[ABO gene subtypes and gene expression analysis in three cases of hematological malignancies patients].

Objective: To explore the application and discovery of genotyping, gene sequencing, and gene expression analysis in the determination of ABO blood group subtypes and antigen expression abnormalities in hematological malignancies patients. Methods: From June 2019 to May 2020, three clinical cases were found with forward and reverse ABO typing discrepancy or atypical serologic agglutination pattern in the laboratory and blood transfusion department of Hebei Yanda Ludaopei Hospital were selected. Sequence-specific primer PCR (PCR-SSP) and Sanger sequencing of ABO gene coding regions were performed to determine the ABO genotypes, and whole transcriptome sequencing was used to analyze ABO and FUT1 gene expression levels. Results: A 12-year-old female acute lymphoblastic leukemia patient was determined as O.01.02 and BA.04 sub-genotype, corresponding to the serological B(A) subtype, and her ABO gene expression was normal (354.80). A 41-year-old female acute myeloid leukemia patient was determined as A1.02 and B.01 genotype, corresponding to the serological A(1)B phenotype, and her ABO gene expression was significantly reduced (45.70). A 42-year-old male with myelodysplastic syndrome and myelofibrosis was determined as A1.02 and A2.05 sub-genotype, corresponding to the serological A(1) and A(2) phenotype, respectively, and his ABO expression was negative. FUT1 expression was in the normal range in all three cases. The clinical blood product infusion strategy was formulated according to the genotype and the corresponding immunological subtype, and no significant transfusion-related adverse reactions occurred. Conclusion: Blood group sub-genotypes or aberrant gene expression can lead to ambiguities in serological blood group determination in hematological malignancies patients. ABO genotyping and gene expression analysis can help in this scenario and escort blood product infusion safety.

Evaluation of the combined use of two different respiratory monitoring systems for 4D CT simulation and gated treatment.

PURPOSE: Two different respiratory monitoring systems (Varian's Real-Time Position Management (RPM) System and Siemens' ANZAI belt Respiratory Gating System) are compared in the context of respiratory signals and 4D CT images that are accordingly reconstructed. This study aims to evaluate the feasibility of combined use of RPM and ANZAI systems for 4DCT simulation and gated radiotherapy treatment, respectively. METHODS: The RPM infrared reflecting marker and the ANZAI belt pressure sensor were both placed on the patient's abdomen during 4DCT scans. The respiratory signal collected by the two systems was synchronized. Fifteen patients were enrolled for respiratory signal collection and analysis. The discrepancies between the RPM and ANZAI traces can be characterized by phase shift and shape distortion. To reveal the impact of the changes in respiratory signals on 4D images, two sets of 4D images based on the same patient's raw data were reconstructed using the RPM and ANZAI data for phase sorting, respectively. The volume of whole lung and the position of diaphragm apex were measured and compared for each respiratory phase. RESULTS: The mean phase shift was measured as 0.2 ± 0.1 s averaged over 15 patients. The shape of the breathing trace was found to be in disagreement. For all the patients, the ANZAI trace had a steeper falloff in exhalation than RPM. The inhalation curve, however, was matched for nine patients, steeper in ANZAI for five patients and steeper in RPM for one patient. For 4D image comparison, the difference in whole-lung volume was about -4% to +4% and the difference in diaphragm position was about -5 mm to +4 mm, compared in each individual phase and averaged over seven patients. CONCLUSIONS: Combined use of one system for 4D CT simulation and the other for gated treatment should be avoided as the resultant gating window would not fully match with each other due to the remarkable discrepancy in breathing traces acquired by the two different surrogate systems.

Treatment optimization with concurrent SBRT and intracavitary brachytherapy for locally advanced cervical cancer.

This work is aimed at investigating treatment planning strategies to optimally com-bine stereotactic body radiation therapy (SBRT) with intracavitary brachytherapy (ICBT) for the treatment of locally advanced cervical cancer. Forty patients (stage IIB - IIIB) previously treated with combined SBRT and ICBT were randomly selected for this retrospective study. All patients were CT- and MR-scanned with a ring applicator in situ. HR-CTV and OARs were contoured according to fused CT and MR images. Several ICBT plans were generated for each patient based on different dose prescription points, and then a matching SBRT plan was generated for each ICBT plan. The dose distribution of each composite plan was analyzed with a focus on the doses received by 90% and 100% of the target volume (D90 and D100), the target volume receiving 100% of the prescription dose (V100%), and the doses received by 2 cc and 40% of the OARs (D2 cc and D40). As the distance, d, between the prescription point and the tandem varied within 1.0 and 1.9 cm, the D90, D100 and V100% for the target, as well as D2 cc and D40 for the bladder and rectum approached their optimal values for d value between 1.0 and 1.4 cm. When design-ing a combined ICBT + SBRT plan, one should measure the size of the cervix and set the prescription isodose line 1.0 to 1.4 cm away from the tandem for the ICBT plan first and then optimize the SBRT plan based on the ICBT dose distribution to achieve the best target coverage and critical structures sparing.

Measurement and Monte Carlo simulation for energy- and intensity-modulated electron radiotherapy delivered by a computer-controlled electron multileaf collimator.

The dosimetric advantage of modulated electron radiotherapy (MERT) has been explored by many investigators and is considered to be an advanced radiation therapy technique in the utilization of electrons. A computer-controlled electron multileaf collimator (MLC) prototype, newly designed to be added onto a Varian linac to deliver MERT, was investigated both experimentally and by Monte Carlo simulations. Four different electron energies, 6, 9, 12, and 15 MeV, were employed for this investigation. To ensure that this device was capable of delivering the electron beams properly, measurements were performed to examine the electron MLC (eMLC) leaf leakage and to determine the appropriate jaw positioning for an eMLC-shaped field in order to eliminate a secondary radiation peak that could otherwise appear outside of an intended radiation field in the case of inappropriate jaw positioning due to insufficient radiation blockage from the jaws. Phase space data were obtained by Monte Carlo (MC) simulation and recorded at the plane just above the jaws for each of the energies (6, 9, 12, and 15 MeV). As an input source, phase space data were used in MC dose calculations for various sizes of the eMLC shaped field (10 × 10 cm2, 3.4 × 3.4 cm2, and 2 × 2 cm2) with respect to a water phantom at source-to-surface distance (SSD) = 94 cm, while the jaws, eMLC leaves, and some accessories associated with the eMLC assembly as well were modeled as modifiers in the calculations. The calculated results were then compared with measurements from a water scanning system. The results showed that jaw settings with 5 mm margins beyond the field shaped by the eMLC were appropriate to eliminate the secondary radiation peak while not widening the beam penumbra; the eMLC leaf leakage measurements ranged from 0.3% to 1.8% for different energies based on in-phantom measurements, which should be quite acceptable for MERT. Comparisons between MC dose calculations and measurements showed agreement within 1%/1 mm based on percentage depth doses (PDDs) and off-axis dose profiles for a range of field sizes for each of the electron energies. Our current work has demonstrated that the eMLC and other relevant components in the linac were correctly modeled and simulated via our in-house MC codes, and the eMLC is capable of accurately delivering electron beams for various eMLC-shaped field sizes with appropriate jaw settings. In the next stage, patient-specific verification with a full MERT plan should be performed.

Measurement comparison and Monte Carlo analysis for volumetric-modulated arc therapy (VMAT) delivery verification using the ArcCHECK dosimetry system.

The objective of this study is to validate the capabilities of a cylindrical diode array system for volumetric-modulated arc therapy (VMAT) treatment quality assurance (QA). The VMAT plans were generated by the Eclipse treatment planning system (TPS) with the analytical anisotropic algorithm (AAA) for dose calculation. An in-house Monte Carlo (MC) code was utilized as a validation tool for the TPS calculations and the ArcCHECK measurements. The megavoltage computed tomography (MVCT) of the ArcCHECK system was adopted for the geometry reconstruction in the TPS and for MC simulations. A 10 × 10 cm2 open field validation was performed for both the 6 and 10 MV photon beams to validate the absolute dose calibration of the ArcCHECK system and also the TPS dose calculations for this system. The impact of the angular dependency on noncoplanar deliveries was investigated with a series of 10 × 10 cm2 fields delivered with couch rotation 0° to 40°. The sensitivity of detecting the translational (1 to 10 mm) and the rotational (1° to 3°) misalignments was tested with a breast VMAT case. Ten VMAT plans (six prostate, H&N, pelvis, liver, and breast) were investigated to evaluate the agreement of the target dose and the peripheral dose among ArcCHECK measurements, and TPS and MC dose calculations. A customized acrylic plug holding an ion chamber was used to measure the dose at the center of the ArcCHECK phantom. Both the entrance and the exit doses measured by the ArcCHECK system with and without the plug agreed with the MC simulation to 1.0%. The TPS dose calculation with a 2.5 mm grid overestimated the exit dose by up to 7.2% when the plug was removed. The agreement between the MC and TPS calculations for the ArcCHECK without the plug improved significantly when a 1 mm dose calculation grid was used in the TPS. The noncoplanar delivery test demonstrated that the angular dependency has limited impact on the gamma passing rate (< 1.2% drop) for the 2%-3% dose and 2mm-3 mm DTA criteria. A 1° rotational misalignment introduces 11.3% (3%/3mm) to 21.3% (1%/1 mm) and 0.2% (3%/3 mm) to 0.8% (1%/1 mm) Gamma passing rate drop for ArcCHECK system and MatriXX system, respectively. Both systems have comparable sensitivity to the AP misalignments. However, a 2 mm RL misalignment introduces gamma passing rate drop ranging from 0.9% (3%/3 mm) to 4.0% (1%/1 mm) and 5.0% (3%/3 mm) to 12.0% (1%/1 mm) for ArcCHECK and MatriXX measurements, respectively. For VMAT plan QA, the gamma analysis passing rates ranged from 96.1% (H&N case) to 99.9% (prostate case), when using the 3%/3 mm DTA criteria for the peripheral dose validation between the TPS and ArcCHCEK measurements. The peripheral dose validation between the MC simulation and ArcCHECK measurements showed at least 97.9% gamma passing rates. The central dose validation also showed an agreement within 2.2% between TPS/MC calculations and ArcCHECK measurements. The worst discrepancy was found in the H&N case, which is the most complex VMAT case. The ArcCHECK system is suitable for VMAT QA evaluation based on the sensitivity to detecting misalignments, the clinical impact of the angular dependency, and the correlation between the dose agreements in the peripheral region and the central region. This work also demonstrated the importance of carrying out a thorough validation of both the TPS and the dosimetry system prior to utilizing it for QA, and the value of having an independent dose calculation tool, such as the MC method, in clinical practice.

An in-vivo study of the combined therapeutic effects of pulsed non-thermal focused ultrasound and radiation for prostate cancer.

PURPOSE: The purpose of this study was to investigate the in vivo combined effects of pulsed focused ultrasound (pFUS) and radiation (RT) for prostate cancer treatment. MATERIALS AND METHODS: An animal prostate tumor model was developed by implanting human LNCaP tumor cells in the prostates of nude mice. Tumor-bearing mice were treated with pFUS, RT or both (pFUS + RT) and compared with a control group. Non-thermal pFUS treatment was delivered by keeping the body temperature below 42 °C as measured real-time by MR thermometry and using a pFUS protocol (1 MHz, 25 W focused ultrasound; 1 Hz pulse rate with a 10% duty cycle for 60 sec for each sonication). Each tumor was covered entirely using 4-8 sonication spots. RT treatment with a dose of 2 Gy was delivered using an external beam (6 MV photon energy with dose rate 300MU/min). Following the treatment, mice were scanned weekly with MRI for tumor volume measurement. RESULTS: The results showed that the tumor volume in the control group increased exponentially to 142 ± 6%, 205 ± 12%, 286 ± 22% and 410 ± 33% at 1, 2, 3 and 4 weeks after treatment, respectively. In contrast, the pFUS group was 29% (p < 0.05), 24% (p < 0.05), 8% and 9% smaller, the RT group was 7%, 10%, 12% and 18% smaller, and the pFUS + RT group was 32%, 39%, 41% and 44% (all with p < 0.05) smaller than the control group at 1, 2, 3, and 4 weeks post treatment, respectively. Tumors treated by pFUS showed an early response (i.e. the first 2 weeks), while the RT group showed a late response. The combined pFUS + RT treatment showed consistent response throughout the post-treatment weeks. CONCLUSIONS: These results suggest that RT combined with non-thermal pFUS can significantly delay the tumor growth. The mechanism of tumor cell killing between pFUS and RT may be different. Pulsed FUS shows early tumor growth delay, while RT contributes to the late effect on tumor growth delay. The addition of pFUS to RT significantly enhanced the therapeutic effect for prostate cancer treatment.

2D IMRT QA passing rate dependency on coronal plane.

Intensity modulated radiation therapy (IMRT) delivery involves a complex series of beam angles and multileaf collimator (MLC) arrangements, requiring quality assurance to be performed to validate delivery before treatment. The purpose of this work is to investigate the effect of dose gradient on quality assurance (QA) passing rate. Many (n = 40) IMRT plans were delivered and measured using a 2D planar array of ion chambers; additionally, eleven plans were measured at several coronal planes. For each measurement, dose gradient was assessed using a number of metrics and passing rate assessed at both 3%/3 mm and 3%/2 mm criteria. The passing rates of the various IMRT plans were shown to be generally correlated to gradient, with an average distance correlation of 0.54 ± 0.04 for the lateral dose gradient. The passing rate for an individual plan was shown to vary with coronal slice, though the correlation to dose gradient was not predictable. Even though the passing rate was strongly related to dose gradient for many of the plans, the signs of the correlations were not always negative, as hypothesized. The coronal plane at which QA is performed affects passing rate, though dose gradient may not easily be used to predict slices at which passing rate is higher.

A new target localization method for image-guided radiation therapy of prostate cancer.

In imaged-guided radiation therapy (IGRT), target localization is usually done with rigid-body registration based on anatomy matching. Problems arise when the target volume can only be matched partially due to inter-fractional organ motion and deformation, resulting in deteriorated target coverage and critical structure sparing. A new target localization method is investigated in which the treatment target volume is aligned with the prescription isodose surface. Our study included 15 prostate patients previously treated with intensity-modulated radiation therapy (IMRT). Patient setup and target localization were performed using a CT-on-rails system before and after the IMRT treatment. IMRT plans were generated on the original simulation CTs (15) and the same MUs and leaf sequences were used to compute the dose distributions on post-treatment CTs (98) with the isocenter adjustments based on either anatomical structure matching or prescription isodose surface alignment. When patients were aligned with the traditional anatomy matching method, the dose to 95% of the CTV, D95, received 74.0 - 77.6 Gy and the minimum CTV dose, Dmin, was 61.9 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions. When patients were aligned using the new localization method, the dose to 95% of the CTV, D95, received 74.0 - 78.2 Gy and the minimum CTV dose, Dmin, was 68.4 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 17.3% of the treatment fractions. Traditional IGRT target localization based on anatomy matching is effective for population-based PTV margins but not ideal for those patients with large inter-fractional prostate rotation/deformation due to large rectal and bladder volume variation. The new method using the prescription isodose surface to align the target volume could improve the target coverage and rectal sparing for these patients, which can be implemented clinically to improve target dose delivery accuracy.

Quantitative study of focused ultrasound enhanced doxorubicin delivery to prostate tumor in vivo with MRI guidance.

PURPOSE: The purpose of this study was to investigate the potential of MR-guided pulsed focused ultrasound (pFUS) for the enhancement of drug uptake in prostate tumors in vivo using doxorubicin (Dox). METHODS: An antitumor drug Dox, an orthotopic animal prostate tumor model using human prostate cancer, LNCaP cell line, and a clinical FUS treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner were used in this study. First, experiments on a tissue mimic phantom to determine the optimal acoustic power and exposure durations with a 10% duty cycle and a 1 Hz pulse rate were performed. The temperature variation was monitored using real-time MR thermometry. Second, tumor-bearing animals were treated with pFUS. There were three groups (n = 8/group): group 1 received pFUS + Dox (10 mg/kg i.v. injection immediately after pFUS exposure), group 2 received Dox only (10 mg/kg i.v. injection), and group 3 was a control. Animals were euthanized 2 h after the pFUS treatment. The Dox concentration in the treated tumors was measured by quantifying fluorescent tracers using a fluorometer. Third, the histological changes of tumors with and without pFUS treatments were evaluated. Finally, experiments were performed to study the spatial drug distribution in tumors after the pFUS treatment, in which two animals received pFUS + Dox, two animals received Dox only, and one animal was used as control. Two hours following the treatment, animals were euthanized and processed. The Dox distribution was determined using a fluorescence microscope. RESULTS: Parametric measurements using a tissue phantom showed that the temperature increased with an increasing acoustic power (from 10 to 50 W) or sonication duration (from 10 to 60 s) with a given acoustic frequency of 1 MHz, duty cycle 10%, and pulse rate 1 Hz. A set of ultrasound parameters was identified with which the temperature elevation was less than 5 °C, which was used for nonthermal pFUS sonication. Increased Dox concentration (14.9 ± 2.5 µg/g) was measured in the pFUS-treated group compared to the Dox-only group (9.5 ± 1.6 µg/g), indicating an approximate 60% increase with p = 0.05. The results were consistent with the increased spatial drug distributions by fluorescence imaging. Histological analysis showed increased extravasation in pFUS-treated prostate tumors suggesting increased drug delivery with pFUS. CONCLUSIONS: The results showed that pFUS-enhanced drug uptake in prostate tumors was significant. This increased uptake may be due to increased extravasation by pFUS. Optimal pFUS parameters may exist to maximize the drug uptake, and this study using Dox demonstrated a quantitative method for such systematic parametric studies. In addition, this study may provide useful data for the potential application of pFUS-mediated Dox delivery for prostate tumor therapy.

4D patient dose reconstruction using online measured EPID cine images for lung SBRT treatment validation.

PURPOSE: This study aims to develop an EPID-guided 4D patient dose reconstruction framework and to investigate its feasibility for lung SBRT treatment validation. METHODS: Both the beam apertures and tumor movements were detected based on the continuously acquired EPID images during the treatment. Instead of directly using the transit photon fluence measured by the EPID, this method reconstructed the entrance fluence with the measured beam apertures and the delivered MUs. The entrance fluence distributions were sorted into their corresponding phases based on the detected tumor motion pattern and then accumulated for each phase. Together with the in-room 4DCT taken before every treatment to consider the interfractional-motion, the entrance fluence was then used for the patient dose calculation. Deformable registration was performed to sum up the phase doses for final treatment assessment. The feasibility of using the transit EPID images for entrance fluence reconstruction was evaluated against EPID in-air measurements. The accuracy of 3D- and 4D-dose reconstruction was validated by experiments with a motor-driven cylindrical diode array for six clinical-SBRT plans. RESULTS: The average difference between the measured and reconstructed fluence maps was within 0.16%. The reconstructed 3D-dose showed a less than 1.4% difference for the CAX-dose and at least a 98.3% gamma-passing-rate (2%∕2 mm) for the peripheral dose. Distorted dose distributions were observed in the measurement with the moving phantom. The comparison between the measured and the reconstructed 4D-dose without considering temporal information failed the gamma-evaluation for most cases. In contrast, when temporal information was considered, the dose distortion phenomena were successfully represented in the reconstructed dose (97.6%-99.7% gamma-passing rate). CONCLUSIONS: The proposed method considered uncertainties of the beam delivery system, the interfractional- and intrafractional-motion, and the interplay effect. The experimental validation demonstrates that this method is practical and accurate for online or offline SBRT patient dose verification.

Target repositional accuracy and PTV margin verification using three-dimensional cone-beam computed tomography (CBCT) in stereotactic body radiotherapy (SBRT) of lung cancers.

The purpose of this study was to assess target repositional accuracy with respect to the bony structures using daily CBCT, and to validate the planning target volume (PTV) margin used in the lung SBRT. All patients underwent 4D CT scanning in preparation for lung SBRT. The internal target volume (ITV) was outlined from the reconstructed 4D data using the maximum-intensity projection (MIP) algorithm. A 6 mm margin was added to the ITV to create the PTV. Conformal treatment planning was performed on the helical images, to which the MIP images were fused. Prior to each treatment, CBCT was taken after a patient was set up in the treatment position. The CBCT images were fused with the simulation CT based on the bony anatomy, in order to derive setup errors and separate them from the tumor repositional errors. The treating physician then checked and modified the alignment based on target relocalization within the PTV. The shifts determined in such a method were recorded and the subtractions of these shifts with respect to the corresponding setup errors were defined as the target relocalization accuracy. Our study of 36 consecutive patients, treating 38 targets for a total of 153 fractions shows that, after setup error correction, the target repositional accuracy followed a normal distribution with the mean values close to 0 in all directions, and standard deviations of 0.25 cm in A-P, 0.24 cm in Lat, and 0.28 cm in S-I directions, respectively. The probability of having the shifts ? 0.6 cm is less than 0.8% in A-P, 0.6% in Lat, and 1.7 % in S-I directions. For the patient population studied, the target centroid position relative to the bony structures changed minimally from day to day. This demonstrated that the PTV margin that is designed on the MIP image-based ITV was adequate for lung SBRT.

Pulsed low dose-rate radiotherapy: radiobiology and dosimetry.

Pulsed low dose-rate radiotherapy (PLDR) relies on two radiobiological findings, the hyper-radiosensitivity of tumor cells at small doses and the reduced normal tissue toxicity at low dose rates. This is achieved by delivering the daily radiation dose of 2 Gy in 10 sub-fractions (pulses) with a 3 min time interval, resulting in an effective low dose rate of 0.067 Gy min-1.In vitrocell studies andin vivoanimal experiments demonstrated the therapeutic potential of PLDR treatments and provided useful preclinical data. Various treatment optimization strategies and delivery techniques have been developed for PLDR on existing linear accelerators. Preliminary results from early clinical studies have shown favorable outcomes for various treatment sites especially for recurrent cancers. This paper reviews the experimental findings of PLDR and dosimetric requirements for PLDR treatment planning and delivery, and summarizes major clinical studies on PLDR cancer treatments.

Monte Carlo Dose Calculation - A QA Method for SRT and SBRT Plans in Treating Multiple and Small Metastatic Lesions.

To provide accurate and fast 3-D dose verification for hypofractionated stereotactic radiotherapy (SRT/SBRT) of small and multi targets calculated with a Varian Eclipse treatment planning system (TPS) delivered on a Varian accelerator. Ten brain and lung hypofractionated SRT/SBRT linac-based and CyberKnife plans were generated by the Eclipse system for delivery on the accelerator with the Millenium-120 leaf multileaf collimator (MLC) and Multiplan for the CyberKnife machine. These clinical SRT/SBRT plans required accurate quality assurance measurements to obtain absolute point dose and 3-D dose distributions due to the low number of fractions and high fraction doses. For small-field and multi-target plans, the EGS4/MCSIM code was used to calculate the dose distribution. A 0.125 cc ion chamber, a 0.016 cc pin-point chamber and Kodak EDR2 film were used for the measurements and the results were compared with Monte Carlo (MC) calculations. The dosimetry for small-field and multi-target treatment plans is challenging due to the comparable range of secondary electrons and the field sizes defined by SRT/SBRT MLC segments. Our MC simulations can accurately reproduce the linac dose distributions (within 1%/1 mm) three dimensionally. For the clinical SRT/SBRT plans investigated in this work, the MC doses agreed within 3% with ion chamber measurements and within 2%/2 mm with film measurements. The doses calculated by the Eclipse AAA algorithm and Multiplan differed by no more than 5% from MC calculations for small (4-40 cc) Planning Target Volumes (PTVs). MC dose calculation provides accurate and fast 3-D dose verification for hypofractionated SRT for small and multi-target treatment plans generated by a Varian Eclipse TPS on a Varian accelerator and Multiplan treatment planning on the CyberKnife System.

A narrative review of pyrolysis and its role in ulcerative colitis.

Cell death is one of the inevitable life activities of cells during the growth and development of the body. Regulated cell death (RCD) is a type of cell death mode that can be regulated and depends on specific molecular mechanisms which play an essential role in various pathophysiological environments. Pyrolysis is a newly discovered method of programmed cell death mediated by members of the Gasdermin protein family which is characterized by the activation of inflammatory factors and the formation of cell membrane pores. The specific manifestations are the swelling of cells, the appearance of plasma membrane bullae and the release of cell contents after cell rupture. A cascade of inflammation occurs after cell death. Activation of inflammasomes activates the classic pyrolysis pathway depending on caspase-1 or the non-classical pyrolysis pathway depending on Caspase-4/5 /11 and the subsequent inflammation reaction, excessive immune response caused by microbial infection and danger signals can lead to a variety of inflammatory diseases. In the inflammatory response, large numbers of inflammasomes activate the substrate protein GSDMD. GSDMD mediates pyrolysis by forming pores in the plasma membrane and mitochondria. Many studies have shown that pyrolysis plays an essential role in inflammatory bowel disease and other inflammatory diseases. This article aims to elaborate on the molecular mechanisms of pyroptosis in ulcerative colitis (UC) pathogenesis and provide new therapeutic ideas for UC.

Therapeutic effects of in-vivo radiodynamic therapy (RDT) for lung cancer treatment: a combination of 15MV photons and 5-aminolevulinic acid (5-ALA).

Objective.Radiodynamic therapy (RDT) uses high-energy photon beams instead of visible/near-infrared light to treat deep-seated tumors that photodynamic therapy cannot achieve due to the low penetration depth of laser beams. The purpose of this study is to investigate the therapeutic effect of RDT with 15 MV photon beams combined with 5-aminolevulinic acid (5-ALA) using a mouse model.Approach.A subcutaneous C57BL/6 mouse model of KP1 small-cell lung cancer cell line was used. The tumors (N = 120) were randomized into four groups to observe individual and synergistic effects of 5-ALA and radiation treatment: control (untreated, N = 42), radiation treatment (RT) only (N = 20), 5-ALA only (N = 20), and RDT (N = 38). For the RT only and RDT groups, 4 Gy in a single fraction was delivered to the tumors using 15 MV photons. For the 5-ALA only and RDT groups, 5-ALA was injected at a dose of 100 mg kg-1by tail-vein 4 h prior to RT. The tumor response was assessed by monitoring tumor growth using 1.5 T MR, maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) using [18F]FDG PET/CT, and animal survival.Main results.RDT achieved a statistically significant delay in tumor growth by 52.1%, 48.1%, and 57.9% 7 days post-treatment compared to 5-ALA only, RT only, and control group (P < 0.001), respectively. There were no significant differences in tumor growth between 5-ALA only and RT only groups. An additional 38.5%-40.9% decrease in tumor growth was observed, showing a synergistic effect with RDT. Furthermore, RDT significantly decreased [18F]FDG uptakes in SUVmaxand TLG 7 days post-treatment by 47.4% and 66.5% (P < 0.001), respectively. RDT mice survived the longest of all treatment groups.Significance.RDT with 15 MV photons and 5-ALA resulted in greater tumor control compared to the control and other treatment groups. A significant synergistic effect was also observed with RDT. These preliminary results demonstrate an effective cancer treatment modality.

Evaluating suggested stricter gamma criteria for linac-based patient-specific delivery QA in the conventional and SBRT environments.

PURPOSE: To evaluate AAPM TG-218 recommended tolerances for IMRT QA for conventional and SBRT delivery. METHODS: QA analysis was repeated for 150 IMRT/VMAT patients with varying gamma criteria. True composite delivery was utilized, corrected for detector and output variation. Universal tolerance (TLuniv) and action limits (ALuniv) were compared with statistical process control (SPC) TLSPC and ALSPC values. Analysis was repeated as a function of plan complexity for 250 non-stereotactic body radiotherapy (SBRT) VMAT patients at 3%/2mm and a threshold of 10% and for 75 SBRT VMAT patients at 2%/2 mm and a threshold of 50% with results plotted as a function of PTV volume. Regions of failure were dose-scaled on the planning CT data sets based on delivery results. RESULTS: The IMRT/VMAT TLSPC and ALSPC for gamma criteria of 3%/3 mm were 96.5% and 95.6% and for 3%/2 mm were 91.2% and 89.2%, respectively. Correlation with plan complexity for conventional fractionation VMAT was "low" for all sites with pelvis having the highest r value at -0.35. The equivalent SBRT PTV diameter ranged from 2.0 cm to 5.6 cm. Negative low correlation was found for 38 of 75 VMAT cases below ALuniv. CONCLUSIONS: The ALuniv and ALSPC are similar for 3%/2 mm. However, our 5% failure rate for ALuniv, may result in treatment start delays approximately 2 times/month, given 40 new cases/month. VMAT QA failure at stricter criteria did not correlate strongly with plan complexity. Site-specific action limits vary less than 3% from the average. SBRT QA results do not strongly correlate with target size over the range studied.

On Monte Carlo modeling of megavoltage photon beams: a revisited study on the sensitivity of beam parameters.

PURPOSE: To commission Monte Carlo beam models for five Varian megavoltage photon beams (4, 6, 10, 15, and 18 MV). The goal is to closely match measured dose distributions in water for a wide range of field sizes (from 2 x 2 to 35 x 35 cm2). The second objective is to reinvestigate the sensitivity of the calculated dose distributions to variations in the primary electron beam parameters. METHODS: The GEPTS Monte Carlo code is used for photon beam simulations and dose calculations. The linear accelerator geometric models are based on (i) manufacturer specifications, (ii) corrections made by Chibani and Ma ["On the discrepancies between Monte Carlo dose calculations and measurements for the 18 MV Varian photon beam," Med. Phys. 34, 1206-1216 (2007)], and (iii) more recent drawings. Measurements were performed using pinpoint and Farmer ionization chambers, depending on the field size. Phase space calculations for small fields were performed with and without angle-based photon splitting. In addition to the three commonly used primary electron beam parameters (E(AV) is the mean energy, FWHM is the energy spectrum broadening, and R is the beam radius), the angular divergence (theta) of primary electrons is also considered. RESULTS: The calculated and measured dose distributions agreed to within 1% local difference at any depth beyond 1 cm for different energies and for field sizes varying from 2 x 2 to 35 x 35 cm2. In the penumbra regions, the distance to agreement is better than 0.5 mm, except for 15 MV (0.4-1 mm). The measured and calculated output factors agreed to within 1.2%. The 6, 10, and 18 MV beam models use theta = 0 degrees, while the 4 and 15 MV beam models require theta = 0.5 degrees and 0.6 degrees, respectively. The parameter sensitivity study shows that varying the beam parameters around the solution can lead to 5% differences with measurements for small (e.g., 2 x 2 cm2) and large (e.g., 35 x 35 cm2) fields, while a perfect agreement is maintained for the 10 x 10 cm2 field. The influence of R on the central-axis depth dose and the strong influence of theta on the lateral dose profiles are demonstrated. CONCLUSIONS: Dose distributions for very small and very large fields were proved to be more sensitive to variations in E(AV), R, and theta in comparison with the 10 x 10 cm2 field. Monte Carlo beam models need to be validated for a wide range of field sizes including small field sizes (e.g., 2 x 2 cm2).

Hong Kong Chinese community leaders' perspectives on family health, happiness and harmony: a qualitative study.

This paper examines the views of Hong Kong community leaders on the underlying issues that affect family health, happiness and harmony (3Hs) in Hong Kong. Using a community reconnaissance method, a series of individual in-depth interviews with 26 leaders that represent neighbourhoods of diverse socio-economic status (SES) from June to August 2008 were conducted. Participants considered that changing family structure, economic situation and strong work ethic are the most salient factors that affect family 3Hs. The deprived comprehensive social security assistance recipients, single-parent families and migrant women were considered to be the most vulnerable groups to breakdown in family 3Hs and particularly, they lack family resources. Families from different SES have to overcome different challenges in order to achieve and sustain family 3Hs. Leaders from low SES neighbourhood were concerned more about providing tangible help such as child care facilities to improve family resources, whereas leaders from high SES neighbourhood focused more on preventive interventions such as education on relationship skills to achieve better family well-being. The findings offer insights in designing effective social marketing education campaigns and family-friendly workplace policy to promote social harmony through the maintenance of 3Hs families.

A new method to deliver supraclavicular radiation in breast radiotherapy for lung sparing.

Due to the angulation of the breast board used for tangential breast irradiation, additional normal lung tissues are included in the supraclavicular field. This work investigates a method to reduce the lung volume and dose delivered during supraclavicular irradiation for breast cancer. Ten patients included for this retrospective study received chest wall and supraclavicular irradiation following radical surgery or breast-conserving surgery. Three-dimensional conformal radiation therapy plans were generated using the CMS XiO treatment planning system. The clinical target volume (CTV) of the supraclavicular irradiation is defined as the subcutaneous tissues from 0.5 cm under the anterior skin surface to a 3 cm depth. Only the ipsilateral lung is defined as the organ at risk. In the new method, the couch is rotated 90° and the supraclavicular field is tilted to maintain a normal incident angle to the breast board rather than the couch surface to spare more normal lung tissues. The absolute volume of the ipsilateral lung irradiated, and the volumes of lung tissues receiving 5 Gy and 20 Gy (V5 and V20) are analyzed. The new method can reduce the lung volume irradiated by the supraclavicular field significantly. For the ten patients investigated, only 5.3% of the ipsilateral lung is irradiated with the new method, while 14.9% of the ipsilateral lung is irradiated using the conventional method. Compared with the conventional method, the new method reduces V5 by 53.6% and V20 by 59.0%. Our new method does not alter the patient positioning for breast treatment but rotates the couch to deliver a tilted supraclavicular field to maintain adequate CTV coverage and spare more normal lung tissues. The results of this study demonstrated that our new method is effective, and that the reduction of normal lung tissue volume in the field is significant.

Dosimetric evaluation of image-guided radiation therapy for prostate cancer.

The aim of this study was to investigate the dosimetric accuracy of imaged-guided radiation therapy for prostate patients using the in-room computed tomography (CT) target localization technique. A Siemens CT-on-rails system was used for patient setup and target localization for intensity-modulated radiation therapy (IMRT) of prostate cancer. Fifteen previously treated prostate patients were included in this retrospective study. CT-on-Rails scans were performed before and after the IMRT treatment under local IRB approval. A total of 15 original simulation CT scans and 98 post-treatment CT scans were contoured by the same oncologist to delineate the prostate target, bladder, and rectum. IMRT plans were generated on the original simulation CTs and the same MUs and leaf sequences were used to compute the dose distributions using post-treatment CTs. Varian Velocity deformable registration was used for the summation of the fractional doses and the cumulative doses were compared with the planned doses. For the 15 patients investigated, the mean isocenter shift was up to 4.0 mm in the left-right direction, 5.9 mm in the anterior-posterior direction and 5.6 mm in the superior-inferior direction due to interfractional organ motion. The mean rectal volume varied from 0.6 to 1.73 times and the mean bladder volume varied from 0.59 to 3.65 times between simulation and the end of treatment. The prescription dose to 95% of the PTV, Dp, was set to 76 Gy for all treatment plans. The dose to 95% of the clinical treatment volume (CTV), D95, was 74.0 to 77.6 Gy and the minimum CTV dose, Dmin, was 61.0 to 71.6 Gy, respectively, in the cumulative dose distributions. Detailed analyses showed that 7.1% of the treatment fractions had cold spots (< 85% of Dp) in the peripheral CTV, leading to Dmin < 64 Gy in the cumulative dose distributions for 4 patients. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions while the bladder dose was much improved in 82.7% of the treatment fractions. The current IGRT procedure for patient setup and target localization using rigid-body registration based on contour/anatomy matching is effective for population-based PTV margins. For a small group of patients, specific PTV margins and/or real-time target monitoring/tracking will be necessary due to significant prostate deformation/rotation caused by inter- and intrafractional bladder and rectal volume variation.