Experimental Investigation of Cumulative Damage and Self-Healing Properties of Smart Cementitious Composite under Continuous Compression Load.

This study investigated the effect of sustained loading on the cumulative damage of a newly developed smart cement-based self-healing composite material (SMA-ECC). SMA-ECC is composed of engineered cementitious composite (ECC) and shape memory alloy (SMA) fibers. A uniaxial compressive test with five predefined loading levels (0%, 30%, 40%, 50%, and 60% of compressive strength) was conducted on SMA-ECC hollow-cylindrical specimens and ECC control hollow-cylindrical specimens. The cumulative damage was mainly determined by changes in the total water absorption of different groups of specimens during three different periods (not loaded, at a predefined loading level, and after unloading). A normalized water content index was proposed to couple the effects of self-healing, sustained loading, and cumulative damage. The test results indicate that the cumulative water absorption of SMA-ECC was 35% lower than that of ECC, which may indicate less irreparable damage. In addition, the self-healing ability of SMA-ECC specimens under different compression load levels was evaluated through normalized water content analysis. SMA-ECC exhibited a 100% repair rate at load levels of 30% and 40%. At a higher load level of 60%, the repair rate of SMA-ECC was 76%. These results collectively emphasize the significant impermeability and self-healing performance of SMA-ECC after unloading.

Evaluation of repeatability and reproducibility of radiomic features produced by the fan-beam kV-CT on a novel ring gantry-based PET/CT linear accelerator.

BACKGROUND: The RefleXion X1 is a novel radiotherapy delivery system on a ring gantry equipped with fan-beam kV-CT and PET imaging subsystems. The day-to-day scanning variability of radiomics features must be evaluated before any attempt to utilize radiomics features. PURPOSE: This study aims to characterize the repeatability and reproducibility of radiomic features produced by the RefleXion X1 kV-CT. MATERIALS AND METHODS: The Credence Cartridge Radiomics (CCR) phantom includes six cartridges of varied materials. It was scanned 10 times on the RefleXion X1 kVCT imaging subsystem over a 3-month period using the two most frequently used scanning protocols (BMS and BMF). Fifty-five radiomic features were extracted for each ROI on each CT scan and analyzed using LifeX software. The coefficient of variation (COV) was computed to evaluate the repeatability. Intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) were used to evaluate the repeatability and reproducibility of the scanned images using 0.9 as the threshold. This process is repeated on a GE PET-CT scanner using several built-in protocols as a comparison. RESULTS: On average, 87% of the features on both scan protocols on the RefleXion X1 kVCT imaging subsystem can be considered repeatable as they met COV < 10% criteria. On GE PET-CT, this number is similar at 86%. When we tighten the criteria to COV <5%, the RefleXion X1 kVCT imaging subsystem showed much better repeatability with 81% of features on average whereas GE PET-CT showed only 73.5% on average. About 91% and 89% of the features with ICC > 0.9 respectively for BMS and BMF protocols on RefleXion X1. On the other hand, the percentage of features with ICC > 0.9 on GE PET-CT ranges from 67% to 82%. The RefleXion X1 kVCT imaging subsystem showed excellent intra-scanner reproducibility between the scanning protocols much better than the GE PET CT scanner. For the inter-scanner reproducibility, the percentage of features with CCC > 0.9 ranged from 49% to 80%. between X1 and GE PET-CT scanning protocols. CONCLUSIONS: Clinically useful CT radiomic features produced by the RefleXion X1 kVCT imaging subsystem are reproducible and stable over time, demonstrating its utility as a quantitative imaging platform.

Application and Comparison of Different Models for Quantifying the Aquatic Community in a Dam-Controlled River.

In order to develop a better model for quantifying aquatic community using environmental factors that are easy to get, we construct quantitative aquatic community models that utilize the different relationships between water environmental impact factors and aquatic biodiversity as follows: a multi-factor linear-based (MLE) model and a black box-based 'Genetic algorithm-BP artificial neural networks' (GA-BP) model. A comparison of the model efficiency and their outputs is conducted by applying the models to real-life cases, referring to the 49 groups of seasonal data observed over seven field sampling campaigns in Shaying River, China, and then performing model to reproduce the seasonal and inter-annual variation of the water ecological characteristics in the Huaidian (HD) site over 10 years. The results show that (1) the MLE and GA-BP models constructed in this paper are effective in quantifying aquatic communities in dam-controlled rivers; and (2) the performance of GA-BP models based on black-box relationships in predicting the aquatic community is better, more stable, and reliable; (3) reproducing the seasonal and inter-annual aquatic biodiversity in the HD site of Shaying River shows that the seasonal variation of species diversity for phytoplankton, zooplankton, and zoobenthos are inconsistent, and the inter-annual levels of diversity are low due to the negative impact of dam control. Our models can be used as a tool for aquatic community prediction and can become a contribution to showing how quantitative models in other dam-controlled rivers to assisting in dam management strategies.

3D Microfluidic System for Evaluating Inhibitory Effect of Chinese Herbal Medicine Oldenlandia diffusa on Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis.

OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS: ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.

Long-term follow up of patients with hematological malignancies treated with total body irradiation using intensity modulated radiation therapy.

Background: With the advent of modern radiation treatment technologies such as intensity modulated radiation therapy (IMRT), there has been increasing interest in its use for total body irradiation (TBI) conditioning regimens for hematopoietic cell transplantation (HCT) to achieve lower doses to critical organs such as the lungs and kidneys. Although this has been reported on in early studies, long-term safety and efficacy data is limited. Methods: We performed a single institution matched-pair retrospective analysis of patients treated with IMRT TBI and standard TBI between 2010 and 2020 to provide data on long-term outcomes. Patients with hematologic malignancies, who could not tolerate standing for traditional TBI or who received prior radiation received IMRT TBI. Patients were matched based on age, diagnosis, disease status, and year of transplant, and were matched 2:1 to the standard TBI and IMRT TBI cohorts. Patient and treatment characteristics, toxicity, graft-versus-host disease (GVHD), dosimetry, and outcomes were evaluated for each cohort. Results: A total of 13 patients met inclusion criteria for the IMRT cohort, leading to 26 patients in the standard TBI cohort. There was no significant difference in relevant clinical factors between the cohorts. Reasons for using IMRT over conventional TBI included being unable to stand (n=5), prior radiation (n=5), and pediatric patient requiring anesthesia (n=3). Among living patients, median follow-up for all patients was 5.1 years in the IMRT TBI cohort and 5.5 years in the standard TBI cohort. The 5-yr estimate of OS was 68% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.706). The 5-yr estimate of RFS was 54% in the IMRT TBI cohort and 60% in the standard TBI cohort (p=0.529). There was no clinically significant pneumonitis, nephritis, hypothyroidism, or cataracts reported in the IMRT TBI cohort. 41.7% of patients in the IMRT TBI cohort and 79.2% of patients in the standard TBI cohort experienced Grade II-IV acute GVHD (p=0.023). Conclusions: IMRT TBI appears to lead to favorable long-term outcome and dosimetry, and therefore potentially improved long-term toxicity profile compared to conventional TBI. IMRT TBI warrants further investigation as part of larger prospective trials.

Role of radiotherapy in treatment of extramedullary relapse following total marrow and lymphoid irradiation in high-risk and/or relapsed/refractory acute leukemia.

Background: Total Marrow and Lymphoid Irradiation (TMLI) is a promising component of the preparative regimen for hematopoietic cell transplantation in patients with high-risk acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Extramedullary (EM) relapse after TMLI is comparable to TBI and non-TBI conditioning regimens. This study evaluates outcomes of patients treated with radiotherapy (RT) with EM relapse previously treated with TMLI. Methods: A retrospective analysis of five prospective TMLI trials was performed. TMLI targeted bones and major lymphoid tissues using image-guided tomotherapy, with total dose ranging from 12 to 20 Gy. EM recurrences were treated at the discretion of the hematologist and radiation oncologist using RT ± chemotherapy. Descriptive statistics and survival analysis were then performed on this cohort. Results: In total, 254 patients with refractory or relapsed AML or ALL were treated with TMLI at our institution. Twenty-one patients were identified as receiving at least one subsequent course of radiation. A total of 67 relapse sites (median=2 sites/patient, range=1-16) were treated. Eleven relapsed patients were initially treated with curative intent. Following the initial course of subsequent RT, 1-year, 3-year and 5-year estimates of OS were 47.6%, 32.7% and 16.3%, respectively. OS was significantly better in patients treated with curative intent, with median OS of 50.7 months vs 1.6 months (p<0.001). 1-year, 3-year and 5-year estimates of PFS were 23.8%, 14.3% and 14.3%, respectively. PFS was significantly better in patients treated with curative intent, with median PFS of 6.6 months vs 1.3 months (p<0.001). Following RT, 86.6% of the sites had durable local control. Conclusions: RT is an effective modality to treat EM relapse in patients with acute leukemia who relapse after HCT achieving high levels of local control. In patients with limited relapse amenable to curative intent, radiation confers favorable long-term survival. Radiation as salvage treatment for EM relapse after HCT warrants further evaluation.

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review.

Purpose: TMI utilizes IMRT to deliver organ sparing targeted radiotherapy in patients undergoing hematopoietic cell transplantation (HCT). TMI addresses an unmet need, specifically patients with refractory or relapsed (R/R) hematologic malignancies who have poor outcomes with standard HCT regimens and where attempts to improve outcomes by adding or dose escalating TBI are not possible due to increased toxicities. Over 500 patients have received TMI at this center. This review summarizes this experience including planning and delivery, clinical results, and future directions. Methods: Patients were treated on prospective allogeneic HCT trials using helical tomographic or VMAT IMRT delivery. Target structures included the bone/marrow only (TMI), or the addition of lymph nodes, and spleen (total marrow and lymphoid irradiation, TMLI). Total dose ranged from 12 to 20 Gy at 1.5-2.0 Gy fractions twice daily. Results: Trials demonstrate engraftment in all patients and a low incidence of radiation related toxicities and extramedullary relapses. In R/R acute leukemia TMLI 20 Gy, etoposide, and cyclophosphamide (Cy) results in a 1-year non-relapse mortality (NRM) rate of 6% and 2-year overall survival (OS) of 48%; TMLI 12 Gy added to fludarabine (flu) and melphalan (mel) in older patients (≥ 60 years old) results in a NRM rate of 33% comparable to flu/mel alone, and 5-year OS of 42%; and TMLI 20 Gy/flu/Cy and post-transplant Cy (PTCy) in haplo-identical HCT results in a 2-year NRM rate of 13% and 1-year OS of 83%. In AML in complete remission, TMLI 20 Gy and PTCy results in 2-year NRM, OS, and GVHD free/relapse-free survival (GRFS) rates of 0%, 86·7%, and 59.3%, respectively. Conclusion: TMI/TMLI shows significant promise, low NRM rates, the ability to offer myeloablative radiation containing regimens to older patients, the ability to dose escalate, and response and survival rates that compare favorably to published results. Collaboration between radiation oncology and hematology is key to successful implementation. TMI/TMLI represents a paradigm shift from TBI towards novel strategies to integrate a safer and more effective target-specific radiation therapy into HCT conditioning beyond what is possible with TBI and will help expand and redefine the role of radiotherapy in HCT.

Auto-segmentation for total marrow irradiation.

Purpose: To evaluate the accuracy and efficiency of Artificial-Intelligence (AI) segmentation in Total Marrow Irradiation (TMI) including contours throughout the head and neck (H&N), thorax, abdomen, and pelvis. Methods: An AI segmentation software was clinically introduced for total body contouring in TMI including 27 organs at risk (OARs) and 4 planning target volumes (PTVs). This work compares the clinically utilized contours to the AI-TMI contours for 21 patients. Structure and image dicom data was used to generate comparisons including volumetric, spatial, and dosimetric variations between the AI- and human-edited contour sets. Conventional volume and surface measures including the Sørensen-Dice coefficient (Dice) and the 95th% Hausdorff Distance (HD95) were used, and novel efficiency metrics were introduced. The clinical efficiency gains were estimated by the percentage of the AI-contour-surface within 1mm of the clinical contour surface. An unedited AI-contour has an efficiency gain=100%, an AI-contour with 70% of its surface<1mm from a clinical contour has an efficiency gain of 70%. The dosimetric deviations were estimated from the clinical dose distribution to compute the dose volume histogram (DVH) for all structures. Results: A total of 467 contours were compared in the 21 patients. In PTVs, contour surfaces deviated by >1mm in 38.6% ± 23.1% of structures, an average efficiency gain of 61.4%. Deviations >5mm were detected in 12.0% ± 21.3% of the PTV contours. In OARs, deviations >1mm were detected in 24.4% ± 27.1% of the structure surfaces and >5mm in 7.2% ± 18.0%; an average clinical efficiency gain of 75.6%. In H&N OARs, efficiency gains ranged from 42% in optic chiasm to 100% in eyes (unedited in all cases). In thorax, average efficiency gains were >80% in spinal cord, heart, and both lungs. Efficiency gains ranged from 60-70% in spleen, stomach, rectum, and bowel and 75-84% in liver, kidney, and bladder. DVH differences exceeded 0.05 in 109/467 curves at any dose level. The most common 5%-DVH variations were in esophagus (86%), rectum (48%), and PTVs (22%). Conclusions: AI auto-segmentation software offers a powerful solution for enhanced efficiency in TMI treatment planning. Whole body segmentation including PTVs and normal organs was successful based on spatial and dosimetric comparison.

Risk of Subsequent Malignant Neoplasms Following Hematopoietic Stem Cell Transplantation with Total Body Irradiation or Total Marrow Irradiation: Insights from Early Follow-Up.

Total marrow irradiation (TMI) is an alternative to total body irradiation (TBI) as a component of the conditioning regimen for hematopoietic cell transplantation (HCT), offering the ability to deliver more targeted doses and facilitating organ-sparing. The organ-sparing effect of TMI is theorized to decrease the risk of complications associated with radiation, including subsequent malignant neoplasms (SMNs), while allowing for dosage escalation to improve oncologic outcomes. The purpose of this study was to compare SMNs rates among patients treated with TBI- or TMI-based conditioning regimens. We hypothesized that TMI would yield a rate of SMNs comparable to, if not lower than, TBI. A retrospective matched-pair analysis of patients who underwent allogeneic HCT and received either TBI- or TMI-based conditioning regimens to a total dose of 12 to 20 Gy was performed. A total of 171 patients received TMI-based conditioning and 171 received TBI-based conditioning, matched based on age, sex, diagnosis, and length of follow-up. SMNs were identified from an established long-term follow-up protocol, our institutional cancer registry, and the California Cancer Registry. There were no significant differences in patient and clinical characteristics between the TMI and TBI cohorts except for clinical response status at transplantation and radiation dose. As expected, patients in the TMI received higher radiation doses (median dose, 16.0 Gy for the TMI cohort versus 13.2 Gy for the TBI cohort; P < .001). The median follow-up for both cohorts was 2.0 years (range, .5 to 12.3 years). There was no significant difference in the risk of developing SMNs between the 2 cohorts (P = .81). A total of 9 patients (5.3%) conditioned with TBI and 10 patients (5.8%) conditioned with TMI developed SMNs, at a median of 3.3 years and 1.7 years following HCT, respectively. Excluding nonmelanoma skin cancers and noninvasive neoplasms, 2 patients in the TBI cohort developed SMNs (both melanomas), and 1 patient in the TMI cohort developed an SMN (colon cancer). No patients developed a subsequent hematologic malignancy. TMI-based conditioning is not associated with a significant difference in the risk of developing SMNs compared with TBI-based conditioning during early post-HCT follow-up. Future studies with longer follow-up may be needed to further characterize the risk of SMNs associated with TMI-based conditioning regimens compared with TBI-based regimens.

Target Coverage and Normal Organ Sparing in Dose-Escalated Total Marrow and Lymphatic Irradiation: A Single-Institution Experience.

Purpose/Objectives: The aim of this study is to report historical treatment planning experience at our institution for patients receiving total marrow and lymphatic irradiation (TMLI) as part of the conditioning regimen prior to hematopoietic stem cell transplant. Materials/Methods: Based on a review of all historical clinical TMLI treatments plans, we retrieved a 12-Gy cohort of 108 patients with a prescription dose of 12 Gy to the skeletal bones, lymph nodes, spleen, and spinal canal, and retrieved a 20-Gy cohort of 120 patients with an escalated prescription dose of 20 Gy to the skeletal bones, lymph nodes, spleen, and spinal cord, and 12 Gy to the brain and liver. Representative dosimetric parameters including mean and median dose, D80, and D10 (dose covering 80% and 10% of the structure volume, respectively) for targets and normal organs were extracted and compared between the two groups of patients. Results: For the 12-Gy cohort, the average mean dose for normal organs ranged from 18.3% to 78.3% of 12 Gy, and the average median dose ranged from 18.3% to 77.5% of 12 Gy. For the 20-Gy cohort, the average mean dose for normal organs ranged from 13.0% to 76.0% of 20 Gy, and the average median dose ranged from 12.5% to 75.0% of 20 Gy. Compared to the mean dose to normal organs in the 12-Gy cohort, the average mean dose to normal organs increased from 0.0% to 73.1%, with only four normal organs showing a >50% increase. Normal organ dose in TMLI plans using volumetric modulated arc therapy fields fell within the dose range in historical TMLI plans. Conclusion: Dosimetric data in historical TMLI plans at our institution are summarized at prescription dose levels of 12 Gy and 20 Gy, respectively. Compared to the normal organ dose with a prescription dose of 12 Gy, the mean and median dose to most normal organs at an escalated prescription dose of 20 Gy had an increase less than prescription dose scaling. Dosimetric results from this study can be used as reference data to facilitate clinical implementation of TMLI at other institutions.

Treatment planning of total marrow irradiation with intensity-modulated spot-scanning proton therapy.

Purpose: The goal of this study is to investigate treatment planning of total marrow irradiation (TMI) using intensity-modulated spot-scanning proton therapy (IMPT). The dosimetric parameters of the intensity-modulated proton plans were evaluated and compared with the corresponding TMI plans generated with volumetric modulated arc therapy (VMAT) using photon beams. Methods: Intensity-modulated proton plans for TMI were created using the Monte Carlo dose-calculation algorithm in the Raystation 11A treatment planning system with spot-scanning proton beams from the MEVION S250i Hyperscan system. Treatment plans were generated with four isocenters placed along the longitudinal direction, each with a set of five beams for a total of 20 beams. VMAT-TMI plans were generated with the Eclipse-V15 analytical anisotropic algorithm (AAA) using a Varian Trilogy machine. Three planning target volumes (PTVs) for the bones, ribs, and spleen were covered by 12 Gy. The dose conformity index, D80, D50, and D10, for PTVs and organs at risk (OARs) for the IMPT plans were quantified and compared with the corresponding VMAT plans. Results: The mean dose for most of the OARs was reduced substantially (5% and more) in the IMPT plans for TMI in comparison with VMAT plans except for the esophagus and thyroid, which experienced an increase in dose. This dose reduction is due to the fast dose falloff of the distal Bragg peak in the proton plans. The conformity index was found to be similar (0.78 vs 0.75) for the photon and proton plans. IMPT plans provided superior superficial dose coverage for the skull and ribs in comparison with VMAT because of increased entrance dose deposition by the proton beams. Conclusion: Treatment plans for TMI generated with IMPT were superior to VMAT plans mainly due to a large reduction in the OAR dose. Although the current IMPT-TMI technique is not clinically practical due to the long overall treatment time, this study presents an enticing alternative to conventional TMI with photons by providing superior dose coverage of the targets, increased sparing of the OARs, and enhanced radiobiological effects associated with proton therapy.

Comparison of intrafractional motion with two frameless immobilization systems in surface-guided intracranial stereotactic radiosurgery.

PURPOSE/OBJECTIVES: The aim of this study is to compare intrafractional motion using two commercial non-invasive immobilization systems for linac-based intracranial stereotactic radiosurgery (SRS) under guidance with a surface-guided radiotherapy (SGRT) system. MATERIALS/METHODS: Twenty-one patients who received intracranial SRS were retrospectively selected. Ten patients were immobilized with a vacuum fixation biteplate system, while 11 patients were immobilized with an open-face mask system. A setup margin of 1 mm was used in treatment planning. Real-time surface motion data in 37 treatment fractions using the vacuum fixation system and 44 fractions using the open-face mask were recorded by an SGRT system. Variances of intrafractional motion along three translational directions and three rotational directions were compared between the two immobilization techniques with Levene's tests. Intrafractional motion variation over time during treatments was also evaluated. RESULTS: Using the vacuum fixation system, the average and standard deviations of the shifts were 0.01 ± 0.18 mm, -0.06 ± 0.30 mm, and  0.02 ± 0.26 mm in the anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions, and -0.02 ± 0.19°, -0.01 ± 0.13°, and 0.01 ± 0.13° for rotations in yaw, roll, and pitch, respectively; using the open-face mask system, the average and standard deviations of the shifts were -0.06 ± 0.20 mm, -0.02 ± 0.35 mm, and 0.01 ± 0.40 mm in the AP, SI, and LR directions, and were 0.05 ± 0.23°, 0.02 ± 0.21°, and 0.00 ± 0.16° for rotations in yaw, roll, and pitch, respectively. There was a significant increase in intrafractional motion variance over time during treatments. CONCLUSION: Patients with the vacuum fixation system had significantly smaller intrafractional motion variation compared to those with the open-face mask system. Using intrafractional motion techniques such as surface imaging system is recommended to minimize dose deviation due to intrafractional motion. The increase in intrafractional motion over time indicates clinical benefits with shorter treatment time.

Automatic organ contour check: One essential step in autonomous treatment planning.

Geometric and nomenclature errors are commonly encountered in automated treatment planning. We describe a novel algorithm to extract organ geometry relationships from patient structure DICOM data to construct a database that can be used to detect organ contour inaccuracies including relational and naming errors. Twenty-five sets of head and neck patients' treatment plan data (CT, structures) were retrospectively retrieved from our institution. For each dataset, various organs were contoured and verified by experienced physicians. The relative position and orientation between organs were extracted from each patient and the data were used to construct an organ relationship database model. The model was tested using a dataset originating from an in-house organ renaming software that often-introduced organ contour naming mismatches. As part of the validation test, the renamed organs relative positions were compared with the database model to identify mismatches. Within the forty head and neck patients, we extracted the geometric relationship between 201 organ pairs. The average number of unique types of organ pairs (for example, left parotid with left eye is one type of organ pair) stored in the database was 12. Fifteen head and neck structure sets automatically renamed using our in-house organ renaming tool was used as validation data. All of the 30 random assigned wrong name labels present in these structure sets were identified using the established organ geometry relationship database. We successfully constructed a head and neck organ geometry relationship database and validated it in a contour naming quality assurance process. This novel scheme can be expanded to the entire body and shows a great potential in automatic plan physics QA procedure. It should be one essential QA step in an autonomous treatment planning process.

Lignans from Bupleurum marginatum and their antioxidant activity.

A new aryltetralin lignan, bupleroid A (1), along with ten known analogues (2-11) were isolated from Bupleurum marginatum. The structures of these isolates were determined by 1D and 2D NMR, HRESIMS, and ECD data analysis. In addition, the DPPH radical scavenging capacities of all compounds were evaluated. Compound 6 exhibited good DPPH radical scavenging activity at a concentration of 50 µM.[Formula: see text].

Volumetric modulated arc therapy based total marrow and lymphoid irradiation: Workflow and clinical experience.

Background: The aim of this study is to report historical treatment planning experience at our institution for patients receiving total marrow and lymphatic irradiation (TMLI) using volumetric modulated arc therapy (VMAT) as part of the conditioning regimen prior to hematopoietic stem cell transplant. Methods: We identified a total of fifteen patients with VMAT TMLI, ten with a prescription dose of 20 Gy (targeting the skeletal bones, lymph nodes, spleen, and spinal canal, with 12 Gy to the brain and liver) and five with a prescription dose of 12-16 Gy (targeting the skeletal bones, lymph nodes, spleen, and spinal canal). Representative dosimetric parameters including total treatment time, mean and median dose, D80, and D10 (dose covering 80% and 10% of the structure volume, respectively) for targets and normal organs were extracted and compared to historical patients treated with helical tomotherapy. Results: The median treatment time for the first and subsequent fractions was 1.5 and 1.1 hours, respectively. All the target volumes had a mean dose greater than the prescribed dose except the ribs, which had an average mean dose of 19.5 Gy. The skeletal bones had an average mean dose of 21.1 Gy. The brain and liver have average mean doses of 14.8 and 14.1 Gy, respectively. The mean lung dose had an average of 7.6 ± 0.6 Gy for the 20-Gy cohort. Relative to the prescription dose of 20 Gy, the average mean dose for the normal organ volumes ranged from 16.5% to 72.0%, and the average median dose for the normal organs ranged from 16.5% to 71.0%. Dosimetry for patients treated to 12-16 Gy fell within expected ranges based on historical helical tomotherapy plans. Conclusions: Dosimetric data in the VMAT TMLI plans at our institution are summarized for 20 Gy and 12-16 Gy cohorts. Dose distributions and treatment times are overall similar to plans generated with helical tomotherapy. TMLI may be delivered effectively using a VMAT technique, even at escalated doses.

Setup Accuracy in Craniospinal Irradiation: Implications for Planning Treatment Volume Margins.

PURPOSE: Craniospinal irradiation (CSI) using tomotherapy has advantages over standard 3-dimensional techniques. However, there is a paucity of published data on craniospinal setup reproducibility to guide appropriate planning treatment volume (PTV) margins. We sought to evaluate the setup accuracy of patients undergoing CSI to optimize PTV margins. METHODS AND MATERIALS: We measured residual setup deviation between simulation computed tomography (CT) and daily megavoltage CT after couch shifts made by therapists after megavoltage CT-based image registration for 10 patients who completed CSI at our institution. Translational displacement values were recorded at the sella, top of T1, and top of L5 in the anteroposterior (AP) and lateral planes. Systematic and random error were calculated from displacement values. Using z score analysis, we calculated minimal PTV margins to encompass 90% of recorded fractions at each level. We evaluated whether patient characteristics predict for increased setup error using standard statistical techniques. RESULTS: The mean setup deviation in the AP plane across all treatments was 2.49, 3.40, and 3.83 mm at the sella, T1, and L5, respectively. Mean lateral setup error was 2.86, 4.02, and 5.46 mm at the sella, T1, and L5, respectively. Systematic error ranged from 0.75 to 1.01 mm at the sella, 1.09 to 1.37 mm at T1, and 1.30 to 1.50 mm at L5. Random error ranged from 1.35 to 1.41 mm at the sella, 1.48 to 1.73 mm at T1, and 2.26 to 2.37 mm at L5. The minimum margin to cover 90% of the treatments was 6.4, 8.2, and 10.5 mm at the sella, T1, and L5, respectively. There appeared to be a correlation between older age and lateral setup error in the L spine approaching statistical significance (R, 0.629; P = .052). CONCLUSIONS: Setup error increases in the caudal direction of the spine and is greater in the lateral plane compared with the AP plane. We recommend a PTV margin of 5 to 7 mm in the brain and 10 mm in the spine.

Dosimetric comparison of multiple vs single isocenter technique for linear accelerator-based stereotactic radiosurgery: The Importance of the six degree couch.

PURPOSE: Single isocenter technique (SIT) for linear accelerator-based stereotactic radiosurgery (SRS) is feasible. However, SIT introduces the potential for rotational error which can lead to geographical miss. Additional planning treatment volume (PTV) margin is required when using SIT. With the six degrees of freedom (6DoF) couch, rotational error can be minimized. We sought to evaluate the effect of the 6DoF couch on the dosimetry of patients with multiple brain metastases treated with SIT. MATERIALS AND METHODS: Ten consecutive patients treated with SRS to ≥3 metastases were identified. Original treatments had MIT plans (MITP). The lesions were replanned using SIT. Lesions 5-10 cm from isocenter had an additional 1mm of margin. Patients were replanned with these additional margins to account for inability to correct rotational error (SITPM). Multiple dosimetric variables and time metrics were evaluated. Dosimetry planning time (DPT) and patient treatment time (PTT) were evaluated. Statistics were calculated using the Wilcoxon signed-rank test. RESULTS: A total of 73 brain metastases receiving SRS, to a median of 6 lesions per patient, were identified. MITPs treated 73 lesions with 63 isocenters. On average, MITPs had a 19.2% higher brain V12 than SITPs (P = 0.017). For creation of SITPM, 30 lesions required 1 mm of additional margin, while none required 2 mm of margin. This increased V12 by 47.8% on average per patient (P = 0.008) from SITP to SITPM. DPT was 5.5 hours for SITP, while median for MITP was 12.5 hours (P = 0.005) PTT was 30 minutes for SITP, while median for MITP was 144 minutes (P = 0.005). CONCLUSIONS: SITPs are comparable to MITPs if rotational error can be corrected with the use of a 6DoF couch. Increasing margin to account for rotational error leads to a nearly 50% increase in V12, which could result in higher rates of radiation necrosis. Time savings are significant using SIT.

Dosimetric Predictors of Genitourinary Toxicity From a Phase I Trial of Prostate Bed Stereotactic Body Radiation Therapy.

PURPOSE: Our purpose was to analyze dose-volume parameters associated with genitourinary (GU) toxicity from a phase I clinical trial of prostate bed stereotactic body radiation therapy. METHODS AND MATERIALS: Patients were treated in escalating dose levels of 35, 40, and 45 Gy, over 5 fractions. Data from all 26 patients enrolled in the protocol were analyzed using multiple dose-volume cut points for multiple GU organs at risk. Univariate logistical regression and Fisher exact test were used to assess statistical significance associated with incidence of toxicity. RESULTS: The median follow-up was 36 months for all patients. Acute GU toxicity was mild and resolved spontaneously. Eight out of 26 patients (30.7%) developed late GU toxicity of grade 2 or higher. Two patients developed grade 3 ureteral stenosis, 1 in the 35 Gy arm and the other in the 45 Gy arm. Three patients developed grade 2 or higher hematuria/cystitis, and 3 developed grade 2 or higher incontinence. Incidence of grade 3 ureteral stenosis was related to the absolute volume of bladder wall receiving greater than 20, 25, and 30 Gy (P < .01). Grade 2 cystitis and hematuria were related to the volume of bladder wall receiving 20 Gy less than 34% and 35 Gy less than 25% (18.8% vs 60% and 23.8% vs 80%, respectively, P < .05). Incontinence was related to mean urethral dose less than 35 Gy and 25 Gy (4.3% vs 66.7% and 0% vs 37.5%, respectively, P < .05) and volume of urethra receiving 35 Gy less than 24% (8.3% vs 50%, P < .05). CONCLUSIONS: This is the first analysis to report dose-volume thresholds associated with late GU toxicity in patients receiving prostate bed stereotactic body radiation therapy. We recommend limiting the bladder wall receiving 25 Gy to less than 18 cubic centimeters to reduce the risk for late grade 3 ureteral stenosis.