Associations between single nucleotide polymorphisms of cytokines and hepatitis B virus-related liver cirrhosis: A case-control study.

BACKGROUND AND AIMS: Various inflammatory and immune cytokines play key roles in the progression of hepatitis B virus (HBV)-related liver cirrhosis (LC). This study explored the relationship between single nucleotide polymorphisms (SNPs) in cytokines with the combined effect of polymorphisms and gender-polymorphisms interaction and LC risk. METHODS: In this study, a case-control design was used, samples were selected from 45 patients with hepatitis B-related cirrhosis and 45 age-gender-matched chronic HBV-infected patients without cirrhosis attending the tumor hospital of Wuwei Academy of Medical Sciences. Fifteen SNPs were examined using a real-time polymerase chain reaction allelic discrimination system. Logistic regression was utilized to assess cytokine-associated SNPs and the association between SNPs and LC progression in HBV-infected patients. RESULTS: The multivariate-adjusted logistic model revealed that the GG/AG dominant model (OR, 16.38; 95% CI, 1.13-236.70) and G allele (OR, 5.93; 95% CI, 0.98-36.01) of rs1800896 were associated with an increased risk of cirrhosis in CHB patients. Instead, rs2227306 CT presented a reduced cirrhosis risk (OR, 0.22; 95% CI, 0.04-1.38). Rs2055979 AA/AC was negatively associated with the risk of cirrhosis, potentially reversed in males (p = 0.021). Rs1799964 CC/CT was positively related to the risk of cirrhosis but reduced the risk of cirrhosis in males (OR, 0.13; 95% CI, 0.022-0.808; p = 0.028). Both rs1799964 TT and rs1799724 CT/TT genotype showed a synergistic effect in reducing the risk of cirrhosis with rs1800896 AA (OR, 0.08; 95% CI, 0.01-1.43 and OR, 0.12; 95% CI, 0.01-2.21). CONCLUSION: Polymorphisms rs1800896 and rs2227306 are potentially associated with the risk of cirrhosis. For the first time, the study highlights that the rs2055979 AA/AC and rs1799964 CC/CT polymorphism interact with gender and its potential reversal of cirrhosis risk in males. Furthermore, rs1800896 AA showed a synergistic effect with rs1799964 TT and rs1799724 CT/TT to prevent the progression of HBV infection to cirrhosis.

Carbon-ion radiotherapy alone vs. standard dose photon radiation with carbon-ion radiotherapy boost for high-grade gliomas: a retrospective study.

BACKGROUND: This study aimed to compare the survival outcome and side effects in patients with primary high-grade glioma (HGG) who received carbon ion radiotherapy (CIRT) alone or as a boost strategy after photon radiation (photon + CIRTboost). PATIENTS AND METHODS: Thirty-four (34) patients with histologically confirmed HGG and received CIRT alone or Photon + CIRTboost, with concurrent temozolomide between 2020.03-2023.08 in Wuwei Cancer Hospital & Institute, China were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and acute and late toxicities were analyzed and compared. RESULTS: Eight WHO grade 3 and 26 grade 4 patients were included in the analysis. The median PFS in the CIRT alone and Photon + CIRTboost groups were 15 and 19 months respectively for all HGG cases, and 15 and 17.5 months respectively for grade 4 cases. The median OS in the CIRT alone and Photon + CIRTboost groups were 28 and 31 months respectively for all HGG cases, and 21 and 19 months respectively for grade 4 cases. No significant difference in these survival outcomes was observed between the CIRT alone and Photon + CIRTboost groups. Only grade 1 acute toxicities were observed in CIRT alone and Photon + CIRTboost groups. CIRT alone group had a significantly lower ratio of acute toxicities compared to Photon + CIRTboost (3/18 vs. 9/16, p = 0.03). No significant difference in late toxicities was observed. CONCLUSION: Both CIRT alone and Photon + CIRTboost with concurrent temozolomide are safe, without significant differences in PFS and OS in HGG patients. It is meaningful to explore whether dose escalation of CIRTboost might improve survival outcomes of HGG patients in future randomized trials.

Cytokine profiles and virological markers highlight distinctive immune statuses, and effectivenesses and limitations of NAs across different courses of chronic HBV infection.

PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.

The study of virtual source position with the geometric convergent ratio errors prevention management method of spot scanning beam in carbon ion therapy.

INTRODUCTION: We developed a technique including preventing errors management method capable of dealing with the virtual source position delivered by different carbon ion energies from the pattern of spot scanning beam in this study. MATERIALS AND METHODS: A homemade large-format complementary metal-oxide-semiconductor (CMOS) sensor and Gaf Chromic EBT3 films were used for the virtual source position measurement. The Gaf films were embedded in a self-designed rectangular plastic frame to tighten the films and set up on a treatment couch for irradiation in the air with the film perpendicular to the carbon ion beam at the nominal source-axis-distance (SAD) as well as upstream and downstream from the SAD. The horizontal carbon ion beam with five energies at a machine opening field size was carried out in this study. The virtual source position was determined mainly with a linear regression by back projecting the full width half maximum (FWHM) to zero at a distance upstream from the various source-film-distance and double checks additionally with a geometric convergent method to avoid any mistakes caused by manual measurement on FWHM. RESULTS: The virtual source position for higher carbon ion energy has an obvious longer distance from the SAD since the more carbon ion beam energy, the less spreading affected by the horizontal and vertical magnetism, therefore, the distance of virtual source positions is decreased from SAD with high to low energy. CONCLUSION: The method for investigating the virtual source position in the carbon ion beam in this study can also be used for electrons and the proton. We have developed a technique capable of dealing with the virtual source position with a geometric convergent method to avoid any mistakes in spot scanning carbon ion beam.

Determination of virtual source position using back projecting zero and convergent arcTAN method for scanning-passive scatter beam in carbon ion therapy.

OBJECTIVE: This study aims to develop and test a new technique by using the convergent arcTAN (cATAN) method capable of dealing with the virtual source position delivered by different carbon ion energies from the pattern of scanning-passive scatter beam. MATERIALS AND METHODS: A homemade large-format CMOS sensor and Gaf Chromic EBT3 films are used for the virtual source position measurement. The Gaf films are embedded in a self-designed rectangular plastic frame to tighten films and set up on a treatment couch for irradiation in air with the film perpendicular to the carbon ion beam at the nominal source-axis-distance (SAD) as well as upstream and downstream from the SAD. The horizontal carbon ion beam with 5 energies at a machine opening field size is carried out in this study. The virtual source position is determined by using the convergent arcTAN (cATAN) method and compared with a linear regression by back projecting FWHM to zero at a distance upstream from the various source-film-distance. RESULTS: The film FWHM measurement error of 0.5 mm leads to 0.001% deviation of α (cATAN) at every assumed textend. The overall uncertainty for the reproducibility of calculated virtual source position by the assumed textend in the vertical and horizontal directions amounts to 0.1%. The errors of calculated virtual source position by assumed textend with back projecting FWHM to zero methods are within 1.1±0.001, p = 0.033. CONCLUSION: We develop a new technique capable of dealing with the virtual source position with a convergent arcTAN method to avoid any manual measurement mistakes in scanning-passive scatter carbon ion beam. The readers are encouraged to conduct the proposed cATAN method in this study to investigate the virtual source position in the Linac-based external electron beams and the proton beams.

Non-invasive high frequency oscillatory ventilation inhibiting respiratory motion in healthy volunteers.

Precision radiotherapy needs to manage organ movements to prevent critical organ injury. The purpose of this study is to examine the feasibility of motion control of the lung by suppressing respiratory motion. The non-invasive high frequency oscillatory ventilation (NIHFOV) is a technique commonly used in the protection of lung for patients with acute lung disease. By using a very high respiratory frequency and a low tidal volume, NIHFOV allows gas exchange, maintains a constant mean airway pressure and minimizes the respiratory movements. We tested healthy volunteers NIHFOV to explore the optimal operational parameter setting and the best possible motion suppression achievable. This study was conducted with the approval of Institutional Review Boards of the Wuwei Cancer hospital (approval number: 2021-39) and carried out in accordance with Declaration of Helsinki. The study comprises two parts. Twenty three healthy volunteers participated in the first part of the study. They had 7 sessions of training with the NIHFOV. The duration of uninterrupted, continuous breathing under the NIHFOV and the optimal operational machine settings were defined. Eight healthy volunteers took part in the second part of the study and underwent 4-dimensional CT (4DCT) scanning with and without NIHFOV. Their respiratory waveform under free breathing (FB) and NIHFOV were recorded. The maximum range of motion of the diaphragm from the two scannings was compared, and the variation of bilateral lung volume was obtained to evaluate the impact of NIHFOV technique on lung volume. The following data were collected: comfort score, transcutaneous partial pressure of oxygen (PtcO2), transcutaneous partial pressure of carbon dioxide (PtcCO2), and pulse rate. Data with and without NIHFOV were compared to evaluate its safety, physiological impacts and effect of lung movement suppression. All the volunteers completed the training sessions eventlessly, demonstrating a good tolerability of the procedure. The median NIHFOV-on time was 32 min (22-45 min), and the maximum range of motion in the cephalic-caudal direction was significantly reduced on NIHFOV compared with FB (1.8 ± 0.8 cm vs 0.3 ± 0.1 cm, t = - 3.650, P = 0.003); the median range of motion was only 0.3 ± 0.1 cm on NIHFOV with a good reproducibility. The variation coefficient under NIHFOV of the right lung volume was 2.4% and the left lung volume was 9.2%. The PtcO2 and PtcCO2 were constantly monitored during NIHFOV. The medium PtcCO2 under NIHFOV increased lightly by 4.1 mmHg (interquartile range [IQR], 4-6 mmHg) compared with FB (t = 17.676, P < 0.001). No hypercapnia was found, PtcO2 increased significantly in all volunteers during NIHFOV (t = 25.453, P < 0.001). There was no significant difference in pulse rate between the two data sets (t = 1.257, P = 0.233). NIHFOV is easy to master in healthy volunteers to minimize respiratory movement with good tolerability and reproducibility. It is a feasible approach for lung motion control and could potentially be applied in accurate radiotherapy including carbon-ion radiotherapy through suppression of respiratory movement.

Clinical significance of novel biomarkers to predict the natural course of hepatitis B infection.

Background and aim: Chronic hepatitis B (CHB) can be divided into immune tolerance (IT), immune clearance (IC), hepatitis B e antigen (HBeAg)-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. The conventional biomarkers used to distinguish these phases have limitations. We examined the clinical significance of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as novel biomarkers. Methods: One hundred eighty-nine patients without treatment currently were categorized by CHB phase (IT = 46, IC = 45, ENQ = 49, ENH = 49). The associations of HBV RNA and HBcrAg with HBV DNA and alanine transaminase (ALT) were analyzed. The decision tree model was used to distinguish the four phases in the natural course of CHB. Results: The concentrations of HBV RNA and HBcrAg were highest in the IT and IC phases (P < 0.01). Serum HBV RNA was similar to HBcrAg in treatment-naïve patients. HBV RNA and HBcrAg correlated with HBV DNA in the HBeAg+ and HBeAg- status (HBV RNA: e+ r = 0.51, e- r = 0.62; HBcrAg: e+ r = 0.51, e- r = 0.71), but their association with HBV DNA differed among phases. The accuracy, sensitivity, and specificity of HBcrAg with ALT in distinguishing the CHB phases were 95.65%, 95.83%, and 95.55%, respectively. Conclusion: Serum HBV RNA and HBcrAg may be useful to monitor CHB progression.

Describing immune factors associated with Hepatitis B surface antigen loss: A nested case-control study of a Chinese sample from Wuwei City.

Background: Hepatitis B surface antigen (HBsAg) loss is considered a functional cure for chronic hepatitis B (CHB), however, several factors influence HBsAg loss. Methods: 29 CHB patients who had achieved HBsAg loss, were selected and 58 CHB patients with persistent HBsAg were matched, according to gender and age (+/- 3 years). Logistic regression and restricted cubic spline (RCS) modelling were performed. Results: Multivariate-adjusted logistic regression, based on stepwise selection, showed that baseline HBsAg levels negatively correlated with HBsAg loss (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.98-0.99). Interferon treatment positively related with HBsAg loss (OR = 7.99, 95%CI = 1.62-44.88). After adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment, MMP-1 (OR = 0.66, 95%CI = 0.44-0.97), CXCL9 (OR = 0.96, 95%CI = 0.93-0.99) and TNF-R1 (OR = 0.97, 95%CI = 0.94-0.99) baseline levels all negatively correlated with HBsAg loss. Our multivariate-adjusted RCS model showed that baseline CXCL10 was associated with HBsAg loss although the relationship was "U-shaped". Conclusions: Cytokines such as MMP-1, CXCL9, CXCL10 and TNF-R1 are important factors which influence HBsAg loss. It may be possible to develop a nomogram which intercalates these factors; however, further research should consider immune processes involved in HBsAg loss.

Association of single nucleotide polymorphisms (SNPs) with gastric cancer susceptibility and prognosis in population in Wuwei, Gansu, China.

BACKGROUND: Gastric cancer (GC) is the sixth most common cancer. China is one of the most frequent GC occurred countries, and Wuwei, Gansu, is one of the highest incidence area in China. Possible biomarkers of GC susceptibility and prognosis among the population in Wuwei are urgently needed. METHODS: All participants in this study were recruited from the Wuwei Cancer Hospital in Gansu, including 303 patients diagnosed with GC and 200 non-cancer controls. DNA was extracted for further single nucleotide polymorphisms (SNP) genotyping. All SNPs were firstly screened by additive logistic regression model then selected SNPs were subjected to univariate Cox regression analysis and multivariate Cox regression analysis for their associations with GC occurrence. RESULTS: The results showed that 31 SNPs were significantly related to the incidence of GC in Wuwei, Gansu, China. Genotype rs4823921 was significantly related to the overall survival of GC patients and AC/AA genotype of rs4823921 polymorphism was significantly associated with an increased risk of GC in Wuwei population. CONCLUSIONS: Thirty-one SNPs were significantly related to the incidence of GC in Wuwei and rs4823921 genotype AC/AA was significantly associated with poor prognosis of GC patients in Wuwei, Gansu.

Analyzing the Spatiotemporal Distribution and Characteristics of Liver Cirrhosis in Hospitalized Patients in Wuwei, Gansu Province During 1995-2016: A Long-Term Retrospective Study.

Objectives: This was a long-term retrospective study, aiming to understand the temporal and spatial trend of cirrhosis in Wuwei from 1995 to 2016, explore its spatio-temporal aggregation, and find out the high incidence areas. To provide theoretical basis for the formulation of comprehensive prevention and treatment strategy of cirrhosis in Wuwei. Methods: Herein, we extracted data of cirrhosis patients who were treated in 12 sentinel hospitals in Wuwei from their medical records. We used SAS and Joinpoint Regression Program for data analysis, SaTScan 9.4 software for clustering area detection, and ArcGIS 10.2 software for geographical distribution mapping. Results: Among 3308 patients with liver cirrhosis (average age, 55.34 years) included in this study, 15.9% were aged 50-54 years. The majority were men (2716, 65.8%), with a sex ratio of 1.92:1 and peasants by occupation (1369, 60.3%). The basic social medical insurance system covered the healthcare costs of 1271 patients (63%). A Joinpoint regression analysis done for 1995-2016 revealed an increase in the standardized cirrhosis rate [average annual percent change (AAPC) = 16.7% (95% CI, 10.2-23.5%)] with three joinpoints in 2010, 2013, and 2016. The annual percent change (APC) from 1995 to 2010 was 11.13% (95% CI: 6.5-16.0), and APC from 2010 to 2013 was 66.48% (95% CI:16.0-138.9); conversely, from 2013 to 2016, APC was 4.4% (95% CI, -7.5-17.8%). Hongshagang Town showed the highest average incidence. Each township showed a gradual increase in the incidence after 2010. The results revealed that in each township, liver cirrhosis incidence had some spatial aggregation and was nonrandom. Four liver cirrhosis clusters were noted in 75 townships in Wuwei. Data were gathered from 2011 to 2016. Conclusions: From 1995 to 2016, the incidence of cirrhosis in Wuwei still showed an increasing trend, but the growth rate slowed down since 2013. In Wuwei, the rate of standardization of cirrhosis in female patients increased steadily and faster than in male patients. It is necessary to strengthen the diagnosis, treatment, prevention, and control measures of cirrhosis-related diseases. The results of spatial scanning, basic spatial distribution, aggregation time, and time trend analysis were consistent.

Carbon ion radiotherapy for recurrent ameloblastoma: A case report.

Ameloblastoma is a kind of benign, odontogenic tumor of epithelial origin, and surgery is mainstay treatment method; however, recurrence is common, and usually the treatment for recurrence is still surgery. We report on a patient of recurrent ameloblastoma treated with carbon ion radiation therapy and achieved a good efficacy. A 25-year-old female with relapse of an ameloblastoma was referred to the Wuwei Heavy Ion Center for carbon ion therapy. She had been initially diagnosed with ameloblastoma 8 years ago and underwent operation of right mandible ameloblastoma. After she transferred to our center, she accepted a dose of 60 GyE carbon ion radiation therapy, and the efficacy is good. Carbon ion radiation therapy can be an effective treatment option for ameloblastoma.

Carbon ion radiotherapy with complete tumor regression for primary malignant melanoma of female urethra orifice: a case report.

Primary malignant melanoma of the female urethra (PMMFU) is extremely rare, accounting for 0.2% of all melanomas, and fewer than 200 cases have been reported worldwide. Because of the small number of clinical cases and unclear biological characteristics, there is no uniform and standard treatment protocol. We herein describe the treatment of PMMFU using carbon ion radiotherapy. The radiotherapy was delivered at 60.8 Gy (RBE) in 16 fractions, once daily, five times per week. The patient achieved complete tumor disappearance within 1 year after carbon ion radiotherapy and remained disease-free thereafter. She developed acute grade 1 radiation dermatitis and urethritis, which resolved quickly; no other toxic effects were observed. At the time of this writing, her survival duration was 33 months. This case demonstrates that carbon ion radiotherapy may be a good option for primary genitourinary mucosal malignancies.

Empirical modeling of the percent depth dose for megavoltage photon beams.

INTRODUCTION: This study presents an empirical method to model the high-energy photon beam percent depth dose (PDD) curve by using the home-generated buildup function and tail function (buildup-tail function) in radiation therapy. The modeling parameters n and µ of buildup-tail function can be used to characterize the Collimator Scatter Factor (Sc) either in a square field or in the different individual upper jaw and lower jaw setting separately for individual monitor unit check. METHODS AND MATERIALS: The PDD curves for four high-energy photon beams were modeled by the buildup and tail function in this study. The buildup function was a quadratic function in the form of [Formula: see text] with the main parameter of d (depth in water) and n, while the tail function was in the form of e-µd and was composed by an exponential function with the main parameter of d and µ. The PDD was the product of buildup and tail function, PDD = [Formula: see text]. The PDD of four-photon energies was characterized by the buildup-tail function by adjusting the parameters n and µ. The Sc of 6 MV and 10 MV can then be expressed simply by the modeling parameters n and µ. RESULTS: The main parameters n increases in buildup-tail function when photon energy increased. The physical meaning of the parameter n expresses the beam hardening of photon energy in PDD. The fitting results of parameters n in the buildup function are 0.17, 0.208, 0.495, 1.2 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The parameter µ can be treated as attenuation coefficient in tail function and decreases when photon energy increased. The fitting results of parameters µ in the tail function are 0.065, 0.0515, 0.0458, 0.0422 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The values of n and µ obtained from the fitted buildup-tail function were applied into an analytical formula of Sc = nE(S)0.63µE to get the collimator to scatter factor Sc for 6 and 10 MV photon beam, while nE, µE, S denotes n, µ at photon energy E of field size S, respectively. The calculated Sc were compared with the measured data and showed agreement at different field sizes to within ±1.5%. CONCLUSIONS: We proposed a model incorporating a two-parameter formula which can improve the fitting accuracy to be better than 1.5% maximum error for describing the PDD in different photon energies used in clinical setting. This model can be used to parameterize the Sc factors for some clinical requirements. The modeling parameters n and µ can be used to predict the Sc in either square field or individual jaws opening asymmetrically for treatment monitor unit double-check in dose calculation. The technique developed in this study can also be used for systematic or random errors in the QA program, thus improves the clinical dose computation accuracy for patient treatment.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report.

BACKGROUND: Despite being the most common intraocular malignancy among adults, choroidal melanoma is a rare cancer type, even more so when accompanied by lung cancer. We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy (CIRT). CASE SUMMARY: A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye. During the examination, we found a right lung tumor that was histologically diagnosed as lung cancer. The patient was treated with CIRT for both malignant neoplasms. The CIRT dose was 70 photon equivalent doses (GyE) in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer. At 3 mo after CIRT, the choroidal melanoma completely disappeared, as did the right lung cancer 7 mo after; the patient was in complete remission. CONCLUSION: CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

A Mathematical Method to Adjust MLC Leaf End Position for Accurate Dose Calculation in Carbon Ion Beam Radiation Therapy Treatment Planning System.

INTRODUCTION: We present a mathematical method to adjust the leaf end position for dose calculation correction in the carbon ion radiation therapy treatment planning system. METHODS AND MATERIALS: A straggling range algorism of 400 MeV/n carbon ion beam in nine different multileaf collimator (MLC) materials was conducted to calculate the dose 50% point to derive the offset corrections in the carbon ion treatment planning system (ciPlan). The visualized light field edge position in the treatment planning system is denoted as X tang.p, and MLC position (X mlc.p) is defined as the source to leaf end midpoint projection on axis for monitor unit calculation. The virtual source position of energy at 400 MeV/n and straggling range in MLC at different field sizes were used to calculate the dose 50% position on axis. On-axis MLC offset (correction) could then be obtained from the position corresponding to 50% of the central axis dose minus the X mlc.p. RESULTS: The exact MLC position in the carbon ion treatment planning system can be used as an offset to do the correction. The offset correction of pure tungsten is the smallest among the others due to its shortest straggling range of carbon ion beam in MLC. The positions of 50% dose of all MLC materials are always located in between X tang.p and X mlc.p under the largest field of 12 cm by 12 cm. CONCLUSIONS: MLC offset should be adjusted carefully at different field sizes in the treatment planning systems especially of its small penumbra characteristic in the carbon ion beam. It is necessary to find out the dose 50% position for adjusting MLC leaf edge on-axis location in the treatment planning system to reduce dose calculation error.

Energy-Related Scatter Analysis for Determining the Effective Point of Measurement of Cylindrical Ion Chamber in Heavy Charged Particle Carbon Ion Beam.

PURPOSE: An experimental and mathematical study for determining the effective point of measurement (P eff) for a Farmer-type cylindrical chamber in a carbon ion passive scatter beam is presented. METHODS: The ionization depth curves measured by the Bragg peak chamber were plotted according to the position of the inner surface of the entrance window, while the Farmer chamber was plotted at the tip of the cylindrical geometric center. The ionization depth curves measured by a cylindrical chamber in the 3D water phantom were then compared with a high-precision parallel-plate PTW Bragg peak chamber for inspecting the upstream shift correction of the cylindrical chamber in the carbon ion beam. A component of the vertical and horizontal integration method and the barrier model, cosφ = 1 - [2αR L /(1 + α - R L )], for analyzing the shift of effective point of measurement in different carbon ion energies and various field sizes, were studied. RESULTS: The shift between the maximum peak of the Bragg peak chamber and the Farmer chamber in a field size of 10 cm × 10 cm with an energy of 330 MeV/u of carbon ion is 2.3 mm. This upstream shift corresponds to (0.744 ± 0.07)r, where r is the Farmer chamber inner radius of 3.05 mm. Carbon ion energy from 120 MeV/u to 400 MeV/u with different field sizes show different shifts of effective point of measurement in a range of (0.649 ± 0.02)r to (0.843 ± 0.06)r of 3 cm × 3 cm at an energy of 400 MeV/u and 10 cm × 10 cm at an energy of 120 MeV/u, respectively. The vertical and horizontal scatter analysis by the barrier model can precisely describe the shift of the effective point of measurement at different carbon ion energies with various field sizes. CONCLUSIONS: We conclude that the Farmer chamber can be used for a patient-specific dose verification check in carbon ion beam treatment if P eff is well calibrated.

The Study of Field Equivalence Determined by the Modeled Percentage Depth Dose in Electron Beam Radiation Therapy.

INTRODUCTION: This study presents an empirical method to model the curve of electron beam percent depth dose (PDD) by using the primary-tail function in electron beam radiation therapy. The modeling parameters N and n can be used to predict the minimal side length when the field size is reduced below that required for lateral scatter equilibrium (LSE) in electron radiation therapy. METHODS AND MATERIALS: The electrons' PDD curves were modeled by the primary-tail function in this study. The primary function included the exponential function and the main parameters of N and µ, while the tail function was composed of a sigmoid function with the main parameter of n. The PDD of five electron energies was modeled by the primary and tail function by adjusting the parameters of N, µ, and n. The R 50 and R p can be derived from the modeled straight line of 80% to 20% region of PDD. The same electron energy with different cone sizes was also modeled by the primary-tail function. The stopping power of different electron energies in different depths can also be derived from the parameters N, µ, and n. RESULTS: The main parameters N and n increase but µ decreases in the primary-tail function for characterizing the electron beam PDD when the electron energy increased. The relationship of parameter n, N, and ln(-µ) with electron energy are n = 31.667E 0 - 88, N = 0.9975E 0 - 2.8535, and ln(-µ) = -0.1355E 0 - 6.0986, respectively. Percent depth dose was derived from the percent reading curve by multiplying the stopping power relevant to the depth in water at a certain electron energy. The stopping power of different electron energies can be derived from n and N with the following equation: stopping power = (-0.042ln(N E 0 ) + 1.072)e (-nE0 · 5 · 10-5 + 0.0381)·x , where x is the depth in water. The lateral scatter equivalence (LSE) of the clinical electron beam can be described by the parameters E 0, n, and N in the equation of Seq = (n E 0 - N E 0 )0.288/(E 0/n E 0 )0.0195. The LSE was compared with the root mean square scatter angular distribution method and shows the agreement of depth dose distributions within ±2%. CONCLUSIONS: The PDD of the electron beam at different energies and cone sizes can be modeled with an empirical model to deal with what is the minimal field size without changing the percent depth dose when approximate LSE is given in centimeters of water.

Bystander effect and abscopal effect in recurrent thymic carcinoma treated with carbon-ion radiation therapy: A case report.

BACKGROUND: Although the bystander effect and abscopal effect are familiar in medicine, they are relatively rare in clinical practice. Herein, we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma. CASE SUMMARY: A 44-year-old female presented with shortness of breath. Eleven years prior, she was diagnosed with athymic tumor located in the anterosuperior mediastinum. She underwent extensive tumor resection, and the postoperative pathologic diagnosis was thymic carcinoma. She was administered 50 Gy/25 Fx of postoperative radiation. In 2019, she was diagnosed with a recurrence of thymic carcinoma, with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity, the largest of which was in the diaphragm pleura proximal to the pericardium, with a size of 6.7 cm × 5.3 cm × 4.8 cm. She received carbon-ion radiotherapy. After carbon-ion radiotherapy treatment, the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging. We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case. CONCLUSION: This report is the first of obvious abscopal and bystander effects following carbon-ion irradiation in a human patient, and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.

Carbon ion radiotherapy for recurrent calf myxoid liposarcoma: a case report.

Liposarcoma (LPS) is the most common soft tissue sarcoma. Myxoid LPS (MLPS) is the second most common subtype of LPS and accounts for 25% to 50% of all LPSs. Like most other soft tissue sarcomas, the mainstay of treatment for LPS is inevitably surgery. Multidisciplinary approaches, including surgery, chemotherapy, and radiotherapy, have been successful in the treatment of LPS during the last three decades. Even so, recurrence of LPS remains challenging. Carbon ion beams produce increased energy deposition at the end of their range to form a Bragg peak while minimizing irradiation damage to surrounding tissues, which facilitates more precise dosage and localization than that achieved with photon beams. Furthermore, carbon ion beams have high relative biologic effectiveness. We herein describe a patient who developed recurrent MLPS in the right calf after two surgeries and underwent carbon ion radiotherapy (CIRT), achieving complete disappearance of the tumor. The patient developed Grade 1 radiation dermatitis 30 days after CIRT, but no other acute toxicities were observed. The tumor had completely disappeared by 120 days after CIRT, and the patient remained disease-free for 27 months after CIRT. The CARE guidelines were followed in the reporting of this case.

circ_0007385 served as competing endogenous RNA for miR-519d-3p to suppress malignant behaviors and cisplatin resistance of non-small cell lung cancer cells.

BACKGROUND: Circular RNAs (circRNAs) have been closely implicated in competing endogenous RNA (ceRNA) network among human cancers including non-small cell lung cancer (NSCLC). However, the role of most circRNAs in NSCLC remains to be determined. Here, we aimed to investigate the role of hsa_circ_0007385 (circ_0007385) in NSCLC cells. METHODS: Expression of hsa_circ_0007385 (circ_0007385), miRNA (miR)-519d-5p and high-mobility group box 1 (HMGB1) was measured by real-time quantitative PCR and western blotting. Functional experiments were evaluated by cell counting kit (CCK)-8, flow cytometry, fluorescein active caspase-3 staining kit, transwell assays, western blotting, and xenograft experiment. The relationship among circ_0007385,miR-519d-5p and HMGB1 was testified by dual-luciferase reporter assay. Kaplan-Meiersurvival curve identified overall survival in NSCLC patients. RESULTS: circ_0007385 expression was higher in NSCLC tissues and cell lines, and was associated with poor overall survival. Silencing circ_0007385 could suppress cell proliferation, migration and invasion in A549 and H1975 cells, as well as cisplatin (DDP) resistance. Moreover, circ_0007385 silence retarded tumor growth of A549 cells in vivo. Molecularly, there was a direct interaction between miR-519d-3p and either circ_0007385 or HMGB1; expression of miR-519d-3p was downregulated in NSCLC tumors in a circ_0007385-correlated manner, and circ_0007385 could indirectly regulate HMGB1 via miR-519d-3p. Functionally, both inhibiting miR-519d-3p and restoring HMGB1 could overturn the suppressive effect of circ_0007385 knockdown on cell proliferation, migration, invasion, and DDP resistance. CONCLUSIONS: Collectively, circ_0007385 deletion could function anti-tumor role in NSCLC by suppressing malignant behaviors and DDP resistance in vitro and in vivo via circ_0007385/miR-519d-3p/HMGB1 axis. These outcomes might enhance our understanding of the molecular mechanisms underlying the malignant progression of NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: circ_0007385 was upregulated in NSCLC tissues and cells, and was associated with poor overall survival. Silenced circ_0007385 suppressed NSCLC cell proliferation, migration, invasion, and DDP resistance in vitro, and tumor growth in vivo. circ_0007385 was upregulated in NSCLC tissues and cells, and was associated with poor overall survival. WHAT THIS STUDY ADDS: miR-519d-3p could directly interact with circ_0007385 and HMGB1 in NSCLC cells. A promising circ_0007385/miR-519d-3p/HMGB1 regulatory pathway was determined in NSCLC cells.