams, such as anterior-posterior, will reduce the skin dose due to the ESE. A 1 cm thick shielding of either a bolus placed on the patient or mounted on the present RF coils would greatly reduce the ESE dose contributions. Further exploration of the capabilities of treatment planning systems to screen for this effect is required.

Sensitive volume effects on Monte Carlo calculated ion chamber response in magnetic fields.

PURPOSE: The development of magnetic resonance-guided radiation therapy (MRgRT) necessitates accurate Monte Carlo (MC) models of ion chambers for computing ion chamber corrections to compensate for the presence of the magnetic field. This study evaluates the sensitivity of the ion chamber dose response in a magnetic field on the collection volume used in the MC simulation. METHODS: The EGSnrc system's egs_chamber application is used with a recently developed and validated magnetic field transport code. The calculated dose to the sensitive volume of the chamber per unit incident photon fluence, normalized to that at 0 T, is evaluated as a function of magnetic field for the PTW 30013, PTW 31006, PTW 31010, Exradin A12S, and Exradin A1SL chambers. The sensitive region is varied by excluding the volume corresponding to either 0, 0.5, or 1 mm of distance away from the stem. The photon field, magnetic field, and ion chamber are all oriented perpendicular to each other as in the majority of published experimental works. RESULTS: The calculations for a Co-60 source demonstrate that variations from the 0 mm simulations are on the order of several percent with a maximum deviation, occurring at 0.5 T, of 1.75 ± 0.03% and 3.39 ± 0.06% for the 0.5 mm or 1 mm simulations, respectively, for a 0.057 cm3 A1SL chamber. Larger volume chambers showed smaller, but still non-negligible, variations. Simulations of the A1SL chamber with a 7 MV photon source, corresponding to the Elekta MR-linac machine, demonstrate that the effect is slightly reduced but still persists with a maximum deviation of 1.97 ± 0.08% for the 1 mm reduction. CONCLUSIONS: Usually, the geometric sensitive volume of the ion chamber is used in MC calculation as a substitute for the potentially unknown, smaller, true collection volume (governed by the complex electric field distribution inside the chamber). The calculations in this study demonstrate that even a small variation in simulated volume can lead to fairly large variations in the MC calculated ion chamber response in a magnetic field. This is an important effect that must be addressed to ensure proper calibration of MRgRT machines using MC ion chamber correction factors. This effect may play a role, even where there is no magnetic field, in small-field dosimetry when volume averaging effect are important.